A dose-response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change.

PubMed

Honchel, R; Carraway, J; Gopee, N; Callicott, R; Chen, J; Patton, R; Xu, Q; Zalkkar, J; Laniyonu, A; Krefting, I; Cato, M; Robie-Suh, K; Rieves, R

2011-08-01

The United States Pharmacopeia (USP) monograph for unfractionated heparin (UFH) was revised in October 2009. This revision was anticipated, based upon in vitro tests, to reduce UFH potency by approximately 10%. To study the potential in vivo consequences of the monograph change, we evaluated activated partial thromboplastin time (aPTT) and activated clotting time (ACT) responses in animals. Female mini-pigs and monkeys (n=8/species) were administered intravenously 60, 54, 48, or 42 U/kg and 50, 45, 40, or 35 U/kg "old" (pre-USP revision) UFH, respectively, in a Williams 4×4 crossover design. Blood samples for aPTT and ACT were collected at 15 min after dosing. The same study design was then repeated using "new" (post-USP revision) UFH. Mean "new" UFH aPTT and ACT values were generally lower than those for "old" UFH although individual animal responses varied considerably. The aPTT and ACT response was generally dose-proportional for both "old" and "new" UFH. These studies indicate that the USP monograph alteration for UFH may result in a modest reduction in the anticoagulant response across a population, but the variability in animal responses underscores the importance of individualization of clinical UFH dosing and the importance of anticoagulant test monitoring. Published by Elsevier Inc.

Effect of Centrifuge Temperature on Routine Coagulation Tests.

PubMed

Yazar, Hayrullah; Özdemir, Fatma; Köse, Elif

2018-01-01

This study investigated the effects of cooled and standard centrifuges on the results of coagulation tests to examine the effects of centrifugation temperature. Equal-volume blood samples from each patient were collected at the same time intervals and subjected to standard (25°C) and cooled centrifugation (2-4°C). Subsequently, the prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer values were determined in runs with the same lot numbers in the same coagulation device using the Dia-PT R (PT and INR), Dia-PTT-liquid (aPTT), Dia-FIB (fibrinogen), and Dia-D-dimer kits, respectively. The study enrolled 771 participants. The PT was significantly (p < 0.018) higher in participants on anticoagulant therapy. The respective median values of the test parameters determined using the standard and cooled centrifuges were as follows: PT 10.30 versus 10.50 s; PT (INR) 1.04 versus 1.09 s; APTT 28.90 versus 29.40 s; fibrinogen 321.5 versus 322.1 mg/dL; and D-dimer 179.5 versus 168.7 µg FEU/mL. There were significant differences (p < 0.001) in the parameters between the values obtained with the standard and cooled centrifuges. Centrifuge temperature can have a significant effect on the results of coagulation tests. However, broad and specific disease-based studies are needed. © 2018 S. Karger AG, Basel.

Monitoring of unfractionated heparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent (PiCT®).

PubMed

Schaden, E; Jilch, S; Hacker, S; Schober, A; Kozek-Langenecker, S

2012-12-24

To achieve sufficient and safe anticoagulation with unfractionated heparin (UFH) a close and reliable drug monitoring is necessary. In general, the activated partial thromboplastin time (APTT) is used for this purpose. In acute phase response, however, the APTT test procedure might be unreliable e.g. with false low results in the presence of elevated factor VIII. In this so called heparin resistance, measurement of anti-Xa activity is recommended over APTT to avoid potentially harmful dose escalation. A combination of anti-Xa measurement and global hemostatic testing with ROTEM® employing the anti-Xa sensitive PiCT® reagent showed high correlation with enoxaparin levels. This test modification could also be suitable for monitoring UFH. Aim of the study was to evaluate the correlation between PiCT®-ROTEM® and levels of UFH. In this in-vitro study blood samples from healthy volunteers were spiked with UFH and subjected to different ROTEM® tests. There was a linear correlation between UFH level and clotting time (CT) in the PiCT®-ROTEM® test with an excellent correlation coefficient of 0.92. Additional endpoints showed similar results (PiCT®-ROTEM® MaxVel r = -0.85 and PiCT®-ROTEM® t_MaxVel r = 0.88). As a point-of-care applicable tool ROTEM® is immediately at hand. If further clinical studies confirm sensitivity in heparin resistance, PiCT®-ROTEM® could permit rapid UFH dose adjustments especially required in critical illness with acute phase response. Copyright © 2012 Elsevier B.V. All rights reserved.

An international survey of current practice in the laboratory assessment of anticoagulant therapy with heparin.

PubMed

Favaloro, Emmanuel J; Bonar, Roslyn; Sioufi, John; Wheeler, Michael; Low, Joyce; Aboud, Margaret; Lloyd, John; Street, Alison; Marsden, Katherine

2005-06-01

We conducted a survey of laboratory practice for assessment of heparin anticoagulant therapy by participants of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP). A questionnaire was sent to 646 laboratories enrolled in the Haematology component of the QAP, requesting details of tests used for monitoring heparin therapy. Seventy laboratories (10.8%) returned results that indicated that they performed laboratory monitoring of heparin therapy. Most laboratories (69/70 = 98.6%) use the activated partial thromboplastin time (APTT) to monitor unfractionated heparin, with eight (11.4%) also using the APTT for monitoring low molecular weight (LMW) heparin. Five (7.1%) laboratories use the thrombin time (TT) test to help monitor heparin therapy and 37 (52.9%) laboratories use an anti-Xa assay to monitor heparin (either LMW or unfractionated). Normal reference ranges (NRR) for APTT differed considerably between laboratories, even those using the same reagent. Therapeutic ranges (TR) also differed considerably between laboratories, for both APTT and the anti-Xa assay. Laboratory differences in NRR and TR using the same reagents could only be partly explained by the use of different instrumentation. There is a large variation in current laboratory practice relating to monitoring of heparin anticoagulant therapy. This finding is similar to that of a similar survey conducted by the RCPA QAP almost a decade ago. This study suggests that better standardisation is still required for laboratory monitoring of heparin therapy.

Ankle Bracing, Fatigue, and Time to Stabilization in Collegiate Volleyball Athletes

PubMed Central

Shaw, Megan Y; Gribble, Phillip A; Frye, Jamie L

2008-01-01

Context: Fatigue has been shown to disrupt dynamic stability in healthy volunteers. It is not known if wearing prophylactic ankle supports can improve dynamic stability in fatigued athletes. Objective: To determine the type of ankle brace that may be more effective at providing dynamic stability after a jump-landing task during normal and fatigued conditions. Design: Two separate repeated-measures analyses of variance with 2 within-subjects factors (condition and time) were performed for each dependent variable. Setting: Research laboratory. Patients or Other Participants: Ten healthy female collegiate volleyball athletes participated (age  =  19.5 ± 1.27 years, height  =  179.07 ± 7.6 cm, mass  =  69.86 ± 5.42 kg). Intervention(s): Athletes participated in 3 separate testing sessions, applying a different bracing condition at each session: no brace (NB), Swede-O Universal lace-up ankle brace (AB), and Active Ankle brace (AA). Three trials of a jump-landing task were performed under each condition before and after induced functional fatigue. The jump-landing task consisted of a single-leg landing onto a force plate from a height equivalent to 50% of each participant's maximal jump height and from a starting position 70 cm from the center of the force plate. Main Outcome Measure(s): Time to stabilization in the anterior-posterior (APTTS) and medial-lateral (MLTTS) directions. Results: For APTTS, a condition-by-time interaction existed (F2,18  =  5.55, P  =  .013). For the AA condition, Tukey post hoc testing revealed faster pretest (2.734 ± 0.331 seconds) APTTS than posttest (3.817 ± 0.263 seconds). Post hoc testing also revealed that the AB condition provided faster APTTS (2.492 ± 0.271 seconds) than AA (3.817 ± 0.263 seconds) and NB (3.341 ± 0.339 seconds) conditions during posttesting. No statistically significant findings were associated with MLTTS. Conclusions: Fatigue increased APTTS for the AA condition. Because the AB condition was more effective than the other 2 conditions during the posttesting, the AB appears to be the best option for providing dynamic stability in the anterior-posterior direction during a landing task. PMID:18345341

Influence of blood lipids on global coagulation test results.

PubMed

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung

2015-01-01

High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

Influence of Blood Lipids on Global Coagulation Test Results

PubMed Central

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon

2015-01-01

Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). Results The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. Conclusion High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels. PMID:25553275

Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial.

PubMed

Beiderlinden, Martin; Werner, Patrick; Bahlmann, Astrid; Kemper, Johann; Brezina, Tobias; Schäfer, Maximilian; Görlinger, Klaus; Seidel, Holger; Kienbaum, Peter; Treschan, Tanja A

2018-02-09

Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients. This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor. To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] μg/ml argatroban and 0.17 [0.1-0.32] μg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs. In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT. ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.

Measurement of rivaroxaban concentrations demonstrates lack of clinical utility of a PT, dPT and APTT test in estimating levels.

PubMed

Thom, I; Cameron, G; Robertson, D; Watson, H G

2018-05-02

Rivaroxaban concentrations were measured in 127 inpatient samples using an HPLC-MS/MS assay. We compared this measurement with a calibrated anti-Xa assay and performed PT, aPTT and dilute PT tests to assess the value of clot-based assays in clinical decision-making. The correlation between the anti-Xa assay and the HPLC-MS/MS at therapeutic concentrations was strong (R 2  = 0.98). The PT, RecombiPlasTin 2G, and aPTT, Actin FS, showed a linear dose-response but poor correlation (R 2  = 0.32 and 0.44, respectively) and at dilutions of 1 in 150 to 1 in 750 the dilute PT assay also showed poor correlation with rivaroxaban concentrations measured by specific assays. A normal PT or aPTT alone did not identify a likely safe rivaroxaban concentration to allow surgery or invasive procedures, but the combination of normal PT and aPTT identified a group of patients with rivaroxaban levels less than 90 ng/mL. Combined normal PT and aPTT had specificity and sensitivity of 0.97 (95% CI 0.92-0.99) and 0.37 (95% CI 0.1-0.74) for a rivaroxaban concentration < 32 ng/mL. The PT and aPTT show poor correlation with rivaroxaban levels measured by calibrated anti-Xa and HPLC-MS/MS assays. A normal combined PT and APTT identified low rivaroxaban levels with high specificity but lacked sensitivity. The dPT assay at several dilutions could not be used to quantify rivaroxaban in clinical samples. The utility of these PT, aPTT and dilute PT assays in a clinical setting is very limited, and results generated must be interpreted with caution. © 2018 John Wiley & Sons Ltd.

Association between Activated Partial Thromboplastin Time and the Amount of Infused Heparin at Bone Marrow Transplantation.

PubMed

Kusuda, Machiko; Kimura, Shun-Ichi; Misaki, Yukiko; Yoshimura, Kazuki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Ugai, Tomotaka; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Tanihara, Aki; Kanda, Yoshinobu

2018-03-27

The actual heparin concentration of harvested allogeneic bone marrow varies among harvest centers. We monitor the activated partial thromboplastin time (APTT) of the patient during bone marrow infusion and administer prophylactic protamine according to the APTT. We retrospectively reviewed the charts of consecutive patients who underwent bone marrow transplantation without bone marrow processing at our center between April 2007 and March 2016 (n = 94). APTT was monitored during marrow transfusion in 52 patients. We analyzed the relationship between the APTT ratio and several parameters related to heparin administration. As a result, the weight-based heparin administration rate (U/kg/hour) seemed to be more closely related to the APTT ratio (r = .38, P = .005) than to the total amount of heparin. There was no significant correlation between the APTT ratio and renal or liver function. Bleeding complications during and early after infusion were seen in 3 of 52 patients, and included intracranial, nasal, and punctured-skin bleeding. The APTT ratio during transfusion was over 5.88 in the former 2 patients and 2.14 in the latter. All of these patients recovered without sequelae. In conclusion, slow bone marrow infusion is recommended to decrease the weight-based heparin administration rate when the heparin concentration per patient body weight is high. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed Using Destiny Plus.

PubMed

Arslan, Fatma Demet; Serdar, Muhittin; Merve Ari, Elif; Onur Oztan, Mustafa; Hikmet Kozcu, Sureyya; Tarhan, Huseyin; Cakmak, Ozgur; Zeytinli, Merve; Yasar Ellidag, Hamit

2016-06-01

In order to apply the right treatment for hemostatic disorders in pediatric patients, laboratory data should be interpreted with age-appropriate reference ranges. The purpose of this study was to determining age-dependent reference range values for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests. A total of 320 volunteers were included in the study with the following ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11 - 17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a survey to exclude hemostatic system disorder. Using a nonparametric method, the lower and upper limits, including 95% distribution and 90% confidence intervals, were calculated. No statistically significant differences were found between PT and aPTT values in the groups consisting of children. Thus, the reference ranges were separated into child and adult age groups. PT and aPTT values were significantly higher in the children than in the adults. Fibrinogen values in the 6 - 10 age group and the adult age group were significantly higher than in the other groups. D-dimer levels were significantly lower in those aged 2 - 17; thus, a separate reference range was established. These results support other findings related to developmental hemostasis, confirming that adult and pediatric age groups should be evaluated using different reference ranges.

Effect of rivaroxaban on blood coagulation using the viscoelastic coagulation test ROTEM™.

PubMed

Casutt, M; Konrad, C; Schuepfer, G

2012-11-01

This study investigated the influence of the oral direct inhibitor of factor Xa rivaroxaban on blood coagulation measured by rotation thrombelastometry ROTEM™. Blood was obtained from 11 healthy male volunteers before and 2.5 h after oral administration of 10 mg rivaroxaban. In addition to standard coagulation tests clot formation was measured by ROTEM™ analyzing extrinsic (Extem) and intrinsic thrombelastometry (Intem). Significant differences to the baseline values were found in the Extem clotting time (Extem-CT, 58 ± 9 s and 87 ± 17 s, p < 0.01), Intem-CT (194 ± 26 s and 239 ± 43 s; p = 0.02), prothrombin time (PT, 86 ± 9% and 67 ± 7%; p < 0.01) and activated partial thromboplastin time (aPTT, 28 ± 1 s and 35 ± 2 s; p < 0.01). There was a low correlation between Extem-CT and PT as well as between Intem-CT and aPTT before and after rivaroxaban intake. The receiver operating characteristic curve (ROC) analysis determined aPTT to be the most appropriate parameter for the prediction of rivaroxaban-induced anticoagulation, Intem-CT and Extem-CT proved to be moderate tests and PT had no significance in the prediction of rivaroxaban-induced anticoagulation. Of utmost clinical importance was the fact that rivaroxaban treated patients could still show normal ROTEM™ values. Thus, ROTEM™ cannot be a suitable test method to exclude inhibition of blood coagulation by rivaroxaban.

Short-term effect of dark chocolate consumption on routine haemostasis testing.

PubMed

Montagnana, Martina; Danese, Elisa; Salvagno, Gian Luca; Lippi, Giuseppe

2017-08-01

This experimental study was designed to investigate the sort-term impact of dark chocolate ingestion on routine haemostasis tests in healthy volunteers. The study population consisted in 15 healthy male volunteers who ingested 50 g of 90% cocoa chocolate within 3-5 min. Blood was drawn early in the morning, immediately before chocolate ingestion and 4 h afterwards, for assessment of activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen. A significant increase of triglycerides (1.4 ± 0.6 versus 1.0 ± 0.5 mmol/L; p < .001), APTT (32.1 ± 2.2 versus 31.1 ± 2.0 s; p < .001) and PT (9.8 ± 0.5 versus 9.7 ± 0.4 s; p = .008) was observed 4 h after ingestion of dark chocolate, whereas fibrinogen values remained unchanged (2.6 ± 0.5 versus 2.5 ± 0.5 g/L; p = .063). Overall, we observed a mean percentage increase of 3.1% for APTT and 1.2% for PT. These results suggest that dark chocolate intake may have an impact on secondary haemostasis.

Stability enhanced, repeatability improved Parylene-C passivated on QCM sensor for aPTT measurement.

PubMed

Yang, Yuchen; Zhang, Wei; Guo, Zhen; Zhang, Zhiqi; Zhu, Hongnan; Yan, Ruhong; Zhou, Lianqun

2017-12-15

Determination of blood clotting time is essential in monitoring therapeutic anticoagulants. In this work, Parylene-C passivated on quartz crystal microbalance (P-QCM) was developed for the activated partial thromboplastin time (aPTT) measurement. Compared with typical QCM, P-QCM possessed a hydrophobic surface and sensitive frequency response to viscoelastic variations on electrode surface. Fibrin could be adsorbed effectively, due to the hydrophobicity of the P-QCM surface. Comparing with typical QCM, the peak-to-peak value (PPV) of P-QCM was increased by 1.94% ± 0.63%, which indicated enhancement of signal-to-noise ratio. For P-QCM, the coefficient of variation (CV) of frequency decrease and aPTT were 2.58% and 1.24% separately, which demonstrated improvement of stability and reproducibility. Moreover, compared with SYSMEX CS 2000i haematology analyzer, clinical coefficient index (R 2 ) was 0.983. In conclusion, P-QCM exhibited potential for improving stability, reproducibility and linearity of piezoelectric sensors, and might be more promising for point of care testing (POCT) applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of saline or albumin resuscitation on standard coagulation tests.

PubMed

Bellomo, Rinaldo; Morimatsu, Hiroshi; Presneill, Jeff; French, Craig; Cole, Louise; Story, David; Uchino, Shigehiko; Naka, Toshio; Finfer, Simon; Cooper, D James; Myburgh, John

2009-12-01

To explore whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in routine clinical coagulation tests. Substudy from a large double-blind randomised controlled trial, the SAFE (Saline versus Albumin Fluid Evaluation) study. Three general intensive care units. Cohort of 687 critically ill patients. We randomly allocated patients to receive either 4% human albumin or normal saline for fluid resuscitation, and collected demographic and haematological data. Albumin was administered to 338 patients and saline to 349. At baseline, the two groups had similar mean activated partial thromboplastin time (APTT) of 37.2 s (albumin) v 39.1 s (saline); mean international normalised ratio (INR) of 1.38 v 1.34, and mean platelet count of 244 x 10(9)/L v 249 x 10(9)/L. After randomisation, during the first day of treatment, the APTT in the albumin group was prolonged by a mean of 2.7 s, but shortened slightly by a mean of -0.9 s in the saline group. The INR did not change in either group, while the platelet count decreased transiently in both groups. Using multivariate analysis of covariance to account for baseline coagulation status, albumin fluid resuscitation (P = 0.01) and a greater overall volume of resuscitation (P = 0.03) were independently associated with prolongation of APTT during the first day. Administration of albumin or of larger fluid volumes is associated with a prolongation of APTT. In ICU patients, the choice and amount of resuscitation fluid may affect a routinely used coagulation test.

What Are Anticoagulants and Antiplatelet Agents?

MedlinePlus

... activated partial thromboplastin time (aPTT) test. • Never take aspirin with anticoagulants unless your doctor tells you to. • ... before taking other medicines or supplements, such as aspirin, vitamins, cold medicine, pain medicine, sleeping pills or ...

Impact of different storage times at room temperature of unspun citrated blood samples on routine coagulation tests results. Results of a bicenter study and review of the literature.

PubMed

Toulon, P; Metge, S; Hangard, M; Zwahlen, S; Piaulenne, S; Besson, V

2017-10-01

A maximum delay between blood collection and coagulation testing of 4 hours is recommended by most guidelines. As information on optimal storage times is limited, we investigated the potential effect of different storage times of unspun tubes, that is, ≤2, 4, 6, and 8 hours, on routine coagulation test results. Four evacuated polymer tubes containing 0.109 mol/L tri-Na citrate were drawn from 144 patients, including 39 patients on vitamin K-antagonists. Except for storage time, all tubes underwent the same preanalytical process. Prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, factor V (FV), FVIII, and D-dimer were evaluated in two centers using the same technical conditions. Analytical comparison of aPTT, fibrinogen, FV, and FVIII results evaluated after prolonged storage times vs a <2-hours storage demonstrated significant difference, whereas PT/INR and D-dimer remained unchanged up to 8 hours. Mean bias between test results obtained after prolonged storage times remained below the desirable values for all studied parameters except for FVIII evaluated after 6- and 8-hours storages, but only in patients with FVIII above 100 IU/dL. Even though the corresponding bias of -5.2% and -8.5%, respectively, remained within the GEHT recommended limits of variation, its evaluation after an 8-hours storage could lead to significant underestimation of FVIII. These results suggest that, in the studied technical conditions, PT/INR, aPTT, fibrinogen, FV, and D-dimer can be reliably evaluated in tubes stored unspun at room temperature for up to 8 hours after blood collection. That optimal delay should be of 6 hours for FVIII. © 2017 The Authors. International Journal of Laboratory Hematology Published by John Wiley & Sons Ltd.

Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed Using Destiny Plus

PubMed Central

Arslan, Fatma Demet; Serdar, Muhittin; Merve Ari, Elif; Onur Oztan, Mustafa; Hikmet Kozcu, Sureyya; Tarhan, Huseyin; Cakmak, Ozgur; Zeytinli, Merve; Yasar Ellidag, Hamit

2016-01-01

Background In order to apply the right treatment for hemostatic disorders in pediatric patients, laboratory data should be interpreted with age-appropriate reference ranges. Objectives The purpose of this study was to determining age-dependent reference range values for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests. Materials and Methods A total of 320 volunteers were included in the study with the following ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11 - 17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a survey to exclude hemostatic system disorder. Using a nonparametric method, the lower and upper limits, including 95% distribution and 90% confidence intervals, were calculated. Results No statistically significant differences were found between PT and aPTT values in the groups consisting of children. Thus, the reference ranges were separated into child and adult age groups. PT and aPTT values were significantly higher in the children than in the adults. Fibrinogen values in the 6 - 10 age group and the adult age group were significantly higher than in the other groups. D-dimer levels were significantly lower in those aged 2 - 17; thus, a separate reference range was established. Conclusions These results support other findings related to developmental hemostasis, confirming that adult and pediatric age groups should be evaluated using different reference ranges. PMID:27617078

Unsuitability of evacuated tubes for monitoring heparin therapy by activated partial thromboplastin time.

PubMed Central

Heyns, A D; van den Berg, D J; Kleynhans, P H; du Toit, P W

1981-01-01

Activated partial thromboplastin times (APTT) for monitoring heparin therapy for venous thromboembolism tended to be inappropriately short if blood was collected in commercially available evacuated glass tubes. Five types of evacuated tubes marketed under the trade names Vacutainer and Venoject were examined. The APTT of heparinized blood collected in these tubes correlated poorly (r = 0.04 to 4 = 0.25) with that of blood samples from the same patients collected in plastic tubes. Most of the evacuated tube APTT were shorter than that of blood collected in plastic or siliconised glass tubes, but the results were unpredictable and varied from tube to tube and from batch to batch. This effect on heparin is apparently due to an unidentified substances which is eluted from the rubber stoppers of the tubes. Heparin control according to the APTT blood collected in these evacuated tubes is hazardous. PMID:7462439

Coagulation Testing in the Core Laboratory.

PubMed

Winter, William E; Flax, Sherri D; Harris, Neil S

2017-11-08

Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors.In vitro the intrinsic pathway is initiated when fresh whole blood is placed in a glass tube. The negative charge of the glass initiates the "contact pathway" where FXII is activated and then FXIa cleaves FIX to FIXa. The extrinsic pathway is triggered when tissue factor, phospholipid and calcium are added to plasma anticoagulated with citrate. In vitro, FVII is activated to FVIIa, and TF-FVIIa preferentially converts FX to FXa activating the common pathway.The prothrombin time is commonly used to monitor warfarin anticoagulant therapy. To correct for differences in reagent and instrument, the international normalized ratio was developed to improve standardization of PT reporting globally. The activated partial thromboplastin time (aPTT) is used to evaluate the intrinsic and common pathways of coagulation. The aPTT is useful clinically as a screening test for inherited and acquired factor deficiencies as well as to monitor unfractionated heparin therapy although the anti-Xa assay is now the preferred measure of the effects of unfractionated heparin. The Clauss assay is the most commonly performed fibrinogen assay and uses diluted plasma where clotting is initiated with a high concentration of reagent thrombin.The mixing study assists in the assessment of an abnormally prolonged PT or aPTT. An equal volume of citrated patient plasma is mixed with normal pooled plasma and the PT or aPTT are repeated on the 1:1 mix. Factor activity assays are most commonly performed as a one-stage assay. The patient's citrated plasma is diluted and mixed 1-to-1 with a single factor-deficient substrate plasma. A PT or aPTT is performed on the above mix, depending on the factor being tested.Factor inhibitors are antibodies that are most commonly diagnosed in male patients with severe hemophilia A (FVIII deficiency) where they are induced by factor replacement therapy.Factor inhibitors can also appear in the form of spontaneous autoantibodies in both male and female individuals who were previously well. This is an autoimmune condition called "acquired hemophilia."Most coagulation laboratories can measure the plasma concentration of VWF protein (VWF antigen) by an immunoturbidimetric technique. Testing the functional activity of VWF, utilizes the drug ristocetin.The state of multimerization of VWF is important and is assessed by electrophoresis on agarose gels. Type 2a and 2b VWD are associated with the lack of intermediate- and high molecular weight multimers.The antiphospholipid syndrome (APLS) is an acquired autoimmune phenomenon associated with an increased incidence of both venous and arterial thromboses, as well as fetal loss. Typically, there is a paradoxical prolongation of the aPTT in the absence of any clinical features of bleeding. This is the so-called "lupus anticoagulant (LA) effect." The laboratory definition of the APLS requires the presence of either a "lupus anticoagulant" or a persistent titer of antiphospholipid antibodies.There are now 2 broad classes of direct-acting oral anticoagulants (DOACs): [1] The oral direct thrombin inhibitors (DTIs) such as dabigatran; and [2] The oral direct factor Xa inhibitors such as rivaroxaban and apixaban. The PT and aPTT are variably affected by the DOACs and are generally unhelpful in monitoring their concentrations. Most importantly, a normal PT or aPTT does NOT exclude the presence of any of the DOACs. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Coagulation indices in very preterm infants from cord blood and postnatal samples.

PubMed

Neary, E; McCallion, N; Kevane, B; Cotter, M; Egan, K; Regan, I; Kirkham, C; Mooney, C; Coulter-Smith, S; Ní Áinle, F

2015-11-01

Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests. The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH). Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates. One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH. In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants. © 2015 International Society on Thrombosis and Haemostasis.

Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models.

PubMed

Maduwage, Kalana P; Scorgie, Fiona E; Lincz, Lisa F; O'Leary, Margaret A; Isbister, Geoffrey K

2016-01-01

Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory.

PubMed

Belley, Adam; Robson, Richard; Francis, John L; Adcock, Dorothy M; Tiefenbacher, Stefan; Rubino, Christopher M; Moeck, Greg; Sylvester, David; Dudley, Michael N; Loutit, Jeffery

2017-02-01

Previous studies have shown that some lipoglycopeptide and lipopeptide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic anti-factor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing. Copyright © 2017 American Society for Microbiology.

Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory

PubMed Central

Robson, Richard; Francis, John L.; Adcock, Dorothy M.; Tiefenbacher, Stefan; Rubino, Christopher M.; Moeck, Greg; Sylvester, David; Dudley, Michael N.; Loutit, Jeffery

2016-01-01

ABSTRACT Previous studies have shown that some lipoglycopeptide and lipopeptide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic anti-factor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing. PMID:27956417

The effects of transport by car on coagulation tests.

PubMed

Ergin, Merve; Erdogan, Serpil; Akturk, Onur; Erel, Ozcan

2017-10-26

This research investigated the effects of the transport of blood samples between centers/laboratories by car on coagulation tests. Five tubes of blood samples were taken from 20 healthy volunteers. The samples consisted of a baseline (control) group, centrifuged and noncentrifuged transported samples; centrifuged and noncentrifuged untransported samples. The groups of centrifuged and noncentrifuged samples were transported by car for 2 h. The centrifuged and noncentrifuged untransported samples were incubated in the laboratory until the transported samples arrived. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests were conducted for all samples. Significant differences between the baseline group and the centrifuged and noncentrifuged transported samples and the noncentrifuged untransported samples were found for APTT levels (p<0.05, for all). In addition, significant mean percentage differences in PT values were found between the baseline group and the noncentrifuged transported samples (p<0.001) and the noncentrifuged untransported samples (p=0.005). The mean level of PT in the noncentrifuged transported samples was outside the upper limit of the clinical decision level. Noncentrifuged transported samples showed clinically significant differences in PT test results that may have stemmed from mechanical agitation during transportation. Therefore, we recommend not transporting noncentrifuged specimens for PT testing by car.

Performance of coagulation tests in patients on therapeutic doses of rivaroxaban. A cross-sectional pharmacodynamic study based on peak and trough plasma levels.

PubMed

Francart, Suzanne J; Hawes, Emily M; Deal, Allison M; Adcock, Dorothy M; Gosselin, Robert; Jeanneret, Cheryl; Friedman, Kenneth D; Moll, Stephan

2014-06-01

Knowledge of anticoagulation status during rivaroxaban therapy is desirable in certain clinical situations. It was the study objective to determine coagulation tests most useful for assessing rivaroxaban's anticoagulant effect. Peak and trough blood samples from 29 patients taking rivaroxaban 20 mg daily were collected. Mass spectrometry and various coagulation assays were performed. "On-therapy range" was defined as the rivaroxaban concentrations determined by LC-MS/MS. A "misprediction percentage" was calculated based on how often results of each coagulation assay were in the normal reference range, while the rivaroxaban concentration was in the "on-therapy" range. The on-therapy range was 8.9-660 ng/ml. The misprediction percentages for prothrombin time (PT) and activated partial thromboplastin time (aPTT), using multiple reagents and coagulometers, ranged from 10%-52% and 31%-59%, respectively. PT, aPTT and activated clotting time (ACT) were insensitive to trough rivaroxaban: 59%, 62%, and 80% of samples had a normal result, respectively. Over 95% of PT and ACT values were elevated at peak. Four different rivaroxaban calibrated anti-Xa assays had R² values >0.98, demonstrating strong correlations with rivaroxaban drug levels. In conclusion, PT, aPTT and ACT are often normal in patients on therapeutic doses of rivaroxaban. However, PT and ACT may have clinical utility at higher drug plasma levels. Rivaroxaban calibrated anti-factor Xa assays can accurately identify low and high on-therapy rivaroxaban drug levels and, therefore, have superior utility in all clinical situations where assessment of anticoagulation status may be beneficial.

In Vivo Bleeding Time and In Vitro Thrombelastography Measurements are Better Indicators of Dilutional Hypothermic Coagulopathy Than Prothrombin Time

DTIC Science & Technology

2007-06-01

of increased bruising, hematomas, and oozing from the recent surgical sites, or in massive hemorrhage from silent, pre-existing lesions such as peptic ... ulcers . Severe reduction of the vitamin K-dependent coagulation factors II, VII, IX, and X prolongs both PT and aPTT tests. Treatment with sodium

Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

PubMed

Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

2016-01-01

To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

PubMed

Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen

2016-06-01

Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (-7%, P = 0.009; -7.8%, P < 0.0001; -6.9%, P < 0.0001; and -4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

A Pilot Study of Tissue Factor-Tissue Factor Pathway Inhibitor Axis and Other Selected Coagulation Parameters in Broiler Chickens Administered in Ovo with Selected Prebiotics*.

PubMed

Buzala, Mateusz; Ponczek, Michal Blazej; Slomka, Artur; Roslewska, Aleksandra; Janicki, Bogdan; Zekanowska, Ewa; Bednarczyk, Marek

The tissue factor (TF) - tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics on the hemostasis system has not been characterized in poultry yet. This study was designed to determine the effect of in ovo administration ofprebiotics on blood coagulation parameters of broiler chickens depending on their age. The study was conducted with 180 broiler chick embryos, the air cells of which were injected on day 12 of incubation with prebiotics (experimental groups: Bi2tos, DiNovoo and RFO) or physiological saline solution (control group). At 1, 21 and 42 days of rearing, blood was sampled from 15 broiler chickens from each group. An enzyme immunoassay was performed to determine plasma TF and TFPI levels, and PT, aPTT and PFC were determined in the chicken blood. We demonstrated that: 1) total TF levels increased with age in the experimental groups, 2) prebiotics had no significant effect on TF levels between the groups at a particular age, 3) total TFPI levels differed between both the type of in ovo injected substance and the broiler chicken age, 4) in the control group, PT and aPTT were found to increase with age whilst fibrinogen concentration decreased. The main conclusion from this pilot study is that total TF and TFPI levels change with age, however no clear patterns regarding TFPI were detected yet. The levels of PT, aPTT and PFC varied with the prebiotics administered in ovo as well as with the age of broiler chickens.

Hemostatic abnormalities in dogs with naturally occurring heatstroke.

PubMed

Bruchim, Yaron; Kelmer, Efrat; Cohen, Adar; Codner, Carolina; Segev, Gilad; Aroch, Itamar

2017-05-01

To investigate hemostatic analyte abnormalities and their association with mortality in dogs with naturally occurring heatstroke. Prospective observational study. University teaching hospital. Thirty client-owned dogs with naturally occurring heatstroke. None. Citrated and EDTA blood samples were collected at presentation and at 4, 12, 24, 36, and 48 hours postpresentation (PP). Hemostatic tests performed included platelet count, prothrombin and activated partial thromboplastin times (PT and aPTT, respectively), antithrombin activity (ATA), total protein C activity (tPCA), fibrinogen, and D-dimer concentrations. The overall survival rate was 60% (18/30 dogs). Older age, higher heart rate and rectal temperature at presentation, and time from onset of clinical signs to presentation were significantly associated with mortality. Hemostatic analytes at presentation were not associated with mortality. Prolonged PT and aPTT at 12-24 hours PP, lower tPCA at 12 hours PP, and hypofibrinogenemia at 24 hours PP were significantly (P < 0.05) associated with mortality. Increased D-dimer concentration and low ATA were common at all time points, but were not associated with mortality. The frequency of disseminated intravascular coagulation (DIC) increased in nonsurvivors throughout hospitalization, but the development of DIC was not associated with mortality. The number of abnormal coagulation disturbances during the first 24 hours was significantly higher in nonsurvivors (P = 0.04). Hemostatic derangements are common in dogs with naturally occurring heatstroke. Alterations in PT, aPTT, tPCA, and fibrinogen concentrations appear to be associated with the outcome at 12-24 hours PP, exemplifying the need for serial measurement of multiple laboratory hemostatic tests during hospitalization, even when within reference interval on presentation. The development of DIC, as defined in this cohort, was not associated with mortality; however, nonsurvivors had significantly more coagulation abnormalities during the first 24 hours PP. © Veterinary Emergency and Critical Care Society 2017.

In vitro anticoagulant and antioxidant activities of Jatropha gossypiifolia L. (Euphorbiaceae) leaves aiming therapeutical applications.

PubMed

Félix-Silva, Juliana; Souza, Thiago; Camara, Rafael Barros Gomes; Cabral, Bárbara; Silva-Júnior, Arnóbio Antônio; Rebecchi, Ivanise Marina Moretti; Zucolotto, Silvana Maria; Rocha, Hugo Alexandre Oliveira; Fernandes-Pedrosa, Matheus de Freitas

2014-10-20

Jatropha gossypiifolia L. (Euphorbiaceae) is a medicinal plant largely used in folk medicine. Teas from the leaves are popularly used as an antithrombotic agent and the branches are frequently employed as a "thick blood" agent. Considering that the anticoagulant activity associated with antioxidant properties could be beneficial for various cardiovascular diseases, this study's aim is the evaluation of anticoagulant and antioxidant activities of J. gossypiifolia leaves, seeking new therapeutic purposes for this plant. The aqueous leaf crude extract (CE) was prepared by decoction and was fractionated by liquid-liquid partition with solvents of increasing polarity. The phytochemical analysis was performed by thin layer chromatography (TLC) and by the spectrophotometric quantification of sugars, proteins and phenolic compounds. The anticoagulant activity was evaluated by prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. The capacity to act in the fibrinolytic system (fibrinolytic and fibrinogenolytic activities) was also assessed. The antioxidant activity was evaluated by total antioxidant capacity, reducing power, copper chelating activity, iron chelating activity, hydroxyl radical scavenging activity and superoxide radical scavenging assays. The potential toxicity was evaluated using hemolytic assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay on HEK-293 cells. CE showed significant anticoagulant activity in aPTT test, while no action was observed in PT test, suggesting a preferential action toward the intrinsic and/or common pathway of coagulation. No effect was observed in the fibrinolytic system. Using the aPTT test, it was observed that the residual aqueous (RA) fraction was the most active, being two times more active than CE. RA presented very significant antioxidant activity in all models tested comparable to or even higher than CE. Regarding the safety, CE and RA did not produce significant cytotoxicity in both tests employed. Phytochemical analysis revealed the presence of alkaloids, flavonoids, proteins, tannins, steroids and/or terpenoids and sugars. CE and RA possessed significant anticoagulant and antioxidant activity and absence of cytotoxic effect in vitro, thus showing the potential of the plant, especially RA fraction, as a new source of bioactive molecules for therapeutic purposes, with particular emphasis on the treatment of cardiovascular diseases.

Sodium citrate vacuum tubes validation: preventing preanalytical variability in routine coagulation testing.

PubMed

Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Picheth, Geraldo; Guidi, Gian Cesare

2013-04-01

Sometimes in-vitro diagnostic devices (e.g. blood collection tubes) are not validated before use or when the producer's brand is changed. The aim of this study was to validate five brands of sodium citrate vacuum tubes. Blood specimens from 50 volunteers were collected in five different tube brands (I: Venosafe, II: VACUETTE, III: BD Vacutainer, IV: LABOR IMPORT and V: S-Monovette). Routine coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen (FIB)] were performed on ACL TOP instrument using HemosIL reagents. The significance of the differences between samples was assessed by paired Student's t-test, set at P < 0.005. Significant differences were observed for: PT when comparing I vs. II, I vs. III, I vs. V, II vs. III, II vs. IV, II vs. V, III vs. IV, III vs. V and IV vs. V; aPTT when comparing I vs. II, I vs. III, I vs. IV, II vs. IV, III vs. IV and IV vs. V. No differences were observed among brands for FIB determination. We suggest that every laboratory management should both standardize the procedures and frequently evaluate the quality of in-vitro diagnostic devices.

Could light meal jeopardize laboratory coagulation tests?

PubMed

Lima-Oliveira, Gabriel; Salvagno, Gian Luca; Lippi, Giuseppe; Danese, Elisa; Gelati, Matteo; Montagnana, Martina; Picheth, Geraldo; Guidi, Gian Cesare

2014-01-01

Presently the necessity of fasting time for coagulation tests is not standardized. Our hypothesis is that this can harm patient safety. This study is aimed at evaluating whether a light meal (i.e. breakfast) can jeopardize laboratory coagulation tests. A blood sample was firstly collected from 17 fasting volunteers (12 h). Immediately after blood collection, the volunteers consumed a light meal. Then samples were collected at 1, 2 and 4 h after the meal. Coagulation tests included: activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fbg), antithrombin III (AT), protein C (PC) and protein S (PS). Differences between samples were assessed by Wilcoxon ranked-pairs test. The level of statistical significance was set at P < 0.05. Mean % differences were determined and differences between and baseline and 1, 2 and 4h samples were compared with reference change value (RCV). A significantly higher % activity of AT was observed at 1 h and 4 h after meal vs. baseline specimen [113 (104-117) and 111 (107-120) vs. 109 (102-118), respectively; P = 0.029 and P = 0.016]. APTT at 2 h was found significantly lower than baseline samples [32.0 (29.9-34.8) vs. 34.1 (32.2-35.2), respectively; P = 0.041]. The results of both Fbg and PS tests were not influenced by a light meal. Furthermore, no coagulation tests had significant variation after comparison with RCV. A light meal does not influence the laboratory coagulation tests we assessed, but we suggest that the laboratory quality managers standardize the fasting time for all blood tests at 12 hours, to completely metabolize the lipids intake.

The mechanical effect of anterior pelvic tilt taping on slump sitting by seated workers.

PubMed

Lee, Jung-Hoon; Yoo, Won-Gyu

2011-01-01

The objectives of this study were to determine whether there is a change in the pelvic inclination after about 30 min of slump sitting by seated workers, and if so, to determine whether these changes can be prevented by the application of anterior pelvic tilt taping (APTT). The subjects who consented to participate in the experiment were randomly allocated to two groups: no-APTT group and APTT group. The no-APTT group performed slump sitting for 30 min, and the both pelvic inclinations were remeasured. In the APTT group, the both pelvic inclinations were measured immediately after the application of the APTT, and then again after 30 min of slump sitting. The both pelvic inclinations in the no-APTT group were significantly decreased (p<0.05) after they returned to the upright standing posture. The both pelvic inclinations in the APTT group were significantly increased immediately after the APTT (p<0.05), and this increase was maintained when returning to the upright standing posture after 30 min of slump sitting (p>0.05). We suggest that APTT can be applied as an auxiliary treatment method for preventing changes in pelvic inclination and musculoskeletal problems of low back area by awkward sitting posture in the seated worker.

An Easy Method to Eliminate the Effect of Lupus Anticoagulants in the Coagulation Factor Assay.

PubMed

Tang, Ning; Yin, Shiyu

2016-07-01

To build and evaluate intrinsic coagulation factor assays which can eliminate the effect of lupus anticoagulants (LAC). Commercial silica clotting time confirmatory (SCT-C) reagent containing sufficient synthetic phospholipid and routine activated partial thromboplastin time (APTT) reagent were each used for one-stage detection of FVIII, FIX, and FXI activities, in samples with or without LAC, and the results were compared. For samples without LAC, consistent results of FVIII, FIX, and FXI using both SCT-C reagent and APTT reagent were obtained. For samples with LAC, the assays with SCT-C reagent not only could eliminate the effect of strong lupus anticoagulants but also needed fewer dilutions than that with routine APTT reagent. The intrinsic factor detections by SCT-C reagent are credible and convenient to be used for samples with LAC.

Investigations on blood coagulation in the green iguana (Iguana iguana).

PubMed

Kubalek, S; Mischke, R; Fehr, M

2002-05-01

The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, kaolin clotting time (KCT), dilute Russell's viper venom time (DRVVT) and reptilase time, as well as five different plasma fibrinogen assays [gravimetry, Jacobsson method (extinction at 280 nm), Millar method (heat precipitation), kinetic turbidometry, Clauss method] and resonance thrombography were performed in 26 clinically healthy green iguanas. All assays were carried out in comparison with pooled normal canine plasma. In iguana plasma, the PT [median (x0.50) = 453-831 s, dependent on the reagent], APTT (x0.50 = 170-242 s, dependent on the reagent), thrombin time (x0.50 = 118 - > 1000 s, dependent on thrombin activity), KCT (x0.50 = 274 s), DRVVT (x0.50 = 349 s) and reptilase time (all samples > 1000 s) were widely scattered at the limit of measurability. Only fibrinogen concentrations measured using the Jacobsson method (x0.50 = 4.40 g/l) correlated well (r = 0.91) with gravimetry (x0.50 = 4.22 g/l). The results of this study indicate a limited suitability and a confined diagnostic significance of the selected methods in the green iguana. This may be caused by the species specificity of certain components of the reagents used, as well as a less optimal test system, i.e. relationship of test reagent to clotting factor concentrations in iguana plasma.

Importance of fibrinogen in dilutional coagulopathy after neurosurgical procedures: A descriptive study.

PubMed

Nair, Shalini; Nair, Bijesh Ravindran; Vidyasagar, Ajay; Joseph, Mathew

2016-08-01

The routine management of coagulopathy during surgery involves assessing haemoglobin, prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets. Correction of these parameters involves administration of blood, fresh frozen plasma and platelet concentrates. The study was aimed at identifying the most common coagulation abnormality during neurosurgical procedures and the treatment of dilutional coagulopathy with blood components. During 2 years period, all adult patients undergoing neurosurgical procedures who were transfused two or more units of red cells were prospectively evaluated for the presence of a coagulopathy. PT, aPTT, platelet count and fibrinogen levels were estimated before starting a component therapy. After assessing PT, aPTT, platelet count and fibrinogen levels following two or more blood transfusions, thirty patients were found to have at least one abnormal parameter that required administration of a blood product. The most common abnormality was a low fibrinogen level, seen in 26 patients; this was the only abnormality in three patients. No patient was found to have an abnormal PT or aPTT without either the fibrinogen concentration or platelet count or both being low. Low fibrinogen concentration was the most common coagulation abnormality found after blood transfusions for neurosurgical procedures.

Laboratory heterogeneity of the lupus anticoagulant: a multicentre study using different clotting assays on a panel of 78 samples. Hemostasis Committee of the "Société Française de Biologie Clinique".

PubMed

1992-05-15

The laboratory heterogeneity of the lupus anticoagulant (LA) was investigated in a multicentre study using a panel of 78 plasma samples diagnosed as containing a LA. Consecutive samples were collected by 12 participants using various screening tests, and sent to 7 laboratories which performed one or more clotting assays among the following: activated partial thromboplastin time (APTT), dilute Russell viper venom time, kaolin clotting time (KCT), dilute tissue thromboplastin time (dTTI) and a platelet neutralization test. For APTT and dTTI, 10 versions of these tests including standard and mixing procedures were carried out. They varied by reagents, phospholipid concentration or methodology. Cut-off times were determined for each test by comparing the results of the panel to those of a control population. When the data of all clotting assays were pooled, 70 of the 78 selected plasmas were considered to contain LA, 15 of them having a low-titer inhibitor. Sensitivity, defined as the proportion of positive results among LA-containing plasmas, varied from 62 to 100% and was positively related to responsiveness (defined as the mean ratio of clotting time to cut-off time). Laboratory heterogeneity of LA-containing plasma was illustrated by a star symbol plot analysis. Different populations of samples, with LA preferentially recognized by one assay (or group of assays) irrespective of the overall sensitivity of this assay, were identified. Multiple component analysis demonstrated the heterogeneity of low-titer inhibitors, which complicates their recognition in routine laboratory investigation.

Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation.

PubMed

Depreter, Barbara; Devreese, Katrien M J

2016-09-01

Lupus anticoagulant (LAC) testing includes a screening, mixing and confirmation step. Although recently published guidelines on LAC testing are a useful step towards standardization, a lack of consensus remains whether to express mixing tests in clotting time (CT) or index of circulating anticoagulant (ICA). The influence of anticoagulant therapy, e.g. vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) on both methods of interpretation remains to be investigated. The objective of this study was to contribute to a simplification and standardization of the LAC three-step interpretation on the level of the mixing test. Samples from 148 consecutive patients with LAC request and prolonged screening step, and 77 samples from patients non-suspicious for LAC treated with VKA (n=37) or DOAC (n=30) were retrospectively evaluated. An activated partial thromboplastin time (aPTT) and dilute Russell's viper venom time (dRVVT) were used for routine LAC testing. The supplemental anticoagulant samples were tested with dRVVT only. We focused on the interpretation differences for mixing tests expressed as CT or ICA and compared the final LAC conclusion within each distinct group of concordant and discordant mixing test results. Mixing test interpretation by CT resulted in 10 (dRVVT) and 16 (aPTT) more LAC positive patients compared to interpretation with ICA. Isolated prolonged dRVVT screen mix ICA results were exclusively observed in samples from VKA-treated patients without suspicion for LAC. We recommend using CT in respect to the 99th percentile cut-off for interpretation of mixing steps in order to reach the highest sensitivity and specificity in LAC detection.

[Comparison of thromboelastography and routine coagulation tests for evaluation of blood coagulation function in patients].

PubMed

Chen, Guan-Yi; Ou Yang, Xi-Lin; Wu, Jing-Hui; Wang, Li-Hua; Yang, Jin-Hua; Gu, Li-Nan; Lu, Zhu-Jie; Zhao, Xiao-Zi

2015-04-01

To investigate the correlation and consistency between thromboelastography(TEG) and routine coagulation tests, and to evaluate the value of the two methods in determining the blood coagulation of patients. The TEG, routine coagulation tests and platelet counts of 182 patients from the Intensive Care Unit(ICU) and Department of Gastroenterology in our hospital from January to September 2014 were performed and analyzed retrospectively for their correlation, Kappa identity test analysis and chi-square test, and the diagnostic sensitivity and specificity of both methods in the patients with bleeding were evaluated. The TEG R time and PT, R time and APTT showed a linear dependence (P<0.01). The relationship between the TEG K value, α-Angle, MA and Fibrinogen showed a linear dependence (P<0.001). And the relationship between the TEG K value, α-Angle, MA and the platelet count were in a linear dependent way (P<0.001). The Kappa values of the TEG R time with PT and APTT were 0.038 (P>0.05) and 0.061 (P>0.05), respectively. The chi-square test values of the TEG R time with PT and APTT were 35.309 (P<0.001) and 15.848 (P<0.001), respectively. The Fibrinogen and the TEG K value, α-Angle, MA value had statistical significance (P<0.001), with a Kappa value of 0.323, 0.288 and 0.427, respectively. The chi-square test values between Fibrinogen and the TEG K value, α-Angle, MA value were not statistically significant, with X2=1.091 (P=0.296), X2=1.361 (P=0.243), X2=0.108 (P=0.742). The Kappa values of the platelet count and the TEG K value, α-Angle, MA value were 0.379, 0.208 and 0.352, respectively, which were also statistically significant difference (P<0.001). The chi-square test values between the platelet count and the TEG K value, α-Angle, MA value showed a statistically significant difference (P<0.001), with X2=37.5, X2=37.23, X2=26.630. The diagnostic sensitivity of the two methods for the patients with bleeding was less than 50%. There was a significant correlation between some TEG parameters and routine coagulation tests, but the consistency is weak. Moreover, the diagnostic sensitivity of two methods in the patients with bleeding is low. It was concluded that the TEG cannot replace the conventional coagulation tests, and the preferable method remains uncertain which could reflect the risk of bleeding.

Autovalidation and automation of the postanalytical phase of routine hematology and coagulation analyses in a university hospital laboratory.

PubMed

Mlinaric, Ana; Milos, Marija; Coen Herak, Désirée; Fucek, Mirjana; Rimac, Vladimira; Zadro, Renata; Rogic, Dunja

2018-02-23

The need to satisfy high-throughput demands for laboratory tests continues to be a challenge. Therefore, we aimed to automate postanalytical phase in hematology and coagulation laboratory by autovalidation of complete blood count (CBC) and routine coagulation test results (prothrombin time [PT], international normalized ratio [PT-INR], activated partial thromboplastin time [APTT], fibrinogen, antithrombin activity [AT] and thrombin time [TT]). Work efficacy and turnaround time (TAT) before and after implementation of automated solutions will be compared. Ordering panels tailored to specific patient populations were implemented. Rerun and reflex testing rules were set in the respective analyzers' software (Coulter DxH Connectivity 1601, Beckman Coulter, FL, USA; AutoAssistant, Siemens Healthcare Diagnostics, Germany), and sample status information was transferred into the laboratory information system. To evaluate if the automation improved TAT and efficacy, data from manually verified results in September and October of 2015 were compared with the corresponding period in 2016 when autovalidation was implemented. Autovalidation rates of 63% for CBC and 65% for routine coagulation test results were achieved. At the TAT of 120 min, the percentage of reported results increased substantially for all analyzed tests, being above 90% for CBC, PT, PT-INR and fibrinogen and 89% for APTT. This output was achieved with three laboratory technicians less compared with the period when the postanalytical phase was not automated. Automation allowed optimized laboratory workflow for specific patient populations, thereby ensuring standardized results reporting. Autovalidation of test results proved to be an efficient tool for improvement of laboratory work efficacy and TAT.

Value of Routine Preoperative Tests for Coagulation Before Elective Cranial Surgery. Results of an Institutional Audit and a Nationwide Survey of Neurosurgical Centers in Pakistan.

PubMed

Akhunzada, Naveed Zaman; Tariq, Muhammad Bilal; Khan, Saad Akhtar; Sattar, Sidra; Tariq, Wajeeha; Shamim, Muhammad Shahzad; Dogar, Samie Asghar

2018-05-03

Routine preoperative blood testing has become a dogma. The general practice is to order preoperative workup as a knee-jerk response rather than individualize it for each patient. The fact that the bleeding brain tends to swell, which coupled with limited options for proximal control, packing, and overall hemostasis, leads to an overemphasis on the preoperative coagulation profile. This is a retrospective review of the medical records of patients admitted at Aga Khan University Hospital from January 2010 to December 2015 for an elective craniotomy. The hospital registry was used to identify files for review. Data were collected on a predefined proforma. A nationwide survey was performed, and 30 neurosurgery centers were contacted across Pakistan to confirm the practice of preoperative workup. The survey revealed that all centers had a similar practice of preoperative workup. This included complete blood count, serum electrolytes, and coagulation profile, including prothrombin time, activated partial thromboplastin time (aPTT), and international normalized ratio (INR). A total of 1800 files were reviewed. Nine (0.5%) patients were found to have deranged clotting profile without any predictive history of clotting derangement; 56% were male and 44% were female. Median age was 32 years with an interquartile range of 27 years. Median aPTT was (40.8 with 20.8 IQR). Median INR was (1.59 with 0.48 IQR). Median blood loss was (400 with 50 IQR). No significant association between coagulation profile (aPTT, INR) and blood loss was found (P = 0.85, r = -0.07). We conclude that patients without a history of coagulopathy and normal physical examination do not require routine coagulation screening before elective craniotomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Structural characterization of coagulant Moringa oleifera Lectin and its effect on hemostatic parameters.

PubMed

Luz, Luciana de Andrade; Silva, Mariana Cristina Cabral; Ferreira, Rodrigo da Silva; Santana, Lucimeire Aparecida; Silva-Lucca, Rosemeire Aparecida; Mentele, Reinhard; Oliva, Maria Luiza Vilela; Paiva, Patricia Maria Guedes; Coelho, Luana Cassandra Breitenbach Barroso

2013-07-01

Lectins are carbohydrate recognition proteins. cMoL, a coagulant Moringa oleifera Lectin, was isolated from seeds of the plant. Structural studies revealed a heat-stable and pH resistant protein with 101 amino acids, 11.67 theoretical pI and 81% similarity with a M. oleifera flocculent protein. Secondary structure content was estimated as 46% α-helix, 12% β-sheets, 17% β-turns and 25% unordered structures belonging to the α/β tertiary structure class. cMoL significantly prolonged the time required for blood coagulation, activated partial thromboplastin (aPTT) and prothrombin times (PT), but was not so effective in prolonging aPTT in asialofetuin presence. cMoL acted as an anticoagulant protein on in vitro blood coagulation parameters and at least on aPTT, the lectin interacted through the carbohydrate recognition domain. Copyright © 2013 Elsevier B.V. All rights reserved.

Neprilysin Inhibits Coagulation through Proteolytic Inactivation of Fibrinogen

PubMed Central

Burrell, Matthew; Henderson, Simon J.; Ravnefjord, Anna; Schweikart, Fritz; Fowler, Susan B.; Witt, Susanne; Hansson, Kenny M.; Webster, Carl I.

2016-01-01

Neprilysin (NEP) is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ), the main pathological component of Alzheimer’s disease (AD). We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT) and activated partial thromboplastin time (APTT). The objective of the current study was to investigate the effect of wild type NEP and the engineered variant on coagulation and define the mechanism by which this effect is mediated. PT and APTT were measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP (HSA-NEPv) as well as in control plasma spiked with wild type or variant enzyme. The coagulation factor targeted by NEP was determined using in vitro prothrombinase, calibrated automated thrombogram (CAT) and fibrin formation assays as well as N-terminal sequencing of fibrinogen treated with the enzyme. We demonstrate that HSA-NEP wild type and HSA-NEPv unexpectedly impaired coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect was mediated through cleavage of the N-termini of the Aα- and Bβ-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. Fibrinogen has therefore been identified for the first time as a substrate for NEP wild type suggesting that the enzyme may have a role in regulating fibrin formation. Reductions in NEP levels observed in AD and cerebral amyloid angiopathy may contribute to neurovascular degeneration observed in these conditions. PMID:27437944

A study on indices of apixaban anticoagulation: A single-center prospective study.

PubMed

Komiyama, Maki; Miyazaki, Yusuke; Wada, Hiromichi; Iguchi, Moritake; Abe, Mitsuru; Ogawa, Hisashi; Akao, Masaharu; Yamakage, Hajime; Satoh-Asahara, Noriko; Sunagawa, Yoichi; Morimoto, Tatsuya; Hasegawa, Koji

2018-05-16

Depending on the characteristics of patients, the blood concentration of apixaban can unexpectedly increase, possibly leading to bleeding events. Anti-FXa activity reflects the apixaban blood concentration; however, measurement of this activity is both time-consuming and expensive. The current study aimed to evaluate the usefulness of routinely measured coagulation indices as future indicators of the efficacy and safety of apixaban. Eighteen nonvalvular atrial fibrillation patients administered apixaban (average, 52.5 days) were prospectively enrolled in our hospital. The prothrombin time (PT) and the activated partial thromboplastin time (APTT) were measured by using the Coagpia® Reagent kits. The PT and the APTT increased significantly after the administration of apixaban (PT: p < 0.001, APTT: p < 0.001). While the apixaban plasma concentration by evaluating anti-FXa activity was not significantly correlated with the APTT after administration of apixaban, the concentration closely correlated with the PT (β = 0.765, p < 0.001) and the percentage change in the PT from before and after the administration of apixaban (β = 0.650, p = 0.005). The usefulness of routinely monitoring PT in patients administered apixaban during the ordinary clinical medicine should be investigated further by large clinical trials. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Acetaminophen and Meloxicam Inhibit Platelet Aggregation and Coagulation in Blood Samples from Humans

DTIC Science & Technology

2014-01-01

not change by acetaminophen at any of the tested doses. Consistent to our results, prolonged aPTT from meloxicam has been reported in dogs undergoing...orthopedic surgery [16] as well as in healthy dogs [17]. The significant changes in aPTT and lack of changes in PT by meloxicam suggest that melox- icam...Papazoglou LG, Rallis T, Tsimopoulos G, Adamama-Moraitou K, Tea A. Effects of meloxicam on the haemostatic profile of dogs undergoing orthopaedic

Lack of grading agreement among international hemostasis external quality assessment programs

PubMed Central

Olson, John D.; Jennings, Ian; Meijer, Piet; Bon, Chantal; Bonar, Roslyn; Favaloro, Emmanuel J.; Higgins, Russell A.; Keeney, Michael; Mammen, Joy; Marlar, Richard A.; Meley, Roland; Nair, Sukesh C.; Nichols, William L.; Raby, Anne; Reverter, Joan C.; Srivastava, Alok; Walker, Isobel

2018-01-01

Laboratory quality programs rely on internal quality control and external quality assessment (EQA). EQA programs provide unknown specimens for the laboratory to test. The laboratory's result is compared with other (peer) laboratories performing the same test. EQA programs assign target values using a variety of methods statistical tools and performance assessment of ‘pass’ or ‘fail’ is made. EQA provider members of the international organization, external quality assurance in thrombosis and hemostasis, took part in a study to compare outcome of performance analysis using the same data set of laboratory results. Eleven EQA organizations using eight different analytical approaches participated. Data for a normal and prolonged activated partial thromboplastin time (aPTT) and a normal and reduced factor VIII (FVIII) from 218 laboratories were sent to the EQA providers who analyzed the data set using their method of evaluation for aPTT and FVIII, determining the performance for each laboratory record in the data set. Providers also summarized their statistical approach to assignment of target values and laboratory performance. Each laboratory record in the data set was graded pass/fail by all EQA providers for each of the four analytes. There was a lack of agreement of pass/fail grading among EQA programs. Discordance in the grading was 17.9 and 11% of normal and prolonged aPTT results, respectively, and 20.2 and 17.4% of normal and reduced FVIII results, respectively. All EQA programs in this study employed statistical methods compliant with the International Standardization Organization (ISO), ISO 13528, yet the evaluation of laboratory results for all four analytes showed remarkable grading discordance. PMID:29232255

A PK-PD model-based assessment of sugammadex effects on coagulation parameters.

PubMed

Bosch, Rolien; van Lierop, Marie-José; de Kam, Pieter-Jan; Kruithof, Annelieke C; Burggraaf, Jacobus; de Greef, Rik; Visser, Sandra A G; Johnson-Levonas, Amy O; Kleijn, Huub-Jan

2016-03-10

Exposure-response analyses of sugammadex on activated partial thromboplastin time (APTT) and prothrombin time international normalized ratio (PT(INR)) were performed using data from two clinical trials in which subjects were co-treated with anti-coagulants, providing a framework to predict these responses in surgical patients on thromboprophylactic doses of low molecular weight or unfractionated heparin. Sugammadex-mediated increases in APTT and PT(INR) were described with a direct effect model, and this relationship was similar in the presence or absence of anti-coagulant therapy in either healthy volunteers or surgical patients. In surgical patients on thromboprophylactic therapy, model-based predictions showed 13.1% and 22.3% increases in respectively APTT and PT(INR) within 30min after administration of 16mg/kg sugammadex. These increases remain below thresholds seen following treatment with standard anti-coagulant therapy and were predicted to be short-lived paralleling the rapid decline in sugammadex plasma concentrations. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Are laboratory tests always needed? Frequency and causes of laboratory overuse in a hospital setting.

PubMed

Cadamuro, Janne; Gaksch, Martin; Wiedemann, Helmut; Lippi, Giuseppe; von Meyer, Alexander; Pertersmann, Astrid; Auer, Simon; Mrazek, Cornelia; Kipman, Ulrike; Felder, Thomas K; Oberkofler, Hannes; Haschke-Becher, Elisabeth

2018-04-01

Inappropriate utilization of laboratory resources is an increasing concern especially in high-throughput facilities. Until now, no reliable information has been published addressing to which extent laboratory results are actually used for clinical decision-making. Therefore, we aimed to close this gap using a novel retrospective approach including a survey of clinicians and nurses. We retrospectively evaluated the number of re-orders for potassium (K), lactate dehydrogenase (LD), aspartate-aminotransferase (AST), activated partial thromboplastin-time (APTT) and prothrombin-time/INR (PT/INR), after the initial order had to be cancelled due to preanalytical non-conformities. We analyzed subgroups regarding time to re-order, ward and sample priority (urgent vs. routine). Subsequently, we surveyed clinicians and nurses, asking for their estimate of the amount of failed re-orders as well as for possible reasons. From initially cancelled tests, only ~20% of K, LD, AST and ~30% of APTT and PT/INR tests were re-ordered within 24 h. 70% of the investigated clinical chemistry and 60% of coagulation tests were re-ordered one week after cancellation or not at all. Survey participants quite accurately estimated these numbers. Routine laboratory panels, short stay of out-patients, obsolete test results and avoiding additional phlebotomies were the main reasons for not re-ordering cancelled tests. Overall, 60-70% of test results in the investigated assays ordered in a high throughput laboratory are potentially inappropriate or of doubtful clinically importance. Although clinicians and nurses are aware of this situation, it is the duty of laboratory specialists to overcome overutilization in close collaboration with all involved healthcare workers. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effects of hemolysis and lipemia interference on kaolin-activated thromboelastography, and comparison with conventional coagulation tests.

PubMed

Tang, Ning; Jin, Xi; Sun, Ziyong; Jian, Cui

2017-04-01

The effects of hemolysis and lipemia on thromboelastography (TEG) analysis have been scarcely evaluated in human samples, and neglected in clinical practice. We aimed to investigate the effects of in vitro mechanical hemolysis and lipemia on TEG analysis and conventional coagulation tests. Twenty-four healthy volunteers were enrolled in the study. Besides the controls, three groups with slight, moderate and severe mechanical hemolysis were constituted according to free hemoglobin (Hb) concentrations of 0.5-1.0, 2.0-6.0 and 7.0-13.0 g/L, respectively; and three groups with mild, moderate and high lipemia were established according to triglyceride concentrations of ∼6.0, ∼12.0, and ∼18.0 mmol/L, respectively. Four TEG parameters, reaction time (R), coagulation time (K), angle (α), and maximum amplitude (MA), were measured alongside conventional plasma tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) by mechanical method, and platelet count by optical method. Results showed that the median R and MA values at moderate and severe hemolysis and K at severe hemolysis exceeded respective reference intervals, and were considered unacceptable. Median values of TEG parameters in lipemic samples were all within reference intervals. Bias values of conventional plasma tests PT, APTT and FIB in hemolyzed or lipemic samples were all lower than the Clinical Laboratory Improvement Amendments (CLIA) allowable limits. Bias values of platelet count at moderate to severe hemolysis and lipemia exceeded the CLIA allowable limits. In conclusion, the detection of TEG was in general more affected by mechanical hemolysis than plasma coagulation tests. Pre-analytical variables should be taken into account when unexpected TEG results are obtained.

Purification and characterization of a heteromultimeric glycoprotein from Artocarpus heterophyllus latex with an inhibitory effect on human blood coagulation.

PubMed

Siritapetawee, Jaruwan; Thammasirirak, Sompong

2011-01-01

Plant latex has many health benefits and has been used in folk medicine. In this study, the biological effect of Artocarpus heterophyllus (jackfruit) latex on human blood coagulation was investigated. By a combination of heat precipitation and ion-exchange chromatography, a heat stable heteromultimeric glycoprotein (HSGPL1) was purified from jackfruit milky latex. The apparent molecular masses of the monomeric proteins on SDS/PAGE were 33, 31 and 29 kDa. The isoelectric points (pIs) of the monomers were 6.63, 6.63 and 6.93, respectively. Glycosylation and deglycosylation tests confirmed that each subunit of HSGPL1 formed the native multimer by sugar-based interaction. Moreover, the multimer of HSGPL1 also resisted 2-mercaptoethanol action. Peptide mass fingerprint analysis indicated that HSGPL1 was a complex protein related to Hsps/chaperones. HSGPL1 has an effect on intrinsic pathways of the human blood coagulation system by significantly prolonging the activated partial thrombin time (APTT). In contrast, it has no effect on the human extrinsic blood coagulation system using the prothrombin time (PT) test. The prolonged APTT resulted from the serine protease inhibitor property of HSGPL1, since it reduced activity of human blood coagulation factors XI(a) and α-XII(a).

Performance Evaluation of the Sysmex CS-5100 Automated Coagulation Analyzer.

PubMed

Chen, Liming; Chen, Yu

2015-01-01

Coagulation testing is widely applied clinically, and laboratories increasingly demand automated coagulation analyzers with short turn-around times and high-throughput. The purpose of this study was to evaluate the performance of the Sysmex CS-5100 automated coagulation analyzer for routine use in a clinical laboratory. The prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fbg), and D-dimer were compared between the Sysmex CS-5100 and Sysmex CA-7000 analyzers, and the imprecision, comparison, throughput, STAT function, and performance for abnormal samples were measured in each. The within-run and between-run coefficients of variation (CV) for the PT, APTT, INR, and D-dimer analyses showed excellent results both in the normal and pathologic ranges. The correlation coefficients between the Sysmex CS-5100 and Sysmex CA-7000 were highly correlated. The throughput of the Sysmex CS-5100 was faster than that of the Sysmex CA-7000. There was no interference at all by total bilirubin concentrations and triglyceride concentrations in the Sysmex CS-5100 analyzer. We demonstrated that the Sysmex CS-5100 performs with satisfactory imprecision and is well suited for coagulation analysis in laboratories processing large sample numbers and icteric and lipemic samples.

Screening test for direct oral anticoagulants with the dilute Russell viper venom time.

PubMed

Pratt, Jackie; Crispin, Philip

2018-06-01

To evaluate the dilute Russell viper venom time (DRVVT) for the detection of direct-acting oral anticoagulants (DOACs) and to investigate the effect of DOACS on coagulation assays. Patients with DOACs and controls had plasma levels determined by an anti-Xa assay and dilute thrombin clotting time (TCT). Levels were correlated with the DRVVT as well as TCT, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C, protein S and antithrombin levels. The utility of the DRVVT for detecting clinically significant levels of DOACs was evaluated. There were 44 samples from patients taking dabigatran, 83 with rivaroxaban, 18 with apixaban and 55 controls. The PT and APTT failed to detect clinically significant doses of anticoagulants adequately. The TCT was increased in patients taking dabigatran and normal in controls and patients on FXa inhibitors. There was a linear correlation with all DOAC levels and the DRVVT, with moderate precision, but it showed high sensitivity (95%) and specificity (90%) for clinically significant DOAC levels. The DRVVT detects clinically significant levels of DOACs and, in conjunction with the TCT, may be used as a screen for the presence and type of DOAC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alteration of Hemostatic Parameters in Patients with Different Levels of Subclinical Hypothyroidism and the Effect of L-thyroxine Treatment.

PubMed

Gao, Fang; Wang, Guangya; Xu, Jinxiu

2017-01-01

Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 μIU/mL

Impact of a pneumatic tube system transport on hemostasis parameters measurement: the experiment of Cochin universitary hospital (AP-HP, Paris, France).

PubMed

Calmette, Leyla; Ibrahim, Firas; Gouin, Isabelle; Horellou, Marie-Hélène; Mazoyer, Élisabeth; Fontenay, Michaela; Flaujac, Claire

2017-02-01

Samples transported by pneumatic tube system are submitted to forces of acceleration and deceleration which can affect laboratory parameters. At Cochin hospital, majority of samples of hemostasis, except for platelets tests, are transported by pneumatic tube system. The objective of this study was to evaluate the impact of a pneumatic tube system (PTS) transport compared to hand-delivered transport on samples and to qualify Cochin hospital PTS according to requirements of standard ISO 15189. A bibliographical study was made and showed that pneumatic tube system particularly influences platelets tests. Four citrate tubes were collected in 5 healthy volunteers in the maternity: 2 tubes were transported by PTS and 2 others were hand-delivered to the laboratory. Five coagulation tests were analyzed: prothrombine time (PT), activated partial thromboplastin time (aPTT), factor (F) V, FVIII and platelet closure time with PFA-100TM collagen/epinephrine. For each volunteer, the results obtained by PTS and by hand-delivered transport were compared with formula usually used for biological analysis retake: 2.8 x standard deviation of reproductibility variation coefficient (SH GTA 01, COFRAC). This study did not show an impact of PTS on PT, aPTT, FV and FVIII. For PFA-100TM collagen/epinephrine, we noted an impact on 2/5 volunteers. These results, in agreement with the literature, led to the conclusion that Cochin hospital PTS is in compliance to transport samples for usual coagulation tests except platelet tests. This study allowed to issue French recommendations for PTS transport of hemostasis tubes qualification available on "Groupe français d'hémostase et thrombose" Web site.

Inhibitory Effects of Medium Molecular Weight Heparinyl Amino Acid Derivatives on Ischemic Paw Edema in Mice.

PubMed

Takeda, Seiichi; Toda, Takao; Nakamura, Kazuki

2016-01-01

We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

PubMed

Isbister, Geoffrey K; Maduwage, Kalana; Scorgie, Fiona E; Shahmy, Seyed; Mohamed, Fahim; Abeysinghe, Chandana; Karunathilake, Harendra; O'Leary, Margaret A; Gnanathasan, Christeine A; Lincz, Lisa F

2015-01-01

Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming. In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y) and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13), associated with low fibrinogen [median,<0.01 g/L; IQR: <0.01-0.9 g/L), low factor V levels [median,<5%; IQR: <5-4%], low factor VIII levels [median,40%; IQR: 12-79%] and low factor X levels [median, 48%; IQR: 29-67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48 h post-antivenom. The median INR remained >3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec) at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis). Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

Betrixaban: Impact on Routine and Specific Coagulation Assays-A Practical Laboratory Guide.

PubMed

Siriez, Romain; Evrard, Jonathan; Dogné, Jean-Michel; Pochet, Lionel; Gheldof, Damien; Chatelain, Bernard; Mullier, François; Douxfils, Jonathan

2018-06-11

 Betrixaban is a novel direct oral factor Xa inhibitor approved by the Food and Drug Administration for prophylaxis of venous thromboembolism in adult patients hospitalized for an acute illness at risk for thromboembolic complications. Assessment of the anti-coagulant effect of betrixaban may be useful in some situations. Also, clinicians need to know how routine coagulation assays are influenced.  The aim of this study is to determine which coagulation assay(s) should be used to assess the impact of betrixaban on haemostasis and provide laboratory guidance for their interpretation.  Betrixaban was spiked at final concentrations ranging from 0 to 250 ng/mL in platelet-poor plasma. Different reagents from several manufacturers were tested and the impact of betrixaban on pro-thrombin time (PT), activated partial thromboplastin time (aPTT), dilute Russel viper venom time (dRVV-T), chromogenic anti-Xa assays, thrombin generation assay (TGA), and a large panel of haemostasis diagnostic tests has been assessed.  A concentration-dependent prolongation of aPTT, PT and dRVV-T is observed. The sensitivity mainly depends on the reagent. Chromogenic anti-Xa assays show high sensitivity depending on the reagent and/or the methodology. These assays applicable for other direct factor Xa inhibitors have to be adapted to obtain a relevant range of measurement. TGA may also be attractive to assess the anti-coagulant activity of betrixaban.  Adapted chromogenic anti-Xa assays are the most appropriate assays to estimate the concentration of betrixaban. Betrixaban significantly affects several haemostasis diagnostic tests and this needs to be taken into consideration when requesting and interpreting such tests. Schattauer GmbH Stuttgart.

The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Sanzari, Jenine K.; Kennedy, Ann R.

2013-01-01

Purpose To determine whether proton radiation affects coagulation. Material and methods Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3–7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved. Results HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0. Conclusions PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy. PMID:22221163

Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A.

PubMed

Ku, Sae-Kwang; Bae, Jong-Sup

2014-03-01

Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. However, antiplatelet, anticoagulant, and profibrinolytic properties of WFA have not been studied. In this study, the anticoagulant activities of WFA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), fibrin polymerization, platelet aggregation, thrombus formation, and the activities of cell-based thrombin and activated factor X (FXa). The effects of WFA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Our data showed that WFA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, FeCl3-induced thrombus formation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. WFA prolonged in vivo and ex vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by WFA. Collectively, these results indicate that WFA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents. Copyright © 2014 Elsevier Inc. All rights reserved.

The Usefulness of Clinical-Practice-Based Laboratory Data in Facilitating the Diagnosis of Dengue Illness

PubMed Central

Liu, Jien-Wei; Lee, Ing-Kit; Wang, Lin; Chen, Rong-Fu; Yang, Kuender D.

2013-01-01

Alertness to dengue and making a timely diagnosis is extremely important in the treatment of dengue and containment of dengue epidemics. We evaluated the complementary role of clinical-practice-based laboratory data in facilitating suspicion/diagnosis of dengue. One hundred overall dengue (57 dengue fever [DF] and 43 dengue hemorrhagic fever [DHF]) cases and another 100 nondengue cases (78 viral infections other than dengue, 6 bacterial sepsis, and 16 miscellaneous diseases) were analyzed. We separately compared individual laboratory variables (platelet count [PC] , prothrombin time [PT], activated partial thromboplastin time [APTT], alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) and varied combined variables of DF and/or DHF cases with the corresponding ones of nondengue cases. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) in the diagnosis of DF and/or DHF were measured based on these laboratory variables. While trade-off between sensitivity and specificity, and/or suboptimal PPV/NPV was found at measurements using these variables, prolonged APTT + normal PT + PC < 100 × 109 cells/L had a favorable sensitivity, specificity, PPV, and NPV in diagnosis of DF and/or DHF. In conclusion, these data suggested that prolonged APTT + normal PT + PC < 100 × 109 cells/L is useful in evaluating the likelihood of DF and/or DHF. PMID:24455678

Relation of thromboelastography parameters to conventional coagulation tests used to evaluate the hypercoagulable state of aged fracture patients

PubMed Central

Liu, Chen; Guan, Zhao; Xu, Qinzhu; Zhao, Lei; Song, Ying; Wang, Hui

2016-01-01

Abstract Fractures are common among aged people, and rapid assessment of the coagulation status is important. The thromboelastography (TEG) test can give a series of coagulation parameters and has been widely used in clinics. In this research, we looked at fracture patients over 60 and compared their TEG results with those of healthy controls. Since there is a paucity of studies comparing TEG assessments with conventional coagulation tests, we aim to clarify the relationship between TEG values and the values given by conventional coagulation tests. Forty fracture patients (27 femur and 13 humerus) over 60 years old were included in the study. The change in their coagulation status was evaluated by TEG before surgery within 4 hours after the fracture. Changes in TEG parameters were analyzed compared with controls. Conventional coagulation test results for the patients, including activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, and platelets, were also acquired, and correlation analysis was done with TEG parameters, measuring similar aspects of the coagulation cascade. In addition, the sensitivity and specificity of TEG parameters for detecting raised fibrinogen levels were also analyzed. The K (time to 20 mm clot amplitude) and R (reaction time) values of aged fracture patients were lower than controls. The values for angle, maximal amplitude (MA), and coagulation index (CI) were raised compared with controls, indicating a hypercoagulable state. Correlation analysis showed that there were significant positive correlations between fibrinogen and MA/angle, between platelets and MA, and between APTT and R as well. There was significant negative correlation between fibrinogen and K. In addition, K values have better sensitivity and specificity for detecting elevated fibrinogen concentration than angle and MA values. Aged fracture patients tend to be in a hypercoagulable state, and this could be effectively reflected by a TEG test. There were correlations between TEG parameters and corresponding conventional tests. K values can better predict elevated fibrinogen levels in aged fracture patients. PMID:27311005

Relation of thromboelastography parameters to conventional coagulation tests used to evaluate the hypercoagulable state of aged fracture patients.

PubMed

Liu, Chen; Guan, Zhao; Xu, Qinzhu; Zhao, Lei; Song, Ying; Wang, Hui

2016-06-01

Fractures are common among aged people, and rapid assessment of the coagulation status is important. The thromboelastography (TEG) test can give a series of coagulation parameters and has been widely used in clinics. In this research, we looked at fracture patients over 60 and compared their TEG results with those of healthy controls. Since there is a paucity of studies comparing TEG assessments with conventional coagulation tests, we aim to clarify the relationship between TEG values and the values given by conventional coagulation tests.Forty fracture patients (27 femur and 13 humerus) over 60 years old were included in the study. The change in their coagulation status was evaluated by TEG before surgery within 4 hours after the fracture. Changes in TEG parameters were analyzed compared with controls. Conventional coagulation test results for the patients, including activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, and platelets, were also acquired, and correlation analysis was done with TEG parameters, measuring similar aspects of the coagulation cascade. In addition, the sensitivity and specificity of TEG parameters for detecting raised fibrinogen levels were also analyzed.The K (time to 20 mm clot amplitude) and R (reaction time) values of aged fracture patients were lower than controls. The values for angle, maximal amplitude (MA), and coagulation index (CI) were raised compared with controls, indicating a hypercoagulable state. Correlation analysis showed that there were significant positive correlations between fibrinogen and MA/angle, between platelets and MA, and between APTT and R as well. There was significant negative correlation between fibrinogen and K. In addition, K values have better sensitivity and specificity for detecting elevated fibrinogen concentration than angle and MA values.Aged fracture patients tend to be in a hypercoagulable state, and this could be effectively reflected by a TEG test. There were correlations between TEG parameters and corresponding conventional tests. K values can better predict elevated fibrinogen levels in aged fracture patients.

Disposable cartridge biosensor platform for portable diagnostics

NASA Astrophysics Data System (ADS)

Yaras, Yusuf S.; Cakmak, Onur; Gunduz, Ali B.; Saglam, Gokhan; Olcer, Selim; Mostafazadeh, Aref; Baris, Ibrahim; Civitci, Fehmi; Yaralioglu, Goksen G.; Urey, Hakan

2017-03-01

We developed two types of cantilever-based biosensors for portable diagnostics applications. One sensor is based on MEMS cantilever chip mounted in a microfluidic channel and the other sensor is based on a movable optical fiber placed across a microfluidic channel. Both types of sensors were aimed at direct mechanical measurement of coagulation time in a disposable cartridge using plasma or whole blood samples. There are several similarities and also some important differences between the MEMS based and the optical fiber based solutions. The aim of this paper is to provide a comparison between the two solutions and the results. For both types of sensors, actuation of the cantilever or the moving fiber is achieved using an electro coil and the readout is optical. Since both the actuation and sensing are remote, no electrical connections are required for the cartridge. Therefore it is possible to build low cost disposable cartridges. The reader unit for the cartridge contains light sources, photodetectors, the electro coil, a heater, analog electronics, and a microprocessor. The reader unit has different optical interfaces for the cartridges that have MEMS cantilevers and moving fibers. MEMS based platform has better sensitivity but optomechanical alignment is a challenge and measurements with whole blood were not possible due to high scattering of light by the red blood cells. Fiber sensor based platform has relaxed optomechanical tolerances, ease of manufacturing, and it allows measurements in whole blood. Both sensors were tested using control plasma samples for activated-Partial-Thromboplastin-Time (aPTT) measurements. Control plasma test results matched with the manufacturer's datasheet. Optical fiber based system was tested for aPTT tests with human whole blood samples and the proposed platform provided repeatable test results making the system method of choice for portable diagnostics.

Severe Coagulopathy after Ingestion of "Snake Wine".

PubMed

Moon, Jeong Mi; Chun, Byeong Jo

2016-06-01

This report describes a patient who developed coagulopathy after ingesting snake wine, which is an alcoholic libation containing an entire venomous snake. A 68-year-old man was admitted to the hospital 19 h after ingesting snake wine. The laboratory features upon admission included unmeasurable activated partial thromboplastin (aPTT) values, prolonged prothrombin time (PT) values, increased fibrinogen levels, modestly elevated fibrin degradation product and D-dimer values, uncorrected aPTT and PT values after a mixing test, and normal levels of aspartate transaminase and alanine transaminase. No pesticides, warfarin, or superwarfarin in the patient's blood or urine were detected. His coagulation profile normalized on the 6(th) day after admission after antivenom treatment. He was discharged 10 days later without sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The physician should be aware that ingesting snake wine may lead to systemic envenomation. As for coagulopathy, which may develop by ingesting snake venom, related laboratory findings may differ from the features observed after direct envenomation by snakebite. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic Error of a Patient with Combined Inherited Factor VII and Factor X Deficiency due to Accidental Ingestion of a Diphacinone Rodenticide.

PubMed

Li, Min; Jin, Yanhui; Wang, Mingshan; Xie, Yaosheng; Ding, Hongxiang

2016-11-01

To explore the characteristics of laboratory examination and confirm the diagnosis of a patient with combined inherited FVII and FX deficiency after he ingested diphacinone rodenticide accidentally. The coagulant parameter screening tests and coagulation factor activities were tested many times in the patient due to accidental ingestion of a diphacinone rodenticide. After the patient was treated for more than one year, gene analysis of correlated coagulation factors was analyzed in the patient and other family members by DNA direct sequencing. 106 persons were selected as controls from routine health examinations. After the patient was admitted to hospital, routine coagulation screening tests revealed the prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) and low levels of vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) activity, which was 102.4 seconds, 88.5 seconds, 7%, 3%, 8%, and 2%, respectively. During more than one year of treatment, the value of PT and APTT still showed significantly prolonged activity and FVII and FX activity levels were about 5%. While FII and FIX activity levels were in the normal range after 12 weeks of treatment. Two homozygous mutations, g.11267C>T of F7 gene resulting in the substitution Arg277Cys and g.28139G>T of F10 gene leading to the substitution Val384Phe, were identified in the patient. The patient's parents and sister was heterozygous for Arg277Cys and Val384Phe mutations. FVII and FX antigen levels in the patient were 7% and 30%, respectively. There were many similarities in the characteristics of laboratory examination between combined inherited FVII and FX deficiency and acquired vitamin K deficiency. The best way to identify them was gene analysis.

Single center review of clinicopathological characterization in 77 patients with positive lupus anticoagulant antibodies.

PubMed

Owaidah, Tarek M; Qurashi, Fat-Hiya M; Al Nounou, Randa M; Al Zahrani, Hazza; Al Mussa, Abdulrahman; Tbakhi, Abdelghani I; Al Daama, Saad; Elkum, Nasser; Roberts, George T

2003-08-01

The antiphospholipid syndrome (APS) is a thrombophillic disorder characterized by the presence of antiphospholipid antibodies (APA). It often occurs in patients with systemic lupus erythematosus (SLE) and may be associated with recurrent abortions and thrombocytopenia and, occasionally, catastrophic thrombotic events. To examine, retrospectively, the clinico-pathological features of patients with APS detected by the presence of the lupus anticoagulant (LAC). Patients were selected for study on the basis of a positive LAC test on review of the laboratory computer records of the King Faisal Specialist Hospital and Research Center. Following this, a clinical chart review was conducted in order to determine the clinical presentations, treatment and the course of patients identified. The information obtained was entered into an electronic database and subsequently analyzed. Seventy-seven patients were identified and reviewed. Fifty-six (73%) were female and 16 (21%) were children less than 15-years-old. Thirty-two patients (42%) had no clinical events (incidental APS). The syndrome was classified as primary in 40 (52%) patients and secondary in 37 (48%). Out of the 45 (58%) patients who presented with symptoms related to APA 22 (49%) had thrombosis, 24 (53%) had pregnancy failure, and 4 (9%) presented with catastrophic APS. The activated partial thromboplastin time (aPTT) was elevated and not corrected by mixing with normal plasma in 47 (61%). On the other hand, the prothrombin time (PT) was normal in 66 (90%). There is a significant difference between aPTT and PT as a screening test with P value of < 0.0001. Tests for anticardiolipin antibodies (ACA) were positive in 39 patients (70%). Only 13 (17%) patients had thrombocytopenia. All patients who presented with thrombosis were treated with warfarin but only 5 (23%) had received aspirin. Out of the 22 patients presenting with thrombosis, 12 (55%) had one or more recurrent thrombotic events while only 6 (25%) out of the 24 patients who presented with pregnancy failure had events other than pregnancy failure. Fifty-two patients were followed up regularly and were alive. We find that thrombosis, venous or arterial, and obstetric complications are the most frequent clinical findings in our patients with circulating LAC. Incidental APS is not an uncommon finding in patients screened for APS. There is a clear association between the presence of LAC and an abnormal aPTT, which is much less obvious with the PT.

Effect of leukapheresis on blood coagulation in patients with hyperleukocytic acute myeloid leukemia.

PubMed

Van de Louw, Andry

2017-04-01

Leukapheresis has been proposed to reduce white blood cell (WBC) count in hyperleukocytic acute myeloid leukemia (AML). However, no survival benefit has been proven and leukapheresis can potentially affect coagulation and worsen bleeding and disseminated intravascular coagulation (DIC). We analyzed the effect of leukapheresis on coagulation tests in a cohort of hyperleukocytic AML patients. Retrospective chart review of hyperleukocytic AML patients who underwent leukapheresis between 2003 and 2014. Blood coagulation tests (platelets, PT, INR, aPTT, fibrinogen, D-Dimers and fibrin degradation products (FDP)) were collected before and after each procedure and DIC score was computed. Transfusions of platelets and coagulation factors were collected. Ninety patients and 129 leukapheresis sessions were screened. After exclusion of the sessions associated with transfusions, we observed in 44 patients a significant decrease in platelets (from 75.69±89.48 to 44.59±47.71.10 9 /L, p=0.001) and fibrinogen (from 4.05±1.29 to 3.35±1.37g/L, p<0.0005) along with an increase in PT (from 14.62±2.73 to 15.62±3.63s, p=0.001), aPTT (from 33.70±6.32 to 39.24±13.53s, p=0.009) and INR (from 1.33±0.2 to 1.45±0.34, p=0.002) after the first procedure. Bleeding complications, all intracerebral hemorrhages, were documented in 3 patients within 24h of leukapheresis. After combining 73 repeat procedures, we observed similar significant results except for the aPTT prolongation. The platelets and PT components of the DIC score, but not the fibrinogen component, were significantly increased after leukapheresis. In hyperleukocytic AML patients, leukapheresis is associated with clinically significant decreases in platelets and fibrinogen and prolonged clotting times. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sodium citrate blood contamination by K2 -ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing.

PubMed

Lima-Oliveira, G; Salvagno, G L; Danese, E; Favaloro, E J; Guidi, G C; Lippi, G

2015-06-01

The potential cross-contamination of additives between primary blood tubes is a well-known problem during sample collection. The aim of this study was to assess the impact of citrated blood contamination with different amounts of dipotassium ethylenediaminetetraacetic (K2 EDTA blood) on activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen. Blood was collected from 15 ostensibly healthy volunteers into four 0.109 m citrate blood tubes followed by one K2 EDTA blood tube. The citrate tubes of each subject were pooled and divided in five aliquots. The whole blood of the K2 EDTA tube was then added in scalar amounts to autologous citrated blood aliquots, to obtain K2 EDTA contamination ranging from 0% to 43%, and thus mimic potential pre-analytical contamination. A statistically and clinically significant prolongation was observed for both APTT and PT between 29% and 43% K2 EDTA contamination, whereas the decrease of fibrinogen values became statistically and clinically significant at 43% K2 EDTA contamination. The results of this investigation show that contamination of citrated blood with as much as 29% of K2 EDTA blood generates a significant bias in results of routine clotting assays. This has serious implications for patient safety and management. © 2014 John Wiley & Sons Ltd.

[Study on the difference of blood coagulation function in patients with traumatic brain injury in plain and plateau area].

PubMed

Sun, J; Tian, Y; Jiang, R C; Dong, X L; Wang, Y; Wu, W B; Wu, K X; Zhang, J N

2016-10-25

Objective: In this study, we tested platelet count (PC), prothrombin time (PT), activated partial thromboplastin time (APTT), and other indicators of coagulation function, and revealed their difference in patients with traumatic brain injury (TBI) between plain and plateau area. Base on the results, we may provide research basis for the therapy of TBI associated coagulopathy in different areas. Methods: 151 TBI patients from Tianjin Medical University General Hospital, and 74 from People's Hospital of Tibet Autonomous Region in the period from Dec 2013 to Dec 2015 were enrolled.Coagulation function, including PC, platelet distribution width (PDW), mean platelet volume (MPV), platelet - large cell ratio (P- LCR), PT, APTT, fibrinogen (FIB), and D- Dimer were tested within 8 h. The difference in patients with TBI between plain and plateau areas were compared and analyzed. Results: Compared with plain area, the PC of patients with TBI in plateau area is lower [(168±49)×10 9 /L vs (196±72)×10 9 /L, P <0.05], while PT and APTT were extended [(13.5±1.3) s vs (12.0±4.0) s, (38±4) s vs(27±6) s, P <0.01]. On the other hand, FIB increases [(3.1±1.2) g/L vs (2.6±1.0) g/L, P <0.01] and D-Dimer decreases [(3.1±3.3) μg/L vs (4.7±3.6) μg/L, P <0.01] in plateau area compared with plain area. Conclusion: Due to the people of plateau area living in hypoxia state, the coagulation function is activated for a long time.Once TBI happens, the platelets and coagulation factors may be excessive consumption, resulting in hypocoagulable state and high risk of rebleeding, while the fibrinolysis system in patients with TBI of plateau area is not activated obviously.Therefore, it should give full consideration to these differences in the treatment of patients with TBI in plateau area, instead of directly copying the standard therapy of the people in plain area.The treatment recommendations should primarily supplement coagulation materials, and antifibrinolytics may unlikely have the therapy effect.

In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

NASA Astrophysics Data System (ADS)

Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

2011-05-01

Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

2018-01-01

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

Anticoagulant and Antiplatelet Activities of Artemisia princeps Pampanini and Its Bioactive Components.

PubMed

Ryu, Ri; Jung, Un Ju; Kim, Hye-Jin; Lee, Wonhwa; Bae, Jong-Sup; Park, Yong Bok; Choi, Myung-Sook

2013-09-01

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 (TXA2) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and TXA2, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation.

Anticoagulant and Antiplatelet Activities of Artemisia princeps Pampanini and Its Bioactive Components

PubMed Central

Ryu, Ri; Jung, Un Ju; Kim, Hye-jin; Lee, Wonhwa; Bae, Jong-Sup; Park, Yong Bok; Choi, Myung-Sook

2013-01-01

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 (TXA2) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and TXA2, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation. PMID:24471130

Sulfonation and anticoagulant activity of botryosphaeran from Botryosphaeria rhodina MAMB-05 grown on fructose.

PubMed

Mendes, Simone Ferreira; dos Santos, Osvaldo; Barbosa, Aneli M; Vasconcelos, Ana Flora D; Aranda-Selverio, Gabriel; Monteiro, Nilson K; Dekker, Robert F H; Sá Pereira, Mariana; Tovar, Ana Maria F; Mourão, Paulo A de Souza; da Silva, Maria de Lourdes Corradi

2009-10-01

Botryosphaeran (EPS(FRU)), an exopolysaccharide of the beta-(1-->3,1-->6)-d-glucan type with 31% branching at C-6, is produced by the fungus Botryosphaeria rhodina MAMB-05 when grown on fructose as carbon source. Botryosphaeran was derivatized by sulfonation to induce anticoagulant activity. The effectiveness of the sulfonation reaction by chlorosulfonic acid in pyridine was monitored by the degree of substitution and FT-IR analysis of the sulfonated EPS(FRU) (once sulfonated, EPS(FRUSULF); and re-sulfonated, EPS(FRURESULF)). Activated partial thromboplastin time (APTT) and thrombin time (TT) tests of EPS(FRURESULF) indicated significant in vitro anticoagulant activity that was dose-dependent. EPS(FRU) did not inhibit any of the coagulation tests.

Presurgical levels of circulating cell-derived microparticles discriminate between patients with and without transfusion in coronary artery bypass graft surgery.

PubMed

Jy, Wenche; Gómez-Marín, Orlando; Salerno, Tomas A; Panos, Anthony L; Williams, Donald; Horstman, Lawrence L; Ahn, Yeon S

2015-01-01

Improved understanding of presurgical risk factors for transfusions will lead to reduction in their number and related complications. The goal of this study is to identify these factors in coronary artery bypass graft (CABG) surgery. Presented herein are results of analyses of data from an ongoing study of transfusion in CABG surgery. Of 122 patients, 81 received transfusion (Tx) and 41 did not (NoTx). In addition to routine tests, presurgical levels of microparticles from platelets (PMPs), red cells (RMPs), and other lineages were assayed. The Tx and NoTx groups were similar with respect to most presurgical variables but differed in distribution of gender, blood type, diabetes prevalence, activated partial thromboplastin time (aPTT), hemoglobin (HGB), and microparticle levels. Stepwise multiple logistic regression was used to evaluate presurgical variables and to develop a model to assess risk factors for transfusion. CD41(+) PMP and CD235(+) RMP levels were found to be the main risk factors for transfusion. The Model's discriminating ability was assessed using receiver operating characteristic curve analysis, which showed that the area under the model curve (± standard error) was 0.86 ± 0.04 (95% confidence interval, 0.77-0.94). According to the model, patients with higher presurgical levels of circulating CD41(+) PMP, CD235a(+) RMP, and HGB, as well as a shorter aPTT, are less likely to receive transfusion(s). Presurgical levels of CD41(+) PMPs and CD235a(+) RMPs are the main risk factors for transfusion in CABG, followed by HGB and aPTT. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

[Effects of perioperative thermoregulation on patients' body temperature, peripheral circulation and blood coagulation time in patients undergoing elective vertical hemi laryngectomy].

PubMed

Zheng, X; Sun, D; Zhou, F; Zhang, Y J

2017-07-20

Objective: To compare the effects of different thermal insulation measures on perioperative body temperature, peripheral circulation and blood coagulation time in patients undergoing vertical hemi laryngectomy. Method: Sixty eligible patients with elective vertical hemi laryngectomy were randomly divided into 3 groups: preoperative inflatable heating blanket group (A group, n=20), warmed irrigation group (B group, n=20), and control group (C group, n=20). The core temperature were recorded after entering the operating room, before induction, 20th minute during operation, entering PACU and 2nd hour after operation respectively. Blood samples were got at the end of operation to test pH, lactic acid, PT and APTT. After waking patients' SpO₂ and thermal comfort were recorded. Result: The core temperatures at time points of 20th minute during operation and entering PACU were significantly different between C group and A group, C group and B group. There were significant difference in lactic acid, PT, APTT and SpO₂ between C group and A group, C group and B group. Patients' thermal comfort in all three groups were different. Conclusion: Inflatable heating blanket during operation combined with using it before operation or fluid warmers during operation for perioperative body temperature protection duringelective vertical partial laryngectomy surgery can effectively prevent perioperative hypothermia, improve peripheral circulation and blood coagulation time changes, improve patients' comfort after operation. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Clinical presentation and blood gas analysis of multiple trauma patients for prediction of standard coagulation parameters at emergency department arrival.

PubMed

Hilbert-Carius, P; Hofmann, G O; Lefering, R; Stuttmann, R; Struck, M F

2016-04-01

Trauma-induced coagulopathy (TIC) in multiple trauma patients is a potentially lethal complication. Whether quickly available laboratory parameters using point-of-care (POC) blood gas analysis (BGA) may serve as surrogate parameters for standard coagulation parameters is unknown. The present study evaluated TraumaRegister DGU® of the German Trauma Society for correlations between POC BGA parameters and standard coagulation parameters. In the setting of 197 trauma centres (172 in Germany), 86,442 patients were analysed between 2005 and 2012. Of these, 40,129 (72% men) with a mean age 46 ± 21 years underwent further analysis presenting with direct admission from the scene of the accident to a trauma centre, injury severity score (ISS) ≥ 9, complete data available for the calculation of revised injury severity classification prognosis, and blood samples with valid haemoglobin (Hb) measurements taken immediately after emergency department (ED) admission. Correlations between standard coagulation parameters and POC BGA parameters (Hb, base excess [BE], lactate) were tested using Pearson's test with a two-tailed significance level of p < 0.05. A subgroup analysis including patients with ISS > 16, ISS > 25, ISS > 16 and shock at ED admission, and patients with massive transfusion was likewise carried out. Correlations were found between Hb and prothrombin time (r = 0.497; p < 0.01), Hb and activated partial thromboplastin time (aPTT; r = -0.414; p < 0.01), and Hb and platelet count (PLT; r = 0.301; p < 0.01). Patients presenting with ISS ≥ 16 and shock (systolic blood pressure < 90 mmHg) at ED admission (n = 4,329) revealed the strongest correlations between Hb and prothrombin time (r = 0.570; p < 0.01), Hb and aPTT (r = -0.457; p < 0.01), and Hb and PLT (r = 0.412; p < 0.01). Significant correlations were also found between BE and prothrombin time (r = -0.365; p < 0.01), and BE and aPTT (r = 0.327, p < 0.01). No correlations were found between Hb, BE and lactate lactate. POC BGA parameters Hb and BE of multiple trauma patients correlated with standard coagulation parameters in a large database analysis. These correlations were particularly strong in multiple trauma patients presenting with ISS > 16 and shock at ED admission. This may be relevant for hospitals with delayed availability of coagulation studies and those without viscoelastic POC devices. Future studies may determine whether clinical presentation/BGA-oriented coagulation therapy is an appropriate tool for improving outcomes after major trauma.

Influence of centrifuge brake on residual platelet count and routine coagulation tests in citrated plasma.

PubMed

Daves, Massimo; Giacomuzzi, Katia; Tagnin, Enrico; Jani, Erika; Adcock Funk, Dorothy M; Favaloro, Emmanuel J; Lippi, Giuseppe

2014-04-01

Sample centrifugation is an essential step in the coagulation laboratory, as clotting tests are typically performed on citrated platelet (PLT) poor plasma (PPP). Nevertheless, no clear indication has been provided as to whether centrifugation of specimens should be performed with the centrifuge brake set to on or off. Fifty consecutive sodium citrate anticoagulated samples were collected and divided into two aliquots. The former was centrifuged as for Clinical Laboratory Standards Institute (CLSI) guidelines with the centrifuge brake set to on, whereas the latter was centrifuged again as for CLSI guidelines, but with the brake set to off. In the PPP of all samples, a PLT count was performed, followed by the analysis of activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FBG). The PLT count after samples centrifugation was substantially reduced, either with centrifuge brake set to on or off (5 ± 1 versus 3 ± 1 × 10/l; P = 0.009). The frequency of samples exceeding a PLT count less than 10 × 10/l was nearly double in samples centrifuged with the brake on than in those with the brake off (14 versus 8%; P < 0.01). Although no significant difference was found for APTT values, PT was slightly prolonged using the centrifuge brake set to on (mean bias 0.2 s; P < 0.001). FBG values were also significantly higher using the centrifuge brake set to on (mean bias 0.29 g/l; P < 0.001). The results of this study indicate that sample centrifugation for routine coagulation testing should be preferably performed with the centrifuge brake set to off for providing a better quality specimen.

Comparison of postoperative coagulation profiles and outcome for sugammadex versus pyridostigmine in 992 living donors after living-donor hepatectomy

PubMed Central

Moon, Young-Jin; Kim, Sung-Hoon; Kim, Jae-Won; Lee, Yoon-Kyung; Jun, In-Gu; Hwang, Gyu-Sam

2018-01-01

Abstract Donor safety is the major concern in living donor liver transplantation, although hepatic resection may be associated with postoperative coagulopathy. Recently, the use of sugammadex has been gradually increased, but sugammadex is known to prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the postoperative coagulation profiles and outcomes of sugammadex versus pyridostigmine group in donors receiving living donor hepatectomy. Consecutive donor hepatectomy performed between September 2013 and August 2016 was retrospectively analyzed. For reversal of rocuronium-induced neuromuscular blockade, donors received sugammadex 4 mg/kg or pyridostigmine 0.25 mg/kg. The primary end-points were laboratory findings (PT, aPTT, hemoglobin, platelet count) and clinically evaluated postoperative bleeding (relaparotomy for bleeding, cumulative volume collected in drains). Secondary outcomes were anesthesia time, postoperative hospital day. Of 992 donors, 383 treated with sugammadex and 609 treated with pyridostigmine for the reversal of neuromuscular blockade. There were no significant differences between both groups for drop in hemoglobin and platelet, prolongation in PT, aPTT, and the amount of 24-h drain volume. Bleeding events within 24 h were reported in 2 (0.3%) for pyridostigmine group and 0 (0%) for sugammadex group (P = .262). Anesthesia time was significantly longer in pyridostigmine group than that in sugammadex group (438.8 ± 71.4 vs. 421.3 ± 62.3, P < .001). Postoperative hospital stay was significantly longer in pyridostigmine group than that in sugammadex group (P = .002). Sugammadex 4 mg/kg was not associated with increased bleeding tendency, but associated with reduced anesthesia time and hospital stay. Therefore, sugammadex may be safely used and will decrease morbidity in donor undergoing living-donor hepatectomy. PMID:29538210

Comparison of postoperative coagulation profiles and outcome for sugammadex versus pyridostigmine in 992 living donors after living-donor hepatectomy.

PubMed

Moon, Young-Jin; Kim, Sung-Hoon; Kim, Jae-Won; Lee, Yoon-Kyung; Jun, In-Gu; Hwang, Gyu-Sam

2018-03-01

Donor safety is the major concern in living donor liver transplantation, although hepatic resection may be associated with postoperative coagulopathy. Recently, the use of sugammadex has been gradually increased, but sugammadex is known to prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the postoperative coagulation profiles and outcomes of sugammadex versus pyridostigmine group in donors receiving living donor hepatectomy.Consecutive donor hepatectomy performed between September 2013 and August 2016 was retrospectively analyzed. For reversal of rocuronium-induced neuromuscular blockade, donors received sugammadex 4 mg/kg or pyridostigmine 0.25 mg/kg. The primary end-points were laboratory findings (PT, aPTT, hemoglobin, platelet count) and clinically evaluated postoperative bleeding (relaparotomy for bleeding, cumulative volume collected in drains). Secondary outcomes were anesthesia time, postoperative hospital day.Of 992 donors, 383 treated with sugammadex and 609 treated with pyridostigmine for the reversal of neuromuscular blockade. There were no significant differences between both groups for drop in hemoglobin and platelet, prolongation in PT, aPTT, and the amount of 24-h drain volume. Bleeding events within 24 h were reported in 2 (0.3%) for pyridostigmine group and 0 (0%) for sugammadex group (P = .262). Anesthesia time was significantly longer in pyridostigmine group than that in sugammadex group (438.8 ± 71.4 vs. 421.3 ± 62.3, P < .001). Postoperative hospital stay was significantly longer in pyridostigmine group than that in sugammadex group (P = .002).Sugammadex 4 mg/kg was not associated with increased bleeding tendency, but associated with reduced anesthesia time and hospital stay. Therefore, sugammadex may be safely used and will decrease morbidity in donor undergoing living-donor hepatectomy.

The effects of 7.5% NaCl/6% dextran 70 on coagulation and platelet aggregation in humans

NASA Technical Reports Server (NTRS)

Hess, J. R.; Dubick, M. A.; Summary, J. J.; Bangal, N. R.; Wade, C. E.

1992-01-01

The combination solution of 7.5% NaCl/6% dextran 70 (HSD) administered IV gives hemodynamic improvement in the treatment of hemorrhagic hypotension. Since earlier dextran solutions were reported to interfere with blood coagulation, the effects of HSD on the prothrombin time (PT), the activated partial thromboplastin time (APTT), platelet aggregation, and platelet concentration were studied. The HSD mixed with human plasma (1:5 and 1:10) slightly prolonged PT, but had no effect on the APTT, compared with saline controls. The HSD also decreased human platelet aggregation at the 1:5 dilution. In separate mixing studies, the hypertonic saline component of HSD was associated with the prolongation of PT and decreased platelet aggregation. The data from these studies indicate that at its proposed therapeutic dose, HSD is expected to have minimal effect on blood coagulation.

Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair.

PubMed

Bergmann, Hannes M L; Nolte, Ingo J A; Kramer, Sabine

2005-08-01

To evaluate effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing general anesthesia for fracture repair. 26 client-owned dogs. Anesthesia was induced with levomethadone, diazepam, and propofol and maintained by administration of isoflurane in oxygen-nitrous oxide. Carprofen (4 mg/kg, SC) was administered 1 hour before induction to 13 dogs (group 1) and after extubation to the other 13 dogs (group 2). All dogs also received carprofen (4 mg/kg, SC, q 24 h) for the first 4 days after surgery. Renal function (glomerular filtration rate [GFR], urinary protein-to-urinary creatinine ratio [UP:UC], and results of urinalysis and biochemical analysis of plasma), hemostatic variables (bleeding time, platelet aggregation, prothrombin time [PT], activated partial thromboplastin time [APTT], and platelet count), and Hct were assessed before and at various time points after surgery. Analysis of results for renal function tests, most of the hemostatic and plasma biochemical variables, and Hct did not reveal significant differences between treatment groups. Values for GFR, UP:UC, PT, APTT, and platelet aggregation were outside reference ranges in many dogs before surgery and during the first 6 hours after surgery. In most dogs, these trauma-induced pathologic changes returned to within reference ranges during the 4-day period after surgery. Carprofen did not cause clinically relevant adverse effects in dogs anesthetized for fracture repair after 5 days of treatment, even when it was administered before surgery or given to patients with trauma-induced alterations in renal function or hemostasis.

Anticoagulant effect and safety assessment of an aqueous extract of Pseudocedrela kotschyi (Schweinf.) harms and Adenia cissampeloides (Planch. Ex Hook.) harms.

PubMed

Nyansah, Wilson Bright; Koffuor, George Asumeng; Asare, Frederick; Gyanfosu, Linda

2016-01-01

Currently available therapeutic options for thromboembolic disorders are often very expensive and are associated with unfavorable side effects. To establish the anticoagulant effect and safety profile of an extract made from of the root bark of Pseudocedrela kotschyi (Schweinf.) Harms and the aerial part of Adenia cissampeloides (Planch. ex Hook.) Harms (PAE). PAE (0.5-2.0 g/L) effect on prothrombin time (PT) and activated partial thromboplastin time (aPTT) were evaluated on whole blood drawn from the marginal ear vein of New Zealand White rabbits. Effect of PAE (250-2000 mg/kg) on bleeding time (BT) and clotting time (CT) in Sprague-Dawley rats were also assessed. Histopathological, hematological, and liver function studies were also carried out to assess the safety for use of PAE (250-2000 mg/kg). PAE had no significant effect (P > 0.05) on PT, but resulted in a significant increase (P ≤ 0.05-0.0001) in aPTT. The PAE treatment resulted in a significant increase (P ≤ 0.05-0.0001) in BT and CT in vivo compared with control. Safety studies indicated no deaths with PAE treatment with hematological and liver function tests being normal. Histological studies revealed pathological changes in the liver at a PAE treatment dose of 2000 mg/kg but all doses had no detrimental effect on kidney and stomach tissue. The no-observed-adverse-effect-level was <2000 mg/kg when given orally. PAE has anticoagulant effect in vitro and is safe to use at oral doses <2000 mg/kg.

Antithrombotic effect and mechanism of Rubus spp. Blackberry.

PubMed

Xie, Pingyao; Zhang, Yong; Wang, Xuebiao; Wei, Jinfeng; Kang, Wenyi

2017-05-24

The compounds of Rubus spp. Blackberry (RSB) were isolated and identified by a bioassay-guided method, and their antithrombotic effects and mechanism were investigated with the acute blood stasis rat model. The RSB extract was evaluated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) assays in vitro. Results indicated that RSB extract exhibited anticoagulant activity. In addition to compounds 1 and 6, the other compounds also exhibited anticoagulant activity in vitro. Therefore, the in vivo antithrombosis effects of RSB extract were investigated by measuring whole blood viscosity (WBV), plasma viscosity (PV), APTT, PT, TT, and FIB. Meanwhile, the levels of thromboxane B2 (TXB 2 ), 6-keto prostaglandin F1α (6-keto-PGF1α), endothelial nitric oxide synthase (eNOS) and ET-1 (endothelin-1) were measured. Results suggested that RSB extract had inhibitory effects on thrombus formation, and its antithrombotic effects were associated with the regulation of vascular endothelium active substance, activation of blood flow and an anticoagulation effect.

Evaluation of the anticoagulant potential of polysaccharide-rich fractions extracted from macroalgae.

PubMed

Adrien, Amandine; Dufour, Delphine; Baudouin, Stanislas; Maugard, Thierry; Bridiau, Nicolas

2017-09-01

The aim of this study was to evaluate the potential anticoagulant activity of sulphated polysaccharide-containing extracts of six french edible marine macroalgae. Aqueous extracts of brown (Himanthalia elongata, Laminaria digitata, Ascophyllum nodosum, Fucus vesiculosus), green (Ulva lactuca) and red (Chondrus crispus) macroalgae were prepared and their biochemical properties were determined, including major biomolecules, sulphate and ash contents. The anticoagulant activity of each extract was investigated using different scales from the specific antithrombin-dependent pathway (anti-Xa and anti-IIa) to the intrinsic and/or common (Activated Partial Thromboplastin Time, APTT), extrinsic (Prothrombin Time, PT) or common (Thrombin Time, TT) anticoagulant pathways, and compared with those of commercial anticoagulants, heparin and Lovenox®. Laminaria digitata, Fucus vesiculosus and Chondrus crispus extracts showed a significant APTT anticoagulant capacity, only 5-fold lower than that of Lovenox®, which is a pure low molecular weight heparin used as an anticoagulant agent to prevent pulmonary embolism in patients undergoing surgery.

Impact of nonsynonymous mutations of factor X on the functions of factor X and anticoagulant activity of edoxaban.

PubMed

Noguchi, Kengo; Morishima, Yoshiyuki; Takahashi, Shinichi; Ishihara, Hiroaki; Shibano, Toshiro; Murata, Mitsuru

2015-03-01

Edoxaban is an oral direct factor Xa (FXa) inhibitor and its efficacy as an oral anticoagulant is less subject to drug-food and drug-drug interaction than existing vitamin K antagonists. Although this profile of edoxaban suggests it is well suited for clinical use, it is not clear whether genetic variations of factor X influence the activity of edoxaban. Our aim was to investigate a possible impact of single-nucleotide polymorphisms (SNPs) in the factor X gene on the functions of factor X and the activity of edoxaban. Two nonsynonymous SNPs within mature factor X, Ala152Thr and Gly192Arg, were selected as possible candidates that might affect the functions of FXa and the activity of edoxaban. We measured catalytic activities of wild type and mutant FXas in a chromogenic assay using S-2222 and coagulation times including prothrombin time (PT) and activated partial thrombin time (aPTT) of plasma-containing recombinant FXs in the presence and absence of edoxaban. Michaelis-Menten kinetic parameters of FXas, Km and Vmax values, PT and aPTT were not influenced by either mutation indicating these mutations do not affect the FXa catalytic and coagulation activities. The Ki values of edoxaban for the FXas and the concentrations of edoxaban required to double PT and aPTT were not different between wild type and mutated FXas indicating that both mutations have little impact on the activity of edoxaban. In conclusion, these data suggest that edoxaban has little interpatient variability stemming from SNPs in the factor X gene.

[Perioperative changes of coagulation functions in the local advanced liver cancer patients receiving liver transplantation].

PubMed

Wang, Hao-Yuan; Zhao, Qing-Yu; Yuan, Yun-Fei

2008-07-01

Liver transplantation is widely accepted as an effective therapy of hepatoma. Perioperative dynamic observation of coagulation function is important for graft-receivers. This study was to explore perioperative changes of coagulation functions in the local advanced liver cancer patients who received liver transplantation. Clinical data of 31 local advanced liver cancer patients, underwent liver transplantation from Sep. 2003 to Jan. 2007, were analyzed. Platelet (PLT) counting, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) and international normalized ratio (INR) before operation, at anhepatic phase and the first week after operation were analyzed to evaluate congulation function. The coagulation functions of most patients were normal before operation. The six parameters varied significantly at anhepatic phase and on most days of the first week after operation when compared with the preoperative levels (P<0.05). The elevation of PT, APTT, TT and INR and the decrease of Fib and PLT were more apparent at anhepatic phase when compared with the preoperative levels [PT: (19.51+/-3.78) s vs. (14.16+/-1.46) sû APTT: (77.01+/-30.51) s vs. (40.19+/-4.11) sû TT: (27.50+/-15.10) s vs. (19.46+/-3.05) sû INR: 1.61+/-0.37 vs. 1.11+/-0.16û Fib: (1.73+/-0.70) g/L vs. (3.38+/-1.00) g/Lû PLT: (108+/-60)x10(9)/L vs. (184+/-108)x10(9)/L, all P<0.01]. In the first week after operation, the elevated PT, APTT, TT and INR levels decreased gradually, APTT was even lower than the preoperative level [(32.05+/-6.50) s vs. (40.19+/-4.11) s, P<0.01]. These changes appeared usually on 1-2 days after operation. Decreased PLT and Fib regained slowly at the first week after operation when compared with the preoperative levels [Fib: (2.13+/-0.53) g/L vs. (3.38+/-1.00) g/L, P<0.01û PLT: (145+/-90)x10(9)/L vs. 184+/-108]x10(9)/L, P<0.05], but the values were normal. According to stratification analysis, the hypocoagulability was more obvious in the patients with moderate or severe cirrhosis and those with Child-Pugh B level than in their counterparts. The coagulation functions of local advanced liver cancer patients shift from hypocoagulatory to hypercoagulatory or normal in perioperative period, therefore, prevention of bleeding should be focused on at anhepatic phase and on 1-2 days after operation while prevention of thrombosis should be focused on after the first week after operation. The degree of liver cirrhosis and Child-Pugh level could help to evaluate postoperative coagulation disorder.

Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways

PubMed Central

Muralidharan-Chari, Vandhana; Kim, Jaehan; Abuawad, Ahlam; Naeem, Mubeena; Cui, Huadong; Mousa, Shaker A.

2016-01-01

Thymoquinone (THQ) is a major component of black seeds. Given that both THQ and black seeds exhibit anti-cancer and anti-inflammatory activities, we hypothesized that THQ will affect cancer-associated thrombosis (CAT), which is primarily triggered by tissue factor (TF) and inflammation. The effect of both black seed-extracted and purchased (“pure”) THQ on normal blood coagulation was tested with in vitro thromboelastography (TEG) and activated partial thromboplastin time (aPTT) coagulation assays. The effect of pure THQ on CAT was tested with aPTT assay using pancreatic cancer cell lines that are either positive or negative for TF, and with TEG assay using lipopolysaccharide as an inflammatory trigger. Additionally, the direct effect of THQ on the inactivation of factors IIa and Xa was assessed. Since TNF-α facilitates crosstalk between inflammation and thrombosis by triggering the NF-κB pathway, we tested THQ’s ability to interfere with this communication with a luciferase assay. Both extracted and pure THQ had minimal effects on normal blood coagulation. Pure THQ reversed CAT initiated by both TF and inflammation to basal levels (p < 0.001). Mechanistically, while THQ had minimal to no effect on factor IIa and Xa inactivation, it strongly reduced the effects of TNF-α on NF-κB elements (p < 0.001). THQ has a minimal effect on basal coagulation and can reverse CAT in vitro, possibly by interfering with the crosstalk between inflammation and coagulation. This study suggests the utility of THQ as a preventative anticoagulant and/or as a supplement to existing chemotherapies and anticoagulant therapies. PMID:27043539

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

PubMed

Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

2017-01-01

Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Preparation and anticoagulant activity of N-succinyl chitosan sulfates.

PubMed

Wang, Tan; Zhou, Yue; Xie, Weiguo; Chen, Lingyun; Zheng, Hua; Fan, Lihong

2012-12-01

In order to develop a promising substitute for heparin, N-succinyl chitosan (NSC) was chemically modified by sulfating agent N(SO(3)Na)(3), which were synthesized with sodium bisulfite and sodium nitrite in aqueous solution. The N-succinyl chitosan sulfates (NSCS) products were characterized by infrared spectroscopy (FT-IR) and (13)C NMR. The degree of substitution (DS) of NSCS depended on the ratio of sulfating agent to N-succinyl chitosan, reaction temperature, reaction time and pH of sulfation agent. N-succinyl chitosan sulfates with DS of 1.97 were obtained under optimal conditions. The in vitro coagulation assay of NSCS was determined by activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) assays. The results showed that NSCS obviously prolonged APTT. The anticoagulant activity strongly depended on DS, molecular weight (M(w)) and concentration of NSCS. The anticoagulant activity of NSCS promoted with the increase of DS and concentration, and NSCS exhibited the best anticoagulant activity with the M(w) of 1.37×10(4). Copyright © 2012. Published by Elsevier B.V.

Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakurada, Isao; Endo, Toshiya; Hikita, Katsuyoshi

2017-06-01

Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated.

Hypofibrinogenemia induced by tigecycline: a potentially life-threatening coagulation disorder.

PubMed

Sabanis, Nikolaos; Paschou, Eleni; Gavriilaki, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2015-01-01

A 74-year-old female patient with end-stage renal disease, undergoing periodic hemodialysis, was hospitalized due to infection by multidrug-resistant Acinetobacter baumannii after hip replacement surgery. She was treated with tigecycline, a glycylcycline agent. Subsequently she developed coagulation disorders as substantiated by increased international normalized ratio (INR), prolonged partial thromboplastin time (aPTT), and severe hypofibrinogenemia, followed by transaminasemia, cholestasis, and anemia. Ultrasonography and computed tomography revealed no underlying pathological entities. Tigecycline was discontinued and the patient underwent daily hemodialysis and received multiple fresh frozen plasma transfusions. Additionally, she was treated with colistin. Her clinical and laboratory status improved. We suggest that patients treated with tigecycline should be monitored for changes in INR, aPTT, and fibrinogen levels to avoid severe, life-threatening coagulation disturbances.

Evaluation of the coagulometer STA R Max® (Stago) for routine coagulation parameters.

PubMed

Brulé, Justine; Sinegre, Thomas; Pereira, Bruno; Berger, Marc G; Serre-Sapin, Anne-Françoise; Lebreton, Aurélien

2018-04-01

The STA R Max ® is a fully automated multiparameter coagulometer using clotting (viscosity-based detection system), chromogenic and immunologic assays. STA R Max ® is equipped with an innovative software (STA Coag Expert ® ) designed to assist laboratory in accreditation. The aim of this study was to evaluate its performances for the certification according to ISO 15189 quality standard in the haemostasis unit of our university hospital. The following tests were evaluated: prothrombin time (PT), activated partial thromboplastin time (aPTT), kaolin cephalin clotting time (KCCT), fibrinogen, anti-Xa assay and D-dimers. In normal and pathological range, the intra-assay coefficients of variation (CV) for PT, aPTT, KCCT and fibrinogen were below 4.0%. Intra-assay CV was of 4.0% for the anti-Xa assay and intra-assay CV was of 7.9% for D-dimers. Inter-assay CV were below 5.0% for PT, aPPT, KCCT and fibrinogen, 14.9% for anti-Xa assay and 8.6% for D-dimers. The interlaboratory comparisons were below 8.7% for PT, aPPT and KCCT, 5.0% for fibrinogen and 15.5% for anti-Xa assay. All results were acceptable according to suitable CV established by GFHT and the provider. The concordance between all coagulometers was excellent, with correlation coefficient close to 1 (0.99 for all parameters except for aPPT which was 0.98) calculated thanks to an intra-class correlation study. In conclusion, the STA R Max ® analyser is suitable for haemostasis laboratories and facilitates certification of a laboratory.

Assessment of the effects of dalteparin on coagulation variables and determination of a treatment schedule for use in cats.

PubMed

Schönig, Jette C; Mischke, Reinhard H

2016-07-01

OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti-activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants.

PubMed

Cuker, Adam; Siegal, Deborah M; Crowther, Mark A; Garcia, David A

2014-09-16

Non-vitamin K oral anticoagulants (NOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. This study's objective was to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R(2) = 0.92 to 0.99) and ecarin-based assays (R(2) = 0.92 to 1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linear (R(2) = 0.89 to 1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in NOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Fabrication and characterization of chitosan nanoparticles and collagen-loaded polyurethane nanocomposite membrane coated with heparin for atrial septal defect (ASD) closure.

PubMed

Kaiser, Eva; Jaganathan, Saravana Kumar; Supriyanto, Eko; Ayyar, Manikandan

2017-07-01

Atrial septal defect (ASD) constitutes 30-40% of all congenital heart diseases in adults. The most common complications in the treatment of ASD are embolization of the device and thrombosis formation. In this research, an occluding patch was developed for ASD treatment using a well-known textile technology called electrospinning. For the first time, a cardiovascular occluding patch was fabricated using medical grade polyurethane (PU) loaded with bioactive agents namely chitosan nanoparticles (Cn) and collagen (Co) which is then coated with heparin (Hp). Fourier transform infrared spectrum showed characteristic vibrations of several active constituents and changes in the absorbance due to the inclusion of active ingredients in the patch. The contact angle analysis demonstrated no significant decrease in contact angle compared to the control and the composite patches. The structure of the electrospun nanocomposite (PUCnCoHp) was examined through scanning electron microscopy. A decrease in nanofiber diameter between control PU and PUCnCoHp nanocomposite was observed. Water uptake was found to be decreased for the PUCnCoHp nanocomposite against the control. The hemocompatibility properties of the PUCnCoHp ASD occluding patch was inferred through in vitro hemocompatibility tests like activated partial thromboplastin time (APTT), prothrombin time (PT) and hemolysis assay. It was found that the PT and APTT time was significantly prolonged for the fabricated PUCnCoHp ASD occluding patch compared to the control. Likewise, the hemolysis percentage was also decreased for the PUCnCoHp ASD patch against the control. In conclusion, the developed PUCnCoHp patch demonstrates potential properties to be used for ASD occlusion.

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro

PubMed Central

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-01-01

Aim: To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Methods: Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Results: Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca2+ concentration, while Na+ and K+ concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca2+ and Na+ concentrations. Si4+ (0.2434 g/L) and Al3+ (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca2+ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Conclusion: Zeolite releases Ca2+ into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time. PMID:23334236

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

PubMed

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-03-01

To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca(2+) concentration, while Na(+) and K(+) concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca(2+) and Na(+) concentrations. Si(4+) (0.2434 g/L) and Al(3+) (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca(2+) concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca(2+) into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

Acquired antiprothrombin antibodies: an unusual cause of bleeding.

PubMed

Carvalho, Cristiana; Viveiro, Carolina; Maia, Paulo; Rezende, Teresa

2013-01-07

Acquired inhibitors of coagulation causing bleeding manifestations are rare in children. They emerge, normally in the context of autoimmune diseases or drug ingestion, but transient and self-limiting cases can occur after viral infection. We describe, an otherwise healthy, 7-year-old girl who had gingival bleeding after a tooth extraction. The prothrombin time (PT) and the activated partial thromboplastin time (APTT) were both prolonged with evidence of an immediate acting inhibitor (lupic anticoagulant). Further coagulation studies demonstrated prothrombin (FII) deficiency and prothrombin directed (FII) antibodies. The serological tests to detect an underlying autoimmune disease were all negative. The coagulation studies normalised alongside the disappearance of the antibody. This article presents lupus anticoagulant hypoprothrombinaemia syndrome (LAHS) as a rare case of acquired bleeding diathesis in childhood.

Preparation, characterization and in vitro anticoagulant activity of corn stover xylan sulfates.

PubMed

Cheng, He-Li; Liu, Hao; Feng, Qing-Hua; Xie, Yi-Min; Zhan, Huai-Yu

2017-02-01

A new anticoagulant agent was prepared by introducing sulfate groups into corn stover xylan through homogeneous reactions. Three organic solvents, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and formamide (FA), were adopted as reaction media, with the assistance of LiCl. Structural characterization by FT-IR and 13 CNMR showed that xylan sulfate (XS) could be successfully synthesized with SO 3 ∙Pyridine (SO 3 ∙Py) complexes sulfation reagent in the three media. The effect of sulfation temperature, sulfation time, media type and molar ratio of -SO 3 /-OH on the degree of substitution (DS) and degree of the polymerization (DP) were studied. DMF/LiCl were more effective than DMSO/LiCl and FA/LiCl in preparation of xylan sulfate with high DS. The optimal conditions for sulfation were obtained when SO 3 ∙Py complex was added to DMF/LiCl with -SO 3 /-OH ratio of 1.5:1 and maintained at 50 °C for 3 h. Degree of polymerization of xylan was decreased during the sulfation process and DMF/LiCl offered the least xylan degradation as compared with DMSO/LiCl or FA/LiCl. Anticoagulant activities of the resultant xylan sulfates with different DS were evaluated by using activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Results indicated that the introducing of sulfate groups into xylan did endow the polysaccharides with anticoagulant activity. The APTT and TT of XS with DS of 1.20 reached 141 and 45.3 s at a dosage of 20 μg/mL, while the APTT and TT values for the blank sample were only 35.5 and 15.6 s. Furthermore, coagulation time was prolonged with the increase of DS and the concentration of XS. Our findings provide new insights into the value-added utilization of agricultural biomass.

Thromboelastography in Dogs with Chronic Hepatopathies.

PubMed

Fry, W; Lester, C; Etedali, N M; Shaw, S; DeLaforcade, A; Webster, C R L

2017-03-01

The coagulation status of dogs with liver disease is difficult to predict using conventional coagulation testing. To evaluate thromboelastography (TEG) results and associations with conventional coagulation results and indicators of disease severity and prognosis in dogs with chronic hepatopathies (CH). Twenty-one client-owned dogs. Dogs with CH were prospectively (10 dogs) and retrospectively (11 dogs) enrolled from 2008 to 2014. Kaolin-activated TEG was performed and compared with reference intervals by t-tests or Mann-Whitney tests. Correlation coefficients for TEG results and conventional coagulation and clinicopathologic results were determined. Significance was set at P < .05. Dogs with CH had significant increases in R (5.30 min vs 4.33 min), K (3.77 min vs 2.11 min), and LY30 (4.77% vs 0.68%) and decreased angles (55.3° vs 62.4°). G value defined 9 of 21, 7 of 21, and 5 of 21 dogs as normocoagulable, hypercoagulable, and hypocoagulable, respectively. G and MA were correlated with fibrinogen (r = 0.68, 0.83), prothrombin time (PT; r = -0.51, -0.53), and activated partial thromboplastin time (aPTT; r = -0.50, -0.50). K was correlated with PT (r = 0.75) and protein C activity (r = -0.92). Angle was correlated with aPTT (r = -0.63). Clinical score was correlated with PT (r = 0.60), MA (r = -0.53), and R (r = -0.47). Dogs with hyperfibrinolysis (LY30 > 3.04%; 5 of 21) had significantly higher serum transaminase activities. Dogs with portal hypertension had significantly lower G, MA, and angle and prolonged, K, R, and PT. Dogs with CH have variable TEG results. Negative prognostic indicators in CH correlate with hypocoagulable parameters on TEG. Hyperfibrinolysis in dogs with CH is associated with high disease activity. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Purification, characterization and in vitro anticoagulant activity of polysaccharides from Gentiana scabra Bunge roots.

PubMed

Cai, Weirong; Xu, Huiling; Xie, Liangliang; Sun, Jian; Sun, Taotao; Wu, Xiaoyan; Fu, Qinbao

2016-04-20

Three water-soluble polysaccharide fractions (GSP-1, GSP-2 and GSP-3) were obtained from Gentiana scabra Bunge roots by DEAE-Sepharose CL-6B and Sepharose CL-6B column chromatography. Their chemical characterizations were determined by high performance gel permeation chromatography (HPGPC), high performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) and Fourier transform infrared (FT-IR) spectrometer. Moreover, their in vitro anticoagulant activities were evaluated by activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays. GSP-1 and GSP-2 were composed of rhamnose, arabinose, galactose, glucose and galacturonic acid, while GSP-3 consisted of rhamnose, arabinose, galactose and galacturonic acid with a weight-average molecular weight of 5.8×10(4)Da. In comparison with the control group (saline), GSP, GSP-1, GSP-2 and GSP-3 could prolong APTT and TT, but not PT. Overall, GSP-3 exhibited potent anticoagulant activity and would be expected to be a potential source of anticoagulant. Copyright © 2015 Elsevier Ltd. All rights reserved.

Indications and Effects of Plasma Transfusions in Critically Ill Children.

PubMed

Karam, Oliver; Demaret, Pierre; Shefler, Alison; Leteurtre, Stéphane; Spinella, Philip C; Stanworth, Simon J; Tucci, Marisa

2015-06-15

Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. To identify patient characteristics and to characterize indications leading to plasma transfusions in critically ill children, and to assess the effect of plasma transfusions on coagulation tests. Point-prevalence study in 101 pediatric intensive care units in 21 countries, on 6 predefined weeks. All critically ill children admitted to a participating unit were included if they received at least one plasma transfusion. During the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%) received at least one plasma transfusion and were included. The primary indications for plasma transfusion were critical bleeding in 22.3%, minor bleeding in 21.2%, planned surgery or procedure in 11.7%, and high risk of postoperative bleeding in 10.6%. No bleeding or planned procedures were reported in 34.1%. Before plasma transfusion, the median international normalized ratio (INR) and activated partial thromboplastin time (aPTT) values were 1.5 and 48, respectively. After plasma transfusion, the median INR and aPTT changes were -0.2 and -5, respectively. Plasma transfusion significantly improved INR only in patients with a baseline INR greater than 2.5. One-third of transfused patients were not bleeding and had no planned procedure. In addition, in most patients, coagulation tests are not sensitive to increases in coagulation factors resulting from plasma transfusion. Studies assessing appropriate plasma transfusion strategies are urgently needed.

PIVKA-II correlates with INR but not protein C or protein S concentrations in cord blood among newborns.

PubMed

Teruya, M; Soundar, E; Hui, S R; Eldin, K; Adcock, D; Teruya, J

2016-05-18

Protein induced by vitamin K absence (PIVKA)-II, inactive precursor of prothrombin, is elevated in vitamin K (VK) deficiency. Our aims were to find the prevalence of VK deficiency in neonates, assess the utility of international normalized ratio (INR) as a screening tool, and explore the relationship between PIVKA-II, activated partial thromboplastin time (aPTT) and VK dependent anticoagulants. INR, aPTT, PIVKA-II, and proteins C and S activities were measured in neonatal cord blood prior to VK administration. We found 45% of neonates had subclinical VK deficiency based on PIVKA-II levels and 7% based on INR. Receiver operating characteristic (ROC) analysis assessed the utility of INR in detecting >4 ng/mL of PIVKA-II and ROC of the area under the curve was 0.70 (95% CI 0.46-0.92, p = 0.07). Proteins C and S activities were normal for age and did not correlate with PIVKA-II [(r = 0.40, p = 0.14) and (r = 0.29, p = 0.29), respectively]. There was no association between aPTT and PIVKA-II (p = 0.83). PIVKA-II seems to be a sensitive indicator of mild VK deficiency. Further studies are needed to investigate the lack of relationship between PIVKA-II and functional protein C or S levels.

Circuit lifespan during continuous renal replacement therapy for combined liver and kidney failure.

PubMed

Chua, Horng-Ruey; Baldwin, Ian; Bailey, Michael; Subramaniam, Ashwin; Bellomo, Rinaldo

2012-12-01

To evaluate circuit lifespan (CL) and bleeding risk during continuous renal replacement therapy (CRRT), in combined liver and renal failure. Single-center retrospective analysis of adults with acute liver failure or decompensated cirrhosis who received CRRT, without anticoagulation or with heparinization in intensive care unit. Seventy-one patients with 539 CRRT circuits were evaluated. Median overall CL was 9 (6-16) hours. CL was 12 (7-24) hours in 51 patients never anticoagulated for CRRT. In 20 patients who subsequently received heparinization, CL was 7 (5-11) hours without anticoagulation, which did not improve with systemic or regional heparinization (P = .231), despite higher peri-circuit activated partial thromboplastin time (APTT) and heparin dose. Using multivariate linear regression, patients with higher baseline APTT or serum bilirubin, or who were not mechanically ventilated, had longer CL (P < .05). Additionally, peri-circuit thrombocytopenia (P < .0001) or higher international normalized ratio (P < .05) predicted longer CL. Of 71 patients, 33 had significant bleeding events. Using multivariate logistic regression, patients with higher baseline APTT, vasoactive drug use >24 hours, or thrombocytopenia, had more bleeding complications (P < .05). Decreasing platelet counts (especially <50 × 10(9)/mm(3)) had an incremental effect on CL (P < .0001). CRRT CL is short in patients with liver failure despite apparent coagulopathy. Thrombocytopenia predicts longer CL and bleeding complications. Copyright © 2012 Elsevier Inc. All rights reserved.

Synthesis and anticoagulant activity of the quaternary ammonium chitosan sulfates.

PubMed

Fan, Lihong; Wu, Penghui; Zhang, Jinrong; Gao, Song; Wang, Libo; Li, Mingjia; Sha, Mingming; Xie, Weiguo; Nie, Min

2012-01-01

Quaternary ammonium chitosan sulfates with diverse degrees of substitution (DS) ascribed to sulfate groups between 0.52 and 1.55 were synthesized by reacting quaternary ammonium chitosan with an uncommon sulfating agent (N(SO(3)Na)(3)) that was prepared from sodium bisulfite (NaHSO(3)) through reaction with sodium nitrite (NaNO(2)) in the aqueous system homogeneous. The structures of the derivatives were characterized by FTIR, (1)H NMR and (13)C NMR. The factors affecting DS of quaternary ammonium chitosan sulfates which included the molar ratio of NaNO(2) to quaternary ammonium chitosan, sulfated temperature, sulfated time and pH of sulfated reaction solution were investigated in detail. Its anticoagulation activity in vitro was determined by an activated partial thromboplastin time (APTT) assay, a thrombin time (TT) assay and a prothrombin time (PT) assay. Results of anticoagulation assays showed quaternary ammonium chitosan sulfates significantly prolonged APTT and TT, but not PT, and demonstrated that the introduction of sulfate groups into the quaternary ammonium chitosan structure improved its anticoagulant activity obviously. The study showed its anticoagulant properties strongly depended on its DS, concentration and molecular weight. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Effects of thromboprophylactic doses of apixaban and rivaroxaban on coagulation and thrombin generation in association with total hip replacement.

PubMed

Helin, Tuukka A; Virtanen, Lauri; Manninen, Mikko; Leskinen, Jarkko; Leppilahti, Juhana; Joutsi-Korhonen, Lotta; Lassila, Riitta

2017-05-01

Factor Xa inhibitors (FXaI) apixaban and rivaroxaban are used for thromboprophylaxis after major elective orthopaedic surgery. Because few patient sample studies exist, we postoperatively assessed patients undergoing unilateral total hip arthroplasty, including 22 treated with apixaban (2.5 mg BID) and 20 treated with rivaroxaban (10 mg OD). We collected blood samples before and 3 h after drug intake at 4 time points, preoperatively, as well as on day 1, week 1 (day 2-8) and day 28 post-operation. APTT and PT were immediately analysed. Calibrated anti-FXa activity, Russel's Viper Venom Time (RVVT) and thrombin generation (TG; Calibrated Automated Thrombogram ® ) captured the effects of FXaI on coagulation and TG. APTT and PT remained within the reference interval throughout, and did not correlate with FXaI levels (PT R 2  = 0.44, APTT R 2  = 0.07). Mean apixaban concentration at the peak varied by eightfold (19-153 ng/mL), but rivaroxaban only by 1.5-fold (111-183 ng/mL). Rivaroxaban, but not apixaban prolonged RVVT at peak levels. Both FXaIs had a prolonged lag time of TG (p < 0.001). Rivaroxaban decreased ETP peak at all time points and reached a minimum at day 28 (540 nM/min at rivaroxaban 184 ng/mL, p < 0.001), while rivaroxaban trough levels were low and ETP values normal. However, with apixaban, after an initial decrease, ETP did not differ between peak and trough levels until decreasing on day 28 at peak (990 nM/min at apixaban 112 ng/mL, p = 0.005). In conclusion, due to different dosing and pharmacology rivaroxaban and apixaban distinctly inhibited TG under postoperative conditions.

Thromboelastographic Evaluation of Dogs with Acute Liver Disease.

PubMed

Kelley, D; Lester, C; Shaw, S; de Laforcade, A; Webster, C R L

2015-01-01

Given the liver's pivotal role in hemostasis and fibrinolysis, the coagulopathy accompanying hepatic disease is complex. To prospectively evaluate kaolin-activated thromboelastography (TEG) in dogs with acute liver disease (ALD) and compare with plasma-based coagulation tests. Twenty-one dogs with a diagnosis of ALD based on recent onset of clinical signs accompanied by increases in serum bilirubin concentration and alanine aminotransferase activity. Clinical presentation, CBC, serum biochemistry, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and TEG analysis were evaluated in 21 dogs with a subset also having fibrinogen, antithrombin (AT) activity, protein C (PC) activity, d-dimers, and von Willebrand's factor (vWF) activity analyzed. A PT >1.5 times the upper limit of normal defined acute liver failure (ALF). Dogs with ALD had mean increases in R, K, LY30, PT, aPTT, and vWF activity, and decreases in angle, maximal amplitude (MA), G, AT activity, and PC activity. The TEG results defined dogs as hypocoagulable (11/21), normocoagulable (8/21), or hypercoagulable (2/21). Increases in LY30 defined 8/21 dogs as hyperfibrinolytic. Hypocoagulable and hyperfibrinolytic dogs had lower fibrinogen and PC activity than dogs without these abnormalities. Overall, ALF dogs had greater increases in K and LY30, and decreases in MA, G, and PC activity than dogs with less severe hepatic impairment. Results for MA and LY30 were positively correlated with serum bilirubin concentration and white blood cell count, and negatively correlated with serum cholesterol concentration. ALD dogs have a range of coagulation abnormalities that trend toward hypocoagulability and hyperfibrinolysis as functional impairment occurs. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The acute effect of moderate intensity aquatic exercise on coagulation factors in haemophiliacs.

PubMed

Beltrame, Luis Gustavo Normanton; Abreu, Laurinda; Almeida, Jussara; Boullosa, Daniel Alexandre

2015-05-01

The objective of this cross-sectional study was to analyse the acute effect of aquatic exercise on haemostasis in persons with haemophilia. Ten adult haemophiliacs (8 type A, 2 type B) familiarized with aquatic training performed a 20-min exercise session in a swimming pool at an intensity of ~70% maximum heart rate (HR). Blood samples were collected immediately after the training session. The haemostatic parameters selected for analyses were factor VIII (FVIII), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen. There were unclear effects of the exercise bout on FVIII and APTT, with a possibly beneficial effect on PT (-11·4%; 90% confidence interval: -26·1;3·3%), and a trivial change on fibrinogen levels. It was found an association between the mean rise in HR during exercise and the decrement in PT after exercise (r = 0·729; P = 0·026). The greater changes were observed in the patients diagnosed with a moderate level of haemophilia. It is concluded that a short bout of moderate intensity of aquatic exercise may have a positive influence on PT in adults with haemophilia with greater changes in those individuals exhibiting a greater rise in HR during exercise. This may be an important issue to the haemostatic control of haemophiliacs in clinical settings. Further studies are warranted for testing the influence of different aquatic exercise intensities on haemostasis. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Predictors of poor outcomes in patients with wild mushroom-induced acute liver injury.

PubMed

Kim, Taerim; Lee, Danbi; Lee, Jae Ho; Lee, Yoon-Seon; Oh, Bum Jin; Lim, Kyoung Soo; Kim, Won Young

2017-02-21

To identify early predictive markers of poor outcomes in patients with acute liver injury from wild mushroom intoxication. This observational, retrospective record review involved adults aged ≥ 18 years admitted to emergency department with mushroom intoxication from January 2005 to December 2015. The diagnosis of mushroom intoxication was based on the following: (1) a positive history of recent wild mushroom intake (either raw or cooked); (2) the onset of gastrointestinal symptoms, such as watery diarrhea, vomiting, and/or abdominal pain, after ingestion; and (3) the exclusion of other possible causes of acute liver injury. Acute liver injury was defined by a > 5-fold elevation of liver enzymes or moderate coagulopathy [international normalized ratio (INR) > 2.0]. Clinical and laboratory findings were compared in survivors and non-survivors. Of 93 patients with mushroom intoxication, 23, 11 men (47.8%) and 12 women (52.2%), of median age 61 years, developed acute liver injury. The overall in-hospital mortality rate was 43.5% (10/23). Among the laboratory variables, mean serum alkaline phosphatase (73.38 ± 10.89 mg/dL vs 180.40 ± 65.39 mg/dL, P < 0.01), total bilirubin (2.312 ± 1.16 mg/dL vs 7.16 ± 2.94 mg/dL, P < 0.01) concentrations and indirect/direct bilirubin (2.45 ± 1.39 mg/dL vs 0.99 ± 0.45 mg/dL, P < 0.01) ratio as well as prothrombin time (1.88 ± 0.83 mg/dL vs 10.43 ± 4.81 mg/dL, P < 0.01), and activated partial thromboplastin time (aPTT; 32.48 ± 7.64 s vs 72.58 ± 41.29 s, P = 0.01), were significantly higher in non-survivors than in survivors. Logistic regression analysis showed that total bilirubin concentration (OR = 3.58, 95%CI: 1.25-10.22), indirect/direct bilirubin ratio (OR = 0.14, 95%CI: 0.02-0.94) and aPTT (OR = 1.30, 95%CI: 1.04-1.63) were significantly associated with mortality. All patients with total bilirubin > 5 mg/dL or aPTT > 50 s on day 3 died. Monitoring of bilirubin concentrations and aPTT may help in predicting clinical outcomes in patients with acute liver injury from wild mushroom intoxication.

Effect of oral administration of unfractionated heparin (UFH) on coagulation parameters in plasma and levels of urine and fecal heparin in dogs

PubMed Central

Erickson, Malathi; Hiebert, Linda M.; Carr, Anthony P.; Stickney, Jocelyn D.

2014-01-01

The effects of heparin administration, by the oral route, were evaluated in dogs. In single and multiple dose studies (single 7.5 mg/kg, multiple 3 × 7.5 mg/kg per 48 h), plasma, urine, and fecal samples were collected at various times up to 120 h after oral administration of unfractionated heparin. Changes in plasma and urine anti-Xa activity, plasma and urine anti-IIa activity, plasma activated partial thromboplastin time (APTT) and antithrombin (ATIII), and chemical heparin in urine and feces were examined with time. There was support for heparin absorption, with significant differences in APTT, heparin in plasma as determined by anti-Xa activity (Heptest) in the single dose study and plasma anti-Xa activity, anti-IIa activity and ATIII; and chemical heparin in urine in the multiple dose study. No clinical evidence of bleeding was detected in any dog during the studies. Oral heparin therapy may be applicable for thromboembolic disease in animals. Further studies are warranted to determine the effects of oral heparin at the endothelial level in the dog. PMID:24982550

An apparent case of brodifacoum toxicosis in a whelping dog.

PubMed

Fitzgerald, Scott D; Martinez, Jennifer; Buchweitz, John P

2018-01-01

A 7-y-old Weimaraner bitch was presented to emergency service after 3 h of active labor with no puppies produced. Hemoabdomen and hemothorax were present at the time of surgery; prothrombin time (PT) and activated partial thromboplastin time (aPTT) were both found to be within normal ranges. Surgical cesarean section was performed; 4 dead puppies and 5 live puppies were delivered. Because hemostasis was difficult to achieve, a hysterectomy was performed; however, the dog died as the operation was being completed. At autopsy, the pleural cavity contained 1.5 L of unclotted blood; the peritoneal cavity was relatively normal, and no obvious hemorrhage was associated with the surgical sites. All 4 dead fetuses were opened, and their pleural cavities were filled with unclotted blood. An anticoagulant screen was performed, and brodifacoum was identified in the liver of the bitch. This case is unusual in that the PT and aPTT were within reference intervals, but brodifacoum was present in sufficient amounts to potentially result in this dog bleeding to death, and also is suspected to have crossed the placenta and caused hemothorax and death in 4 of 9 puppies in utero.

Pharmacological Differentiation of Thrombomodulin Alfa and Activated Protein C on Coagulation and Fibrinolysis In Vitro.

PubMed

Tanaka, Kosuke; Tawara, Shunsuke; Tsuruta, Kazuhisa; Hoppensteadt, Debra; Fareed, Jawed

2018-01-01

Although thrombomodulin alfa (TM alfa), recombinant human soluble thrombomodulin, exerts antithrombogenic effects through activated protein C (APC), clinical trials suggested that TM alfa has a lower bleeding risk than does recombinant human APC. To address the mechanism explaining this difference, effects of TM alfa and APC on thrombogenic, coagulation, and fibrinolytic processes were compared in vitro. TM alfa and APC inhibited generation of thrombogenic markers, thrombin, and prothrombin fragment F1+2 and prolonged coagulation parameters, activated clotting time (ACT), and activated partial thromboplastin time (APTT). Concentrations of TM alfa effective for thrombin and F1+2 generation inhibition were comparable to those of APC. However, effects of TM alfa on ACT and APTT were clearly weaker than those of APC. TM alfa significantly prolonged clot lysis time (CLT) and decreased LY30, a parameter of degree of fibrinolysis in thromboelastography, whereas APC significantly shortened CLT and increased LY30. These results suggested that while the antithrombogenic effects of TM alfa were similar to those of APC, its anticoagulant effects were lower. In addition, effects of TM alfa were antifibrinolytic, while those of APC were profibrinolytic.

Assessment of effects of phenolic fractions from leaves and petals of dandelion in selected components of hemostasis.

PubMed

Lis, Bernadetta; Jędrejek, Dariusz; Stochmal, Anna; Olas, Beata

2018-05-01

Aerial parts and roots of Taraxacum officinale (dandelion) have been found to be rich sources of polyphenols, including cinnamic acid derivatives, flavonoids and triterpenoids, which exert different biological activities, such as anti-inflammatory, anticancer and antimicrobial. Additionally, the whole plant is recognized as safe and well tolerated by humans, with no reported adverse effects. Nowadays, dandelion is a commonly available dietary supplement and a component of pharmaceutical preparations used for the treatment of bladder, liver, and spleen. Nevertheless, the effect of dandelion on blood platelets and plasma - components of hemostasis involved in the functioning of a cardiovascular system and linked with various cardiovascular diseases, has not been studied yet. Thus, the main objective of our in vitro experiments was to examine the anti-platelet and antioxidant properties of four standardized dandelion phenolic fractions, i.e. leaves 50% and 85% methanol fractions, and petals 50% and 85% methanol fractions, in blood platelets. Additionally, aforementioned plant preparations were investigated for hemostatic activity in plasma, using three selected hemostatic parameters: the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). None of the studied dandelion fractions, caused the damage of human blood platelets, at the whole tested range. The inhibition of lipid peroxidation in platelets treated with H 2 O 2 /Fe (the donor of OH) was observed for two fractions: leaves and petals 50% fractions, both at the dose 50 μg/mL. Analysis of the effect on the coagulation activity of human plasma demonstrated that three fractions: petals 50% fraction, and leaves and petals 85% fractions, significantly prolonged the thrombin time, at the whole tested range. On the contrary, none of the fractions changed the APTT and the PT. The obtained results demonstrate that dandelion preparations, based on aerial parts, especially rich in hydroxycinnamic acid derivatives (leaves and petals 50% fractions) are promising plant materials exerting both antioxidant and anticoagulant activities of the hemostatic system that is beneficial in the prevention and treatment of cardiovascular diseases. Published by Elsevier Ltd.

Interaction between the LMWH reviparin and aspirin in healthy volunteers

PubMed Central

Klinkhardt, Ute; Breddin, Hans Klaus; Esslinger, Heinz Ulrich; Haas, Silvia; Kalatzis, Andreas; Harder, Sebastian

2000-01-01

Aims To investigate potential interactions between reviparin and acetylsalicylic acid (ASA 300 mg o.d. from day 1–5). Methods In an open, randomized, three-way-cross over study nine healthy volunteers received reviparin (s.c. injection of 6300 anti-Xa units) or placebo from days 3 to 5 and acetylsalicylic acid (ASA 300 mg) or placebo from days 1 to 5. Assessments included bleeding time (BT), collagen (1 µg ml−1) induced platelet aggregation (CAG), heptest, plasma antifactor Xa-activity and activated partial thromboplastin time (aPTT). Results Median bleeding time at day 5 was 5.5 min after reverparin alone and after ASA alone and was 9.6 min after the combination of reviparin and ASA. ASA treatment reduced CAG from 84% to 40 to 50% of Amax; values after combined treatment of reviparin with ASA were not different from those after ASA alone. aPTT was prolonged to 32 s after reviparin; this effect was not modified if subjects received ASA. Combined treatment with ASA and reviparin had no effect on plasma anti-Xa-activity and heptest compared with reviparin alone. Conclusions We could not entirely exclude a small interaction between reviparin and ASA on bleeding time, but the effect is probably without clinical significance. PMID:10759689

Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid anaphylactoid reactions.

PubMed

Mi, Yan-Ni; Ping, Na-Na; Li, Bo; Xiao, Xue; Zhu, Yan-Bing; Cao, Lei; Ren, Jian-Kang; Cao, Yong-Xiao

2017-10-01

Vitamin K1 injection induces severe dose-related anaphylactoid reactions and overdose for the treatment of vitamin K deficiency. We aimed to find an optimal and small dose of vitamin K1 injection to treat vitamin K deficiency and avoid anaphylactoid reactions in animal. Rats were administered a vitamin K-deficient diet and gentamicin to establish vitamin K deficiency model. Behaviour tests were performed in beagle dogs to observe anaphylactoid reactions. The results showed an increased protein induced by vitamin K absence or antagonist II (PIVKA-II) levels, a prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT) and a decrease in vitamin K-dependent coagulation factor (F) II, VII, IX and X activities in the model group. In vitamin K1 0.01 mg/kg group, the liver vitamin K1 levels increased fivefold and the liver vitamin K2 levels increased to the normal amount. Coagulation markers PT, APTT, FVII and FIX activities returned to normal. Both in the 0.1 and 1.0 mg/kg vitamin K1 groups, coagulation functions completely returned to normal. Moreover, the amount of liver vitamin K1 was 40 (0.1 mg/kg) or 100 (1.0 mg/kg) times as in normal. Vitamin K2 was about 4 (0.1 mg/kg) or 5 (1.0 mg/kg) times as the normal amount. There was no obvious anaphylactoid symptom in dogs with the dose of 0.03 mg/kg, which is equivalent to the dose of 0.01 mg/kg in rats. These results demonstrated that a small dose of vitamin K1 is effective to improve vitamin K deficiency and to prevent anaphylactoid reactions, simultaneously. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Primary Hemostatic Capacity of Whole Blood: A Comprehensive Analysis of Pathogen Reduction and Refrigeration Effects Over Time

DTIC Science & Technology

2013-01-01

reduction and refrigeration is intriguing and suggests that PRT WB may complement the beneficial effects of the antifibrinolytic, tranexamic acid in...and ABBREVIATIONS: aPTT = activated partial thromboplastin time; ASPI = arachidonic acid agonist; COL = collagen; GPIba = glycoprotein Ib alpha; K...riboflavin and ultraviolet (UV) light to damage the nucleic acids of white blood cells (WBCs), parasites, bacteria, and viruses, is being consid- ered

Prediction of thrombophilia in patients with unexplained recurrent pregnancy loss using a statistical model.

PubMed

Wang, Tongfei; Kang, Xiaomin; He, Liying; Liu, Zhilan; Xu, Haijing; Zhao, Aimin

2017-09-01

To establish a statistical model to predict thrombophilia in patients with unexplained recurrent pregnancy loss (URPL). A retrospective case-control study was conducted at Ren Ji Hospital, Shanghai, China, from March 2014 to October 2016. The levels of D-dimer (DD), fibrinogen degradation products (FDP), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), and platelet aggregation in response to arachidonic acid (AA) and adenosine diphosphate (ADP) were collected. Receiver operating characteristic curve analysis was used to analyze data from 158 UPRL patients (≥3 previous first trimester pregnancy losses with unexplained etiology) and 131 non-RPL patients (no history of recurrent pregnancy loss). A logistic regression model (LRM) was built and the model was externally validated in another group of patients. The LRM included AA, DD, FDP, TT, APTT, and PT. The overall accuracy of the LRM was 80.9%, with sensitivity and specificity of 78.5% and 78.3%, respectively. The diagnostic threshold of the possibility of the LRM was 0.6492, with a sensitivity of 78.5% and a specificity of 78.3%. Subsequently, the LRM was validated with an overall accuracy of 83.6%. The LRM is a valuable model for prediction of thrombophilia in URPL patients. © 2017 International Federation of Gynecology and Obstetrics.

Coagulation profiles of healthy Andalusian donkeys are different than those of healthy horses.

PubMed

Mendoza, F J; Perez-Ecija, R A; Monreal, L; Estepa, J C

2011-01-01

Coagulation disorders are frequently diagnosed, especially in hospitalized equidae, and result in increased morbidity and mortality. However, hemostatic reference intervals have not been established for donkeys yet. To determine whether the most common coagulation parameters used in equine practice are different between healthy donkeys and horses. Thirty-eight healthy donkeys and 29 healthy horses. Blood samples were collected to assess both coagulation and fibrinolytic systems by determination of platelet count, fibrinogen concentration, clotting times (prothrombin time [PT] and activated partial thromboplastin time [aPTT]), fibrin degradation products (FDP) and D-Dimer concentrations. PT and aPTT in donkeys were significantly (P < .05) shorter than those of horses. In contrast, FDP and D-Dimer concentrations were significantly (P < .05) higher in donkeys than in horses. The coagulation parameters most commonly determined in equine practice are different in donkeys compared with horses. Thus, the use of normal reference ranges reported previously for healthy horses in donkeys might lead to a misdiagnosis of coagulopathy in healthy donkeys, and unnecessary treatments in sick donkeys. This is the first report of normal coagulation profile results in donkeys, and further studies are warranted to elucidate the physiological mechanisms of the differences observed between donkeys and horses. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Acquired absolute vitamin K deficiency in a patient undergoing warfarin therapy.

PubMed

Takada, Hiroaki; Toru, Hifumi; Bunya, Naofumi; Kiriu, Nobuaki; Kato, Hiroshi; Koido, Yuichi; Yasuhiro, Kuroda

2014-06-01

We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old woman was admitted to our hospital because of dyspnea and sore throat diagnosed as pharyngitis 1 week before admission. On admission, the sore throat had exacerbated and dyspnea developed. She had history of atrial fibrillation, for which warfarin 1.5 mg/d was started approximately 10 years prior and her international normalized ratio (INR) had been maintained at an acceptable therapeutic level. Blood results revealed unmeasurable INR and abnormally prolonged activated partial thromboplastin time (APTT). She was diagnosed with adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20 mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the coagulopathy responded to intravenous VK administration, the patient was clinically diagnosed with warfarin-related relative VKD. Approximately 1 month later, she returned with complaints of sore throat. Blood results indicated abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent adenoiditis and VK deficient coagulopathy. The patient’s serum VK levels were low (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg) and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated. Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in patients undergoing warfarin therapy is primarily caused by, relative VKD. However, the possibility of warfarin-related absolute VKD should be suspected when INRis not sufficiently improved by intravenous VK administration.

Prophylaxis of thromboembolism in bariatric surgery with parnaparin.

PubMed

Forestieri, Pietro; Quarto, Gennaro; De Caterina, Maurizio; Cuocolo, Alberto; Pilone, Vincenzo; Formato, Antonio; Ruocco, Aldo; Ferrari, Patrizio

2007-12-01

There are limited data on appropriate dosing of low-molecular-weight heparins (LMWHs) for venous thromboembolism (VTE) prophylaxis in bariatric surgery. The primary objective of this preliminary study was to evaluate the preoperative effects of increasing doses of the LMWH parnaparin on coagulation in severely obese patients undergoing bariatric surgery. Severely obese patients (BMI > 50 kg/m(2)) were administered three increasing single doses of parnaparin (3200, 4250, and 6400 IU) on the three consecutive days leading up to biliointestinal bypass surgery. Activated partial thromboplastin time (APTT), anti-factor IIa and anti-factor Xa levels were measured 1 h before and 4 h after dosing. The highest dose (6400 IU/day) was continued from the day of surgery until day 30 (recovery period). Intermittent pneumatic compression and stockings were applied during surgery and the recovery period, respectively. Lower limb echoDoppler and phleboscintigraphy, and pulmonary scintigraphy were used for VTE detection. Ten patients (mean BMI 52.4 kg/m(2)) were recruited into this study. During the preoperative dosing phase, parnaparin dose-dependently prolonged APTT, with the 6400 IU dose significantly prolonging APTT versus the lower doses. Meanwhile, anti-factor Xa and anti-factor IIa activity was increased by the 4250 and 6400 IU doses. After surgery, one patient with heparin resistance experienced pulmonary embolization. No bleeding complications were observed. The dose-response data reported in this preliminary study suggest that parnaparin doses of 4250 and 6400 IU may provide effective prophylaxis for VTE in patients undergoing bariatric surgery. However, given the small number of patients, larger, well-controlled trials are required to confirm these findings.

Haemostatic alterations in a group of canine cancer patients are associated with cancer type and disease progression

PubMed Central

2012-01-01

Background Haemostatic alterations are commonly detected in human and canine cancer patients. Previous studies have described haemostatic dysfunction in canine patients with haemangiosarcomas and carcinomas, and haemostasis has been assessed in dogs with various malignant and benign neoplasias. Few studies have addressed the effect of cancer type and progression of disease on the presence of haemostatic alterations in canine patients. The objective of the present study was to evaluate haemostatic variables of coagulation and fibrinolysis in a group of canine cancer patients, and to compare haemostatic changes to the cancer type and progression of disease. Methods The study population consisted of 71 dogs with malignant neoplasia presented to the University Hospital for Companion Animals, Faculty of Life Sciences, University of Copenhagen, Denmark. The study was designed as a prospective observational study evaluating the haemostatic function in canine cancer patients stratified according to type of cancer disease and disease progression. The coagulation response was evaluated by thromboelastrography (TEG), platelet count, activated partial thromboplastin time (aPTT), prothombin time (PT), fibrinogen and antithrombin (AT); and fibrinolysis by d-dimer and plasminogen. Results Hypercoagulability was the most common haemostatic dysfunction found. Non mammary carcinomas had increased clot strength (TEG G), aPTT and fibrinogen compared to the other groups. When stratifying the patients according to disease progression dogs with distant metastatic disease exhibited significantly increased fibrinogen, and d-dimer compared to dogs with local invasive and local non-invasive cancers. Conclusion Hypercoagulability was confirmed as the most common haemostatic abnormality in canine cancer patients and haemostatic dysfunction in canine cancer patients was found related to the cancer type and progression of disease. Increase in TEG G, aPTT and fibrinogen were observed in non-mammary carcinomas and were speculated to overall represent a proinflammatory response associated with the disease. Dogs with distant metastatic disease exhibited increased fibrinogen and d-dimer. Future studies are needed to elucidate the clinical importance of these results. PMID:22280938

Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects

PubMed Central

Frost, Charles; Wang, Jessie; Nepal, Sunil; Schuster, Alan; Barrett, Yu Chen; Mosqueda-Garcia, Rogelio; Reeves, Richard A; LaCreta, Frank

2013-01-01

Aims To evaluate apixaban single dose safety, tolerability, pharmacokinetics and pharmacodynamics and assess the effect of food on apixaban pharmacokinetics. Methods A double-blind, placebo-controlled, single ascending-dose, first-in-human study assessed apixaban safety, pharmacokinetics and pharmacodynamics in healthy subjects randomized to oral apixaban (n = 43; 0.5–2.5 mg as solution or 5–50 mg as tablets) or placebo (n = 14) under fasted conditions. An open label, randomized, two treatment crossover study investigated apixaban pharmacokinetics/pharmacodynamics in healthy subjects (n = 21) administered apixaban 10 mg in fasted and fed states. Both studies measured apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT) or a modified PT (mPT). Results In the single ascending-dose study increases in apixaban exposure appeared dose-proportional. Median tmax occurred 1.5–3.3 h following oral administration. Mean terminal half-life ranged between 3.6 and 6.8 h following administration of solution doses ≤2.5 mg and between 11.1 and 26.8 h for tablet doses ≥5 mg. Concentration-related changes in pharmacodynamic assessments were observed. After a 50 mg dose, peak aPTT, INR and mPT increased by 1.2-, 1.6- and 2.9-fold, respectively, from baseline. In the food effect study: 90% confidence intervals of geometric mean ratios of apixaban Cmax and AUC in a fed vs. fasted state were within the predefined no effect (80–125%) range. Apixaban half-life was approximately 11.5 h. The effect of apixaban on INR, PT and aPTT was comparable following fed and fasted administration. Conclusions Single doses of apixaban were well tolerated with a predictable pharmacokinetic/pharmacodynamic profile and a half-life of approximately 12 h. Apixaban can be administered with or without food. PMID:22759198

Acetaminophen and meloxicam inhibit platelet aggregation and coagulation in blood samples from humans.

PubMed

Martini, Angela K; Rodriguez, Cassandra M; Cap, Andrew P; Martini, Wenjun Z; Dubick, Michael A

2014-12-01

Acetaminophen (Ace) and meloxicam (Mel) are the two types of analgesic and antipyretic medications. This study investigated the dose responses of acetaminophen and meloxicam on platelet aggregation and coagulation function in human blood samples. Blood samples were collected from six healthy humans and processed to make platelet-adjusted (100 × 10 cells/μl) blood samples. Acetaminophen (Tylenol, Q-PAP, 100 mg/ml) was added at the doses of 0 μg/ml (control), 214 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Similarly, meloxicam (Metacam, 5 mg/ml) was added at doses of 0 μg/ml (control), 2.85 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Fifteen minutes after the addition of acetaminophen and/or meloxicam, platelet aggregation was stimulated with collagen (2 μg/ml) or arachidonic acid (0.5 mmol/l) and assessed using a Chrono-Log 700 aggregometer. Coagulation function was assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT), and using Rotem thrombelastogram. A robust inhibition by acetaminophen and/or meloxicam was observed in arachidonic acid-stimulated platelet aggregation starting at 1 × dose. Collagen-stimulated platelet aggregation was inhibited by ACE starting at 1 × (78 ± 10% of control), and by meloxicam starting at 4 × (72 ± 5% of control, both P < 0.05). The inhibitions by acetaminophen and meloxicam combined were similar to those by acetaminophen or meloxicam. aPTT was prolonged by meloxicam starting at 4 ×. No changes were observed in PT or any of Rotem measurements by acetaminophen and/or meloxicam. Acetaminophen and meloxicam compromised platelet aggregation and aPTT. Further effort is warranted to characterize the effects of acetaminophen and meloxicam on bleeding in vivo.

Haematology and coagulation profiles in cats with congenital portosystemic shunts.

PubMed

Tzounos, Caitlin E; Tivers, Michael S; Adamantos, Sophie E; English, Kate; Rees, Alan L; Lipscomb, Vicky J

2017-12-01

Objectives The objectives of this study were, first, to report the haematological parameters and coagulation times for cats with a congenital portosystemic shunt (CPSS) and the influence of surgical shunt attenuation on these parameters; and, second, to identify any association between prolongation in coagulation profiles and incidence of perioperative haemorrhage. Methods This was a retrospective clinical study using client-owned cats with a CPSS. Signalment, shunt type (extra- or intrahepatic), degree of shunt attenuation (complete or partial), haematological parameters, prothrombin time (PT) and activated partial thromboplastin time (aPTT) test results, and occurrence of any perioperative clinical bleeding complications were recorded for cats undergoing surgical treatment of a CPSS at the Royal Veterinary College, UK, between 1994 and 2011. Results Forty-two cats were included. Thirty-six (85.7%) had an extrahepatic CPSS and six (14.3%) had an intrahepatic CPSS. Preoperatively, mean cell volume (MCV) and mean cell haemoglobin (MCH) were below the reference interval (RI) in 32 (76.2%) and 31 (73.8%) cats, respectively. Red blood cell count and mean cell haemoglobin concentration (MCHC) were above the RI in 10 (23.8%) and eight (19.1%) cats, respectively. Postoperatively, there were significant increases in haematocrit ( P = 0.044), MCV ( P = 0.008) and MCH ( P = 0.002). Despite the significant increase in MCV postoperatively, the median MCV postoperatively was below the RI, indicating persistence of microcytosis. Preoperatively, PT was above the upper RI in 14 cats (87.5%), and aPTT was above the upper RI in 11 cats (68.8%). No cat demonstrated a perioperative clinical bleeding complication. Conclusions and relevance Cats with a CPSS are likely to present with a microcytosis, but rarely present with anaemia, leukocytosis or thrombocytopenia. Surgical attenuation of the CPSS results in a significant increase in the HCT and MCV. Coagulation profiles in cats with a CPSS are likely to be prolonged, irrespective of shunt type, but do not appear to be associated with an increased risk of clinical bleeding.

Effects of extracts and isolated compounds from safflower on some index of promoting blood circulation and regulating menstruation.

PubMed

Yao, Dong; Wang, Zheng; Miao, Li; Wang, Linyan

2016-09-15

Carthamus tinctorius is used as one of the Traditional Chinese Medicine (TCM) materials in prescriptions and composite to promote blood circulation to remove blood stasis, regulate menstruation and alleviate pain for over 2500 years. Modern pharmacological experiments have demonstrated that safflower has wide-reaching biological activities, including dilating coronary artery, modulating immune system, improving myocardial ischemia, anticoagulation and thromboprophylaxis, antioxidation, antihypoxic, antiaging, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. Platelet aggregation of safflower extract and main constituents in safflower were determined by PAF-induced or ADP-induced platelet aggregation in vitro. Anticoagulation activity was measured by clotting assay of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) according to the methods provided by the biological reagents provider (Sun Biochemical). Antioxidant effects of safflower were assessed using DPPH radical-scavenging activity test, ABTS radical-scavenging activity test and ferric reducing antioxidant power test. In addition, rats ovary granulosa cell proliferation activity was used for the bio-activity index on regulate menstruation of safflower. Safflower extract at the concentration of 0.7g/mL (P<0.001) and 0.5g/mL (P<0.01) had significantly antagonistic effect on PAF-induced platelet aggregation, compared with negative control. And the anti-platelet aggregation of 0.7g/mL safflower extract was significantly stronger than that of positive control (P<0.001). 0.7g/mL of hydroxysafflor yellow A (P<0.01), anhydrosafflor yellow B (P<0.05), 6-hydroxykaempferol-3-O-rutinoside (P<0.05), keampferol-3-O-β-rutinoside (P<0.01) had significant effect on platelet aggregation compared with negative control. Safflower extract at the concentration of 0.5g/mL (P<0.001) and 0.125g/mL (P<0.01) could significantly inhibit ADP-induced platelet aggregation, compared with negative control. And antagonistic effect of safflower extract was significantly stronger than the effect of positive control (P<0.001). Adenosine (P<0.001), anhydrosafflor yellow B (P<0.01) and 6-hydroxykaempferol-3-O-rutinoside (P<0.01) at the concentration of 0.5g/mL had significant effect on ADP-induced platelet aggregation compared with negative control. 0.125g/mL of adenosine (P<0.05) had significant effect on ADP-induced platelet aggregation compared with negative control. The effect of 0.5g/mL adenosine (P<0.01) and 6-hydroxykaempferol-3-O-rutinoside (P<0.05) was significantly stronger than that of positive control. Safflower extract at the concentration of 0.7mg/mL (P<0.001) and 0.5mg/mL (P<0.001) had significantly anticoagulation activity in PT, TT and APTT, compared with negative control. However, the respective compound didn't have significant effect on PT and TT at experiment concentration. At the concentration of 0.7mg/mL, hydroxysafflor yellow A (P<0.01), 6-hydroxykaempferol-3,6,7-tri-O-β-d-glucoside (P<0.05), 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide (P<0.01), anhydrosafflor yellow B (P<0.001), 6-hydroxykaempferol-3-O-rutinoside (P<0.05) and keampferol-3-O-β-rutinoside (P<0.05) significantly prolonged APTT, compared with negative control. At the concentration of 0.5mg/mL, hydroxysafflor yellow A (P<0.05), 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide (P<0.05), anhydrosafflor yellow B (P<0.001), 6-hydroxykaempferol-3-O-rutinoside (P<0.05) and keampferol-3-O-β-rutinoside (P<0.05) could significantly prolong APTT, compared with negative control. From the results of DPPH, ABTS radical scavenging activity test and Fe(3+) reduction power test, 5mg/mL, 2.5mg/mL and 1.25mg/mL safflower extract had antioxidant effects. Every compound with each concentration (5mg/mL, 2.5mg/mL and 1.25mg/mL) had significant effect on Fe(3+) reduction power (P<0.001 vs. negative control). Safflower extract, cytidine, 6-hydroxy-kaempferol-3,6-di-O-β-d-glucoside-7-O-β-d-glucuronide, 6-hydroxykaemp-ferol-3,6,7-tri-O-β-D-glucoside and keampferol-3-O-β-rutinoside significantly promoted ovarian granulosa cell proliferation. Based on previous researches, the activities of safflower extract and pure compounds isolated from safflower were studied in this paper. This study found some compounds with the effects of anti-platelet aggregation, anticoagulation, antioxidation and ovarian granulosa cell proliferation, and further revealed the possible pharmacological mechanism of safflower. Copyright © 2016. Published by Elsevier Ireland Ltd.

Numerical assessment and comparison of pulse wave velocity methods aiming at measuring aortic stiffness.

PubMed

Obeid, Hasan; Soulat, Gilles; Mousseaux, Elie; Laurent, Stéphane; Stergiopulos, Nikos; Boutouyrie, Pierre; Segers, Patrick

2017-10-31

Pulse waveform analyses have become established components of cardiovascular research. Recently several methods have been proposed as tools to measure aortic pulse wave velocity (aPWV). The carotid-femoral pulse wave velocity (cf-PWV), the current clinical gold standard method for the noninvasive assessment of aPWV, uses the carotid-to-femoral pulse transit time difference (cf-PTT) and an estimated path length to derive cf-PWV. The heart-ankle PWV (ha-PWV), brachial-ankle PWV (ba-PWV) and finger-toe (ft-PWV) are also methods presuming to approximate aPWV based on time delays between physiological cardiovascular signals at two locations (~heart-ankle PTT, ha-PTT; ~brachial-ankle PTT, ba-PTT; ~finger-toe PTT, ft-PTT) and a path length typically derived from the subject's height. To test the validity of these methods, we used a detailed 1D arterial network model (143 arterial segments) including the foot and hand circulation. The arterial tree dimensions and properties were taken from the literature and completed with data from patient scans. We calculated PTTs with all the methods mentioned above. The calculated PTTs were compared with the aortic PTT (aPTT), which is considered as the absolute reference method in this study. The correlation between methods and aPTT was good and significant, cf-PTT (R 2   =  0.97; P  <  0.001; mean difference 5  ±  2 ms), ha-PTT (R 2   =  0.96; P  <  0.001; 150  ±  23 ms), ba-PTT (R 2   =  0.96; P  <  0.001; 70  ±  13 ms) and ft-PTT (R 2   =  0.95; P  <  0.001; 14  ±  10 ms). Consequently, good correlation was also observed for the PWV values derived with the tested methods, but absolute values differed because of the different path lengths used. In conclusion, our computer model-based analyses demonstrate that for PWV methods based on peripheral signals, pulse transit time differences closely correlate with the aortic transit time, supporting the use of these methods in clinical practice.

Monitoring of anticoagulant therapy in heart disease: considerations for the current assays.

PubMed

Boroumand, Mohammadali; Goodarzynejad, Hamidreza

2010-01-01

Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio (INR) was introduced to "normalize" all PT reagents to a World Health Organization (WHO) reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists (VKAs) (i.e., at least 6 weeks of VKA therapy), and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation, and congenital factor deficiencies. In contrast to marked progress in the standardization of PT reagents for INR reporting, no standardization system has been globally adopted for standardization of PTT reagents. Recently College of American Pathologists recommend that individual laboratories establish their own therapeutic range by using aPTT values calibrated against accepted therapeutic unfractionated heparin (UFH) levels calibrated against accepted therapeutic UFH levels performing anti-Xa test (which is the most accurate assay for monitoring UFH therapy).Herein, we review recent data on the monitoring of conventional anticoagulant agents. Marked interlaboratory variability still exists for PT, INR, and PTT tests. Further research should be focused on improving the standardization and calibration of these assays.

Interactions of oversulfated chondroitin sulfate (OSCS) from different sources with unfractionated heparin.

PubMed

Gray, Angel; Litinas, Evangelos; Jeske, Walter; Fareed, Jawed; Hoppensteadt, Debra

2012-01-01

In 2008, oversulfated chondroitin sulfate (OSCS) was identified as the main contaminant in recalled heparin. Oversulfated chondroitin sulfate can be prepared from bovine (B), porcine (P), shark (Sh), or skate (S) origin and may produce changes in the antithrombotic, bleeding, and hemodynamic profile of heparins. This study examines the interactions of various OSCSs on heparin in animal models of thrombosis and bleeding, as well as on the anticoagulant and antiprotease effects in in vitro assays. Mixtures of 70% unfractionated heparin (UFH) with 30% OSCS from different sources were tested. In the in vitro activated partial thromboplastin time (aPTT) assay, all contaminant mixtures showed a decrease in clotting times. In addition, a significant increase in bleeding time compared to the control (UFH/saline) was observed. In the thrombosis model, no significant differences were observed. The OSCSs significantly increased anti-Xa activity in ex vivo blood samples. These results indicate that various sources of OSCS affect the hemostatic properties of heparin.

Accidental fatal aflatoxicosis due to contaminated commercial diet in 50 dogs.

PubMed

Bruchim, Y; Segev, G; Sela, U; Bdolah-Abram, T; Salomon, A; Aroch, I

2012-08-01

Aflatoxins, produced by Aspergillus spp., are toxic contaminants of stored grain. This study describes 50 dogs presented with foodborne aflatoxicosis. Common clinical signs included lethargy (78%), vomiting (76%), anorexia (74%), icterus (66%), depression (66%), melena (60%), haematuria (36%) and diarrhoea (36%). Common laboratory abnormalities included increased activities of aspartate aminotransferase (86%), alkaline phosphatase (84%) and alanine aminotransferase (79%), hypoantithrombinaemia (86%), prolonged prothrombin (PT, 82%) and activated partial thromboplastin times (aPTT, 80%), hyperbilirubinaemia (73%), hypocholesterolaemia (60%) hypoalbuminemia (47%) and thrombocytopenia (42%). Non-survivors had longer PT and aPTT and lower antithrombin (P<0.001) at presentation compared to survivors (23.8s vs.10.5; 37.9 vs.17.6s and 5% vs. 54%, respectively). Hyperbilirubinaemia (>56.6 μmol/L) and albumin concentration <32.5 g/L at presentation were risk factors for mortality (P<0.0001). Common complications included disseminated intravascular coagulation (58%), hepatic encephalopathy (35%) and acute kidney injury (4%). The mortality rate was 68%, suggesting that dogs with aflatoxicosis have poor prognosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Surgical management and outcome of blunt major liver injuries: experience of damage control laparotomy with perihepatic packing in one trauma centre.

PubMed

Lin, Being-Chuan; Fang, Jen-Feng; Chen, Ray-Jade; Wong, Yon-Cheong; Hsu, Yu-Pao

2014-01-01

This retrospective study aimed to assess the clinical experience and outcome of damage control laparotomy with perihepatic packing in the management of blunt major liver injuries. From January 1998 to December 2006, 58 patients of blunt major liver injury, American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) equal or greater than III, were operated with perihepatic packing at our institute. Demographic data, intra-operative findings, operative procedures, adjunctive managements and outcome were reviewed. To determine whether there was statistical difference between the survivor and non-survivor groups, data were compared by using Mann-Whitney U test for continuous variables, either Pearson's chi-square test or with Yates continuity correction for contingency tables, and results were considered statistically significant if p<0.05. Of the 58 patients, 20 (35%) were classified as AAST-OIS grade III, 24 (41%) as grade IV, and 14 (24%) as grade V. At laparotomy, depending on the severity of injuries, all 58 patients underwent various liver-related procedures and perihepatic packing. The more frequent liver-related procedures included debridement hepatectomy (n=21), hepatorrhaphy (n=19), selective hepatic artery ligation (n=11) and 7 patients required post-laparotomy hepatic transarterial embolization. Of the 58 patients, 28 survived and 30 died with a 52% mortality rate. Of the 30 deaths, uncontrolled liver bleeding in 24-h caused 25 deaths and delayed sepsis caused residual 5 deaths. The mortality rate versus OIS was grade III: 30% (6/20), grade IV: 54% (13/24), and grade V: 79% (11/14), respectively. On univariate analysis, the significant predictors of mortality were OIS grade (p=0.019), prolonged initial prothrombin time (PT) (p=0.004), active partial thromboplastin time (APTT) (p<0.0001) and decreased platelet count (p=0.005). The mortality rate of surgical blunt major liver injuries remains high even with perihepatic packing. Since prolonged initial PT, APTT and decreased platelet count were associated with high risk of mortality, we advocate combination of damage control resuscitation with damage control laparotomy in these major liver injuries. Copyright © 2013 Elsevier Ltd. All rights reserved.

Internal Quality Control Practices in Coagulation Laboratories: recommendations based on a patterns-of-practice survey.

PubMed

McFarlane, A; Aslan, B; Raby, A; Moffat, K A; Selby, R; Padmore, R

2015-12-01

Internal quality control (IQC) procedures are crucial for ensuring accurate patient test results. The IQMH Centre for Proficiency Testing conducted a web-based survey to gather information on the current IQC practices in coagulation testing. A questionnaire was distributed to 174 Ontario laboratories licensed to perform prothrombin time (PT) and activated partial thromboplastin time (APTT). All laboratories reported using two levels of commercial QC (CQC); 12% incorporate pooled patient plasma into their IQC program; >68% run CQC at the beginning of each shift; 56% following maintenance, with reagent changes, during a shift, or with every repeat sample; 6% only run CQC at the beginning of the day and 25% when the instruments have been idle for a defined period of time. IQC run frequency was determined by manufacturer recommendations (71%) but also influenced by the stability of test (27%), clinical impact of an incorrect test result (25%), and sample's batch number (10%). IQC was monitored using preset limits based on standard deviation (66%), precision goals (46%), or allowable performance limits (36%). 95% use multirules. Failure actions include repeating the IQC (90%) and reporting patient results; if repeat passes, 42% perform repeat analysis of all patient samples from last acceptable IQC. Variability exists in coagulation IQC practices among Ontario clinical laboratories. The recommendations presented here would be useful in encouraging standardized IQC practices. © 2015 John Wiley & Sons Ltd.

New prodrugs of metformin do not influence the overall haemostasis potential and integrity of the erythrocyte membrane.

PubMed

Markowicz-Piasecka, Magdalena; Sikora, Joanna; Mateusiak, Łukasz; Mikiciuk-Olasik, Elżbieta; Huttunen, Kristiina M

2017-09-15

Although metformin, an oral anti-diabetic drug, has been found to have multidirectional effects over the past decade, it is characterised by unfavourable pharmacokinetic properties. This study discusses the effects of metformin, phenformin and three prodrugs of metformin on the haemostasis and integrity of Red Blood Cells (RBCs). The influence of examined biguanide derivatives on haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test) at 405nm. The extrinsic and intrinsic coagulation pathway were examined by measuring the PT (Prothrombin Time) and aPTT (Activated Partial Tromboplastin Time). Haemolysis assay, microscopy and flow cytometry studies were used to assess the effect of the tested compounds on RBCs. Although none of the tested biguanide derivatives significantly influenced the overall potential of clot formation and fibrinolysis (CL AUC constants), statistically significant changes were seen in the values of the kinetic parameters of fibrinolysis. Furthermore, only prodrug 2, with an 8-carbon alkyl chain, unfavourably affected RBCs by interaction with the erythrocyte membrane leading to significant haemolysis. Our results provide a further insight into the effects of metformin and its prodrugs on haemostasis and RBCs and underscore the necessity for further research. Copyright © 2017 Elsevier B.V. All rights reserved.

Bromelain has paradoxical effects on blood coagulability: a study using thromboelastography.

PubMed

Kaur, Harmanpreet; Corscadden, Kathryn; Lott, Carlene; Elbatarny, Hisham S; Othman, Maha

2016-10-01

Bromelain is a crude extract from pineapple that is known for a wide array of pharmacological effects including protein digestion, fibrinolytic and anti-immune inflammatory effects and has been popularly used as a phytotherapeutic drug. However, its clinical values and applications remain understudied. The aim of this study was to investigate the effect of bromelain on the coagulability of blood using thromboelastography (TEG). We identified 0.4 U/ml as the minimum concentration of bromelain that results in modification of a normal TEG tracing. We studied the effects of this dose on whole blood samples obtained from normal and hypercoagulable individuals using TEG and evaluated their plasma using conventional tests including prothrombin time (PT) and activated partial thromboplastin time (APTT). We extended this analysis to investigate the effect of bromelain on platelet aggregation in normal blood and on the coagulability of mice blood in vivo in response to a clinically relevant dose injected intraperitoenally. The addition of bromelain ex vivo reduced coagulability of both normal and hypercoagulable blood significantly and resulted in 47 and 22% prolongation of PT and 20 and 10% prolongation of APTT in normal and hypercoagulable samples, respectively and inhibited adenosine di-phosphate (ADP)-induced platelet aggregation by 19%. In vivo, there was a considerable variation in TEG parameters in blood obtained from mice and unexpectedly a paradoxical effect toward hypercoagulability was shown in response to 1.5 mg/kg bromelain injected intraperitoneally into seven different animals. However, these results were not statistically significant when compared with the saline-injected animals. Although the in-vitro findings in this small study indicate a potential anticoagulant effect for bromelain, this needs to be interpreted with caution as neither an oral nor intravenous routes were evaluated. The paradoxical in-vivo data following intraperitoneal administration show the complexity of the effects of bromelain beyond platelets and indicate possible effects on other cells or proteins that require further investigations.

Correlation between hematologic profile and transaminase enzymes with hospitalization duration dengue

NASA Astrophysics Data System (ADS)

Tinambunan, E.; Suryani; Katu, S.; Halim, R.; Mubin, A. H.; Sahyuddin

2018-03-01

Dengue is an infectious disease that can be found from mild to severe andaffected the clinical spectrum of the disease. Various hematologic profiles and transaminase enzymes are thought to reflect the severity of the disease thus affecting the hospitalization duration. For determining the correlation between hematological profile and transaminase enzyme to the hospitalization duration in dengue patients, an observational design study with the cross-sectional approach on dengue subjects was from 2 hospitals in Makassar. Hemoglobin, leukocyte, thrombocyte, AST, ALT, PT, and APTT were examined for hospitalization duration. There were 65 samples (34 men, 31 women) with the length of stay <5 days 34 people and ≥ 5 days 31 people. The result of the analysis showed that there was a low correlation of leukocyte value (p = 0.036) and APTT prolongation (p = 0.023) with hospitalization duration of dengue patients. There was no correlation between the elevated of hematocrit value (p = 0.429), thrombocytopenia (p = 1.000), elevated of AST (p = 0.456) and ALT (p = 0.285) on hospitalization duration. In conclusion, low leukocyte values and APTT prolongation correlate with hospitalization duration but did not correlate significantly with hospitalization duration for elevated hematocrit, thrombocytopenia, elevated AST, and ALT.

Evaluation of the Becton-Dickinson rapid serum tube: does it provide a suitable alternative to lithium heparin plasma tubes?

PubMed

Dimeski, Goce; Masci, Paul P; Trabi, Manuela; Lavin, Martin F; de Jersey, John

2010-05-01

Obtaining a suitable specimen for analysis in a timely manner is pivotal in clinical chemistry service provision. Serum is recognized as the preferred specimen for most assays, but because of time constraints for completion of clotting and an increasing number of patients on anti-coagulant therapy, latent clotting or no clotting is an outcome which can lead to errors and delay in delivery of critical results. Although lithium heparin plasma has unique problems, it has become an alternative in hospital-based laboratories. The Becton-Dickinson (BD) rapid serum tube (RST) was evaluated in a hospital environment using a total of 53 participants, both healthy and anticoagulated, for 31 analytes against BD PST II and BD SST II tubes measured with Beckman DxC800 and DxI800 analyzers. Most results from the RST tube were comparable with those from the SST II tube. Potassium results were closer to the PST II plasma concentrations. Incomplete and latent clotting was encountered in the RST specimens from participants (cardiac and dialysis) who had received a total of >7000 units of heparin [activated partial thromboplastin time (APTT) >150 s], warfarin/heparin combination, and specimens from cardiac surgery patients who had received a total of >25,000 units of heparin (APTT >200 s) at the time of collection of specimens. The RST tube provides a suitable alternative to lithium heparin plasma tubes for most patients in a hospital environment. However, latent clotting continued to occur in specimens collected from participants who had received high concentrations of anticoagulants.

Coagulation is more affected by quick than slow bleeding in patients with massive blood loss.

PubMed

Zhao, Juan; Yang, Dejuan; Zheng, Dongyou

2017-03-01

Profuse blood loss affects blood coagulation to various degrees. However, whether bleeding speed affects coagulation remains uncertain. This study aimed to evaluate the effect of bleeding speed on coagulation function. A total of 141 patients in the Department of Thoracic Surgery of our hospital were evaluated between January 2007 and February 2014. There are two groups of patients, those who received decortication for chronic encapsulated empyema were called the slow-bleeding group, and those who received thoracoscopic upper lobectomy were called the fast bleeding group; each group was further subdivided into three: group A, 1000 ml ≤ bleeding amount < 1500 ml; group B, 1500 ml ≤ bleeding amount < 1700 ml; group C, 1700 ml ≤ bleeding amount < 2000 ml. Then, coagulation function was assessed in all patients before and during surgery and at 1, 2, and 24 h after surgery, measuring prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, blood pressure, hematocrit, hemoglobin, and platelets. Bleeding duration was overtly longer in the slow-bleeding group than that in quick bleeding individuals (2.3 ± 0.25 h vs. 0.41 ± 0.13 h, P < 0.001). Fibrinogen, hematocrit, hemoglobin, and platelets strikingly decreased, whereas prothrombin time and APTT values significantly increased with bleeding amounts in both quick and slow-bleeding groups. Interestingly, compared with slow-bleeding patients, coagulation indices at each time point and bleeding amounts had significant differences in the quick bleeding group.Increased consumption of coagulation factors in quick bleeding may have greater impact on coagulation function.

Preparation of low molecular weight Sargassum fusiforme polysaccharide and its anticoagulant activity

NASA Astrophysics Data System (ADS)

Sun, Yuhao; Chen, Xiaolin; Liu, Song; Yu, Huahua; Li, Rongfeng; Wang, Xueqin; Qin, Yukun; Li, Pengcheng

2017-10-01

Heparin has been used as an anticoagulant drug for many years, but it has significant side effects. In the search for good substitutes, low molecular weight (MW) polysaccharides from Sargassum fusiforme have been examined and confirmed to possess biological activities. Here, S. fusiforme polysaccharides (SFP) were extracted and subjected to a hydrogen peroxide (H2O2) oxidation method for the preparation of low-MW SFP (LSFP). The effects of temperature, pH, and H2O2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin (APTT), prothrombin (PT) and thrombin times (TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these effects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined effects. The details of this mechanism require further verification.

Potential effects of vildagliptin on biomarkers associated with prothrombosis in diabetes mellitus.

PubMed

Khan, Sana; Khan, Saba; Panda, Bibhu Prasad; Akhtar, Mohd; Najmi, Abul Kalam

2015-01-01

Diabetes mellitus (DM) is one of the risks linked with susceptibility of thrombosis. We tried to inspect the effect of a novel oral antidiabetic agent, vildagliptin, in preventing prothrombosis associated with DM. DM was produced by a dose of streptozotocin (STZ) or in albino wistar rats. Rats were treated orally with pioglitazone, standard treatment and vildagliptin alone and in combination for 3 weeks. Finally, the varied levels of coagulation biomarkers, including activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen and inflammatory parameters, nitric oxide (NO), C-reactive protein (CRP) and TNF-α and lipid profile were estimated along with platelet count and total leukocyte count (TLC). In vitro fibrinolytic activity of both the drugs was also determined. Vildagliptin significantly reduced cholesterol, triglycerides, TLC, CRP and TNF-α and increased aPTT and NO levels in STZ diabetic rats. However, pioglitazone was more successful in reducing fibrinogen and platelet count. Nevertheless, combination of the drugs was also effective than pioglitazone or vildagliptin alone in improvising hypercoagulation and inflammatory biomarkers. It is evident from the present study that vildagliptin has an influence on the biomarkers linked to the progression of thrombosis and may delay thrombogenesis linked to DM. Hence, vildagliptin alone and in combination might prove as an encouraging therapy for DM-linked thrombosis marked by inflammation and hypercoagulation.

In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste.

PubMed

Suleria, Hafiz Ansar Rasul; Hines, Barney M; Addepalli, Rama; Chen, Wei; Masci, Paul; Gobe, Glenda; Osborne, Simone A

2016-12-31

Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone ( Haliotis rubra ) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin.

In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste

PubMed Central

Suleria, Hafiz Ansar Rasul; Hines, Barney M.; Addepalli, Rama; Chen, Wei; Masci, Paul; Gobe, Glenda; Osborne, Simone A.

2016-01-01

Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin. PMID:28042854

Hemocompatibility evaluation of poly(1,8-octanediol citrate) blend polyethersulfone membranes.

PubMed

Zailani, Muhamad Zulhilmi; Ismail, Ahmad Fauzi; Sheikh Abdul Kadir, Siti Hamimah; Othman, Mohd Hafiz Dzarfan; Goh, Pei Sean; Hasbullah, Hasrinah; Abdullah, Mohd Sohaimi; Ng, Be Cheer; Kamal, Fatmawati

2017-05-01

In this study, poly (1,8-octanediol citrate) (POC) was used to modify polyethersulfone (PES)-based membrane to enhance its hemocompatibility. Different compositions of POC (0-3%) were added into the polyethersulfone (PES) dope solutions and polyvinylpyrrolidone (PVP) was used as pore forming agent. The hemocompatible POC modified PES membranes were fabricated through phase-inversion technique. The prepared membranes were characterized using attenuated total reflectance-Fourier transform infrared (ATR-FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Atomic-force microscopy (AFM), contact angle, Zeta-potential, membrane porosity and pore size and pure water flux (PWF) and BSA rejection. The hemocompatibility of the modified PES membranes was evaluated by human serum fibrinogen (FBG) protein adsorption, platelet adhesion, activated partial thromboplastin time (APTT) and prothrombin time (PT), and thrombin-antithrombin III (TAT), complement (C3a and C5a) activation and Ca 2+ absorption on membrane. Results showed that by increasing POC concentration, FBG adsorption was reduced, less platelets adhesion, prolonged APTT and PT, lower TAT, C5a and C3a activation and absorb more Ca 2+ ion. These results indicated that modification of PES with POC has rendered improved hemocompatibility properties for potential application in the field of blood purification, especially in hemodialysis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1510-1520, 2017. © 2017 Wiley Periodicals, Inc.

Evidence of hypercoagulability in dogs with parvoviral enteritis.

PubMed

Otto, C M; Rieser, T M; Brooks, M B; Russell, M W

2000-11-15

To determine whether dogs with naturally occurring canine parvoviral (CPV) enteritis have laboratory evidence of hypercoagulability. Case-control study. Animals-9 dogs with naturally occurring CPV enteritis and 9 age-matched control dogs. Blood was collected from all dogs within 24 hours of admission for thromboelastography (TEG) and determination of activated partial thromboplastin time (aP-TT), prothrombin time (PT), antithrombin III (AT) activity, and fibrinogen concentration. Fibrin-fibrinogen degradation product (FDP) concentration, D-dimer concentration, and platelet count were obtained in dogs with CPV enteritis only. Records were reviewed for evidence of thrombosis or phlebitis. All 9 dogs with CPV enteritis had evidence of hypercoagulability, determined on the basis of significantly increased TEG maximum amplitude and decreased AT activity. Fibrinogen concentration was significantly higher in dogs with CPV enteritis than in control dogs. The aPTT was moderately prolonged in dogs with CPV enteritis, and FDP concentration was < 5 mg/ml in 7 of 9 dogs. No dogs had a measurable D-dimer concentration. Platelet counts were within reference range. Four of 9 dogs had clinical evidence of venous thrombosis or phlebitis associated with catheters. One dog had multifocal splenic thrombosis identified at necropsy. Dogs with CPV enteritis have a high prevalence of clinical thrombosis or phlebitis and laboratory evidence of hypercoagulability without disseminated intravascular coagulopathy. Thromboelastography may help identify hypercoagulable states in dogs.

Biological evaluation of the effect of sugammadex on hemostasis and bleeding

PubMed Central

Guerci, Philippe; Harter, Valentin; Fuchs-Buder, Thomas; Meistelman, Claude

2015-01-01

Background Notification of sugammadex has been supplemented with a section on hemostasis, including a longer clotting time in the first minutes following injection, without any documented clinical consequences. The objective of this observational study was to analyze the effects of sugammadex administration on routine coagulation tests and bleeding in the clinical setting. Methods After Institutional Review Board approval, a prospective observational study was conducted between January and December 2011. Adult patients scheduled for laparotomies were analyzed in groups according to the type of reversal (without sugammadex versus 2 or 4 mg/kg sugammadex). There were no changes in our current clinical practice. Blood samples drawn from these patients were standardized at the same time and tested using the same daily calibrated machine. The endpoint was a comparison of the activated partial thromboplastin time (aPTT), prothrombin time (PT), hemoglobin (Hb) level and hematocrit (Ht), immediately before sugammadex administration (H0) and 1 h after neuromuscular block reversal (H1). Results One hundred and forty-two patients in three groups were included as follows: 11 in the "without sugammadex" group, 64 in the "2 mg/kg sugammadex" group and 67 in the "4 mg/kg sugammadex" group. Results did not differ significantly among the groups. Conclusions In this prospective observational study, the use of 2 and 4 mg/kg sugammadex was not associated with a longer clotting time or decreased hemoglobin concentrations. Future prospective investigations should study patients receiving 16 mg/kg sugammadex and/or with abnormal coagulation tests. PMID:25664150

[Effects and mechanisms of platycladi cacumen carbonisatum on rats with blood-heat and hemorrhage syndrome].

PubMed

Liu, Jia; Zhang, Li; Yao, Ying-Zhi; Ding, An-Wei; Yu, Bin; Shan, Ming-Qiu; Yao, Wei-Feng

2013-01-01

To discuss the effect and mechanism of Platycladi Cacumen Carbonisatum (PCC) on rats with blood heat and hemorrhage syndromes. Rats were fed with 15 g x kg(-1) water decoctions of Zingiberis Rhizoma and 5% alcohol for 15 days to establish the blood-heat and hemorrhage syndrome model. Yunnan Baiyao was taken as the positive control drug, and PCC decoctions (5.0, 10.0 g x kg(-1)) were given simultaneously, in order to detect changes in general physical signs of rats, such as body weight, daily diet, volume of daily drinking and urine and stool, and rectal temperature. Automatic hematology analyzers was used to determine white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT), blood time by docking (BT). Blood rheometers was used to detect whole blood and plasma viscosities, thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen content (FIB). Indexes related to thyroid functions, such as triiodothyronine (T3), tetraiodothyronine (T4), reverse triiodothyronine (rT3) and thyroid stimulating hormone (TSH) were measured by radio-immunoassay, and changes in lung tissues were observed by hematoxylin-eosin (HE) stain. After modeling, rats witnessed slow-down in weight growth rate, significant increase in daily diet, volume of daily drinking, urine and temperature, significant decrease in stools and their water content (P < 0.05, P < 0.01), rise in plasma T4 level, notable growth in T3 and rT3 concentrations (P < 0.05), decline in TSH concentration. Additionally, their WBC, RBC, HGB and HCT remarkably increased (P < 0.05, P < 0.01), with significant increase in high, middle and low whole blood viscosities and plasma viscosity (P < 0.01); their BT, TT, APTT were notably prolonged (P < 0.01), with significant increase in FIB content (P < 0.01). After oral administration of Yunnan Baiyao or PCC, rats of all groups showed significant improvement in blood heat syndromes (P < 0.05, P < 0.01), and their blood coagulation indexes including BT, TT, APTT, FIB, thyroid function indexes including T4, T3, rT3, TSH, WBC, RBC, HGB, HCT, whole blood viscosity and plasma viscosity were getting normal (P < 0.05, P < 0.01). PCC can ameliorate blood heat symptoms and pathologic hemorrhage among rats with blood heat and hemorrhage syndromes by inhibiting thyroid functions and correcting hemorheological and coagulation disorders.

Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

NASA Astrophysics Data System (ADS)

Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

2017-07-01

Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0:1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy

PubMed Central

Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian

2017-01-01

Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

Association between coagulation function and patients with primary angle closure glaucoma: a 5-year retrospective case-control study.

PubMed

Li, Shengjie; Gao, Yanting; Shao, Mingxi; Tang, Binghua; Cao, Wenjun; Sun, Xinghuai

2017-11-04

To evaluate the association between coagulation function and patients with primary angle closure glaucoma (PACG). A retrospective, hospital-based, case-control study. Shanghai, China. A total of 1778 subjects were recruited from the Eye & ENT Hospital of Fudan University from January 2010 to December 2015, including patients with PACG (male=296; female=569) and control subjects (male=290; female=623). Sociodemographic data and clinical data were collected. The one-way analysis of variance test was used to compare the levels of laboratory parameters among the mild, moderate and severe PACG groups. Multivariate logistic regression analyses were performed to identify the independent risk factors for PACG. The nomogram was constructed based on the logistic regression model using the R project for statistical computing (R V.3.3.2). The activated partial thromboplastin time (APTT) of the PACG group was approximately 4% shorter (p<0.001) than that of the control group. The prothrombin time (PT) was approximately 2.40% shorter (p<0.001) in patients with PACG compared with the control group. The thrombin time was also approximately 2.14% shorter (p<0.001) in patients with PACG compared with the control group. The level of D-dimer was significantly higher (p=0.042) in patients with PACG. Moreover, the mean platelet volume (MPV) of the PACG group was significantly higher (p=0.013) than that of the control group. A similar trend was observed when coagulation parameters were compared between the PACG and control groups with respect to gender and/or age. Multiple logistic regression analyses revealed that APTT (OR=1.032, 95% CI 1.000 to 1.026), PT (OR=1.249, 95% CI 1.071 to 1.457) and MPV (OR=1.185, 95% CI 1.081 to 1.299) were independently associated with PACG. Patients with PACG had a shorter coagulation time. Our results suggest that coagulation function is significantly associated with patients with PACG and may play an important role in the onset and development of PACG. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Laboratory and Molecular Characterization of Dengue Viruses in a 2014 Outbreak in Guangfo Region, Southern China.

PubMed

Luo, Zhao-Fan; Hu, Bo; Zhang, Feng-Yi; Lin, Xiang-Hua; Xie, Xiao-Ying; Pan, Kun-Yi; Li, Hong-Yu; Ren, Rui-Wen; Zhao, Wen-Zhong

2017-09-25

Non-specific symptoms and low viremia levels make early diagnosis of dengue virus (DENV) infection challenging. This study aimed to i) identify laboratory markers that can be used to predict a DENV-positive diagnosis and ii) perform a molecular characterization of DENVs from the 2014 Guangdong epidemic. This retrospective study analyzed 1,044 patients from the Guangdong epidemic who were clinically suspected cases of dengue. Viral RNA was detected by real-time RT-PCR, and viral-specific NS1 antigen was detected using enzyme-linked immuno sorbent assay. A molecular phylogenetic analysis was performed for the with the DENV C-prM gene junction. Patients with dengue infection had leukopenia (2.8 × 10 9 /L), thrombocytopenia (109.0 × 10 9 /L), elevated aspartate aminotransferase (56.0 IU/L) and alanine aminotransferase (43.5 IU/L), and prolonged activated partial thromboplastin time (APTT, 33.5 s) (all P ＜ 0.001) compared to patients without dengue. The positive predictive value of leukopenia and thrombocytopenia for DENV infection were 96.9% and 93.0%, respectively. Leukopenia, thrombocytopenia, elevated aminotransferases, and prolonged APTT were useful predictive markers for an early diagnosis of DENV infection. Phylogenetic analysis indicated that the DENVs from the 2014 epidemic were closely related to a 2010 New Delhi strain and a 2013 Guangzhou strain. The 2014 epidemic consisted of co-circulating DENV-1 genotypes I and V from multiple origins. Efficient dengue surveillance can facilitate rapid response to future outbreaks.

Cosmonauts' haemostasis system status before and after space flights

NASA Astrophysics Data System (ADS)

Kuzichkin, Dmitry; Markin, Andrey; Morukov, Boris

Introduction. It is known that cosmonauts expose themselves to psychophysical effort in different phases of space flights as well as in pre- and post-flight period. Stress affects different body systems functioning changes including haemostasis system. It is shown that adrenalin directly activates XII coagulation cascade factor [McKay D. G., Latour I. G., Parrish M. N.,1970], initiating intrinsic clotting pathway and affects fibrinogen concentration increase in plasma [Zubairov D. M., 1978]. A post-flight increase in the fibrinogen concentration was revealed with its drop up to the pre-flight level within rehabilitation period [T. Peter Stein, Margaret D., 2006]. Stress agents influence on haemostasis system is physiologically determined and directed to body preparation before probable blood loss. One can consider this process as a function of intrinsic clotting pathway. But in case of blood loss absence the preliminary permanent coagulation activation can lead to appearance of thrombosis risk. Purpose. The purpose was to study haemostasis system main components functional activity features before and after space flights. Methods. In the citrated plasma of astronauts who performed short-term (10 to 11 days) or long-term (196 to 199 days) the following values were determined: activated partial thrombin time (APTT); prothrombin time; prothrombin index; international normalized ratio; thrombin time (TT); activity of enzymes influencing the function of proteins involved in the formation and lysis of a clot such as antithrombin III, protein C, plasminogen, antiplasmin; content of fibrinogen, as well as intermediate products of formation and degradation of fibrin such as D-dimer, soluble fibrin-monomer complexes (SFMC). Sampling of biomaterial was perfomed 30 to 45 days prior to the flight, during the 1st day of the post flight period (all the examined persons), and in the 7th and 14th day (long-term flights member only) Results. In pre-flight period cosmonauts’ APTT indices was increased as compared with general population physiological norms. During the 1st day after long- and short-term flights a tendency for activation of coagulation system along inner and terminal pathways emerged (APTT, TT shortening, an increase in the SFMC concentration). After short-term space flights a tendency for activation of fibrin forming (an increase in the fibrin concentration) was evidenced, and, as a compensatory factor, for activation of fibrinolysis (an increase in fibrynolytic activity and D-dimer concentration). On the contrary, after long-term space flights, a tendency for fibrinolysys decline was observed (fibrinolytic activity and D-dimer concentration decreased at this the fibrinogen concentration remained virtually constant relative to the background level). During the 14th day of the post-flight period normalization of all studied parameters was observed. Discussion. After space flights a tendency for activation of haemostasis procoagulant component is observed. However, during short-term space flights compensatory systems become activated, which may be connected with developing of stress reactions of adaptation to weightlessness conditions and post-flight re-adaptation to ground conditions, while after long-term spaceflights the compensatory effect of fibrinolysis is not pronounced, possibly, due to metabolic process intensity reduction developing during long-duration stay in weightlessness conditions [Grigoriev A.I., Kaplansky A.S., Popova I.A., 1992]. Probably the relatively inactivated cosmonauts’ intrinsic pathway coagulation in pre-flight period (prolonged APTT) is one of the prerequisites of the high resistance to stress factors influence. Plausible this status of intrinsic pathway subject to consequent activation by adrenalin promotes body protection against thrombophilic tendency.

Warfarin hypersensitivity due to gluten-sensitive enteropathy: a case study.

PubMed

Kwolek, Sara; Deming, Paula

2012-01-01

A 53 year old female who was maintained on long-term warfarin therapy due to history of pulmonary embolism, repeatedly presents with an abnormally prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). After many asymptomatic episodes were corrected with Vitamin K therapy to temporarily reverse the effects of the warfarin, the cause of the apparent coagulopathy was further investigated. Factor Activity Assays of the common pathway factors II, IX, and X all revealed critically low values; below the threshold even a loading dose of warfarin is typically capable of eliciting. The patient tested strongly positive for Tissue Transglutaminase IgA, which is highly suggestive of a gluten-sensitive enteropathy. One effect of this condition is malabsorption due to flattened intestinal villi. The patient was determined to have an acquired vitamin K deficiency secondary to gluten-sensitive enteropathy. Her condition was exacerbated by the long-term warfarin therapy, resulting in the prolonged PT and PTT. The patient was treated with vitamin K therapy, which reversed the deficiency and corrected her abnormal coagulation results.

Evaluation of antioxidant activities and chemical analysis of sulfated chitosan from Sepia prashadi.

PubMed

Seedevi, Palaniappan; Moovendhan, Meivelu; Vairamani, Shanmugam; Shanmugam, Annaian

2017-06-01

The chitin and chitosan of S. prashadi was prepared through demineralization, deproteinzation, deacetylation process and sulfation were carried by chlorosulfonic acid in N,N-dimethylformamide. The sulfate content in chitosan was found to be 18.9%. The carbon, hydrogen and nitrogen composition of the sulfated chitosan were recorded 39.09%, 6.95% and 6.58% respectively. The structural analysis was done by using FT-IR and NMR spectroscopy technique. The DSC curves of sulfated chitosan showed a large endothermic peak resolved with T o value of 54.57°C and T P value of 97.46°C. The morphology of sulfated chitin and sulfated chitosan were studied by SEM. The Further in vitro antioxidant activity of sulfated chitosan was screened by scavenging activity of superoxide radical assay, hydroxyl radical scavenging assay, metal-ion chelating effect and reducing power. Its anticoagulant activity was tested for human plasma with respect to Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT). Results prove that sulfated chitosan has potent antioxidant and anticoagulant activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Improvement and application of an acute blood stasis rat model aligned with the 3Rs (reduction, refinement and replacement) of humane animal experimentation.

PubMed

Huang, Shuai; Xu, Feng; Wang, Yin-Ye; Shang, Ming-Ying; Wang, Chao-Qun; Wang, Xuan; Cai, Shao-Qing

2014-12-23

To establish a novel cardiocentesis method for withdrawing venous blood from the right atrium, and to improve an acute blood stasis rat model using an ice bath and epinephrine hydrochloride (Epi) while considering the 3Rs (reduction, refinement, and replacement) of humane animal experimentation. An acute blood stasis model was established in male Sprague-Dawley rats by subcutaneous injection (s.c.) Epi (1.2 mg/kg) administration at 0 h, followed by a 5-min exposure to an ice-bath at 2 h and s.c. Epi administration at 4 h. Control rats received physiological saline. Rats were fasted overnight and treated with Angelicae Sinensis Lateralis Radix (ASLR) and Pheretima the following day. Venous blood was collected using our novel cardiocentesis method and used to test whole blood viscosity (WBV), prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) content. The rats survived the novel cardiocentesis technique; WBV value returned to normal while hematological parameters such as hemoglobin level and red blood cell count were restored to >94% of the corresponding values in normal rats following a 14-day recovery. Epi (1.2 mg/kg, s.c.) combined with a 5-min exposure to the ice bath replicated the acute blood stasis rat model and was associated with the highest WBV value. In rats showing acute blood stasis, ASLR treatment [4 g/(kg·d) for 8 days] decreased WBV by 9.98%, 11.09%, 9.34%, 9.00%, 7.66%, and 7.03% (P<0.05), while Pheretima treatment [2.6 g/(kg·d), for 8 days] decreased WBV by 25.49%, 25.94%, 16.28%, 17.76%, 11.07%, and 7.89% (P<0.01) at shear rates of 1, 3, 10, 30, 100, and 180 s -1 , respectively. Furthermore, Pheretima treatment increased APTT significantly (P<0.01). We presented a stable, reproducible, and improved acute blood stasis rat model, which could be applied to screen drugs for promoting blood circulation and eliminating blood stasis.

Thromboelastographic evaluation of dogs with congenital portosystemic shunts.

PubMed

Kelley, D; Lester, C; DeLaforcade, A; Webster, C R L

2013-01-01

On plasma-based assays, dogs with congenital portosystemic shunts (CPSS) have changes in serum concentrations of both pro- and anticoagulant proteins, but how these abnormalities affect whole blood coagulation assays (eg, thromboelastography) are unknown. To conduct kaolin-activated thromboelastography (TEG) analysis in dogs with CPSS and to compare TEG coagulation status with clinical presentation, routine serum biochemistry, and plasma-based coagulation tests. Twenty-one client-owned dogs with CPSS confirmed by ultrasound examination or nuclear scintigraphy. In a prospective study, signalment, clinical presentation, TEG analysis, CBC, serum biochemistry, and hemostatic tests (platelet count, prothrombin time [PT], activated partial thromboplastin time [aPTT], quantitative fibrinogen, antithrombin [AT] activity, protein C [PC] activity, d-dimers, and factor VIII activity) were analyzed in dogs with CPSS. Dogs with CPSS had significantly shorter K values and increased angle, maximum amplitude (MA), and G values compared with the reference population. On plasma-based coagulation testing, dogs with CPSS had significantly prolonged PT, lower platelet counts, lower AT and PC activities, and increased d-dimers and factor VIII activity. Evaluation of G value defined 9/21 dogs with CPSS as hypercoagulable. These dogs were more likely to have hepatic encephalopathy (HE) than CPSS dogs that had normal coagulation. TEG analysis detected hemostatic abnormalities consistent with a hypercoagulable state in some dogs with CPSS. The presence of a hypercoagulable state was 40 times more likely in dogs with symptomatic HE. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Thrombelastography is Better Than PT, aPTT, and Activated Clotting Time in Detecting Clinically Relevant Clotting Abnormalities After Hypothermia, Hemorrhagic Shock and Resuscitation in Pigs

DTIC Science & Technology

2008-09-01

hypothermia group using a cold blanket with 4°C circulating water. In the combined group, hemorrhagic shock and LR re- suscitation were induced the same... circulation and a decrease in platelet counts. Fibrinogen levels, in con- trast, were not changed significantly from baseline by hypo- thermia in this...et al. Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. J Thorac Cardiovasc Surg. 1992;104:108–116. The

Simple and rapid assay for effect of the new oral anticoagulant (NOAC) rivaroxaban: preliminary results support further tests with all NOACs

PubMed Central

2014-01-01

Background New oral anticoagulant (NOAC) drugs are known to influence the results of some routine hemostasis tests. Further data are needed to enable routine assessment of the effects of NOAC on clotting parameters in some special circumstances. Methods Following administration of rivaroxaban to patients, at the likely peak and trough activity times, we assessed the effects on prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and clotting time using Russell’s viper venom, and in the presence of phospholipids and calcium reagent available as DVVreagent® and DVVconfirm®. The data were used to determine an adequate NOAC plasma level based on anticoagulant activities expressed as a ratio (patients/normal, R-C). Results DVVconfirm as R-C could be rapidly performed, and the results were reasonably sensitive for rivaroxaban and probably for other FX inhibitors. This assay is not influenced by lupus anticoagulant and heparin, does not require purified NOAC as control, and will measure whole-plasma clotting activity. Conclusions We propose a cut-off R-C value of 4.52 ± 0.33 for safety, but clinical studies are needed to establish whether this cut-off is useful for identifying patients at increased risk of hemorrhage or exhibiting low anticoagulation effect. It also seems possible that normal R-C could indicate an absence of anticoagulant activity when rivaroxaban is discontinued due to episodes of uncontrolled bleeding during anticoagulation or for emergency surgery. PMID:24656069

Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant.

PubMed

Posch, Florian; Gebhart, Johanna; Rand, Jacob H; Koder, Silvia; Quehenberger, Peter; Pengo, Vittorio; Ay, Cihan; Pabinger, Ingrid

2017-03-10

Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA. We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs). During a median follow-up of 9.5 years (range: 12 days-13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07--5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42-13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14-5.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22). Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.

Interval and continuous exercise regimens suppress neutrophil-derived microparticle formation and neutrophil-promoted thrombin generation under hypoxic stress.

PubMed

Chen, Yi-Ching; Ho, Ching-Wen; Tsai, Hsing-Hua; Wang, Jong-Shyan

2015-04-01

Acute hypoxic exposure increases vascular thrombotic risk. The release of procoagulant-rich microparticles from neutrophils accelerates the pathogenesis of inflammatory thrombosis. The present study explicates the manner in which interval and continuous exercise regimens affect neutrophil-derived microparticle (NDMP) formation and neutrophil/NDMP-mediated thrombin generation (TG) under hypoxic condition. A total of 60 sedentary males were randomized to perform either aerobic interval training [AIT; 3-min intervals at 40% and 80% V̇O2max (maximal O2 consumption)] or moderate continuous training (MCT; sustained 60% V̇O2max) for 30 min/day, 5 days/week for 5 weeks, or to a control (CTL) group who did not receive any form of training. At rest and immediately after hypoxic exercise test (HE, 100 W under 12% O2 for 30 min), the NDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, HE (i) elevated coagulant factor VIII/fibrinogen concentrations and shortened activated partial thromboplastin time (aPTT), (ii) increased total and tissue factor (TF)-rich/phosphatidylserine (PS)-exposed NDMP counts and (iii) enhanced the peak height and rate of TG promoted by neutrophils/NDMPs. Following the 5-week intervention, AIT exhibited higher enhancement of V̇O2max than did MCT. Notably, both MCT and AIT attenuated the extents of HE-induced coagulant factor VIII/fibrinogen elevations and aPTT shortening. Furthermore, the two exercise regimens significantly decreased TF-rich/PS-exposed NDMP formation and depressed neutrophil/NDMP-mediated dynamic TG at rest and following HE. Hence, we conclude that AIT is superior to MCT for enhancing aerobic capacity. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors during HE, which may reduce thrombotic risk evoked by hypoxia. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors during HE, which may reduce thrombotic risk evoked by hypoxia.

A New Route of Fucoidan Immobilization on Low Density Polyethylene and Its Blood Compatibility and Anticoagulation Activity

PubMed Central

Ozaltin, Kadir; Lehocký, Marián; Humpolíček, Petr; Pelková, Jana; Sáha, Petr

2016-01-01

Beside biomaterials’ bulk properties, their surface properties are equally important to control interfacial biocompatibility. However, due to the inadequate interaction with tissue, they may cause foreign body reaction. Moreover, surface induced thrombosis can occur when biomaterials are used for blood containing applications. Surface modification of the biomaterials can bring enhanced surface properties in biomedical applications. Sulfated polysaccharide coatings can be used to avoid surface induced thrombosis which may cause vascular occlusion (blocking the blood flow by blood clot), which results in serious health problems. Naturally occurring heparin is one of the sulfated polysaccharides most commonly used as an anticoagulant, but its long term usage causes hemorrhage. Marine sourced sulfated polysaccharide fucoidan is an alternative anticoagulant without the hemorrhage drawback. Heparin and fucoidan immobilization onto a low density polyethylene surface after functionalization by plasma has been studied. Surface energy was demonstrated by water contact angle test and chemical characterizations were carried out by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Surface morphology was monitored by scanning electron microscope and atomic force microscope. Finally, their anticoagulation activity was examined for prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT). PMID:27294915

Detection of bleeding disorders in Lebanon: outcomes of a pilot programme.

PubMed

Djambas Khayat, C; Samaha, H; Noun, P; Bakhos Asmar, J D; Taher, A; Adib, S; Inati, A; Sakr, S

2014-03-01

To promote management and awareness of bleeding disorders in Lebanon, a pilot programme was launched in 2009 by the Lebanese Hemophilia Association assisted by World Federation of Hemophilia. The aim of this study was to diagnose patients with bleeding disorders and to assess the potential challenges in implementing a screening programme. The pilot project was launched in 26 social health centres in the Bekaa valley. The study tools included the evaluation of the Tossetto Bleeding Score and the Pictorial Bleeding Assessment Chart (PBAC) for menstruation. Persons with a bleeding score higher than 2 and PBAC higher than 185 were eligible for further blood tests including the prothrombin time, partial thromboplastin time, complete blood count, bleeding time and von Willebrand ristocetin cofactor activity. 643 patients were enrolled, of whom 60.6% were women. Overall, 91 persons had an abnormal score. 50 eligible patients were tested: 32 had normal tests, nine new patients with severe Von Willebrand were discovered, 4 had VW:RiCo of 40, 3 prolonged APTT and 2 thrombocytopaenia. There was a clear correlation between the severity of the score and the willingness to perform the tests (P = 0.02). Women were reluctant to participate fully when investigators were men. The probability of adherence to the screening protocol is significantly increased when directed by women health care professional. For patients with milder forms, global screening programmes were neither feasible nor acceptable but those more severely affected have to be identified. Providers are crucial in preselecting patients with blood problems who are not coping well. © 2013 John Wiley & Sons Ltd.

NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities.

PubMed

Kuo, Heng-Lan; Lien, Jin-Cherng; Chung, Ching-Hu; Chang, Chien-Hsin; Lo, Shyh-Chyi; Tsai, I-Chun; Peng, Hui-Chin; Kuo, Sheng-Chu; Huang, Tur-Fu

2010-06-01

The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP-184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders.

Chemical characteristics and anticoagulant activities of two sulfated polysaccharides from Enteromorpha linza (Chlorophyta)

NASA Astrophysics Data System (ADS)

Qi, Xiaohui; Mao, Wenjun; Chen, Yin; Chen, Yanli; Zhao, Chunqi; Li, Na; Wang, Chunyan

2013-03-01

Two sulfated polysaccharides, designated MP and SP, were extracted from the marine green alga Enteromorpha linza using hot water and then purified using ion-exchange and size-exclusion chromatography. The anticoagulant activities of MP and SP were examined by determination of their activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) using human plasma. Results showed that MP and SP were composed of abundant rhamnose with small amounts of xylose and glucuronic acid, whereas SP also contained a small amount of galactose. Approximate molecular weights of MP and SP were 535 and 502 kDa, respectively. As compared with SP, MP had higher contents of sulfate ester (19.0%) and uronic acid (14.9%). The MP mainly consisted of (1→4)-linked rhamnose residues with partially sulfated groups at the C-3 position, and small amounts of (1→3, 4)-linked rhamnose, (1→2, 4)-linked rhamnose, (1→4)-linked glucuronic acid and (1→4)-linked xylose residues. The SP contained abundant (1→4)-linked rhamnose with minor amounts of (1→3)-linked rhamnose, (1→3, 4)-linked rhamnose, (1→2, 4)-linked rhamnose, (1→4)-linked glucuronic acid, (1→4)-linked xylose, and (1→3)-linked galactose residues. The sulfate groups were mainly located at C-3 of (1→4)-linked rhamnose residues. Both MP and SP, in particular the former, effectively prolonged APTT and TT. This work demonstrates that MP and SP have unique structural characteristics distinct from those of other sulfated polysaccharides from Enteromorpha. The MP is a potential source of anticoagulant, and the difference in anticoagulant activities of the two sulfated polysaccharides is directly linked to the discrepancy of their chemical features.

Stability of hemostatic proteins in canine fresh-frozen plasma thawed with a modified commercial microwave warmer or warm water bath.

PubMed

Pashmakova, Medora B; Barr, James W; Bishop, Micah A

2015-05-01

To compare stability of hemostatic proteins in canine fresh-frozen plasma (FFP) thawed with a modified commercial microwave warmer (MCM) or warm water bath (37°C; WWB) or at room temperature (22°C). Fresh-frozen plasma obtained from 8 canine donors of a commercial blood bank. A commercial microwave warmer was modified with a thermocouple to measure surface temperature of bags containing plasma. The MCM and a WWB were each used to concurrently thaw a 60-mL bag of plasma obtained from the same donor. Two 3-mL control aliquots of FFP from each donor were thawed to room temperature without use of a heating device. Concentrations of hemostatic proteins, albumin, and D-dimers; prothrombin time (PT); and activated partial thromboplastin time (aPTT) were determined for all samples. Significant decreases in concentrations of factors II, IX, X, XI, fibrinogen, von Willebrand factor, antithrombin, protein C, and albumin and significant increases in PT and aPTT were detected for plasma thawed with the MCM, compared with results for samples thawed with the WWB. Concentrations of factors VII, VIII, and XII were not significantly different between plasma thawed with the MCM and WWB. Concentrations of D-dimers were above the reference range for all thawed samples regardless of thawing method. No significant differences in factor concentrations were detected between control and WWB-thawed samples. Significant differences in hemostatic protein concentrations and coagulation times were detected for plasma thawed with an MCM but not between control and WWB-thawed samples. Clinical importance of these changes should be investigated.

Heparin free coating on PLA membranes for enhanced hemocompatibility via iCVD

NASA Astrophysics Data System (ADS)

Wang, Hui; Shi, Xiao; Gao, Ailin; Lin, Haibo; Chen, Yongliang; Ye, Yumin; He, Jidong; Liu, Fu; Deng, Gang

2018-03-01

In the present work, we report one-step immobilization of nano-heparin coating on PLA membranes via initiated chemical vapor deposition (iCVD) for enhanced hemocompatibility. The nano-coating introduced onto the membrane surface via the crosslinking of P(MAA-EGDA) was confirmed by the FTIR, SEM and weight measurement respectively. The negative carboxyl groups could form the hydration interaction with the protein and platelets and electrostatic interaction with amide groups of thrombin by the mediation of antithrombin, which is similar but different with heparin. The P(MAA-EGDA) coated membranes showed suppressed platelet adhesion and prolonged clotting time (APTTs increased to 59 s, PTs increased to 20.4 s, TTs increased to 17.5 s, and the FIBs declined by 30 mg/dL). Moreover, the complement activation tests demonstrated the formation of C3a and C5a was inhibited. All results demonstrated that the nano-coating of P(MAA-EGDA) via iCVD significantly enhanced the hemocompatibility of PLA membranes, which is also applicable for various membranes.

Alterations in homeostasis after open surgery. A prospective randomized study

PubMed Central

DEDEJ, T.; LAMAJ, E.; MARKU, N.; OSTRENI, V.; BILALI, S.

2013-01-01

Summary Introduction Alterations in homeostasis, and a subsequent increased risk for postoperative thromboembolic complications, are observed as a result of open surgery. Additionally, the stress response to surgical trauma precipitates a transient hypercoagulable state as well as inflammation. This study was conducted to evaluate the patterns in postoperative alterations of blood coagulation, and to detect their correlations with inflammatory markers. Patients and methods The study included 50 patients with comparable demographic data, who were randomly assigned to undergo abdominal surgery. No previous coagulation disorders were noted. Blood samples were collected preoperatively and 72 h postoperatively. The following parameters were measured: prothrombin time (PT) and activated partial thromboplastin time (APTT); fibrinogen (FIB), D-dimer (D-D), and C-reactive protein (CRP) levels; and platelet (PLT) count. Prophylactic doses of low molecular weight heparin were administered to all patients. Results The PT mean value significantly changed from 90.38% before surgery to 81.25% after surgery. No statistical difference was observed between APTT values before and after surgery. FIB levels significantly increased from 381.50 mg/dL preoperatively to 462.57 mg/dL postoperatively. Mean D-D levels also significantly increased from 235.54 μg/L preoperatively to 803.59 μg/L postoperatively. PLT count significantly declined after surgery. Mean CRP levels significantly increased from 12.33 mg/L preoperatively to 44.28 mg/L postoperatively. A strong correlation was observed between D-D and C-RP levels after surgery. Conclusion These results indicate that, despite administering an-tithromboembolic prophylaxis, a hypercoagulable state was observed following surgery. This state was enhanced by inflammation. PMID:24091175

Intentional overdose with tinzaparin: management dilemmas.

PubMed

Balla, Iliana; Karafotias, Ioasaf; Christopoulos, Constantinos

2014-02-01

Low-molecular-weight heparin (LMWH) is increasingly being prescribed for prophylaxis and treatment of thromboembolic diseases. Despite the fact that its therapeutic use is considered to be safe, it can be complicated by major hemorrhage and, in contrast to unfractionated heparin, it can only partially be neutralized by protamine. Recent reports of LMWH overdose illustrate the need for a consensus on its management. To describe a case of self-poisoning with a very large dose of tinzaparin and discuss management options in patients with LMWH overdose. A 69-year-old woman was brought to the Emergency Department 2 h after injecting herself with 280,000 IU of tinzaparin subcutaneously in an attempt to commit suicide. Despite an unrecordable activated partial thromboplastin time (APTT > 180 s) and prolonged prothrombin time, there was no evidence of active bleeding. She was given an intravenous infusion of 100 mg protamine sulfate and was admitted to the intensive care unit, where further infusions of protamine were administered. Normalization of the APTT occurred 40-50 h post admission, reflecting normal tinzaparin clearance rather than neutralization by protamine. No hemorrhagic complications occurred during her hospitalization except for prolonged bleeding from venipuncture sites. In this case of massive tinzaparin overdose, conventional doses of protamine failed to rapidly normalize the deranged coagulation parameters. The favorable clinical outcome suggests that, regardless of the LMWH amount injected, no active treatment is needed in the absence of hemorrhage. This is in accordance with the limited published data concerning cases of overdose with other LMWHs. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between JAK2V617F mutation, allele burden and coagulation function in Ph-negative myeloproliferative neoplasms.

PubMed

Hu, Linhui; Pu, Lianfang; Ding, Yangyang; Li, Manman; Cabanero, Michael; Xie, Jingxin; Zhou, Dejun; Yang, Dongdong; Zhang, Cui; Wang, Huiping; Zhai, Zhimin; Ru, Xiang; Li, Jingrong; Xiong, Shudao

2017-07-01

Our aim was to explore the relationship between JAK2V617F mutation allele burden and hematological parameters especially in coagulation function in Chinese population. This study included 133 Ph-negative myeloproliferative neoplasms (MPNs) patients between 2013 and 2016. All the clinical and experimental data of patients were collected at the time of the diagnosis without any prior treatment, including blood parameters, coagulation function, splenomegaly, vascular events and chromosome karyotype. PCR and qPCR were used to detect JAK2V617F mutation and JAK2V617F mutation allele burden. In polycythemia vera patients, a positive correlation between the allele burden of JAK2V617F mutation and PLT counts was found; in essential thrombocythemia (ET) patients, WBC counts, RBC counts, HB, and HCT were higher in mutated patients than in wild-type patients. Furthermore, PT-INR was higher in ET and PMF mutated patients. In addition, a positive correlation between the allele burden of JAK2V617F mutation and activated partial thromboplastin time (APTT) was observed in JAK2V617F mutated ET patients. Higher hematologic parameters including counts of WBC, RBC, and PLT are closely associated with JAK2V617F mutation and its burden in Ph-negative MPNs; importantly, PT-INR, APTT are also related to JAK2V617F mutation and allele burden. Thus, our data indicate that JAK2V617F mutation allele burden might not only represent the burden of MPN but also alter the coagulation function.

Safety and potential anticoagulant effects of nebulised heparin in burns patients with inhalational injury at Singapore General Hospital Burns Centre.

PubMed

Yip, Lian Yee; Lim, Yen Fang; Chan, Hong Ngee

2011-11-01

Nebulised heparin, N-acetylcysteine (NAC) and salbutamol were shown to decrease reintubation rates, incidence of atelectasis and mortality in paediatric patients and reduce lung injury scores in adult burns patients with inhalational lung injury (ILI). Nebulised heparin, NAC and salbutamol treatment protocol was introduced in Singapore General Hospital (SGH) Burns Centre in 2006. However, safety data on the use of nebulised heparin and NAC for burns patients with ILI is not well established. In this study, we investigated the safety and potential anticoagulant effects of nebulised heparin in burns patients with ILI. A retrospective study with historical control was conducted. The treatment group consisted of 52 mechanically ventilated adult patients, with a diagnosis of ILI as confirmed by bronchoscopy, admitted to burn intensive care unit (BICU) from the year 2006 to 2009. The group was treated with nebulised heparin, NAC and salbutamol. The control group consists of 11 mechanically ventilated BICU ILI patients treated from year 2001 to 2005 before protocol initiation. Blood coagulation indices (prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count) were monitored and bleeding incidences were assessed. Blood coagulation indices did not suggest an increase risk of bleeding with nebulised heparin. The APTT, PT and platelet count followed a similar trend for both groups over 7 days. No clinically significant increase in bleeding risk was found to be associated with nebulised heparin. Nebulised heparin was not found to potentiate the risk of bleeding in burns patients with ILI. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

Comparative Study of the Effects of Combined Oral Contraceptives in Hemostatic Variables

PubMed Central

Stocco, Bianca; Fumagalli, Helen F.; Franceschini, Silvio A.; Martinez, Edson Z.; Marzocchi-Machado, Cleni M.; de Sá, Marcos Felipe S.; Toloi, Maria Regina T.

2015-01-01

Abstract Thrombotic risk is associated with the estrogen dose and type of progestin in combined oral contraceptives. Studies published since 1990 showed that third-generation progestins have larger risk to contribute to thrombosis development than the second-generation. However, there are conflicts in the literature regarding the thrombotic risk associated to the drospirenone progestin. So, this study aimed to evaluate the effects of 3 formulations of contraceptives containing ethinylestradiol (EE) (20 and 30 μg) combined with drospirenone versus levonorgestrel combined with EE (30 μg) in hemostatic parameters. This cross-sectional study included 70 healthy women between 18 and 30 years, BMI 19 to 30 kg/m2, not pregnant, non-smokers, and users or non-users (control) of contraceptives for a minimum period of 6 months. The following parameters were assessed: prothrombin time (PT), Factor VII, activated partial thromboplastin time (aPTT), Factor XII, fibrinogen, Factor 1 + 2, Protein C, Protein S, antithrombin, D-dimers, and plasminogen activator inhibitor-1. Significant alterations were found in PT, aPTT, fibrinogen, D-dimers, and protein S, all favoring a state of hypercoagulation for contraceptive containing DRSP/20EE. Both contraceptives containing DRSP/30EE and LNG/30EE promoted changes that favor the hypercoagulability in the coagulant variable PT and in the anticoagulant variables Protein S and Protein C, respectively. We suggest that the progestin drospirenone can contribute to an inadequate balance among procoagulant, anticoagulant, and fibrinolytic factors, since that the contraceptive containing the lowest dose of estrogen and drospirenone (DRSP/20EE) caused a higher number of hemostatic changes. PMID:25634167

Self-assembled, bivalent aptamers on graphene oxide as an efficient anticoagulant.

PubMed

Lai, Pei-Xin; Mao, Ju-Yi; Unnikrishnan, Binesh; Chu, Han-Wei; Wu, Chien-Wei; Chang, Huan-Tsung; Huang, Chih-Ching

2018-06-25

Graphene oxide (GO) has unique structural properties, can effectively adsorb single-strand DNA through π-π stacking, hydrogen bonding and hydrophobic interactions, and is useful in many biotechnology applications. In this study, we developed a thrombin-binding-aptamers (15- and 29-mer) conjugated graphene oxide (TBA15/TBA29-GO) composite for the efficient inhibition of thrombin activity towards the formation of fibrin from fibrinogen. The TBA15/TBA29-GO composite was simply obtained by the self-assembly of TBA15/TBA29 hybrids on GO. The high density and appropriate orientation of TBA15/TBA29 on the GO surface enabled TBA15/TBA29-GO to acquire an ultrastrong binding affinity for thrombin (dissociation constant = 2.9 × 10-12 M). Compared to bivalent TBA15h20A20/TBA29h20A20 hybrids, the TBA15/TBA29-GO composite exhibited a superior anticoagulant potency (ca. 10-fold) against thrombin-mediated coagulation as a result of steric blocking effects and a higher binding affinity for thrombin. In addition, the prolonged thrombin clotting time, prothrombin time (PT), and activated partial thromboplastin time (aPTT) of TBA15/TBA29-GO were at least 2 times longer than those of commercially available drugs (heparin, argatroban, hirudin, and warfarin). The in vitro cytotoxicity and hemolysis analyses revealed the high biocompatibility of TBA15/TBA29-GO. The rat-tail bleeding assay of the hemostasis time and ex vivo PT and aPTT further revealed that TBA15/TBA29-GO is superior (>2-fold) to heparin, which is commonly used in the treatment and prevention of thrombotic diseases. Our multivalent, oligonucleotide-modified GO nanocomposites are easy to prepare, cost-effective, and highly biocompatible and they show great potential as effective anticoagulants for the treatment of thrombotic disorders.

Development of PEG-PLGA based Intravenous Low Molecular Weight Heparin (LMWH) Nanoparticles Intended to Treat Venous Thrombosis.

PubMed

Jogala, Satheesh; Rachamalla, Shyam Sunder; Aukunuru, Jithan

2016-01-01

Anticoagulant therapy is effective in the treatment of DVT. In this regard, LMWH demonstrated significant promise. It is widely used clinically. The goal of this study was to prepare and evaluate intravenous sustained release stealth nanoparticles encapsulating LMWH using PLGA (polylactidecoglycolide) and different grades of PEG (poly ethylene glycols). The nanoparticles were prepared using w/o/w solvent evaporation technique. Prepared nanoparticles were evaluated for particle size, encapsulation efficiency, in-vitro drug release, anti-thrombotic activity in venous thrombosis rat model, estimation of aPTT, tissue bio-distribution studies and stability. Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) studies confirmed the formation of smooth spherical particles. FTIR study reveals successful coating of PEG on the nanoparticles. DSC and XRD results demonstrated that drug changed its physical form in the formulation. The encapsulation efficiency was 63-74%. In vitro drug release was 57-75% for 48 hrs. Macrophage uptake of LMWH with pegylated nanoparticles was less compared to conventional PLGA nanoparticles. In vivo drug release was sustained for 48hrs; Optimized formulation exhibited good enhancement in pharmacokinetic parameters when compared to free drug solution. In vivo sustained release was also demonstrated with antithrombotic activity as well aPTT activity. Optimized formulation demonstrated significant stability, excellent antithrombotic activity in venous thrombosis rat model, improved aPTT levels when compared to free drug solution. An effective stealth LMWH nanoparticle formulation to treat venous thrombosis was successfully developed using w/o/w solvent evaporation technique.

Study on extraction of agaropectin from Gelidium amansii and its anticoagulant activity

NASA Astrophysics Data System (ADS)

Qi, Huimin; Li, Daxin; Zhang, Jingjing; Liu, Li; Zhang, Quanbin

2008-05-01

Gelidium amansii agar was fractionated on DEAE-cellulose and four fractions were obtained sequentially. The yields of 1.0 mol/L NaCl fraction and 2.5 mol/L NaCl fraction were 2.80% and 2.03%. They are highly sulfated agar, and named as agaropectin with sulfate content being 22.8% and 32.5%, respectively. The anticoagulant experiment results show that agaropectin could effectively prolong the coagulation time in a dose-dependent manner in vitro. Agaropection could be absorbed and effectively prolong the plasma coagulation time in vivo. After intragastric administration at the doses of 100, 200, and 400 mg/kg·d in rats for 15 days, TT (thrombin time), CT (coagulation time), PT (prothrombin time), and APTT (activated partial thromboplastin time) could be effectively prolonged and the plasma Fib level could be significantly lowered.

The revised dengue fever classification in German travelers: clinical manifestations and indicators for severe disease.

PubMed

Hoffmeister, B; Suttorp, N; Zoller, T

2015-02-01

The number of dengue cases imported to Germany has increased significantly in recent years. Among returning travelers, dengue is now a frequent cause of hospitalization. The aim of this study was to determine the proportion of patients with severe disease hospitalized in a European, non-endemic country applying the revised 2009 WHO classification system and to determine predictors of severe disease. A retrospective single-center analysis of clinical data from 56 patients, 31 (55 %) women and 25 (45 %) men, between 14 and 70 years of age treated in a tertiary care hospital between 1996 and 2010 was conducted. Thirty-nine patients (69.6 %) presented with dengue fever without warning signs, 11 (19.6 %) with warning signs and 6 (10.7 %) with signs for severe dengue fever. Two patients (4 %) developed dengue shock syndrome. Non-European descent (p = 0.001), plasma protein level <6.5 mg/dl (p = 0.001), platelets <30/nl (p = 0.017) and activated partial thromboplastin time (aPTT) >44 s (p = 0.003) were associated with severe disease. A significant proportion of patients hospitalized with symptomatic imported dengue fever in Germany have evidence of severe disease. Simple routine laboratory parameters such as complete blood count, plasma protein level and aPTT are helpful tools for identifying adult patients at risk for severe disease.

[State of homeostasis under administration of bear fat in rats with exogenous and endogenous thrombinemia].

PubMed

Kalashnikova, S P; Solovyov, V G

2016-01-01

In experimental studies on 448 rats treated with bear fat diet (0.08 ml/100 g body weight), the nature and mechanisms of influence of this additive on the process of blood coagulation in experimental thromboplastinemia of different origin has been studied. As a result of intravenous injection in the jugular vein of a suspension of thrombin (exog­enous thrombinemia) all clothingsee tests lengthened in the control animals (p<0.05): prothrombin time by 11.1%, activated partial thromboplastin time - by 13.4%, thrombin time by 16.8%. Fibrinogen fell by 1.9 fold, that was accompanied by increase of the level of soluble fibrin monomer complexes and reduce of activity of antithrombin III by 20.2%. At the same time severe thrombocytopenia developed with a relative increase in the num­ber of activated forms (by 73.1%). Consumption coagulopathy was also observed in rats treated with bear fat, but the potential of hemostatic cascade and anticoagulation system remained high (judging by the tests PTV, thrombin time and content of antithrombin III). Under endogenous thromboplastinemia caused by combined stress (hypothermia + physi­cal activity) in animals of the control group on the background of the shortening of the APTT (by 24.9%) and PTV (16.8%), RCMP concentration increased by 52% and activity of antithrombin III increased compensatory. There was an increase of platelet count, due to the activated forms. To 3 h signs of hypocoagulation aggravated even more. In animals treated with bear fat, the results of clothing tests did not differ from the original figures, and by 3 h, the majority of the indicators have reached their original values. The increase in platelet count has not been observed.

The effects of a transcontinental flight on markers of coagulation and fibrinolysis in healthy men after vigorous physical activity.

PubMed

Kupchak, Brian R; Kraemer, William J; Hooper, David R; Saenz, Cathy; Dulkis, Lexie L; Secola, Paul J; Brown, Lee E; Galpin, Andrew J; Coburn, Jared W; DuPont, William H; Caldwell, Lydia K; Volek, Jeff S; Maresh, Carl M

2017-01-01

Athletes and military service members are known to undergo strenuous exercise and sometimes have to take long haul flights soon afterwards; however, its combined effect on many physiological functions is relatively unknown. Therefore, we examined the combined effects of a full-body muscle-damaging workout and transcontinental flight on coagulation and fibrinolysis in healthy, resistance trained men. We also determined the efficacy of a full-body compression garment in limiting their coagulation responses. Nineteen healthy, resistance trained men flew from Connecticut (CT) to California (CA), performed a full-body muscle-damaging workout and then flew back to CT. Ten participants wore full-body compression garments (FCG) for the duration of both flights and during all other portions of the study except during workouts and blood draws, when they wore loose clothing. Nine controls wore loose clothing (CON) throughout the study. Blood samples were collected at 16 h and 3 h before the initial flight from CT, immediately after landing in CA, immediately before and immediately after the full-body workout in CA, immediately after landing in CT, and at 29 h after landing in CT. Plasma markers of coagulation included activated partial thromboplastin time (aPTT), prothrombin fragment 1+2 (PTF 1+2) and thrombin ant-thrombin (TAT). Markers of the fibrinolytic system included the tissue plasmigen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and D-Dimer. Both FCG and CON groups exhibited a faster aPTT after the full-body workout compared to all other time points.  Thrombin generation markers, TAT and PTF 1+2, increased significantly after the full-body workout and immediately after landing in CT. Additionally, tPA increased after the full-body workout, while PAI-1 increased before the flight to CA, after the full-body workout, and just after landing in CT. The D-Dimer significantly increased after the full-body workout and at 29 h post-flight in both groups. Between groups, aPTT was significantly faster and TAT elevated with the CON group at 29 h post-flight. Also, PAI-1 demonstrated higher concentrations immediately after landing in CT for the CON group. A full-body muscle-damaging workout in conjunction with a trans-continental flight activated the coagulation and fibrinolytic systems. Additionally, wearing a full-body compression garment may limit coagulation following a workout through the recovery period.

The effect of corn trypsin inhibitor and inhibiting antibodies for FXIa and FXIIa on coagulation of plasma and whole blood.

PubMed

Hansson, K M; Nielsen, S; Elg, M; Deinum, J

2014-10-01

Corn trypsin inhibitor (CTI), an inhibitor of FXIIa, is used to prevent plasma coagulation by contact activation, to specifically investigate tissue factor (TF)-initiated coagulation. In the present work the specificity of CTI for factor (F) XIIa is questioned. In the commercial available plasma coagulation assays CTI was found to double activated partial thromboplastin time (APTT) at a plasma concentration of 7.3 ± 1.5 μm CTI (assay concentration 2.4 μm). No effect was found on the prothrombin time (PT) when high TF concentrations were used. Also, with specific antibodies for FXIIa and for FXIa only APTT was found to be extended but not PT. With specific enzyme assays using chromogenic substrates CTI was shown to be a strong inhibitor of FXIIa and a competitive inhibitor of FXIa with Ki  = 8.1 ± 0.3 μm, without effect on the coagulation factors FVIIa, FIXa, FXa and thrombin. In thrombin generation and coagulation (free oscillation rheometry, FOR) assays, initiated with low TF concentrations, no effect of CTI (plasma concentrations of 4.4 and 13.6 μm CTI, 25 resp. 100 mg L(-1) in blood) was found with ≥ 1 pm TF. At ≤ 0.1 pm TF in the FOR whole blood assay the coagulation time (CT) concentration dependently increased while the plasma CT became longer than the observation time. To avoid inhibition of FXIa and the thrombin feedback loop we recommend that for coagulation assays the concentration of CTI in blood should be below 20 mg L(-1) (1.6 μm) and in plasma below 3 μm. © 2014 International Society on Thrombosis and Haemostasis.

Surface properties and cytocompatibillity of silk fibroin films cast from aqueous solutions in different concentrations

NASA Astrophysics Data System (ADS)

Lian, Xiao-Jie; Wang, Song; Zhu, He-Sun

2010-03-01

Silk fibroin film (SFF) has been widely used in biomaterials. SFF is usually prepared from a regenerated silk aqueous solution and its properties depend remarkably on the preparation conditions. However, the effect of the silk fibroin concentration ( C 0) on the SFF surface properties as well as the cytocompatibility has rarely been investigated. In this work we prepared a series of Bombyx mori SFFs by casting SF aqueous solutions with the concentration from 10° to 102 mg/mL on TCPS substrate at 60°C. The test results of atomic force microscopy, attenuated total reflection Fourier transform infrared and contact angles analysis showed that the film surface roughness and β-sheet structure increased with the increase of C 0, whereas the surface hydrophilicity increased with the decrease of C 0. The in vitro clotting time measurement results revealed that the SFFs prepared from the thinner solution showed a longer APTT (activated partial thromboplastin time) and TT (thrombin time). The results of microscopy and MTT assay also revealed that cell adhesion and growth were enhanced on the SFF cast from lower C 0 for fibroblasts. In contrast, endothelial cells showed a similar behavior on all those films that were prepared from the solution in different concentrations.

Pharmacokinetics and tolerability of human mouse chimeric anti-CD22 monoclonal antibody in Chinese patients with CD22-positive non-Hodgkin lymphoma.

PubMed

Li, Su; Zhang, Dongsheng; Sun, Jian; Li, Zhinming; Deng, Liting; Zou, Benyan; Zhan, Jing; Jiang, Wenqi

2012-01-01

The safety and pharmacokinetics assessment of antibodies targeting CD22 (e.g., epratuzumab) have been established in western Caucasian populations, but there are no reports of the effects in Chinese populations. This dose-escalation study examines the safety, pharmacokinetics and biologic effects of multiple doses of anti-CD22 human-murine chimeric monoclonal antibody SM03 in 21 Chinese patients with CD22-positive non-Hodgkin lymphoma. Most of drug-related adverse events (AEs) were mild and reversible. Two patients experienced serious AEs (hemorrhage); one patient had grade 4 neutropenia; one patient had asymptomatic grade III prolongation of activated partial thromboplastin time (APTT). Major AEs included fever (71%), prolongation of APTT (42.8%), leukocytopenia (44.4%), alanine transaminase elevation (28.6%), elevated serum creatinine (23.8%) and injection site skin redness (14.3%). Circulating B cells transiently decreased without significant effects on T cells or immunoglobulin levels. Pharmacokinetic data revealed that mean maximum observed SM03 concentration and mean AUC from time zero to infinity increased in a dose-dependent manner up to 360 mg/m (2) SM03. Mean clearance was similar at doses ≤ 360 mg/m (2) and decreased significantly at dose 480 mg/m (2), supporting saturation of B-cell binding at 360 mg/m (2). Across all dose levels and histologies, one patient achieved partial response at 480 mg/m (2) dose; 14 patients had stable disease as best response and four patients progressed. Overall, SM03 was tolerated at doses ranging from 60-480 mg/m (2) and had potential efficacy in Chinese patients with follicular lymphoma.

Effects of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.

PubMed

Blois, Shauna L; Allen, Dana G; Wood, R Darren; Conlon, Peter D

2010-03-01

To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs. 10 hound-crossbred dogs. Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B(2) and 6-keto prostaglandin (PG)F(1alpha) were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation. Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50microM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB(2) and 6-keto PGF(1alpha) concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval. Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB(2) and 6-keto PGF(1alpha) concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2-selective inhibitors on hemostasis should be performed.

Reference Intervals of Routine Coagulation Assays During the Pregnancy and Puerperium Period.

PubMed

Gong, Jiao-Mei; Shen, Yong; He, Yan-Xia

2016-11-01

Significant changes occur in the coagulation and fibrinolytic systems during pregnancy and puerperium in the plasma levels. However, reference ranges based on healthy people are not optimal for informing clinical decisions during the pregnancy and puerperium. Therefore, it is essential to explore coagulation assays' reference ranges during the pregnancy and puerperium. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib.), and D-dimer were all measured according to the manufacturer's specifications and laboratory standard operating procedure of the STA-R evolution coagulation analyzer. A total of 11,601 women were enrolled in this study. The reference ranges for PT, APTT, TT, Fib., and D-dimer in nonpregnancy period were 10.87-13.76 s, 29.22-44.61 s, 15.39-20.15 s, 1.59-3.97 g/l, and 0-0.56 mg/l, respectively. In early-pregnancy period, the ranges were 11.14-14.07 s, 29.97-44.69 s, 14.92-19.03 s, 1.98-4.13 g/l, and 0-1.67 mg/l, respectively. In midpregnancy period, the ranges were 9.98-12.84 s, 28.53-40.70 s, 13.51-19.82 s, 2.63-5.19 g/l, and 0-2.81 mg/l, respectively. In late-pregnancy period, the ranges were 9.48-12.58 s, 28.61-40.80 s, 14.10-19.61 s, 2.80-5.56 g/l, and 0-27.08 mg/l, respectively. In puerperium period, the ranges were 10.85-13.72 s, 30.51-43.02 s, 15.31-19.64 s, 1.14-5.07 g/l, and 1.27-4.85 mg/l, respectively. We presented reference intervals for coagulation assays from the nonpregnancy to puerperium period that can be adopted in other laboratories after further validation. © 2016 Wiley Periodicals, Inc.

Haemostatic agent etamsylate in vitro and in vivo antagonizes anti-coagulant activity of heparin.

PubMed

Cobo-Nuñez, M Yolanda; El Assar, Mariam; Cuevas, Pedro; Sánchez-Ferrer, Alberto; Martínez-González, Jennifer; Rodríguez-Mañas, Leocadio; Angulo, Javier

2018-05-15

Etamsylate is indicated for several anti-hemorrhagic indications in human and veterinary medicine. However, etamsylate has been shown to be effective only in specific hemorrhagic situations. Furthermore, mechanism of action of etamsylate is not known but recent research has shown its ability to inhibit heparin binding to several growth factors. We have evaluated the ability of etamsylate to interfere with the activities of heparin. Effects of etamsylate on vasodilatory activity of heparin were evaluated in rat aortic segments. Influence of etamsylate on anticoagulant activity of heparin was evaluated in vitro by determining prothrombin (PT) time and activated partial thromboplastin time (aPTT) in dog blood and in vivo by determining the interference of systemic and topical etamsylate on heparin-induced extension in bleeding time (BT) in rats. Despite failing to inhibit heparin-induced vasodilation of rat aorta, etamsylate significantly reduced the increase in aPTT caused by heparin (+30.4 ± 6.7% vs. +15.0 ± 2.8% for etamsylate at 100 µM, P < 0.05). Etamsylate also antagonized the anticoagulant effects driven by heparin in vivo since prevented the heparin-induced increase in BT when systemically (i.p.) administered (+94.6 ± 7.5% vs. +57.9 ± 9.2% at 10 mg/kg, P < 0.05, vs. +22.2 ± 16.8% at 30 mg/kg, P < 0.01). Additionally, topically applied etamsylate (125 mg/ml) significantly reduced heparin-induced BT increase (+102.5 ± 3.2% vs. +54.0 ± 5.8%, P < 0.01). These evidences show a pharmacological interference by etamsylate on heparin activities antagonizing pro-hemorrhagic effects of heparin in vitro and in vivo without inhibiting its vasodilatory properties. This ability could help to explain pharmacological effects of etamsylate and proposes its role for reversing pro-hemorrhagic states. Copyright © 2018 Elsevier B.V. All rights reserved.

Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

PubMed

Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

2012-06-01

Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.

The practice of platelet transfusion prior to central venous catheterization in presence of coagulopathy: a national survey among clinicians.

PubMed

van de Weerdt, E K; Peters, A L; Goudswaard, E J; Binnekade, J M; van Lienden, K P; Biemond, B J; Vlaar, A P J

2017-05-01

Correction of coagulopathy prior to central venous catheter (CVC) placement is advocated by guidelines, while retrospective studies support restrictive use of transfusion products. We conducted a mixed vignette and questionnaire web survey to investigate current practice and preferences for CVC placement. Clinical vignettes were used to quantify the tendency to administer platelet concentrate. A positive ß-coefficient is in favour of administering platelet concentrate. Ninety-seven physicians answered the survey questions (36 critical care physicians, 14 haematologists, 20 radiologists and 27 anaesthesiologist). Eighty-six physicians subsequently completed the clinical vignettes (response rate 71%). Preferences in favour of correcting thrombocytopenia prior CVC placement were platelet counts of 10 × 10 9 /L and 20 × 10 9 /L (ß = 3·9; ß = 3·2, respectively), the subclavian insertion site (ß = 0·8). An elevated INR (INR = 3; ß = 0·6) and an elevated aPTT (aPTT = 60 s; ß = 0·4) showed a positive trend towards platelet transfusion. Platelet transfusion was less likely in an emergency setting (ß = -0·4). Reported transfusion thresholds for CVC placement varied from <10 × 10 9 /L to 80 × 10 9 /L for platelet count, from 1·0 to 10·0 for INR and from 25 s to 150 s for aPTT. Implementation of ultrasound guidance as standard practice was limited. Current transfusion practice prior to CVC placement is highly variable. Physicians adjust the decision to correct coagulopathy prior CVC placement based on clinical parameters, insertion site and technique applied. © 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Association of interleukin-18 gene polymorphism and its protein expression with the lower extremity deep venous thrombosis in the chinese han population: A case-control study.

PubMed

Chen, Ye-Long; Shou, Li-Hong; Zhang, Zong-Xin

2018-05-01

We aim to explain the correlation among IL-18 gene polymorphism, its protein expression and LEDVT in the Chinese Han population. A total of 138 LEDVT patients and 150 healthy people volunteered as LEDVT and control groups. All the data, including the gender, age, BMI, levels of TG, LDL/HDL, TC, GLU, APTT, BUN, Cr, ALT, AST, ApoA1, ApoB, and Fg was detected. IL-18 level, IL-18 -137G/C and -607C/A polymorphism, and risk factors of LEDVT were detected using ELISA, PCR-RFLP and multivariate logistic regression analysis, respectively. Increased BMI, GLU, Fg, BUN, ApoB and IL-18 and decreased APTT were found in the LEDVT group. The GC + CC genotype and C allele in -137G/C polymorphism was elevated in the control group when compared to that in the LEDVT group. The IL-18 level was elevated in the case group when compared to the control group with respect to the same genotype in -607C/A and -137G/C polymorphisms, and in the LEDVT group, IL-18 level was higher in the GG genotype than that in the GC + CC genotype of -137G/C polymorphism. BUN, GG genotype and IL-18 level were independent risk factors, but APTT was a protective factor of LEDVT. On the basis of our results, we concluded that the GG genotype of -137G/C polymorphism and IL-18 level are independent risk factors of LEDVT, and IL-18 gene polymorphism affects the level of IL-18 in LEDVT patients. © 2017 Wiley Periodicals, Inc.

Validation of a New Small-Volume Sodium Citrate Collection Tube for Coagulation Testing in Critically Ill Patients with Coagulopathy.

PubMed

Adam, Elisabeth H; Zacharowski, Kai; Hintereder, Gudrun; Raimann, Florian; Meybohm, Patrick

2018-06-01

Blood loss due to phlebotomy leads to hospital-acquired anemia and more frequent blood transfusions that may be associated with increased risk of morbidity and mortality in critically ill patients. Multiple blood conservation strategies have been proposed in the context of patient blood management to minimize blood loss. Here, we evaluated a new small-volume sodium citrate collection tube for coagulation testing in critically ill patients. In 46 critically adult ill patients admitted to an interdisciplinary intensive care unit, we prospectively compared small-volume (1.8 mL) sodium citrate tubes with the conventional (3 mL) sodium citrate tubes. The main inclusion criterium was a proven coagulopathy (Quick < 60% and/or aPTT > 40 second) due to anticoagulation therapy or perioperative coagulopathy. In total, 92 coagulation analyses were obtained. Linear correlation analysis detected a positive relationship for 7 coagulation parameters (Prothrombin Time, r = 0.987; INR, r = 0.985; activated Partial Thromboplastin Time, r = 0.967; Thrombin Clotting Time, r = 0.969; Fibrinogen, r = 0.986; Antithrombin, r = 0.988; DDimer, r = 0.969). Bland-Altman analyses revealed an absolute mean of differences of almost zero. Ninety-five percent of data were within two standard deviations of the mean difference suggesting interchangeability. As systematic deviations between measured parameters of the two tubes were very unlikely, test results of small-volume (1.8 mL) sodium citrate tubes were equal to conventional (3 mL) sodium citrate tubes and can be considered interchangeable. Small-volume sodium citrate tubes reduced unnecessary diagnostic-related blood loss by about 40% and, therefore, should be the new standard of care for routine coagulation analysis in critically ill patients.

A retrospective discussion of the prognostic value of combining prothrombin time(PT) and fibrinogen(Fbg) in patients with Hepatocellular carcinoma.

PubMed

Wang, Xue-Ping; Mao, Min-Jie; He, Zhong-Lian; Zhang, Lin; Chi, Pei-Dong; Su, Jia-Rui; Dai, Shu-Qin; Liu, Wan-Li

2017-01-01

Aims: The levels of coagulation system tests have been studied in various cancers. In this study, our aim is to evaluate the prognostic value of pretreatment plasma coagulation tests in hepatocellular carcinoma (HCC) patients. Patient and methods: A retrospective study was performed in 539 patients with HCC, and follow-up period was at least 60 months until recurrence or death. The prognostic significance of coagulation system tests (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen) were determined by univariate and multivariate Cox hazard models. Then, according to the results of the multivariate analyses, we proposed the coagulation-Based Stage, which combined the independent risk factors (prothrombin time and fibrinogen). Results: Coagulation system tests including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg) were analyzed. Patients with prolonged PT (≥12.1 sec) levels had significantly poor overall survival (OS) and disease-free survival (DFS), not only in the entire cohort (HR: 1.661, 95%CI: 1.125-2.451, p= 0.011 vs. HR: 1.660, 95%CI: 1.125-2.451, p= 0.011), but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). Additionally, high Fbg (≥2.83 g/L) levels experienced significantly decreased OS and DFS (HR: 2.158, 95%CI: 1.427-3.263, p< 0.001 vs. HR: 2.161, 95%CI: 1.429-3.267, p< 0.001), not only in the entire cohort but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). All the patients were then stratified (based on combined PT and Fbg) into three groups, The OS for HCC patients were (41.37±17.76), (31.83±19.84) and (18.68±18.41) months, and the DFS for HCC patients were (41.15±17.88), (31.65±19.81) and (18.66±18.39) months. Conclusions: Our findings suggest that the combination of plasma PT and Fbg levels should be evaluated as the valuable predictor of survival in patients with HCC.

Changes in hemostasis caused by different replacement fluids and outcome in therapeutic plasma exchange in pediatric patients in a retrospective single center study.

PubMed

Witt, Volker; Pichler, Herbert; Beiglboeck, Elisabeth; Kursten, Friedrich; Weidner, Lisa

2017-02-01

Therapeutic plasma exchange (TPE) is a generally accepted and frequently performed procedure for numerous therapeutic indications in adults. Slowly, TPE is also becoming more and more popular in the treatment of pediatric patients. Although, we know that TPE is safe in pediatric patients, the outcome of children treated with TPE is rarely reported. Furthermore, there are only general recommendations regarding the plasma replacement fluid for children and these are adopted from adults. Data concerning outcome and the influence of different types of replacement fluids on hemostasis in children are scarce. We retrospectively evaluated 324 TPE treatments performed in 35 patients between 2008 and 2013 in our level 4 institution for pediatric hematology and oncology. The plasmapheresis procedures were categorized into three groups based on the replacement fluid used. The first group received solvent/detergent-treated (S/D) plasma (70.0% of patients), the second group was administered 5% human albumin (7.7% of patients) and the third group was treated with a combination of human albumin 5% and S/D plasma (22.3% of patients). To assess hemostasis, data on INR, aPTT, fibrinogen and ATIII were collected before and after plasmapheresis from the patients' charts. A modified Multi Organ Dysfunction Syndrome (MODS) Index was used to classify organ failure. Patient outcome, survival rate and adverse events were evaluated. We found a significant increase in the INR by 35.83% and of the aPTT by 18.53% within the human albumin group. The INR and aPTT of patients allocated to the S/D plasma group decreased by 1.58% and 15.77% on average, respectively. The combination group revealed a mild increase of the INR (9.47%), accompanied by a reduction of aPTT (5.97%). Furthermore we found that the survival rate was significantly associated with a MODS Index of <2 (p<0.001). Overall, the number of adverse events was low (1.2%) and none of these were considered life-threatening. Hemostasis could be preserved in a clinically acceptable range for a variety of underlying diseases with SD plasma alone or in combination with human albumin. Based on our results we would recommend practitioners to closely pre-estimate the hemostatic situation before using human albumin alone in critically ill pediatric patients with a limited ability to produce coagulation factors. The outcome of the patients in our collective exprience is correlated to the extent of organ dysfunction. Therefore further controlled studies are highly recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of halloysite nanotubes on the structure and function of important multiple blood components.

PubMed

Wu, Keke; Feng, Ru; Jiao, Yanpeng; Zhou, Changren

2017-06-01

Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV-vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Freshwater plants synthesize sulfated polysaccharides: heterogalactans from Water Hyacinth (Eicchornia crassipes).

PubMed

Dantas-Santos, Nednaldo; Gomes, Dayanne Lopes; Costa, Leandro Silva; Cordeiro, Sara Lima; Costa, Mariana Santos Santana Pereira; Trindade, Edvaldo Silva; Franco, Célia Regina Chavichiolo; Scortecci, Kátia Castanho; Leite, Edda Lisboa; Rocha, Hugo Alexandre Oliveira

2012-01-01

Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway.

Comparison platelet indices in diabetic patients with and without diabetic foot ulcer

NASA Astrophysics Data System (ADS)

Mardia, A. I.; Gatot, D.; Lindarto, D.

2018-03-01

Diabetes Mellitus is a group of metabolic disease which incidence increases every year. Some diabetic patients have diabetic foot ulcer as acomplication. The occurrence of ulcers in diabetic patients can be caused by the presence of thrombosis due to increased platelet function. Therefore, a cross-sectional study on 40 diabetic patients was performed at RSUP Adam Malik Medan to see whether there were differences in platelet indices between diabetic patients with and without diabetic foot ulcers. Platelets indices were examined and looked for differences in diabetic patients with and without diabetic foot ulcers. Data were analyzed using Chi-Square and Mann-Whitney U test with 95% CI. P-value<0.05 was considered statistically significant. There were differences in hemostasis function (prothrombin time, thrombin time, INR, aPTT, and fibrinogen) between the two groups with p values of 0.001; 0.004; 0.015; 0.021; 0.009, respectively. From the platelet indices examination, there were differences in the number of platelets, PDW and PCT with p values of 0.041; 0.027; 0.007, respectively, whereas there was no difference for MPV value (p=0,05). Platelet indices were found to increase in diabetic patients with diabetic foot ulcers indicating more reactive and aggregatable platelet function.

Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

PubMed

Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

2018-02-01

Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly Absorbent Antibacterial Hemostatic Dressing for Healing Severe Hemorrhagic Wounds

PubMed Central

Li, Ting-Ting; Lou, Ching-Wen; Chen, An-Pang; Lee, Mong-Chuan; Ho, Tsing-Fen; Chen, Yueh-Sheng; Lin, Jia-Horng

2016-01-01

To accelerate healing of severe hemorrhagic wounds, a novel highly absorbent hemostatic dressing composed of a Tencel®/absorbent-cotton/polylactic acid nonwoven base and chitosan/nanosilver antibacterial agent was fabricated by using a nonwoven processing technique and a freeze-drying technique. This study is the first to investigate the wicking and water-absorbing properties of a nonwoven base by measuring the vertical wicking height and water absorption ratio. Moreover, blood agglutination and hemostatic second tests were conducted to evaluate the hemostatic performance of the resultant wound dressing. The blending ratio of fibers, areal weight, punching density, and fiber orientation, all significantly influenced the vertical moisture wicking property. However, only the first two parameters markedly affected the water absorption ratio. After the nonwoven base absorbed blood, scanning electron microscope (SEM) observation showed that erythrocytes were trapped between the fibrin/clot network and nonwoven fibers when coagulation pathways were activated. Prothrombin time (PT) and activated partial thromboplastin time (APTT) blood agglutination of the resultant dressing decreased to 14.34 and 50.94 s, respectively. In the femoral artery of the rate bleeding model, hemostatic time was saved by 87.2% compared with that of cotton cloth. Therefore, the resultant antibacterial wound dressing demonstrated greater water and blood absorption, as well as hemostatic performance, than the commercially available cotton cloth, especially for healing severe hemorrhagic wounds. PMID:28773912

Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study: correlation with coagulopathy

PubMed Central

Matijevic, Nena; Wang, Yao-Wei W.; Wade, Charles E.; Holcomb, John B.; Cotton, Bryan A.; Schreiber, Martin A.; Muskat, Peter; Fox, Erin E.; del Junco, Deborah J.; Cardenas, Jessica C.; Rahbar, Mohammad H.; Cohen, Mitchell Jay

2014-01-01

Background Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. Methods As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. Results 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001). Conclusions Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding. PMID:25086657

Taoren-Honghua herb pair and its main components promoting blood circulation through influencing on hemorheology, plasma coagulation and platelet aggregation.

PubMed

Liu, Li; Duan, Jin-ao; Tang, Yuping; Guo, Jianming; Yang, Nianyun; Ma, Hongyue; Shi, Xuqin

2012-01-31

Persicae Semen (Taoren) and Carthami Flos (Honghua) used in pair which is named as Taoren-Honghua (TH) herb pair has been used in traditional Chinese medicine (TCM) for promoting blood circulation to dissipate blood stasis for many years in China. This paper investigated the effects of TH and its main components amygdalin and hydroxysafflor yellow A (HSYA) on hemorheological disorders of blood stasis in rats. Rats were randomly divided into seven groups (control group, model group, TH group, amygdalin group, HSYA group, amygdalin+HSYA group, and aspirin group) with eight animals in each, whose gender was equally distributed throughout groups. All treatments were performed by gavage and administered seven times with an interval of 12h. After the fifth administration, the model rats except those in control group with blood stasis were established by being placed in ice-cold water during the interval between two injections of adrenaline hydrochloride (Adr); and blood samples were collected 30min after the last administration on the following day. TH could significantly decrease whole blood viscosity (WBV), plasma viscosity (PV) and packed cell volume (PCV). It also significantly prolonged thrombin time (TT) and thromboplastin time (APTT), increased prothrombin time (PT) and lowered fibrinogen content (FIB). HSYA which significantly decreased WBV and PV had no effect on plasma coagulation parameters. Amygdalin could significantly decrease PV, prolong APTT and decrease FIB, showing few effects on WBV. TH and its main components amygdalin and HSYA could significantly reduce platelet aggregation and protect vascular endothelial cells. Based on the above results, amygdalin and HSYA were responsible for the main curative effects of TH and usually had synergetic effects, such as decreasing PV and platelet aggregation percentage. The study may provide scientific information to further understanding of the mechanism(s) of TH and its main components in activating blood circulation to dissipate blood. It may also create valuable insight into the possible effects and utilization of TH and its components as a feasible alternative therapeutic agent for patients with hemorheological disorders. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The effect of hirudin modification of silk fibroin on cell growth and antithrombogenicity.

PubMed

Wang, Qiongyu; Tu, Fangfang; Liu, Yunfei; Zhang, Yujin; Li, Helei; Kang, Zhao; Yin, Yin; Wang, Jiannan

2017-06-01

Thrombus formation remains a particular challenge for small-diameter vascular grafts. In this study, the direct thrombin inhibitor hirudin (Hir) was used to modify silk fibroin films in an attempt to enhance its antithrombogenic properties. Hir was successfully attached to silk fibroin and uniformly distributed in the regenerative material. Hir-modified films showed good cytocompatibility, and supported adhesion and proliferation of fibroblasts (L929), human umbilical vascular endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs). Proliferation of HAVSMCs was inhibited by increasing Hir concentration. Activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT) of Hir-modified silk fibroin tubular scaffolds (SFTSs) were all increased markedly compared with fresh rabbit blood, ethanol-treated SFTS and unmodified SFTS, demonstrating the improved antithrombogenicity of SFTSs following modification with Hir. Copyright © 2017 Elsevier B.V. All rights reserved.

Sulfated modification and anticoagulant activity of pumpkin (Cucurbita pepo, Lady Godiva) polysaccharide.

PubMed

Liang, Li; Ao, Le; Ma, Tao; Ni, Yuanying; Liao, Xiaojun; Hu, Xiaosong; Song, Yi

2018-01-01

Sulfated modification of pumpkin polysaccharide using CAS with pyridines as catalysts under different conditions was conducted to obtain different degrees of sulfation on a laboratory scale. Anticoagulant activities of pumpkin polysaccharide and its sulfated derivatives were also investigated employing various established in vitro systems. Results showed that addition of high ratio of CAS/pyridine under constant conditions could increase the degree of substitution. Sulfate substitution was further confirmed by the FT-IR and 13 C NMR analysis. The d f values between 2.11-2.73 indicated the relatively expanded conformation of the sulfated derivatives. The sulfated polysaccharides showed higher anticoagulant activities through activated partial thrombosis time (aPTT), thrombin time (TT), prothrombin time (PT) and anti-Xa activity assay, which revealed that better anticoagulant activities could be obtained when DS remained higher and M w maintained in a moderate range. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of heparin rinse on the biocompatibility of continuous veno-venous hemodiafiltration.

PubMed

Opatrný, K; Polanská, K; Krouzecký, A; Vít, L; Novák, I; Kasal, E

2002-06-01

The aims of our cross-over randomized study were (1) to assess hemostasis in patients with acute renal failure (ARF) and (2) to determine whether or not the generally recommended heparin rinse of the extracorporeal circuit (ECC) prior to the procedure affects thrombogenicity, complement activation, and leukocyte count in blood during continuous venovenous hemodiafiltration (CVVHDF). Eleven critically ill ARF patients were treated, in random order, using CVVHDF in postdilution setup following ECC rinse with saline (A) with heparin at a concentration of 2,000 IU/L (10 procedures), (B) with heparin at a concentration of 10,000 IU/L (7 procedures), and (C) without heparin (9 procedures). Except for the rinse, anticoagulation therapy did not differ in individual patients during the procedures. Blood was withdrawn before, and at minutes 15, 60, and 360 invariably at diafilter inlet and outlet. Compared with healthy individuals, patients showed lower blood thrombocyte counts (153 vs 233*10(9)/L, p<0.01, arithmetic means, Student's t test), longer aPTT (44 vs 36 s, p<0.05), higher plasma levels of heparin (0.1 vs 0.0 U/mL, p<0.05), D-dimer (1129 vs 36 ng/mL, p<0.001) and beta-thromboglobulin (BTG) (159 vs 37 U/mL, p<0.001) prior to CVVHDF. The comparison of procedures with different rinsing technique did not reveal any significant difference in their effects on blood thrombocyte and leukocyte counts, aPTT, plasma levels of heparin, BTG, thrombin-antithrombin III complexes, D-dimer, or the C5a complement component. (1) Patients indicated for CVVHDF show impaired hemostasis involving thrombocytes, coagulation, and fibrinolysis, (2) no beneficial effect of heparin rinse on CVVHDF ECC thrombogenicity, complement activation or blood leukocyte counts was demonstrated.

Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

PubMed Central

Kang, Yoogoo; Lewis, Jessica H.; Navalgund, Ashok; Russell, Michael W.; Bontempo, Franklin A.; Niren, Lawrence S.; Starzl, Thomas E.

2010-01-01

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F < 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with ε-aminocaproic acid (0.09%) and an untreated sample. Blood treated with ε-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of ε-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, ε-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with ε-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 ± 29.5% to 94.8 ± 7.4% (mean ± SD, P < 0.001). None of the treated patients had hemorrhagic or thrombotic complications. In patients undergoing liver transplantation, the judicious use of a small dose of ε-aminocaproic acid, when its efficacy was confirmed in vitro, effectively treated the severe fibrinolysis without clinical thrombotic complications. PMID:3296855

Development and blood compatibility assessment of electrospun polyvinyl alcohol blended with metallocene polyethylene and plectranthus amboinicus (PVA/mPE/PA) for bone tissue engineering.

PubMed

Qi, Jie; Zhang, Huang; Wang, Yingzhou; Mani, Mohan Prasath; Jaganathan, Saravana Kumar

2018-01-01

Currently, the design of extracellular matrix (ECM) with nanoscale properties in bone tissue engineering is challenging. For bone tissue engineering, the ECM must have certain properties such as being nontoxic, highly porous, and should not cause foreign body reactions. In this study, the hybrid scaffold based on polyvinyl alcohol (PVA) blended with metallocene polyethylene (mPE) and plectranthus amboinicus (PA) was fabricated for bone tissue engineering via electrospinning. The fabricated hybrid nanocomposites were characterized by scanning electron microscopy (SEM), Fourier transform and infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), contact angle measurement, and atomic force microscopy (AFM). Furthermore, activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolytic assays were used to investigate the blood compatibility of the prepared hybrid nanocomposites. The prepared hybrid nanocomposites showed reduced fiber diameter (238±45 nm) and also increased porosity (87%) with decreased pore diameter (340±86 nm) compared with pure PVA. The interactions between PVA, mPE, and PA were identified by the formation of the additional peaks as revealed in FTIR. Furthermore, the prepared hybrid nanocomposites showed a decreased contact angle of 51°±1.32° indicating a hydrophilic nature and exhibited lower thermal stability compared to pristine PVA. Moreover, the mechanical results revealed that the electrospun scaffold showed an improved tensile strength of 3.55±0.29 MPa compared with the pristine PVA (1.8±0.52 MPa). The prepared hybrid nanocomposites showed delayed blood clotting as noted in APTT and PT assays indicating better blood compatibility. Moreover, the hemolysis assay revealed that the hybrid nanocomposites exhibited a low hemolytic index of 0.6% compared with pure PVA, which was 1.6% suggesting the safety of the developed nanocomposite to red blood cells (RBCs). The prepared nanocomposites exhibited better physico-chemical properties, sufficient porosity, mechanical strength, and blood compatibility, which favors it as a valuable candidate in bone tissue engineering for repairing the bone defects.

Benzene inhalation effects upon tetanus antitoxin. Responses and leukemogenesis in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoner, R D; Drew, R T; Bernstein, D M

1980-01-01

The effects of inhaled benzene on primary and secondary antibody responses and the incidence of leukemia in mice are reported. Young adult mice were given 5, 12, or 22 exposures to 400 ppM benzene for 6 hrs/day 5 days/week. After the exposure periods, the mice were immunized with absorbed tetanus toxoid (APTT) and/or fluid tetanus toxid (FTT). Exposure to benzene increasingly suppressed primary antibody responses to both antigens. Secondary antibody responses to FTT were nearly normal in animals given 10, 15, or 20 exposures to 400 ppM benzene. Other groups of mice were exposed to either 200 ppM or 50more » ppM benzene. Primary antibody responses elicited with FTT and/or APTT were nearly normal in all mice exposed to 50 ppM benzene and in mice exposed to 200 ppM benzene for 5 days. However, 10 and 20 exposures to 200 ppM benzene inhibited antibody production. The effects of chronically inhaled 300 ppM benzene on the time of onset and incidence of leukemia in 400 7-month-old female HRS/J mice were also studied. Two genotypes were used; the (hr/hr) hairless mice are leukemia-prone, whereas the (hr/+) haired mice are more resistant to leukemia. The exposure continued for a period of 6 months. Lymphoid, myeloid, and mixed (lymphoid and myeloid) leukemias were observed. Ninety percent of the (hr/hr) mice exposed to benzene died from leukemia as compared with 91% for the (hr/hr) air control group. Eighty-five percent of the (hr/+) mice exposed to benzene died from leukemia as compared with 81% for the (hr/+) air control group. Exposures to 300 ppM benzene did not alter the time of onset or the incidence of leukemia commonly expected in HRS/J mice.« less

Laboratory measurement of apixaban using anti-factor Xa assays in acute ischemic stroke patients with non-valvular atrial fibrillation.

PubMed

Shin, Hyoshim; Cho, Min-Chul; Kim, Rock Bum; Kim, Chang-Hun; Choi, Nack-Cheon; Kim, Soo-Kyung; Koh, Eun-Ha

2018-02-01

Apixaban is effective and safe for preventing stroke, and its usage has increased exponentially in recent years. However, data concerning the therapeutic range of apixaban is limited. This study determined the trough and peak levels of apixaban-specific anti-factor Xa activity (AFXaA) in acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF) in Korea. The study included 85 patients who received apixaban. Blood samples were taken to measure the trough and peak levels of AFXaA using a chromogenic anti-factor assay, as well as prothrombin time (PT) and activated partial thromboplastin time (aPTT). We also reviewed complications such as major bleeding of patients treated with apixaban. In patients given a 5.0-mg apixaban dose, the median trough and peak levels of AFXaA were 104.5 and 202.0 ng/mL. In patients given a 2.5-mg apixaban dose, the median trough and peak AFXaA levels were 76.0 and 151.0 ng/mL. The PT showed a positive correlation with increased AFXaA activity at both levels (Trough R = 0.486, Peak R = 0.592), but the aPTT had no relationship with AFXaA activity at both levels (Trough R = 0.181, Peak R = 0.129). Two cases with intracranial bleeding belonged to the highest AFXaA quartile (Trough, p = 0.176; Peak, p = 0.053). In conclusion, we determined the trough and peak levels of AFXaA in patients with NVAF while being treated with the apixaban in Korea. Our results could be used as a starting point when setting the reference ranges for laboratories using anti-Xa assay. Large-scale studies are needed to establish the reference range for AFXaA in patients with NVAF.

Building and validation of a prognostic model for predicting extracorporeal circuit clotting in patients with continuous renal replacement therapy.

PubMed

Fu, Xia; Liang, Xinling; Song, Li; Huang, Huigen; Wang, Jing; Chen, Yuanhan; Zhang, Li; Quan, Zilin; Shi, Wei

2014-04-01

To develop a predictive model for circuit clotting in patients with continuous renal replacement therapy (CRRT). A total of 425 cases were selected. 302 cases were used to develop a predictive model of extracorporeal circuit life span during CRRT without citrate anticoagulation in 24 h, and 123 cases were used to validate the model. The prediction formula was developed using multivariate Cox proportional-hazards regression analysis, from which a risk score was assigned. The mean survival time of the circuit was 15.0 ± 1.3 h, and the rate of circuit clotting was 66.6 % during 24 h of CRRT. Five significant variables were assigned a predicting score according to the regression coefficient: insufficient blood flow, no anticoagulation, hematocrit ≥0.37, lactic acid of arterial blood gas analysis ≤3 mmol/L and APTT < 44.2 s. The Hosmer-Lemeshow test showed no significant difference between the predicted and actual circuit clotting (R (2) = 0.232; P = 0.301). A risk score that includes the five above-mentioned variables can be used to predict the likelihood of extracorporeal circuit clotting in patients undergoing CRRT.

Heparin Saline Versus Normal Saline for Flushing and Locking Peripheral Venous Catheters in Decompensated Liver Cirrhosis Patients

PubMed Central

Wang, Rui; Zhang, Ming-Guang; Luo, Ou; He, Liu; Li, Jia-Xin; Tang, Yun-Jing; Luo, Yan-Li; Zhou, Min; Tang, Li; Zhang, Zong-Xia; Wu, Hao; Chen, Xin-Zu

2015-01-01

Abstract A prospective randomized, controlled, single-blinded trial to compare the effectiveness and safety of heparin saline (HS) to those of normal saline (NS) as flushing and locking solutions for peripheral venous catheter (PVC) in decompensated liver cirrhosis (DLC) patients. Patients with DLC at our institution between April 2012 and March 2013 were enrolled after obtaining informed consent. The patients were randomly allocated into 2 groups: the NS group received preservative-free 0.9% sodium chloride as the flushing and locking solution, while the HS group received HS (50 U/mL). PVC-related events and the duration of PVC maintenance were compared between the 2 groups. Moreover, the preinfusion and postinfusion levels of prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet (PLT) were also compared. A total of 32 and 36 DLC patients in the NS (125 PVCs) and HS (65 PVCs) groups, respectively, were analyzed. Baseline characteristics, including gender, age, Child–Pugh grade, PVC type and administration of anticoagulant, and irritant agents, were comparable between the 2 groups (P > 0.05). The maintenance times of the HS and NS groups were 80.27 ± 26.47 and 84.19 ± 29.32 hours, respectively (P = 0.397). Removal of PVC for abnormal reasons occurred in 30.7% and 22.4% of patients in the HS and NS groups (P = 0.208). The PVC occlusion rates were 6.2% and 5.6% in the HS and NS groups, respectively (OR = 1.11, 95% CI 0.31–3.92). The PT, APTT, and PLT levels were comparable between the 2 groups both before and after infusion (P > 0.05). Incremental analyses showed that Child–Pugh grade C might be a risk factor for the suppression of PLT in the HS group. We consider NS to be as effective as and safer than conventional HS for flushing and locking PVC in decompensated liver cirrhosis patients. PMID:26252305

Evaluation of hemostasis parameters and the role of the oxidative damage to plasma proteins in the modulation of hemostasis in patients with nephrolithiasis before and after extracorporeal shock wave lithotripsy.

PubMed

Woźniak, Paweł; Kontek, Bogdan; Różański, Waldemar; Olas, Beata

2017-01-01

Extracorporeal shock wave lithotripsy (ESWL) is a commonly-used method in urology, which may modulate hemostasis and may induce lipid peroxidation in patients with nephrolithiasis. However, previous studies only examine changes occurring in patients 30-240 min after ESWL. The main aim of the present study was to determine whether oxidative stress may modulate the hemostatic activity of plasma in patients with nephrolithiasis before ESWL and the day after treatment ESWL. This will be performed by measuring selected parameters of hemostasis in these patients, both before ESWL and the following day, and assessing the level of oxidative damage to plasma proteins in these patients by measuring two biomarkers. Twelve patients with nephrolithiasis and 10 healthy participants were included. The following parameters of hemostasis were measured: the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of plasma, the level of fibrinogen, the level of D-dimer and blood platelet count. In addition, two selected biomarkers of oxidative stress were measured: protein carbonylation level and the number of protein thiol groups. No difference was observed between patients with nephrolithiasis before and after ESWL and healthy controls with regard to PT, TT or APTT. Fibrinogen concentration and blood platelet count were lower in the nephrolithiasis patients in the period after ESWL than before ESWL. The nephrolithiasis patients demonstrated elevated D-dimer concentration after ESWL. However, although oxidative damage was observed in the plasma proteins in the nephrolithiasis patients, this was not influenced by ESWL. Oxidative stress may induce changes of hemostasis in patients with nephrolithiasis, both before and after ESWL. In addition, changes of hemostasis parameters such as fibrinogen, blood platelet count and D-dimer level can be observed in these patients, especially after ESWL, and this may suggest that ESWL modulates hemostasis. By having a better understanding of the influence of ESWL on hemostasis, this could lead to modifying patient care for those patients at increased risk of bleeding.

An in vitro comparison of the effects of voluven (6% hydroxyethyl starch 130/0.4) and hespan (6% hydroxyethyl starch 670/0.75) on measures of blood coagulation in canine blood.

PubMed

Griego-Valles, Michelle; Buriko, Yekaterina; Prittie, Jennifer E; Fox, Philip R

2017-01-01

To assess primary and secondary hemostasis following in vitro dilution of canine whole blood (WB) with hydroxyethyl starch (HES) 130/0.4 and HES 670/0.75. In vitro experimental study. Private practice, teaching hospital. Twenty-five healthy dogs. Each dog underwent venipuncture and 18 mL of venous blood was sampled once. Collected blood was separated in 4 aliquots. Aliquot A served as baseline sample. The remaining tubes of WB were diluted with 0.9% saline, HES 670/0.75 and HES 130/0.4 at a ratio of 1:5.5. Dilutional effects were evaluated using prothrombin time (PT), activated partial thromboplastin time (aPTT), packed cell volume (PCV), thromboelastography (TEG), and platelet closure time (Ct), which was measured using a platelet function analyzer (PFA). Clot strength (ie, G value) was calculated from measured TEG values. Significant increases in PT (P < 0.05) and aPTT (P < 0.05) were documented following WB dilution with saline. Dilution of WB with HES 670/0.75 and HES 130/0.4 resulted in significant hypocoagulable changes in K, MA and G (P < 0.05) compared to baseline and saline. When comparing saline to HES 670/0.75, both R and K values were significantly increased (P < 0.05). K value was significantly increased (P < 0.05) when comparing baseline to HES 130/0.4 and HES 670/0.75. Ct (P < 0.05) was significantly prolonged after WB dilution with HES solutions but not after saline. Dilution of WB with HES 670/0.75 and HES 130/0.4 resulted in changes in primary and secondary hemostasis. Although there were small differences between saline and HES 670/0.75, no differences between HES solutions were evident in this small study. This may suggest there would be minimal increases in bleeding risk when either solution is administered to dogs at low doses. Clinical relevance of our findings requires further investigation. © Veterinary Emergency and Critical Care Society 2016.

[Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance].

PubMed

Xiao, Fang-Fang; Hu, Kai-Xun; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Ai, Hui-Sheng; Yu, Chang-Lin

2013-04-01

To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.

Dissociation between the pharmacokinetics and pharmacodynamics of once-daily rivaroxaban and twice-daily apixaban: a randomized crossover study.

PubMed

Kreutz, R; Persson, P B; Kubitza, D; Thelen, K; Heitmeier, S; Schwers, S; Becka, M; Hemmrich, M

2017-10-01

Essentials In this crossover study the anticoagulant effects of rivaroxaban and apixaban were compared. Healthy volunteers received rivaroxaban 20 mg once daily or apixaban 5 mg twice daily. Rivaroxaban was associated with more prolonged inhibition of thrombin generation than apixaban. Rivaroxaban induced a clear prolongation of prothrombin time and activated partial thromboplastin time. Background The anticoagulant actions of the oral direct activated factor Xa inhibitors, rivaroxaban and apixaban, have not previously been directly compared. Objectives To compare directly the steady-state pharmacokinetics and anticoagulant effects of rivaroxaban and apixaban at doses approved for stroke prevention in patients with non-valvular atrial fibrillation. Methods Twenty-four healthy Caucasian male volunteers were included in this open-label, two-period crossover, phase 1 study (EudraCT number: 2015-002612-32). Volunteers were randomized to receive rivaroxaban 20 mg once daily or apixaban 5 mg twice daily for 7 days, followed by a washout period of at least 7 days before they received the other treatment. Plasma concentrations and anticoagulant effects were measured at steady state and after drug discontinuation. Results Overall exposure was similar for both drugs: the geometric mean area under the plasma concentration-time curve for the 0-24-h interval was 1830 μg h L -1 for rivaroxaban and 1860 μg h L -1 for apixaban. Rivaroxaban was associated with greater inhibition of endogenous thrombin potential (geometric mean area under the curve relative to baseline during the 0-24-h interval: 15.5 h versus 17.5 h) and a more pronounced maximal prolongation relative to baseline of prothrombin time (PT) (1.66-fold versus 1.14-fold) and activated partial thromboplastin time (APTT) (1.43-fold versus 1.16-fold) at steady state than apixaban. Conclusions Despite similar exposure to both drugs, rivaroxaban 20 mg once daily was associated with greater and more sustained inhibition of thrombin generation than apixaban 5 mg twice daily. Sensitive PT and APTT assays can be used to estimate the anticoagulant effects of rivaroxaban. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Plasma D-dimer as a Prognostic Marker in ICU Admitted Egyptian Children with Traumatic Brain Injury.

PubMed

Foaud, Hala Mohamed Amin; Labib, John Rene; Metwally, Hala Gabr; El-Twab, Khaled Mohamed Abd

2014-09-01

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. This study aimed at evaluation of the D-dimer blood levels as a new marker to predict prognosis and outcome of traumatic brain injuries among children. This case control study was conducted at the Paediatric Intensive Care Unit (ICU), Alharm Hospital in Giza, Egypt during 2012-2013, on 46 Paediatric cases admitted to ICU with head injury and 20 normal age-matched controls. Clinical data and venous blood samples were prospectively collected at 1(st), 3(rd) and 14(th) day of admission, in addition to examination finding as Glasgow coma scale (GCS), cranial brain computed tomography (CT), routine laboratory investigations (CBC, CRP, SGOT, SGPT, urea, creatinine, random blood glucose, Na, K and arterial blood gases) plasma D-dimer, INR, PT, aPTT and PC. Data analysis was carried out accordingly and ROC curve was performed to explore the discriminating ability of D-dimer through estimation of its accuracy in differentiating temporal survivorship of those with TBI. Cases were classified according to outcome into survivors and non-survivors. Significant difference was observed between cases and controls and between survivors and non-survivors during 1(st), 3(rd) and 14(th) day of the follow up including GCS, blood levels of D-dimer, PT and aPTT. ROC curve analysis for D-dimer showed decline in both sensitivity from 89.5% to 73.7% and specificity from 100% to 81.5% along the study days respectively. D-dimer time measurements showed significant decline among survivors from 4.2 to 0.7, while in the non survivor group this decline was much higher from 27.9 to 1.4. Low plasma D-dimer suggests the absence of brain injury, and good prognosis.

Colloid osmotic pressure and extravasation of plasma proteins following infusion of Ringer's acetate and hydroxyethyl starch 130/0.4.

PubMed

Zdolsek, J H; Bergek, C; Lindahl, T L; Hahn, R G

2015-11-01

During fluid infusion therapy, plasma proteins are diluted and leak from the intravascular space, which alters the colloid osmotic pressure (COP) and potentially affects coagulation. We hypothesised that acetated Ringer's and starch solution, alone or in combination, influence these mechanisms differently. On different occasions, 10 male volunteers were infused with 20 ml/kg acetated Ringer's and 10 ml/kg 6% hyroxyethyl starch 130/0.4 (Voluven(®) ) alone or in combination (first with starch solution followed by Ringer's solution). Blood samples were collected every 30-min for measurements of COP, blood haemoglobin, platelets, and plasma concentrations of albumin, immunoglobulins (IgG and IgM), coagulation factor VII (FVII), fibrinogen, cystatin C, activated partial thromboplastin time (APTT) and prothrombin international normalised ratio (PT-INR). Changes were compared with the haemoglobin-derived plasma dilution. The COP increased by 8.4% (SD 3) with starch and decreased by 26.2% (7.9) with Ringer's. These infusions diluted the plasma by 23.4% (5.3) and 18.7% (4.9) respectively. The COP changes in the combined experiment followed the same pattern as the individual infusions. Albumin and IgG changes in excess of the plasma dilution were very subtle. The intravascular contents of the IgM and platelets decreased, whereas FVII, fibrinogen and cystatin C increased. PT-INR increased by 1/3 of the plasma dilution, whereas changes in APTT did not correlate with the plasma dilution. The starch increased COP and only minor capillary leak occurred in healthy volunteers. The fluid-induced plasma dilution correlated with mild impairment of the extrinsic coagulation pathway but not of the intrinsic pathway. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Thrombin-inhibiting perfluorocarbon nanoparticles provide a novel strategy for treatment and magnetic resonance imaging of acute thrombosis

PubMed Central

Myerson, J.; He, L.; Lanza, G.; Tollefsen, D.; Wickline, S.

2013-01-01

Background As a regulator of the penultimate step in the coagulation cascade, thrombin represents a principal target of direct and specific anticoagulants. Objective A potent thrombin inhibitor complexed with a colloidal nanoparticle was devised as a first-in-class anticoagulant with prolonged and highly localized therapeutic impact conferred by its multivalent thrombin-absorbing particle surface. Methods PPACK (Phe(D)-Pro-Arg-Chloromethylketone) was secured covalently to the surface of perfluorocarbon-core nanoparticle structures. PPACK and PPACK nanoparticle inhibition of thrombin were assessed in vitro via thrombin activity against a chromogenic substrate. In vivo antithrombotic activity of PPACK, heparin, non-functionalized nanoparticles, and PPACK nanoparticles was assessed through IV administration prior to acute photochemical injury of the common carotid artery. Perfluorocarbon particle retention in extracted carotid arteries from injured mice was assessed via 19F magnetic resonance spectroscopy (MRS) and imaging (MRI) at 11.7 T. APTT measurements determined the systemic effects of the PPACK nanoparticles at various times after injection. Results Optical assay verified that PPACK nanoparticles exceeded PPACK’s intrinsic activity against thrombin. Application of the an in vivo acute arterial thrombosis model demonstrated that PPACK nanoparticles outperformed both heparin (p=.001) and uncomplexed PPACK (p=.0006) in inhibiting thrombosis. 19F MRS confirmed that PPACK nanoparticles specifically bound to sites of acute thrombotic injury. APTT normalized within twenty minutes of PPACK nanoparticles injection. Conclusions PPACK nanoparticles present thrombin-inhibiting surfaces at sites of acutely forming thrombi that continue to manifest local clot inhibition even as systemic effects rapidly diminish and thus represent a new platform for localized control of acute thrombosis. PMID:21605330

Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study.

PubMed

Lanini, Simone; Portella, Gina; Vairo, Francesco; Kobinger, Gary P; Pesenti, Antonio; Langer, Martin; Kabia, Soccoh; Brogiato, Giorgio; Amone, Jackson; Castilletti, Concetta; Miccio, Rossella; Capobianchi, Maria Rosaria; Strada, Gino; Zumla, Alimuddin; Di Caro, Antonino; Ippolito, Giuseppe

2018-01-06

Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Characterization of bioactive chitosan and sulfated chitosan from Doryteuthis singhalensis (Ortmann, 1891).

PubMed

Ramasamy, Pasiyappazham; Subhapradha, Namasivayam; Thinesh, Thangadurai; Selvin, Joseph; Selvan, Kanagaraj Muthamizh; Shanmugam, Vairamani; Shanmugam, Annaian

2017-06-01

Chitosan was extracted from the pen of squid Doryteuthis singhalensis and characterized using FT-IR, NMR, CHN, SEM and DSC analysis. Purified chitosan was sulfated with chlorosulfonic acid in N,N-dimethylformamide and the added sulfate group was confirmed with FT-IR analysis. The molecular weight and degree of deacetylation (DDA) of chitosan was found 226.6kDa and 83.76% respectively. Chitosan exhibited potent antioxidant activity evidenced by reducing power, chelating ability on ferrous ions and scavenging activity on DPPH, superoxide and hydroxyl radicals. The anticoagulant assay using activated partial thromboplastin time (APTT) and prothrombin time (PT) showed chitosan as a strong anticoagulant. The results of this study showed possibility of using D. singhalensis pen as a non-conventional source of natural antioxidants and anticoagulant which can be incorporated in functional food formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin.

PubMed

Stupnisek, Mirjana; Franjic, Sandra; Drmic, Domagoj; Hrelec, Masa; Kolenc, Danijela; Radic, Bozo; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2012-05-01

Recently, in rat abdominal aorta terminoterminal-anastomosis the stable gastric pentadecapeptide BPC 157 prevents obstructive thrombus formation and rapidly destroys already formed obstructive thrombus. Also, BPC 157 wound healing may signify the clot as conductive matrix or "scaffold" to speed up wound healing process, and decrease bleeding. Here, in rats, BPC 157 (10 μg/kg, 10 ng/kg) improved always reduced bleeding time and amount of bleeding after (tail) amputation only, heparin (250 mg/kg, 25mg/kg, 10mg/kg i.v.), warfarin (1.5mg/kg i.g. once daily for 3 consecutive days), aspirin (0.1g/kg i.g. (once daily/3 consecutive days) or 1.0 g/kg i.p. once), and amputation associated with those agents application. BPC 157 counteracting regimens (i.v., i.p., i.g. (immediately after any challenge)) correspondingly follow the route of bleeding-agents application. All heparin-, warfarin-, and aspirin-rats and normal-rats that received BPC 157 exhibited lesser fall in platelets count. BPC 157 attenuated over-increased APTT-, TT-values in 10mg/kg heparin-rats, but did not influence heparin activity (anti-Xa test). Indicatively, unless counteracted in BPC 157 rats, excessive bleeding-acute thrombocytopenia (<20% of initial values in heparin-rats) approaches substantial fall in platelets count known in type II HIT. Also, BPC 157 markedly prolongs the survival time (heparin-rats, 25mg/kg, right foot amputation). Copyright © 2011 Elsevier Ltd. All rights reserved.

Freshwater Plants Synthesize Sulfated Polysaccharides: Heterogalactans from Water Hyacinth (Eicchornia crassipes)

PubMed Central

Dantas-Santos, Nednaldo; Gomes, Dayanne Lopes; Costa, Leandro Silva; Cordeiro, Sara Lima; Costa, Mariana Santos Santana Pereira; Trindade, Edvaldo Silva; Franco, Célia Regina Chavichiolo; Scortecci, Kátia Castanho; Leite, Edda Lisboa; Rocha, Hugo Alexandre Oliveira

2012-01-01

Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway. PMID:22312297

Constructing bio-layer of heparin and type IV collagen on titanium surface for improving its endothelialization and blood compatibility.

PubMed

Zhang, Kun; Chen, Jun-ying; Qin, Wei; Li, Jing-an; Guan, Fang-xia; Huang, Nan

2016-04-01

The modification of cardiovascular stent surface for a better micro-environment has gradually changed to multi-molecule, multi-functional designation. In this study, heparin (Hep) and type IV collagen (IVCol) were used as the functional molecule to construct a bifunctional micro-environment of anticoagulation and promoting endothelialization on titanium (Ti). The surface characterization results (AFM, Alcian Blue 8GX Staining and fluorescence staining of IVCol) indicated that the bio-layer of Hep and IVCol were successfully fabricated on the Ti surface through electrostatic self-assembly. The APTT and platelet adhesion test demonstrated that the bionic layer possessed better blood compatibility compared with Ti surface. The adhesion, proliferation, migration and apoptosis tests of endothelial cells proved that the Hep/IVCol layer was able to enhance the endothelialization of the Ti surface. The in vivo animal implantation results manifested that the bionic surface could encourage new endothelialization. This work provides an important reference for the construction of multifunction micro-environment on the cardiovascular scaffold surface.

Preparation of carboxymethyl cellulose sulfates and its application as anticoagulant and wound dressing.

PubMed

Fan, Lihong; Zhou, Xiaoyu; Wu, Penghui; Xie, Weiguo; Zheng, Hua; Tan, Wang; Liu, Shuhua; Li, Qingyuan

2014-05-01

Tissue engineering is aiming to build an artificial environment or biological scaffold material that imitates the living environment of cells in the body. In this work, carboxymethyl cellulose sulfates were prepared by reacting carboxymethyl cellulose with N(SO3Na)3 which was synthesized by sodium bisulfite and sodium nitrite in aqueous solution. The reaction conditions affected the degree of substitution (DS) were measured by the barium sulfate nephelometry method. And the anticoagulant activity of carboxymethyl cellulose sulfates with different DS, concentration and molecular weights were investigated by the activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT). In addition, the effect of carboxymethyl cellulose sulfates on wound healing had been evaluated by the rate of wound healing and the histological examinations. The results indicated that the introduction of sulfate groups into the carboxymethyl cellulose sulfates improved its anticoagulant activity, and the wound dressings treated with carboxymethyl cellulose sulfates obviously promoted wound healing. Copyright © 2014 Elsevier B.V. All rights reserved.

[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog].

PubMed

Lutze, G; Römhild, W; Elwert, J; Leppelt, J; Kutschmann, K

2003-01-01

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

[Massive bleeding symptoms in two patients with factor V inhibitor and antiphospholipid antibodies after treatment with ciprofloxacin].

PubMed

Miesbach, Wolfgang; Voigt, Jochen; Peetz, Dirk; Scharrer, Inge

2003-06-15

The development of factor V inhibitor is very rare, especially in combination with antiphospholipid antibodies. The paper describes the course of two patients with factor V inhibitor, antiphospholipid antibodies and massive bleeding symptoms after treatment with ciprofloxacin. At that time, ciprofloxacin was the only new drug given. DIAGNOSIS AND CLINICAL COURSE: First changes of the coagulation system were detected 4 days after start of treatment. In one case, occurrence was transient, and normalization was observed after terminating ciprofloxacin treatment. The other case ended with massive muscular and visceral bleedings and cardiovascular failure. Factor V inhibitor and antiphospholipid antibodies could be demonstrated even after termination of ciprofloxacin therapy. The association of treatment with ciprofloxacin and development of factor V inhibitor and antiphospholipid antibodies is probably diagnosed to rarely. These two cases emphasize the necessity of meticulous clarification of a prolonged activated partial thromboplastin time (aPTT) and a drop in prothrombin time (PT) during and after ciprofloxacin treatment.

[The influence of lactate Ringer solution versus hydroxyethyl starch on coagulation and fibrinolytic system in patients with septic shock].

PubMed

Lv, Jie; Zhao, Hui-ying; Liu, Fang; An, You-zhong

2012-01-01

To investigate the influence of lactate Ringer solution (RL) versus hydroxyethyl starch 130/0.4 (HES130/0.4) solution on coagulation and fibrinolytic system in the patients with septic shock. Forty-two consecutive patients with septic shock diagnosed between September 2009 and June 2011 were randomized to two study groups: RL resuscitation group (RL group) with 20 patients, and HES130/0.4 resuscitation group (HES group) with 22 patients. In all of them peripheral blood was collected at four points of time: before resuscitation, 6, 12, 24 hours after resuscitation, and then prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of plasma tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI) were determined. Meanwhile, the patients' outcome and the length of intensive care unit stay (ICU-LOS) were recorded. ICU-LOS (days) in HES group was significantly shorter than the RL group (12.5 ± 8.8 vs. 17.1 ± 16.6, P < 0.01). Meanwhile, the volume of fluid (L: 2.77 ± 0.59) as well as vasoactive drugs [μg×kg(-1)×min(-1): 0.56 ± 0.15] used in the HES group were significantly lower than RL group (3.46 ± 0.73, 0.81 ± 0.41, both P < 0.01). In RL group, 12 patients died and 8 patients survived, while in HES group, 7 patients died and 15 patients survived, showing no difference between two groups. PT, APTT and the levels of t-PA showed no significant differences between two groups at different time points, but the levels of plasma PAI (μg/L) of the HES group decreased gradually, and was significantly lower than that before resuscitation and RL group at 24 hours after resuscitation (41.76 ± 25.95 vs. 89.11 ± 14.27, 55.08 ± 35.43, both P < 0.05). Both RL and HES130/0.4 fluid resuscitation did not affect the outcome of the patients with septic shock, but the resuscitation efficiency of HES130/0.4 is much better than RL. Both type of fluids did not show the effect on coagulability of the septic patients, but colloid fluid resuscitation may protect the vascular endothelial cell, reduce the inhibition of fibrinolytic system, and alleviate hypercoagulability state of patients in early stage.

Fabrication of anticoagulation layer on titanium surface by sequential immobilization of poly (ethylene glycol) and albumin.

PubMed

Pan, Chang-Jiang; Hou, Yan-Hua; Zhang, Bin-Bin; Zhang, Lin-Cai

2014-01-01

This paper presents a simple method to sequentially immobilize poly (ethylene glycol) (PEG) and albumin on titanium surface to enhance the blood compatibility. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated that PEG and albumin were successfully immobilized on the titanium surface. Water contact angle results showed a better hydrophilic surface after the immobilization. The immobilized PEG or albumin can not only obviously prevent platelet adhesion and activation but also prolong activated partial thromboplastin time (APTT), leading to the improved anticoagulation. Moreover, immobilization of albumin on PEG-modified surface can further improve the anticoagulation. The approach in the present study provides an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Coagulation tests show significant differences in patients with breast cancer.

PubMed

Tas, Faruk; Kilic, Leyla; Duranyildiz, Derya

2014-06-01

Activated coagulation and fibrinolytic system in cancer patients is associated with tumor stroma formation and metastasis in different cancer types. The aim of this study is to explore the correlation of blood coagulation assays for various clinicopathologic factors in breast cancer patients. A total of 123 female breast cancer patients were enrolled into the study. All the patients were treatment naïve. Pretreatment blood coagulation tests including PT, APTT, PTA, INR, D-dimer, fibrinogen levels, and platelet counts were evaluated. Median age of diagnosis was 51 years old (range 26-82). Twenty-two percent of the group consisted of metastatic breast cancer patients. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group except for PT (p<0.001 for all variables except for PT; p=0.08). Elderly age (>50 years) was associated with higher D-dimer levels (p=0.003). Metastatic patients exhibited significantly higher D-dimer values when compared with early breast cancer patients (p=0.049). Advanced tumor stage (T3 and T4) was associated with higher INR (p=0.05) and lower PTA (p=0.025). In conclusion, coagulation tests show significant differences in patients with breast cancer.

Purified polysaccharides of Geoffroea spinosa barks have anticoagulant and antithrombotic activities devoid of hemorrhagic risks.

PubMed

Souza, Racquel O S; Assreuy, Ana M S; Madeira, Juliana C; Chagas, Francisco D S; Parreiras, Luane A; Santos, Gustavo R C; Mourão, Paulo A S; Pereira, Maria G

2015-06-25

Polysaccharides were extracted from the barks of Geoffroea spinosa, purified using anion exchange chromatography and characterized by chemical and methylation analysis, complemented by infrared and NMR spectroscopies. These polysaccharides were tested for their anticoagulant, antithrombotic and antiplatelet activities and also for their effects on bleeding. Unfractionated polysaccharide contains low levels of protein and high levels of carbohydrate (including hexuronic acid). The purified polysaccharides (fractions FII and FIII) are composed of arabinose (Ara), rhamnose (Rha), hexuronic acid, small amounts of galactose, but no sulfate ester. They have highly complex structure, which was partially characterized. NMR and methylation analysis indicate that the polysaccharides have a core of α-Rhap and branches of 5-linked α-Araf. Residues of 4-linked α-GalpA are also found in the structure. The unfractionated (TPL) and fraction FIII, but not fractions FI and FII, prolonged the activated partial thromboplastin time (aPTT). TPL, FII and FIII inhibited the platelet aggregation induced by ADP. More significantly, both unfractionated and purified fractions exhibited potent antithrombotic effect (31-60%) and the fractions did not modify the bleeding tendency. These plant polysaccharides could be alternative source of new anticoagulant, antiplatelet and antithrombotic compounds devoid of the undesirable risk of hemorrhage. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adsorption of tranexamic acid on hydroxyapatite: Toward the development of biomaterials with local hemostatic activity.

PubMed

Sarda, Stéphanie; Errassifi, Farid; Marsan, Olivier; Geffre, Anne; Trumel, Catherine; Drouet, Christophe

2016-09-01

This work proposes to combine tranexamic acid (TAX), a clinically used antifibrinolytic agent, and hydroxyapatite (HA), widely used in bone replacement, to produce a novel bioactive apatitic biomaterial with intrinsic hemostatic properties. The aim of this study was to investigate adsorptive behavior of the TAX molecule onto HA and to point out its release in near physiological conditions. No other phase was observed by X-ray diffraction or transmission electron microscopy, and no apparent change in crystal size was detected. The presence of TAX on the powders was lightly detected on Raman spectra after adsorption. The adsorption data could be fitted with a Langmuir-Freundlich equation, suggesting a strong interaction between adsorbed molecules and the formation of multilayers. The concentration of calcium and phosphate ions in solution remained low and stable during the adsorption process, thus ion exchange during the adsorption process could be ruled out. The release of TAX was fast during the first hours and was governed by a complex process that likely involved both diffusion and dissolution of HA. Preliminary aPTT (activated partial thromboplastin time) hemostasis tests offered promising results for the development of osteoconductive apatitic biomaterials with intrinsic hemostatic properties, whether for dental or orthopedic applications. Copyright © 2016. Published by Elsevier B.V.

CYP2E1 immunoglobulin G4 subclass antibodies after desflurane anesthesia

PubMed Central

Batistaki, Chrysanthi; Michalopoulos, George; Matsota, Paraskevi; Nomikos, Tzortzis; Kalimeris, Konstantinos; Riga, Maria; Nakou, Maria; Kostopanagiotou, Georgia

2014-01-01

AIM: To investigate CYP2E1 IgG4 autoantibody levels and liver biochemical markers in adult patients after anesthesia with desflurane. METHODS: Forty patients who were > 18 years old and undergoing elective surgery under general anesthesia with desflurane were studied. Alpha-glutathione-S-transferase (αGST) and IgG4 antibodies against CYP2E1 were measured preoperatively and 96 h postoperatively, as well as complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), g-glutamyl-transpeptidase (gGT), alkaline phosphatase, total serum proteins, albumin and bilirubin. A separate group of 8 patients who received regional anesthesia was also studied for calibration of the methodology used for CYP2E1 IgG4 and αGST measurements. Student’s t-test and the Mann-Whitney U test were used for comparison of the continuous variables, and Fisher’s exact test was used for the categorical variables. All tests were two-tailed, with statistical significance set as P < 0.05. RESULTS: None of the patients developed postoperative liver dysfunction, and all patients were successfully discharged from the hospital. No statistically significant difference was observed regarding liver function tests (SGOT, SGPT, γGT, bilirubin, INR), αGST and CYP2E1 IgG4, before and after exposure to desflurane. After dividing patients into two subgroups based on whether or not they had received general anesthesia in the past, no significant difference in the levels of CYP2E1 IgG4 was observed at baseline or 96 h after desflurane administration (P = 0.099 and P = 0.051, respectively). Alpha-GST baseline levels and levels after the intervention also did not differ significantly between these two subgroups (P > 0.1). The mean αGST differences were statistically elevated in men by 2.15 ng/mL compared to women when adjusted for BMI, duration of anesthesia, number of times anesthesia was administered previously and length of hospital stay. No significant difference was observed between patients who received desflurane and those who received regional anesthesia at any time point. CONCLUSION: There was no difference in CYP2E1 IgG4 or αGST levels after desflurane exposure; further research is required to investigate their role in desflurane-induced liver injury. PMID:24868327

The impact of intratracheally instilled carbon black on the cardiovascular system of rats: elevation of blood homocysteine and hyperactivity of platelets.

PubMed

Kim, Hwa; Oh, Seok-Jeong; Kwak, Hui-Chan; Kim, Jong-Kyu; Lim, Cheol-Hong; Yang, Jeong-Sun; Park, Kwangsik; Kim, Sang-Kyum; Lee, Moo-Yeol

2012-01-01

Carbon black (CB) is an industrial chemical with high potential for human exposure. Although the relationship between exposure to particulate matter (PM) and cardiovascular disease is well documented, the risk of adverse cardiovascular effects attributed to CB particles has not been clearly characterized. This study was performed to (1) investigate the effects of CB on cardiovascular system and (2) identify the target tissue or potential biomarkers. Carbon black with a distinct particle size, N330 (ultrafine particle) and N990 (fine particle), was intratracheally instilled into rats at a doses of 1, 3, or 10 mg/kg. Measurements of thrombotic activity and determination of plasma homocysteine levels, cardiac functionality, and inflammatory responses were conducted at 24-h and 1-wk time points. Exposure to N330 accelerated platelet-dependent blood clotting at 10 mg/kg, the highest exposure tested. Unexpectedly, both N330 and N990 led to prolongation of activated partial thromboplastin time (aPTT), whereas these CB particles failed to affect prothrombin time (PT). N990 produced a significant elevation in the level of plasma homocysteine, a well-established etiological factor in cardiovascular diseases. Both N330 and N990 induced apparent inflammation in the lungs; however, both particles failed to initiate systemic inflammation. Neither CB particle produced observable cardiac symptoms as detected by electrocardiography. Taken together, data show CB exposure enhanced the cardiovascular risk by inducing hyperhomocysteinemia and platelet hyperactivity, although these effects may be variable depending on particle size and exposure duration. Homocysteine may be a potential biomarker for cardiovascular toxicity following CB exposure.

Evaluation of thrombogenicity of beta-propiolactone/ultraviolet (beta-PL/UV) treated PPSB in chimpanzees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kotitschke, R.; Stephan, W.; Prince, A.M.

1983-05-01

The thrombogenicity of beta-PL/UV-treated PPSB (factor IX concentrate) was evaluated in chimpanzees. PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma was injected into chimpanzees at a dose of approximately 100 units/kg body weight. An FDA licensed PPSB preparation served as the negative control, and a preparation containing activated as well as precursor clotting factors served as the positive control. 15 minutes, 1 h, 4 h, and 24 h after the PPSB application the following parameters were determined in the chimpanzee blood: factors II, VII, IX, X, VIII, fibrinogen, AT III, thrombin coagulase, Quick value, APTT and platelet count. Neither the untreatedmore » control preparation, nor the PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma, showed signs of thrombogenicity in the chimpanzee model. The positive control indicated that the chimpanzee is a suitable model for the thrombogenicity testing of activated clotting factors.« less

90-Day Inhalation Toxicity Study of FT Fuel

DTIC Science & Technology

2011-08-01

per group for PT and APTT, there did not appear to be any effect in clotting factors. From the clinical chemistry results, chloride was increased...calcium (CA), cholesterol (CHOL), chloride (CL), creatine kinase (CPK), creatinine (CREA), glucose (GLU), potassium (K), sodium (NA), phosphorus... Chloride was increased and ALT and albumin were decreased in the 2000 mg/m 3 groups of female rats. These changes were not believed to be

Effect of Sugammadex on Postoperative Bleeding and Coagulation Parameters After Septoplasty: A Randomized Prospective Study

PubMed Central

Taş, Nilay; Korkmaz, Hakan; Yağan, Özgür; Korkmaz, Mukadder

2015-01-01

Backround Sugammadex is a reversal agent with well known advantages but it’s effects on haemostasis and bleeding have been a topic of interest. Septoplasty is a common surgical procedure with postoperative respiratory complications and bleeding. The aim of this study is to investigate the effects of sugammadex on postoperative coagulation parameters and bleeding after septoplasty procedure. Material/Methods In this randomized controlled study, fifty patients were grouped into two groups; neostigmine (Group N) vs. sugammadex (Group S). For the evaluation of PT, aPTT and INR, blood samples were taken for at the postoperative 120th minutes and alteration of these values with respect to preoperative values were documented. Postoperative bleeding was measured by evaluating the amount of blood absorbed on the nasal tip dressing during 3 hours postoperatively. Results Postoperative bleeding amount was significantly higher in the Group S compared to Group N (p=0.013). No significant difference was observed between two groups according to coagulation parameters (PT; p=0.953, aPTT; p=0.734, INR; p=0.612). Conclusions Sugammadex was associated with higher amount of postoperative bleeding than neostigmine in septoplasty patients. In surgical procedures having high risk of bleeding the safety of sugammadex need to be verified. PMID:26271275

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A

PubMed Central

Huth-Kühne, Angela; Baudo, Francesco; Collins, Peter; Ingerslev, Jørgen; Kessler, Craig M.; Lévesque, Hervé; Castellano, Maria Eva Mingot; Shima, Midori; St-Louis, Jean

2009-01-01

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group. PMID:19336751

Anticoagulant activity of marine green and brown algae collected from Jeju Island in Korea.

PubMed

Athukorala, Yasantha; Lee, Ki-Wan; Kim, Se-Kwon; Jeon, You-Jin

2007-07-01

Twenty-two algal species were evaluated for their potential anticoagulant activities. Hot water extracts from selected species, Codium fragile and Sargassum horneri showed high activated partial thromboplastin time (APTT). Ultraflo extract of C. fragile and S. horneri exhibited the most potent anticoagulant activity. Furthermore, in both algal species, active compounds were mainly concentrated in >30kDa faction. The crude polysaccharide fraction (>30kDa; CpoF) of C. fragile composed of approximately 80% carbohydrate and approximately 19% of protein; the crude polysaccharide fraction (>30kDa; CpoF) of S. horneri was composed of 97% of carbohydrate and approximately 2% of protein. Therefore, most probably the active compound, or compounds of the algal species were related to high molecular weight polysaccharide, or a complex form with carbohydrate and protein (proteoglycan).

Chemical characteristics and antithrombotic effect of chondroitin sulfates from sturgeon skull and sturgeon backbone.

PubMed

Gui, Meng; Song, Juyi; Zhang, Lu; Wang, Shun; Wu, Ruiyun; Ma, Changwei; Li, Pinglan

2015-06-05

Chondroitin sulfates (CSs) were extracted from sturgeon skull and backbone, and their chemical composition, anticoagulant, anti-platelet and thrombolysis activities were evaluated. The average molecular weights of CS from sturgeon skull and backbone were 38.5kDa and 49.2kDa, respectively. Disaccharide analysis indicated that the sturgeon backbone CS was primarily composed of disaccharide monosulfated in position four of the GalNAc (37.8%) and disaccharide monosulfated in position six of the GalNAc (59.6%) while sturgeon skull CS was primarily composed of nonsulfated disaccharide (74.2%). Sturgeon backbone CS showed stronger antithrombotic effect than sturgeon skull CS. Sturgeon backbone CS could significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT), inhibited ADP-induced platelet aggregation and dissolved platelet plasma clots in vitro. The results suggested that sturgeon backbone CS can be explored as a functional food with antithrombotic function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Erythrocyte and Biochemical Abnormalities as Diagnostic Markers in Dogs With Hemangiosarcoma Related Hemoabdomen.

PubMed

Wong, Richard W; Gonsalves, Mishka N; Huber, Michael L; Rich, Lon; Strom, Adam

2015-10-01

To investigate: 1) acanthocytosis and presence of acanthocytes in peritoneal fluid as a diagnostic marker for hemangiosarcoma (HSA) in dogs with non-traumatic hemoabdomen; and 2) the association between other erythrocyte, biochemical, and hematologic abnormalities as a mean of differentiating HSA from other disease. Prospective double-blinded cohort study. Dogs (n = 40) with non-traumatic hemoabdomen. Dogs diagnosed with hemoabdomen (January 2012 to May 2013) had cytologic evaluation of abdominal effusion and peripheral blood smears. Peripheral blood CBC, PT, and aPTT, as well as blood and effusion acanthocytes, keratocytes, schistocytes, lactate, glucose, PCV, and TP results were compared using the paired t-test or Fisher's exact test. Based on histologic confirmation of HSA, dogs were divided into 2 groups (HSA, non-HSA) and variables compared. There was no significant difference in erythrocyte morphology in abdominal effusion or peripheral blood between dogs with HSA or non-HSA related hemoabdomen. Platelet concentration and peripheral blood PCV were significantly lower in the HSA group. A reliable preoperative biochemical or cytologic test to differentiate between HSA and non-HSA related hemoabdomen was not identified. © Copyright 2015 by The American College of Veterinary Surgeons.

Effect of MCM09, an active site-directed inhibitor of factor Xa, on B16-BL6 melanoma lung colonies in mice.

PubMed

Rossi, C; Hess, S; Eckl, R W; di Lena, A; Bruno, A; Thomas, O; Poggi, A

2006-03-01

Treatment with anticoagulant drugs has shown potential inhibitory effect on tumor invasion, although the relationship with clotting inhibition was not clear. The aim of our study was to evaluate the potential antitumor activity of MCM09, a newly developed, active site-directed, small molecule inhibitor of factor Xa (FXa) [WO0216312], and to relate the findings to anticlotting potency. MCM09 (0.1-10 mg kg(-1)) or heparin (H; 10 mg kg(-1)) was injected intravenously (i.v.), with 5 x 10(4) B16-BL6 melanoma cells, in C57BL/6 mice. Mice were killed after 18 days, to count lung colonies. Ex vivo anticoagulant activity was measured by activated partial thromboplastin time (APTT) on mouse plasma. MCM09, a selective inhibitor of FXa (IC-50 = 2.4 nm against human FXa), inhibited in a dose-dependent manner B16-BL6 melanoma lung colonies in mice. Mean lung metastasis number was 20.9 +/- 4.8 in controls (n = 10), 1.2 +/- 0.4 in mice treated with H, 10 mg kg(-1) i.v. (P < 0.01), 0.9 +/- 0.3, 9.2 +/- 2.2 and 15.5 +/- 2.6 in mice treated with MCM09, at 10 (P < 0.01), 1 (P < 0.05) and 0.1 mg kg(-1) i.v. (ns), respectively. MCM09 (10 mg kg(-1) i.v.) significantly prolonged APTT (57.1 +/- 10.2 s) 30 min after i.v. injection when compared with controls (25.3 +/- 1.6 s; P < 0.05). Lung colonies were 74.2-72.6% reduced by MCM09 (10 mg kg(-1)) given 60 or 120 min before cells, but not by MCM09 given 60 min thereafter, suggesting a direct cell interaction as a mechanism underlying antitumor activity.

Concentration-dependent effect of hypocalcaemia on in vitro clot strength in patients at risk of bleeding: a retrospective cohort study.

PubMed

Ho, K M; Yip, C B

2016-02-01

It is uncertain whether hypocalcaemia is associated with an increased risk of bleeding. This study assessed the dose-related relationship between ionised calcium concentrations and in vitro clot strength measured by maximum amplitude (MA) on the thromboelastograph (TEG). A total of 610 patients who were at risk of bleeding or had active bleeding between 2010 and 2014 were considered in this retrospective cohort study. A scatter plot with Pearson correlation coefficient (r) and multiple linear regression was used to assess the dose-related relationship between ionised calcium concentrations and MA on the TEG. The mean ionised calcium of the patients was 1·10 mmol L(-1) (interquartile range: 1·04-1·17) and 235 (38·5%) of them had hypocalcaemia (<1·1 mmol L(-1) ). Hypocalcaemia was more common in patients with significant coexisting coagulopathy. Ionised calcium concentrations (r = 0·285, 95% confidence interval (CI) 0·211-0·356, P = 0·001), as well as fibrinogen concentrations, platelet counts, international normalised ratio (INR) and activated Partial Thromboplastin Time (aPTT), had a significant linear correlation with the MA on the TEG. Ionised calcium concentrations and its interaction term with platelet count were both significantly associated with the MA on the TEG (slope of the regression line 1·1 per 0·1 mmol L(-1) increment, 95%CI 0·3 to 1·9, P = 0·011), after adjusting for fibrinogen concentrations, platelet counts, INR and aPTT. Ionised calcium concentrations had a concentration-dependent association with in vitro clot strength after adjusting for other coagulation abnormalities in patients with coexisting coagulopathy. Maintaining a normal ionised calcium concentration, >1 mmol L(-1) , during critical bleeding is recommended. © 2016 British Blood Transfusion Society.

Molecular size is important for the safety and selective inhibition of intrinsic factor Xase for fucosylated chondroitin sulfate.

PubMed

Yan, Lufeng; Li, Junhui; Wang, Danli; Ding, Tian; Hu, Yaqin; Ye, Xingqian; Linhardt, Robert J; Chen, Shiguo

2017-12-15

Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (FCS-Ib) showed potent anticoagulant activities without selectivity. The present study focused on developing safe FCS-Ib oligomers showing selective inhibition of intrinsic factor Xase (anti-FXase) prepared through partial N-deacetylation-deaminative cleavage. The N-deacetylation degree was regulated by reaction time, controlling the resulting oligomer distribution. Structure analysis confirmed the selectivity of degradation, and 12 high purity fractions with trisaccharide-repeating units were separated. In vitro anticoagulant assays indicated a decrease in molecular weight (Mw) dramatically reduced activated partial thromboplastin time (APTT), thrombin time (TT), AT-dependent anti-FIIa and anti-FXa activities, while the oligomers retained potent anti-FXase activity until they fell below 3kDa. Meanwhile, human FXII activation and platelet aggregation were markedly reduced with decreasing Mw and were moderate when under 12.0kDa. Thus, fragments of 3-12.0kDa should be safe and effective as selective inhibitors of intrinsic tenase complex for application as clinical anticoagulants. Copyright © 2017 Elsevier Ltd. All rights reserved.

A small amount can make a difference: a prospective human study of the paradoxical coagulation characteristics of hemothorax.

PubMed

Smith, W Zachary; Harrison, Hannah B; Salhanick, Marc A; Higgins, Russell A; Ortiz, Alfonso; Olson, John D; Schwacha, Martin G; Harrison, Chantal R; Aydelotte, Jayson D; Stewart, Ronald M; Dent, Daniel L

2013-12-01

The evacuated hemothorax has been poorly described because it varies with time, it has been found to be incoagulable, and its potential effect on the coagulation cascade during autotransfusion is largely unknown. This is a prospective descriptive study of adult patients with traumatic chest injury necessitating tube thoracostomy. Pleural and venous samples were analyzed for coagulation, hematology, and electrolytes at 1 to 4 hours after drainage. Pleural samples were also analyzed for their effect on the coagulation cascade via mixing studies. Thirty-four subjects were enrolled with a traumatic hemothorax. The following measured coagulation factors were significantly depleted compared with venous blood: international normalized ratio (>9 vs 1.1) (P < .001) and activated partial thromboplastin time (aPTT) (>180 vs 24.5 seconds) (P < .001). Mixing studies showed a dose-dependent increase in coagulation dilutions through 1:8 (P < .05). An evacuated hemothorax does not vary in composition significantly with time and is incoagulable alone. Mixing studies with hemothorax plasma increased coagulation, raising safety concerns. Copyright © 2013 Elsevier Inc. All rights reserved.

In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

NASA Astrophysics Data System (ADS)

Zhang, Jiang; Liu, Yang; Luo, Rifang; Chen, Si; Li, Xin; Yuan, Shuheng; Wang, Jin; Huang, Nan

2015-02-01

Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

[Reference values for the blood coagulation tests in Mexico: usefulness of the pooled plasma from blood donors].

PubMed

Calzada-Contreras, Adriana; Moreno-Hernández, Manuel; Castillo-Torres, Noemi Patricia; Souto-Rosillo, Guadalupe; Hernández-Juárez, Jesús; Ricardo-Moreno, María Tania; Sánchez-Fernández, Maria Guadalupe de Jesús; García-González, América; Majluf-Cruz, Abraham

2012-01-01

The blood coagulation system maintains the blood in a liquid state and bleeding and thrombosis are the manifestations of its malfunction. Blood coagulation laboratory evaluates the physiology of this system. To establish both, the reference values for several tests performed at the blood coagulation laboratory as well as the utility of the pooled plasma to perform these assays. MATERIAL AND: In this descriptive, cross-sectional, randomized study, we collected plasma from Mexican Mestizos. Each pooled plasma was prepared with the plasma from at least 20 blood donors. We performed screening and special tests and the Levey-Jennings graphs were built and interpreted after each pass. Results of the tests were analyzed and their distribution was established using the Kolmogorov-Smirnov test. To establish the reference values we used 95% confidence intervals. We collected 72 pooled plasmas. The distribution for PT, APTT, and TT tests was abnormal. Although the PT test showed a bimodal distribution it was normal for factor VII. The reference values for the hemostatic, anticoagulant, and fibrinolytic factors were different from those suggested by the manufacturers. We established the reference values for the blood coagulation tests in the adult Mexican population. We have shown that the pooled plasma must be used for the screening tests. We suggest that each clinical laboratory should establish its own reference values (at least for the screening tests). To reach this objective, we encourage the use of the pooled plasma.

Effect of rivaroxaban on preventing deep vein thrombosis in aged diabetics with femoral neck fractures after hip replacement

PubMed Central

Jiang, Xin; Sun, Yan-Shan

2017-01-01

The present study estimates the effect of rivaroxaban on preventing deep vein thrombosis (DVT) in aged diabetics with femoral neck fractures after hip replacement. Our study consisted of 236 aged diabetics with femoral neck fractures, which were divided into the rivaroxaban and control groups. Reaction time (R time), clot formation time (K time), α angle (α), maximum amplitude (MA), clot elasticity (G) and coagulation index (CI), prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. DVT was diagnosed by color duplex Doppler ultrasound (CDDU). The risk factors of DVT were analysed by logistic regression analysis. Compared with the control group, in the rivaroxaban group, R time and K time were extended and α, MA and G decreased 1 day before operation. One day after operation, the rivaroxaban group had less PT and APPT and lower incidence of DVT than the control group. In the two groups, preoperative and postoperative PT and APPT significantly differed. Body mass index (BMI) ≥25, abnormal coagulation indicators, use of cemented femoral hip prosthesis, high haemoglobin content and non-ankle pump exercise after operation were the risk factors for DVT. Rivaroxaban could prevent DVT in aged diabetics with femoral neck fractures after hip replacement. PMID:28442600

Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A

PubMed Central

PORADA, C. D.; SANADA, C.; LONG, C. R.; WOOD, J. A.; DESAI, J.; FREDERICK, N.; MILLSAP, L.; BORMANN, C.; MENGES, S. L.; HANNA, C.; FLORES-FOXWORTH, G.; SHIN, T.; WESTHUSIN, M. E.; LIU, W.; GLIMP, H.; ZANJANI, E. D.; LOZIER, J. N.; PLISKA, V.; STRANZINGER, G.; JOERG, H.; KRAEMER, D. C.; ALMEIDA-PORADA, G.

2010-01-01

Summary Background Large animal models that accurately mimic human hemophilia A (HA) are in great demand for developing and testing novel therapies to treat HA. Objectives To re-establish a line of sheep exhibiting a spontaneous bleeding disorder closely mimicking severe human HA, fully characterize their clinical presentation, and define the molecular basis for disease. Patients/methods Sequential reproductive manipulations were performed with cryopreserved semen from a deceased affected ram. The resultant animals were examined for hematologic parameters, clinical symptoms, and responsiveness to human FVIII (hFVIII). The full coding region of sheep FVIII mRNA was sequenced to identify the genetic lesion. Results and conclusions The combined reproductive technologies yielded 36 carriers and 8 affected animals. The latter had almost non-existent levels of FVIII:C and extremely prolonged aPTT, with otherwise normal hematologic parameters. These animals exhibited bleeding from the umbilical cord, prolonged tail and nail cuticle bleeding time, and multiple episodes of severe spontaneous bleeding, including hemarthroses, muscle hematomas and hematuria, all of which responded to hFVIII. Inhibitors of hFVIII were detected in four treated animals, further establishing the preclinical value of this model. Sequencing identified a premature stop codon and frame-shift in exon 14, providing a molecular explanation for HA. Given the decades of experience using sheep to study both normal physiology and a wide array of diseases and the high homology between human and sheep FVIII, this new model will enable a better understanding of HA and facilitate the development and testing of novel treatments that can directly translate to HA patients. PMID:19943872

Pre-analytical effects of pneumatic tube system transport on routine haematology and coagulation tests, global coagulation assays and platelet function assays.

PubMed

Le Quellec, Sandra; Paris, Mickaël; Nougier, Christophe; Sobas, Frédéric; Rugeri, Lucia; Girard, Sandrine; Bordet, Jean-Claude; Négrier, Claude; Dargaud, Yesim

2017-05-01

Pneumatic tube system (PTS) in hospitals is commonly used for the transport of blood samples to clinical laboratories, as it is rapid and cost-effective. The aim was to compare the effects on haematology samples of a newly acquired ~2km-long PTS that links 2 hospitals with usual transport (non-pneumatic tube system, NPTS). Complete blood cell count, routine coagulation assays, platelet function tests (PFT) with light-transmission aggregometry and global coagulation assays including ROTEM® and thrombin generation assay (TGA) were performed on blood samples from 30 healthy volunteers and 9 healthy volunteers who agreed to take aspirin prior to blood sampling. The turnaround time was reduced by 31% (p<0.001) with the use of PTS. No statistically significant difference was observed for most routine haematology assays including PFT, and ROTEM® analysis. A statistically significant, but not clinically relevant, shortening of the APTT after sample transport by PTS was found (mean±SD: 30s±1.8 vs. 29.5s±2.1 for NPTS). D-dimer levels were 7.4% higher after transport through PTS but were not discordant. A statistically significant increase of thrombin generation was found in both platelet poor- and platelet rich- plasma samples after PTS transport compared to NPTS transport. PTS is suitable for the transport of samples prior to routine haematology assays including PFT, but should not be used for samples intended for thrombin generation measurement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tailoring of the titanium surface by immobilization of heparin/fibronectin complexes for improving blood compatibility and endothelialization: an in vitro study.

PubMed

Li, Guicai; Yang, Ping; Liao, Yuzhen; Huang, Nan

2011-04-11

To improve the blood compatibility and endothelialization simultaneously and to ensure the long-term effectiveness of the cardiovascular implants, we developed a surface modification method, enabling the coimmobilization of biomolecules to metal surfaces. In the present study, a heparin and fibronectin mixture (Hep/Fn) covalently immobilized on a titanium (Ti) substrate for biocompatibility was investigated. Different systems [N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and N-hydroxysuccinimide, electrostatic] were used for the formation of Hep/Fn layers. Atomic force microscopy (AFM) showed that the roughness of the silanized Ti surface decreased after the immobilization of Hep/Fn. Fourier transform infrared spectroscopy (FTIR), Toluidine Blue O (TBO) test, and immunochemistry assay showed that Hep/Fn mixture was successfully immobilized on Ti surface. Blood compatibility tests (hemolysis rate, APTT, platelet adhesion, fibrinogen conformational change) showed that the coimmobilized films of Hep/Fn mixture reduced blood hemolysis rate, prolonged blood coagulation time, reduced platelets activation and aggregation, and induced less fibrinogen conformational change compared with a bare Ti surface. Endothelial cell (EC) seeding showed more EC with better morphology on pH 4 samples than on pH 7 and EDC/NHS samples, which showed rounded and aggregated cells. Systematic evaluation showed that the pH 4 samples also had much better blood compatibility. All results suggest that the coimmobilized films of Hep/Fn can confer excellent antithrombotic properties and with good endothelialization. We envisage that this method will provide a potential and effective solution for the surface modification of cardiovascular implant materials.

Comparison of two blood sampling techniques for the determination of coagulation parameters in the horse: Jugular venipuncture and indwelling intravenous catheter.

PubMed

Mackenzie, C J; McGowan, C M; Pinchbeck, G; Carslake, H B

2018-05-01

Evaluation of coagulation status is an important component of critical care. Ongoing monitoring of coagulation status in hospitalised horses has previously been via serial venipuncture due to concerns that sampling directly from the intravenous catheter (IVC) may alter the accuracy of the results. Adverse effects such as patient anxiety and trauma to the sampled vessel could be avoided by the use of an indwelling IVC for repeat blood sampling. To compare coagulation parameters from blood obtained by jugular venipuncture with IVC sampling in critically ill horses. Prospective observational study. A single set of paired blood samples were obtained from horses (n = 55) admitted to an intensive care unit by direct jugular venipuncture and, following removal of a presample, via an indwelling IVC. The following coagulation parameters were measured on venipuncture and IVC samples: whole blood prothrombin time (PT), fresh plasma PT and activated partial thromboplastin time (aPTT) and stored plasma antithrombin activity (AT) and fibrinogen concentration. D-dimer concentration was also measured in some horses (n = 22). Comparison of venipuncture and IVC results was performed using Lin's concordance correlation coefficient. Agreement between paired results was assessed using Bland Altman analysis. Correlation was substantial and agreement was good between sample methods for all parameters except AT and D-dimers. Each coagulation parameter was tested using only one assay. Sampling was limited to a convenience sample and timing of sample collection was not standardised in relation to when the catheter was flushed with heparinised saline. With the exception of AT and D-dimers, coagulation parameters measured on blood samples obtained via an IVC have clinically equivalent values to those obtained by jugular venipuncture. © 2017 EVJ Ltd.

Bilateral orbital haematomas in an anticoagulated patient with severe H1N1 influenza.

PubMed

Mansurali, Naseem; Maclaren, Graeme; Sundar, Gangadhara

2011-03-01

A previously healthy woman was admitted to the intensive care unit (ICU) with severe H1N1 influenza. She had prolonged hospital stay due to multiple complications of critical illness, including pelvic deep vein thrombosis (DVT), which was treated with subcutaneous enoxaparin. The patient was referred to the ophthalmology service for bilateral proptosis. On examination, she had bilateral tense proptosis, worse on the left side with exposure keratopathy. Laboratory tests showed that she had thrombocytopenia and raised activated partial thromboplastin time (APTT). A CT scan revealed well-circumscribed soft tissue density lesions in the superolateral orbits and was reported as bilateral lacrimal gland enlargement. However, based on a clinical suspicion of subperiosteal hematoma collection, a diagnostic tap was performed. Following aspiration of six mls of dark blood from the left superior orbit, there was a reduction of proptosis with improvement in chemosis and resolution of exposure keratopathy. Enoxaparin is one of several antithrombotic agents which are increasingly being used for DVT prophylaxis in severely compromised patients. Furthermore, ICU patients ventilated for prolonged periods are at risk of developing chemosis and exposure keratopathy. Thus, the clinician should maintain a high index of suspicion in identifying subperiosteal hematomas, when managing such cases. The spontaneous bilateral vision threatening subperiosteal hematoma was probably caused by a combination of enoxaparin therapy and prolonged ventilation.

Immobilization of heparin/poly-(L)-lysine nanoparticles on dopamine-coated surface to create a heparin density gradient for selective direction of platelet and vascular cells behavior.

PubMed

Liu, Tao; Liu, Yang; Chen, Yuan; Liu, Shihui; Maitz, Manfred F; Wang, Xue; Zhang, Kun; Wang, Jian; Wang, Yuan; Chen, Junying; Huang, Nan

2014-05-01

Restenosis, thrombosis formation and delayed endothelium regeneration continue to be problematic for coronary artery stent therapy. To improve the hemocompatibility of the cardiovascular implants and selectively direct vascular cell behavior, a novel kind of heparin/poly-l-lysine (Hep/PLL) nanoparticle was developed and immobilized on a dopamine-coated surface. The stability and structural characteristics of the nanoparticles changed with the Hep:PLL concentration ratio. A Hep density gradient was created on a surface by immobilizing nanoparticles with various Hep:PLL ratios on a dopamine-coated surface. Antithrombin III binding quantity was significantly enhanced, and in plasma the APTT and TT times as coagulation tests were prolonged, depending on the Hep density. A low Hep density is sufficient to prevent platelet adhesion and activation. The sensitivity of vascular cells to the Hep density is very different: high Hep density inhibits the growth of all vascular cells, while low Hep density could selectively inhibit smooth muscle cell hyperplasia but promote endothelial progenitor cells and endothelial cell proliferation. These observations provide important guidance for modification of surface heparinization. We suggest that this method will provide a potential means to construct a suitable platform on a stent surface for selective direction of vascular cell behavior with low side effects. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of tranexamic acid on coagulation indexes of patients undergoing heart valve replacement surgery under cardiopulmonary bypass

PubMed Central

Liu, Fei; Xu, Dong; Zhang, Kefeng; Zhang, Jian

2016-01-01

This study aims to explore the effects of tranexamic acid on the coagulation indexes of patients undergoing heart valve replacement surgery under the condition of cardiopulmonary bypass (CPB). One hundred patients who conformed to the inclusive criteria were selected and divided into a tranexamic acid group and a non-tranexamic acid group. They all underwent heart valve replacement surgery under CPB. Patients in the tranexamic acid group were intravenously injected with 1 g of tranexamic acid (100 mL) at the time point after anesthesia induction and before skin incision and at the time point after the neutralization of heparin. Patients in the non-tranexamic acid group were given 100 mL of normal saline at corresponding time points, respectively. Then the coagulation indexes of the two groups were analyzed. The activated blood clotting time (ACT) of the two groups was within normal scope before CPB, while four coagulation indexes including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), and fibrinogen (FIB) had significant increases after surgery; the PT and INR of the tranexamic acid group had a remarkable decline after surgery. All the findings suggest that the application of tranexamic acid in heart valve replacement surgery under CPB can effectively reduce intraoperative and postoperative blood loss. PMID:27694613

Comparative Study of Biological Activities of Venom from Colubrid Snakes Rhabdophis tigrinus (Yamakagashi) and Rhabdophis lateralis

PubMed Central

Komori, Yumiko; Hifumi, Toru; Yamamoto, Akihiko; Sakai, Atsushi; Sawabe, Kyoko; Nikai, Toshiaki

2017-01-01

Rhabdophis lateralis, a colubrid snake distributed throughout the continent of Asia, has recently undergone taxonomic revisions. Previously, Rhabdophis lateralis was classified as a subspecies of R. tigrinus (Yamakagashi) until 2012, when several genetic differences were discovered which classified this snake as its own species. To elucidate the toxicity of venom from this poorly studied colubrid, various biological activities were compared between the venom from the two snake species. The components of their venom were compared by the elution profiles of reversed-phase HPLC and SDS-PAGE, and gel filtrated fractions were tested for effects on blood coagulation. Proteolytic activities of these fractions were also assayed by using synthetic substrates, fibrinogen, and matrix proteins. Similar to the R. tigrinus venom, the higher molecular weight fraction of R. lateralis venom contained a prothrombin activator. Both prothrombin time (PT) and activated partial thromboplastin time (APTT) of human plasma were shortened by the addition of R. lateralis and R. tigrinus venom. The thrombin formation was estimated by the uses of SDS-PAGE and chromogenic substrates. These venom fractions also possessed very specific proteinase activity on human fibrinogen, but the substrates for matrix metalloproteinase, such as collagen and laminin, were not hydrolyzed. However, there were some notable differences in reactivity to synthetic substrates for matrix metalloproteinase, and R. tigrinus venom possessed relatively higher activity. Our chemical investigation indicates that the components included in both venoms resemble each other closely. However, the ratio of components and proteolytic activity of some ingredients are slightly different, indicating differences between two closely-related snakes. PMID:29149042

Polyguluronate sulfate, polymannuronate sulfate, and their oligosaccharides have antithrombin III- and heparin cofactor II-independent anticoagulant activity

NASA Astrophysics Data System (ADS)

Zeng, Xuan; Lan, Ying; Zeng, Pengjiao; Guo, Zhihua; Hao, Cui; Zhang, Lijuan

2017-04-01

Cardiovascular disease is the leading causes of death. However, the complications can be treated with heparin and heparinoids, such as heparin pentasaccharide Fondaparinux, dermatan sulfate, and PSS made from alginate extracted from brown seaweeds by chemical sulfation. Alginate is composed of a linear backbone of polymannuronate (PM), polyguluronate (PG), and alternate residues of mannuronic acid and guluronic acid. It is unknown if heparin and sulfated PG (PGS)/PM (PMS) have the same or different anticoagulant molecular targets. In the current study, the anticoagulant activities of PGS, PMS, and their oligosaccharides were directly compared to that of heparin, Fondaparinux, and dermatan sulfate by the activated partial thrombinplastin time (aPTT) assay using normal, antithrombin III (ATIII)-deficient, heparin co-factor II (HCII)-deficient, and ATIII- and HCII-double deficient human plasmas. Our results showed that PGS, PMS, and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested. As expected, heparin was the best anticoagulant in normal plasma. Moreover, PGS, PGS6, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma. Most strikingly, PGS, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than that of heparin in ATIII- and HCII-double deficient human plasma. The results revealed for the first time that sulfated alginate had ATIII- and HCII-independent anticoagulant activities. Therefore, developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.

Traditional Chinese and western medicine for the prevention of deep venous thrombosis after lower extremity orthopedic surgery: a meta-analysis of randomized controlled trials.

PubMed

Zhu, Shibai; Song, Yi; Chen, Xi; Qian, Wenwei

2018-04-10

Chinese herbal medicine has traditionally been considered to promote blood circulation to remove obstruction in the channels and clear pathogenic heat to drain dampness effects. We conducted this meta-analysis to evaluate its benefits for the prevention of deep venous thrombosis (DVT) after lower extremity orthopedic surgery. Relevant, published studies were identified using the following keywords: lower extremity orthopedic surgery, arthroplasty, joint replacement, fracture, traditional Chinese and western medicine, Chinese herbal medicine, deep venous thrombosis (DVT), and Venous thromboembolism (VTE). The following databases were used to identify the literature consisting of RCTs with a date of search of 31 May 2017: PubMed, Cochrane Library, Web of knowledge, the Chinese National Knowledge Infrastructure Database, the Chongqing VIP Database, the Chinese Biomedical Database, and the Wanfang Database (including three English and four Chinese databases). All relevant data were collected from studies meeting the inclusion criteria. The outcome variables were the incidence rate of DVT, activated partial thromboplastin time (APTT), prothrombin time (PT), and D-dimer; subcutaneous hematoma; and other reported outcomes. RevMan5.2. software was adopted for the meta-analysis. A total of 20 published studies (1862 cases) met the inclusion criteria. The experimental group, 910 patients (48.87%), received the Chinese herbal medicine or traditional Chinese and western medicine for prevention of DVT; the control group, 952 patients (51.13%), received the standard western treatment. The meta-analysis showed that traditional Chinese and western medicine therapy reduced the incidence rates of DVT significantly when compared with controls (risk ratio [RR] = 0.40; 95% CI, 0.30 to 0.54; P < 0.00001), and the D-dimer was lower in the experimental group (P = 0.01). Besides, the incidence rate of subcutaneous hematoma was lower in the experimental group (P < 0.0001). However, no significant difference was found in the PT (P = 0.98) and APTT (P = 0.75) in two groups. No serious adverse events were reported. Traditional Chinese and western medicine therapy may be a safe, effective prevention modality for DVT after lower extremity orthopedic surgery. Further rigorously designed, randomized trials are warranted.

Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats.

PubMed

Deng, Zu-Yue; Shan, Wei-Guang; Wang, Shen-Feng; Hu, Meng-Mei; Chen, Yan

2017-12-01

Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively. ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold). ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats. These activities were closely correlated with ASTX, maintaining the balance of t-PA/PAI-1, NO/ROS and TXA2/PGI2 in vivo.

Fourteen-Day Subacute Intravenous Toxicity Study of Hypertonic Saline/ Dextran 70 and its Constituents in Beagle Dogs

DTIC Science & Technology

1989-11-01

hepatic changes. The magnitude of the enzyme elevations, subsequent decreases in ALK and ALT levels, and -e absence of morphologic changes in the liver...of PT and A-PTT are not uncommon findings in severe, acute, hepatopathies in dogs (17). The increases in hepatic enzymes observed in HSD- and D70...clinical signs referable to liver disease, and the lack of .eaato lesions on histopathological examination, suggest tat the enzyme elevations may have

[Effects of the adsorbent CAA for hemopurification on normal components of human plasma in removing methylene blue].

PubMed

Ma, Yu; Xia, Yun; Yang, Xiaolan; Yu, Ming'an

2003-06-01

Virus inactivation of plasma can be achieved by phototreatment with methylene blue (MB). Subsequently, elimination of MB may reduce the adverse effects of MB. This study examined the effects of adsorbing MB with the use of cross-linked agar bead entrapped attapulgite clay (CAA) on normal ingredients in MB-treated plasma units. The biomedical characteristics of CAA were assessed by determination of partial biochemical indexes, coagulation potency and some cationic concentration in a control sample and the MB-treated plasma eluted from CAA column. The biochemistry indexes or K+, Na+ in plasma were almost unaltered before and after CAA adsorption. In contrast, the concentrations of CA2+ and Mg2+ increased and the blood ammonium decreased obviously. The activated partial thromboplastin time (APTT) was prolonged from 42 s to 53 s, and prothrombin time (PT) from 13 s to 14 s. The result indicates that CAA as an adsorbent for hemopurification retains the most important characters of human plasma. CAA can be useful for the elimination of MB in MB-treated plasma and does not bring on harmful alteration in clinical significance.

Acquired Dysfibrinogenemia Caused by Autoantibody Inhibiting Fibrin Polymerization in a Patient with MELAS Syndrome and Bleeding Tendency.

PubMed

Lee, Nuri; Kim, Ji-Eun; Yoo, Hyun Ju; Gu, JaYoon; Kim, Hyori; Chung, Junho; Koh, Youngil; Kim, Hyun Kyung

2016-12-01

We present a case of acquired dysfibrinogenemia caused by an autoantibody that inhibited fibrin polymerization in a patient previously diagnosed with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes). The patient showed prolonged PT, aPTT, and thrombin time. There was no factor deficiency but fibrinogen antigen and activity were decreased. ELISA for detection of fibrinogen antibodies were performed and IgG purified from the patient's plasma bound to fibrinogen more strongly than did control IgG, indicating the presence of a fibrinogen-specific antibody. Thrombin-mediated fibrin polymerization was severely impaired in the patient, although thrombin-induced fibrinopeptide A release was normal. Scanning electron microscopy was used to investigate the structure of fibrin clots and revealed many pores on the surface of patient's fibrin clots. Since MELAS is often associated with autoimmune disorders, a work-up for the presence of anti-fibrinogen antibody is necessary when bleeding tendency occurs in MELAS patients along with prolonged thrombin time. © 2016 by the Association of Clinical Scientists, Inc.

In vitro antioxidant, anticoagulant and antimicrobial activity and in inhibition of cancer cell proliferation by xylan extracted from corn cobs.

PubMed

Melo-Silveira, Raniere Fagundes; Fidelis, Gabriel Pereira; Costa, Mariana Santana Santos Pereira; Telles, Cinthia Beatrice Silva; Dantas-Santos, Nednaldo; de Oliveira Elias, Susana; Ribeiro, Vanessa Bley; Barth, Afonso Luis; Macedo, Alexandre José; Leite, Edda Lisboa; Rocha, Hugo Alexandre Oliveira

2012-01-01

Xylan is one of most abundant polymer after cellulose. However, its potential has yet to be completely recognized. Corn cobs contain a considerable reservoir of xylan. The aim of this work was to study some of the biological activities of xylan obtained from corn cobs after alkaline extraction enhanced by ultrasonication. Physical chemistry and infrared analyses showed 130 kDa heteroxylan containing mainly xylose:arabinose: galactose:glucose (5.0:1.5:2.0:1.2). Xylan obtained exhibited total antioxidant activity corresponding to 48.5 mg of ascorbic acid equivalent/g of xylan. Furthermore, xylan displayed high ferric chelating activity (70%) at 2 mg/mL. Xylan also showed anticoagulant activity in aPTT test. In antimicrobial assay, the polysaccharide significantly inhibited bacterial growth of Klebsiella pneumoniae. In a test with normal and tumor human cells, after 72 h, only HeLa tumor cell proliferation was inhibited (p < 0.05) in a dose-dependent manner by xylan, reaching saturation at around 2 mg/mL, whereas 3T3 normal cell proliferation was not affected. The results suggest that it has potential clinical applications as antioxidant, anticoagulant, antimicrobial and antiproliferative compounds.

In Vitro Antioxidant, Anticoagulant and Antimicrobial Activity and in Inhibition of Cancer Cell Proliferation by Xylan Extracted from Corn Cobs

PubMed Central

Melo-Silveira, Raniere Fagundes; Fidelis, Gabriel Pereira; Costa, Mariana Santana Santos Pereira; Telles, Cinthia Beatrice Silva; Dantas-Santos, Nednaldo; de Oliveira Elias, Susana; Ribeiro, Vanessa Bley; Barth, Afonso Luis; Macedo, Alexandre José; Leite, Edda Lisboa; Rocha, Hugo Alexandre Oliveira

2012-01-01

Xylan is one of most abundant polymer after cellulose. However, its potential has yet to be completely recognized. Corn cobs contain a considerable reservoir of xylan. The aim of this work was to study some of the biological activities of xylan obtained from corn cobs after alkaline extraction enhanced by ultrasonication. Physical chemistry and infrared analyses showed 130 kDa heteroxylan containing mainly xylose:arabinose: galactose:glucose (5.0:1.5:2.0:1.2). Xylan obtained exhibited total antioxidant activity corresponding to 48.5 mg of ascorbic acid equivalent/g of xylan. Furthermore, xylan displayed high ferric chelating activity (70%) at 2 mg/mL. Xylan also showed anticoagulant activity in aPTT test. In antimicrobial assay, the polysaccharide significantly inhibited bacterial growth of Klebsiella pneumoniae. In a test with normal and tumor human cells, after 72 h, only HeLa tumor cell proliferation was inhibited (p < 0.05) in a dose-dependent manner by xylan, reaching saturation at around 2 mg/mL, whereas 3T3 normal cell proliferation was not affected. The results suggest that it has potential clinical applications as antioxidant, anticoagulant, antimicrobial and antiproliferative compounds. PMID:22312261

Antioxidant and Antiproliferative Activities of Heterofucans from the Seaweed Sargassum filipendula

PubMed Central

Costa, Leandro Silva; Fidelis, Gabriel Pereira; Telles, Cinthia Beatrice Silva; Dantas-Santos, Nednaldo; Camara, Rafael Barros Gomes; Cordeiro, Sara Lima; Pereira Costa, Mariana Santana Santos; Almeida-Lima, Jailma; Melo-Silveira, Raniere Fagundes; Oliveira, Ruth Medeiros; Albuquerque, Ivan Rui Lopes; Andrade, Giulianna Paiva Viana; Rocha, Hugo Alexandre Oliveira

2011-01-01

Fucan is a term used to denominate a type of polysaccharide which contains substantial percentages of l-fucose and sulfate ester groups. We obtained five heterofucans from Sargassum filipendula by proteolytic digestion followed by sequential acetone precipitation. These heterofucans are composed mainly of fucose, glucose, glucuronic acid, galactose and sulfate. These fucans did not show anticoagulant activity in PT and aPTT tests. Their antioxidant activity was evaluated using the follow tests; total antioxidant capacity, scavenging hydroxyl and superoxide radicals, reducing power and ferrous ion [Fe(II)] chelating. All heterofucans displayed considerable activity, especially SF-1.0v which showed the most significant antioxidant potential with 90.7 ascorbic acid equivalents in a total antioxidant capacity test and similar activity when compared with vitamin C in a reducing power assay. The fucan antiproliferative activity was performed with HeLa, PC3 and HepG2 cells using MTT test. In all tested conditions the heterofucans exhibited a dose-dependent effect. The strongest inhibition was observed in HeLa cells, where SF-1.0 and SF-1.5 exhibited considerable activity with an IC50 value of 15.69 and 13.83 μM, respectively. These results clearly indicate the beneficial effect of S. filipendula polysaccharides as antiproliferative and antioxidant. Further purification steps and additional studies on structural features as well as in vivo experiments are needed to test the viability of their use as therapeutic agents. PMID:21747741

Evaluation of protein C and protein S levels in patients with diabetes mellitus receiving therapy with statins and ACE inhibitors or angiotensin II receptor blockers.

PubMed

Aktaş, Şerife; Uçak, Sema; Kurt, Fatma; Taşdemir, Mehmet; Kutlu, Orkide; Eker, Pınar

2018-01-01

To evaluate protein C, protein S level in patients with diabetes mellitus receiving statin and ACE inhibitor/ARB therapy. 95 patients were included in the study and divided into four groups depending on the use of statin and ACE inhibitor/ARB therapy. Group 1 comprised of patients receiving statin therapy (n = 15), Group 2 comprised of patients receiving ACE inhibitor/ARB therapy (n = 31), Group 3 comprised of patients receiving statin and ACE inhibitor/ARB therapy (n = 23), and Group 4 comprised of patients who did not receive either statin or ACE inhibitor/ARB therapy (n = 26). These four groups were compared with respect to protein C, protein S, fibrinogen, D-dimer, INR, and aPTT levels. There were statistically significant differences with respect to protein C levels. Group 1 and group 2 had higher protein C levels compared with group 4. (p < .01). Similarly, Group 3 had higher protein C levels compared with group 4. (p < .01). There was no significant difference between the groups with respect to protein S, INR, aPTT, and D-dimer levels. Diabetic patients receiving statin or ACE inhibitor/ARB therapy had higher protein C levels. Use of statin and ACE inhibitor/ARB therapy in diabetic patients decrease hypercoagulability and therefore could reduce the occurrence of cardiovascular events. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Chitin and Sepia Ink Hybrid Hemostatic Sponge on the Blood Parameters of Mice

PubMed Central

Zhang, Wei; Sun, Yu-Lin; Chen, Dao-Hai

2014-01-01

Chitin and sepia ink hybrid hemostatic sponge (CTSH sponge), a new biomedical material, was extensively studied for its beneficial biological properties of hemostasis and stimulation of healing. However, studies examining the safety of CTSH sponge in the blood system are lacking. This experiment aimed to examine whether CTSH sponge has negative effect on blood systems of mice, which were treated with a dosage of CTSH sponge (135 mg/kg) through a laparotomy. CTSH sponge was implanted into the abdominal subcutaneous and a laparotomy was used for blood sampling from abdominal aortic. Several kinds of blood parameters were detected at different time points, which were reflected by coagulation parameters including thrombin time (TT), prothrombin time (PT), activated partial thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4); anticoagulation parameter including antithrombin III (AT-III); fibrinolytic parameters including plasminogen (PLG), fibrin degradation product (FDP) and D-dimer; hemorheology parameters including blood viscosity (BV) and plasma viscosity (PV). Results showed that CTSH sponge has no significant effect on the blood parameters of mice. The data suggested that CTSH sponge can be applied in the field of biomedical materials and has potential possibility to be developed into clinical drugs of hemostatic agents. PMID:24727395

Laboratory assessment of Activated Protein C Resistance/Factor V-Leiden and performance characteristics of a new quantitative assay.

PubMed

Amiral, Jean; Vissac, Anne Marie; Seghatchian, Jerard

2017-12-01

Activated Protein C Resistance is mainly associated to a factor V mutation (RQ506), which induces a deficient inactivation of activated factor V by activated protein C, and is associated to an increased risk of venous and arterial thrombosis in affected individuals, caused by the prolonged activated factor V survival. Its prevalence is mainly in Caucasians (about 5%), and this mutation is absent in Africans and Asians. Presence of Factor V-Leiden is usually evidenced with clotting methods, using a two-step APTT assay performed without or with APC: prolongation of blood coagulation time is decreased if this factor is present. The R506Q Factor V-Leiden mutation is now usually characterized using molecular biology, and this technique tends to become the first intention assay for characterization of patients. Both techniques are qualitative, and allow classifying tested individuals as heterozygotes or homozygotes for the mutation, when present. A new quantitative assay for Factor V-Leiden, using a one-step clotting method, has been developed, and designed with highly purified human coagulation proteins. Clotting is triggered with human Factor Xa, in presence of calcium and phospholipids (mixture which favours APC action over clotting process). Diluted tested plasma, is supplemented with a clotting mixture containing human fibrinogen, prothrombin, and protein S at a constant concentration. APC is added, and clotting is initiated with calcium. Calibration is performed with a pool of plasmas from patients carrying the R506Q Factor V mutation, and its mixtures with normal plasma. Homozygous patients have clotting times of about <40sec; heterozygous patients have clotting times of about 40-60sec and normal individuals yield clotting times >70sec. Factor V-Leiden concentration is usually >75% in homozygous patients, 30-60% in heterozygous patients and below 5% in normal. The assay is insensitive to clotting factor deficiencies (II, VII, VIII: C, IX, X), dicoumarol or heparin therapies, and has no interference with lupus anticoagulant (LA). This new assay for Factor V-Leiden can be easily used in any coagulation laboratory, is performed as a single test, and is quantitative. This assay has a high robustness, is accurate and presents a good intra- (<3%) and inter-assay (<5%) variability. It contributes solving most of the laboratory issues faced when testing factor V-Leiden. Quantitation of Factor V-L could contribute to a better assessment of thrombotic risk in affected patients, as this complication is first associated to and caused by the presence of a defined amount of FVa. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of tranexamic acid on coagulation indexes of patients undergoing heart valve replacement surgery under cardiopulmonary bypass.

PubMed

Liu, Fei; Xu, Dong; Zhang, Kefeng; Zhang, Jian

2016-12-01

This study aims to explore the effects of tranexamic acid on the coagulation indexes of patients undergoing heart valve replacement surgery under the condition of cardiopulmonary bypass (CPB). One hundred patients who conformed to the inclusive criteria were selected and divided into a tranexamic acid group and a non-tranexamic acid group. They all underwent heart valve replacement surgery under CPB. Patients in the tranexamic acid group were intravenously injected with 1 g of tranexamic acid (100 mL) at the time point after anesthesia induction and before skin incision and at the time point after the neutralization of heparin. Patients in the non-tranexamic acid group were given 100 mL of normal saline at corresponding time points, respectively. Then the coagulation indexes of the two groups were analyzed. The activated blood clotting time (ACT) of the two groups was within normal scope before CPB, while four coagulation indexes including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), and fibrinogen (FIB) had significant increases after surgery; the PT and INR of the tranexamic acid group had a remarkable decline after surgery. All the findings suggest that the application of tranexamic acid in heart valve replacement surgery under CPB can effectively reduce intraoperative and postoperative blood loss. © The Author(s) 2016.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Dawei; Han, Baoqin, E-mail: baoqinh@ouc.edu.cn; Dong, Wen

Highlights: {yields} We report, for the first time, the safety of carboxymethyl chitosan in blood system. {yields} CM-Chitosan has no significant effects on coagulation function of rats. {yields} CM-Chitosan has no significant effects on anticoagulation performance of rats. {yields} CM-Chitosan has no significant effects on fibrinolytic function of rats. {yields} CM-Chitosan has no significant effects on hemorheology of rats. -- Abstract: Carboxymethyl chitosan (CM-chitosan), a derivative of chitosan, was extensively studied in the biomedical materials field for its beneficial biological properties of hemostasis and stimulation of healing. However, studies examining the safety of CM-chitosan in the blood system are lacking.more » In this study CM-chitosan was implanted into the abdominal cavity of rats to determine blood indexes at different times and to evaluate the effects of CM-chitosan on the blood system of rats. Coagulation function was reflected by thrombin time (TT), prothrombin time (PT), activated partial thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4) indexes; anti-coagulation performance was assessed by the index of antithrombinIII (ATIII); fibrinolytic function was reflected by plasminogen (PLG) and fibrin degradation product (FDP) indexes; and blood viscosity (BV) and plasma viscosity (PV) indexes reflected hemorheology. Results showed that CM-chitosan has no significant effects on the blood system of rats, and provides experimental basis for CM-chitosan to be applied in the field of biomedical materials.« less

Increased Efficacy of Antivenom Combined with Hyperbaric Oxygen on Deinagkistrodon acutus Envenomation in Adult Rats

PubMed Central

Li, Mo; Xie, Zhi-Hui; Yu, An-Yong; He, Dong-Po

2018-01-01

Background: Snakebites are a neglected threat to global human health with a high morbidity rate. The present study explored the efficacy of antivenom with hyperbaric oxygen (HBO) intervention on snakebites, which could provide the experimental basis for clinical adjuvant therapy. Methods: Male Sprague–Dawley rats (n = 96) were randomized into four groups: the poison model was established by injecting Deinagkistrodon acutus (D. acutus) venom (0.8 LD50) via the caudal vein; the antivenom group was injected immediately with specific antivenom via the caudal vein after successful establishment of the envenomation model; and the antivenom + HBO group was exposed to HBO environment for 1 h once at predetermined periods of 0 h, 4 h, 12 h, and 23 h after antivenin administration. Each HBO time point had six rats; the control group was left untreated. The rats in the experimental group were euthanized at the corresponding time points after HBO therapy, and brain tissue and blood were harvested immediately. Hematoxylin and eosin (H&E) staining was used to investigate the pathological changes in the rat brain. Immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Western blotting were used to detect the expression of Nestin mRNA and protein in the subventricular zone (SVZ) of the brain. The levels of coagulation function (prothrombin time, activated partial thromboplastin time [APTT], and fibrinogen) and oxidation/antioxidation index (malondialdehyde [MDA] and superoxide dismutase [SOD]) were analyzed. Data were analyzed using one-way analysis of variance. Results: The brain tissue from rats in the poison model was observed for pathological changes using H&E staining. Tissues showed edema, decreased cell number, and disordered arrangement in the SVZ in the snake venom group. The antivenom − HBO intervention significantly alleviated these observations and was more prominent in the antivenom + HBO group. The serum levels of SOD and MDA in the snake venom group were increased and the antivenom − HBO intervention further increased the SOD levels but significantly decreased the MDA levels; however, this was enhanced within 1 h after HBO administration (MDA: F = 5.540, P = 0.008, SOD: F = 7.361, P = 0.000). Activated partial thromboplastin time (APTT) was significantly abnormal after venom administration but improved after antivenom and was even more significant in the antivenom + HBO group 5 h after envenomation (F = 25.430, P = 0.000). Only a few nestin-positive cells were observed in the envenomation model. The expression levels were significant in the antivenom and antivenom + HBO groups within 1 and 5 h after envenomation and were more significant in the antivenom + HBO group as determined by IHC, real-time PCR, and Western blotting (P < 0.05). D. acutus envenomation has neurotoxic effects in the brain of rats. Conclusions: Antivenin and HBO, respectively, induced a neuroprotective effect after D. acutus envenomation by attenuating brain edema, upregulating nestin expression in SVZ, and improving coagulopathy and oxidative stress. The intervention efficacy of antivenom with HBO was maximum within 5 h after envenomation and was more efficacious than antivenom alone. PMID:29363648

Dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan.

PubMed

Wang, Jianglin; Hu, Wei; Liu, Qun; Zhang, Shengmin

2011-07-01

Heparinized biomaterials exhibit great anticoagulant properties. However, they promote proliferation of Staphylococcus aureus (S. aureus) and therefore cause infection within the bloodstream upon implantation in vivo. In the present study, an interesting dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan was synthesized. First, heparin was grafted onto the silk fibroin by covalent immobilization with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). All data gathered from Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and elemental analysis (EA) indicated that the heparin was successfully immobilized onto the silk fibroin. The dual-functional composite of heparinized silk fibroin and chitosan was then fabricated by a blending method. The anticoagulant activity of the heparinized materials was evaluated using the prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). The results showed that both heparinized silk fibroin and the composite material exhibited better hemocompatibility in comparison with single silk fibroin or chitosan. The antibacterial property of the materials was investigated by the pour-plate method. Results further suggested that the composite antibacterial property with respect to S. aureus was significantly enhanced. The dual-functionality of the composite material may supply a potential choice in blood contact devices. Copyright © 2011 Elsevier B.V. All rights reserved.

Identifying coagulopathies in the pathophysiology of cold stress syndrome in the Florida manatee Trichechus manatus latirostris.

PubMed

Barratclough, Ashley; Conner, Bobbi J; Brooks, Marjory B; Pontes Stablein, Alyssa; Gerlach, Trevor J; Reep, Roger L; Ball, Ray L; Floyd, Ruth Francis

2017-08-09

Cold stress syndrome (CSS) in the Florida manatee Trichechus manatus latirostris has been defined as morbidity and mortality resulting from prolonged exposure to water temperatures <20°C. The pathophysiology is described as multifactorial, involving nutritional, immunological and metabolic disturbances; however, the exact mechanisms are unknown. We hypothesized that thromboembolic complications contribute to the pathophysiology of CSS in addition to the previously described factors. During the winter of 2014-2015, 10 Florida manatees with clinical signs of CSS were presented to Lowry Park Zoo, Tampa, FL, USA. Thromboelastography (TEG) and coagulation panels were performed at admission. In addition, coagulation panel data from 23 retrospective CSS cases were included in the analyses. There were numerous differences between mean values of TEG and coagulation parameters for healthy manatees and those for CSS cases. Among TEG parameters, reaction time (R), clot formation time (K) and percentage of clot lysed after 30 min (LY30) values were significantly different (p < 0.05) between the 2 groups. CSS cases also had significantly higher mean D-dimer concentration and coagulation factor XI activity, prolonged mean activated partial thromboplastin time (aPTT) and significantly decreased mean antithrombin activity. These combined abnormalities include clinicopathologic criteria of disseminated intravascular coagulation, indicating an increased risk of thromboembolic disease associated with manatee CSS.

The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

PubMed

Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

2014-05-01

The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of sensitivity and specificity of a standardized procedure using different reagents for the detection of lupus anticoagulants. The Working Group on Hemostasis of the Société Française de Biologie Clinique and for the Groupe d'Etudes sur I'Hémostase et la Thrombose.

PubMed

Goudemand, J; Caron, C; De Prost, D; Derlon, A; Borg, J Y; Sampol, J; Sié, P

1997-02-01

This study was designed to test the sensitivity and specificity of a combination of 3 phospholipid-dependent assays performed with various reagents, for the detection of lupus anticoagulant (LA). Plasmas containing an LA (n = 56) or displaying various confounding pathologies [58 intrinsic pathway factor deficiencies, 9 factor VIII inhibitors, 28 plasmas from patients treated with an oral anticoagulant (OAC)] were selected. In a first step, the efficiency of each assay and reagent was assessed using the Receiving Operating Characteristic (ROC) method. Optimal cut-offs providing both sensitivity and specificity > or = 80% were determined. The APTT assay and most of the phospholipid neutralization assays failed to discriminate factor VIII inhibitors from LA. In a second step, using the optimal cut-offs determined above, the results of all the possible combinations of the 3 assays performed with 4 different reagents were analyzed. Thirteen combinations of reagents allowed > or = 80% of plasmas of each category (LA, factor deficiency or OAC) to be correctly classified (3/3 positive test results in LA-containing plasmas and 0/3 positive results in LA-negative samples).

Qualification of a select one-stage activated partial thromboplastin time-based clotting assay and two chromogenic assays for the post-administration monitoring of nonacog beta pegol.

PubMed

Tiefenbacher, S; Bohra, R; Amiral, J; Bowyer, A; Kitchen, S; Lochu, A; Rosén, S; Ezban, M

2017-10-01

Essentials Nonacog beta pegol (N9-GP) is an extended half-life, recombinant human factor IX (FIX). One-stage clotting (OSC) and chromogenic FIX activity assays were assessed for N9-GP recovery. OSC STA ® -Cephascreen ® , ROX FIX and BIOPHEN FIX chromogenic assays were qualified for N9-GP. Other extended half-life factor products should be assessed in a similar way prior to approval. Background Nonacog beta pegol (N9-GP) is an extended half-life, glycoPEGylated recombinant human factor IX that is under development for the prophylaxis and treatment of bleeding episodes in hemophilia B patients. Considerable reagent-dependent variability has been observed when one-stage clotting assays are used to measure the recovery of recombinant FIX products, including N9-GP. Objective To qualify select one-stage clotting and chromogenic FIX activity assays for measuring N9-GP recovery. Methods The accuracy and precision of the one-stage clotting assay (with the STA-Cephascreen activated partial thromboplastin [APTT] reagent) and the ROX Factor IX and BIOPHEN Factor IX chromogenic assays for measuring N9-GP recovery were assessed in N9-GP-spiked hemophilia B plasma samples in a systematic manner at three independent sites, with manufacturer-recommended protocols and/or site-specific assay setups, including different instruments. Results For each of the three FIX activity assays qualified on five different reagent-instrument systems, acceptable intra-assay and interassay accuracy and precision, dilution integrity, reagent robustness and freeze-thaw and short-term sample stabilities were demonstrated. The STA-Cephascreen assay showed a limited reportable range at one of the three qualification sites, and the BIOPHEN Factor IX assay showed suspect low-end sensitivity at one of the three qualification sites. An individual laboratory would account for these limitations by adjusting the assay's reportable range; thus, these findings are not considered to impact the respective assay qualifications. Conclusion The one-stage clotting assay with the STA-Cephascreen APTT reagent, the ROX Factor IX chromogenic assay and the BIOPHEN Factor IX chromogenic assay are considered to be qualified for the measurement of N9-GP in 3.2% (0.109 m) citrated human plasma. © 2017 International Society on Thrombosis and Haemostasis.

Clinical evaluation of laboratory methods to monitor apixaban treatment in patients with atrial fibrillation.

PubMed

Skeppholm, Mika; Al-Aieshy, Fadiea; Berndtsson, Maria; Al-Khalili, Faris; Rönquist-Nii, Yuko; Söderblom, Lisbeth; Östlund, Annika Y; Pohanka, Anton; Antovic, Jovan; Malmström, Rickard E

2015-07-01

The direct factor-Xa inhibitor apixaban is approved e.g. for the prevention of stroke in patients with atrial fibrillation (AF). Although routine monitoring of apixaban therapy is currently not recommended, selective monitoring could be useful to optimize efficacy and safety in certain clinical situations. We studied the exposure and effect of apixaban using different laboratory methods in a clinical setting with a well-defined cohort of AF patients. Seventy AF patients (72±7.4years, 64 % men, mean CHADS2 score 1.7) treated with apixaban 2.5 (n=10) or 5mg BID (n=60). Trough plasma apixaban concentrations determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to the coagulation assays Anti-factor Xa, PT-INR and aPTT. The apixaban plasma concentration determined by LC-MS/MS varied more than 10-fold overall. The range was between 15-83 and 29-186ng/mL for the 2.5mg BID and 5mg BID respectively, with patients receiving 5mg BID having significantly higher apixaban concentrations (p<0.001). A strong correlation between LC-MS/MS and anti-FXa-assay was found (p<0.001), while aPTT and PT-INR were not sensitive enough. There were no significant correlations between gender, creatinine clearance, body weight or age and apixaban exposure. Anti-FXa-assay performed well upon apixaban concentrations in a normal exposure range. Still LC-MS/MS remains the "gold standard" method, covering also low concentrations. Compared to clinical trials, we observed relatively lower apixaban exposure and a more pronounced difference between high and low dose. Additional information regarding apixaban exposure and benefit-risk profile is needed in order to individualize treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Losartan and captopril treatment rescue normal thrombus formation in microfibril associated glycoprotein-1 (MAGP1) deficient mice.

PubMed

Vassequi-Silva, Tallita; Pereira, Danielle Sousa; Nery Diez, Ana Cláudia C; Braga, Guilherme G; Godoy, Juliana A; Mendes, Camila B; Dos Santos, Leonardo; Krieger, José E; Antunes, Edson; Costa, Fábio T M; Vicente, Cristina P; Werneck, Claudio C

2016-02-01

MAGP1 is a glycoprotein present in the elastic fibers and is a part of the microfibrils components. MAGP1 interacts with von Willebrand factor and the active form of TGF-β and BMP. In mice lacking MAGP1, thrombus formation is delayed, increasing the occlusion time of carotid artery despite presenting normal blood coagulation in vitro. MAGP1-containing microfibrils may play a role in hemostasis and thrombosis. In this work, we evaluated the function of MAGP1 and its relation to TGF-β in the arterial thrombosis process. We analyzed thrombus formation time in wild type and MAGP1-deficient mice comparing Rose Bengal and Ferric Chloride induced arterial lesion. The potential participation of TGF-β in this process was accessed when we treated both wild type and MAGP1-deficient mice with losartan (an antihypertensive drug that decreases TGF-β activity) or captopril (an angiotensin converting enzyme inhibitor that was used as a control antihypertensive drug). Besides, we evaluated thrombus embolization and the gelatinolytic activity in the arterial walls in vitro and ex vivo. Losartan and captopril were able to recover the thrombus formation time without changing blood pressure, activated partial thromboplastin time (aPTT), PT (prothrombin time), platelet aggregation and adhesion, but decreased gelatinase activity. Our results suggest that both treatments are effective in the prevention of the sub-endothelial ECM degradation, allowing the recovery of normal thrombus formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rotational Thromboelastometry or Conventional Coagulation Tests in Liver Transplantation: Comparing Blood Loss, Transfusions, and Cost.

PubMed

Smart, Laura; Mumtaz, Khalid; Scharpf, Danielle; Gray, Nicole O'Bleness; Traetow, Daniel; Black, Sylvester; Michaels, Anthony J; Elkhammas, Elmahdi; Kirkpatrick, Robert; Hanje, A James

Orthotopic liver transplantation (OLT) can be associated with significant bleeding requiring multiple blood product transfusions. Rotational thromboelastometry (ROTEM) is a point-of-care device that has been used to monitor coagulation during OLT. Whether it reduces blood loss/transfusions during OLT remains controversial. We aim to compare ROTEM with conventional coagulation tests (aPTT, PT, INR, platelet count, fibrinogen) to guide transfusion of platelets, cryoprecipitate, and fresh frozen plasma (FFP) during OLT over 3 years. Thirty-four patients who had transfusions guided by ROTEM were compared to 34 controls who received transfusions guided by conventional coagulation tests (CCT). Intraoperative blood loss, type/ amount of blood products transfused, and direct costs were compared between the two groups. The ROTEM group had significantly less intra-operative blood loss (2.0 vs. 3.0 L, p = 0.04) and fresh frozen plasma (FFP) transfusion (4 units vs. 6.5 units, p = 0.015) compared to the CCT group (2.0L vs. 3.0L, p = 0.04). However, total number of patients transfused cryoprecipitate was increased in ROTEM (n = 25;73%) as compared to CCT (n = 19; 56%), p = 0.033. The direct cost of blood products plus testing was reduced in the ROTEM group ($113,142.89 vs. $127,814.77). In conclusion implementation of a ROTEM-guided transfusion algorithm resulted in a reduction in intra-operative blood loss, FFP transfusion and a decrease in direct cost during OLT. ROTEM is a useful and safe point of care device in OLT setting.

A case report of idiopathic iliopsoas hematoma which occurred soon after transfer to the wheelchair after total hip arthroplasty.

PubMed

Okumura, Tomoo; Fujita, Hiroshi; Harada, Hideto; Nishimura, Ryuuichi; Tominaga, Tomohiro

2017-02-01

A 79-year-old woman was diagnosed with osteoarthritis of the left hip and scheduled for total hip arthroplasty. As two lesions were detected in branches of the coronary arteries, she was treated with catheter treatment. The patient was receiving anticoagulant treatment, which was suspended eight days before the operation; however, heparin was started at 6 days before the operation and was stopped 9 hours before the operation. On the 2nd postoperative day soon after transfer to the wheel chair, she was feeling unwell and was suffering from severe pain in her left buttock and left thigh. Her blood pressure had decreased to 70 mmHg. During abdominal contrast-enhanced CT, a hematoma was detected in the left iliopsoas muscle. Catheter therapy was started by the cardiovascular department and bleeding had stopped spontaneously. The patient was able to walk with a cane and was discharged on the 40th postoperative day. THA: total hip arthroplasty, CT: computed tomography, JOA score: Japanese Orthopaedic Association hip score, HA: hydroxyapatite, PMMA: polymethyl-methacrylate, APTT: activated partial thromboplastin time.

Effect of flomoxef on blood coagulation and alcohol metabolism.

PubMed

Uchida, K; Matsubara, T

1991-01-01

The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.

Restraint stress enhances arterial thrombosis in vivo--role of the sympathetic nervous system.

PubMed

Stämpfli, Simon F; Camici, Giovanni G; Keller, Stephan; Rozenberg, Izabela; Arras, Margarete; Schuler, Beat; Gassmann, Max; Garcia, Irene; Lüscher, Thomas F; Tanner, Felix C

2014-01-01

Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 h of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor (TF) activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall TF, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1) and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. Tumor necrosis factor alpha (TNF-α) plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne TF contributes, at least in part, to the observed effect whereas vessel wall TF, platelets, circulating coagulation factors, fibrinolysis and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.

Comparison of a standardized procedure with current laboratory practices for the detection of lupus anticoagulant in France. Working Group on Hemostasis of the Société Française de Biologie Clinique.

PubMed

1993-11-15

A multicenter study involving 13 laboratories was designed to compare a common procedure for screening lupus anticoagulants (LA) to the different practices currently in use in these laboratories. The common procedure combined 3 phospholipid-dependent assays, including mixing studies and a phospholipid neutralizing test. Due to the heterogeneity of LA expression, an abnormal result in at least one of the tests was sufficient to classify a sample as positive for LA. Consecutive samples referred for LA diagnosis were evaluated in parallel by each participant and the data found using the common procedure were analyzed independently according to mutually agreed cut-offs and criteria for sample classification. Within a period of 3 months, 535 samples were included, of which 147 were judged LA positive, 29 undetermined and 359 negative by the respective laboratories using their current practice. When using the common procedure, 149 plasmas were said to be positive, 38 undetermined and 348 negative. Absolute concordance occurred for 81% of the specimen population and absolute discordance (positive versus negative) for 7%. The level of agreement between the common procedure and the current practices, assessed by kappa indexes, indicated noticeable variations in the rates of detection from laboratory to laboratory. Among the different tests used in the common procedure, regular APTT was the least sensitive (about 50% detection) but none of the other tests alone recognized more than 73% of specimens from the LA positive population. This yield increased to about 90% with any combination of 2 sensitive tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Polysulfone hemodiafiltration membranes with enhanced anti-fouling and hemocompatibility modified by poly(vinyl pyrrolidone) via in situ cross-linked polymerization.

PubMed

Zhu, Lijing; Song, Haiming; Wang, Jiarong; Xue, Lixin

2017-05-01

Poly(vinyl pyrrolidone) (PVP) and its copolymers have been widely employed for the modification of hemodiafiltration membranes due to their excellent hydrophilicity, antifouling and hemocompatibility. However, challenges still remain to simplify the modification procedure and to improve the utilization efficiency. In this paper, antifouling and hemocompatibility polysulfone (PSf) hemodiafiltration membranes were fabricated via in situ cross-linked polymerization of vinyl pyrrolidone (VP) and vinyltriethoxysilane (VTEOS) in PSf solutions and non-solvent induced phase separation (NIPS) technique. The prepared membranes were characterized by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), which suggested that VP and VTEOS have been cross-linked copolymerized in PSf membranes. The modified PSf membranes with high polymer content showed improved hydrophilicity, ultrafiltration and protein antifouling ability. In addition, the modified PSf membranes showed lower protein adsorption, inhibited platelet adhesion and deformation, prolonged the activated partial thromboplastin time (APTT), prothrombin time (PT), and decreased the content of fibrinogen (FIB) transferring to fibrin, indicating enhanced hemocompatibility. In a word, the present work provides a simple and effective one-step modification method to construct PSf membranes with improved hydrophilicity, antifouling and hemocompatibility. Copyright © 2017 Elsevier B.V. All rights reserved.

[The comparison of clinical features and laboratory indexes between flat descending hearing loss and total hearing loss].

PubMed

Wang, R L; Zhang, D M

2017-12-20

Objective: To discuss similarities and differences in clinical features and laboratory indexes between patients with flat descending type sudden hearing loss and those with total hearing loss. Method: The clinical data of 123 patients with full frequencies hearing loss were retrospectively analyzed. The differences in clinical features and laboratory tests(platelet, coagulation series, D-dimer, blood lipids, hemorheology) between patients with flat descending hearing loss and those with total hearing loss were analyzed by gender, age and ear side, treatment time, concomitant symptom (tinnitus, dizziness), original underlying diseases (hypertension, diabetes), etc. Result: In the clinical features,among 51 flat descending cases, the ratio of male and female was 2.401:1; among 72 total hearing loss cases, the ratio of men and women ratio was 1.058:1 ( P <0.05). Among two groups of patients,the majority received treatment within 7 days, among whom 66.7% were flat descending population, and 83.3% were total hearing loss population ( P <0.05). Flat descending population with dizziness only accounted for 35.3% while this figure was up to 70.8% when it came to total hearing loss patients ( P <0.01). Two groups showed no differences in age, ear side, tinnitus, the original underlying diseases (hypertension, diabetes). In the laboratory tests, the total hearing loss population overtopped the plat descending population in PLT and PCT ( P <0.05), while falling below the plat descending population in APTT ( P <0.01). Two groups showed no differences in other indicators of platelet and coagulation series and laboratory data of D-dimer, blood lipids, hemorheology. Conclusion: Compared with flat descending sudden hearing loss, sudden total hearing loss more frequently happened to females who also were accompanied by dizziness. The treatment rate within 7 days was high and the patients with hypercoagulable state accounted for a higher proportion. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

[Comparative study on promoting blood effects of Danshen-Honghua herb pair with different preparations based on chemometrics and multi-attribute comprehensive index methods].

PubMed

Qu, Cheng; Tang, Yu-Ping; Shi, Xu-Qin; Zhou, Gui-Sheng; Shang, Er-Xin; Shang, Li-Li; Guo, Jian-Ming; Liu, Pei; Zhao, Jing; Zhao, Bu-Chang; Duan, Jin-Ao

2017-08-01

To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine. Copyright© by the Chinese Pharmaceutical Association.

[Effect of early intervention with heparin on function of coagulopathy, liver and kidney in rats with exertional heatstroke under the ambient air of high temperature and low humidity].

PubMed

Yu, Yang; Wei, Yuying; Zhang, Xiangrong; Li, Xinyu

2018-03-01

To explore the effects of early intervention with heparin on function of coagulopathy, liver and kidney as well as the prognosis in rats with exertional heatstroke (EHS) under the ambient air of high temperature and low humidity. 108 healthy SPF male Sprague-Dawley (SD) rats were randomly divided into normal temperature control group, EHS + normal saline (NS) group and EHS + heparin group. Of which 54 rats were collected for survival analysis (18 rats in each group), the weight change and 8-hour survival rate were observed, and Kaplan-Meier survival curves were drawn. Other 54 rats were collected for intervention experiment, the rats in each group were subdivided into 0, 1, 2 hours subgroups according to the time points of intervention with heparin after model reproduction, with 6 rats in each subgroup. The rats were placed in an artificial experiment cabin with northwest special environment, and the temperature and the relative humidity were (25.0±1.0) centigrade and (35±5)%, respectively, in normal temperature control group, and the rats were not treated in the cabin. The rats in EHS + NS group and EHS + heparin group kept running in the cabin which temperature and relative humidity were set at (43.0±0.5) centigrade and (35±5)% until the anus temperature of rats reached 43.0 centigrade, and then the rats were placed in room temperature. The rats were injected with 1 mL/kg NS or 250 U/kg heparin sodium injection through their caudal veins at 0, 1, and 2 hours, respectively, and then the blood was collected after 1.5 hours to determine the biochemical parameters including coagulation, liver and kidney as well as platelet count (PLT). (1) The weight loss of EHS + NS group and EHS + heparin group was more significant than that of normal temperature control group (g: 8.28±1.41, 8.39±1.38 vs. 2.06±1.06, both P < 0.05), but there was no significant difference between EHS + NS group and EHS + heparin group. (2) As the time went on after modeling, serum creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), activated partial thromboplastin time (APTT), and D-dimer of EHS rats showed a tendency of increasing, but fibrinogen (FBG), antithrombin III (AT III) and PLT were decreased gradually, which were obviously abnormal as compared with those at corresponding time point of the normal temperature control group. Heparin intervention 0 hour after modeling could improve the function of liver and kidney, FBG, D-dimer, AT III and PLT, but APTT was prolonged further. The SCr, BUN, ALT, AST and CK in EHS 2 hours + heparin group were still better than EHS + NS group [SCr (μmol/L): 93.33±7.69 vs. 110.50±13.56, BUN (mmol/L): 20.55±1.35 vs. 24.88±2.41, ALT (U/L): 322.17±36.36 vs. 492.33±64.19, AST (U/L): 1 252.33±240.86 vs. 2 725.67±461.17, CK (U/L): 1 4628.67±2 784.68 vs. 2 6843.00±2 637.16, all P < 0.01], APTT was significantly prolonged (s: 51.83±6.11 vs. 33.83±4.31, P < 0.01), and AT III and PLT were significantly increased [AT III: (78.03±9.15)% vs. (64.28±12.55)%, PLT (×10 9 /L): 457.67±32.33 vs. 415.83±26.45, both P < 0.05], however, there was no obvious influence on FBG or D-dimer. (3) The rats in normal temperature control group were all survived within 8 hours, and all dead in EHS + NS group. The survival rate of rats given heparin intervention at 0, 1, 2 hours after successfully modeling was 50.0%, 33.3% and 0%, respectively. Kaplan-Meier survival curve analysis showed that 8-hour cumulative survival rate in EHS 0 hour, 1 hour + heparin groups was higher than that in EHS 0 hour, 1 hour + NS groups (χ 1 2 = 7.930, P 1 = 0.005; χ 2 2 = 4.408, P 2 = 0.036), however, there was no significant difference between EHS 2 hours + heparin group and EHS 2 hours + NS group (χ 2 = 2.660, P = 0.103). Early heparin intervention can improve the coagulation function and organ function of EHS rats, while improving the survival rate of rats, indicating the earlier intervention of heparin, the better prognosis of rats is.

Chronic, not acute, skin-specific inflammation promotes thrombosis in psoriasis murine models.

PubMed

Golden, Jackelyn B; Wang, Yunmei; Fritz, Yi; Diaconu, Doina; Zhang, Xiufen; Debanne, Sara M; Simon, Daniel I; McCormick, Thomas S; Ward, Nicole L

2015-12-16

Psoriasis patients exhibit an increased risk of atherothrombotic events, including myocardial infarction and stroke. Clinical evidence suggests that psoriasis patients with early onset and more severe disease have the highest risk for these co-morbidities, perhaps due to the extent of body surface involvement, subsequent levels of systemic inflammation, or chronicity of disease. We sought to determine whether acute or chronic skin-specific inflammation was sufficient to promote thrombosis. We used two experimental mouse models of skin-specific inflammation generated in either an acute (topical Aldara application onto wild-type C57Bl/6 mice for 5 days) or chronic (a genetically engineered K5-IL-17C mouse model of psoriasiform skin inflammation) manner. Arterial thrombosis was induced using carotid artery photochemical injury (Rose Bengal-green light laser) and carotid artery diameters were measured post-clot formation. We also examined measures of clot formation including prothrombin (PT) and activated partial thromboplastin time (aPTT). Skin inflammation was examined histologically and we profiled plasma-derived lipids. The number of skin-draining lymph-node (SDLN) and splenic derived CD11b(+)Ly6C(high) pro-inflammatory monocytes and CD11b(+)Ly6G(+) neutrophils was quantified using multi-color flow cytometry. Mice treated with topical Aldara for 5 days had similar carotid artery thrombotic occlusion times to mice treated with vehicle cream (32.2 ± 3.0 vs. 31.4 ± 2.5 min, p = 0.97); in contrast, K5-IL-17C mice had accelerated occlusion times compared to littermate controls (15.7 ± 2.1 vs. 26.5 ± 3.5 min, p < 0.01) while carotid artery diameters were similar between all mice. Acanthosis, a surrogate measure of inflammation, was increased in both Aldara-treated and K5-IL-17C mice compared to their respective controls. Monocytosis, defined as elevated SDLN and/or splenic CD11b(+)Ly6C(high) cells, was significantly increased in both Aldara-treated (SDLN: 3.8-fold, p = 0.02; spleen: 2.0-fold, p < 0.01) and K5-IL-17C (SDLN: 3.4-fold, p = 0.02; spleen: 3.5-fold, p < 0.01) animals compared to controls while neutrophilia, defined as elevated SDLN and/or splenic CD11b(+)Ly6G(+) cells, was significantly increased in only the chronic K5-IL-17C model (SDLN: 11.6-fold, p = 0.02; spleen: 11.3-fold, p < 0.01). Plasma-derived lipid levels, PT and aPTT times showed no difference between the Aldara-treated mice or the K5-IL-17C mice and their respective controls. Chronic, but not acute, skin-specific inflammation was associated with faster arterial thrombotic occlusion. Increased numbers of splenic and SDLN monocytes were observed in both acute and chronic skin-specific inflammation, however, increased splenic and SDLN neutrophils were observed only in the chronic skin-specific inflammation model. Understanding the cellular response to skin-specific inflammation may provide insights into the cellular participants mediating the pathophysiology of major adverse cardiovascular events associated with psoriasis.

A global quantitative survey of hemostatic assessment in postpartum hemorrhage and experience with associated bleeding disorders.

PubMed

James, Andra H; Cooper, David L; Paidas, Michael J

2017-01-01

Coagulopathy may be a serious complicating or contributing factor to postpartum hemorrhage (PPH), and should be promptly recognized to ensure proper bleeding management. This study aims to evaluate the approaches of obstetrician-gynecologists worldwide towards assessing massive PPH caused by underlying bleeding disorders. A quantitative survey was completed by 302 obstetrician-gynecologists from 6 countries (the UK, France, Germany, Italy, Spain, and Japan). The survey included questions on the use of hematologic laboratory studies, interpretation of results, laboratory's role in coagulation assessments, and experience with bleeding disorders. Overall, the most common definitions of "massive" PPH were >2,000 mL (39%) and >1,500 mL (34%) blood loss. The most common criteria for rechecking a "stat" complete blood count and for performing coagulation studies were a drop in blood pressure (73%) and ongoing visible bleeding (78%), respectively. Laboratory coagulation (prothrombin time/activated partial thromboplastin time [PT/aPTT]) and factor VIII/IX assays were performed on-site more often than were mixing studies (laboratory coagulation studies, 93%; factor VIII/IX assays, 63%; mixing studies, 22%). Most commonly consulted sources of additional information were colleagues within one's own specialty (68%) and other specialists (67%). Most respondents had consulted with a hematologist (78%; least, Germany [56%]; greatest, UK [98%]). The most common reason for not consulting was hematologist unavailability (44%). The most commonly reported thresholds for concern with PT and aPTT were 13 to 20 seconds (36%) and 30 to 45 seconds (50%), respectively. Most respondents reported having discovered an underlying bleeding disorder (58%; least, Japan [35%]; greatest, Spain [74%]). Global survey results highlight similarities and differences between countries in how PPH is assessed and varying levels of obstetrician-gynecologist experience with identification of underlying bleeding disorders and engagement of hematology consultants. Opportunities to improve patient management of PPH associated with bleeding disorders include greater familiarity with interpreting PT/aPTT test results and identification of and consistent consultation with hematologists with relevant expertise.

Zoanthid mucus as new source of useful biologically active proteins.

PubMed

Guarnieri, Míriam Camargo; de Albuquerque Modesto, Jeanne Claíne; Pérez, Carlos Daniel; Ottaiano, Tatiana Fontes; Ferreira, Rodrigo da Silva; Batista, Fabrício Pereira; de Brito, Marlon Vilela; Campos, Ikaro Henrique Mendes Pinto; Oliva, Maria Luiza Vilela

2018-03-01

Palythoa caribaeorum is a very common colonial zoanthid in the coastal reefs of Brazil. It is known for its massive production of mucus, which is traditionally used in folk medicine by fishermen in northeastern Brazil. This study identified biologically active compounds in P. caribaerum mucus. Crude mucus was collected during low tides by the manual scraping of colonies; samples were maintained in an ice bath, homogenized, and centrifuged at 16,000 g for 1 h at 4 °C; the supernatant (mucus) was kept at -80 °C until use. The enzymatic (proteolytic and phospholipase A 2 ), inhibitory (metallo, cysteine and serine proteases), and hemagglutinating (human erythrocyte) activities were determined. The results showed high levels of cysteine and metallo proteases, intermediate levels of phosholipase A 2 , low levels of trypsin, and no elastase and chymotrypsin like activities. The mucus showed potent inhibitory activity on snake venom metalloproteases and cysteine proteinase papain. In addition, it showed agglutinating activity towards O + , B + , and A + erythrocyte types. The hemostatic results showed that the mucus prolongs the aPTT and PT, and strongly inhibited platelet aggregation induced by arachidonic acid, collagen, epinephrine, ADP, and thrombin. The antimicrobial activity was tested on 15 strains of bacteria and fungi through the radial diffusion assay in agar, and no activity was observed. Compounds in P. caribaeorum mucus were analyzed for the first time in this study, and our results show potential pharmacological activities in these compounds, which are relevant for use in physiopathological investigations. However, the demonstration of these activities indicates caution in the use of crude mucus in folk medicine. Furthermore, the present or absent activities identified in this mucus suggest that the studied P. caribaeorum colonies were in thermal stress conditions at the time of sample collection; these conditions may precede the bleaching process in zoanthids. Hence, the use of mucus as an indicator of this process should be evaluated in the future. Copyright © 2018. Published by Elsevier Ltd.

Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs.

PubMed

Shen, Chenlin; Huang, Xiaohui; Li, Jun; Zhang, Ping; Li, Lin; Zhang, Wei; Hu, Tingting; Pappoe, Faustina; Huang, Jihan; Tang, Haiqin

2016-01-01

1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients.

Blood transfusion and the anaesthetist: management of massive haemorrhage

PubMed Central

Thomas, D; Wee, M; Clyburn, P; Walker, I; Brohi, K; Collins, P; Doughty, H; Isaac, J; Mahoney, PF; Shewry, L

2010-01-01

Hospitals must have a major haemorrhage protocol in place and this should include clinical, laboratory and logistic responses. Immediate control of obvious bleeding is of paramount importance (pressure, tourniquet, haemostatic dressings). The major haemorrhage protocol must be mobilised immediately when a massive haemorrhage situation is declared. A fibrinogen < 1 g.l−1 or a prothrombin time (PT) and activated partial thromboplastin time (aPTT) of > 1.5 times normal represents established haemostatic failure and is predictive of microvascular bleeding. Early infusion of fresh frozen plasma (FFP; 15 ml.kg−1) should be used to prevent this occurring if a senior clinician anticipates a massive haemorrhage. Established coagulopathy will require more than 15 ml.kg−1 of FFP to correct. The most effective way to achieve fibrinogen replacement rapidly is by giving fibrinogen concentrate or cryoprecipitate if fibrinogen is unavailable. 1:1:1 red cell:FFP:platelet regimens, as used by the military, are reserved for the most severely traumatised patients. A minimum target platelet count of 75 × 109.l−1 is appropriate in this clinical situation. Group-specific blood can be issued without performing an antibody screen because patients will have minimal circulating antibodies. O negative blood should only be used if blood is needed immediately. In hospitals where the need to treat massive haemorrhage is frequent, the use of locally developed shock packs may be helpful. Standard venous thromboprophylaxis should be commenced as soon as possible after haemostasis has been secured as patients develop a prothrombotic state following massive haemorrhage. PMID:20963925

High levels of the AR-V7 Splice Variant and Co-Amplification of the Golgi Protein Coding YIPF6 in AR Amplified Prostate Cancer Bone Metastases.

PubMed

Djusberg, Erik; Jernberg, Emma; Thysell, Elin; Golovleva, Irina; Lundberg, Pia; Crnalic, Sead; Widmark, Anders; Bergh, Anders; Brattsand, Maria; Wikström, Pernilla

2017-05-01

The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistant prostate cancer (CRPC), such as expression of constitutively active AR variants and steroid-converting enzymes has been poorly examined. Specific aim was to examine AR amplification in PC bone metastases and to explore molecular and functional consequences of this, with the long-term goal of identifying novel molecular targets for treatment. Gene amplification was assessed by fluorescence in situ hybridization in cryo-sections of clinical PC bone metastases (n = 40) and by PCR-based copy number variation analysis. Whole genome mRNA expression was analyzed using H12 Illumina Beadchip arrays and specific transcript levels were quantified by qRT-PCR. Protein localization was analyzed using immunohistochemistry and confocal microscopy. The YIPF6 mRNA expression was transiently knocked down and stably overexpressed in the 22Rv1 cell line as representative for CRPC, and effects on cell proliferation, colony formation, migration, and invasion were determined in vitro. Extracellular vesicles (EVs) were isolated from cell cultures using size-exclusion chromatography and enumerated by nanoparticle tracking analysis. Protein content was identified by LC-MS/MS analysis. Blood coagulation was measured as activated partial thromboplastin time (APTT). Functional enrichment analysis was performed using the MetaCore software. AR amplification was detected in 16 (53%) of the bone metastases examined from CRPC patients (n = 30), and in none from the untreated patients (n = 10). Metastases with AR amplification showed high AR and AR-V7 mRNA levels, increased nuclear AR immunostaining, and co-amplification of genes such as YIPF6 in the AR proximity at Xq12. The YIPF6 protein was localized to the Golgi apparatus. YIPF6 overexpression in 22Rv1 cells resulted in reduced cell proliferation and colony formation, and in enhanced EV secretion. EVs from YIPF6 overproducing 22Rv1 cells were enriched for proteins involved in blood coagulation and, accordingly, decreased the APTT in a dose-dependent fashion. AR amplified CRPC bone metastases show high AR-V7 expression that probably gives resistance to AR-targeting drugs. Co-amplification of the Golgi protein coding YIPF6 gene with the AR may enhance the secretion of pro-coagulative EVs from cancer cells and thereby stimulate tumor progression and increase the coagulopathy risk in CRPC patients. Prostate 77: 625-638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng.

PubMed

Fung, Foon Yin; Wong, Wan Hui; Ang, Seng Kok; Koh, Hwee Ling; Kun, Mei Ching; Lee, Lai Heng; Li, Xiaomei; Ng, Heng Joo; Tan, Chuen Wen; Zhao, Yan; Linn, Yeh Ching

2017-08-15

Herbs with "blood-activating" properties by traditional medicine theory often raise concerns for their possible anti-platelet or anticoagulation effects based on reports from in vitro studies. Such herbs have been implicated for bleeding manifestations based on only anecdotal reports. In particular, the combination of such herbs with anti-platelet agents is often empirically advised against despite lack of good clinical evidence. Here we studied 3 commonly used herbal preparations Curcuma longa, Angelica sinensis and Panax ginseng on their respective anti-platelet and anticoagulation effect, alone and in combination with aspirin. This is a randomized, double-blind, placebo-controlled trial involving 25 healthy volunteers for each herbal preparation. Each subject underwent 3 phases comprising of herbal product alone, aspirin alone and aspirin with herbal product, where each phase lasted for 3 weeks with 2 weeks of washout between phases. PT/APTT, platelet function by light transmission aggregometry and thrombin generation assay by calibrated automated thrombogram were measured at baseline and after each phase. Information on adverse reaction including bleeding manifestations was collected after each phase. On the whole there was no clinically relevant impact on platelet and coagulation function. With the exception of 5 of 24 subjects in the Curcuma longa group, 2 of 24 subjects in the Angelica sinensis group and 1 of 23 subjects in the Panax ginseng group who had an inhibition in arachidonic-acid induced platelet aggregation, there was no effect of these 3 herbals products on platelet aggregation by other agonists. Combination of these herbal products with aspirin respectively did not further aggravate platelet inhibition caused by aspirin. None of the herbs impaired PT/APTT or thrombin generation. There was no significant bleeding manifestation. This study on healthy volunteers provides good evidence on the lack of bleeding risks of Curcuma longa, Angelica sinensis and Panax ginseng either used alone or in combination with aspirin. Copyright © 2017 Elsevier GmbH. All rights reserved.

Laboratory and clinical predictors of 30-day survival for patients on Extracorporeal Membrane Oxygenation (ECMO): 8-Year experience at Albert Einstein College of Medicine, Montefiore Medical Center.

PubMed

Francischetti, Ivo M B; Szymanski, James; Rodriguez, Daniel; Heo, Moonseong; Wolgast, Lucia R

2017-08-01

Survival of patients on ECMO has remained stable in every population. Laboratory values predictors of survival are required to improve patient care. Clinical Looking Glass software was used to assess Electronic Medical Records (EMRs) of patients at Albert Einstein College of Medicine, Montefiore Medical Center (2007-2014). Our population comprises of 166 adults and was divided in survivors and non-survivors, within 30days. Indications for ECMO were cardiac (65%), respiratory (25%) and infectious diseases (<10%). Eighty six patients (51.8%) survived the procedure. Gender, body weight, ejection fraction, diastolic blood pressure, and socio-economic status did not differ among survivors and non-survivors. In contrast, younger patients (45yo vs 55yo, p=0.0001) and higher systolic blood pressure (115mmHg vs 103mmHg, p=0.025) have favorable outcome. Univariate analysis shows that pre-cannulation values for creatinine (p=0.0003), chloride (p=0.009), bicarbonate (p=0.015) and pH (p=0.03) have prognostic value. Post-cannulation aPTT, pH, platelet and lymphocyte counts also have discriminative power. Notably, multiple logistic regressions for Multivariate Analysis identified chloride (OR 1.07; 95% CI 1.02-1.13; p=0.004), pH (OR 3.35; 95% CI 1.89-5.9; p<0.0001) and aPTT (OR 0.98; 95% CI 0.976-0.998; p=0.024) as independent risk factors for 30-day mortality. These results imply that pre-existing renal conditions and hemostatic dysregulation contribute to poor outcome. Finally, patients on VV-ECMO have increase odds of survival (OR 1.88; 95% CI 1.06-3.34; p=0.029). Laboratory markers identified herein may guide the management of patients on ECMO. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of Prognostic Values of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Crimean-Congo Hemorrhagic Fever Patients

PubMed Central

Gurbuz, Yunus; Ozturk, Baris; Tutuncu, Emin Ediz; Sencan, Irfan; Cicek Senturk, Gonul; Altay, Fatma Aybala

2015-01-01

Background: Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease in Turkey, and was responsible for many deaths in endemic regions during the last decade. The pathogenesis of the disease is not fully understood yet. Objectives: In this study we aimed to determine the levels of tissue plasminogen activator (tPA) and Plasminogen activator inhibitor-1 (PAI-1) as predictors of prognosis in CCHF. Patients and Methods: Patients who were diagnosed by the polymerase chain reaction (PCR) and IgM positivity in the reference laboratory were included in this study. Tissue Plasminogen activator and PAI-1 levels were measured by the enzyme linked immunosorbent assay (ELISA) using a commercial kit (human t-PA ELISA and human PAL-1 ELISA; BioVendor research and diagnostic products, BioVendor-Laboratorni medicina a.s., Brno, Czech Republic). Results: A total of 46 patients participated in this study. The significant differences between recovering patients and the patients who died, regarding Aspartate aminotransferase (AST), Creatine Phosphokinase (CPK), Lactate Dehydrogenase (LDH), Prothrombin Time (PT), activated Partial Thromboplastin time (aPTT), and thrombocyte and fibrinogen levels, were consistent with many clinical studies in the literature. The fatal cases were found to have higher tPA and PAI-1 levels in contrast to the patients who completely recovered. Conclusions: We think that these findings may help the progress of understanding of CCHF pathogenesis. PMID:26587219

Replacement of acetate with citrate in dialysis fluid: a randomized clinical trial of short term safety and fluid biocompatibility

PubMed Central

2013-01-01

Background The majority of bicarbonate based dialysis fluids are acidified with acetate. Citrate, a well known anticoagulant and antioxidant, has been suggested as a biocompatible alternative. The objective of this study was to evaluate short term safety and biocompatibility of a citrate containing acetate-free dialysis fluid. Methods Twenty four (24) patients on maintenance dialysis three times per week, 13 on on-line hemodiafiltration (HDF) and 11 on hemodialysis (HD), were randomly assigned to start with either citrate dialysis fluid (1 mM citrate, 1.5 mM calcium) or control fluid (3 mM acetate, 1.5 mM calcium) in an open-labeled cross-over trial (6 + 6 weeks with 8 treatments wash-out in between). Twenty (20) patients, 11 on HDF and 9 on HD were included in the analyses. Main objective was short term safety assessed by acid–base status, plasma ionized calcium and parathyroid hormone (PTH). In addition, biocompatibility was assessed by markers of inflammation (pentraxin 3 (PTX-3), CRP, IL-6, TNF-α and IL-1β) and thrombogenicity (activated partial thromboplastin time (APTT) and visual clotting scores). Results No differences dependent on randomization order or treatment mode (HD vs. HDF) were detected. Citrate in the dialysis fluid reduced the intra-dialytic shift in pH (+0.04 week 6 vs. +0.06 week 0, p = 0.046) and base excess (+3.9 mM week 6 vs. +5.6 mM week 0, p = 0.006) over the study period. Using the same calcium concentration (1.5 mM), citrate dialysis fluid resulted in lower post-dialysis plasma ionized calcium level (1.10 mM vs. 1.27 mM for control, p < 0.0001) and higher post-dialysis PTH level (28.8 pM vs. 14.7 pM for control, p < 0.0001) while pre-dialysis levels were unaffected. Citrate reduced intra-dialytic induction of PTX-3 (+1.1 ng/ml vs. +1.4 ng/ml for control, p = 0.04) but had no effect on other markers of inflammation or oxidative stress. Citrate reduced visual clotting in the arterial air chamber during HDF (1.0 vs. 1.8 for control, p = 0.03) and caused an intra-dialytic increase in APTT (+6.8 s, p = 0.003) without affecting post-dialysis values compared to control. Conclusions During this small short term study citrate dialysis fluid was apparently safe to use in HD and on-line HDF treatments. Indications of reduced treatment-induced inflammation and thrombogenicity suggest citrate as a biocompatible alternative to acetate in dialysis fluid. However, the results need to be confirmed in long term studies. Trial registration ISRCTN: ISRCTN28536511 PMID:24103587

Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects

PubMed Central

Frost, Charles; Nepal, Sunil; Wang, Jessie; Schuster, Alan; Byon, Wonkyung; Boyd, Rebecca A; Yu, Zhigang; Shenker, Andrew; Barrett, Yu Chen; Mosqueda-Garcia, Rogelio; LaCreta, Frank

2013-01-01

Aim Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban. Method This double-blind, randomized, placebo-controlled, parallel group, multiple dose escalation study was conducted in six sequential dose panels – apixaban 2.5, 5, 10 and 25 mg twice daily and 10 and 25 mg once daily– with eight healthy subjects per panel. Within each panel, subjects were randomized (3:1) to oral apixaban or placebo for 7 days. Subjects underwent safety assessments and were monitored for adverse events (AEs). Blood samples were taken to measure apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and modified prothrombin time (mPT). Results Forty-eight subjects were randomized and treated (apixaban, n = 36; placebo, n = 12); one subject receiving 2.5 mg twice daily discontinued due to AEs (headache and nausea). No dose limiting AEs were observed. Apixaban maximum plasma concentration was achieved ∼3 h post-dose. Exposure increased approximately in proportion to dose. Apixaban steady-state concentrations were reached by day 3, with an accumulation index of 1.3–1.9. Peak : trough ratios were lower for twice daily vs. once daily regimens. Clotting times showed dose-related increases tracking the plasma concentration–time profile. Conclusion Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures. PMID:23451769

Late vitamin K deficiency bleeding leading to a diagnosis of cystic fibrosis: a case report.

PubMed

Ngo, B; Van Pelt, K; Labarque, V; Van De Casseye, W; Penders, J

2011-01-01

Vitamin K deficiency bleeding (VKDB) in infants still occurs despite worldwide use of prophylaxis. Clinical manifestations can be dramatic with over 50% of patients presenting with intracranial haemorrhage and a mortality rate of 20% in late vitamin K deficiency bleeding. Special attention should be given to infants with a high risk profile (preterm, breast feeding, cholestasis, malabsorption). A tentative diagnosis can be made observing quick normalisation of some easy-to-perform haemostatic parameters (PT, aPTT) after administration of vitamin K. Nowadays, VKDB can still be the first clinical sign of diseases causing malabsorption of fat-soluble vitamins. In this case report, VKDB led to the diagnosis of cystic fibrosis, the most common fatal autosomal recessive disease among Caucasian people.

Age dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges.

PubMed

Toulon, Pierre; Berruyer, Micheline; Brionne-François, Marie; Grand, François; Lasne, Dominique; Telion, Caroline; Arcizet, Julien; Giacomello, Roberta; De Pooter, Neila

2016-07-04

Understanding of developmental haemostasis is critical to ensure optimal prevention, diagnosis, and treatment of haemorrhagic and thrombotic diseases in children. As coagulation test results are known to be dependent on the reagents/analysers used, it is recommended for each laboratory to define the age-dependent reference ranges by using its own technical condition. That study was carried out in seven centers to establish age-specific reference ranges using the same reagents and analyser. Plasma samples were obtained from 1437 paediatric patients from the following age groups: 15 days-4 weeks (n=36), 1-5 months (n=320), 6-12 months (n=176), 1-5 years (n=507), 6-10 years (n=132) and 11-17 years (n=262). Indication of coagulation testing was pre-operative screening for non-acute diseases in most cases. PT values were similar in the different age groups to those in adults, whereas longer aPTTs were demonstrated in the younger children. Plasma levels of all clotting factors, except for FV, were significantly decreased (p<0.0001) in the youngest children, adult values being usually reached before the end of the first year. The same applied to antithrombin, protein C/S, and plasminogen. In contrast, FVIII and VWF levels were elevated in the youngest children and returned to adult values within six months. The same applied to D-dimer levels, which were found elevated, particularly until six months of life, until puberty. These data suggest that most coagulation test results are highly dependent on age, mainly during the first year of life, and that age-specific reference ranges must be used to ensure proper evaluation of coagulation in children.

[Application of laboratory information system in the management of the key indicators of quality inspection].

PubMed

Guo, Ye; Chen, Qian; Wu, Wei; Cui, Wei

2015-03-31

To establish a system of monitoring the key indicator of quality for inspection (KIQI) on a laboratory information system (LIS), and to have a better management of KIQI. Clinical sample made in PUMCH were collected during the whole of 2014. Next, interactive input program were designed to accomplish data collecting of the disqualification rate of samples, the mistake rate of samples and the occasions of losing samples, etc. Then, a series moment of sample collection, laboratory sample arrived, sample test, sample check, response to critical value, namely, trajectory information left on LIS were recorded and the qualification rate of TAT, the notification rate of endangering result were calculated. Finally, the information about quality control were collected to build an internal quality control database and the KIQI, such as the out-of-control rate of quality control and the total error of test items were monitored. The inspection of the sample management shows the disqualification rates in 2014 were all below the target, but the rates in January and February were a little high and the rates of four wards were above 2%. The mistake rates of samples was 0.47 cases/10 000 cases, attaining the target (< 2 cases/10 000 cases). Also, there was no occasion of losing samples in 2014, attaining the target too. The inspection of laboratory reports shows the qualification rates of TAT was within the acceptable range (> 95%), however the rates of blood routine in November (94.75%) was out of range. We have solved the problem by optimizing the processes. The notification rate of endangering result attained the target (≥ 98%), while the rate of timely notification is needed to improve. Quality inspection shows the CV of APTT in August (5.02%) was rising significantly, beyond the accepted CV (5.0%). We have solved the problem by changing the reagent. The CV of TT in 2014 were all below the allowable CV, thus the allowable CV of the next year lower to 10%. It is an objective and effective method to manage KIQI with the powerful management mode of database and information process capability on LIS.

Haemostatic profile of healthy premature small for gestational age neonates.

PubMed

Mitsiakos, George; Giougi, Evaggelia; Chatziioannidis, Ilias; Karagianni, Paraskevi; Papadakis, Emmanouil; Tsakalidis, Christos; Papaioannou, Georgia; Malindretos, Pavlos; Nikolaidis, Nikolaos

2010-08-01

The pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood. To evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration. We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) <37 weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, von Willebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters. Premature SGA infants presented significantly lower levels of fibrinogen (p<0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p<0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters. Despite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms. (c) 2010 Elsevier Ltd. All rights reserved.

Recombinant activated factor VII (NovoSeven): addition to replacement therapy in acute, uncontrolled and life-threatening bleeding.

PubMed

Mayo, A; Misgav, M; Kluger, Y; Geenberg, R; Pauzner, D; Klausner, J; Ben-Tal, O

2004-07-01

Recombinant activated factor VII (rFVIIa, NovoSeven) has been used off-label for various conditions. A protocol for its use in acute, uncontrolled life-threatening bleeding, was devised and employed. A haematologist/transfusion specialist was assigned as a member of the team. The clinical data were reviewed and summarized. A scoring system for the assessment and monitoring of coagulopathy was employed. Each parameter of prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet number and fibrinogen level was allocated points according to the degree of abnormality. Three scoring levels emerged. Between April 2001 and April 2003, 13 patients received rFVIIa for acute, uncontrolled life-threatening bleeding. Nine of 13 patients remained alive for 15 days or longer after rFVIIa infusion. All patients who experienced a reduction or cessation of bleeding after rFVIIa infusion, also had a lower coagulopathy score after replacement therapy, prior to rFVIIa infusion, compared with their score at rFVIIa request. There was a reduction in the average use of blood products after rFVIIa infusion. The coagulopathy score was statistically predictive of response to rFVIIa and survival. In an area where very little data exists, we report the usefulness of rFVIIa. We propose that transfusion replacement should aim to correct coagulopathy before infusion of rFVIIa and that a haematologist/transfusion specialist should be involved in the management of these patients. A prognostically significant coagulopathy scoring system is offered.

Physiological and biological predictors of length of stay and recovery in adults with acute asthma: An observational cohort study.

PubMed

Jones, Thomas L; Owen, Jonathon; Elliott, Scott; Brown, Thomas; Reynish, Dominic; Mistry, Heena; Kerley, Sumita; Matti, Salah; Shute, Janis K; Chauhan, Anoop J

2018-01-01

Asthma is a prevalent, chronic disease associated with significant risk to patients and cost to healthcare systems. Accurate estimates of length of stay and recovery are important for patient information, physician prognostication, and management of inpatient beds. To assess factors affecting length of stay and time to recovery in adults with acute asthma. We prospectively recruited adult asthmatic non-smokers admitted with an asthma exacerbation. Participants were assessed for demographics, symptoms, medications, bloods including blood count, clotting status, and cytokines. Results were analyzed for correlation and subsequently in a regression model. One hundred twenty-six participants were recruited of which 75.4% were female. Mean age was 40.0 and mean length of stay was 3.98 days. Length of stay was associated with lower APTT ratio (1 pg/mL (P = 0.04). Older participants with lower FEV1 and supplemental oxygen requirements are likely to remain in hospital longer. Activation of the "intrinsic" clotting pathway correlates with an increased length of stay as does a raised serum AST. Detectable IL-12 in plasma correlates with slower recovery and this may be due to poor response to corticosteroids. © 2016 John Wiley & Sons Ltd.

Changes in the haemostatic system after thermoneutral and hyperthermic water immersion.

PubMed

Boldt, Leif-Hendrik; Fraszl, Waltraud; Röcker, Lothar; Schefold, Jörg Christian; Steinach, Mathias; Noack, Thilo; Gunga, Hanns-Christian

2008-03-01

Warm water bathing is a popular recreational activity and is frequently used in rehabilitation medicine. Although well tolerated in most cases, there are reports indicating an increased risk of thrombotic events after hot tub bathing. The effects of a 45 min thermoneutral bath followed by a 50 min bath with increasing water temperature (maximum 41 degrees C) until reaching a body core temperature of 39 degrees C on factors of blood coagulation and fibrinolysis were studied in eight healthy male volunteers. Blood was obtained after a 45-min resting period as control and after the thermoneutral and hyperthermic bath as well as after another 45 min recovery period at the end of the study. Hyperthermic immersion (HI) lead to a shortening of activated partial thromboplastin time (aPTT) (P < 0.05). Fibrinogen concentration decreased immediately after HI (P < 0.05) but increased during recovery (P < 0.05). Plasminogen activator inhibitor (PAI) activity decreased during HI (P < 0.05), D-dimer concentration was not found to change. Thrombocyte count increased (P < 0.05) during HI. The increases in tissue-type plasminogen activator concentration as well as leucocyte count during HI were due to haemoconcentration. Prothrombin time, PAI-activity and granulocyte count decreased during thermoneutral immersion (P < 0.05). Warm water bathing leads to haemoconcentration and minimal activation of coagulation. The PAI-1 activity is decreased. A marked risk for thrombotic or bleeding complications during warm water bathing in healthy males could not be ascertained.

The long term immunological response of swine after two exposures to a salmon thrombin and fibrinogen hemostatic bandage

PubMed Central

Rothwell, Stephen W.; Settle, Timothy; Wallace, Shannon; Dorsey, Jennifer; Simpson, David; Bowman, James R.; Janmey, Paul; Sawyer, Evelyn

2014-01-01

Experimental salmon thrombin/fibrinogen dressings have been shown to provide effective hemostasis in severe hemorrhage situations. The hypothesis for this study was that swine would still remain healthy without coagulopathy six months after exposure to salmon thrombin/fibrinogen dressings. Initial exposure was by insertion of the salmon dressing into the peritoneal cavity. Three months after the initial exposure, the same animals were subjected to two full thickness dermal wounds on the dorsal surface. One wound was bandaged with the salmon thrombin/fibrinogen bandage and the other wound was dressed with a standard bandage. The animals were monitored for an additional three months. Blood was drawn every 14 days over the six months for immunological and coagulation function analysis. All of the animals (8 pigs) remained healthy during the six month period and the dermal wounds healed without incidence. Lymph nodes and spleen showed signs of normal immune response and Western blots showed development of antibodies against salmon fibrinogen, but none of the animals made antibodies that recognized any species of thrombin. Coagulation parameters (fibrinogen concentration, thrombin time, PT and aPTT) and hematological parameters remained normal over the course of the study when compared to initial values of the subject swine. PMID:20705479

Polysaccharides and their depolymerized fragments from Costaria costata: Molecular weight and sulfation-dependent anticoagulant and FGF/FGFR signal activating activities.

PubMed

Hou, Ningning; Zhang, Meng; Xu, Yingjie; Sun, Zhongmin; Wang, Jing; Zhang, Lijuan; Zhang, Quanbin

2017-12-01

Crude polysaccharides from Costaria costata were extracted by hot water and further fractionated by anion exchange chromatography into three polysaccharide fractions. Three low molecular weight fragments were then prepared by degradation of the polysaccharides with hydrogen peroxide and ascorbic acid. The structural features of the polysaccharides and their low molecular weight fragments were elucidated for the first time based on the HGPC, FT-IR, NMR, MS, monosaccharide composition, and other chemical analyses. Their anticoagulant and FGF-1, -2, -7, -8, -9, -10/FGFR1c signaling activation activities in BaF3 cells were also examined. Our studies showed that the polysaccharides were sulfated at different positions of galactose and fucose residues. The APTT-, PT- and TT-based anticoagulant assay results indicated that a high molecular weight and a higher degree of sulfation were essential for their anticoagulant activities. In contrast, not only the polysaccharides but also the depolymerized fragments showed significant FGF/FGFR signal activating activities in a FGF-, molecular weight-, and sulfation-dependent manner. The results presented in current study demonstrated the potential use of the polysaccharides and their fragments as anticoagulants and FGF signal regulators. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-thrombogenicity and permeability of polyethersulfone hollow fiber membrane with sulfonated alginate toward blood purification.

PubMed

Salimi, Esmaeil; Ghaee, Azadeh; Ismail, Ahmad Fauzi; Karimi, Majid

2018-04-30

The main aim of this study was to evaluate the suitability of sulfonated alginate as a modifying agent to enhance the hemocompatibility of self-fabricated polyethersulfone (PES) hollow fiber membrane for blood detoxification. Sodium alginate was sulfonated with a degree of 0.6 and immobilized on the membrane via surface amination and using glutaraldehyde as cross-linking agent. Coating layer not only improved the membrane surface hydrophilicity, but also induced -39.2 mV negative charges on the surface. Water permeability of the modified membrane was enhanced from 67 to 95 L/m 2 ·h·bar and flux recovery ratio increased more than 2-fold. Furthermore, the modified membrane presented higher platelet adhesion resistance (reduced by more than 90%) and prolonged coagulation time (35 s for APTT and 14 s for PT) in comparison with the pristine PES hollow fiber membrane, which verified the improved anti-thrombogenicity of the modified membrane. On the other hand, obtained membrane after 3 h coating could remove up-to 60% of the uremic toxins. According to the obtained data, sulfonated alginate can be a promising modifying agent for the future blood-contacting membrane and specially blood purification issues. Copyright © 2018 Elsevier B.V. All rights reserved.

Antioxidant and anticoagulant activity of sulfated polysaccharide from Gracilaria debilis (Forsskal).

PubMed

Sudharsan, Sadhasivam; Subhapradha, Namasivayam; Seedevi, Palaniappan; Shanmugam, Vairamani; Madeswaran, Perumal; Shanmugam, Annaian; Srinivasan, Alagiri

2015-11-01

Sulfated polysaccharide was isolated from Gracilaria debilis and purified through gel chromatography and their molecular weight was determined through AGE and PAGE. The total sugars in the crude, fractionated and purified polysaccharide were estimated as 52.65%, 59.70% and 67.60%, respectively. The ash and moisture content of crude and purified polysaccharide was found to be 14.2% and 23.5% and the polysaccharide was free from protein contamination. The sulfate and uronic acid contents in the crude, fractionated and purified were estimated as 14.08%, 15.33% and 16.01% and 10.12%, 13.56%, 16.70%. The elemental composition including carbon (crude - 23.12%, purified - 21.05%), hydrogen (crude - 3.4%, purified - 4.13%) and nitrogen (crude - 1.22%, purified - 0.56%) were also analyzed. The anticoagulant activity of the sulfated polysaccharide through APTT and PT was estimated at 14.11 and 8.23IU/mg. The purified polysaccharide with the molecular mass of 20kDa showed highest antioxidant activity (38.57%, 43.48% and 38.88%) in all the assays tested such as DPPH hydroxyl radical, superoxide radical, hydroxyl radical scavenging activities and the structural property was analyzed through FT-IR and (1)H NMR spectrum. The results together suggest that the isolated low molecular weight sulfated polysaccharide will demonstrate as a enormously available alternative natural source of antioxidant for industrial uses. Copyright © 2015 Elsevier B.V. All rights reserved.

Whole blood coagulation assays ROTEM and T-TAS to monitor dabigatran treatment.

PubMed

Taune, Viktor; Wallén, Håkan; Ågren, Anna; Gryfelt, Gunilla; Sjövik, Carolina; Wintler, Anna M; Malmström, Rickard E; Wikman, Agneta; Skeppholm, Mika

2017-05-01

A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery. To evaluate how the viscoelastic point-of-care test Rotational thromboelastometry (ROTEM) and Total Thrombus-formation system (T-TAS), which studies thrombus formation under flowing conditions, correlate with dabigatran concentrations in patients with atrial fibrillation (AF). ROTEM using the reagents In-tem, Ex-tem, Fib-tem or low tissue factor concentration (TF), and T-TAS with the AR-chip (shear rate 600s -1 , representing flow in large arteries) were investigated in whole blood samples. Plasma concentrations were determined by mass spectrometry (LC-MS/MS) at trough and post-dose in 30 patients on dabigatran 150mg BID. Median plasma dabigatran concentrations at trough were 86ng/mL (29-150) and post-dose (2.8h after ingestion) 175ng/mL (67-490). The ROTEM clotting time (CT) correlated strongly with dabigatran concentrations when activated with the reagents Ex-tem (r=0.92, p<0.01) and Fib-tem (r=0.93, p<0.01), while with In-tem and low TF the correlation was weaker (r=0.72 and r=0.36, p<0.01). There were significant but weaker correlations also between dabigatran concentrations and T-TAS variables (r-values 0.39-0.41, p<0.01), aPTT (r=0.70, p<0.01) and PT-INR (r=0.43, p<0.01) respectively. ROTEM Ex-tem and Fib-tem CT shows a strong correlation with dabigatran concentrations in real-life AF-patients, and results are obtained within minutes. This could make ROTEM useful in acute situations. T-TAS detect differences in hemostasis caused by dabigatran, but the relationships to plasma concentrations of dabigatran are weaker than for ROTEM CT with the settings used in this study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial.

PubMed

Treschan, Tanja A; Schaefer, Maximilian S; Geib, Johann; Bahlmann, Astrid; Brezina, Tobias; Werner, Patrick; Golla, Elisabeth; Greinacher, Andreas; Pannen, Benedikt; Kindgen-Milles, Detlef; Kienbaum, Peter; Beiderlinden, Martin

2014-10-25

Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients. Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events. We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI -13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population. This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation. Clinical Trials.gov NCT00798525. Registered 25 November 2008.

Hemostatic variables, plasma lactate concentration, and inflammatory biomarkers in dogs with gastric dilatation-volvulus.

PubMed

Verschoof, J; Moritz, A; Kramer, M; Bauer, N

2015-01-01

Prospective characterization of hemostastatic variables, plasma lactate concentration, and inflammatory biomarkers in dogs with gastric dilatation-volvulus (GDV). Coagulation variables (platelets, prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen, antithrombin [AT], protein C [PC], protein S [PS], D-dimers), plasma lactate concentration and inflammatory biomarkers (C-reactive protein, white blood cell [WBC] count, lymphocyte and neutrophil numbers) were assessed in 20 dogs with GDV presented between 2011 and 2012. Blood was taken preoperatively and at days 1 and 3 postoperatively. The prognostic value of these variables before and after surgery was evaluated as well as the behavior of variables during the study. Overall, 7/20 (35%) dogs did not survive; two dogs (29%) were euthanized during surgery due to severe gastric necrosis and 5 (71%) dogs after surgery due to sepsis and disseminated intravascular coagulopathy. Prior to surgery, median plasma lactate concentration was significantly (p = 0.01) lower in survivors (6.2 mmol/l, range 1.9-9.7 mmol/l) when compared to non-survivors (11.8 mmol/l, range 7.5-16.2 mmol/l). In dogs dying after surgery, significantly higher plasma lactate concentration, coagulation times and D-dimer concentration were present as well as lower fibrinogen concentration and activity of PC and AT compared to survivors. At discharge, activity of AT, PC and PS were markedly below the reference interval in 6/13 (46%), 11/13 (85%), and 8/13 (62%) dogs, respectively. Only lactate plasma concentration was of preoperative prognostic value. After surgery, severe abnormalities of coagulation variables, especially the endogenous anticoagulants were present in most of the dogs. The severity of the abnormalities was associated with survival.

Flux and Passage Enhancement in Hemodialysis by Incorporating Compound Additive into PVDF Polymer Matrix

PubMed Central

Zhang, Qinglei; Lu, Xiaolong; Zhang, Qingzhao; Zhang, Lei; Li, Suoding; Liu, Shaobin

2016-01-01

In this study, Polyvinylidene fluoride (PVDF) hollow fiber hemodialysis membranes were prepared by non-solvent induced phase separation (NIPS) with compound addtive. The compound additive was made with polyvinyl pyrrolidone (PVP) and Poly ethylene glycol (PEG). The results showed that the modified PVDF membrane had better separation performance than virgin PVDF membrane. The UF flux of modified PVDF membrane can reach 684 L·h−1·m−2 and lysozyme (LZM) passage is 72.6% while virgin PVDF membrane is 313 L·h−1·m−2 and 53.2%. At the same time, the biocompatibility of PVDF membranes was also improved. Compared with commercial polysulfone hemodialysis membrane (Fresenius F60S membrane), the modified PVDF membrane had better mechanical and separation performance. The stress and tensile elongation of modified PVDF membrane was 0.94 MPa and 352% while Fresenius F60S membrane was 0.79 MPa and 59%. The LZM passage reached 72.6% while Fresenius F60S membrane was 54.4%. It was proven that the modified PVDF membrane showed better hydrophilicity, antithrombogenicity, less BSA adsorption, and lower hemolytic ratio and adhesion of platelets. Water contact angle and BSA adsorption of the modified PVDF membrane are 38° and 45 mg/m2 while Fresenius F60S membrane are 64° and 235 mg/m2. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of the modified PVDF membrane are 56.5 s and 25.8 s while Fresenius F60S membrane is 35.7 s and 16.6 s. However, further biocompatibility evaluation is needed to obtain a more comprehensive conclusion. PMID:27775566

Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency.

PubMed

Jones, Kareen L; Greenberg, Robert S; Ahn, Edward S; Kudchadkar, Sapna R

2016-01-01

Congenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss. A two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa. Important considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period. A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Flux and Passage Enhancement in Hemodialysis by Incorporating Compound Additive into PVDF Polymer Matrix.

PubMed

Zhang, Qinglei; Lu, Xiaolong; Zhang, Qingzhao; Zhang, Lei; Li, Suoding; Liu, Shaobin

2016-10-19

In this study, Polyvinylidene fluoride (PVDF) hollow fiber hemodialysis membranes were prepared by non-solvent induced phase separation (NIPS) with compound addtive. The compound additive was made with polyvinyl pyrrolidone (PVP) and Poly ethylene glycol (PEG). The results showed that the modified PVDF membrane had better separation performance than virgin PVDF membrane. The UF flux of modified PVDF membrane can reach 684 L·h -1 ·m -2 and lysozyme (LZM) passage is 72.6% while virgin PVDF membrane is 313 L·h -1 ·m -2 and 53.2%. At the same time, the biocompatibility of PVDF membranes was also improved. Compared with commercial polysulfone hemodialysis membrane (Fresenius F60S membrane), the modified PVDF membrane had better mechanical and separation performance. The stress and tensile elongation of modified PVDF membrane was 0.94 MPa and 352% while Fresenius F60S membrane was 0.79 MPa and 59%. The LZM passage reached 72.6% while Fresenius F60S membrane was 54.4%. It was proven that the modified PVDF membrane showed better hydrophilicity, antithrombogenicity, less BSA adsorption, and lower hemolytic ratio and adhesion of platelets. Water contact angle and BSA adsorption of the modified PVDF membrane are 38° and 45 mg/m² while Fresenius F60S membrane are 64° and 235 mg/m². Prothrombin time (PT) and activated partial thromboplastin time (APTT) of the modified PVDF membrane are 56.5 s and 25.8 s while Fresenius F60S membrane is 35.7 s and 16.6 s. However, further biocompatibility evaluation is needed to obtain a more comprehensive conclusion.

Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis

PubMed Central

Muders, Thomas; Theuerkauf, Nils; Spitzhüttl, Juliane; Schellhaas, Torsten; Schewe, Jens-Christian; Guenther, Ulf; Wrigge, Hermann; Putensen, Christian

2017-01-01

Background Despite being still invasive and challenging, technical improvement has resulted in broader and more frequent application of extracorporeal membrane oxygenation (ECMO), to prevent hypoxemia and to reduce invasiveness of mechanical ventilation (MV). Heparin-coated ECMO-circuits are currently standard of care, in addition to heparin based anticoagulation (AC) regimen guided by activated clotting time (ACT) or activated partial thromboplastin time (aPTT). Despite these advances, a reliable prediction of hemorrhage is difficult and the risk of hemorrhagic complication remains unfortunately high. We hypothesized, that there are coagulation parameters that are indices for a higher risk of hemorrhage under veno-venous (VV)-ECMO therapy. Methods Data from 36 patients with severe respiratory failure treated with VV-ECMO at a University Hospital intensive care unit (ICU) were analyzed retrospectively. Patients were separated into two groups based on severity of hemorrhagic complications and transfusion requirements. The following data were collected: demographics, hemodynamic data, coagulation samples, transfusion requirements, change of ECMO-circuit during treatment and adverse effects, including hemorrhage and thrombosis. Results In this study 74 hemorrhagic events were observed, one third of which were severe. Patients suffering from severe hemorrhage had a lower survival rate on VV-ECMO (43% vs. 91%; P=0.002) and in ICU (36% vs. 86%; P=0.002). SAPS II, factor VII and X were different between mild and severe hemorrhage group. Conclusions Severe hemorrhage under VV-ECMO is associated with higher mortality. Only factor VII and X differed between groups. Further clinical studies are required to determine the timing of initiation and targets for AC therapies during VV-ECMO. PMID:29312706

Metabolic aspects and viability of heparin/CPDA-1-stored red cell concentrate as a by-product of a high-yield factor VIII production method.

PubMed

de Jonge, J; Smit Sibinga, C T; Das, P C

1983-01-01

As a by-product of a new high-yield method of production of freeze-dried factor VIII, red cell concentrate (RCC) containing a small amount of heparin besides CPDA-1 was studied. Compared to CPDA-1 stored RCC no difference was found in hematology parameters and 2,3-DPG levels during 28 days storage. Although still in the normal range for transfusion, ATP levels were significantly lower compared to CPDA-1-stored RCC after 30 days shelf life. A survival study with 51Cr-labelled red cells showed good recovery and normal red cell half-life. Rapid transfusion of heparin/CPDA-1 RCC in 6 volunteers did not have any effect on aPTT. Heparin could not be detected in posttransfusion plasma samples.

Inhibition of B16-BL6 melanoma lung colonies by semisynthetic sulfaminoheparosan sulfates from E. coli K5 polysaccharide.

PubMed

Poggi, Andreina; Rossi, Cosmo; Casella, Nicola; Bruno, Cristiana; Sturiale, Luisella; Dossi, Carla; Naggi, Annamaria

2002-08-01

Heparin (H), heparan sulfate (HS), and related glycosaminoglycans can inhibit cancer cell invasion, possibly due to their ability to interact with vascular growth factors, adhesion molecules, endoglycosidases, and signaling proteins, in addition to the well-known effects on the clotting system. We evaluated the antitumor activity of a series of semisynthetic sulfaminoheparosan sulfates (SAHSs) with different degree and distribution of sulfates, obtained by chemical modifications of the E. coli K5 polysaccharide, namely type A, B, and C compounds. B16-BL6 melanoma cells (10 5 cells/mouse) were injected intravenously (i.v.) in a lateral tail vein of C57BL6 mice at a dose of 0.5 mg/ mouse together with test compounds. Tumor lung nodules were significantly reduced as compared with controls only by H (95.5 +/- 1.0% inhibition), SAHS-2 (84.2 +/- 5.0% inhibition), and SAHS-4 (91.1 +/- 4.2% inhibition), among compounds tested. SAHS-2 and SAHS-4 are type B compounds, with a sulfate/carboxylate ratio similar to that of H. A typical mammalian HS showed only 54.8% inhibition. Supersulfated low-molecular-weight heparin and heparan sulfate (ssLMWH and ssLMWHS) showed an activity similar to that of unfractionated compounds. H and SAHS-4 inhibited dose dependently B16-BL6 lung colonies, with IC-50 values of 0.05 and 0.1 mg/mouse, respectively. The relationship with ex vivo anticoagulant potency was evaluated by activated partial thromboplastin time (aPTT) on mouse plasma at different time intervals after i.v. injection (0.1 to 0.5 mg/mouse) of the compound. H showed a dose-dependent anticoagulant activity lasting up to 2 hours, whereas SAHS-4 showed a potent anticoagulant effect only at a dose of 0.5 mg/mouse. Accordingly, H but not SAHS-4 consistently inhibited B16-BL6 lung colonies when given 1 hour before tumor cells. SAHS-4 derivatives, with different size and/or affinity depleted of AT binding sites, showed an inhibitory effect on B16-BL6 melanoma similar to that of SAHS-4, suggesting that the greater antitumor effect of H was not due to AT-mediated inhibition of blood clotting. Interactions with other blood inhibitors, such as heparin cofactor II or tissue factor pathway inhibitory protein cannot be ruled out. The better effect of H may be due to persistence in the circulation and/or ability to inhibit tumor neoangiogenesis.

[Clinical use of virally inactived plasma. The experience of Blood Transfusion Unit in Mantova, Italy].

PubMed

Lepri, Debora; Capuzzo, Enrico; Mattioli, Anna Vittoria; Dall'Oglio, Daniela; Sgarioto, Vincenzo; Terenziani, Isabella; Caramaschi, Giacomo; Manzato, Franco; Franchini, Massimo

2013-03-01

Fresh Frozen Plasma (FFP) is a blood component whose clinical use is widespread worldwide. Transfusion safety of this product is ensured by legally obligatory tests. Although these tests are carried out on each plasma donation, safety levels can be further improved by using some technical procedures, such as, among others, methylene blue (MB) and solvent-detergent (SD) viral inactivation methods. The DMTE (Blood Transfusion Unit) in Mantova has used the pharmaceutical-like SD virally inactivated plasma since 2007 (Plasmasafe, Kedrion) as replacement of the PFC by each single donor. Guidelines for the usage of both products are the same. With the main aim of assessing the therapeutic effectiveness and safety of Plasmasafe, we decided to clinically monitor transfusions performed with this product on patients of the Intensive Care Unit at the city hospital in Mantova. In addition, we controlled some coagulation parameters (PT, aPTT, ATIII, Fibrinogen, PC, PS, FV, FVII, FVIII) before and 24 hours after the Plasmasafe infusion. From a clinical point of view, the use of Plasmasafe always led to a significant reduction, or complete stop, of the bleeding. No transfusion-related adverse events were recorded. As regards, the most relevant laboratory results, a marked increase in the above mentioned hemostatic parameters was detected. Furthermore, patients transfused with this product received a mean volume significantly lower than an historical cohort of patients treated with FFP (503 mL with Plasmasafe versus 1549 mL with FFP, P<0.001). The results of our study clearly document that Plasmasafe, a virally inactivated pharmaceutical-like product with a standardized content of coagulation factors, is a safe and cost-effective treatment, able to rapidly correct hemostatic abnormalities, for critical patients.

Combination treatment with Gua Sha and Blood-letting causes attenuation of systemic inflammation, activated coagulation, tissue ischemia and injury during heatstroke in rats.

PubMed

Tu, Wen-zhan; Cheng, Rui-dong; Hu, Jie; Wang, Jie-zhi; Lin, Hai-yan; Zou, En-miao; Wang, Wan-sheng; Lou, Xin-fa; Jiang, Song-he

2015-08-01

Gua Sha and Blood-letting at the acupoints were Chinese traditional therapies for heatstroke. The purpose of present study was to assess the therapeutic effect of Gua Sha on the DU Meridian and Bladder Meridian combined with Blood-letting acupoints at Shixuan (EX-UE 11) and Weizhong (BL 40) on heatstroke. Anesthetized rats, immediately after the onset of heatstroke, were divided into four major groups: Gua Sha group, Blood-letting group, Gua Sha combined with Blood-letting group and model group. They were exposed to ambient temperature of 43 °C to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normal control group. Their survival times were measured. In addition, their physiological and biochemical parameters were continuously monitored. When rats underwent heatstroke, their survival time values were found to be 21-25 min. Treatment of Gua Sha combined with Bloodletting greatly improved the survival time (230±22 min) during heatstroke. All heatstoke animals displayed and activated coagulation evidenced by increased prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, and decreased platelet count, protein C. Furthermore, the animals displayed systemic inflammation evidenced by increased the serum levels of cytokines interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α) and malondialdehyde (MDA). Biochemical markers evidenced by cellular ischemia and injury/dysfunction included increased plasma levels of blood urea nitrogen (BUN), creatinine, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP) were all elevated during heatstroke. Core temperatures (Tco) were also increased during heatstroke. In contrast, the values of mean arterial pressure were signifificantly lower during heatstroke. These heatstroke reactions were all signifificantly suppressed by treatment of Gua Sha and Blood-letting, especially the combination therapy. Gua Sha combined with Blood-letting after heatstroke may improve survival by ameliorating systemic inflflammation, hypercoagulable state, and tissue ischemia and injury in multiple organs.

Tailoring treatment of haemophilia B: accounting for the distribution and clearance of standard and extended half-life FIX concentrates.

PubMed

Iorio, Alfonso; Fischer, Kathelijn; Blanchette, Victor; Rangarajan, Savita; Young, Guy; Morfini, Massimo

2017-06-02

The prophylactic administration of factor IX (FIX) is considered the most effective treatment for haemophilia B. The inter-individual variability and complexity of the pharmacokinetics (PK) of FIX, and the rarity of the disease have hampered identification of an optimal treatment regimens. The recent introduction of extended half-life recombinant FIX molecules (EHL-rFIX), has prompted a thorough reassessment of the clinical efficacy, PK and pharmacodynamics of plasma-derived and recombinant FIX. First, using longer sampling times and multi-compartmental PK models has led to more precise (and favourable) PK for FIX than was appreciated in the past. Second, investigating the distribution of FIX in the body beyond the vascular space (which is implied by its complex kinetics) has opened a new research field on the role for extravascular FIX. Third, measuring plasma levels of EHL-rFIX has shown that different aPTT reagents have different accuracy in measuring different FIX molecules. How will this new knowledge reflect on clinical practice? Clinical decision making in haemophilia B requires some caution and expertise. First, comparisons between different FIX molecules must be assessed taking into consideration the comparability of the populations studied and the PK models used. Second, individual PK estimates must rely on multi-compartmental models, and would benefit from adopting a population PK approach. Optimal sampling times need to be adapted to the prolonged half-life of the new EHL FIX products. Finally, costs considerations may apply, which is beyond the scope of this manuscript but might be deeply connected with the PK considerations discussed in this communication.

Plasma markers of inflammation and hemostatic and endothelial activity in naturally overweight and obese dogs.

PubMed

Barić Rafaj, R; Kuleš, J; Marinculić, A; Tvarijonaviciute, A; Ceron, J; Mihaljević, Ž; Tumpa, A; Mrljak, V

2017-01-06

Obesity is one of the most prevalent health problems in the canine population. While haemostatic parameters and markers of endothelial function have been evaluated in various disease conditions in dogs, there are no studies of these markers in canine obesity. This study was designed to evaluate the effect of naturally gained weight excess and obesity on inflammatory, hemostatic and endothelial biomarkers in dogs. A total of 37 overweight and obese dogs were compared with 28 normal weight dogs. Overweight and obese dogs had significantly elevated concentrations of serum interleukin-6 (IL-6) and C-reactive protein (hsCRP). Number of platelets, activity of factor X and factor VII were significantly higher, while activated partial thromboplastine time (aPTT) and soluble plasminogen activator receptor (suPAR) were significantly decreased. Statistical analysis of high mobility group box - 1 protein (HMGB-1), soluble intercellular adhesive molecule -1 (sICAM-1) and plasminogen activator inhibitor type 1 (PAI-1) concentrations did not show significant differences between the total overweight and obese group and the normal weight group of dogs. Analytical changes in the dogs in our study reflects that weight excess in dogs can be associated with a chronic low degree of inflammation and a hypercoagulable state, where primary and secondary hemostasis are both affected. However obesity is not associated with impairment of endothelial function in dogs.

Assessment of penetration potential of pH responsive double walled biodegradable nanogels coated with eucalyptus oil for the controlled delivery of 5-fluorouracil: In vitro and ex vivo studies.

PubMed

Sahu, Prashant; Kashaw, Sushil K; Jain, Sanyog; Sau, Samaresh; Iyer, Arun K

2017-05-10

Penetration enhancers coated biodegradable polymeric nanogels loaded with cytotoxic drugs applied via the topical route, can be a promising strategy for improving the chemotherapeutic efficiency of skin cancers. The major objective of proposed research was to investigate the in vitro and ex vivo chemotherapeutic potential of double walled PLGA-chitosan biodegradable nanogel entrapped with 5-fluororuacil (5-FU) coated with eucalyptus oil, topically applied onto the skin. 5-FU was first entrapped in PLGA core by solvent evaporation technique followed by coating with cationic chitosan for ionic interaction with anionic skin cancer cell membrane. A surface coating of eucalyptus oil (1%) was employed to improve the penetration efficacy of the nanogel into stratum corneum. The surface modified biodegradable double walled nanogel was characterized for particle size, charge and thermal properties followed by pH dependent in vitro analysis. Human keratinocyte (HaCaT) cell line was employed for the bio- and cyto-compatibility testing prior to the hemolysis assay and coagulation assessment. A porcine skin ex vivo screening was performed for assessing the penetration potential of the nanogels. DLS and TEM revealed a particle size about 170nm for the double walled nanogels. The nanogels also exhibited high thermal stability as analyzed by thermogravimetry (TG) and differential thermal analysis (DTA). The drug entrapment efficacy was about ~40%. The drug release showed sustained release pattern noted up to 24h. The low hemolysis of 2.39% with short prothrombin time (PT) and activated partial thromboplastin time (APTT) of 14.2 and 35.5s respectively, revealed high biocompatibility of the nanogels. The cellular uptake and localization was assessed by confocal microscopy. The cytotoxicity (MTT assay) on HaCaT cell line demonstrated high cytocompatibilty of the nanogels. An ex vivo evaluation using porcine skin displayed efficient and steady state flux of 5-FU from the biodegradable nanogles into the skin, while the histology of the porcine skin revealed enhanced penetration potential of eucalyptus oil coated PLGA-chitosan double walled nanogels. Taken together the in vivo and ex vivo results portend promising potential for the utility of the biodegradable nanogels for treating skin cancers. Copyright © 2017. Published by Elsevier B.V.

Apixaban Inhibits Cerebral Microembolic Signals Derived from Carotid Arterial Thrombosis in Rabbits.

PubMed

Zhou, Xueping; Wu, Weizhen; Chu, Lin; Gutstein, David E; Seiffert, Dietmar; Wang, Xinkang

2016-09-01

Cerebral microembolic signal (MES) is an independent predictor of stroke risk and prognosis. The objective of this study is to assess the effects of apixaban, as a representative of the novel oral anticoagulant class, on a rabbit model of cerebral MES. A clinical transcranial Doppler ultrasound instrument was used to assess MESs in the middle cerebral artery in a 30% FeCl3-induced carotid arterial thrombosis model in male New Zealand White rabbits. Ascending doses of apixaban were evaluated as monotherapy and in combination with aspirin on both arterial thrombosis and MES. Pharmacokinetic and pharmacodynamic responses were also evaluated. The effective dose for 50% inhibition (ED50) of thrombus formation for monotherapy was 0.04 mg/kg per hour apixaban, i.v. (0.03 μM plasma exposure) for the integrated blood flow, 0.13 mg/kg per hour apixaban (0.10 μM plasma exposure) for thrombus weight, and 0.03 mg/kg per hour apixaban (0.02 μM plasma exposure) for MES. Dual treatment with aspirin (5 mg/kg, PO) and apixaban (0.015 mg/kg per hour, i.v.) resulted in a significant reduction in cerebral MES (P < 0.05) compared with monotherapy with either agent. Pharmacokinetic analysis of apixaban and pharmacodynamic assays using activated partial thromboplastin time (aPTT) and prothrombin time (PT) for apixaban- and arachidonic acid-induced platelet aggregation for aspirin were used to confirm the exposure-response relationships. In summary, our study demonstrates that apixaban in a concentration-dependent manner inhibits both arterial thrombosis and MES, suggesting a potential association between factor Xa (FXa) blockade and the reduction in MES in patients at risk of ischemic stroke. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Catechol chemistry inspired approach to construct self-cross-linked polymer nanolayers as versatile biointerfaces.

PubMed

Liu, Xinyue; Deng, Jie; Ma, Lang; Cheng, Chong; Nie, Chuanxiong; He, Chao; Zhao, Changsheng

2014-12-16

In this study, we proposed a catechol chemistry inspired approach to construct surface self-cross-linked polymer nanolayers for the design of versatile biointerfaces. Several representative biofunctional polymers, P(SS-co-AA), P(SBMA-co-AA), P(EGMA-co-AA), P(VP-co-AA), and P(MTAC-co-AA), were first synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and then the catecholic molecules (dopamine, DA) were conjugated to the acrylic acid (AA) units by the facile carbodiimide chemistry. Then, the catechol (Cat) group conjugated biofunctional polymers, named PSS-Cat, PSBMA-Cat, PEGMA-Cat, PVP-Cat, and PMTAC-Cat, were applied for the construction of self-cross-linked nanolayers on polymeric substrates via the pH induced catechol cross-linking and immobilization. The XPS spectra, surface morphology, and wettability gave robust evidence that the catechol conjugated polymers were successfully coated, and the coated substrates possessed increased surface roughness and hydrophilicity. Furthermore, the systematic in vitro investigation of protein adsorption, platelet adhesion, activated partial thromboplastin time (APTT), thrombin time (TT), cell viability, and antibacterial ability confirmed that the coated nanolayers conferred the substrates with versatile biological performances. The PSS-Cat coated substrate had low blood component activation and excellent anticoagulant activity; while the PEGMA-Cat and PSBMA-Cat showed ideal resistance to protein fouling and inhibition of platelet activation. The PSS-Cat and PVP-Cat coated substrates exhibited promoted endothelial cell proliferation and viability. The PMTAC-Cat coated substrate showed an outstanding activity on bacterial inhibition. In conclusion, the catechol chemistry inspired approach allows the self-cross-linked nanolayers to be easily immobilized on polymeric substrates with the stable conformation and multiple biofunctionalities. It is expected that this low-cost and facile bioinspired coating system will present great potential in creating novel and versatile biointerfaces.

Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.

PubMed

Li, Junhui; Li, Shan; Yan, Lufeng; Ding, Tian; Linhardt, Robert J; Yu, Yanlei; Liu, Xinyue; Liu, Donghong; Ye, Xingqian; Chen, Shiguo

2017-10-20

Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs. In vitro activities were measured by activated partial thromboplastin time (APTT), thrombin time (TT), thrombin and factor Xa inhibition, and activation of FXII. The results showed that free radicals preferentially acted on GlcA residues affording oligosaccharides that were purified from both fCSs. The inhibition of thrombin and factor X activities, mediated through antithrombin III and heparin cofactor II of fCSs oligosaccharides were affected by their molecular weight and fucose branches. Oligosaccharides with different sulfation patterns of the fucose branching had a similar ability to inhibit the FXa by the intrinsic factor Xase (factor IXa-VIIIa complex). Oligosaccharides with 2,4-O-sulfo fucose branches from fCS-Ib showed higher activities than ones with 3,4-O-disulfo branches obtained from fCS-Pg. Furthermore, a heptasaccharide is the minimum size oligosaccharide required for anticoagulation and FXII activation. This activity was absent for fCS oligosaccharides smaller than nonasaccharides. Molecular size and fucose branch sulfation are important for anticoagulant activity and reduction of size can reverse the activation of FXII caused by native fCSs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Heparin-mimicking multilayer coating on polymeric membrane via LbL assembly of cyclodextrin-based supramolecules.

PubMed

Deng, Jie; Liu, Xinyue; Ma, Lang; Cheng, Chong; Shi, Wenbin; Nie, Chuanxiong; Zhao, Changsheng

2014-12-10

In this study, multifunctional and heparin-mimicking star-shaped supramolecules-deposited 3D porous multilayer films with improved biocompatibility were fabricated via a layer-by-layer (LbL) self-assembly method on polymeric membrane substrates. Star-shaped heparin-mimicking polyanions (including poly(styrenesulfonate-co-sodium acrylate; Star-PSS-AANa) and poly(styrenesulfonate-co-poly(ethylene glycol)methyl ether methacrylate; Star-PSS-EGMA)) and polycations (poly(methyl chloride-quaternized 2-(dimethylamino)ethyl methacrylate; Star-PMeDMA) were first synthesized by atom transfer radical polymerization (ATRP) from β-cyclodextrin (β-CD) based cores. Then assembly of 3D porous multilayers onto polymeric membrane surfaces was carried out by alternating deposition of the polyanions and polycations via electrostatic interaction. The surface morphology and composition, water contact angle, blood activation, and thrombotic potential as well as cell viability for the coated heparin-mimicking films were systematically investigated. The results of surface ATR-FTIR spectra and XPS spectra verified successful deposition of the star-shaped supramolecules onto the biomedical membrane surfaces; scanning electron microscopy (SEM) and atomic force microscopy (AFM) observations revealed that the modified substrate had 3D porous surface morphology, which might have a great biological influence on the biointerface. Furthermore, systematic in vitro investigation of protein adsorption, platelet adhesion, human platelet factor 4 (PF4, indicates platelet activation), activate partial thromboplastin time (APTT), thrombin time (TT), coagulation activation (thrombin-antithrombin III complex (TAT, indicates blood coagulant)), and blood-related complement activation (C3a and C5a, indicates inflammation potential) confirmed that the heparin-mimicking multilayer coated membranes exhibited ultralow blood component activations and excellent hemocompatibility. Meanwhile, after surface coating, endothelial cell viability was also promoted, which indicated that the heparin-mimicking multilayer coating might extend the application fields of polymeric membranes in biomedical fields.

Coagulation profile, haematological and biochemical changes in kids naturally infected with peste des petits ruminants.

PubMed

Sahinduran, Sima; Albay, Metin Koray; Sezer, Kenan; Ozmen, Ozlem; Mamak, Nuri; Haligur, Mehmet; Karakurum, Cagri; Yildiz, Ramazan

2012-03-01

The aim of this study was to examine the coagulation profile in peste des petits ruminant (PPR) in kids. Five kids from a group of 150 animals (72 goats and 78 kids) were brought to the Veterinary Medical Teaching Hospital from a farm in Burdur province (Turkey) with nasal and ocular discharges and diarrhea. Fifteen goats and 41 kids had died due to diarrhea and three kids were presented to the Department of Pathology for diagnosis. Blood samples were taken from 12 ill animals (infected group) for haematological and biochemical analysis. In addition, five healthy kids were examined from another healthy flock (control group). Leukocyte and lymphocyte numbers of infected group showed significant declinations in comparison to control group (≤0.001). Haemorrhages in all organs of digestive system and small haemorrhagic areas in liver were caused to decrease in erythrocyte and haematocrit values (p ≤ 0.001) in infected group. Concentrations of blood urea nitrogen (BUN) (p ≤ 0.01) and creatinine (p ≤ 0.001) in infected group were significantly higher than control group. Compared to control group, significant increases were determined in serum concentrations of alkaline phosphatase (ALP) (p ≤ 0.01), aspartate aminotransferase (AST) (p ≤ 0.001) and alanine aminotransferase (ALT) (p ≤ 0.001) in the infected group. No significant differences were observed between the infected and control groups for serum gamma glutamyl-transferase (GGT) concentration value. In our study, thrombocytopenia (p ≤ 0.001) together with prolonged activated partial thromboplastin time (APTT; p ≤ 0.01) and prothrombin time (PT; p ≤ 0.001) may show that disseminated intravascular coagulopathy which can occur in kids with PPR.

Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model.

PubMed

Grottke, Oliver; van Ryn, Joanne; Spronk, Henri M H; Rossaint, Rolf

2014-02-05

New oral anticoagulants are effective alternatives to warfarin. However, no specific reversal agents are available for life-threatening bleeding or emergency surgery. Using a porcine model of trauma, this study assessed the ability of prothrombin complex concentrate (PCC), activated PCC (aPCC), recombinant FVIIa (rFVIIa) and a specific antidote to dabigatran (aDabi-Fab) to reverse the anticoagulant effects of dabigatran. Dabigatran etexilate (DE) was given orally for 3 days (30 mg/kg bid) and intravenously on day 4 to achieve consistent, supratherapeutic concentrations of dabigatran. Blood samples were collected at baseline, after oral DE, after intravenous dabigatran, and 60 minutes post-injury. PCC (30 and 60 U/kg), aPCC (30 and 60 U/kg), rFVIIa (90 and 180 μg/kg) and antidote (60 and 120 mg/kg) were added to blood samples ex-vivo. Coagulation was assessed by thromboelastometry, global coagulation assays and diluted thrombin time. Plasma concentrations of dabigatran were 380 ± 106 ng/ml and 1423 ± 432 ng/ml after oral and intravenous administration, respectively, and all coagulation parameters were affected by dabigatran. Both PCCs and aDabi-Fab, but not rFVIIa, reversed the effects of dabigatran on thromboelastometry parameters and prothrombin time. In contrast, aPTT was only normalised by aDabi-Fab. Plasma concentration (activity) of dabigatran remained elevated after PCC and rFVIIa therapy, but was not measureable after aDabi-Fab. In conclusion, PCC and aPCC were effective in reducing the anticoagulant effects of dabigatran under different conditions, while aDabi-Fab fully corrected all coagulation measures and decreased the plasma concentration of dabigatran below the limit of detection. No significant effects were observed with rFVIIa.

Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding.

PubMed

Cai, Tian-Quan; Wu, Weizhen; Shin, Myung K; Xu, Yiming; Jochnowitz, Nina; Zhou, Yuchen; Hoos, Lizbeth; Bentley, Ross; Strapps, Walter; Thankappan, Anil; Metzger, Joseph M; Ogletree, Martin L; Tadin-Strapps, Marija; Seiffert, Dietmar A; Chen, Zhu

2015-12-01

This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ellagic acid-triggered thrombin generation assay (TGA) exhibited anticoagulant changes. In contrast, ex-vivo PT or high tissue factor-triggered TGA was indistinguishable from control. Rats receiving single doses (0, 0.01, 0.03, 0.1, 0.3, 1 mg/kg) of FXII siRNA exhibited dose-dependent knockdown in liver FXII mRNA and plasma FXII protein (95 and 99%, respectively, at 1 mg/kg) at day 7 post dosing. FXII knockdown was associated with dose-dependent thromboprotection (maximal efficacy achieved with 1 mg/kg in both models) and negligible change in cuticle bleeding times. Ex-vivo TGA triggered with low-level (0.5 μmol/l) ellagic acid tracked best with the knockdown levels and efficacy. Our findings confirm and extend literature reports of an attractive benefit-to-risk profile of targeting FXII for antithrombotic therapies. Titrating of FXII is instructive for its pharmacological inhibition. The knockout rat is valuable for evaluating both mechanism-based safety concerns and off-target effects of FXII(a) inhibitors. Detailed TGA analyses will inform on optimal trigger conditions in studying pharmacodynamic effects of FXII(a) inhibition.

An instructive case of presumed brown snake (Pseudonaja spp.) envenoming.

PubMed

Ou, Judy; Haiart, Sebastien; Galluccio, Steven; White, Julian; Weinstein, Scott A

2015-01-01

Several species of medically important Australian elapid snakes are frequently involved in human envenoming. The brown snake group (Pseudonaja spp., 9 species) is most commonly responsible for envenoming including life-threatening or fatal cases. Several Pseudonaja spp. can inflict human envenoming that features minor local effects, but may cause serious systemic venom disease including defibrination coagulopathy, thrombocytopenia, micro-angiopathic hemolytic anemia (MAHA) and, rarely, paralysis. Pseudonaja envenoming is typically diagnosed by history, clinical assessment including occasional active clinical bleeding noted on physical examination (e.g. from venipuncture sites, recent cuts, etc.), and laboratory detection of coagulopathy (prolonged activated partial thromboplastin time [APTT]/INR, elevated D-dimer, afibrinogenemia and thrombocytopenia). Lack of verified identity of the envenoming snake species is a common problem in Australia and elsewhere. Identification and confirmation of the envenoming Australian snake taxon is often attempted with enzyme sandwich immunoassay venom detection kits (SVDKs). However, the SVDK has limited utility due to unreliable specificity and sensitivity when used to detect venoms of some Australian elapids. Antivenom (AV) remains the cornerstone of treatment, although there is debate concerning the recommended dose (1 vs. 2 or more vials) necessary to treat serious Pseudonaja envenoming. Envenomed patients receiving timely treatment uncommonly succumb, but a proportion of seriously envenomed patients may exhibit clinical or laboratory evidence of myocardial insult. An 88-year-old woman presented her dog to a veterinarian after it had sustained a bite by a witnessed snake, reportedly an eastern brown snake (Pseudonaja textilis, Elapidae). The woman became suddenly confused, and lost consciousness at the veterinary office. After transport to hospital, she denied any contact with the snake, but developed large haematomas at intravenous (i.v.) catheter insertion sites; blood tests revealed a severe defibrination coagulopathy, consistent with envenoming by a brown snake. An SVDK-tested urine sample was negative. A non-contrast CT of her head showed a minor subacute infarction of the left corona radiata. A twelve-lead ECG was normal, but her troponins were mildly elevated (39 ng/L). A diagnosis of brown snake envenoming was made and she received 2 vials of brown snake AV i.v., without adverse incident. Thirty min post AV her Glasgow Coma Score (GCS) had improved from 13 to 15 (normal). At 3.5 h post AV all bleeding from i.v. sites ceased, although her troponin T level peaked at 639 ng/L, supporting a diagnosis of non-ST elevated myocardial infarction (NSTEMI). Severe brown snake envenoming may occur in the absence of a perceived bite, and AV is temporally associated with improvement in clinical findings and coagulopathy. However, severe envenoming by this species can be complicated by cardiovascular events that in the circumstance of incomplete or absent history may confuse the primary diagnosis and affect patient outcome.

A randomized comparative crossover study to assess the affect on circuit life of varying pre-dilution volume associated with CVVH and CVVHDF.

PubMed

Davies, H T; Leslie, G; Pereira, S M; Webb, S A R

2008-03-01

To determine if circuit life is influenced by a higher pre-dilution volume used in CVVH when compared with a lower pre-dilution volume approach in CVVHDF. A comparative crossover study. Cases were randomized to receive either CVVH or CVVHDF followed by the alternative treatment. All patients >or= 18 yrs of age who required CRRT while in ICU were eligible to participate, but excluded if coagulopathic, thrombocytopenic or unable to receive heparin. Based on an intention-to-treat, 45 patients were randomized to receive either CVVH or CVVHDF followed by the alternative treatment. A 24-bed, tertiary, medical and surgical adult intensive care unit (ICU). Blood flow rate, vascular access device and insertion site, hemofilter, anticoagulation and machine hardware were standardized. An ultrafiltrate dose of 35 ml/ kg/h delivered pre-filter was used for CVVH. A fixed pre-dilution volume of 600 mls/h with a dialysate dose of 1 L was used for CVVHDF. Thirty-one patients received CVVH or CVVHDF out of 45 participants followed by the alternative technique. There was a significant increase in circuit life in favor of CVVHDF (median=16 h 5 min, range=40 h 23 min) compared with CVVH (median=6 h 35 min, range=30 h 45 min). A Mann-Whitney U test was performed to compare circuit life between the two different CRRT modes (Z=-3.478, p<0.001). Measurements of circuit life on the 93 circuits which survived to clotting (50 CVVH and 43 CVVHDF) were log transformed prior to under taking a standard multiple regression analysis. None of the independent variables - activated prothrombin time (aPTT), platelet count, heparin dose, patient hematocrit or urea - had a coefficient partial correlation >0.09 (coefficient of the determination=0.117) or a linear relationship which could be associated with circuit life (p=0.228). Pre-diluted CVVHDF appeared to have a longer circuit life when compared to high volume pre-diluted CVVH. The choice of CRRT mode may be an important independent determinant of circuit life.

pH-responsive thiolated chitosan nanoparticles for oral low-molecular weight heparin delivery: in vitro and in vivo evaluation.

PubMed

Fan, Bo; Xing, Yang; Zheng, Ying; Sun, Chuan; Liang, Guixian

2016-01-01

The aim of present study was to investigate a pH-responsive and mucoadhesive nanoparticle system for oral bioavailability enhancement of low-molecular weight heparin (LMWH). The thioglycolic acid (TGA) was first covalently attached to chitosan (CS) with 396.97 ± 54.54 μmol thiol groups per gram of polymer and then the nanoparticles were prepared with thiolated chitosan (TCS) and pH-sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) by ionic cross-linking method. The obtained nanoparticles were characterized for the shape, particle size, zeta potential, drug entrapment efficiency and loading capacity. In vitro results revealed the acid stability of pH-responsive nanoparticles, which had a significant control over LMWH release and could effectively protect entrapped drugs in simulated gastric conditions. By the attachment of the thiol ligand, an improvement of permeation-enhancing effect on freshly excised carp intestine (1.86-fold improvement) could be found. The mucoadhesive properties were evaluated using fluorescently labeled TCS or CS nanoparticles. As compared with the controls, a significant improvement of mucoadhesion on rat intestinal mucosa was observed in TCS/HPMCP nanoparticles via confocal laser scanning microscopy. The activated partial thromboplastin time (APTT) was significantly prolonged and an increase in the oral bioavailability of LMWH was turned out to be pronounced after oral delivered LMWH-loaded TCS/HPMCP nanoparticles in rats, which suggested enhanced anticoagulant effects and improved absorption of LMWH. In conclusion, pH-responsive TCS/HPMCP nanoparticles hold promise for oral delivery of LMWH.

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

PubMed

Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

2015-01-01

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

Versatile and Rapid Postfunctionalization from Cyclodextrin Modified Host Polymeric Membrane Substrate.

PubMed

Deng, Jie; Liu, Xinyue; Zhang, Shuqing; Cheng, Chong; Nie, Chuanxiong; Zhao, Changsheng

2015-09-08

Surface modification has long been of great interest to impart desired functionalities to the bioimplants. However, due to the limitations of recent technologies in surface modification, it is highly desirable to explore novel protocols, which can advantageously and efficiently endow the inert material surfaces with versatile biofunctionalities. Herein, to achieve versatile and rapid postfunctionalization of polymeric membrane, we demonstrate a new strategy for the fabrication of β-cyclodextrin (β-CD) modified host membrane substrate that can recognize a series of well-designed guest macromolecules. The surface assembly procedure was driven by the host-guest interaction between adamantane (Ad) and β-CD. β-CD immobilized host membrane was fabricated via two steps: (1) epoxy groups enriched poly(ether sulfone) (PES) membrane was first prepared via in situ cross-linking polymerization and subsequently phase separation; (2) mono-6-deoxy-6-ethylenediamine-β-CD (EDA-β-CD) was then anchored onto the surface of the epoxy functionalized PES membrane to obtain PES-CD. Subsequently, three types of Ad-terminated polymers, including Ad-poly(styrenesulfonate-co-sodium acrylate) (Ad-PSA), Ad-methoxypoly(ethylene glycol) (Ad-PEG), and Ad-poly(methyl chloride-quaternized 2-(dimethylamino)ethyl methacrylate (Ad-PMT), were separately assembled onto the β-CD immobilized surfaces to endow the membranes with anticoagulant, antifouling, and antibacterial capability, respectively. Activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) measurements were carried out to explore the anticoagulant activity. The antifouling capability was evaluated via protein adsorption and platelet adhesion measurements. Moreover, Staphyllococcous aureus (S. aureus) was selected as model bacteria to evaluate the antibacterial ability of the functionalized membranes. The results indicated that well-regulated blood compatibility, antifouling capability, and bactericidal activity could be achieved by the proposed rapid postfunctionalization on polymeric membranes. This approach of versatile and rapid postfunctionalization is promising for the preparation of multifunctional polymeric membrane materials to meet with various demands for the further applications.

Comparative studies of pharmacokinetics and anticoagulatory effect in rats after oral administration of Frankincense and its processed products.

PubMed

Pan, Ying-Ni; Liang, Xiao-Xu; Niu, Li-Ying; Wang, Yan-Nian; Tong, Xin; Hua, Hui-Ming; Zheng, Jiang; Meng, Dong-Ya; Liu, Xiao-Qiu

2015-08-22

Frankincense (FRA), Ruxiang, is the resin of Boswellia carterii Birdw and Boswellia bhaw-dajiana Birdw which has been used for centuries as formulas to improve the circulation and to relieve pain against carbuncles. Stir-fried Frankincense (SFF) and vinegar processed Frankincense (VPF) are two major processed Frankincense, and the processing procedures reportedly enhance the curative efficacy or reduce the side effects of FRA. This paper describes the comparisons in plasma pharmacokinetic behaviors of 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA) in FRA and its processed products, and their effects on coagulation factors and blood clotting tetrachoric, using an acute cold blood-stasis animal model after oral administration of FRA, SFF, and VPF. For pharmacokinetic study, Sprague-Dawley (SD) rats were randomly divided into three groups, including group FRA, group SFF and group VPF. And the plasma samples were analyzed by HPLC. For study of anticoagulatory effect, SD rats were randomly divided into six groups, including control, acute cold blood-stasis model, Fu-fang-dan-shen tablet- (0.75g/kg), FRA-, SFF-, and VPF-treated (2.7g/kg) groups, respectively. The serum contents of thrombin-antithrombin complex (TAT), D-dimer (D-D), and prostacyclin (PGI2) of each group were measured by ELISA. The values of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were also assessed by hematology analyzer. Significantly increased levels of Cmax, AUC, T1/2, and MRT were found in rats treated with the processed products. In addition, decreased levels of D-D and TAT and increased contents of PGI2 were observed in rats given FRA and its processed products, compared with that of the model group. Moreover, VPF improved anticoagulation more than SFF in the animals. The observed improvement of anticoagulation by processed FRA may result from the increased absorption and bioavailability of triterpenoids. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Premature birth in patient with cervix incompetence and history of myasthenia gravis].

PubMed

Fuentealba, Maximiliano; Troncoso, Miguel; Vallejos, Joaquin; Ponce, Sebastian; Villablanca, Nelson; Melita, Pablo

2013-09-01

Cervical incompetence it's a dilatation of the cervix during the third trimester of pregnancy that ends with the interruption of it. The incidence in Chile is about 0.1-2% of the total pregnancies and it's one of the causes of preterm birth. A 34 years old pregnant patient. Timectomized at age 18 to treat her miastenia gravis, previously trated with medication, had 4 previous preterm labours all of them under 25 weeks and vaginal births. All fetuses died postpartum. A cerclage was made during the third, fourth and fifth pregnancies. She didn't present hypertension during the gestation and no cervical diameter under 15mm. Since the fourth gestation the following tests are taken: Antifosfolipidic antibodies, APTT,PT. All the results are either normal or negative. Microbial cultures were negative. No amniocentesis was made. A McDonald cervical cerclage was made during pregnancies number 3, 4 and 5 on the 16th week to delay the labor. Also oral micronized progesterone, on a 400mg/24 hours dosis, was administered to avoid preterm birth. On the 24th week the pharmacological treatment started including Intramuscular Betamethasone, 12 mg/24 hours (2 doses), to induce lung maturity on the fetus. It is thought that the administration of progesterone could have improved the situation of the patient, because it acts as a labour repressants. The use of cerclage could have helped, but the factors that may influence the effectiveness of this method are unknown. Perhaps there is some immunologic factor associated with the miastenia gravis that alters the normal course of pregnancy.

Structural analysis and anticoagulant activities of two sulfated polysaccharides from the sea cucumber Holothuria coluber.

PubMed

Yang, Wenjiao; Cai, Ying; Yin, Ronghua; Lin, Lisha; Li, Zhongkun; Wu, Mingyi; Zhao, Jinhua

2018-05-01

Sulfated polysaccharides such as fucosylated glycosaminoglycan and fucan sulfate from echinoderm possess complex chemical structure and various biological activities. The two sulfated polysaccharides were purified from the low-value sea cucumber Holothuria coluber. Their physicochemical properties and chemical structures were analyzed and characterized by chemical and instrumental methods. Structural analysis clarified that the sea cucumber fucosylated glycosaminoglycan contains a chondroitin sulfate-like backbone and fucosyl branches with four various sulfation patterns. The fucan sulfate with molecular weight of 64.6 kDa comprises a central core of regular α(1 → 4)-linked tetrasaccharide repeating units, each of which is linked by a 4-O-sulfated fucose residue. Anticoagulant assays indicated that these sulfated polysaccharides possessed strong APTT prolonging activities and intrinsic factor Xase inhibitory activities, both of which decreased with the reduction of their molecular weights. Our results expand knowledge on the structural types of sulfated polysaccharides from sea cucumbers and further illustrate their functionality. Copyright © 2018. Published by Elsevier B.V.

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue

PubMed Central

Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C.

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection. PMID:27936002

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

PubMed

Ng, Deborah Hl; Wong, Joshua Gx; Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection.

Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: Analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition.

PubMed

Jeansen, Stephanie; Witkamp, Renger F; Garthoff, Jossie A; van Helvoort, Ardy; Calder, Philip C

2018-06-01

The increased consumption of fish oil enriched-products exposes a wide diversity of people, including elderly and those with impaired health to relatively high amounts of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). There is an ongoing debate around the possible adverse effects of n-3 LC-PUFAs on bleeding risk, particularly relevant in people with a medical history of cardiovascular events or using antithrombotic drugs. This analysis of 8 clinical intervention studies conducted with enteral medical nutrition products containing fish oil as a source of n-3 LC-PUFAs addresses the occurrence of bleeding-related adverse events and effects on key coagulation parameters (Prothrombin Time [PT], (activated) and Partial Thromboplastin Time [(a)PTT]). In all the patients considered (over 600 subjects treated with the active product in total), with moderate to severe disease, with or without concomitant use of antithrombotic agents, at home or in an Intensive Care Unit (ICU), no evidence of increased risk of bleeding with use of n-3 LC-PUFAs was observed. Furthermore there were no statistically significant changes from baseline in measured coagulation parameters. These findings further support the safe consumption of n-3 LC-PUFAs, even at short-term doses up to 10 g/day of eicosapentaenoic acid + docosahexaenoic acid (EPA + DHA) or consumed for up to 52 weeks above 1.5 g/day, in selected vulnerable and sensitive populations such as subjects with gastrointestinal cancer or patients in an ICU. We found no evidence to support any concern raised with regards to the application of n-3 LC-PUFAs and the potentially increased risk for the occurrence of adverse bleeding manifestations in these selected patient populations consuming fish oil enriched medical nutrition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

PubMed

Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

2016-08-01

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

Determinants of mortality and prolonged hospital stay among dengue patients attending tertiary care hospital: a cross-sectional retrospective analysis

PubMed Central

Khan, Amer Hayat; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Yusra Habib

2017-01-01

Objectives Dengue imposes substantial economic, societal and personal burden in terms of hospital stay, morbidity and mortality. Early identification of dengue cases with high propensity of increased hospital stay and death could be of value in isolating patients in need of early interventions. The current study was aimed to determine the significant factors associated with dengue-related prolonged hospitalisation and death. Design Cross-sectional retrospective study. Setting Tertiary care teaching hospital. Participants Patients with confirmed dengue diagnosis were stratified into two categories on the basis of prolonged hospitalisation (≤3 days and >3 days) and mortality (fatal cases and non-fatal cases). Clinico-laboratory characteristics between these categories were compared by using appropriate statistical methods. Results Of 667 patients enrolled, 328 (49.2%) had prolonged hospitalisation. The mean hospital stay was 4.88±2.74 days. Multivariate analysis showed that dengue haemorrhagic fever (OR 2.3), elevated alkaline phosphatase (ALP) (OR 2.3), prolonged prothrombin time (PT) (OR 1.7), activated partial thromboplastin time (aPTT) (OR 1.9) and multiple-organ dysfunctions (OR 2.1) were independently associated with prolonged hospitalisation. Overall case fatality rate was 1.1%. Factors associated with dengue mortality were age >40 years (p=0.004), secondary infection (p=0.040), comorbidities (p<0.05), acute kidney injury (p<0.001), prolonged PT (p=0.022), multiple-organ dysfunctions (p<0.001), haematocrit >20% (p=0.001), rhabdomyolosis (p<0.001) and respiratory failure (p=0.007). Approximately half of the fatal cases in our study had prolonged hospital stay of greater than three days. Conclusions The results underscore the high proportion of dengue patients with prolonged hospital stay. Early identification of factors relating to prolonged hospitalisation and death will have obvious advantages in terms of appropriate decisions about treatment and management in high dependency units. PMID:28698348

The first report on coagulation and phospholipase A2 activities of Persian Gulf lionfish, Pterois russelli, an Iranian venomous fish.

PubMed

Memar, Bahareh; Jamili, Shahla; Shahbazzadeh, Delavar; Bagheri, Kamran Pooshang

2016-04-01

Pterois russelli is a venomous fish belonging to scorpionidae family. Regarding to high significance value for tracing potential therapeutic molecules and special agents from venomous marine creatures, the present study was aimed to characterization of the Persian Gulf lionfish venom. Proteolytic, phospholipase, hemolytic, coagulation, edematogenic and dermonecrotic activities were determined for extracted venom. The LD50 of P. russelli venom was determined by intravenous injection in white Balb/c mice. Phospholipase A2 activity was recorded at 20 μg of total venom. Coagulation activity on human plasma was shown by Prothrombin Time (PT) and activated Partial Thromboplastin Time (APTT) assays and coagulation visualized after 7 and 14 s respectively for 60 μg of crude venom. LD50 was calculated as 10.5 mg/kg. SDS-PAGE revealed the presence of major and minor protein bands between 6 and 205 kDa. Different amounts of crude venom ranged from 1.87 to 30 μg showed proteolytic activity on casein. The highest edematic activity was detected at 20 μg. Our findings showed that the edematic activity was dose dependent and persisted for 48 h after injection. The crude venom did not induce dermonecrotic activity on rabbit skin and showed no hemolytic activity on human, mouse and rabbit erythrocytes. This is the first report for phospholipase A2 and coagulation activity in venomous fish and venomous marine animals respectively. Proteolytic activity of P. russelli venom is in accordance with the other genara of scorpionidae family. According to venom activity on intrinsic and extrinsic coagulation pathways, lionfish venom would be contained an interesting pharmaceutical agent. This study is pending to further characterization of phospholipase A2, coagulation, and protease activities and also in vivo activity on animal model of surface and internal bleeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits.

PubMed

Dub, Abdallah M; Dugani, Aisha M

2013-01-01

The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, which has known cardiovascular health benefits, including those on blood pressure, cholesterol level, and thrombogenesis. All previous animal and clinical studies investigating the beneficial antithrombotic effects of olives have focused on olive oil and a few on olive leaves (OLEs). In this study, the ethanolic extract of OLE was evaluated for its antithrombotic activity in the rabbit model of thrombosis induced by ligature of the vena cava and intravenous administration of tissue thromboplastin. Pre-treatment with 100 or 200 mg/kg per day of the ethanolic extract for 8 weeks significantly prolonged the prothrombin time (PT) in comparison to the control group (12.10±0.35 sec and 14.38±0.29 sec vs. 10.8±0.32 sec, p<0.05 and 0.001, respectively). In comparison to the control group, the same doses had no statistically significant effect on thrombus weight (16.85±0.67 mg, 16.32±0.35 mg, and 17.81±0.75 mg; p=0.18 and 0.06) or on activated partial thromboplastin time (APTT) (19.17±0.33 sec, 19.12±0.73 sec, and 18.97±0.41 sec; p=0.36 and 0.43, respectively). One important finding in this study concerns thrombus morphology. In the extract treatment groups, the thrombus was filament-like and did not adhere to blood vessel walls, whereas in the control group the thrombus was thick and almost completely occluded the vein. Therefore, these results suggest that OLE ethanolic extract can modify the extrinsic coagulation pathway as evidenced by the prolongation of PT and changes in thrombus morphology, enough to justify further research to evaluate its possible antithrombotic effects.

Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits.

PubMed

Dub, Abdallah M; Dugani, Aisha M

2013-05-22

The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, which has known cardiovascular health benefits, including those on blood pressure, cholesterol level, and thrombogenesis. All previous animal and clinical studies investigating the beneficial antithrombotic effects of olives have focused on olive oil and a few on olive leaves (OLEs). In this study, the ethanolic extract of OLE was evaluated for its antithrombotic activity in the rabbit model of thrombosis induced by ligature of the vena cava and intravenous administration of tissue thromboplastin. Pre-treatment with 100 or 200 mg/kg per day of the ethanolic extract for 8 weeks significantly prolonged the prothrombin time (PT) in comparison to the control group (12.10 ± 0.35 sec and 14.38 ± 0.29 sec vs. 10.8 ± 0.32 sec, p < 0.05 and 0.001, respectively). In comparison to the control group, the same doses had no statistically significant effect on thrombus weight (16.85 ± 0.67 mg, 16.32 ± 0.35 mg, and 17.81 ± 0.75 mg; p = 0.18 and 0.06) or on activated partial thromboplastin time (APTT) (19.17 ± 0.33 sec, 19.12 ± 0.73 sec, and 18.97 ± 0.41 sec; p = 0.36 and 0.43, respectively). One important finding in this study concerns thrombus morphology. In the extract treatment groups, the thrombus was filament-like and did not adhere to blood vessel walls, whereas in the control group the thrombus was thick and almost completely occluded the vein. Therefore, these results suggest that OLE ethanolic extract can modify the extrinsic coagulation pathway as evidenced by the prolongation of PT and changes in thrombus morphology, enough to justify further research to evaluate its possible antithrombotic effects.

Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits

PubMed Central

Dub, Abdallah M.; Dugani, Aisha M.

2013-01-01

The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, which has known cardiovascular health benefits, including those on blood pressure, cholesterol level, and thrombogenesis. All previous animal and clinical studies investigating the beneficial antithrombotic effects of olives have focused on olive oil and a few on olive leaves (OLEs). In this study, the ethanolic extract of OLE was evaluated for its antithrombotic activity in the rabbit model of thrombosis induced by ligature of the vena cava and intravenous administration of tissue thromboplastin. Pre-treatment with 100 or 200 mg/kg per day of the ethanolic extract for 8 weeks significantly prolonged the prothrombin time (PT) in comparison to the control group (12.10±0.35 sec and 14.38±0.29 sec vs. 10.8±0.32 sec, p<0.05 and 0.001, respectively). In comparison to the control group, the same doses had no statistically significant effect on thrombus weight (16.85±0.67 mg, 16.32±0.35 mg, and 17.81±0.75 mg; p=0.18 and 0.06) or on activated partial thromboplastin time (APTT) (19.17±0.33 sec, 19.12±0.73 sec, and 18.97±0.41 sec; p=0.36 and 0.43, respectively). One important finding in this study concerns thrombus morphology. In the extract treatment groups, the thrombus was filament-like and did not adhere to blood vessel walls, whereas in the control group the thrombus was thick and almost completely occluded the vein. Therefore, these results suggest that OLE ethanolic extract can modify the extrinsic coagulation pathway as evidenced by the prolongation of PT and changes in thrombus morphology, enough to justify further research to evaluate its possible antithrombotic effects. PMID:23702352

Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations.

PubMed

Repplinger, Daniel J; Hoffman, Robert S; Nelson, Lewis S; Hines, Elizabeth Q; Howland, MaryAnn; Su, Mark K

2016-09-01

Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone. A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940 mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2 s; INR 7.2; aPTT, 55.7 s; BUN 28 mg/dL; and creatinine 1.2 mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160 ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization. In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient.

Biological and structural analyses of bovine heparin fractions of intermediate and high molecular weight.

PubMed

Nogueira, Alexsandro V; Drehmer, Daiana L; Iacomini, Marcello; Sassaki, Guilherme L; Cipriani, Thales R

2017-02-10

Low molecular weight heparin, which is generally obtained by chemical and enzymatic depolymerization of unfractionated heparin, has high bioavailability and can be subcutaneously injected. The aim of the present investigation was to fractionate bovine heparin using a physical method (ultrafiltration through a 10kDa cut-off membrane), avoiding structural modifications that can be caused by chemical or enzymatic treatments. Two fractions with different molecular weights were obtained: the first had an intermediate molecular weight (B-IMWH; Mn=9587Da) and the other had a high molecular weight (B-HMWH; 22,396Da). B-IMWH and B-HMWH have anticoagulant activity of 103 and 154IU/mg respectively, which could be inhibited by protamine. Both fractions inhibited α-thrombin and factor Xa in vitro and showed antithrombotic effect in vivo. Moreover, ex vivo aPTT assay demonstrated that B-IMWH is absorbed by subcutaneous route. The results showed that ultrafiltration can be used to obtain two bovine heparin fractions, which differ on their molecular weights, structural components, anticoagulant potency, and administration routes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contact activation: a revision.

PubMed

Schmaier, A H

1997-07-01

In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.

A common standard is inappropriate for determining the potency of ultra low molecular weight heparins such as semuloparin and bemiparin.

PubMed

Jeske, Walter P; Hoppensteadt, Debra; Gray, Angel; Walenga, Jeanine M; Cunanan, Josephine; Myers, Lauren; Fareed, Jawed; Bayol, Alain; Rigal, Hélène; Viskov, Christian

2011-10-01

Lower low-molecular-weight heparins are being developed to improve on the safety and efficacy of antithrombotic therapy. Semuloparin and bemiparin are two depolymerized heparins produced by distinct manufacturing processes. The objective of this investigation was to determine whether a common standard could be used to define their potency. Activities were compared using typical clinical coagulation assays and pharmacological assays required for potency assessment. The activity of semuloparin and bemiparin was comparable in FXa-based assays (anti-FXa, Heptest). However, bemiparin produced a stronger effect in the aPTT, ACT and anti-thrombin assays. Assessment of the parallelism of the concentration-response curves indicated that bemiparin and semuloparin are not equivalent in terms of anti-FIIa activity. Bemiparin had a stronger inhibitory effect on thrombin induced platelet aggregation, and a stronger interaction with HIT antibodies. These data demonstrate that depolymerized heparins can exhibit a range of biologic activities making them unique agents. Pharmacopoeial parameters such as anti-IIa and anti-Xa potency and molecular weight are insufficient to characterize such agents. Copyright © 2011 Elsevier Ltd. All rights reserved.

Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in Combination with rAd5-EnvA in Healthy Adults (VRC 012).

PubMed

Crank, Michelle C; Wilson, Eleanor M P; Novik, Laura; Enama, Mary E; Hendel, Cynthia S; Gu, Wenjuan; Nason, Martha C; Bailer, Robert T; Nabel, Gary J; McDermott, Adrian B; Mascola, John R; Koup, Richard A; Ledgerwood, Julie E; Graham, Barney S

2016-01-01

VRC 012 was a Phase I study of a prototype recombinant adenoviral-vector serotype-35 (rAd35) HIV vaccine, the precursor to two recently published clinical trials, HVTN 077 and 083. On the basis of prior evaluation of multiclade rAd5 HIV vaccines, Envelope A (EnvA) was selected as the standard antigen for a series of prototype HIV vaccines to compare various vaccine platforms. In addition, prior studies of rAd5-vectored vaccines suggested pre-existing human immunity may be a confounding factor in vaccine efficacy. rAd35 is less seroprevalent across human populations and was chosen for testing alone and in combination with a rAd5-EnvA vaccine in the present two-part phase I study. First, five subjects each received a single injection of 109, 1010, or 1011 particle units (PU) of rAd35-EnvA in an open-label, dose-escalation study. Next, 20 Ad5/Ad35-seronegative subjects were randomized to blinded, heterologous prime-boost schedules combining rAd5-EnvA and rAd35-EnvA with a three month interval. rAd35-EnvA was given at 1010 or 1011 PU to ten subjects each; all rAd5-EnvA injections were 1010 PU. EnvA-specific immunogenicity was assessed four weeks post-injection. Solicited reactogenicity and clinical safety were followed after each injection. Vaccinations were well tolerated at all dosages. Antibody responses measured by ELISA were detected at 4 weeks in 30% and 50% of subjects after single doses of 1010 or 1011 PU rAd35, respectively, and in 89% after a single rAd5-EnvA 1010 PU injection. EnvA-specific IFN-γ ELISpot responses were detected at four weeks in 0%, 70%, and 50% of subjects after the respective rAd35-EnvA dosages compared to 89% of subjects after rAd5. T cell responses were higher after a single rAd5-EnvA 1010 PU injection than after a single rAd35-EnvA 1010 PU injection, and humoral responses were low after a single dose of either vector. Of those completing the vaccine schedule, 100% of rAd5-EnvA recipients and 90% of rAd35-EnvA recipients had both T cell and humoral responses after boosting with the heterologous vector. ELISpot response magnitude was similar in both regimens and comparable to a single dose of rAd5. A trend toward more robust CD8 T cell responses using rAd5-EnvA prime and rAd35-EnvA boost was observed. Humoral response magnitude was also similar after either heterologous regimen, but was several fold higher than after a single dose of rAd5. Adverse events (AEs) related to study vaccines were in general mild and limited to one episode of hematuria, Grade two. Activated partial thromboplastin time (aPTT) AEs were consistent with an in vitro effect on the laboratory assay for aPTT due to a transient induction of anti-phospholipid antibody, a phenomenon that has been reported in other adenoviral vector vaccine trials. Limitations of the rAd vaccine vectors, including the complex interactions among pre-existing adenoviral immunity and vaccine-induced immune responses, have prompted investigators to include less seroprevalent vectors such as rAd35-EnvA in prime-boost regimens. The rAd35-EnvA vaccine described here was well tolerated and immunogenic. While it effectively primed and boosted antibody responses when given in a reciprocal prime-boost regimen with rAd5-EnvA using a three-month interval, it did not significantly improve the frequency or magnitude of T cell responses above a single dose of rAd5. The humoral and cellular immunogenicity data reported here may inform future vaccine and study design. ClinicalTrials.gov NCT00479999.

[Application of temporary balloon occlusion of the abdominal aorta in the treatment of complete placenta previa complicated with placenta accreta].

PubMed

Cui, S H; Zhi, Y X; Zhang, K; Zhang, L D; Shen, L N; Gao, Y N

2016-09-25

Objective: To investigate the value of temporary balloon occlusion of the abdominal aorta in the treatment of complete placenta previa with placenta accreta. Methods: From January 2015 to February 2016, 24 cases of complete placenta previa with placenta accreta were treated with temporary balloon occlusion of the abdominal aorta(the study group)before cesarean, and 24 cases of complete placenta previa with placenta accreta did not receive balloon occlusion(the control group). The operation time, intraoperative blood loss, intraoperative blood transfusion volume, the perioperative hemoglobin level, the hysterectomy rate and the related complications were compared retrospectively.Also, the hospitalization time, the blood coagulation parameters after operation, including activated partial thromboplastin time(APTT), fibrinogen(FIB), D-Dimer and reperfusion injury parameters including creatine phosphokinase(CK), creatine phosphokinase isoenzyme(CK-MB), lactate dehydrogenase(LDH)and serum creatinine were compared between the 2 groups. Results: The blood loss[750 ml(400- 2 000 ml)vs 2 000 ml(1 500- 2 375 ml); Z =-3.214, P =0.001]and blood transfusion volume[200 ml(0-800 ml)vs 800 ml(0-1 200 ml); Z =- 2.173, P =0.030]in the study group were lower than in the control group. The hemoglobin difference between before and after operation in the study group was lower than the control group[(12.8±13.4)g/L vs(22.9±20.1)g/L; t =-2.041, P =0.047]. In the study group, there were still bleeding in 13 cases after releasing the balloon, 5 of them received uterine artery embolization, 5 cases received uterine artery ligation, and 3 cases received uterine packing. One case had venous thrombosis in the right lower limb. Two cases(8%,2/24)in the control group had hysterectomy, while none in the study group, there was no statistical significance( P = 0.489). Conclusions: Temporary balloon occlusion of the abdominal aorta can effectively reduce blood loss and blood transfusion in the treatment of complete placenta previa with placenta accreta, but there is still the risk of continuing bleeding after releasing the balloon. Other methods of hemostasis might be needed.

Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats.

PubMed

Germoush, Mousa O; Othman, Sarah I; Al-Qaraawi, Maha A; Al-Harbi, Hanan M; Hussein, Omnia E; Al-Basher, Gadh; Alotaibi, Mohammed F; Elgebaly, Hassan A; Sandhu, Mansur A; Allam, Ahmed A; Mahmoud, Ayman M

2018-06-01

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that occurs as a result of liver failure. Umbelliferone (UMB; 7-hydroxycoumarin) is a natural product with proven hepatoprotective activity; however, nothing has yet been reported on its protective effect against hyperammonemia, the main culprit behind the symptoms of HE. Here, we evaluated the effect of UMB against ammonium chloride (NH 4 Cl)-induced hyperammonemia, oxidative stress, inflammation and hematological alterations in rats. We demonstrated the modulatory role of UMB on the glutamate-nitric oxide (NO)-cGMP pathways in the cerebrum of rats. Rats received intraperitoneal injections of NH 4 Cl (3 times/week) for 8 weeks and concomitantly received 50 mg/kg UMB. NH 4 Cl-induced rats showed significantly elevated blood ammonia and liver function markers. Lipid peroxidation and NO were increased in the liver and cerebrum of rats while the antioxidant defenses were declined. UMB significantly reduced blood ammonia, liver function markers, lipid peroxidation and NO, and enhanced the antioxidant defenses in NH 4 Cl-induced rats. UMB significantly prevented anemia, leukocytosis, thrombocytopenia and prolongation of PT and aPTT. Hyperammonemic rats showed elevated levels of cerebral TNF-α, IL-1β and glutamine as well as increased activity and expression of Na + /K + -ATPase, effects that were significantly reversed by UMB. In addition, UMB down-regulated nitric oxide synthase and soluble guanylate cyclase in the cerebrum of hyperammonemic rats. In conclusion, this study provides evidence that UMB protects against hyperammonemia via attenuation of oxidative stress and inflammation. UMB prevents hyperammonemia associated hematological alterations and therefore represents a promising protective agent against the deleterious effects of excess ammonia. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load.

PubMed

Hasanoglu, Imran; Guner, Rahmet; Carhan, Ahmet; Kocak Tufan, Zeliha; Yagci-Caglayik, Dilek; Guven, Tumer; Yilmaz, Gul Ruhsar; Tasyaran, Mehmet A

2016-02-01

Crimean Congo hemorrhagic fever (CCHF) is a fatal disease with a mortality rate of 5-30%. CCHF can be asymptomatic or it may progress with bleeding and cause mortality. To evaluate relation of viral load with mortality, clinical and laboratory findings in CCHF. A total of 126 CCHF patients were included. Serum samples obtained from all patients on admission for measurement of viral load. In our study, mortality rate was 11.1%. The most important prognostic factor was viral load. Mean viral load was 8.3×10(7)copy/ml and 4.6×10(9)copy/ml in survived and dead patients, respectively (p<0.005). Probability of survival is found to be significantly reduced where AST >1130U/l, ALT >490U/l, CPK >505U/l, LDH >980U/l, platelet count <23×10(3)/l, creatinine >1.4mg/dl, INR >1.3, d-dimer >7100ng/dl, and viral load >1.03×10(8)copy/ml. Patients with 10(8)copy/ml or higher viral load had diarrhea, headache, unconsciousness, bleeding, and seizure significantly more frequently (p<0.05). WBC, hemoglobin, platelet counts were significantly lower whereas AST, ALT, CPK, LDH, creatinine levels, PT and aPTT time, d-dimer levels, and INR were found to be significantly higher in these group. There are several severity criteria for prognosis of CCHF. In addition to these parameters, we introduce creatinine as a predictive factor for prognosis. Our study, which has the largest number of patients among studies that evaluate viral load on CCHF shows that viral load is the most effective parameter on mortality. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of apixaban on antifactor Xa levels in a patient with acute kidney injury.

PubMed

Wendte, Jodi; Voss, Glenn; VanOverschelde, Beau

2016-04-15

The case of a patient requiring conversion from apixaban to heparin in the setting of acute kidney injury is reported. A 70-year-old man was initiated on apixaban 5 mg twice daily for new-onset, nonvalvular atrial fibrillation with a CHA2DS2-VASc score of 4, indicating a high risk of stroke. Soon after starting apixaban, he experienced pulmonary edema with pneumonia requiring hospitalization. During the course of hospitalization, the patient developed acute kidney injury requiring hemodialysis, and apixaban was stopped due to concerns about altered pharmacokinetics and impaired drug elimination in this setting. A heparin infusion was started 36 hours after the last dose of apixaban was administered. Antifactor Xa levels were monitored consistent with the hospital's standard practice protocols. The initial and repeat antifactor Xa concentrations were elevated (1.8-4.4 IU/mL) for up 72 hours after stopping the heparin infusion. Given the suspected interference of apixaban with standard antifactor Xa level monitoring, the heparin protocol was modified to reflect drip-rate adjustments based on activated partial thromboplastin times (aPTTs). The hospital protocol for heparin infusions was reinstituted on hospital day 7, with dosage adjustments based on antifactor Xa levels. The patient remained on a continuous heparin infusion for atrial fibrillation for the remainder of his hospitalization without complications or bleeding events. A 70-year-old man with new-onset nonvalvular atrial fibrillation and receiving apixaban discontinued this therapy and was given heparin instead due to acute kidney injury. His heparin dosage was successfully adjusted based on antifactor Xa levels and aPPTs. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Coagulation Profile in Patients with Different Etiologies for Cushing Syndrome: A Prospective Observational Study.

PubMed

Tirosh, Amit; Lodish, Maya; Lyssikatos, Charalampos; Belyavskaya, Elena; Feelders, Richard A; Stratakis, Constantine A

2017-05-01

Previous studies reported a higher prevalence of venous-thromboembolic events among patients with Cushing disease (CD) compared to those with ACTH-independent Cushing syndrome (CS) from adrenal sources. The objective of the current study was to evaluate the coagulation profile of patients with CS from different etiologies. A prospective observational study was conducted at a clinical research center. The study included adult patients admitted for evaluation of suspected CS (n=85), that were divided into 3 groups: CD (n=22), ACTH-independent CS from an adrenal tumor/hyperplasia (adrenal CS, n=21), and a control group consisting of subjects with negative screening for CS (rule-out CS, n=42). Coagulation profiles were drawn before and 8.5±4.3 months after surgery (trans-sphenoidal or adrenalectomy, n=18), and included fibrinogen, Factor VIII (FVIII), von Willebrand factor antigen (vWF:Ag), plasminogen activator inhibitor-1 (PAI-1), antithrombin III (ATIII), Protein C (PC), Protein S (PS), α2-antiplasmin (α2AP), and aPTT measurements. Patients with CD had higher baseline mean cortisol levels, ATIII activity and vWF:Ag levels compared with adrenal CS. Differences in ATIII activity and vWF:Ag levels remained even after controlling for BMI, and ATIII after also controlling for 24-h urinary free cortisol collections. Our study showed for the first time the differences in coagulation profiles between various etiologies of CS. We assume that the higher cortisol burden among CD patients may explain the differences found in the coagulation profile as well as the higher risk for VTE compared with primary adrenal CS patients. © Georg Thieme Verlag KG Stuttgart · New York.

Efficacy and safety of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) regimen in newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma: interim analysis of a phase 4 study NCT01501149

PubMed Central

Li, Ling; Li, Xin; Wang, Xinhua; Fu, Xiaorui; Ma, Wang; Qin, Yanru; Li, Wencai; Wu, Jingjing; Sun, Zhenchang; Zhang, Xudong; Nan, Feifei; Chang, Yu; Li, Zhaoming; Zhang, Dandan; Wang, Guannan; Yan, Jiaqin; Su, Liping; Wang, Jinghua; Xue, Hongwei; Young, Ken H.; Zhang, Mingzhi

2016-01-01

To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of the cisplatin, dexamethasone, gemcitabine, pegaspargase (DDGP) regimen. The primary end point was the 2-year progression-free survival (PFS) after the protocol treatment. Secondary endpoints included response rate (RR), overall survival (OS) and median survival time (MST). The interim analysis included data only from March 2011 to September 2013, who received six cycles of DDGP chemotherapy. A total of 25 eligible patients were enrolled. Seventeen patients (17/24, 70.83%) achieved complete response (CR) and four (4/24, 16.67%) achieved partial response (PR), three (3/24, 12.50%) had progressive disease (PD). The RR after treatment was 87.50%. After a median follow-up duration of 24.67 months (range 4-48 months). The 2-year PFS and OS rate were 61.80% (95% CI, 42.00% to 81.60%) and 68.50 % (95% CI, 48.70% to 88.30%), respectively. The MST was 36.55 months (95% CI, 29.41 months to 43.70 months). Grade 3/4 leukopenia occurred in fourteen patients (58.33%) and grade 3/4 thrombocytopenia occurred in eleven patients (45.83%). Twelve patients (50.00%) experienced Activated Partial Phromboplastin Ptime (APTT) elongation and fourteen patients (58.33%) experienced hypofibrinogenemia. In conclusion, DDGP regimen is an effective and tolerated treatment for newly diagnosed, advanced-stage ENKTL. This trial was registered at www.ClinicalTrials.gov as #NCT01501149. PMID:27384676

Determinants of the Thrombogenic Potential of Multiwalled Carbon Nanotubes

PubMed Central

Burke, Andrew; Singh, Ravi; Carroll, David L.; Owen, John; Kock, Nancy D.; D’Agostino, Ralph; Torti, Frank M.; Torti, Suzy V.

2011-01-01

Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionalization of MWCNTs on thrombotic activity. In vitro, MWCNT activate the intrinsic pathway of coagulation as measured by activated partial thromboplastin time (aPTT) assays. Functionalization by amidation or carboxylation enhances this procoagulant activity. Mechanistic studies demonstrate that MWCNTs enhance propagation of the intrinsic pathway via a non-classical mechanism strongly dependent on factor IX. MWCNTs preferentially associate with factor IXa and may provide a platform for its activation. In addition to their effects on the coagulation cascade, MWCNTs activate platelets in vitro, with amidated MWCNTs exhibiting greater platelet activation than carboxylated or pristine MWCNTs. However, contrasting trends are obtained in vivo, where functionalization tends to diminish rather than enhance pro-coagulant activity. Thus, following systemic injection of MWCNTs in mice, pristine MWCNTs decreased platelet counts, increased vWF, and increased D-dimers. In contrast, carboxylated MWCNTS exhibited little procoagulant tendency in vivo, eliciting only a mild and transient decrease in platelets. Amidated MWCNTs elicited no statistically significant change in platelet count. Further, neither carboxylated nor amidated MWCNTs increased vWF or D-dimers in mouse plasma. We conclude that the pro-coagulant tendencies of MWCNTs observed in vitro are not necessarily recapitulated in vivo. Further, functionalization can markedly attenuate the procoagulant activity of MWCNTs in vivo. This work will inform the rational development of biocompatible MWCNTs for systemic delivery. PMID:21663954

Tolerogenic β2-glycoprotein I DNA vaccine and FK506 as an adjuvant attenuates experimental obstetric antiphospholipid syndrome.

PubMed

Chao, Ya-Hsuan; Chen, Der-Yuan; Lan, Joung-Liang; Tang, Kuo-Tung; Lin, Chi-Chien

2018-01-01

DNA vaccines have recently emerged as a therapeutic agent for treating autoimmune diseases, such as multiple sclerosis. Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by β2-glycoprotein I (β2-GPI)-targeting antiphospholipid antibodies (APAs) and vascular thrombosis or obstetrical complications. To examine the therapeutic potential of a β2-GPI DNA vaccine, we administered a vaccine mixed with FK506 as an adjuvant to a mouse model of obstetric APS. First, the pCMV3-β2-GPI DNA vaccine, which encodes the full-length human β2-GPI gene, was constructed. Then, we administered the β2-GPI DNA vaccine in 0.1 ml of saline, mixed with or without 100 μg of FK506, intramuscularly to the mice on days 28, 35 and 42. Blood titers of the anti-β2-GPI antibody, platelet counts, activated partial thromboplastin times (aPTTs), and the percentage of fetal loss were measured. We also stimulated murine splenic T cells ex vivo with β2-GPI and determined the T helper cell proportion and cytokine secretion. The administration of the β2-GPI DNA vaccine mixed with FK506 reduced the blood IgG anti-β2-GPI antibody titers and suppressed APS manifestations in mice. The combination also suppressed interferon-γ and interleukin (IL)-17A secretion but increased the Treg cell proportion and IL-10 secretion in murine splenic T cells following ex vivo stimulation with β2-GPI. Our results demonstrated the therapeutic efficacy of a β2-GPI DNA vaccine and FK506 as an adjuvant in a murine model of obstetric APS. Possible mechanisms include the inhibition of Th1 and Th17 responses and the up-regulation of Treg cells.

Tolerogenic β2-glycoprotein I DNA vaccine and FK506 as an adjuvant attenuates experimental obstetric antiphospholipid syndrome

PubMed Central

Chen, Der-Yuan; Lan, Joung-Liang; Tang, Kuo-Tung; Lin, Chi-Chien

2018-01-01

DNA vaccines have recently emerged as a therapeutic agent for treating autoimmune diseases, such as multiple sclerosis. Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by β2-glycoprotein I (β2-GPI)-targeting antiphospholipid antibodies (APAs) and vascular thrombosis or obstetrical complications. To examine the therapeutic potential of a β2-GPI DNA vaccine, we administered a vaccine mixed with FK506 as an adjuvant to a mouse model of obstetric APS. First, the pCMV3-β2-GPI DNA vaccine, which encodes the full-length human β2-GPI gene, was constructed. Then, we administered the β2-GPI DNA vaccine in 0.1 ml of saline, mixed with or without 100 μg of FK506, intramuscularly to the mice on days 28, 35 and 42. Blood titers of the anti-β2-GPI antibody, platelet counts, activated partial thromboplastin times (aPTTs), and the percentage of fetal loss were measured. We also stimulated murine splenic T cells ex vivo with β2-GPI and determined the T helper cell proportion and cytokine secretion. The administration of the β2-GPI DNA vaccine mixed with FK506 reduced the blood IgG anti-β2-GPI antibody titers and suppressed APS manifestations in mice. The combination also suppressed interferon-γ and interleukin (IL)-17A secretion but increased the Treg cell proportion and IL-10 secretion in murine splenic T cells following ex vivo stimulation with β2-GPI. Our results demonstrated the therapeutic efficacy of a β2-GPI DNA vaccine and FK506 as an adjuvant in a murine model of obstetric APS. Possible mechanisms include the inhibition of Th1 and Th17 responses and the up-regulation of Treg cells. PMID:29894515

New synthetic peptide with efficacy for heparin reversal and low toxicity and immunogenicity in comparison to protamine sulfate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Tong; Meng, Zhiyun; Zhu, Xiaoxia

Protamine sulfate (PS), the only clinically approved antidote to unfractionated heparin (UFH), is widely used for cardiopulmonary surgery or other extracorporeal circulation situations. However, the applications of PS have accompanied various severe side-effects. In this study, we presented a novel synthesized peptide compound (RRRRR-RRRRR-RRRRR-sulfate, R15S) served as a safer UFH antidote. Comparison studies were conducted between PS and R15S on efficacy and safety, aided by heparin neutralization studies, drug toxicity studies and anaphylactic analysis. Our research demonstrated that R15S contained comparable UFH neutralization activity in vitro and in rats in vivo as to active partial thromboplastin time (APTT) and anti-FXa assays. Theremore » was no cytotoxicity for R15S at 60 μg mg{sup −1} or below and the median lethal dose (LD{sub 50}) of R15S in mice was 35.4 mg kg{sup −1}, both of which were similar to that of PS. Furthermore, R15S exhibited no immunogenicity while it was obvious in guinea pigs immunized with PS. The level of cross-reactivity to anti-PS antibodies of R15S was about 30%. Both of which indicated much safer properties of R15S than PS. In conclusion, we presented a promising candidate R15S for UFH reversal, which is effective in neutralizing UFH and potentially safer in use. - Highlights: • R15 sulfate has a comparable unfractionated heparin neutralization activity to PS. • R15 sulfate avoided severe anaphylactic responses which happened to PS in clinical use. • R15 sulfate could provide a stricter quality control compared to PS which may vary with different batches.« less

[Comparative analysis on the biological basis of blood stasis syndrome induced by qi-stagnation and qi-deficiency in patients with unstable angina pectoris].

PubMed

Ren, Jian-xun; Liu, Jian-xun; Lin, Cheng-ren

2010-04-01

To comparatively analyse the objective characteristics of different syndrome types of qi-disturbance-induced blood stasis syndrome (QDBS) in the pathogenetic evolution of unstable angina coronary heart disease (UA-CHD). Seventy-eight patients with UA-CHD of QDBS were differentiated into 2 groups: 55 in the qi-deficiency-induced blood-stasis syndrome group (A) and 23 in the qi-stagnation-induced blood-stasis syndrome group (B). The comparative analysis on them was carried out through comparing their blood pressure, glucose and lipid metabolisms, coagulation function, thyroid function and inflammation reaction changes, etc. In the pathogenetic process of qi-disturbance induced blood stasis, the initiating age, levels of HbA1c, TSH, PT and APTT between the two groups were significantly different (P < 0.05). Levels of TNF-alpha and LN were higher and levels of sIgA lower in patients than those in healthy subjects (P < 0.05). Inflammation immune reaction may play an important role in the pathogenetic process of blood-stasis syndrome, and the functional disturbance of hypothalamus, pituitary and endocrinal secretion induced by emotional stress is possibly the essence of qi-stagnation induced blood stasis syndrome.

Etiology of strokes and hemiplegia in children presenting at Ayub Teaching Hospital, Abbottabad.

PubMed

Siddiqui, Tahir Saeed; Rehman, Anis ur; Ahmed, Basharat

2006-01-01

Strokes in pediatric age group are not common. However diagnosing the cause of stroke will help in providing preventive and curative treatment. Present study was conducted to find etiology of strokes/hemiplegia in children. This study was conducted in Department of Pediatrics, Ayub Teaching Hospital Abbottabad from December 2002 to December 2005. All children from two months to fifteen years of age were included in the study. Children with weakness due to acute poliomyelitis and Guillan barre syndrome were excluded. Investigations were based on findings on history and clinical examination and included full blood count, PT, APTT, Platelets count, ECG, Echocardiography, hematocrit, lumber puncture with CSF analysis and culture and CT-scan skull. Data of all the patients presenting with strokes/hemiplegia was entered on prepared proforma. The main etiology of strokes was intracranial infection causing strokes in 23(56.09%)children and majority of children (78.26%) in this group were below five years. Etiology was un-known in 7(17.07%) children after necessary available investigations. Intracranial infection Infections that is meningitis and encephalitis are commonest etiology of strokes and hemiplegia in paediatrics patients presenting at Ayub Teaching Hospital, Abbottabad.

Effect of Qingnao tablet on blood viscosity of rat model of blood stasis induced by epinephrine

NASA Astrophysics Data System (ADS)

Xie, Guoqi; Hao, Shaojun; Ma, Zhenzhen; Liu, Xiaobin; Li, Jun; Li, Wenjun; Zhang, Zhengchen

2018-04-01

To establish a rat model of blood stasis with adrenaline (Adr) subcutaneous injection and ice bath stimulation. The effects of different doses on the blood viscosity of blood stasis model rats were observed. The rats were randomly divided into 6 groups: blank control group (no model), model group, positive control group, high, middle and low dose group. The whole blood viscosity and plasma viscosity were detected by blood viscosity instrument. Compared with the blank group, model group, high shear, low shear whole blood viscosity and plasma viscosity were significantly increased, TT PT significantly shortened, APTT was significantly prolonged, FIB increased significantly, indicating that the model was successful. Compared with the model group, can significantly reduce the Naoluotong group (cut, low cut). Qingnaopian high dose group (low cut), middle dose group (cut, low shear blood viscosity) (P<0.01), Can significantly reduce Naoluotong qingnaopian group, high dose group (P<0.01), plasma viscosity decreased qingnaopian plasma viscosity in low dose group (P<0.05). Conclusion: qingnaopian could improve the blood rheology of blood stasis mice abnormal index, decrease the blood viscosity, blood stasis has certain hemostatic effect.

A 2-year-old boy with circulatory failure owing to streptococcal toxic shock syndrome: case report.

PubMed

Keenswijk, Werner; Vande Walle, Johan

2017-04-20

A 2-year-old boy presented with severe hypotension and acute kidney injury after a prodrome of non-bloody diarrhoea and fever in the preceding 3 days. He had a mild Ebstein cardiac anomaly but otherwise a normal past history and growth. On examination, he looked ill, his temperature was 37.5 °C, circulation was poor, and there were several purpuric lesions on the face, hands and scrotum. Haemoglobin was 7.8 g/dL (11-14), total white cell count 27 × 10 9 /L, platelets 62 × 10 9 /L, blood urea nitrogen 20.7 mmol/L (4.2-17.1), serum creatinine 95.4 μmol/L (21.2-36.2), CRP 154 mg/L (<5), AST 296 U/L (11-50), ALT 909 U/L (7-40) and C 3 component of complement 0.8 g/L (0.9-1.8). Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged and fibrinogen level was 1.0 g/L (2-4). He received immediate fluid resuscitation (IV 0.9% saline solution, 2 × 10 ml/kg boluses, followed by glucose 5/0.45% sodium chloride solution, 2 × 10 ml/kg) and antibiotics (ciprofloxacin and amikacin) but circulation continued to deteriorate with development of decreased consciousness. He was placed on mechanical ventilation and vasopressor agents were added. Despite improved circulation over the next 2 days, he developed oliguria, progressive fluid overload, generalised oedema and a right-sided pleural effusion. Dialysis was commenced on day 3 of admission. Differential diagnosis included sepsis, atypical haemolytic uraemic syndrome and lupus nephritis. Blood and urine cultures remained negative but an anti-streptolysin O titre of 1318 (<200) IU/mL led to the diagnosis of streptococcal toxic shock syndrome which is rare in early childhood and associated with high mortality. Haemodialysis was commenced and continued for 10 days with successful treatment of fluid overload and subsequent extubation. Renal function was completely restored over the following 6 weeks and he was discharged in good clinical condition about 2 months after intial admission. The clinical course and outcome are discussed, and the importance of timely initiation of dialysis when there is fluid overload is emphasised.

Clinical profile and warning sign finding in children with severe dengue and non-severe dengue

NASA Astrophysics Data System (ADS)

Adam, A. S.; Pasaribu, S.; Wijaya, H.; Pasaribu, A. P.

2018-03-01

Dengue fever is one of the most important emerging vector-borne viral diseases. Approximately 500,000 out of 100 million cases develop to severe dengue infection. Patient with severe dengue (SD) can be predicted by clinical profile, laboratory and warning sign which could be saved by early interventions.This was a retrospective descriptive-analytic study to investigate clinical manifestations, laboratory and warning signs ofchildren with dengue infection in Haji Adam Malik hospital during January 2014–May 2016. Through medical records, we had selected 140 cases which fulfilled research criteria.Cases were classified as SD (n=28) and NSD (n=112). Most common clinical manifestations for NSD were abdominal pain (39.3%), myalgia (39.3%), headache (37.1%), mucosal bleeding (36.4%) while for SD were shock (15.7%), mucosal bleeding (15.7%), clinical fluid accumulation (15%), shortness of breath (14.3%). SGPT >1000IU/L (5 cases), SGOT >1000IU/L (9 cases), PT (10 cases) and aPTT (16 cases) were abnormal in SD. Severe dengue was frequently found in the range of white cell count 1000-4000/L and platelet count 20,000-50,000mm/uL. Clinical manifestations, warning sign, and laboratoryfinding, were different between SD and NSD.

Betaine (N,N,N-trimethylglycine) averts photochemically-induced thrombosis in pial microvessels in vivo and platelet aggregation in vitro

PubMed Central

Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

2015-01-01

Betaine (N,N,N-trimethylglycine) is an important food component with established health benefits through its homocysteine-lowering effects, and is used to lower total homocysteine concentration in plasma of patients with homocystinuria. It is well established that hyperhomocysteinemia is an established risk factor for cardiovascular disease and stroke. However, the possible protective effect of betaine on coagulation events in vivo and in vitro has thus far not been studied. Betaine was given to mice at oral doses of either 10 mg/kg (n = 6) or 40 mg/kg (n = 6) for seven consecutive days, and control mice (n = 6) received water only. The thrombotic occlusion time in photochemically induced thrombosis in pial arterioles was significantly delayed in mice pretreated with betaine at doses of 10 mg/kg (P < 0.001) and 40 mg/kg (P < 0.01). Similar effects were observed in pial venules with 10 mg/kg (P < 0.05) and 40 mg/kg (P < 0.05) betaine. In vitro, in whole blood samples collected from untreated mice (n = 3–5), betaine (0.01–1 mg/mL) significantly reversed platelet aggregation induced by adenosine diphosphate (5 µM). The number of circulating platelets and plasma concentration of fibrinogen in vivo were not significantly affected by betaine pretreament compared with the control group. Lipid peroxidation (LPO) in mice pretreated with betaine was significantly reduced compared with the control group. Moreover, betaine (0.01–1 mg/mL) caused a dose-dependent and significant prolongation of PT (n = 5) and aPTT (n = 4–6). In conclusion, our data show that betaine protected against coagulation events in vivo and in vitro and decreased LPO in plasma. PMID:25662827

Betaine (N,N,N-trimethylglycine) averts photochemically-induced thrombosis in pial microvessels in vivo and platelet aggregation in vitro.

PubMed

Nemmar, Abderrahim; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

2015-07-01

Betaine (N,N,N-trimethylglycine) is an important food component with established health benefits through its homocysteine-lowering effects, and is used to lower total homocysteine concentration in plasma of patients with homocystinuria. It is well established that hyperhomocysteinemia is an established risk factor for cardiovascular disease and stroke. However, the possible protective effect of betaine on coagulation events in vivo and in vitro has thus far not been studied. Betaine was given to mice at oral doses of either 10 mg/kg (n = 6) or 40 mg/kg (n = 6) for seven consecutive days, and control mice (n = 6) received water only. The thrombotic occlusion time in photochemically induced thrombosis in pial arterioles was significantly delayed in mice pretreated with betaine at doses of 10 mg/kg (P < 0.001) and 40 mg/kg (P < 0.01). Similar effects were observed in pial venules with 10 mg/kg (P < 0.05) and 40 mg/kg (P < 0.05) betaine. In vitro, in whole blood samples collected from untreated mice (n = 3-5), betaine (0.01-1 mg/mL) significantly reversed platelet aggregation induced by adenosine diphosphate (5 µM). The number of circulating platelets and plasma concentration of fibrinogen in vivo were not significantly affected by betaine pretreament compared with the control group. Lipid peroxidation (LPO) in mice pretreated with betaine was significantly reduced compared with the control group. Moreover, betaine (0.01-1 mg/mL) caused a dose-dependent and significant prolongation of PT (n = 5) and aPTT (n = 4-6). In conclusion, our data show that betaine protected against coagulation events in vivo and in vitro and decreased LPO in plasma. © 2015 by the Society for Experimental Biology and Medicine.

Phase I clinical study of the toll-like receptor 9 agonist MGN1703 in patients with metastatic solid tumours.

PubMed

Weihrauch, Martin R; Richly, Heike; von Bergwelt-Baildon, Michael S; Becker, Hans Jiro; Schmidt, Manuel; Hacker, Ulrich T; Shimabukuro-Vornhagen, Alexander; Holtick, Udo; Nokay, Bahar; Schroff, Matthias; Wittig, Burghardt; Scheulen, Max E

2015-01-01

This study was initiated to evaluate safety, toxicity, pharmacokinetics, and pharmacodynamics of treatment with MGN1703, a novel synthetic DNA-based toll-like receptor 9 (TLR9)-immunomodulator. The study consisted of an escalating single dose regimen followed by a multiple dose part. Dose levels of 0.25, 2, 10, 30, and 60 mg of MGN1703 were administered subcutaneously over 6 weeks twice weekly. Patients with at least stable disease (SD) could participate in the extension phase of the study for six further weeks. Effects on the immune status were monitored. 28 patients with metastatic solid tumours were included. Fatigue and activated partial thromboplastin time (aPTT) prolongation were the only two cases of drug-related grade 3 Common Terminology Criteria adverse events (CTCAE). The most frequently reported drug-related adverse events were of CTC Grade ⩽2. There was no relationship between toxicity and dose and no patient was withdrawn from the study due to drug-related AE. No drug-related serious AE (SAE) were reported. Six out of 24 patients had SD after 6 weeks of treatment and three of those remained in SD after a total of 12 weeks. Four patients were further treated in a compassionate use programme showing long-term disease stabilisation for up to 18 months. Immune assessment of cell compartments showed a non-significant increase of TLR9 expressing naïve B cells during therapy. Twice weekly subcutaneous applications of MGN1703 in a dose of up to 60 mg are safe and well tolerated without dose-limiting toxicities. MGN1703 shows immune activation and anti-tumour efficacy in heavily pretreated patients. The recommended dose of 60 mg twice weekly is currently used in a phase II trial in small cell lung cancer and a phase III trial in colorectal cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety and economic considerations of argatroban use in critically ill patients: a retrospective analysis.

PubMed

Kim, Se-Chan; Tran, Nicole; Schewe, Jens-Christian; Boehm, Olaf; Wittmann, Maria; Graeff, Ingo; Hoeft, Andreas; Baumgarten, Georg

2015-02-07

Heparin-induced thrombocytopenia (HIT) causes thromboembolic complications which threaten life and limb. Heparin is administered to virtually every critically ill patient as a protective measure against thromboembolism. Argatroban is a promising alternative anticoagulant agent. However, a safe dose which still provides effective thromboembolic prophylaxis without major bleeding still needs to be identified. Critically ill patients (n = 42) diagnosed with HIT at a tertiary medical center intensive care unit from 2005 to 2010 were included in this retrospective analysis. Patient records were perused for preexisting history of HIT, heparin dosage before HIT, argatroban dosage, number of transfusions required, thromboembolic complications and length of ICU stay (ICU LOS). Patients were allocated to Simplified Acute Physiology Scores above and below 30 (SAPS >30, SAPS <30), respectively. For calculations, patients (n = 19) without previous history of HIT were compared to patients (n = 23) with a history of HIT before initiation of argatroban. The mean initial argatroban dosage was below 0.4 mcg/kg/min regardless of SAPS score. Maintenance dosage had to be increased in patients with SAPS <30 to 0.54 ± 0.248 mcg/kg/min (p >0.05) to achieve effective anticoagulation. No thromboembolic complications were encountered. Argatroban had to be discontinued temporarily in 16 patients for a total of 57 times due to diagnostic or surgical procedures, supratherapeutic aPTT and bleeding without increasing the number of transfusions. A history of HIT was associated with a shorter ICU LOS and significantly reduced transfusion need when compared to patients with no history of HIT. Cost calculation favour argatroban due to increased transfusion needs during heparin administration and increase ICU LOS. Argatroban can be used at doses < 0.4 mcg/kg/min without an increase in transfusion requirements and at a reduced overall treatment cost compared to heparin.

Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on primary nephrotic syndrome.

PubMed

Luo, Yuezhong; Wang, Chao; Tu, Haitao

2014-03-01

The aim of the present study was to investigate whether the four guanosines (4G)/five guanosines (5G) polymorphism in the gene coding for plasminogen activator inhibitor-1 (PAI-1) affects the clinical features of primary nephrotic syndrome (PNS). A cohort of 200 biopsy-diagnosed PNS patients was studied, with 40 healthy subjects as controls. The PAI-1 gene polymorphism was detected by polymerase chain reaction and DNA sequencing. Associations between the PAI-1 4G/5G polymorphism and clinical features and pathological types of PNS were analyzed. The results indicated that the PAI-1 genotype distribution is significantly different between patients with PNS and healthy controls, with significantly higher numbers of the 4G/4G genotype and lower numbers of the 5G5G genotype detected in PNS patients compared to controls (both P<0.05). The frequency of the 4G allele was also significantly higher in PNS patients compared to healthy controls (P<0.01). Among the different pathological types of PNS, IgA nephropathy (IgAN) and membranous nephropathy (MN) were associated with significantly increased frequencies of the 4G/4G and 4G/5G genotypes, as well as of the 4G allele. The increased 4G frequency was also detected in patients with minimal change disease (MCD). Significantly increased international normalized ratio (INR) and prolonged activated partial thromboplastin time (APTT) were observed in 4G/4G compared to 5G/5G PNS subjects. The response to steroids was not significantly different among the three genotypes. In conclusion, the 4G allele of the PAI-1 gene appears to be associated with PNS, especially in MN and IgAN patients. These findings suggest that specific targeting may be required for the treatment of PNS patients with the 4G/4G genotype.

[Outpatient use of heparin: data from the Midi-Pyrenes Health Fund].

PubMed

Berchery, Delphine; Roussel, Henri; Bourrel, Robert; Sciortino, Vincent

2003-01-01

The risk of haemorrhagic complications associated with heparin therapy can be reduced by good clinical practice. The aim of this study was to describe outpatient heparin therapy by using the database of the National Health Fund. The study population consisted of affiliates of the salaried employees insured by the health fund branch of the Midi-Pyrénées region, and corresponded to 62% of the residents of that region. Analysis of treatments and biological monitoring was carried out on a 1-year period. During this period, 16,462 patients started a treatment with heparin, 92% for a single treatment. The mean age of the patients was 55 years (SD = 19.8) and the majority were women (53%). Nine percent of these patients were switched to oral anticoagulant therapy. Of the other patients, 52% received heparin for less than 10 days, 36% for between 10 days and 5 weeks, and 12% for more than 5 weeks; 33% of the last group where heparin was prescribed for more than 5 weeks corresponds to a prescription of more than 3 months. Seventy-three percent of the heparin treatment durations complied with the authorities' (l'Agence française de sécurité sanitaire des produits de santé [AFSSAPS]) recommendations. Biological monitoring comprised a platelet count, an APTT (activated partial thromboplastin time) or an anti-Xa check in 41.9%, 27.8% and 3.1% of treated patients, respectively. Creatininaemia was measured in 27% of patients aged > 75 years (a group at increased risk of adverse drug reactions). Even considering some of the differences noted between the medical prescriptions and the reimbursement data of the health fund, results from this study allowed an evaluation of medical practices and suggests that monitoring of patients receiving heparin treatments remains insufficient, thus decreasing the benefit/risk ratio of such therapies.

[Evaluation of coagulation disorders with thrombelastography in patients with sepsis].

PubMed

Zhong, Shengjian; Zhang, Chunbao; Hu, Juntao; Tang, Zhanhong

2016-02-01

To compare the results of thrombelastography (TEG) and the conventional coagulability test in patients with sepsis, and to discuss the value of TEG in monitoring blood coagulation dysfunction in patients with sepsis. The clinical data of 92 adult patients with sepsis admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The patients were divided into sequential organ failure assessment (SOFA) score ≥ 12 group (n = 47) and SOFA < 12 group (n = 45). Thirty-five non-sepsis adult patients with normal coagulation function served as control group. The venous blood was collected for conventional blood coagulation test and routine examination of blood, D-dimer, procalcitonin (PCT), and TEG, and the differences were compared among three groups. Correlations between SOFA and various indexes of patients with sepsis were analyzed by Spearman rank correlation method. As shown in the results of the conventional blood coagulation test, D-dimer was gradually increased with the aggravation of the disease, the values in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.523 (0.273, 0.928), 0.863 (0.673, 4.221), and 4.118 (2.420, 5.653) mg/L respectively (Z = 25.163, P = 0.000). Platelet count (PLT) in SOFA ≥ 12 group was significantly lower than that of the SOFA < 12 group and non-sepsis group [×10(9)/L: 28.6 (12.8, 48.9) vs. 257.3 (152.6, 339.8), 182.0 (118.0, 229.0), both P < 0.01]. There was no significant difference in prothrombin time (PT) and international normalized ratio (INR) among three groups, and it indicated that the conventional blood coagulation test might not respond quickly to the change in coagulation status of sepsis patients. As shown in the results of TEG, the values of reaction time (R value) and kinetics time (K value) in SOFA < 12 group were lower than those of the non-sepsis group [R value (minutes): 4.4 (3.6, 6.1) vs. 6.3 (6.0, 6.7), P < 0.01; K value (minutes): 1.1 (1.0, 1.5) vs. 1.5 (1.3, 1.8), P < 0.05], while they were higher in SOFA ≥ 12 group than those of the non-sepsis group [R value (minutes): 7.0 (5.7, 8.7) vs. 6.3 (6.0, 6.7), P > 0.05; K value (minutes): 4.2 (3.4, 7.1) vs. 1.5 (1.3, 1.8), P < 0.01]. The α angle, maximum amplitude (MA) and coagulation index (CI) in SOFA < 12 group were higher than those of the non-sepsis group [α angle (degree angle): 73.3 (68.5, 74.7) vs. 66.8 (62.2, 69.0), P < 0.01; MA (mm): 71.7 (61.9, 73.3) vs. 60.3 (58.2, 63.8), P < 0.01; CI: 3.1 (-0.1, 3.9) vs. 0.9 (-0.4, 1.3), P < 0.05], while they were lower in SOFA ≥ 12 group than those of the non-sepsis group [α angle (degree angle): 48.1 (36.6, 53.0) vs. 66.8 (62.2, 69.0), P < 0.01; MA (mm): 37.8 (30.0, 45.7) vs. 60.3 (58.2, 63.8), P < 0.01; CI: -5.6 (-8.4, -3.6) vs. 0.9 (-0.4, 1.3), P < 0.01]. The above results indicated that TEG could distinguish quickly the hypercoagulability and hypocoagulability status in septic patients. PCT in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.27 (0.05, 1.80), 0.68 (0.10, 10.00), 41.10 (4.24, 100.00) μg/L respectively (Z = 195.475, P = 0.000), which indicate the severity of infectious disease. Correlation analysis results showed that SOFA score was negatively correlated with PLT, α angle, MA, and CI (r value was -0.853, -0.833, -0.881, and -0.859, respectively, all P = 0.000), and it was positively correlated with activated partial thromboplastin time (APTT), D-dimer, R value, K value, and PCT (r value was 0.381, 0.561, 0.587, 0.831, 0.775, respectively, P < 0.05 or P < 0.01), and non correlations was founded with PT, fibrinogen (FBG), and INR (r1 = 0.211, P1 = 0.233; r2 = -0.252, P2 = 0.142; r3 = 0.248, P3 = 0.148). TEG can effectively monitor the change in coagulation in patients with sepsis, and distinguish the hypercoagulable and hypocoagulable state. TEG may be a valuable tool to evaluate degree and risk of sepsis objectively.

[Risk factors of deep venous thrombosis associated with peripherally inserted central venous catheter in upper extremity in ICU].

PubMed

Zhao, Ning; Zhang, Jiale; Jiang, Ting; Chen, Xia; Wang, Jianning; Ding, Chengzhi; Liu, Fen; Qian, Kejian; Jiang, Rong

2017-02-01

To analyze the incidence and its risk factors of peripherally inserted central venous catheter related upper extremity deep venous thrombosis (PICC-UEDVT) in intensive care unit (ICU). Clinical data of the patients received PICCs in ICU of the First Affiliated Hospital of Nanchang University from August 2013 to August 2016 were retrospectively analysed. The inclusion criteria in the study included: the age > 18 years old, catheter indwelling time > 1 week and the complete relevant information. The gender, age, history of deep venous thrombosis (DVT) and PICC; number of illness involved organs; complicated with hypertension, diabetes, infection or not; and acute physiology and chronic health evaluation II (APACHE II), duration of mechanical ventilation; D-dimer, platelet count (PLT), and activated partial thromboplastin time (APTT) were recorded. According to the occurrence of PICC-UEDVT, univariate analysis was performed to identify the risk factors of PICC-UEDVT and variables with statistical difference were selected to do multivariate binary logistic regression analysis for the confirmable independence risk factors. Six patients of the 61 cases occurred PICC-UEDVT with the occurrence rate of 9.8%. Time of occurrence was 9 days, 14 days (2 cases), 22 days, 28 days, 62 days after inserted catheter respectively. Univariate analysis demonstrated that previous DVT, D-dimer and big diameter PICC were risk factors associated with PICC-UEDVT [the previous DVT: 50.00% vs. 7.27%, P = 0.017; D-dimer > 5 mg/L: 66.67% vs. 18.18%, P = 0.021; 5F catheter: 83.33% vs. 29.09%, P = 0.016]. It was shown by multivariate logistic regression analysis that the previous DVT [odds ratio (OR) = 20.539, 95% confidence interval (95%CI) = 1.733-243.875, P = 0.017] and increasing size of catheter (OR = 18.070, 95%CI = 1.317-247.875, P = 0.030) were independent risk factors associated with the development of PICC-UEDVT. For critical patients with a history of DVT and D-dimer > 5 mg/L, especially for those with the catheter placement over 14 days in ICU, clinical staffs should remain on high alert for the development of PICC-UEDVT and take early effective measures to prevent it. Meanwhile the patient's vascular conditions should be precisely assessed using ultrasound before insertion, and the appropriate catheter size be selected to reduce the incidence of PICC-UEDVT. Color Doppler ultrasonography should be used for dynamic monitoring during the indwelling of PICC, so that PICC-UEDVT can be found as early as possible.

Current approach to liver traumas.

PubMed

Kaptanoglu, Levent; Kurt, Necmi; Sikar, Hasan Ediz

2017-03-01

Liver injuries remain major obstacle for successful treatment, due to size and location of the liver. Requirement for surgery should be determined by clinical factors, most notably hemodynamical state. In this present study we tried to declare our approach to liver traumas. We also tried to emphasize the importance of conservative treatment, since surgeries for liver traumas carry high mortality rates. Patients admitted to the Department of Emergency Surgery at Kartal Research and Education Hospital, due to liver trauma were retrospectively analyzed between 2003 and 2013. Patient demographics, hepatic panel, APTT (activated partial thromboplastin time), PT (prothrombin time), INR (international normalized ratio), fibrinogen, biochemistry panel were recorded. Hemodynamic instability was the most prominent factor for surgery decision, in the lead of current Advanced Trauma Life Support (ATLS) protocols. Operation records and imaging modalities revealed liver injuries according to the Organ Injury Scale of the American Association for the Surgery of Trauma. 300 patients admitted to emergency department were included in our study (187 males and 113 females). Mean age was 47 years (range, 12-87). The overall mortality rate was 13% (40 out of 300). Major factor responsible for mortality rates and outcome was stability of cases on admission. 188 (% 63) patients were counted as stable, whereas 112 (% 37) cases were found unstable (blood pressure ≤ 90, after massive resuscitation). 192 patients were observed conservatively, whereas 108 cases received abdominal surgery. High levels of AST, ALT, LDH, INR, creatinine and low levels of fibrinogen and low platelet counts on admission were found to be associated with mortality and these cases also had Grade 4 and 5 injuries. Hemodynamic instability on admission and the type and grade of injury played major role in mortality rates). Packing was performed in 35 patients, with Grade 4 and 5 injuries. Mortality rate was %13 (40 out of 300). A multidisciplinary approach to the management of hepatic injuries has evolved over the last few decades, but the basic principles of trauma continue to be observed. Diagnostic and therapeutic endeavors are chosen based mainly on the stability of the patient. Stable patients with reliable examinations and available resources can be managed nonoperatively. Unstable patients require surgery. Our current approach to liver traumas is non operative technique, if possible. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

First living-related liver transplant to cure factor VII deficiency.

PubMed

Mohan, Neelam; Karkra, Sakshi; Jolly, Anu S; Vohra, Vijay; Mohanka, Ravi; Rastogi, Amit; Soin, A S

2015-09-01

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life-threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Effective combination therapy of plasma exchange and subsequent cyclophosphamide pulses for catastrophic antiphospholipid antibody syndrome: a case report].

PubMed

Miyamae, T; Imagawa, T; Ito, S; Katakura, S; Mori, M; Ibe, M; Mitsuda, T; Aihara, Y; Nakanishi, S; Kohri, T; Yokota, S

1999-06-01

A 7-year-old girl with catastrophic antiphospholipid antibody syndrome was described. She firstly admitted to the local hospital with the complaints of persistent fever and abdominal pain, and was diagnosed as systemic lupus erythematosus with the laboratory findings as follows; positive for antinuclear antibody, anti-DNA antibody, and platelet-associated IgG, thrombocytopenia, and hypocomplementemia. 10 days after the initiation of oral prednisolone, she suddenly manifested tonic convulsion and unconsciousness accompanied by high fever. Because of the unresponsiveness to the methylprednisolone pulse therapy for supposed CNS lupus, she was transferred to our hospital. Her unconsciousness persisted, and pulsation on dorsalis pedis was not palpable on admission. Laboratory investigation revealed the falsely positive VDRL, a prolonged aPTT, positive for lupus-anticoagulant and antiphospholipid antibody. The magnetic resonance image demonstrated multiple spotty hyperintensity (T2) in the brain consistent with multiple hemorrhagic infarcts. Arteriogram demonstrated the infarct of dorsalis pedis, and coronary aneurysms. These findings were compatible with the criteria of catastrophic antiphospholipid antibody syndrome, she was diagnosed as catastrophic antiphospholipid antibody syndrome. The plasma exchange and subsequent cyclophosphamide-pulse therapy, which was given once a month for first 6 months, and later, at 3 months intervals, was effectively administered. This combination and oral anti-thrombotic therapy revealed effective for this kind of fatal disorder.

[Experience of integrated traditional Chinese and Western medicine in first case of imported Zika virus disease in China].

PubMed

Deng, Yichu; Zeng, Liping; Bao, Wen; Xu, Pinghua; Zhong, Gongrong

2016-02-01

Zika virus disease is an acute infectious disease caused by Zika virus transmitted through Aedes mosquitoes. To explore the therapeutic effect of integrated traditional Chinese and Western Medicine for Zika virus disease, the treatment process of the first imported case in China was reviewed. The first imported Zika virus disease in China was admitted to Ganxian People's Hospital in Jiangxi Province on February 6th, 2016, and the patient received isolation treatment for 9 days and cured later. The effect of antiviral treatments including Xiyanping injection was evaluated based on clinical diagnosis and treatment process of the patient. A 34-year old male patient was admitted with chief complaint of fever for 9 days, orbital pain and itching rash for 4 days on February 6th, 2016. (1) Epidemiological characteristics: the patient was bitted by mosquitoes during his business trip in Venezuela since January 1st, where Zika virus disease was spreading. On January 20th he had dizziness without fever, and the symptom disappeared after taking medicines without details. Paroxysmal dizziness, chills and mild fever without myalgia was experienced on January 28th. On February 3rd small red rash appeared in the neck, spreading to anterior part of chest, limbs and trunk, and the fever, fatigue, nausea was continued, and a new symptom of paroxysmal pain in back of ears and orbits appeared, during which he had not go to hospital. The symptoms relieved on February 4th. He returned to Ganxian County on February 5th, he had yellow stool 3 times with normal temperature, without abdominal pain, and red rash still appeared in the neck. He went to Ganxian People's Hospital on February 6th, 2016. (2) Clinical manifestation: the vital signs showed a temperature of 36.8?centigrade, a pulse rate of 80 bpm, a respiratory rate of 20 bpm, and a blood pressure of 110/70 mmHg (1 mmHg = 0.133 kPa). It was showed by physical examination that red rash appeared in the neck, and no superficial enlarged lymph nodes were found. Bilateral conjunctival congestion was obvious, physiological reflex existed and pathological reflex was not found. (3) Auxiliary lab test and examination: no abnormal finding were revealed throughout examination and laboratory tests, including routine blood test, liver function, renal function, serum myocardial enzyme, electrolyte, blood sugar, C-reactive protein (CRP), troponin I (TnI), and procalcitonin (PCT), except slight prolongation in activated partial thromboplastin time (APTT, 38.6 s) on February 6th; and slightly dense shadow in left lung in lung CT scan, considering inflammatory changes and slight emphysema (especially in the left lower lung) as well as bilateral renal calculus on February 8th. No significant abnormalities were found in electrocardiogram and B ultrasound test of liver, spleen, and pancreas. (4) Virus confirmation: Zika virus nucleic acid was positive reported by Jiangxi Province Center for Disease Control and Prevention (CDC) on February 7th and Chinese CDC on February 9th, respectively, though Dengue virus were negative reported by Ganzhou CDC on February 6th. Right after the first diagnosis, anyone who had been in close contact with the patient received medical monitoring. (5)Treatment process: on February 6th, symptomatic treatment was prescribed since admitted into the infectious isolation wards and daily intravenous drip of Xiyanping injection 250 mg was prescribed for antiviral therapy. On February 7th, the patient had no fever, with occasional chills, neck rash was disappeared, orbital pain relieved and bilateral conjunctival hyperemia range was paler and narrowed, and his condition improved. Ibuprofen was administered for defervesce 3 times a day when his temperature reached to 37.5?centigrade at 16:00. On February 8th, the patient had no fever, times of chills was significantly reduced, without myalgia and rash, orbital pain and conjunctival hyperemia further recovered. On February 9th, bilateral eyes slightly tingling, mild conjunctival congestion, no fever chills or other discomfort was found. The chloramphenicol eye drops was prescribed for relieving sting pain with conjunctival congestion twice a day as recombinant human interferon alpha eye drops was out of store. The patient was comfortable from February 11th to February 13th. Blood and urine test for Zika were reported negative by the Chinese CDC and Jiangxi Province CDC. Because all the discharge criteria were satisfied, the patient was discharged on February 14th. At present, there is no specific effective drug to prevent and treat Zika virus disease effectually. After receiving symptomatic treatment and antiviral treatments including Xiyanping injection, the patient's symptoms were relieved. Zika virus nucleic acid in blood and urine was negative. The patient was discharged. Combination of traditional Chinese medicine and Western medicine maybe a good method to prevent and treat Zika virus disease.

[Comparison of different modes of using tranexamic acid administration on reducing hidden blood loss in total hip arthroplasty].

PubMed

Ni, Jin-Rong; Wang, Li-Xin; Chen, Xin-Jun

2016-08-25

To compare the clinical efficacy of using tranexamic acid in different ways to reduce the hidden blood loss in patients who receiving total hip arthroplasty (THA). Totally 68 patients with osteonecrosis of the femeral head treated by total hip arthroplasty in our hospital from February 2010 to July 2015 were randomly divided into the intravenous drip group (group A) and the topical application group (group B). In group A, there were 19 males and 15 females, with an average age of (62.0±6.4) years old, preoperative average hemoglobin was (121.30±8.15) g/L, average Hematocrit was (0.470±0.039) L/L. In group B, there were 18 males and 16 females, with an average age of (64.0±7.5) years old, preoperative average hemoglobin was (125.28±9.37) g/L, average Hematocrit was (0.490±0.041) L/L. The operation incision were performed through the posterolateral approach and the normal operation mode, biological prosthesis was selected. Through different ways the tranexamic acid was used to control of intraoperative and postoperative bleeding. Tranexamic acid was intra articular injection as a dose of 10 mg/kg 10 min to patient before anesthesia in intravenous drip group. In topic group, 3 g of tranexamic acid was dissolved in 120 ml saline and divided into three equal parts, then two pieces of gauze were immersed in 40 ml tranexamic acid solution. One gauze with 40 ml tranexamic acid was used to soak the acetabulum for 5 minutes after the acetabular preparation, another gauze was inserted in the femoral canal for 5 minutes after femoral canal broach preparation. The remaining 40 ml tranexamic acid fluid was injected into the hip joint after fascia closure. Place the drainage tube and clip it for 3 hours. Hemoglobin (Hb) and Hematocrit (Hct) were recorded at 72 hours after operation. The total blood loss, dominant blood loss, and hidden blood loss were calculated. In group A, postoperative hemoglobin difference before and after operation was (32.34±7.42) g/L, total blood loss was (833.6±81.4) ml, the hidden blood loss was (276.3±57.9) ml, red blood cell volume was (10.1±1.4) L/L;In group B, hemoglobin difference before and after operation was (28.2±6.1) g/L, total blood loss was (792.5±61.8) ml, the hidden blood loss was (297.5±50.3) ml, red blood cell volume was (9.2±1.2) L/L. There was no statistical significance about those aspect ( P >0.05). Compared of blood coagulation function between two groups, in group A: PT (12.78±2.03) s, APTT (34.27±3.91) s, INR (32.34±7.42); and in group B: PT (13.17±2.19) s, APTT (32.36±3.18) s, INR (28.24±6.14). There was no significant differences also ( P >0.05). Compared with intravenous application, topical application of tranexamic acid could also effectively reduce total blood loss and hidden blood loss, postoperative blood transfusion rate in primary total hip arthroplasty, while does not increase the risk of DVT.

Corrosion resistance and biocompatibility of magnesium alloy modified by alkali heating treatment followed by the immobilization of poly (ethylene glycol), fibronectin and heparin.

PubMed

Pan, Changjiang; Hu, Youdong; Hou, Yu; Liu, Tao; Lin, Yuebin; Ye, Wei; Hou, Yanhua; Gong, Tao

2017-01-01

In recent years, magnesium alloys are attracting more and more attention as a kind of biodegradable metallic biomaterials, however, their uncontrollable biodegradation speed in vivo and the limited surface biocompatibility hinder their clinical applications. In the present study, with the aim of improving the corrosion resistance and biocompatibility, the magnesium alloy (AZ31B) surface was modified by alkali heating treatment followed by the self-assembly of 3-aminopropyltrimethoxysilane (APTMS). Subsequently, poly (ethylene glycol) (PEG) and fibronectin or fibronectin/heparin complex were sequentially immobilized on the modified surface. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed that the above molecules were successfully immobilized on the magnesium alloy surface. An excellent hydrophilic surface was obtained after the alkali heating treatment while the hydrophilicity decreased to some degree after the self-assembly of APTMS, the surface hydrophilicity was gradually improved again after the immobilization of PEG, fibronectin or fibronectin/heparin complex. The corrosion resistance of the control magnesium alloy was significantly improved by the alkali heating treatment. The self-assembly of APTMS and the following immobilization of PEG further enhanced the corrosion resistance of the substrates, however, the grafting of fibronectin or fibronectin/heparin complex slightly lowered the corrosion resistance. As compared to the pristine magnesium alloy, the samples modified by the immobilization of PEG and fibronectin/heparin complex presented better blood compatibility according to the results of hemolysis assay and platelet adhesion as well as the activated partial thromboplastin time (APTT). In addition, the modified substrates had better cytocompatibility to endothelial cells due to the improved anticorrosion and the introduction of fibronectin. The substrates modified by fibronectin or fibronectin/heparin complex can significantly promote endothelial cell adhesion and proliferation. Taking all these results into consideration, the method of the present study can be used for the surface modification of the magnesium alloy to simultaneously impart it better corrosion resistance, favorable blood compatibility and good cytocompatibility to endothelial cells. Copyright © 2016 Elsevier B.V. All rights reserved.

A bleeding assessment tool correlates with intraoperative blood loss in children and adolescents undergoing major spinal surgery.

PubMed

Anadio, Jennifer M; Sturm, Peter F; Forslund, Johan M; Agarwal, Sunil; Lane, Adam; Tarango, Cristina; Palumbo, Joseph S

2017-04-01

Screening laboratory studies for bleeding disorders are of little predictive value for operative bleeding risk in adults. Predicting perioperative bleeding in pediatric patients is particularly difficult as younger patients often have not had significant hemostatic challenges. This issue is distinctly important for high bleeding risk surgeries, such as major spinal procedures. The aim of this study was to determine if the score of a detailed bleeding questionnaire (BQ) correlated with surgical bleeding in pediatric patients undergoing major spinal surgery. A total of 220 consecutive pediatric patients (mean age 14.2years) undergoing major spinal surgery were administered the BQ preoperatively, as well as having routine screening laboratory studies (i.e., PT, aPTT, PFA) drawn. A retrospective analysis was conducted to determine if there was a correlation between either the results of the BQ and/or laboratory studies with operative outcomes. A BQ score>2 showed a strong positive correlation with intraoperative bleeding based on both univariate and multivariate analyses. In contrast, abnormalities in screening laboratory studies showed no significant correlation with operative bleeding outcomes. Relying on screening laboratory studies alone is inadequate. The BQ used here correlated with increased intraoperative hemorrhage, suggesting this tool may be useful for assessing pediatric surgical bleeding risk, and may also be useful in identifying a subset of patients with a very low bleeding risk that may not require laboratory screening. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prothrombin complex concentrate administration for bleeding associated with non-vitamin K antagonist oral anticoagulants: The SAMURAI-NVAF study.

PubMed

Yoshimura, Sohei; Sato, Shoichiro; Todo, Kenichi; Okada, Yasushi; Furui, Eisuke; Matsuki, Takayuki; Yamagami, Hiroshi; Koga, Masatoshi; Takahashi, Jun C; Nagatsuka, Kazuyuki; Arihiro, Shoji; Toyoda, Kazunori

2017-04-15

Antidotes appropriate for non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are not yet in widespread clinical use. Efficacy of prothrombin complex concentrate (PCC) in NOAC-associated bleeding remains unclarified. Ten NOAC users (4 women, median 74years old) who developed major bleeding and received PCC were prospectively enrolled. Eight single-center NOAC users (0 women, median 74years old) with intracerebral hemorrhage, who over the same period did not receive PCC, were studied for comparison. Of the 10 PCC-treated patients, 8 developed intracerebral hemorrhage, 1 developed subdural hematoma, and another developed gastrointestinal bleeding. The median size of intracerebral hemorrhage was 8mL, relatively lower than the reported size for patients without NOACs. Patients received a median of 1000IU or 16IU/kg of PCC. Before and 1h after PCC administration, the median PT-INR changed from 1.41 to 1.09 (p<0.05) and median aPTT changed from 35.4 to 38.0s (p=0.39). Five patients developed intracranial hematoma expansion and 4 required surgical hematoma evacuation. No symptomatic thrombotic events occurred in either group, no participants died, and 2 participants from each group were independent. Ten NOAC users developed major bleeding and were given relatively low doses of PCC. The effect of PCC on early cessation of bleeding was unclear, while the therapy did not trigger thromboembolic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

[Association between the C46T polymorphism of coagulation factor Ⅻ gene and the involvement of factor Ⅻ activity in patients with unexplained recurrent spontaneous abortion].

PubMed

Jin, Y H; Shen, X L; Wang, M S; Xu, X M; Liu, M N; Zhao, Z S; Zheng, J Y

2016-08-25

To explore the association between the C46T polymorphism of coagulation factor Ⅻ (FⅫ) gene and the involvement of FⅫ activity (FⅫ:C) in patients with unexplained recurrent spontaneous abortion (URSA), and to elucidate its role in the pathogenesis of URSA. This study included 203 patients with URSA (URSA group) and 171 healthy women with at least one child and no history of infertility or miscarriage (control group) in the southern area of Zhejiang Province. The C46T polymorphism of the FⅫ gene was analyzed with matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS) in all subjects. The values of prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, FⅫ:C and other coagulant parameters were determined. The frequency distribution of the wild-type (CC), heterozygote (CT), homozygote (TT) genotypes and C and T alleles were compared between the patients and controls. A comprehensive analysis of association was conducted between C46T genotypes and the FⅫ:C levels in URSA patients. The CC, CT, TT genotypes of the FⅫ gene were observed in 7 (3.4%, 7/203), 83 (40.9%, 83/203) and 113 (55.7%, 113/203) patients with URSA versus 7 (4.1%, 7/171), 46 (26.9%, 46/171) and 118 (69.0%, 118/171) controls. The frequency of CT in the patients with URSA was significantly higher than that in controls, but the frequency of TT in the patients was lower than that in controls (χ(2)=7.939, OR=1.884, 95%CI: 1.210-2.935, P<0.05). The frequencies of allele C and allele T were observed in 97 (23.9%, 97/406) and 309 (76.1%, 309/406) patients with URSA versus 60 (17.5%, 60/342) and 282 (82.5%, 282/342) controls. The distribution frequency of allele T in URSA group was lower than that in control group (χ(2)=4.510, OR=1.475, 95%CI: 1.029-2.115, P<0.05). The FⅫ: C levels in the patients were (102±13)% in CC genotype, (78±11)% in CT genotype and (59±9)% in TT genotype, respectively. The differences of the FⅫ: C levels between the CC and CT, CT and TT, CC and TT genotypes in the patients were significant (all P<0.05). The low level of FⅫ:C maybe result from the T allele of the FⅫ gene in URSA patients. The CT genotype might be relative to the pathogenesis of URSA in a Chinese Han female population from the southern area of Zhejiang province.

[Damage control resuscitation of severe multiple trauma in the pelvic fractures].

PubMed

Fu, Chang-guo

2015-05-01

To discuss the clinical effects of damage control resuscitation (DCR) in treating severe multiple trauma in the pelvic fractures. From March 2009 to September 2013, a restrospective analysis was conducted on the clinical data of 28 patients with multiple trauma in the pelvic fractures, including 19 males and 9 females, ranging in age from 21 to 51 years old with an average of 32.5 years old. According to Tile classification of pelvic fractures, 16 cases were type B and 12 cases were type C. Injury severity score (ISS) averaged 32.0±3.4. All cases were treated with damage contral orthopaedics and DCR strategy, namely that used immediately with small capacity of balanced salt solution on admission so as to maintain the blood pressure between 80 to 90 mmHg. At the same time, emergency phase I simple debridement plus external fixator or bundled with fixed pelvic was done, and the chest or abdomen combined injury was treated at first. And limbs fracture was temporary dealing with bone traction or plaster external fixation, etc. After bleeding was controlled by operation, fluid resuscitation was done as fast as possible and the plasma was transfused early according to the proportion of plasma and red cell suspension (2 U:1 U-3 U:2 U). Dosage of balanced salt solution and blood before remedy shock was recorded, and the removal of time of lactic acid and coagulation were observed. Five cases were died after 4 to 15 hours into hospital (3 cases died for severe trauma-hemorrhagic shock and 2 cases for acute respiratory distress syndrome). Twenty-three cases were remedy shock at 1.6 to 4.3 hours after injury with an average of 2.4 hours. Period I operation duration was (78.2±10.3) minutes. Dosage of balanced salt solution was (3,798±340) ml and red cell suspension was 14 to 18 U, fresh frozen plasma (FFP) was (1,267±58) ml (1U FFP=100 ml), blood platelet was 8 to 12 U for 9 patients. The removal time of lactic acid and PT-APTT was (11.4±2.1) hours and (4.3±0.8) hours. Measures were taken to correct electrolyte and acid-base imbalance was normal. The success rat of recovery was 82.2% (23/28). Damage control resuscitation (DCR) integrates the main links such as damage control operation and allowable low blood pressure (or limited liquid resuscitation) and hemostatic control resuscitation, was early effective treatment measures for the patients with severe multiple trauma in the pelvic fractures.

STAFF OFFICERS AS BLOOD SUPPLIERS: EFFECTS OF REPEATED DONATIONS AND AUTOLOGOUS REINFUSIONS OF UNTRANSFUSED UNITS.

PubMed

Strandenes, Geir; Sivertsen, Joar; Eliassen, Håkon; Braathen, Hanne; Hervig, Tor A

2018-01-24

Limited blood inventory and resupply chains in combat settings can result in preventable deaths from traumatic hemorrhage. One way of mitigating this could be to establish donor pools where blood is collected in advance of high-risk missions and then reinfused back to the donor if not needed to treat casualties. 450+56 mL blood was collected, rested for 2 hours in room temperature and stored at 4 °C. The blood was reinfused 22-24 hours after donation and the donor observed for adverse reactions. Samples were collected before and 20 minutes after each donation for hematology, IgG, ferritin, CRP, total protein, LDH, bilirubin, haptoglobin and APTT. 9 participants went through a total of 36 donation and reinfusion procedures. 4 donors participated in 5 rounds, 2 in 4 rounds, 2 in 3 rounds, and 1 in 2 rounds. A significant drop was seen in hemoglobin (14.6 ± 0.9 to 13.9 ± 0.9) and ferritin (179 ± 70 to 149 ± 78) from before first donation to after the last reinfusion (p<0.05). Other parameters were unaffected. This small pilot study suggests that repeated donations and reinfusions may be both feasible and safe. Blood collected in this way should be labeled with the donor's full name and social security number (or similar) and the identity visually verified by the donor immediately before both donation and reinfusion. To further reduce risk, this form of donation should be restricted to scenarios where there is no other option for making blood available. Therapeutic/care management study, Level V.

Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab.

PubMed

Honickel, Markus; Treutler, Stefanie; van Ryn, Joanne; Tillmann, Sabine; Rossaint, Rolf; Grottke, Oliver

2015-04-01

Urgent surgery or life-threatening bleeding requires prompt reversal of the anticoagulant effects of dabigatran. This study assessed the ability of three- and four-factor prothrombin complex concentrate (PCC) and idarucizumab (specific antidote for dabigatran) to reverse the anticoagulant effects of dabigatran in a porcine model of trauma. Twelve animals were given dabigatran etexilate (DE) orally and dabigatran intravenously, before infliction of trauma. Six animals received tranexamic acid plus fibrinogen concentrate 12 minutes post-injury. Six PCCs (each 30 and 60 U/kg) and idarucizumab (30 and 60 mg/kg) were added to blood samples ex vivo. Coagulation was assessed by several coagulation assays. All coagulation parameters were altered after dabigatran infusion (plasma level: 442 ± 138 ng/ml). Both three- and four-factor PCCs mostly or completely reversed the effects of dabigatran on thromboelastometry variables and PT but not on aPTT. Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the effects of the drug on coagulation variables. Thrombin generation showed dose-dependent over-correction following the addition of PCC, implying that elevated levels of thrombin are required to overcome dabigatran-induced coagulopathy. In contrast, treatment with idarucizumab returned thrombin generation to baseline levels. Following trauma, therapy with tranexamic acid plus fibrinogen improved correction of coagulation parameters by PCC, and thromboelastometry parameters by idarucizumab. All investigated PCCs improved dabigatran- and trauma-induced coagulopathy to a similar degree. In conclusion, this study shows that three- and four-factor PCCs are similarly effective for dabigatran reversal. Idarucizumab also reversed the effects of dabigatran and, unlike PCCs, was not associated with over-correction of thrombin generation.

Effects of self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane and dopamine on the corrosion behaviors and biocompatibility of a magnesium alloy.

PubMed

Pan, Chang-Jiang; Hou, Yu; Wang, Ya-Nan; Gao, Fei; Liu, Tao; Hou, Yan-Hua; Zhu, Yu-Fu; Ye, Wei; Wang, Ling-Ren

2016-10-01

Magnesium based alloys are attracting tremendous interests as the novel biodegradable metallic biomaterials. However, the rapid in vivo degradation and the limited surface biocompatibility restrict their clinical applications. Surface modification represents one of the important approaches to control the corrosion rate of Mg based alloys and to enhance the biocompatibility. In the present study, in order to improve the corrosion resistance and surface biocompatibility, magnesium alloy (AZ31B) was modified by the alkali heating treatment followed by the self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane (APTMS) and dopamine, respectively. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectra (XPS) indicated that the molecules were successfully immobilized on the magnesium alloy surface by the self-assembly. An excellent hydrophilic surface was obtained after the alkali heating treatment and the water contact angle increased to some degree after the self-assembly of dopamine, APTMS and 3-phosphonopropionic acid, however, the hydrophilicity of the modified samples was better than that of the pristine magnesium substrate. Due to the formation of the passivation layer after the alkali heating treatment, the corrosion resistance of the magnesium alloy was obviously improved. The corrosion rate further decreased to varying degrees after the self-assembly surface modification. The blood compatibility of the pristine magnesium was significantly improved after the surface modification. The hemolysis rate was reduced from 56% of the blank magnesium alloy to 18% of the alkali heating treated sample and the values were further reduced to about 10% of dopamine-modified sample and 7% of APTMS-modified sample. The hemolysis rate was below 5% for the 3-phosphonopropionic acid modified sample. As compared to the pristine magnesium alloy, fewer platelets were attached and activated on the modified surfaces and the activated partial thromboplastin times (APTT) were prolonged to some degree. Furthermore, the modified samples showed good cytocompatibility. Endothelial cells exhibited the improved proliferative profiles in terms of CCK-8 assay as compared to those on the pristine magnesium alloy. The modified samples showed better endothelial cell adhesion and spreading than the pristine magnesium alloy. Taking all these results into consideration, the method of this study can be used to modify the magnesium alloy surface to improve the corrosion resistance and biocompatibility simultaneously. Copyright © 2016 Elsevier B.V. All rights reserved.

Management of gastrointestinal bleeding in patients anticoagulated with dabigatran compared with warfarin: a retrospective, comparative case review.

PubMed

Manatsathit, Wuttiporn; Al-Hamid, Hussein; Leelasinjaroen, Pornchai; Hashmi, Usman; McCullough, Peter A

2014-06-01

Dabigatran etexilate, was found to be effective for stroke prevention in patients with non-valvular atrial fibrillation. Given its predictable pharmacodynamics, laboratory monitoring is not required. Moreover, the risks of overall bleeding, intracranial bleeding, and life-threatening hemorrhage from dabigatran were found to be lower than warfarin. However, a higher risk of gastrointestinal (GI) bleeding caused by dabigatran from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial has raised the concern regarding clinical outcomes of patients with GI bleeding caused by dabigatran compared with warfarin. We retrospectively studied patients who were hospitalized for GI bleeding from dabigatran compared with warfarin with therapeutic anticoagulation monitoring during 2009 to 2012. Initial laboratory findings at presentation, number of transfused packed red blood cells (PRBCs), acute kidney injury, clinical outcomes (e.g., hypotension, tachycardia), length of stay, and death were compared. Thirteen patients taking dabigatran and 26 patients who were on warfarin with therapeutic international normalized ratio (INR) were hospitalized during the study period. Demographic data and baseline parameters between the two groups were not significantly different except for concurrent aspirin use (84.6% vs. 50%, P=0.036). Fifty-four percent of patients taking dabigatran did not have activated partial thromboplastin time (aPTT) level performed at presentation (7/13). The patients with GI bleeding from warfarin received significantly more PRBC transfusions compared with the dabigatran group (1.92±2.2 vs. 0.69±1.1 units, P=0.024). After controlling for initial hemoglobin and history of chronic kidney disease by using multivariate analysis, the patients in the warfarin group were likely to receive more PRBC. Hypotension at presentation was more common in GI bleeding caused by warfarin than dabigatran but the P value was insignificant (30.8% vs. 7.7%, P=0.11). Nevertheless, no differences in clinical outcomes or length of stay were found between the two groups. From our data, the patients with GI bleeding from dabigatran were likely to receive fewer PRBC transfusions; however, clinical outcomes and length of stay were comparable to GI bleeding caused by warfarin. Our sample generalizes to an elderly population (mean age of 77.9±10 years old) with creatinine clearance (CrCl) >30 mL/min who experience GI bleeding during chronic anticoagulation.

Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects.

PubMed

Edwards, Jeffrey E; Eliot, Lise; Parkinson, Andrew; Karan, Sharon; MacConell, Leigh

2017-09-01

Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin). OCA showed no substantial suppression/inhibition of S-warfarin, digoxin, and dextromethorphan and weak interactions with caffeine, omeprazole, rosuvastatin, and midazolam. The maximal pharmacodynamic responses (E max ) to warfarin-based INR, PT, and aPTT were reduced by 11%, 11%, and 1%, respectively, for the 10-mg dose group and by 7%, 7% and 0%, respectively, for the 25-mg dose group. Overall, drugs dosed in combination with OCA were well tolerated, and most adverse events were mild in severity. No clinically important trends were noted in laboratory evaluations, vital signs, or 12-lead ECGs. In these studies, OCA showed weak to no suppression/inhibition of metabolic enzymes and drug transporters at the highest recommended therapeutic dose in patients with PBC. On the basis on these analyses, monitoring and maintenance of target INR range are required during coadministration of OCA with drugs that are metabolized by CYP1A2 (R-warfarin). Intercept Pharmaceuticals, Inc.

Physicochemical and Biological Characterization of Fucoidan from Fucus vesiculosus Purified by Dye Affinity Chromatography

PubMed Central

Zayed, Ahmed; Muffler, Kai; Hahn, Thomas; Rupp, Steffen; Finkelmeier, Doris; Burger-Kentischer, Anke; Ulber, Roland

2016-01-01

A comparative study concerning the physicochemical, monomeric composition and biological characters among different fucoidan fractions is presented. Common purification techniques for fucoidan usually involve many steps. During these steps, the important structural features might be affected and consequently alter its biological activities. Three purified fractions were derived from Fucus vesiculosus water extract which, afterwards, were purified by a recently-developed dye affinity chromatography protocol. This protocol is based on dye-sulfated polysaccharide interactions. The first two fractions were obtained from crude precipitated fucoidan at different pH values of the adsorption phase: pH 1 and 6. This procedure resulted in fucoidan_1 and 6 fractions. The other, third, fraction: fucoidan_M, however, was obtained from a buffered crude extract at pH 1, eliminating the ethanol precipitation step. All of the three fractions were then further evaluated. Results revealed that fucoidan_M showed the highest sulfur content (S%), 12.11%, with the lowest average molecular weight, 48 kDa. Fucose, galactose, and uronic acid/glucose dimers were detected in all fractions, although, xylose was only detected in fucoidan_1 and 6. In a concentration of 10 µg·mL−1, Fucoidan_6 showed the highest heparin-like anticoagulant activity and could prolong the APTT and TT significantly to 66.03 ± 2.93 and 75.36 ± 1.37 s, respectively. In addition, fucoidan_M demonstrated the highest potency against HSV-1 with an IC50 of 2.41 µg·mL−1. The technique proved to be a candidate for fucoidan purifaction from its crude extract removing the precipitation step from common purification protocols and produced different fucoidan qualities resulted from the different incubation conditions with the immobilized thiazine toluidine blue O dye. PMID:27092514

UV induced surface modification on improving the cytocompatibility of metallocene polyethylene.

PubMed

Jaganathan, Saravana K; Prasath, Mani M

2018-01-01

Demand for medical implants is rising day by day as the world becomes the place for more diseased and older people. Accordingly, in this research, metallocene polyethylene (mPE), a commonly used polymer was treated with UV rays for improving its biocompatibility. Scanning electron microscopy (SEM) images confirmed the formation of crests and troughs, which depicts the improvement of surface roughness of mPE substrates caused by UV etching. Accordingly, the contact angle measurements revealed that the wettability of mPE-2.5 J/cm2 (68.09º) and mPE-5 J/cm2 (57.93º) samples were found to be increased compared to untreated mPE (86.84º) indicating better hydrophilicity. Further, the UV treated surface exhibited enhanced blood compatibility as determined in APTT (untreated mPE- 55.3 ± 2.5 s, mPE-2.5 J/cm2 - 76.7 ± 4.1 s and mPE-5 J/cm2 - 112.3 ± 2 s) and PT (untreated mPE - 24.7 ± 1.5 s, mPE- 2.5 J/cm2 - 34.3 ± 1.1 s and mPE-5 J/cm2 - 43 ± 2 s) assay. Moreover, the treated mPE-2.5 J/cm2 (4.88%) and mPE-5 J/cm2 (1.79%) showed decreased hemolytic percentage compared to untreated mPE (15.40%) indicating better safety to red blood cells. Interestingly, the changes in physicochemical properties of mPE are directly proportional to the dosage of the UV rays. UV modified mPE surfaces were found to be more compatible as identified through MTT assay, photomicrograph and SEM images of the seeded 3T3 cell population. Hence UV-modified surface of mPE may be successfully exploited for medical implants.

Massive transfusion: an overview of the main characteristics and potential risks associated with substances used for correction of a coagulopathy.

PubMed

Seghatchian, Jerard; Samama, Meyer Michel

2012-10-01

Massive transfusion (MT) is an empiric mode of treatment advocated for uncontrolled bleeding and massive haemorrhage, aiming at optimal resuscitation and aggressive correction of coagulopathy. Conventional guidelines recommend early administration of crystalloids and colloids in conjunction with red cells, where the red cell also plays a critical haemostatic function. Plasma and platelets are only used in patients with microvascular bleeding with PT/APTT values >1.5 times the normal values and if PLT counts are below 50×10(9)/L. Massive transfusion carries a significant mortality rate (40%), which increases with the number of volume expanders and blood components transfused. Controversies still exist over the optimal ratio of blood components with respect to overall clinical outcomes and collateral damage. While inadequate transfusion is believed to be associated with poor outcomes but empirical over transfusion results in unnecessary donor exposure with an increased rate of sepsis, transfusion overload and infusion of variable amounts of some biological response modifiers (BRMs), which have the potential to cause additional harm. Alternative strategies, such as early use of tranexamic acid are helpful. However in trauma settings the use of warm fresh whole blood (WFWB) instead of reconstituted components with a different ratio of stored components might be the most cost effective and safer option to improve the patient's survival rate and minimise collateral damage. This manuscript, after a brief summary of standard medical intervention in massive transfusion focuses on the main characteristics of various substances currently available to overcome massive transfusion coagulopathy. The relative levels of some BRMs in fresh and aged blood components of the same origin are highlighted and some myths and unresolved issues related to massive transfusion practice are discussed. In brief, the coagulopathy in MT is a complex phenomenon, often complicated by chronic activation of coagulation, platelets, complement and vascular endothelial cells, where haemolysis, microvesiculation, exposure of phosphatidyl serine positive cells, altered red cells with reduced adhesive proteins and the presence of some BRM, could play a pivotal role in the coagulopathy and untoward effects. The challenges of improving the safety of massive transfusion remain as numerous and as varied as ever. The answer may reside in appropriate studies on designer whole blood, combined with new innovative tools to diagnosis a coagulopathy and an evidence based mode of therapy to establish the optimal survival benefit of patients, always taking into account the concept of harm reduction and reduction of collateral damage. Copyright © 2012 Elsevier Ltd. All rights reserved.

The culture of time in neuropsychological assessment: exploring the effects of culture-specific time attitudes on timed test performance in Russian and American samples.

PubMed

Agranovich, Anna V; Panter, A T; Puente, Antonio E; Touradji, Pegah

2011-07-01

Cultural differences in time attitudes and their effect on timed neuropsychological test performance were examined in matched non-clinical samples of 100 Russian and American adult volunteers using 8 tests that were previously reported to be relatively free of cultural bias: Color Trails Test (CTT); Ruff Figural Fluency Test (RFFT); Symbol Digit Modalities Test (SDMT); and Tower of London-Drexel Edition (ToL(Dx)). A measure of time attitudes, the Culture of Time Inventory (COTI-33) was used to assess time attitudes potentially affecting time-limited testing. Americans significantly outscored Russians on CTT, SDMT, and ToL(Dx) (p,.05) while differences in RFFT scores only approached statistical significance. Group differences also emerged in COTI-33 factor scores, which partially mediated differences in performance on CTT-1, SDMT, and ToL(Dx) initiation time, but did not account for the effect of culture on CTT-2. Significant effect of culture was revealed in ratings of familiarity with testing procedures that was negatively related to CTT, ToL(Dx), and SDMT scores. Current findings indicated that attitudes toward time may influence results of time limited testing and suggested that individuals who lack familiarity with timed testing procedures tend to obtain lower scores on timed tests.

Improved test time evaluation in an expansion tube

NASA Astrophysics Data System (ADS)

James, Christopher M.; Cullen, Timothy G.; Wei, Han; Lewis, Steven W.; Gu, Sangdi; Morgan, Richard G.; McIntyre, Timothy J.

2018-05-01

Traditionally, expansion tube test times have been experimentally evaluated using test section mounted impact pressure probes. This paper proposes two new methods which can be performed using a high-speed camera and a simple circular cylinder test model. The first is the use of a narrow bandpass optical filter to allow time-resolved radiative emission from an important species to be captured, and the second is using edge detection to track how the model shock standoff changes with time. Experimental results are presented for two test conditions using an air test gas and an optical filter aimed at capturing emission from the 777 nm atomic oxygen triplet. It is found that the oxygen emission is the most reliable experimental method, because it is shown to exhibit significant changes at the end of the test time. It is also proposed that, because the camera footage is spatially resolved, the radiative emission method can be used to examine the `effective' test time in multiple regions of the flow. For one of the test conditions, it is found that the effective test time away from the stagnation region for the cylindrical test model is at most 45% of the total test time. For the other test condition, it is found that the effective test time of a 54° wedge test model is at most a third of the total test time.

Test Methods for Telemetry Systems and Subsystems Volume 1: Test Methods for Vehicle Telemetry Systems

DTIC Science & Technology

2012-05-01

Settling Time Test .............................................................................................. 3-16 3.13 Overload Recovery Test...6-7 6.7 Inter-message Gap Time Test...6-8 6.8 Response Time Test ............................................................................................. 6-9 6.9

Reliability of fitness tests using methods and time periods common in sport and occupational management.

PubMed

Burnstein, Bryan D; Steele, Russell J; Shrier, Ian

2011-01-01

Fitness testing is used frequently in many areas of physical activity, but the reliability of these measurements under real-world, practical conditions is unknown. To evaluate the reliability of specific fitness tests using the methods and time periods used in the context of real-world sport and occupational management. Cohort study. Eighteen different Cirque du Soleil shows. Cirque du Soleil physical performers who completed 4 consecutive tests (6-month intervals) and were free of injury or illness at each session (n = 238 of 701 physical performers). Performers completed 6 fitness tests on each assessment date: dynamic balance, Harvard step test, handgrip, vertical jump, pull-ups, and 60-second jump test. We calculated the intraclass coefficient (ICC) and limits of agreement between baseline and each time point and the ICC over all 4 time points combined. Reliability was acceptable (ICC > 0.6) over an 18-month time period for all pairwise comparisons and all time points together for the handgrip, vertical jump, and pull-up assessments. The Harvard step test and 60-second jump test had poor reliability (ICC < 0.6) between baseline and other time points. When we excluded the baseline data and calculated the ICC for 6-month, 12-month, and 18-month time points, both the Harvard step test and 60-second jump test demonstrated acceptable reliability. Dynamic balance was unreliable in all contexts. Limit-of-agreement analysis demonstrated considerable intraindividual variability for some tests and a learning effect by administrators on others. Five of the 6 tests in this battery had acceptable reliability over an 18-month time frame, but the values for certain individuals may vary considerably from time to time for some tests. Specific tests may require a learning period for administrators.

Isolation and characterization of a heparin with low antithrombin activity from the body of Styela plicata (Chordata-Tunicata). Distinct effects in venous and arterial models of thrombosis

PubMed Central

Santos, Joana C.; Mesquita, Juliana M. F.; Belmiro, Celso L.R.; da Silveira, Carolina B.M.; Viskov, Christian; Mourier, Pierre A.; Pavão., Mauro S.G.

2008-01-01

Introduction a heparin preparation with low antithrombin activity and different disaccharide composition than mammalian heparin was isolated from the body of the ascidian Styela plicata (Chordata-Tunicata). The disaccharide composition and the effect of the invertebrate glycan on venous and arterial models of thrombosis was investigated. Methods and Results High performance liquid chromatography of the products formed by a mixture of heparin-lyases showed that the ascidian heparin is composed mainly by ΔUA(2SO4)-1→4-β-D-GlcN(SO4) (47.5%), ΔUA(2SO4)-1→4-β-D-GlcN(SO4)(6SO4) (38.3%) disaccharides. Smaller amounts of the disaccharides ΔUA(2SO4)-1→4-β-D-GlcN(SO4)(3SO4)(6SO4) (2.8%) and ΔUA(2SO4)-1→4-β-D-GlcN(SO4)(3SO4) (8.0%). The invertebrate heparin has an aPTT activity of 18 IU/mg and an antithrombin-mediated anti-thrombin and anti-factor Xa activities 10-fold lower than that of mammalian heparin. In a venous model of thrombosis in the vena cava, S.plicata heparin inhibits only 80% of thrombosis at a dose 10-fold higher than that of the mammalian heparin that inhibits 100% of thrombosis. However, in an arterio-shunt model of arterial thrombosis, both S.plicata and mammalian heparin possess equivalent antithrombotic activity. It is also shown that at equivalent doses, ascidian heparin has a lower bleeding effect than mammalian heparin. Conclusion the antithrombin-mediated anticoagulant activity of heparin polymers is not directly related to antithrombotic potency in the arterio-venous shunt. The results of the present work suggest that heparin preparations obtained from the body of S.plicata may have a safer therapeutic action in the treatment of arterial thrombosis than mammalian heparin. PMID:17482241

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

PubMed

Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

2015-01-01

HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

Monte Carlo Simulation of Sudden Death Bearing Testing

NASA Technical Reports Server (NTRS)

Vlcek, Brian L.; Hendricks, Robert C.; Zaretsky, Erwin V.

2003-01-01

Monte Carlo simulations combined with sudden death testing were used to compare resultant bearing lives to the calculated hearing life and the cumulative test time and calendar time relative to sequential and censored sequential testing. A total of 30 960 virtual 50-mm bore deep-groove ball bearings were evaluated in 33 different sudden death test configurations comprising 36, 72, and 144 bearings each. Variations in both life and Weibull slope were a function of the number of bearings failed independent of the test method used and not the total number of bearings tested. Variation in L10 life as a function of number of bearings failed were similar to variations in lift obtained from sequentially failed real bearings and from Monte Carlo (virtual) testing of entire populations. Reductions up to 40 percent in bearing test time and calendar time can be achieved by testing to failure or the L(sub 50) life and terminating all testing when the last of the predetermined bearing failures has occurred. Sudden death testing is not a more efficient method to reduce bearing test time or calendar time when compared to censored sequential testing.

Reliability of Fitness Tests Using Methods and Time Periods Common in Sport and Occupational Management

PubMed Central

Burnstein, Bryan D.; Steele, Russell J.; Shrier, Ian

2011-01-01

Context: Fitness testing is used frequently in many areas of physical activity, but the reliability of these measurements under real-world, practical conditions is unknown. Objective: To evaluate the reliability of specific fitness tests using the methods and time periods used in the context of real-world sport and occupational management. Design: Cohort study. Setting: Eighteen different Cirque du Soleil shows. Patients or Other Participants: Cirque du Soleil physical performers who completed 4 consecutive tests (6-month intervals) and were free of injury or illness at each session (n = 238 of 701 physical performers). Intervention(s): Performers completed 6 fitness tests on each assessment date: dynamic balance, Harvard step test, handgrip, vertical jump, pull-ups, and 60-second jump test. Main Outcome Measure(s): We calculated the intraclass coefficient (ICC) and limits of agreement between baseline and each time point and the ICC over all 4 time points combined. Results: Reliability was acceptable (ICC > 0.6) over an 18-month time period for all pairwise comparisons and all time points together for the handgrip, vertical jump, and pull-up assessments. The Harvard step test and 60-second jump test had poor reliability (ICC < 0.6) between baseline and other time points. When we excluded the baseline data and calculated the ICC for 6-month, 12-month, and 18-month time points, both the Harvard step test and 60-second jump test demonstrated acceptable reliability. Dynamic balance was unreliable in all contexts. Limit-of-agreement analysis demonstrated considerable intraindividual variability for some tests and a learning effect by administrators on others. Conclusions: Five of the 6 tests in this battery had acceptable reliability over an 18-month time frame, but the values for certain individuals may vary considerably from time to time for some tests. Specific tests may require a learning period for administrators. PMID:22488138

The Effect of Extended Test Time for Students with Attention-Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Wadley, M. Nichole; Liljequist, Laura

2013-01-01

The purpose of the present study was to investigate whether a specific testing accommodation (extended time) affects test scores for college students with and without ADHD. College students with ADHD (N = 61) and without ADHD (N = 68) took a math test, after having been told they had either standard time or extended time to complete the test.…

Electrical Evaluation of RCA MWS5501D Random Access Memory, Volume 2, Appendix a

NASA Technical Reports Server (NTRS)

Klute, A.

1979-01-01

The electrical characterization and qualification test results are presented for the RCA MWS5001D random access memory. The tests included functional tests, AC and DC parametric tests, AC parametric worst-case pattern selection test, determination of worst-case transition for setup and hold times, and a series of schmoo plots. The address access time, address readout time, the data hold time, and the data setup time are some of the results surveyed.

Setting Time Limits on Tests

ERIC Educational Resources Information Center

van der Linden, Wim J.

2011-01-01

It is shown how the time limit on a test can be set to control the probability of a test taker running out of time before completing it. The probability is derived from the item parameters in the lognormal model for response times. Examples of curves representing the probability of running out of time on a test with given parameters as a function…

The Effect of Triage on Patient Flow in an Outpatient Clinic.

DTIC Science & Technology

1979-12-01

returns the records to the reception desk, and then checks his in- basket to call his next patient. If lab tests or X-rays are indicated and the patient is...Waiting times 7 Start and end of Provider service time provider service Total service time 8 Lab tests Percentage of lab tests ordered by screener 9 Lab... tests Percentage of lab tests ordered by provider Second provider start Provider service time and end of service Total service time 10 Referral to

Relationships among Testing Medium, Test Performance, and Testing Time of High School Students Who Are Visually Impaired

ERIC Educational Resources Information Center

Erin, Jane N.; Hong, Sunggye; Schoch, Christina; Kuo, YaJu

2006-01-01

This study compared the test scores and time required by high school students who are blind, sighted, or have low vision to complete tests administered in written and oral formats. The quantitative results showed that the blind students performed better on multiple-choice tests in braille and needed more time while taking tests in braille. The…

Biochemical methane potential (BMP) tests: Reducing test time by early parameter estimation.

PubMed

Da Silva, C; Astals, S; Peces, M; Campos, J L; Guerrero, L

2018-01-01

Biochemical methane potential (BMP) test is a key analytical technique to assess the implementation and optimisation of anaerobic biotechnologies. However, this technique is characterised by long testing times (from 20 to >100days), which is not suitable for waste utilities, consulting companies or plants operators whose decision-making processes cannot be held for such a long time. This study develops a statistically robust mathematical strategy using sensitivity functions for early prediction of BMP first-order model parameters, i.e. methane yield (B 0 ) and kinetic constant rate (k). The minimum testing time for early parameter estimation showed a potential correlation with the k value, where (i) slowly biodegradable substrates (k≤0.1d -1 ) have a minimum testing times of ≥15days, (ii) moderately biodegradable substrates (0.1

Pattern Generator for Bench Test of Digital Boards

NASA Technical Reports Server (NTRS)

Berkun, Andrew C.; Chu, Anhua J.

2012-01-01

All efforts to develop electronic equipment reach a stage where they need a board test station for each board. The SMAP digital system consists of three board types that interact with each other using interfaces with critical timing. Each board needs to be tested individually before combining into the integrated digital electronics system. Each board needs critical timing signals from the others to be able to operate. A bench test system was developed to support test of each board. The test system produces all the outputs of the control and timing unit, and is delivered much earlier than the timing unit. Timing signals are treated as data. A large file is generated containing the state of every timing signal at any instant. This file is streamed out to an IO card, which is wired directly to the device-under-test (DUT) input pins. This provides a flexible test environment that can be adapted to any of the boards required to test in a standalone configuration. The problem of generating the critical timing signals is then transferred from a hardware problem to a software problem where it is more easily dealt with.

The freckle plot (daily turnaround time chart): a technique for timely and effective quality improvement of test turnaround times.

PubMed

Pellar, T G; Ward, P J; Tuckerman, J F; Henderson, A R

1993-06-01

Test turnaround times are often monitored on a monthly basis. However, such an interval usually means that not all causes for delay in test reporting can be unequivocally identified for institution of remedial action. We have devised a daily chart--the freckle plot--that graphically displays the test turnaround times by laboratory receipt time. Different symbols are used to designate specimens reported within the test's turnaround time limit, those within 10 min beyond that limit, and those well outside the limit. These categories are adjustable to suit different limits of stringency. Freckle plots are produced on a daily basis and can be used to track down causes for test delays. Using the 1-h turnaround time "stat" potassium test as a model, we found 16 causes for test delay, of which 9 were potentially remediable. By applying these remedies, we were able to increase test compliance, in the day shift, from 91.5% (95% confidence interval 88.8%-93.7%) to 97.6% (95% confidence interval 96.4-98.55%), which is significant at P < 10(-7). This daily plot is a useful quality assurance tool, supplementing the more conventional tests used to ensure laboratory quality improvement.

Update on lifetime tests results and analysis carried out on Thales Cryogenics integral coolers (RM family)

NASA Astrophysics Data System (ADS)

Cauquil, Jean-Marc; Martin, Jean-Yves; Bruins, Peter; Benschop, A. A. J.

2003-01-01

The life time tests realised on the serial production of Rotary Mmonoblock RM2 coolers show a measured MTTF of 4900 hours. The conventional test profile applied to these coolers is representative of operation in typical application. The duration of such life time tests is very long. The results of a design change and its impact on MTTF are available only several months after the assembly of the prototypes. We decided to develop a test method in order to reduce the duration of these life time tests. The principle is to define a test protocol easy to implement, more severe than typical application profile in order to accelerate life time tests. The accelerated test profile was defined and tested successfully. This new technique allows us to reduce life time tests costs and duration and thus the costs involved. As a consequence, we decided to have a screening of our production with this accelerated test. This allows us to master continuously the quality of our serial products and to collect additional data. This paper presents the results of life time tests performed on RM2 coolers according to the conventional and accelerated test profiles as well as the first results on the new RM2 design which show a calculated MTTF of 10000 hours.

Generating linear regression model to predict motor functions by use of laser range finder during TUG.

PubMed

Adachi, Daiki; Nishiguchi, Shu; Fukutani, Naoto; Hotta, Takayuki; Tashiro, Yuto; Morino, Saori; Shirooka, Hidehiko; Nozaki, Yuma; Hirata, Hinako; Yamaguchi, Moe; Yorozu, Ayanori; Takahashi, Masaki; Aoyama, Tomoki

2017-05-01

The purpose of this study was to investigate which spatial and temporal parameters of the Timed Up and Go (TUG) test are associated with motor function in elderly individuals. This study included 99 community-dwelling women aged 72.9 ± 6.3 years. Step length, step width, single support time, variability of the aforementioned parameters, gait velocity, cadence, reaction time from starting signal to first step, and minimum distance between the foot and a marker placed to 3 in front of the chair were measured using our analysis system. The 10-m walk test, five times sit-to-stand (FTSTS) test, and one-leg standing (OLS) test were used to assess motor function. Stepwise multivariate linear regression analysis was used to determine which TUG test parameters were associated with each motor function test. Finally, we calculated a predictive model for each motor function test using each regression coefficient. In stepwise linear regression analysis, step length and cadence were significantly associated with the 10-m walk test, FTSTS and OLS test. Reaction time was associated with the FTSTS test, and step width was associated with the OLS test. Each predictive model showed a strong correlation with the 10-m walk test and OLS test (P < 0.01), which was not significant higher correlation than TUG test time. We showed which TUG test parameters were associated with each motor function test. Moreover, the TUG test time regarded as the lower extremity function and mobility has strong predictive ability in each motor function test. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Specimen origin, type and testing laboratory are linked to longer turnaround times for HIV viral load testing in Malawi

PubMed Central

Chipungu, Geoffrey; Kim, Andrea A.; Sarr, Abdoulaye; Ali, Hammad; Mwenda, Reuben; Nkengasong, John N.; Singer, Daniel

2017-01-01

Background Efforts to reach UNAIDS’ treatment and viral suppression targets have increased demand for viral load (VL) testing and strained existing laboratory networks, affecting turnaround time. Longer VL turnaround times delay both initiation of formal adherence counseling and switches to second-line therapy for persons failing treatment and contribute to poorer health outcomes. Methods We utilized descriptive statistics and logistic regression to analyze VL testing data collected in Malawi between January 2013 and March 2016. The primary outcomes assessed were greater-than-median pretest phase turnaround time (days elapsed from specimen collection to receipt at the laboratory) and greater-than-median test phase turnaround time (days from receipt to testing). Results The median number of days between specimen collection and testing increased 3-fold between 2013 (8 days, interquartile range (IQR) = 6–16) and 2015 (24, IQR = 13–39) (p<0.001). Multivariable analysis indicated that the odds of longer pretest phase turnaround time were significantly higher for specimen collection districts without laboratories capable of conducting viral load tests (adjusted odds ratio (aOR) = 5.16; 95% confidence interval (CI) = 5.04–5.27) as well as for Malawi’s Northern and Southern regions. Longer test phase turnaround time was significantly associated with use of dried blood spots instead of plasma (aOR = 2.30; 95% CI = 2.23–2.37) and for certain testing months and testing laboratories. Conclusion Increased turnaround time for VL testing appeared to be driven in part by categorical factors specific to the phase of turnaround time assessed. Given the implications of longer turnaround time and the global effort to scale up VL testing, addressing these factors via increasing efficiencies, improving quality management systems and generally strengthening the VL spectrum should be considered essential components of controlling the HIV epidemic. PMID:28235013

Factors Influencing Ball-Player Impact Probability in Youth Baseball

PubMed Central

Matta, Philip A.; Myers, Joseph B.; Sawicki, Gregory S.

2015-01-01

Background: Altering the weight of baseballs for youth play has been studied out of concern for player safety. Research has shown that decreasing the weight of baseballs may limit the severity of both chronic arm and collision injuries. Unfortunately, reducing the weight of the ball also increases its exit velocity, leaving pitchers and nonpitchers with less time to defend themselves. The purpose of this study was to examine impact probability for pitchers and nonpitchers. Hypothesis: Reducing the available time to respond by 10% (expected from reducing ball weight from 142 g to 113 g) would increase impact probability for pitchers and nonpitchers, and players’ mean simple response time would be a primary predictor of impact probability for all participants. Study Design: Nineteen subjects between the ages of 9 and 13 years performed 3 experiments in a controlled laboratory setting: a simple response time test, an avoidance response time test, and a pitching response time test. Methods: Each subject performed these tests in order. The simple reaction time test tested the subjects’ mean simple response time, the avoidance reaction time test tested the subjects’ ability to avoid a simulated batted ball as a fielder, and the pitching reaction time test tested the subjects’ ability to avoid a simulated batted ball as a pitcher. Results: Reducing the weight of a standard baseball from 142 g to 113 g led to a less than 5% increase in impact probability for nonpitchers. However, the results indicate that the impact probability for pitchers could increase by more than 25%. Conclusion: Pitching may greatly increase the amount of time needed to react and defend oneself from a batted ball. Clinical Relevance: Impact injuries to youth baseball players may increase if a 113-g ball is used. PMID:25984261

Electrical Evaluation of RCA MWS5001D Random Access Memory, Volume 4, Appendix C

NASA Technical Reports Server (NTRS)

Klute, A.

1979-01-01

The electrical characterization and qualification test results are presented for the RCA MWS5001D random access memory. The tests included functional tests, AC and DC parametric tests, AC parametric worst-case pattern selection test, determination of worst-case transition for setup and hold times, and a series of schmoo plots. Statistical analysis data is supplied along with write pulse width, read cycle time, write cycle time, and chip enable time data.

Timed Online Tests: Do Students Perform Better with More Time?

ERIC Educational Resources Information Center

Portolese, Laura; Krause, Jackie; Bonner, Julie

2016-01-01

This article focuses on timed tests and specifically on whether increased time enhances test performance. Three courses during the Winter 2015 term (quizzes n = 573) and three courses over the Spring 2015 term (quizzes n = 600) comprised this sample. Students were given the same tests, but the experimental group (Spring 2015) was given 50% more…

Systemic synergism between codeine and morphine in three pain models in mice.

PubMed

Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2013-01-01

The combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes. This study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models. Intrathecal morphine resulted to be 7.5 times more potent than ip morphine in the writhing test, 55.6 times in the tail flick test and 1.7 times in phase II of the orofacial formalin test; however, in phase I of the same test ip was 1.2 times more potent than it morphine. Intrathecal codeine resulted being 3.4 times more potent than ip codeine in the writhing test, 1.6 times in the tail flick test, 2.5 times in phase I and 6.7 times in phase II of the orofacial formalin test. Opioid coadministration had a synergistic effect in the acute tonic pain (acetic acid writhing test), acute phasic pain (tail flick test) and inflammatory pain (orofacial formalin test). The interaction index ranged between 0.284 (writhing ip) and 0.440 (orofacial formalin phase II ip). This synergy may relate to the different pathways of pain transmission and to the different intracellular signal transduction. The present findings also raise the possibility of potential clinical advantages in combining opioids in pain management.

Testing for Aberrant Behavior in Response Time Modeling

ERIC Educational Resources Information Center

Marianti, Sukaesi; Fox, Jean-Paul; Avetisyan, Marianna; Veldkamp, Bernard P.; Tijmstra, Jesper

2014-01-01

Many standardized tests are now administered via computer rather than paper-and-pencil format. In a computer-based testing environment, it is possible to record not only the test taker's response to each question (item) but also the amount of time spent by the test taker in considering and answering each item. Response times (RTs) provide…

Test results of the STI GPS time transfer receiver

NASA Technical Reports Server (NTRS)

Hall, D. L.; Handlan, J.; Wheeler, P.

1983-01-01

Global time transfer, or synchronization, between a user clock and USNO UTC time can be performed using the Global Positioning System (GPS), and commercially available time transfer receivers. This paper presents the test results of time transfer using the GPS system and a Stanford Telecommunications, Inc. (STI) Time Transfer System (TTS) Model 502. Tests at the GPS Master Control Site (MCS) in Vandenburg, California and at the United States Naval Observatory (USNO) in Washington, D.C. are described. An overview of GPS, and the STI TTS 502 is presented. A discussion of the time transfer process and test concepts is included.

Response Time Analysis and Test of Protection System Instrument Channels for APR1400 and OPR1000

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Chang Jae; Han, Seung; Yun, Jae Hee

2015-07-01

Safety limits are required to maintain the integrity of physical barriers designed to prevent the uncontrolled release of radioactive materials in nuclear power plants. The safety analysis establishes two critical constraints that include an analytical limit in terms of a measured or calculated variable, and a specific time after the analytical limit is reached to begin protective action. Keeping with the nuclear regulations and industry standards, satisfying these two requirements will ensure that the safety limit will not be exceeded during the design basis event, either an anticipated operational occurrence or a postulated accident. Various studies on the setpoint determinationmore » methodology for the safety-related instrumentation have been actively performed to ensure that the requirement of the analytical limit is satisfied. In particular, the protection setpoint methodology for the advanced power reactor 1400 (APP1400) and the optimized power reactor 1000 (OPR1000) has been recently developed to cover both the design basis event and the beyond design basis event. The developed setpoint methodology has also been quantitatively validated using specific computer programs and setpoint calculations. However, the safety of nuclear power plants cannot be fully guaranteed by satisfying the requirement of the analytical limit. In spite of the response time verification requirements of nuclear regulations and industry standards, it is hard to find the studies on the systematically integrated methodology regarding the response time evaluation. In cases of APR1400 and OPR1000, the response time analysis for the plant protection system is partially included in the setpoint calculation and the response time test is separately performed via the specific plant procedure. The test technique has a drawback which is the difficulty to demonstrate completeness of timing test. The analysis technique has also a demerit of resulting in extreme times that not actually possible. Thus, the establishment of the systematic response time evaluation methodology is needed to justify the conformance to the response time requirement used in the safety analysis. This paper proposes the response time evaluation methodology for APR1400 and OPR1000 using the combined analysis and test technique to confirm that the plant protection system can meet the analytical response time assumed in the safety analysis. In addition, the results of the quantitative evaluation performed for APR1400 and OPR1000 are presented in this paper. The proposed response time analysis technique consists of defining the response time requirement, determining the critical signal path for the trip parameter, allocating individual response time to each component on the signal path, and analyzing the total response time for the trip parameter, and demonstrates that the total analyzed response time does not exceed the response time requirement. The proposed response time test technique is composed of defining the response time requirement, determining the critical signal path for the trip parameter, determining the test method for each component on the signal path, performing the response time test, and demonstrates that the total test result does not exceed the response time requirement. The total response time should be tested in a single test that covers from the sensor to the final actuation device on the instrument channel. When the total channel is not tested in a single test, separate tests on groups of components or single components including the total instrument channel shall be combined to verify the total channel response. For APR1400 and OPR1000, the ramp test technique is used for the pressure and differential pressure transmitters and the step function testing technique is applied to the signal processing equipment and final actuation device. As a result, it can be demonstrated that the response time requirement is satisfied by the combined analysis and test technique. Therefore, the proposed methodology in this paper plays a crucial role in guaranteeing the safety of the nuclear power plants systematically satisfying one of two critical requirements from the safety analysis. (authors)« less

Reaction time and anticipatory skill of athletes in open and closed skill-dominated sport.

PubMed

Nuri, Leila; Shadmehr, Azadeh; Ghotbi, Nastaran; Attarbashi Moghadam, Behrouz

2013-01-01

In sports, reaction time and anticipatory skill are critical aspects of perceptual abilities. To date, no study has compared reaction time and anticipatory skill of athletes from open and closed skill-dominated sport. Accordingly, the present study investigated whether a difference exists in sensory-cognitive skills between these two different sport domains. Eleven volleyball players and 11 sprinters participated in this experiment. Reaction time and anticipatory skill of both groups were recorded by a custom-made software called SART (speed anticipation and reaction time test). This software consists of six sensory-cognitive tests that evaluate visual choice reaction time, visual complex choice reaction time, auditory choice reaction time, auditory complex choice reaction time, and anticipatory skill of the high speed and low speed of the ball. For each variable, an independent t-test was performed. Results suggested that sprinters were better in both auditory reaction times (P<0.001 for both tests) and volleyball players were better in both anticipatory skill tests (P = 0.007 and P = 0.04 for anticipatory skill of the high speed and low speed of the ball, respectively). However, no significant differences were found in both visual choice reaction time tests (P > 0.05 for both visual reaction time tests). It is concluded that athletes have greater sensory-cognitive skills related to their specific sport domain either open or closed.

A Search for Factors Causing Training Costs to Rise by Examining the U. S. Navy’s AT, AW, and AX Ratings during their First Enlistment Period

DTIC Science & Technology

1986-09-01

HYPOTHESIS TEST .................... 20 III. TIME TO GET RATED TWO FACTOR ANOVA RESULTS ......... 23 IV. TIME TO GET RATED TUKEY’S PAIRED COvfl’PARISON... TEST RESULTS A ............................................ 24 V. TIME TO GET RATED TUKEY’S PAIRED COMPARISON TEST RESULTS B...25 VI. SINGLE FACTOR ANOVA HYPOTHESIS TEST #I............... 27 VII. AT: TIME TO GET RATED ANOVA TEST RESULTS ............. 30

Determination of service standard time for liquid waste parameter in certification institution

NASA Astrophysics Data System (ADS)

Sembiring, M. T.; Kusumawaty, D.

2018-02-01

Baristand Industry Medan is a technical implementation unit under the Industrial and Research and Development Agency, the Ministry of Industry. One of the services often used in Baristand Industry Medan is liquid waste testing service. The company set the standard of service 9 working days for testing services. At 2015, 89.66% on testing services liquid waste does not meet the specified standard of services company. The purpose of this research is to specify the standard time of each parameter in testing services liquid waste. The method used is the stopwatch time study. There are 45 test parameters in liquid waste laboratory. The measurement of the time done 4 samples per test parameters using the stopwatch. From the measurement results obtained standard time that the standard Minimum Service test of liquid waste is 13 working days if there is testing E. coli.

42 CFR 84.95 - Service time test; open-circuit apparatus.

Code of Federal Regulations, 2013 CFR

2013-10-01

... classified according to the length of time it supplies air or oxygen to the breathing machine. (c) The... 42 Public Health 1 2013-10-01 2013-10-01 false Service time test; open-circuit apparatus. 84.95...-Contained Breathing Apparatus § 84.95 Service time test; open-circuit apparatus. (a) Service time will be...

42 CFR 84.95 - Service time test; open-circuit apparatus.

Code of Federal Regulations, 2012 CFR

2012-10-01

... classified according to the length of time it supplies air or oxygen to the breathing machine. (c) The... 42 Public Health 1 2012-10-01 2012-10-01 false Service time test; open-circuit apparatus. 84.95...-Contained Breathing Apparatus § 84.95 Service time test; open-circuit apparatus. (a) Service time will be...

42 CFR 84.95 - Service time test; open-circuit apparatus.

Code of Federal Regulations, 2014 CFR

2014-10-01

... classified according to the length of time it supplies air or oxygen to the breathing machine. (c) The... 42 Public Health 1 2014-10-01 2014-10-01 false Service time test; open-circuit apparatus. 84.95...-Contained Breathing Apparatus § 84.95 Service time test; open-circuit apparatus. (a) Service time will be...

Ion thruster system (8-cm) cyclic endurance test

NASA Technical Reports Server (NTRS)

Dulgeroff, C. R.; Beattie, J. R.; Poeschel, R. L.; Hyman, J., Jr.

1984-01-01

This report describes the qualification test of an Engineering-Model 5-mN-thrust 8-cm-diameter mercury ion thruster which is representative of the Ion Auxiliary Propulsion System (IAPS) thrusters. Two of these thrusters are scheduled for future flight test. The cyclic endurance test described herein was a ground-based test performed in a vacuum facility with a liquid-nitrogen-cooled cryo-surface and a frozen mercury target. The Power Electronics Unit, Beam Shield, Gimal, and Propellant Tank that were used with the thruster in the endurance test are also similar to those of the IAPS. The IAPS thruster that will undergo the longest beam-on-time during the actual space test will be subjected to 7,055 hours of beam-on-time and 2,557 cycles during the flight test. The endurance test was successfully concluded when the mercury in the IAPS Propellant Tank was consumed. At that time, 8,471 hours of beam-on-time and 599 cycles had been accumulated. Subsequent post-test-evaluation operations were performed (without breaking vacuum) which extended the test values to 652 cycles and 9,489 hours of beam-on-time. The Power Electronic Unit (PEU) and thruster were in the same vacuum chamber throughout the test. The PEU accumulated 10,268 hr of test time with high voltage applied to the operating thruster or dummy load.

40 CFR 797.1330 - Daphnid chronic toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... an extended period of time. In this test guideline, mortality and reproduction (and optionally... exposure over a specified period of time. In this guideline, the effect measured is immobilization. (4..., wet weight) to the volume (liters) of test solution in a test chamber at a point in time or passing...

40 CFR 797.1330 - Daphnid chronic toxicity test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... an extended period of time. In this test guideline, mortality and reproduction (and optionally... exposure over a specified period of time. In this guideline, the effect measured is immobilization. (4..., wet weight) to the volume (liters) of test solution in a test chamber at a point in time or passing...

40 CFR 797.1330 - Daphnid chronic toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... an extended period of time. In this test guideline, mortality and reproduction (and optionally... exposure over a specified period of time. In this guideline, the effect measured is immobilization. (4..., wet weight) to the volume (liters) of test solution in a test chamber at a point in time or passing...

40 CFR 797.1330 - Daphnid chronic toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... an extended period of time. In this test guideline, mortality and reproduction (and optionally... exposure over a specified period of time. In this guideline, the effect measured is immobilization. (4..., wet weight) to the volume (liters) of test solution in a test chamber at a point in time or passing...

40 CFR 797.1330 - Daphnid chronic toxicity test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... an extended period of time. In this test guideline, mortality and reproduction (and optionally... exposure over a specified period of time. In this guideline, the effect measured is immobilization. (4..., wet weight) to the volume (liters) of test solution in a test chamber at a point in time or passing...

Effects of Math Anxiety and Perfectionism on Timed versus Untimed Math Testing in Mathematically Gifted Sixth Graders

PubMed Central

Tsui, Joanne M.; Mazzocco, Michèle M. M.

2009-01-01

This study was designed to examine the effects of math anxiety and perfectionism on math performance, under timed testing conditions, among mathematically gifted sixth graders. We found that participants had worse math performance during timed versus untimed testing, but this difference was statistically significant only when the timed condition preceded the untimed condition. We also found that children with higher levels of either math anxiety or perfectionism had a smaller performance discrepancy during timed versus untimed testing, relative to children with lower levels of math anxiety or perfectionism. There were no statistically significant gender differences in overall test performance, nor in levels of math anxiety or perfectionism; however, the difference between performance on timed and untimed math testing was statistically significant for girls, but not for boys. Implications for educators are discussed. PMID:20084180

Association of unipedal standing time and bone mineral density in community-dwelling Japanese women.

PubMed

Sakai, A; Toba, N; Takeda, M; Suzuki, M; Abe, Y; Aoyagi, K; Nakamura, T

2009-05-01

Bone mineral density (BMD) and physical performance of the lower extremities decrease with age. In community-dwelling Japanese women, unipedal standing time, timed up and go test, and age are associated with BMD while in women aged 70 years and over, unipedal standing time is associated with BMD. The aim of this study was to clarify whether unipedal standing time is significantly associated with BMD in community-dwelling women. The subjects were 90 community-dwelling Japanese women aged 54.7 years. BMD of the second metacarpal bone was measured by computed X-ray densitometry. We measured unipedal standing time as well as timed up and go test to assess physical performance of the lower extremities. Unipedal standing time decreased with increased age. Timed up and go test significantly correlated with age. Low BMD was significantly associated with old age, short unipedal standing time, and long timed up and go test. Stepwise regression analysis revealed that age, unipedal standing time, and timed up and go test were significant factors associated with BMD. In 21 participants aged 70 years and over, body weight and unipedal standing time, but not age, were significantly associated with BMD. BMD and physical performance of the lower extremities decrease with older age. Unipedal standing time, timed up and go test, and age are associated with BMD in community-dwelling Japanese women. In women aged 70 years and over, unipedal standing time is significantly associated with BMD.

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

Double Time? Examining Extended Testing Time Accommodations (ETTA) in Postsecondary Settings

ERIC Educational Resources Information Center

Sokal, Laura; Vermette, Laurie Anne

2017-01-01

Over eight thousand test administrations across two universities were examined to determine whether students with disabilities were being given the necessary extended testing time accommodations and whether their use of extended time decreased over the course of their programs. Findings revealed that commonly accepted recommendations about…

Evaluation of electrical test conditions in MIL-M-38510 slash sheets

NASA Astrophysics Data System (ADS)

Sandgren, K.

1980-08-01

Adequacy of MIL-M-38510 slash sheet requirements for electrical test conditions in an automated test environment were evaluated. Military temperature range commercial devices of 13 types from 6 manufacturers were purchased. Software for testing these devices and for varying the test conditions was written for the Tektronix S-3260 test system. The devices were tested to evaluate the effects of pin-condition settling time, measurement sequence of the same and different D-C parameters, temperature sequence, differently defined temperature ambients, variable measurement conditions, sequence of time measurements, pin-application sequence, and undesignated pin condition ambiguity. An alternative to current tri-state enable and disable time measurements is proposed; S-3260 'open' and 'ground' conditions are characterized; and suggestions for changes in MIL-M-38510 slash sheet specifications and MIL-STD-883 test methods are proposed, both to correct errors and ambiguities and to facilitate the gathering of repeatable data on automated test equipment. Data obtained showed no sensitivity to measurement or temperature sequence nor to temperature ambient, provided that test times were not excessive. V sub ICP tests and some low current measurements required allowance for a pin condition settling time because of the test system speed. Some pin condition application sequences yielded incorrect measurements. Undefined terminal conditions of output pins were found to affect I sub OS and propagation delay time measurements. Truth table test results varied with test frequency and V sub IL for low-power Schottky devices.

Comparison of Fault Detection Algorithms for Real-time Diagnosis in Large-Scale System. Appendix E

NASA Technical Reports Server (NTRS)

Kirubarajan, Thiagalingam; Malepati, Venkat; Deb, Somnath; Ying, Jie

2001-01-01

In this paper, we present a review of different real-time capable algorithms to detect and isolate component failures in large-scale systems in the presence of inaccurate test results. A sequence of imperfect test results (as a row vector of I's and O's) are available to the algorithms. In this case, the problem is to recover the uncorrupted test result vector and match it to one of the rows in the test dictionary, which in turn will isolate the faults. In order to recover the uncorrupted test result vector, one needs the accuracy of each test. That is, its detection and false alarm probabilities are required. In this problem, their true values are not known and, therefore, have to be estimated online. Other major aspects in this problem are the large-scale nature and the real-time capability requirement. Test dictionaries of sizes up to 1000 x 1000 are to be handled. That is, results from 1000 tests measuring the state of 1000 components are available. However, at any time, only 10-20% of the test results are available. Then, the objective becomes the real-time fault diagnosis using incomplete and inaccurate test results with online estimation of test accuracies. It should also be noted that the test accuracies can vary with time --- one needs a mechanism to update them after processing each test result vector. Using Qualtech's TEAMS-RT (system simulation and real-time diagnosis tool), we test the performances of 1) TEAMSAT's built-in diagnosis algorithm, 2) Hamming distance based diagnosis, 3) Maximum Likelihood based diagnosis, and 4) HidderMarkov Model based diagnosis.

Comparison of physical therapy anatomy performance and anxiety scores in timed and untimed practical tests.

PubMed

Schwartz, Sarah M; Evans, Cathy; Agur, Anne M R

2015-01-01

Students in health care professional programs face many stressful tests that determine successful completion of their program. Test anxiety during these high stakes examinations can affect working memory and lead to poor outcomes. Methods of decreasing test anxiety include lengthening the time available to complete examinations or evaluating students using untimed examinations. There is currently no consensus in the literature regarding whether untimed examinations provide a benefit to test performance in clinical anatomy. This study aimed to determine the impact of timed versus untimed practical tests on Master of Physical Therapy student anatomy performance and test anxiety. Test anxiety was measured using the State-Trait Anxiety Inventory (STAI). Differences in performance, anxiety scores, and time taken were compared using paired sample Student's t-tests. Eighty-one of the 84 students completed the study and provided feedback. Students performed significantly higher on the untimed test (P = 0.005), with a significant reduction in test anxiety (P < 0.001). Students who were unsuccessful on the timed test showed the greatest improvement on the untimed test ( x¯ = 20.4 ±10%). Eighty-three percent (n = 69) of students preferred the untimed test, 8.4% (n = 7) the timed test, and 8.4% (n = 7) had no preference. Students took on average eight minutes longer on the untimed test. This study found that physical therapy students perform better on untimed tests, which may be related to a reduction in test anxiety. If the intended goal of evaluating health care professional students is to determine fundamental competencies, these factors should be considered when designing future curricula. © 2014 American Association of Anatomists.

Predictive Cutoff Values of the Five-Times Sit-to-Stand Test and the Timed "Up & Go" Test for Disability Incidence in Older People Dwelling in the Community.

PubMed

Makizako, Hyuma; Shimada, Hiroyuki; Doi, Takehiko; Tsutsumimoto, Kota; Nakakubo, Sho; Hotta, Ryo; Suzuki, Takao

2017-04-01

Lower extremity functioning is important for maintaining activity in elderly people. Optimal cutoff points for standard measurements of lower extremity functioning would help identify elderly people who are not disabled but have a high risk of developing disability. The purposes of this study were: (1) to determine the optimal cutoff points of the Five-Times Sit-to-Stand Test and the Timed "Up & Go" Test for predicting the development of disability and (2) to examine the impact of poor performance on both tests on the prediction of the risk of disability in elderly people dwelling in the community. This was a prospective cohort study. A population of 4,335 elderly people dwelling in the community (mean age = 71.7 years; 51.6% women) participated in baseline assessments. Participants were monitored for 2 years for the development of disability. During the 2-year follow-up period, 161 participants (3.7%) developed disability. The optimal cutoff points of the Five-Times Sit-to-Stand Test and the Timed "Up & Go" Test for predicting the development of disability were greater than or equal to 10 seconds and greater than or equal to 9 seconds, respectively. Participants with poor performance on the Five-Times Sit-to-Stand Test (hazard ratio = 1.88; 95% CI = 1.11-3.20), the Timed "Up & Go" Test (hazard ratio = 2.24; 95% CI = 1.42-3.53), or both tests (hazard ratio = 2.78; 95% CI = 1.78-4.33) at the baseline assessment had a significantly higher risk of developing disability than participants who had better lower extremity functioning. All participants had good initial functioning and participated in assessments on their own. Causes of disability were not assessed. Assessments of lower extremity functioning with the Five-Times Sit-to-Stand Test and the Timed "Up & Go" Test, especially poor performance on both tests, were good predictors of future disability in elderly people dwelling in the community. © 2017 American Physical Therapy Association

Fatigue-test acceleration with flight-by-flight loading and heating to simulate supersonic-transport operation

NASA Technical Reports Server (NTRS)

Imig, L. A.; Garrett, L. E.

1973-01-01

Possibilities for reducing fatigue-test time for supersonic-transport materials and structures were studied in tests with simulated flight-by-flight loading. In order to determine whether short-time tests were feasible, the results of accelerated tests (2 sec per flight) were compared with the results of real-time tests (96 min per flight). The effects of design mean stress, the stress range for ground-air-ground cycles, simulated thermal stress, the number of stress cycles in each flight, and salt corrosion were studied. The flight-by-flight stress sequences were applied to notched sheet specimens of Ti-8Al-1Mo-1V and Ti-6Al-4V titanium alloys. A linear cumulative-damage analysis accounted for large changes in stress range of the simulated flights but did not account for the differences between real-time and accelerated tests. The fatigue lives from accelerated tests were generally within a factor of two of the lives from real-time tests; thus, within the scope of the investigation, accelerated testing seems feasible.

Failure Modes in Capacitors When Tested Under a Time-Varying Stress

NASA Technical Reports Server (NTRS)

Liu, David (Donhang)

2011-01-01

Steady step surge testing (SSST) is widely applied to screen out potential power-on failures in solid tantalum capacitors. The test simulates the power supply's on and off characteristics. Power-on failure has been the prevalent failure mechanism for solid tantalum capacitors for decoupling applications. On the other hand, the SSST can also be reviewed as an electrically destructive test under a time-varying stress. It consists of rapidly charging the capacitor with incremental voltage increases, through a low resistance in series, until the capacitor under test is electrically shorted. Highly accelerated life testing (HALT) is usually a time-efficient method for determining the failure mechanism in capacitors; however, a destructive test under a time-varying stress like SSST is even more effective. It normally takes days to complete a HALT test, but it only takes minutes for a time-varying stress test to produce failures. The advantage of incorporating specific time-varying stress into a statistical model is significant in providing an alternative life test method for quickly revealing the failure modes in capacitors. In this paper, a time-varying stress has been incorporated into the Weibull model to characterize the failure modes. The SSST circuit and transient conditions to correctly test the capacitors is discussed. Finally, the SSST was applied for testing polymer aluminum capacitors (PA capacitors), Ta capacitors, and multi-layer ceramic capacitors with both precious metal electrode (PME) and base-metal-electrodes (BME). It appears that testing results are directly associated to the dielectric layer breakdown in PA and Ta capacitors and are independent on the capacitor values, the way the capacitors being built, and the manufactures. The testing results also reveal that ceramic capacitors exhibit breakdown voltages more than 20 times the rated voltage, and the breakdown voltages are inverse proportional to the dielectric layer thickness. The possibility of ceramic capacitors in front-end decoupling applications to block the surge noise from a power supply is also discussed.

Reliability of the Timed Up and Go test and Ten-Metre Timed Walk Test in Pregnant Women with Pelvic Girdle Pain.

PubMed

Evensen, Natalie M; Kvåle, Alice; Braekken, Ingeborg H

2015-09-01

There is a lack of functional objective tests available to measure functional status in women with pelvic girdle pain (PGP). The purpose of this study was to establish test-retest and intertester reliability of the Timed Up and Go (TUG) test and Ten-metre Timed Walk Test (10mTWT) in pregnant women with PGP. A convenience sample of women was recruited over a 4-month period and tested on two occasions, 1 week apart to determine test-retest reliability. Intertester reliability was established between two assessors at the first testing session. Subjects were instructed to undertake the TUG and 10mTWT at maximum speed. One practise trial and two timed trials for each walking test was undertaken on Day 1 and one practise trial and one timed trial on Day 2. Seventeen women with PGP aged 31.1 years (SD [standard deviation] = 2.3) and 28.7 weeks pregnant (SD = 7.4) completed gait testing. Test-retest reliability using the intraclass correlation coefficient (ICC) was excellent for the TUG (0.88) and good for the 10mTWT (0.74). Intertester reliability was determined in the first 13 participants with excellent ICC values being found for both walking tests (TUG: 0.95; 10mTWT: 0.94). This study demonstrated that the TUG and 10mTWT undertaken at fast pace are reliable, objective functional tests in pregnant women with PGP. While both tests are suitable for use in the clinical and research settings, we would recommend the TUG given the findings of higher test-retest reliability and as this test requires less space and time to set up and score. Future studies in a larger sample size are warranted to confirm the results of this study. Copyright © 2015 John Wiley & Sons, Ltd.

Analysis and test for space shuttle propellant dynamics (1/10th scale model test results). Volume 2: 1/10th scale model test data

NASA Technical Reports Server (NTRS)

Berry, R. L.; Tegart, J. R.; Demchak, L. J.

1979-01-01

Thirty sets of test data selected from the 89 low-g aircraft tests flown by NASA KC-135 zero-g aircraft are listed in tables with their accompanying test conditions. The data for each test consists of the time history plots of digitalized data (in engineering units) and the time history plots of the load cell data transformed to the tank axis system. The transformed load cell data was developed for future analytical comparisons; therefore, these data were transformed and plotted from the time at which the aircraft Z axis acceleration passed through l-g. There are 14 time history plots per test condition. The contents of each plot is shown in a table.

Definition of simulated driving tests for the evaluation of drivers' reactions and responses.

PubMed

Bartolozzi, Riccardo; Frendo, Francesco

2014-01-01

This article aims at identifying the most significant measures in 2 perception-response (PR) tests performed at a driving simulator: a braking test and a lateral skid test, which were developed in this work. Forty-eight subjects (26 females and 22 males) with a mean age of 24.9 ± 3.0 years were enrolled for this study. They were asked to perform a drive on the driving simulator at the University of Pisa (Italy) following a specific test protocol, including 8-10 braking tests and 8-10 lateral skid tests. Driver input signals and vehicle model signals were recorded during the drives and analyzed to extract measures such as the reaction time, first response time, etc. Following a statistical procedure (based on analysis of variance [ANOVA] and post hoc tests), all test measures (3 for the braking test and 8 for the lateral skid test) were analyzed in terms of statistically significant differences among different drivers. The presented procedure allows evaluation of the capability of a given test to distinguish among different drivers. In the braking test, the reaction time showed a high dispersion among single drivers, leading to just 4.8 percent of statistically significant driver pairs (using the Games-Howell post hoc test), whereas the pedal transition time scored 31.9 percent. In the lateral skid test, 28.5 percent of the 2 × 2 comparisons showed significantly different reaction times, 19.5 percent had different response times, 35.2 percent had a different second peak of the steering wheel signal, and 33 percent showed different values of the integral of the steering wheel signal. For the braking test, which has been widely employed in similar forms in the literature, it was shown how the reaction time, with respect to the pedal transition time, can have a higher dispersion due to the influence of external factors. For the lateral skid test, the following measures were identified as the most significant for application studies: the reaction time for the reaction phase, the second peak of the steering wheel angle for the first instinctive response, and the integral of the steering wheel angle for the complete response. The methodology used to analyze the test measures was founded on statistically based and objective evaluation criteria and could be applied to other tests. Even if obtained with a fixed-base simulator, the obtained results represent useful information for applications of the presented PR tests in experimental campaigns with driving simulators.

Computer assisted thermal-vacuum testing

NASA Technical Reports Server (NTRS)

Petrie, W.; Mikk, G.

1977-01-01

In testing complex systems and components under dynamic thermal-vacuum environments, it is desirable to optimize the environment control sequence in order to reduce test duration and cost. This paper describes an approach where a computer is utilized as part of the test control operation. Real time test data is made available to the computer through time-sharing terminals at appropriate time intervals. A mathematical model of the test article and environmental control equipment is then operated on using the real time data to yield current thermal status, temperature analysis, trend prediction and recommended thermal control setting changes to arrive at the required thermal condition. The data acquisition interface and the time-sharing hook-up to an IBM-370 computer is described along with a typical control program and data demonstrating its use.

42 CFR 84.96 - Service time test; closed-circuit apparatus.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Service time test; closed-circuit apparatus. 84.96...-Contained Breathing Apparatus § 84.96 Service time test; closed-circuit apparatus. (a) The closed-circuit apparatus will be classified according to the length of time it supplies adequate breathing gas to the...

42 CFR 84.96 - Service time test; closed-circuit apparatus.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Service time test; closed-circuit apparatus. 84.96...-Contained Breathing Apparatus § 84.96 Service time test; closed-circuit apparatus. (a) The closed-circuit apparatus will be classified according to the length of time it supplies adequate breathing gas to the...

Fragmentation of Solid Materials Using Shock Tubes. Part 1: First Test Series in a Small Diameter Shock Tube

DTIC Science & Technology

2017-01-01

time histories with peak pressures of approximately 250 psi and 500 psi. 1.2 TESTING OBJECTIVES The first goal of this test series was to explore how...finally the late- time at-rest fragments were physically collected and analyzed post-test. Because this test series physically collected over 50,000...for a single fragmenting object. Comparing the three measurement techniques used in this test series , the late- time physically- collected mass

Application of modern tests for stationarity to single-trial MEG data: transferring powerful statistical tools from econometrics to neuroscience.

PubMed

Kipiński, Lech; König, Reinhard; Sielużycki, Cezary; Kordecki, Wojciech

2011-10-01

Stationarity is a crucial yet rarely questioned assumption in the analysis of time series of magneto- (MEG) or electroencephalography (EEG). One key drawback of the commonly used tests for stationarity of encephalographic time series is the fact that conclusions on stationarity are only indirectly inferred either from the Gaussianity (e.g. the Shapiro-Wilk test or Kolmogorov-Smirnov test) or the randomness of the time series and the absence of trend using very simple time-series models (e.g. the sign and trend tests by Bendat and Piersol). We present a novel approach to the analysis of the stationarity of MEG and EEG time series by applying modern statistical methods which were specifically developed in econometrics to verify the hypothesis that a time series is stationary. We report our findings of the application of three different tests of stationarity--the Kwiatkowski-Phillips-Schmidt-Schin (KPSS) test for trend or mean stationarity, the Phillips-Perron (PP) test for the presence of a unit root and the White test for homoscedasticity--on an illustrative set of MEG data. For five stimulation sessions, we found already for short epochs of duration of 250 and 500 ms that, although the majority of the studied epochs of single MEG trials were usually mean-stationary (KPSS test and PP test), they were classified as nonstationary due to their heteroscedasticity (White test). We also observed that the presence of external auditory stimulation did not significantly affect the findings regarding the stationarity of the data. We conclude that the combination of these tests allows a refined analysis of the stationarity of MEG and EEG time series.

Reliability Evaluation of Concentrator Photovoltaic Modules per IEC Qualification Specifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamizhmani, Govindasamy

2012-12-05

This project is related to the qualification testing of new generation CPV (concentrator photovoltaics) modules at lower testing costs and lower turnaround time. In this project, the first testing program was completed for two CPV manufacturers, the second testing program was completed for two manufacturers at 65% of the actual testing cost and at less than 3 months of testing turnaround time and the third testing program was completed for two manufacturers at 65% of the actual testing cost and at less than 3 months of testing turnaround time. Due to their financial situation and restructuring, Amonix (one of themore » CPV manufacturers) intermittently terminated the test programs.« less

Factors affecting accuracy in the Developmental Eye Movement Test measurement for Cantonese-speaking children.

PubMed

Pang, Peter C; Lam, Carly S; Woo, George C

2010-09-01

This study aims to determine the factors affecting the accuracy in the Developmental Eye Movement (DEM) test measurement for Cantonese-speaking children. The voices of 10 Cantonese-speaking children (aged between six and eight years) undertaking the vertical test (40 numbers) of the DEM test were recorded on a digital audio recorder. These voice clips were assessed by an experienced examiner to give the DEM test times. The examiner repeated the measurement five times for each voice clip and completed all 10 voice clips from the 10 children. The average of a single measurement, the mean of two, the mean of three and the mean of five repeated measurements were then compared. Five experienced and five inexperienced examiners of the DEM test were asked to record the results from five Cantonese-speaking children by listening to the playback of prerecorded audio clips. The deviation of the results from the preset values between the two groups was compared. There is no difference between the single measurement and those obtained by mean of two, three, four or five. Both experienced and inexperienced examiners obtained a higher deviation from the preset values in the adjusted compared with the non-adjusted times in both vertical and horizontal times. Experienced examiners measured the vertical times and adjusted vertical times significantly closer to the preset values than the inexperienced examiners (paired t-test, p < 0.05). The DEM test needs to be measured only once for an accurate time measurement. Inaccurate assessment of 'reading errors' in the DEM test can increase the inaccuracy of the adjusted times. It is suggested that an audio recording of the test be made to allow reassessment of reading errors. Experience in using the DEM test yields a more accurate DEM measurement as errors are detected more easily.

Improvement for enhancing effectiveness of universal power system (UPS) continuous testing process

NASA Astrophysics Data System (ADS)

Sriratana, Lerdlekha

2018-01-01

This experiment aims to enhance the effectiveness of the Universal Power System (UPS) continuous testing process of the Electrical and Electronic Institute by applying work scheduling and time study methods. Initially, the standard time of testing process has not been considered that results of unaccurate testing target and also time wasting has been observed. As monitoring and reducing waste time for improving the efficiency of testing process, Yamazumi chart and job scheduling theory (North West Corner Rule) were applied to develop new work process. After the improvements, the overall efficiency of the process possibly increased from 52.8% to 65.6% or 12.7%. Moreover, the waste time could reduce from 828.3 minutes to 653.6 minutes or 21%, while testing units per batch could increase from 3 to 4 units. Therefore, the number of testing units would increase from 12 units up to 20 units per month that also contribute to increase of net income of UPS testing process by 72%.

Effects of Differentially Time-Consuming Tests on Computer-Adaptive Test Scores

ERIC Educational Resources Information Center

Bridgeman, Brent; Cline, Frederick

2004-01-01

Time limits on some computer-adaptive tests (CATs) are such that many examinees have difficulty finishing, and some examinees may be administered tests with more time-consuming items than others. Results from over 100,000 examinees suggested that about half of the examinees must guess on the final six questions of the analytical section of the…

Response Time as an Indicator of Test Taker Speed: Assumptions Meet Reality

ERIC Educational Resources Information Center

Wise, Steven L.

2015-01-01

The growing presence of computer-based testing has brought with it the capability to routinely capture the time that test takers spend on individual test items. This, in turn, has led to an increased interest in potential applications of response time in measuring intellectual ability and achievement. Goldhammer (this issue) provides a very useful…

Evaluation of the Splash Time Test as a Bedside Test for Hiatal Hernia.

PubMed

Lindow, Thomas Akesson; Franzen, Thomas

2014-12-01

Hiatal hernias may present with heartburn, acid regurgitation, dysphagia, chest pain, pulmonary symptoms and globus jugularis. Due to the heterogeneous presentation, there is a need for a simple diagnostic instrument when hiatal hernia is suspected. Hiatal hernia may impair esophageal bolus transportation. The splash time test is a rough measurement of esophageal bolus transportation, where time is measured from the start of swallowing a liquid bolus to the appearance of a "splashing" sound at xiphoid level. We aimed to test the hypothesis that the splash time test is prolonged in patients with hiatal hernia compared to normal subjects. In 30 patients with hiatal hernia, time was measured from swallow to splash using audiosignal recording. Thirty healthy subjects were used as controls. Median time from swallow to splash was 4.9 seconds in the patient group and 4.4 seconds in the control group. Five patients, but none of the controls, performed swallows with absence of splash. Using only absence of splash as a pathological result, sensitivity was 23% and specificity was 100%. The splash time test is not a sensitive instrument in diagnosing hiatal hernias. The absence of splash, however, seems to be a specific marker of hiatal hernia. Further research is needed regarding which other conditions besides hiatal hernia may cause absence of splash. The splash time test can be replaced by the even simpler "splash test".

Time-Dependent Behaviors of Granite: Loading-Rate Dependence, Creep, and Relaxation

NASA Astrophysics Data System (ADS)

Hashiba, K.; Fukui, K.

2016-07-01

To assess the long-term stability of underground structures, it is important to understand the time-dependent behaviors of rocks, such as their loading-rate dependence, creep, and relaxation. However, there have been fewer studies on crystalline rocks than on tuff, mudstone, and rock salt, because the high strength of crystalline rocks makes the detection of their time-dependent behaviors much more difficult. Moreover, studies on the relaxation, temporal change of stress and strain (TCSS) conditions, and relations between various time-dependent behaviors are scarce for not only granites, but also other rocks. In this study, previous reports on the time-dependent behaviors of granites were reviewed and various laboratory tests were conducted using Toki granite. These tests included an alternating-loading-rate test, creep test, relaxation test, and TCSS test. The results showed that the degree of time dependence of Toki granite is similar to other granites, and that the TCSS resembles the stress-relaxation curve and creep-strain curve. A viscoelastic constitutive model, proposed in a previous study, was modified to investigate the relations between the time-dependent behaviors in the pre- and post-peak regions. The modified model reproduced the stress-strain curve, creep, relaxation, and the results of the TCSS test. Based on a comparison of the results of the laboratory tests and numerical simulations, close relations between the time-dependent behaviors were revealed quantitatively.

Barriers to Pap Smear Test for the Second Time in Women Referring to Health Care Centers in the South of Tehran: A Qualitative Approach

PubMed Central

Hassani, Laleh; Dehdari, Tahereh; Hajizadeh, Ebrahim; Shojaeizadeh, Davoud; Abedini, Mehrandokht; Nedjat, Saharnaz

2017-01-01

ABSTRACT Background: Cervical cancer is a preventable disease with a regular screening program. Many studies have reported a large number of barriers that women had for the first time, but this study decided to find other barriers for the second time pap smear. Methods: In this qualitative research, data were gathered through in-depth interviews and expressed through conventional content analysis in the form of constant comparison. The participants were 15 women with family profile at 30 health care centers who lived in the south of Tehran and had done Pap smear for one time but didn’t do it for the second time. Results: Three main themes emerged from the analysis of the interviews: negative experiences of the first Pap test were as follows: results of the first time test, readiness for performing the test, getting the test itself, and the site of the first Pap test. Personal barriers to getting the second Pap test were: inattention to time, physical barriers to the second Pap test, and inhibitory beliefs. Perceived social barriers to getting the second Pap test with two sub-themes included social supports and abstract norms. Conclusion: This study provided other barriers about Pap smear including lack of the spouse’s support, the role of health care providers and physicians in screening program for early diagnosis in women. PMID:29043283

Real-Time Global Nonlinear Aerodynamic Modeling for Learn-To-Fly

NASA Technical Reports Server (NTRS)

Morelli, Eugene A.

2016-01-01

Flight testing and modeling techniques were developed to accurately identify global nonlinear aerodynamic models for aircraft in real time. The techniques were developed and demonstrated during flight testing of a remotely-piloted subscale propeller-driven fixed-wing aircraft using flight test maneuvers designed to simulate a Learn-To-Fly scenario. Prediction testing was used to evaluate the quality of the global models identified in real time. The real-time global nonlinear aerodynamic modeling algorithm will be integrated and further tested with learning adaptive control and guidance for NASA Learn-To-Fly concept flight demonstrations.

Mechanistic evaluation of test data from LTPP flexible pavement test sections, Vol. I

DOT National Transportation Integrated Search

1996-01-01

This report summarizes the process and lessons learned from the Standardized Travel Time Surveys and Field Test project. The field tests of travel time data collection were conducted in Boston, Seattle, and Lexington in 1993. The methodologies tested...

Effects of Math Anxiety and Perfectionism on Timed versus Untimed Math Testing in Mathematically Gifted Sixth Graders

ERIC Educational Resources Information Center

Tsui, Joanne M.; Mazzocco, Michele M. M.

2006-01-01

This study was designed to examine the effects of math anxiety and perfectionism on math performance, under timed testing conditions, among mathematically gifted sixth graders. We found that participants had worse math performance during timed versus untimed testing, but this difference was statistically significant only when the timed condition…

A Flexible Latent Trait Model for Response Times in Tests

ERIC Educational Resources Information Center

Ranger, Jochen; Kuhn, Jorg-Tobias

2012-01-01

Latent trait models for response times in tests have become popular recently. One challenge for response time modeling is the fact that the distribution of response times can differ considerably even in similar tests. In order to reduce the need for tailor-made models, a model is proposed that unifies two popular approaches to response time…

42 CFR 84.95 - Service time test; open-circuit apparatus.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Service time test; open-circuit apparatus. 84.95...-Contained Breathing Apparatus § 84.95 Service time test; open-circuit apparatus. (a) Service time will be measured with a breathing machine as described in § 84.88. (b) The open-circuit apparatus will be...

42 CFR 84.95 - Service time test; open-circuit apparatus.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Service time test; open-circuit apparatus. 84.95...-Contained Breathing Apparatus § 84.95 Service time test; open-circuit apparatus. (a) Service time will be measured with a breathing machine as described in § 84.88. (b) The open-circuit apparatus will be...

Accuracy of the Timed Up and Go test for predicting sarcopenia in elderly hospitalized patients.

PubMed

Martinez, Bruno Prata; Gomes, Isabela Barboza; Oliveira, Carolina Santana de; Ramos, Isis Resende; Rocha, Mônica Diniz Marques; Forgiarini Júnior, Luiz Alberto; Camelier, Fernanda Warken Rosa; Camelier, Aquiles Assunção

2015-05-01

The ability of the Timed Up and Go test to predict sarcopenia has not been evaluated previously. The objective of this study was to evaluate the accuracy of the Timed Up and Go test for predicting sarcopenia in elderly hospitalized patients. This cross-sectional study analyzed 68 elderly patients (≥60 years of age) in a private hospital in the city of Salvador-BA, Brazil, between the 1st and 5th day of hospitalization. The predictive variable was the Timed Up and Go test score, and the outcome of interest was the presence of sarcopenia (reduced muscle mass associated with a reduction in handgrip strength and/or weak physical performance in a 6-m gait-speed test). After the descriptive data analyses, the sensitivity, specificity and accuracy of a test using the predictive variable to predict the presence of sarcopenia were calculated. In total, 68 elderly individuals, with a mean age 70.4±7.7 years, were evaluated. The subjects had a Charlson Comorbidity Index score of 5.35±1.97. Most (64.7%) of the subjects had a clinical admission profile; the main reasons for hospitalization were cardiovascular disorders (22.1%), pneumonia (19.1%) and abdominal disorders (10.2%). The frequency of sarcopenia in the sample was 22.1%, and the mean length of time spent performing the Timed Up and Go test was 10.02±5.38 s. A time longer than or equal to a cutoff of 10.85 s on the Timed Up and Go test predicted sarcopenia with a sensitivity of 67% and a specificity of 88.7%. The accuracy of this cutoff for the Timed Up and Go test was good (0.80; IC=0.66-0.94; p=0.002). The Timed Up and Go test was shown to be a predictor of sarcopenia in elderly hospitalized patients.

Impact of SMS/GPRS Printers in Reducing Time to Early Infant Diagnosis Compared With Routine Result Reporting: A Systematic Review and Meta-Analysis

PubMed Central

Markby, Jessica; Boeke, Caroline; Penazzato, Martina; Urick, Brittany; Ghadrshenas, Anisa; Harris, Lindsay; Ford, Nathan; Peter, Trevor

2017-01-01

Background: Despite significant gains made toward improving access, early infant diagnosis (EID) testing programs suffer from long test turnaround times that result in substantial loss to follow-up and mortality associated with delays in antiretroviral therapy initiation. These delays in treatment initiation are particularly impactful because of significant HIV-related infant mortality observed by 2–3 months of age. Short message service (SMS) and general packet radio service (GPRS) printers allow test results to be transmitted immediately to health care facilities on completion of testing in the laboratory. Methods: We conducted a systematic review and meta-analysis to assess the benefit of using SMS/GPRS printers to increase the efficiency of EID test result delivery compared with traditional courier paper–based results delivery methods. Results: We identified 11 studies contributing data for over 16,000 patients from East and Southern Africa. The test turnaround time from specimen collection to result received at the health care facility with courier paper–based methods was 68.0 days (n = 6835), whereas the test turnaround time with SMS/GPRS printers was 51.1 days (n = 6711), resulting in a 2.5-week (25%) reduction in the turnaround time. Conclusions: Courier paper–based EID test result delivery methods are estimated to add 2.5 weeks to EID test turnaround times in low resource settings and increase the risk that infants receive test results during or after the early peak of infant mortality. SMS/GPRS result delivery to health care facility printers significantly reduced test turnaround time and may reduce this risk. SMS/GPRS printers should be considered for expedited delivery of EID and other centralized laboratory test results. PMID:28825941

Computerized Maze Navigation and On-Road Performance by Drivers With Dementia

PubMed Central

Ott, Brian R.; Festa, Elena K.; Amick, Melissa M.; Grace, Janet; Davis, Jennifer D.; Heindel, William C.

2012-01-01

This study examined the ability of computerized maze test performance to predict the road test performance of cognitively impaired and normal older drivers. The authors examined 133 older drivers, including 65 with probable Alzheimer disease, 23 with possible Alzheimer disease, and 45 control subjects without cognitive impairment. Subjects completed 5 computerized maze tasks employing a touch screen and pointer as well as a battery of standard neuropsychological tests. Parameters measured for mazes included errors, planning time, drawing time, and total time. Within 2 weeks, subjects were examined by a professional driving instructor on a standardized road test modeled after the Washington University Road Test. Road test total score was significantly correlated with total time across the 5 mazes. This maze score was significant for both Alzheimer disease subjects and control subjects. One maze in particular, requiring less than 2 minutes to complete, was highly correlated with driving performance. For the standard neuropsychological tests, highest correlations were seen with Trail Making A (TrailsA) and the Hopkins Verbal Learning Tests Trial 1 (HVLT1). Multiple regression models for road test score using stepwise subtraction of maze and neuropsychological test variables revealed significant independent contributions for total maze time, HVLT1, and TrailsA for the entire group; total maze time and HVLT1 for Alzheimer disease subjects; and TrailsA for normal subjects. As a visual analog of driving, a brief computerized test of maze navigation time compares well to standard neuropsychological tests of psychomotor speed, scanning, attention, and working memory as a predictor of driving performance by persons with early Alzheimer disease and normal elders. Measurement of maze task performance appears to be useful in the assessment of older drivers at risk for hazardous driving. PMID:18287166

Oxytocin treatment does not change cardiovascular parameters, hematology and plasma electrolytes in parturient horse mares.

PubMed

Nagel, Christina; Trenk, Lisa; Wulf, Manuela; Ille, Natascha; Aurich, Jörg; Aurich, Christine

2017-03-15

In mares, foaling is associated with changes in hematology, plasma electrolytes, blood pressure and heart rate and it has been hypothesized that these are induced by oxytocin. To test this hypothesis, mares (n = 8-14/group) were treated with oxytocin (OT; 20 I.U.) or saline (CON) at 1 h (test A) and 12 h after foaling (test B) and during first postpartum diestrus (test C). Heart rate, heart rate variability (HRV), atrioventricular blocks, salivary cortisol concentration, blood pressure, plasma electrolytes and blood count were determined. Heart rate decreased from test A to C (P < 0.001) but at no time differed between groups. The HRV, blood pressure and occurrence of atrioventricular blocks did not change in response to oxytocin. Cortisol concentration decreased from test A to C (P < 0.001). Oxytocin induced a cortisol release in test B (time x treatment P < 0.001, time x test P < 0.001). Plasma sodium and chloride concentrations decreased from test A to C (P < 0.001) but did not differ between groups. In test A, potassium concentration increased in CON but not OT mares (time P < 0.01, time x test P < 0.01, time x treatment P < 0.05). Polymorphnuclear cell (PMN) numbers in blood decreased from test A to C (P < 0.001) while lymphocytes increased (P < 0.05). At no time PMN and lymphocytes differed between groups. Oxytocin treatment had no effect on skin temperature. In conclusion, except for a limited effect on cortisol release, oxytocin was without effect and the hypothesis of oxytocin-induced alterations in cardiac parameters, plasma electrolytes and hematology of foaling mares was not verified. Copyright © 2016 Elsevier Inc. All rights reserved.

Five different tests of reaction time evaluated in HIV seropositive men.

PubMed

Dunlop, O; Bjørklund, R A; Abdelnoor, M; Myrvang, B

1992-09-01

In an attempt to develop a short neuropsychological test battery five different tests of reaction time were assessed according to their ability to discriminate between HIV seropositive men and healthy controls. In all tests a patient group with clinical symptoms was slower than the control group. In the complex reaction time test, which has a large cognitive aspect, even a clinically "asymptomatic" group was slower than the control group. The movement test, a new test with a large motor component, identified most slow responders, defining approximately half of the patients with clinical symptoms and one third of the "asymptomatic" patients as such. A test battery consisting of three tests is suggested for serial assessment and screening.

Testing the accuracy of timing reports in visual timing tasks with a consumer-grade digital camera.

PubMed

Smyth, Rachael E; Oram Cardy, Janis; Purcell, David

2017-06-01

This study tested the accuracy of a visual timing task using a readily available and relatively inexpensive consumer grade digital camera. A visual inspection time task was recorded using short high-speed video clips and the timing as reported by the task's program was compared to the timing as recorded in the video clips. Discrepancies in these two timing reports were investigated further and based on display refresh rate, a decision was made whether the discrepancy was large enough to affect the results as reported by the task. In this particular study, the errors in timing were not large enough to impact the results of the study. The procedure presented in this article offers an alternative method for performing a timing test, which uses readily available hardware and can be used to test the timing in any software program on any operating system and display.

Design and test of an automated version of the modified Jebsen test of hand function using Microsoft Kinect.

PubMed

Simonsen, Daniel; Nielsen, Ida F; Spaich, Erika G; Andersen, Ole K

2017-05-02

The present paper describes the design and evaluation of an automated version of the Modified Jebsen Test of Hand Function (MJT) based on the Microsoft Kinect sensor. The MJT was administered twice to 11 chronic stroke subjects with varying degrees of hand function deficits. The test times of the MJT were evaluated manually by a therapist using a stopwatch, and automatically using the Microsoft Kinect sensor. The ground truth times were assessed based on inspection of the video-recordings. The agreement between the methods was evaluated along with the test-retest performance. The results from Bland-Altman analysis showed better agreement between the ground truth times and the automatic MJT time evaluations compared to the agreement between the ground truth times and the times estimated by the therapist. The results from the test-retest performance showed that the subjects significantly improved their performance in several subtests of the MJT, indicating a practice effect. The results from the test showed that the Kinect can be used for automating the MJT.

Flight Tests of a Remaining Flying Time Prediction System for Small Electric Aircraft in the Presence of Faults

NASA Technical Reports Server (NTRS)

Hogge, Edward F.; Kulkarni, Chetan S.; Vazquez, Sixto L.; Smalling, Kyle M.; Strom, Thomas H.; Hill, Boyd L.; Quach, Cuong C.

2017-01-01

This paper addresses the problem of building trust in the online prediction of a battery powered aircraft's remaining flying time. A series of flight tests is described that make use of a small electric powered unmanned aerial vehicle (eUAV) to verify the performance of the remaining flying time prediction algorithm. The estimate of remaining flying time is used to activate an alarm when the predicted remaining time is two minutes. This notifies the pilot to transition to the landing phase of the flight. A second alarm is activated when the battery charge falls below a specified limit threshold. This threshold is the point at which the battery energy reserve would no longer safely support two repeated aborted landing attempts. During the test series, the motor system is operated with the same predefined timed airspeed profile for each test. To test the robustness of the prediction, half of the tests were performed with, and half were performed without, a simulated powertrain fault. The pilot remotely engages a resistor bank at a specified time during the test flight to simulate a partial powertrain fault. The flying time prediction system is agnostic of the pilot's activation of the fault and must adapt to the vehicle's state. The time at which the limit threshold on battery charge is reached is then used to measure the accuracy of the remaining flying time predictions. Accuracy requirements for the alarms are considered and the results discussed.

King-Devick Test identifies real-time concussion and asymptomatic concussion in youth athletes.

PubMed

Dhawan, Priya S; Leong, Danielle; Tapsell, Lisa; Starling, Amaal J; Galetta, Steven L; Balcer, Laura J; Overall, Trenton L; Adler, Jennifer S; Halker-Singh, Rashmi B; Vargas, Bert B; Dodick, David

2017-12-01

Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms. Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores. Among 141 players tested, 20 had clinically diagnosed concussion. All 20 had immediate postconcussion K-D times >5 seconds from baseline (average 7.3 seconds) and all but 2 had worse postseason scores (46.4 seconds vs 52.4 seconds, p < 0.05, Wilcoxon signed rank test). Nonconcussed athletes saw minimal improvement postseason (43.9 seconds vs 42.1 seconds, p < 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue. Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion. This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

Dynamic of HIV-testing after arrival in France for migrants from sub-Saharan Africa: The role of both health and social care systems.

PubMed

Limousi, Frédérike; Lert, France; Desgrées du Loû, Annabel; Dray-Spira, Rosemary; Lydié, Nathalie

2017-01-01

HIV testing is an important tool in the management of the HIV epidemic among key populations. We aimed to explore the dynamic of first-time HIV testing in France for sub-Saharan migrants after their arrival. ANRS-Parcours is a retrospective life-event survey conducted from 2012 to 2013 in healthcare facilities in the Paris region, among 926 sub-Saharan HIV-infected migrants and 763 non-infected migrants. After describing the time to first HIV test in France and associated circumstances, we performed a discrete-time logistic regression to analyze the influence of socioeconomic position, contact with the healthcare system and sexual behaviors, on first-time HIV testing in France in migrants who arrived after 2000. Median first-time HIV testing occurred during the second year spent in France for non-infected men and women in both groups, and during the first year for men of the HIV group. The probability of testing increased with hospitalization and pregnancy for women of both groups. For non-infected men unemployment and absence of a residence permit were associated with an increased probability of HIV testing [respectively, OR = 2.2 (1.2-4.1) and OR = 2.0 (1.1-3.5)]. Unemployment was also associated with an increased probability of first-time HIV-testing for women of the HIV group [OR: 1.7 (1.0-2.7)]. Occasional and multiple sexual relationships were associated with an increased probability of first-time testing only for HIV-infected women [OR: 2.2 (1.2-4.0) and OR = 2.4 (1.3-4.6)]. Access to first HIV testing in France is promoted by contact with the health care system and is facilitated for unemployed and undocumented migrants after arrival.However, testing should be offered more systematically and repeated in order to reduce time between HIV infection and diagnosis, especially for deprived people which are particularly vulnerable regarding HIV infection.

Timing system for firing widely spaced test nuclear detonations

NASA Technical Reports Server (NTRS)

Partridge, Ralph E.

1992-01-01

The national weapons design laboratories (Los Alamos National Laboratory and Lawrence Livermore National Laboratory) test fire nuclear devices at the Nevada Test Site (NTS), which is spread over an area of over 1200 square miles. On each test there are hundreds of high time resolution recordings made of nuclear output waveforms and other phenomena. In order to synchronize these recordings with each other, with the nuclear device, and with offsite recordings, there is a requirement that the permanent command center and the outlying temporary firing sites be time tied to each other and to UTC to permit firing the shot at a predetermined time with an accuracy of about a microsecond. Various aspects of the test setup and timing system are discussed.

Normalization methods in time series of platelet function assays

PubMed Central

Van Poucke, Sven; Zhang, Zhongheng; Roest, Mark; Vukicevic, Milan; Beran, Maud; Lauwereins, Bart; Zheng, Ming-Hua; Henskens, Yvonne; Lancé, Marcus; Marcus, Abraham

2016-01-01

Abstract Platelet function can be quantitatively assessed by specific assays such as light-transmission aggregometry, multiple-electrode aggregometry measuring the response to adenosine diphosphate (ADP), arachidonic acid, collagen, and thrombin-receptor activating peptide and viscoelastic tests such as rotational thromboelastometry (ROTEM). The task of extracting meaningful statistical and clinical information from high-dimensional data spaces in temporal multivariate clinical data represented in multivariate time series is complex. Building insightful visualizations for multivariate time series demands adequate usage of normalization techniques. In this article, various methods for data normalization (z-transformation, range transformation, proportion transformation, and interquartile range) are presented and visualized discussing the most suited approach for platelet function data series. Normalization was calculated per assay (test) for all time points and per time point for all tests. Interquartile range, range transformation, and z-transformation demonstrated the correlation as calculated by the Spearman correlation test, when normalized per assay (test) for all time points. When normalizing per time point for all tests, no correlation could be abstracted from the charts as was the case when using all data as 1 dataset for normalization. PMID:27428217

16 CFR 1212.4 - Test protocol.

Code of Federal Regulations, 2010 CFR

2010-01-01

... participate. (6) Two children at a time shall participate in testing of surrogate multi-purpose lighters... at the same time. Two children at a time shall participate in testing of surrogate multi-purpose... appearance, including color. The surrogate multi-purpose lighters shall be labeled with sequential numbers...

Cost analysis of a novel HIV testing strategy in community pharmacies and retail clinics.

PubMed

Lecher, Shirley Lee; Shrestha, Ram K; Botts, Linda W; Alvarez, Jorge; Moore, James H; Thomas, Vasavi; Weidle, Paul J

2015-01-01

To document the cost of implementing point-of-care (POC) human immunodeficiency virus (HIV) rapid testing in busy community pharmacies and retail clinics. Providing HIV testing services in community pharmacies and retail clinics is an innovative way to expand HIV testing. The cost of implementing POC HIV rapid testing in a busy retail environment needs to be documented to provide program and policy leaders with adequate information for planning and budgeting. Cost analysis from a pilot project that provided confidential POC HIV rapid testing services in community pharmacies and retail clinics. The pharmacy sites were operated under several different ownership structures (for-profit, nonprofit, sole proprietorship, corporation, public, and private) in urban and rural areas. We included data from the initial six sites that participated in the project. We collected the time spent by pharmacy and retail clinic staff for pretest and posttest counseling in an activity log for time-in-motion for each interaction. Pharmacists and retail clinic staff. HIV rapid testing. The total cost was calculated to include costs of test kits, control kits, shipping, test supplies, training, reporting, program administration, and advertising. The six sites trained 22 staff to implement HIV testing. A total of 939 HIV rapid tests were conducted over a median time of 12 months, of which 17 were reactive. Median pretest counseling time was 2 minutes. Median posttest counseling time was 2 minutes for clients with a nonreactive test and 10 minutes for clients with a reactive test. The average cost per person tested was an estimated $47.21. When we considered only recurrent costs, the average cost per person tested was $32.17. Providing POC HIV rapid testing services required a modest amount of staff time and costs that are comparable to other services offered in these settings. HIV testing in pharmacies and retail clinics can provide an additional alternative venue for increasing the availability and accessibility of HIV testing services in the United States.

Effect of Students' Perceptions of Course Load on Test Anxiety

PubMed Central

Sansgiry, Sujit S.; Sail, Kavita

2006-01-01

Objectives The objective of this study was to examine the association between student perceptions of course load, their ability to manage time, and test anxiety. Methods A survey was self-administered to all students (professional years 1 through 4) enrolled in the PharmD curriculum at the University of Houston (2001) with items measuring test anxiety, perceived course load, and ability to manage time. Results One hundred ninety-eight students participated in the survey (response rate P1 = 48%, P2 = 52%, P3 = 52%, P4 = 72%). There was a significant difference in students' perception of course load, ability to manage time, and test anxiety scores across the 4 years. Test anxiety was positively correlated with students' perceptions of course load and negatively related to their ability to manage time with course work. Conclusions Students' perception of course load and their ability to manage time with their course work is associated with test anxiety. Future studies should evaluate the role of stress/time management programs to reduce stress and anxiety. PMID:17149404

Effect of students' perceptions of course load on test anxiety.

PubMed

Sansgiry, Sujit S; Sail, Kavita

2006-04-15

The objective of this study was to examine the association between student perceptions of course load, their ability to manage time, and test anxiety. A survey was self-administered to all students (professional years 1 through 4) enrolled in the PharmD curriculum at the University of Houston (2001) with items measuring test anxiety, perceived course load, and ability to manage time. One hundred ninety-eight students participated in the survey (response rate P1 = 48%, P2 = 52%, P3 = 52%, P4 = 72%). There was a significant difference in students' perception of course load, ability to manage time, and test anxiety scores across the 4 years. Test anxiety was positively correlated with students' perceptions of course load and negatively related to their ability to manage time with course work. Students' perception of course load and their ability to manage time with their course work is associated with test anxiety. Future studies should evaluate the role of stress/time management programs to reduce stress and anxiety.

Extended Time Testing Accommodations for Students with Disabilities: Answers to Five Fundamental Questions

ERIC Educational Resources Information Center

Lovett, Benjamin J.

2010-01-01

Extended time is one of the most common testing accommodations provided to students with disabilities. It is also controversial; critics of extended time accommodations argue that extended time is used too readily, without concern for how it changes the skills measured by tests, leading to scores that cannot be compared fairly with those of other…

Objective speech quality evaluation of real-time speech coders

NASA Astrophysics Data System (ADS)

Viswanathan, V. R.; Russell, W. H.; Huggins, A. W. F.

1984-02-01

This report describes the work performed in two areas: subjective testing of a real-time 16 kbit/s adaptive predictive coder (APC) and objective speech quality evaluation of real-time coders. The speech intelligibility of the APC coder was tested using the Diagnostic Rhyme Test (DRT), and the speech quality was tested using the Diagnostic Acceptability Measure (DAM) test, under eight operating conditions involving channel error, acoustic background noise, and tandem link with two other coders. The test results showed that the DRT and DAM scores of the APC coder equalled or exceeded the corresponding test scores fo the 32 kbit/s CVSD coder. In the area of objective speech quality evaluation, the report describes the development, testing, and validation of a procedure for automatically computing several objective speech quality measures, given only the tape-recordings of the input speech and the corresponding output speech of a real-time speech coder.

How pH, Temperature, and Time of Incubation Affect False-Positive Responses and Uncertainty of the LAL Gel-Clot Test.

PubMed

Lourenço, Felipe Rebello; Botelho, Túlia De Souza; Pinto, Terezinha De Jesus Andreoli

2012-01-01

The limulus amebocyte lysate (LAL) test is the simplest and most widely used procedure for detection of endotoxin in parenteral drugs. The LAL test demands optimal pH, ionic strength, temperature, and time of incubation. Slight changes in these parameters may increase the frequency of false-positive responses and the estimated uncertainty of the LAL test. The aim of this paper is to evaluate how changes in the pH, temperature, and time of incubation affect the occurrence of false-positive responses in the LAL test. LAL tests were performed in nominal conditions (37 °C, 60 min, and pH 7) and in different conditions of temperature (36 °C and 38 °C), time of incubation (58 and 62 min), and pH (6 and 8). Slight differences in pH increase the frequency of false-positive responses 5-fold (relative risk 5.0), resulting in an estimated of uncertainty 7.6%. Temperature and time of incubation affect the LAL test less, showing relative risks of 1.5 and 1.0, respectively. Estimated uncertainties in 36 °C or 38 °C temperatures and 58 or 62 min of incubation were found to be 2.0% and 1.0%, respectively. Simultaneous differences in these parameters significantly increase the frequency of false-positive responses. The limulus amebocyte lysate (LAL) gel-clot test is a simple test for detection of endotoxin from Gram-negative bacteria. The test is based on a gel formation when a certain amount of endotoxin is present; it is a pass/fail test. The LAL test requires optimal pH, ionic strength, temperature, and time of incubation. Slight difference in these parameters may increase the frequency of false-positive responses. The aim of this paper is to evaluate how changes in the pH, temperature, and time of incubation affect the occurrence of false-positive responses in the LAL test. We find that slight differences in pH increase the frequency of false-positive responses 5-fold. Temperature and time of incubation affect the LAL test less. Simultaneous differences in these parameters significantly increase the frequency of false-positive responses.

Test-Retest Reliability of the Short-Form Survivor Unmet Needs Survey.

PubMed

Taylor, Karen; Bulsara, Max; Monterosso, Leanne

2018-01-01

Reliable and valid needs assessment measures are important assessment tools in cancer survivorship care. A new 30-item short-form version of the Survivor Unmet Needs Survey (SF-SUNS) was developed and validated with cancer survivors, including hematology cancer survivors; however, test-retest reliability has not been established. The objective of this study was to assess the test-retest reliability of the SF-SUNS with a cohort of lymphoma survivors ( n = 40). Test-retest reliability of the SF-SUNS was conducted at two time points: baseline (time 1) and 5 days later (time 2). Test-retest data were collected from lymphoma cancer survivors ( n = 40) in a large tertiary cancer center in Western Australia. Intraclass correlation analyses compared data at time 1 (baseline) and time 2 (5 days later). Cronbach's alpha analyses were performed to assess the internal consistency at both time points. The majority (23/30, 77%) of items achieved test-retest reliability scores 0.45-0.74 (fair to good). A high degree of overall internal consistency was demonstrated (time 1 = 0.92, time 2 = 0.95), with scores 0.65-0.94 across subscales for both time points. Mixed test-retest reliability of the SF-SUNS was established. Our results indicate the SF-SUNS is responsive to the changing needs of lymphoma cancer survivors. Routine use of cancer survivorship specific needs-based assessments is required in oncology care today. Nurses are well placed to administer these assessments and provide tailored information and resources. Further assessment of test-retest reliability in hematology and other cancer cohorts is warranted.