Quasi-dynamical analysis and real-time tissue temperature monitoring during laser vaporization

NASA Astrophysics Data System (ADS)

Wang, Hui; Ray, Aditi; Jebens, Dave; Chia, Ray; Hasenberg, Tom

2014-03-01

Vaporization and coagulation are two fundamental processes that can be performed during laser-tissue ablation. We demonstrated a method allowing quasi-dynamically observing of the cross-sectional images of tissue response during ablation. The results showed that coagulation depth is relatively constant during vaporization, which supports the excellent hemostasis of green laser benign prostate hyperplasia (BPH) treatment. We also verified a new technology for real-time, in situ tissue temperature monitoring, which may be promising for in vivo tissue vaporization degree feedback during laser ablation to improve the vaporization efficiency and avoid complications.

Characteristics of laparoscopic microwave ablation with renal tissue: Experimental in vivo study using a porcine model.

PubMed

Hong, Baoan; Du, Xin; Zhao, Yuan; Chen, Guowei; Zhang, Xiaodong; Zhang, Ning; Yang, Yong

2015-01-01

A model of in vivo porcine kidneys is used to clarify the characteristics of laparoscopic microwave ablation (MWA) of renal tissue. Six pigs were utilised for the experiment using 18G water circulating-cooling microwave needles. The operating frequency was 2450 MHz, and the independent variables were power (50-60 W) and time (300-600 s). The kidneys were dissociated laparoscopically and ablated with a single or double needle at different power/time combinations and depths of puncture. Changes in the kidneys were carefully observed. Specimens of the ablated lesions were stained with haematoxylin-eosin (H&E) to evaluate the pathological features. Thirty-four thermoablations were applied. The effective ablation shape was similar to a chestnut. The ablated lesions could be divided into three zones: carbonization zone, coagulation zone, and inflammatory reaction zone. The ablation zone enlarged with increasing power and time. When combined with two needles, the maximum diameter of the ablated lesions significantly increased. Pathological results indicated that renal tissues of the carbonisation zone were thoroughly necrotic. Coagulative necrosis was observed in the coagulation zone. No 'skipped' areas were noted in any ablation zone. The structure of the inflammatory reaction zone was integrated, and interstitial small blood vessels were highly expanded and congested with infiltrated inflammatory cells. MWA achieved excellent effects in this porcine model. It can be safely and effectively used in renal tissue. For patients with poor physical condition or small renal masses (<4 cm), we can refer to these data and select the appropriate combinations to obtain satisfactory therapeutic efficacy.

Retinotomy using an erbium:YAG laser on human autopsy eyes

NASA Astrophysics Data System (ADS)

Ellsworth, Lansing G.; Kramer, Theresa R.; Noecker, Robert J.; Snyder, Robert W.; Yarborough, J. Michael

1994-06-01

Mid-IR lasers that operate near the absorption peak of water have a short penetration depth in ocular tissues. Ablation of tissue can be accomplished with minimal coagulative damage to underlying structures. We used an erbium:YAG laser equipped with a contact probe to create retinotomy sites in the human retina of eye bank eyes. An erbium:YAG laser (2.94 micrometers ) equipped with an infrared transmitting glass fiber and a sapphire tip (400 micrometers ) was used to directly ablate the surface of the retina. We administered both single and multiple pulses to the macula and peripheral retina using energy levels from 4 to 16 mJ per pulse. The retinas were then examined histopathologically to evaluate the extent of ablation and coagulative damage. Single pulses at low energy levels were noted to cause ablative damage to the nerve fiber layer and ganglion cell layer without a notable coagulative effect. The mean ablation depth at lower energy levels was less than the mean ablation depth at higher energy levels. Extensive laser application produced disruption of the retinal pigment epithelium, choroid and sclera. the erbium:YAG laser equipped with a contact probe is an effective means of creating retinotomies in human autopsy eyes. When used in the single pulse mode at lower energy levels, the erbium:YAG laser appears capable of removing superficial retinal layers without damaging deeper structures.

A new catheter design for combined radiofrequency ablation and optoacoustic treatment monitoring using copper-coated light-guides

NASA Astrophysics Data System (ADS)

Rebling, Johannes; Oyaga Landa, Francisco Javier; Deán-Ben, Xosé Luis; Razansky, Daniel

2018-02-01

Electrosurgery, i.e. the application of radiofrequency current for tissue ablation, is a frequently used treatment for many cardiac arrhythmias. Electrophysiological and anatomic mapping, as well as careful radiofrequency power control typically guide the radiofrequency ablation procedure. Despite its widespread application, accurate monitoring of the lesion formation with sufficient spatio-temporal resolution remains challenging with the existing imaging techniques. We present a novel integrated catheter for simultaneous radiofrequency ablation and optoacoustic monitoring of the lesion formation in real time and 3D. The design combines the delivery of both electric current and optoacoustic excitation beam in a single catheter consisting of copper-coated multimode light-guides and its manufacturing is described in detail. The electrical current causes coagulation and desiccation while the excitation light is locally absorbed, generating OA responses from the entire treated volume. The combined ablation-monitoring capabilities were verified using ex-vivo bovine tissue. The formed ablation lesions showed a homogenous coagulation while the ablation was monitored in realtime with a volumetric frame rate of 10 Hz over 150 seconds.

Effects of Blood Flow and/or Ventilation Restriction on Radiofrequency Coagulation Size in the Lung: An Experimental Study in Swine

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

Anai, Hiroshi; Uchida, Barry T.; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu

2006-10-15

The purpose of this study was to investigate how the restriction of blood flow and/or ventilation affects the radiofrequency (RF) ablation coagulation size in lung parenchyma. Thirty-one RF ablations were done in 16 normal lungs of 8 living swine with 2-cm LeVeen needles. Eight RF ablations were performed as a control (group G1), eight with balloon occlusion of the ipsilateral mainstem bronchus (G2), eight with occlusion of the ipsilateral pulmonary artery (G3), and seven with occlusion of both the ipsilateral bronchus and pulmonary artery (G4). Coagulation diameters and volumes of each ablation zone were compared on computed tomography (CT) andmore » gross specimen examinations. Twenty-six coagulation zones were suitable for evaluation: eight in G1, five in G2, seven in G3, and six in G4 groups. In G1, the mean coagulation diameter was 21.5 {+-} 3.5 mm on CT and 19.5 {+-} 1.78 mm on gross specimen examination. In G2, the mean diameters were 26.5 {+-} 5.1 mm and 23.0 {+-} 2.7 mm on CT and gross specimen examination, respectively. In G3, the mean diameters were 29.4 {+-} 2.2 mm and 27.4 {+-} 2.9 mm on CT and gross specimen examination, respectively, and in G4, they were 32.6 {+-} 3.33 mm and 28.8 {+-} 2.6 mm, respectively. The mean coagulation volumes were 3.39 {+-} l.52 cm{sup 3} on CT and 3.01 {+-} 0.94 cm{sup 3} on gross examinations in G1, 6.56 {+-} 2.47 cm{sup 3} and 5.22 {+-} 0.85 cm{sup 3} in G2, 10.93 {+-} 2.17 cm{sup 3} and 9.97 {+-} 2.91 cm{sup 3} in G3, and 13.81 {+-} 3.03 cm{sup 3} and 11.06 {+-} 3.27 cm{sup 3} in G4, respectively. The mean coagulation diameters on gross examination and mean coagulation volumes on CT and gross examination with G3 and G4 were significantly larger than those in G1 (p < 0.0001, p < 0.0001, p < 0.0001, respectively) or in G2 (p < 0.05, p < 0.005, p < 0.005, respectively). Pulmonary collapse occurred in one lung in G2 and pulmonary artery thrombus in two lungs of G3 and two lungs of G4. The coagulation size of RF ablation of the lung parenchyma is increased by ventilation and particularly by pulmonary artery blood flow restriction. The value of these restrictions for potential clinical use needs to be explored in experimentally induced lung tumors.« less

915MHz microwave ablation with high output power in in vivo porcine spleens.

PubMed

Gao, Yongyan; Wang, Yang; Duan, Yaqi; Li, Chunling; Sun, Yuanyuan; Zhang, Dakun; Lu, Tong; Liang, Ping

2010-07-01

The purpose of this study was to evaluate the efficacy of 915 MHz microwave (MW) ablation with high output power in in vivo porcine spleens. MW ablations were performed in 9 porcine spleens with an internally cooled 915 MHz antenna. Thermocouples were placed at 5, 10, 15, 20 mm away from the antenna to measure temperatures in real-time during MW emission. The energy was applied for 10 min at high output power of 60 W, 70 W or 80 W. Gross specimens were sectioned and measured to determine ablation size. Representative areas were examined by light microscopy and electron microscopy. Coagulation sizes and temperatures were compared among the three power groups. Hematoxylin-eosin staining showed irreversible necrosis in the splenic coagulation area after MW ablation. As the power was increased, long-axis diameter enlarged significantly (p<.05). Short-axis diameter also tended to increase, but there were no statistical difference (p>.05). The coagulation size of long-axis and short-axis diameter with 80 W in vivo spleen ablation was 6.43+/-0.52 and 4.95+/-0.30 cm, respectively. With the increase of output power, maximum temperatures at 5, 10, 15, 20 mm from the antenna were increased accordingly (p<.05). The maximum temperature with 80 W at 5 and 20 mm from the antenna reached 146.17+/-6.65 and 72.38+/-4.23 degrees C respectively. With internally cooled antenna and high output power, 915 MHz MW ablation in the spleen could produce irreversible tissue necrosis of clinical significance. MW ablation may be used as a promising minimally invasive method for the treatment of splenic diseases. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Influence of large intrahepatic blood vessels on the gross and histological characteristics of lesions produced by radiofrequency ablation in a pig liver model.

PubMed

Tamaki, Katsuyoshi; Shimizu, Ichiro; Oshio, Atsuo; Fukuno, Hiroshi; Inoue, Hiroshi; Tsutsui, Akemi; Shibata, Hiroshi; Sano, Nobuya; Ito, Susumu

2004-12-01

To determine whether the presence of large intrahepatic blood vessels (>/=3 mm) affect radiofrequency (RF)-induced coagulation necrosis, the gross and histological characteristics of RF-ablated areas proximal to or around vessels were examined in normal pig livers. An RF ablation treatment using a two-stepwise extension technique produced 12 lesions: six contained vessels (Group A), and the other six were localized around vessels (Group B). Gross examination revealed that the longest and shortest diameters of the ablated lesions were significantly larger in Group B than in Group A. In Group A, patent vessels contiguous to the lesion were present in a tongue-shaped area, whereas the lesions in Group B were spherical. Staining with nicotinamide adenine dinucleotide diaphorase was negative within the ablated area; but, if vessels were present in the ablated area, the cells around the vessels in an opposite direction to the ablation were stained blue. Roll-off can be achieved with 100% cellular destruction within a lesion that does not contain large vessels. The ablated area was decreased in lesions that contained large vessels, suggesting that the presence of large vessels in the ablated area further increases the cooling effect and may require repeated RF ablation treatment to achieve complete coagulation necrosis.

An ex-vivo experimental study on optimization of bipolar radiofrequency liver ablation using perfusion-cooled electrodes.

PubMed

Lee, J M; Han, J K; Kim, S H; Lee, J Y; Shin, K S; Choi, B I

2005-08-01

To determine optimal parameters for bipolar radiofrequency ablation (RFA) using perfusion-cooled electrodes to create a large ablation volume in ex vivo bovine liver. Three sets of RF experiments were performed using a 200-Watt generator and two 15-gauge perfusion-cooled or internally cooled electrodes in ex vivo bovine livers. In the first set of experiments, to find the ideal inter-electrode distance for creating large coagulation necrosis, 30 ablation lesions were created by bipolar RFAs at inter-electrode spacings of 3 cm, 4 cm, and 5 cm. In the second set of experiments, to explore the ideal duration of RF application, bipolar RFAs were performed for 10 min and 20 min. In the first and second experiments, 10 lesions were made for each condition with infusion of 6% hypertonic saline (HS) at 2 ml/min. In the third set of experiments, 10 ablation lesions were created by bipolar RFAs using internally cooled electrodes without HS infusion. The mean volume of those ablation lesions was then compared to that of the lesions created by bipolar RFA using perfusion-cooled electrodes in the second experiments. Tissue impedance, dimension, and shape of the ablated areas were compared in each condition. In the first set of experiments, bipolar RFA created a homogeneous oval or spherical-shaped ablation area between the electrodes at 3-5 cm spacing, but showed a more spherical-shaped lesion at 3 cm inter-electrode spacing than at 4 cm and 5 cm spacing. In the second set of experiments, RF energy delivered for 20 min created a larger dimension of coagulation necrosis than energy delivered for 10 min: 107.6 +/- 34 cm3 versus 59.5 +/- 27 cm3 (P<0.05). In addition, the mean volume of ablation regions obtained with bipolar RFA using the internally cooled electrode was 47.5+/- 17 cm3, which was significantly less than that with bipolar RFA using perfusion-cooled electrodes (P <0.05). Bipolar RFA using perfusion-cooled electrodes achieves homogeneous areas of coagulation necrosis between two electrodes, preferably at 3 or 4 cm inter-electrode distance for 20 min, and is better in creating large coagulation necrosis than bipolar RFA using internally cooled electrodes.

Multiple-electrode radiofrequency ablation: simultaneous production of separate zones of coagulation in an in vivo porcine liver model.

PubMed

Laeseke, Paul F; Sampson, Lisa A; Haemmerich, Dieter; Brace, Chris L; Fine, Jason P; Frey, Tina M; Winter, Thomas C; Lee, Fred T

2005-12-01

A multiple-electrode radiofrequency (RF) system was developed based on switching between electrodes that allows for the simultaneous use of as many as three electrically independent electrodes. The purpose of this study was to determine if each multiple-electrode ablation zone is identical to an ablation zone created with conventional single-electrode mode. Nine female domestic pigs (mean weight, 90 kg) were used for this study. A prototype monopolar multiple-electrode RF ablation system was created with use of an RF generator and an electronic switching algorithm. A maximum of three electrodes can be used simultaneously by switching between electrodes at each impedance spike (30 omega greater than baseline levels). A total of 39 zones of ablation were created at open laparotomy in pig livers with use of a conventional single electrode (n = 9), two single electrodes simultaneously (n = 6 ablations; 12 ablation zones), or three single electrodes simultaneously (n = 6 ablations; 18 ablation zones). RF electrodes were spaced in separate lobes of the liver when multiple zones of coagulation were created simultaneously. Animals were euthanized after RF ablation, livers were removed, and ablation zones were sectioned and measured. Zones of coagulation created simultaneously with two or three electrodes were equivalent to ablation zones created with use of conventional single-electrode ablation. No significant differences were observed among control animals treated with a single electrode, those with two separate zones of ablation created simultaneously, and those with three simultaneously created ablation zones in terms of mean (+/-SD) minimum diameter (1.6 cm +/- 0.6, 1.6 cm +/- 0.5, and 1.7 cm +/- 0.4, respectively), maximum diameter (2.0 cm +/- 0.5, 2.3 cm +/- 0.5, 2.2 cm +/- 0.5, respectively), and volume (6.7 cm3 +/- 3.7, 7.4 cm3 +/- 3.8, and 7.8 cm3 +/- 3.9; P > .30, analysis of variance, pairwise t-test comparisons). A rapid-switching multiple-electrode RF system was able to simultaneously create as many as three separate ablation zones of equivalent size compared with single-electrode controls. This system would allow physicians to simultaneously treat multiple tumors, substantially reducing procedure time and anesthesia risk.

How coagulation zone size is underestimated in computer modeling of RF ablation by ignoring the cooling phase just after RF power is switched off.

PubMed

Irastorza, Ramiro M; Trujillo, Macarena; Berjano, Enrique

2017-11-01

All the numerical models developed for radiofrequency ablation so far have ignored the possible effect of the cooling phase (just after radiofrequency power is switched off) on the dimensions of the coagulation zone. Our objective was thus to quantify the differences in the minor radius of the coagulation zone computed by including and ignoring the cooling phase. We built models of RF tumor ablation with 2 needle-like electrodes: a dry electrode (5 mm long and 17G in diameter) with a constant temperature protocol (70°C) and a cooled electrode (30 mm long and 17G in diameter) with a protocol of impedance control. We observed that the computed coagulation zone dimensions were always underestimated when the cooling phase was ignored. The mean values of the differences computed along the electrode axis were always lower than 0.15 mm for the dry electrode and 1.5 mm for the cooled electrode, which implied a value lower than 5% of the minor radius of the coagulation zone (which was 3 mm for the dry electrode and 30 mm for the cooled electrode). The underestimation was found to be dependent on the tissue characteristics: being more marked for higher values of specific heat and blood perfusion and less marked for higher values of thermal conductivity. Copyright © 2017 John Wiley & Sons, Ltd.

Analysis of Depth of Ablation,Thermal Damage, Wound Healing, and Wound Contraction With Erbium YAG Laser in a Yorkshire Pig Model.

PubMed

Alsaad, Salman M S; Ross, E Victor; Smith, Wiley J; DeRienzo, Damian P

2015-11-01

The erbium YAG laser is commonly used for skin resurfacing. It is known that varying the pulse duration can influence residual thermal damage and wound healing. Our study used a porcine model to evaluate a broad range of settings in a comparison of depth of ablation, depth of residual thermal damage (RTD), and wound contraction employing both a full coverage and fractional hand piece with an erbium YAG laser. The laser delivered an ablative pulse followed by a heating pulse of variable duration using either the full coverage or fractional hand piece. Pulse durations for specific coagulation depths were selected based on existing heat transfer models. The bilateral flanks of a single Yorkshire pig were irradiated. There were 14 treatment groups. 3 sites were treated per group for a total of 42 sites. Two of the 3 sites were for observational assessments and the 3rd site served as a reservoir for biopsies. Biopsy specimens were collected on days 0, 1, 3, 7, 14, and 28. Bleeding, erythema, wound healing, and wound contraction (in the fractional hand piece groups) were assessed. Wound healing is faster for fractional laser skin resurfacing compared with traditional contiguous resurfacing as demonstrated by textural changes and degree of erythema. The laser operator can be confident that the depth of ablation displayed on this system accurately reflects what is occurring in vivo for both confluent and fractional modes. Likewise, the measured degree of coagulation was consistent with panel display settings for the confluent mode. However, the degree of coagulation, as measured by the thickness of residual thermal damage, did not vary significantly between the fractional groups. In other words, the pulse duration of the second (heating) pulse did not impact the degree of coagulation in the fractional mode. There was a 2.3% wound contraction between some groups and a 6.5% wound contraction between other groups. A two way analysis of variance found a statistically significant difference in wound contraction based on ablation depth ( P = 0.012) but the degree of coagulation did not prove to be statistically significant for wound contraction (P = 0.66).

Bronchopleural Fistula After Radiofrequency Ablation of Lung Tumours

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

Cannella, Mathieu; Cornelis, Francois; Descat, Edouard

2011-02-15

The present article describes two cases of bronchopleural fistula (BPF) occurring after radiofrequency ablation of lung tumors. Both procedures were carried out using expandable multitined electrodes, with no coagulation of the needle track. After both ablations, ground-glass opacities encompassed the nodules and abutted the visceral pleura. The first patient had a delayed pneumothorax, and the second had a recurrent pneumothorax. Both cases of BPF were diagnosed on follow-up computed tomography chest scans (i.e., visibility of a distinct channel between the lung or a peripheral bronchus and the pleura) and were successfully treated with chest tubes alone. Our goal is tomore » highlight the fact that BPF can occur without needle-track coagulation and to suggest that minimally invasive treatment is sufficient to cure BPFs of this specific origin.« less

Non-coaxial-based microwave ablation antennas for creating symmetric and asymmetric coagulation zones

NASA Astrophysics Data System (ADS)

Mohtashami, Yahya; Luyen, Hung; Hagness, Susan C.; Behdad, Nader

2018-06-01

We present an investigation of a new class of microwave ablation (MWA) antennas capable of producing axially symmetric or asymmetric heating patterns. The antenna design is based on a dipole fed by a balanced parallel-wire transmission line. The angle and direction of the deployed dipole arms are used to control the heating pattern. We analyzed the specific absorption rate and temperature profiles using electromagnetic and thermal simulations. Two prototypes were fabricated and tested in ex vivo ablation experiments: one was designed to produce symmetric heating patterns and the other was designed to generate asymmetric heating patterns. Both fabricated prototypes exhibited good impedance matching and produced localized coagulation zones as predicted by the simulations. The prototype operating in porcine muscle created an ˜10 cm3 symmetric ablation zone after 10 min of ablation with a power level of 18 W. The prototype operating in egg white created an ˜4 cm3 asymmetric ablation zone with a directionality ratio of 40% after 5 min of ablation with a power level of 25 W. The proposed MWA antenna design shows promise for minimally invasive treatment of tumors in various clinical scenarios where, depending on the situation, a symmetric or an asymmetric heating pattern may be needed.

In vivo comparison of simultaneous versus sequential injection technique for thermochemical ablation in a porcine model.

PubMed

Cressman, Erik N K; Shenoi, Mithun M; Edelman, Theresa L; Geeslin, Matthew G; Hennings, Leah J; Zhang, Yan; Iaizzo, Paul A; Bischof, John C

2012-01-01

To investigate simultaneous and sequential injection thermochemical ablation in a porcine model, and compare them to sham and acid-only ablation. This IACUC-approved study involved 11 pigs in an acute setting. Ultrasound was used to guide placement of a thermocouple probe and coaxial device designed for thermochemical ablation. Solutions of 10 M acetic acid and NaOH were used in the study. Four injections per pig were performed in identical order at a total rate of 4 mL/min: saline sham, simultaneous, sequential, and acid only. Volume and sphericity of zones of coagulation were measured. Fixed specimens were examined by H&E stain. Average coagulation volumes were 11.2 mL (simultaneous), 19.0 mL (sequential) and 4.4 mL (acid). The highest temperature, 81.3°C, was obtained with simultaneous injection. Average temperatures were 61.1°C (simultaneous), 47.7°C (sequential) and 39.5°C (acid only). Sphericity coefficients (0.83-0.89) had no statistically significant difference among conditions. Thermochemical ablation produced substantial volumes of coagulated tissues relative to the amounts of reagents injected, considerably greater than acid alone in either technique employed. The largest volumes were obtained with sequential injection, yet this came at a price in one case of cardiac arrest. Simultaneous injection yielded the highest recorded temperatures and may be tolerated as well as or better than acid injection alone. Although this pilot study did not show a clear advantage for either sequential or simultaneous methods, the results indicate that thermochemical ablation is attractive for further investigation with regard to both safety and efficacy.

Real-time monitoring of radiofrequency ablation and postablation assessment: accuracy of contrast-enhanced US in experimental rat liver model.

PubMed

Wu, Hanping; Wilkins, Luke R; Ziats, Nicholas P; Haaga, John R; Exner, Agata A

2014-01-01

To examine the accuracy of the unenhanced zone at contrast material-enhanced ultrasonography (US) in predicting coagulative necrosis during and 21 days after radiofrequency (RF) ablation by using radiologic-pathologic comparison. Animal studies were approved by the Institutional Animal Care and Use Committee. The livers of 28 rats underwent US-guided RF ablation. In four animals, contrast-enhanced US was performed during ablation and 2 hours and 2, 7, 14, and 21 days after ablation. The unenhanced zone area on US images was measured. DiI-labeled microbubbles were administered during ablation at 2, 4, and 6 minutes or at 2 hours and 2, 7, 14, and 21 days after ablation in the remaining 24 animals (n = 3 at each time point). One minute later, the animal was euthanized, and the ablated liver was harvested. Tissue samples were imaged to quantify total fluorescence, and NADH staining was performed on the same slice. Hematoxylin-eosin staining was also performed. The findings on fluorescence images, NADH-stained images, and hematoxylin-eosin-stained images were compared. The areas of DiI bubble-negative zones, NADH-negative zones, and lightly NADH-staining zones were measured. Data were analyzed by using one-way analysis of variance. The area of the unenhanced zone on contrast-enhanced US images increased during RF ablation and reached a maximum within 2 days after ablation. At histopathologic examination, a transition zone manifested adjacent to the coagulation zone until 2 days after ablation. The DiI-bubble negative zone on fluorescence images and the damaged zone (transition zone plus coagulation zone) on NADH-stained images increased rapidly within 2 hours after ablation, then slowly reached the maximum on day 2. The ratios of the mean areas of these two zones at hour 2 to those at day 2 were 94.6% and 95.6%, respectively. High uniformity between the damaged zone on NADH-stained images and the DiI bubble-negative zone on fluorescence images was noted at all time points. The temporary transition zone in NADH staining is partially damaged and should transition to nonviability 2 days after ablation. These results demonstrate that contrast-enhanced US can help delineate the maximum area of cell damage (to within 5% of the maximum) as early as 2 hours after ablation. Contrast-enhanced US may be a simple and accurate tool for monitoring the effects of RF ablation and quantifying the size of thermal damage after treatment. © RSNA, 2013.

Microwave Ablation Compared with Radiofrequency Ablation for Breast Tissue in an Ex Vivo Bovine Udder Model

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

Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp; Westphal, Saskia, E-mail: swestphal@ukaachen.de; Isfort, Peter, E-mail: isfort@hia.rwth-aachen.de

2012-08-15

Purpose: To compare the effectiveness of microwave (MW) ablation with radiofrequency (RF) ablation for treating breast tissue in a nonperfused ex vivo model of healthy bovine udder tissue. Materials and Methods: MW ablations were performed at power outputs of 25W, 35W, and 45W using a 915-MHz frequency generator and a 2-cm active tip antenna. RF ablations were performed with a bipolar RF system with 2- and 3-cm active tip electrodes. Tissue temperatures were continuously monitored during ablation. Results: The mean short-axis diameters of the coagulation zones were 1.34 {+-} 0.14, 1.45 {+-} 0.13, and 1.74 {+-} 0.11 cm for MWmore » ablation at outputs of 25W, 35W, and 45W. For RF ablation, the corresponding values were 1.16 {+-} 0.09 and 1.26 {+-} 0.14 cm with electrodes having 2- and 3-cm active tips, respectively. The mean coagulation volumes were 2.27 {+-} 0.65, 2.85 {+-} 0.72, and 4.45 {+-} 0.47 cm{sup 3} for MW ablation at outputs of 25W, 35W, and 45W and 1.18 {+-} 0.30 and 2.29 {+-} 0.55 cm{sup 3} got RF ablation with 2- and 3-cm electrodes, respectively. MW ablations at 35W and 45W achieved significantly longer short-axis diameters than RF ablations (P < 0.05). The highest tissue temperature was achieved with MW ablation at 45W (P < 0.05). On histological examination, the extent of the ablation zone in MW ablations was less affected by tissue heterogeneity than that in RF ablations. Conclusion: MW ablation appears to be advantageous with respect to the volume of ablation and the shape of the margin of necrosis compared with RF ablation in an ex vivo bovine udder.« less

A randomised controlled trial of ablation of Barrett's oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results

PubMed Central

Sharma, P; Wani, S; Weston, A P; Bansal, A; Hall, M; Mathur, S; Prasad, A; Sampliner, R E

2006-01-01

Background Many modalities have been used to ablate Barrett's oesophagus (BO). However, long term results and comparative effectiveness are unknown. Aims Our aim was to compare the long term efficacy of achieving complete reversal (endoscopic and histological) between multipolar electrocoagulation (MPEC) and argon plasma coagulation (APC) in BO patients and assess factors influencing successful ablation. Methods Patients with BO, 2–6 cm long, underwent 24 hour pH testing on proton pump inhibitor (PPI) therapy. Patients were then randomised by BO length to undergo ablation with MPEC or APC every 4–8 weeks until endoscopic reversal or maximal of six treatment sessions. Results Thirty five BO patients have been followed for at least two years following endoscopic ablation, 16 treated with MPEC and 19 with APC. There was complete reversal of BO in 24 patients (69%); 75% with MPEC and 63% with APC (p = 0.49). There was no difference in the number of sessions required in the two groups. There was no difference in age, pH results, BO length, PPI dose, or hiatal hernia size between patients with and without complete reversal. One patient developed an oesophageal stricture but there were no major complications such as bleeding or perforation. Conclusions In BO patients treated with MPEC or APC in combination with acid suppression, at long term follow up, complete reversal of BO can be maintained in approximately 70% of patients, irrespective of the technique. There are no predictors associated with achieving complete reversal of BO. Continued surveillance is still indicated in the post ablative setting. As yet, these techniques are not ready for clinical application (other than for high grade dysplasia or early oesophageal adenocarcinoma) and cannot be offered outside the research arena. PMID:16905695

Tissue healing response following hyperthermic vapor ablation in the porcine longissimus muscle

NASA Astrophysics Data System (ADS)

Grantham, John T.; Grisez, Brian T.; Famoso, Justin; Hoey, Michael; Dixon, Chris; Coad, James E.

2015-03-01

As the use of hyperthermic ablation technologies has increased, so too has the need to understand their effects on tissue and their healing responses. This study was designed to characterize tissue injury and healing following hyperthermic vapor ablation in the in vivo porcine longissimus muscle model. The individual ablations were performed using the NxThera Vapor Delivery System (NxThera Inc., Minneapolis, MN). To assess the vapor ablation's evolution, the swine were euthanized post-treatment on Day 0, Day 3, Day 7, Day 14, Day 28, Day 45 and Day 90. Triphenyltetrazolium chloride viability staining (TTC staining) was used to macroscopically assess the extent of each vapor ablation within the tissue. The ablation associated healing responses were then histologically evaluated for acute inflammation, chronic inflammation, foreign body reaction and fibrosis. Two zones of tissue injury were initially identified in the ablations: 1) a central zone of complete coagulative necrosis and 2) an outer "transition zone" of viable and non-viable cells. The ablations initially increased in size from Day 0 to Day 7 and then progressively decreased in size though Day 45. The initial Day 3 healing changes originated in the transition zone with minimal acute and chronic inflammation. As time progressed, granulation tissue began to form by Day 7 and peaked around Day 14. Collagen formation, deposition and remodeling began in the adjacent healthy tissue by Day 28, replaced the ablation site by Day 45 and reorganized by Day 90. In conclusion, this vapor ablation technology provided a non-desiccating form of hyperthermic ablation that resulted in coagulative necrosis without a central thermally/heat-fixed tissue component, followed a classical wound healing pathway, and healed with minimal associated inflammation.

Multiple-electrode radiofrequency ablations using Octopus® electrodes in an in vivo porcine liver model

PubMed Central

Lee, E S; Lee, J M; Kim, W S; Choi, S H; Joo, I; Kim, M; Yoo, D H; Yoo, R-E; Han, J K; Choi, B I

2012-01-01

Objectives The objective of this study was to determine the in vivo efficacy of radiofrequency ablation (RFA) in porcine liver using Octopus® electrodes for creating a large coagulation compared with RFA using clustered electrodes. Methods A total of 39 coagulations were created using a 200-W generator and clustered electrodes or Octopus electrodes during laparotomy in 19 pigs. Radiofrequency was applied to the livers using four protocols: (1) Group A-1, monopolar mode using a clustered electrode (n=11); (2) Group A-2, monopolar mode using an Octopus electrode (n=11); (3) Group B-1, consecutive monopolar mode using three, clustered electrodes (n=8); and (4) Group B-2, switching monopolar mode using two Octopus electrodes (n=9). The energy efficiency, shape, diameters (D) and volume (V) of the coagulation volume were compared in each of the two groups. Results The mean maximum D and V of the coagulations in Group A-2 (4.7 cm and 33.1 cm3, respectively) were significantly larger than those in Group A-1 (4.1 cm and 20.3 cm3, respectively) (p<0.05). Furthermore, the mean minimum D, maximum D and V of the coagulations in Group B-2 were significantly larger than those in Group B-1, i.e. 5.3 vs 4.0 cm, 6.6 vs 4.9 cm and 66.9 vs 30.2 cm3, respectively (p<0.05). The energy efficiencies were also significantly higher in Groups A-2 and B-2 than in Groups A-1 and B-1 (p<0.05). Conclusion The Octopus electrodes were more efficient for creating a large ablation zone than clustered electrodes, and the efficacy of RFA with Octopus electrodes can be amplified in the switching monopolar mode. PMID:22422385

Three-frequency Nd:YAG laser for dental treatment

NASA Astrophysics Data System (ADS)

Kadlecová, Martina; Dostálová, Tat'jana; Jelínková, Helena; Němec, Michal; Å ulc, Jan; Fibrich, Martin; Bradna, Pavel; Nejezchleb, Karel; Kapitch, Nickalai; Å koda, Václav

2018-02-01

In the last decade, lasers found a number of indications in dentistry. However, there is still one problem: the narrow spectrum of usefulness for individual radiation wavelengths. The aim of our study is to demonstrate the use of a compact three-frequency pulsed Nd-YAG laser for more than one treatment, namely disinfection, coagulation, selective ablation, and soft tissue removal. The laser wavelengths and the maximal energies achieved were the following: 1.06 um, 1.32 um, 1.44 um and 830 mJ, 425 mJ, and 200 mJ, respectively. It has been found that all of the investigated wavelengths exhibit disinfection properties. Moreover, radiation of 1.06 um wavelength removes soft tissue and exhibits also coagulation properties. Radiation of 1.44 um is most useful for selective ablation of initial caries and disinfection, and 1.32 um radiation can be used for precise ablation when higher energy is applied.

Real-time Monitoring of Radiofrequency Ablation and Postablation Assessment: Accuracy of Contrast-enhanced US in Experimental Rat Liver Model

PubMed Central

Wu, Hanping; Wilkins, Luke R.; Ziats, Nicholas P.; Haaga, John R.

2014-01-01

Purpose To examine the accuracy of the unenhanced zone at contrast material–enhanced ultrasonography (US) in predicting coagulative necrosis during and 21 days after radiofrequency (RF) ablation by using radiologic-pathologic comparison. Materials and methods Animal studies were approved by the Institutional Animal Care and Use Committee. The livers of 28 rats underwent US-guided RF ablation. In four animals, contrast-enhanced US was performed during ablation and 2 hours and 2, 7, 14, and 21 days after ablation. The unenhanced zone area on US images was measured. DiI-labeled microbubbles were administered during ablation at 2, 4, and 6 minutes or at 2 hours and 2, 7, 14, and 21 days after ablation in the remaining 24 animals (n = 3 at each time point). One minute later, the animal was euthanized, and the ablated liver was harvested. Tissue samples were imaged to quantify total fluorescence, and NADH staining was performed on the same slice. Hematoxylin-eosin staining was also performed. The findings on fluorescence images, NADH-stained images, and hematoxylin-eosin–stained images were compared. The areas of DiI bubble–negative zones, NADH-negative zones, and lightly NADH-staining zones were measured. Data were analyzed by using one-way analysis of variance. Results The area of the unenhanced zone on contrast-enhanced US images increased during RF ablation and reached a maximum within 2 days after ablation. At histopathologic examination, a transition zone manifested adjacent to the coagulation zone until 2 days after ablation. The DiI-bubble negative zone on fluorescence images and the damaged zone (transition zone plus coagulation zone) on NADH-stained images increased rapidly within 2 hours after ablation, then slowly reached the maximum on day 2. The ratios of the mean areas of these two zones at hour 2 to those at day 2 were 94.6% and 95.6%, respectively. High uniformity between the damaged zone on NADH-stained images and the DiI bubble–negative zone on fluorescence images was noted at all time points. Conclusion The temporary transition zone in NADH staining is partially damaged and should transition to nonviability 2 days after ablation. These results demonstrate that contrast-enhanced US can help delineate the maximum area of cell damage (to within 5% of the maximum) as early as 2 hours after ablation. Contrast-enhanced US may be a simple and accurate tool for monitoring the effects of RF ablation and quantifying the size of thermal damage after treatment. © RSNA, 2013 Online supplemental material is available for this article. PMID:23912621

Using synchrotron X-ray phase-contrast micro-computed tomography to study tissue damage by laser irradiation.

PubMed

Robinson, Alan M; Stock, Stuart R; Soriano, Carmen; Xiao, Xianghui; Richter, Claus-Peter

2016-11-01

The aim of this study was to determine if X-ray micro-computed tomography could be used to locate and characterize tissue damage caused by laser irradiation and to describe its advantages over classical histology for this application. A surgical CO 2 laser, operated in single pulse mode (100 milliseconds) at different power settings, was used to ablate different types of cadaveric animal tissues. Tissue samples were then harvested and imaged with synchrotron X-ray phase-contrast and micro-computed tomography to generate stacks of virtual sections of the tissues. Subsequently, Fiji (ImageJ) software was used to locate tissue damage, then to quantify volumes of laser ablation cones and thermal coagulation damage from 3D renderings of tissue image stacks. Visual comparisons of tissue structures in X-ray images with those visible by classic light microscopy histology were made. We demonstrated that micro-computed tomography could be used to rapidly identify areas of surgical laser ablation, vacuolization, carbonization, and thermally coagulated tissue. Quantification and comparison of the ablation crater, which represents the volume of ablated tissue, and the thermal coagulation zone volumes were performed faster than we could by classical histology. We demonstrated that these procedures can be performed on fresh hydrated and non-sectioned plastic embedded tissue. We demonstrated that the application of non-destructive micro-computed tomography to the visualization and analysis of laser induced tissue damage without tissue sectioning is possible. This will improve evaluation of new surgical lasers and their corresponding effect on tissues. Lasers Surg. Med. 48:866-877, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Coagulation necrosis induced by radiofrequency ablation in the liver: histopathologic and radiologic review of usual to extremely rare changes.

PubMed

Kim, Young-sun; Rhim, Hyunchul; Lim, Hyo Keun; Choi, Dongil; Lee, Min Woo; Park, Min Jung

2011-01-01

As the clinical role of radiofrequency ablation (RFA) of the liver grows, the importance of radiologic imaging after liver RFA to depict the diversity of post-RFA manifestations is also increasing. Because RFA induces coagulation necrosis of the hepatic parenchyma, cross-sectional imaging studies, in principle, demonstrate an area with a defect in contrast enhancement. However, for various reasons, such as the occurrence of a complication, the RFA zone may demonstrate different patterns or be accompanied by other abnormalities. In this investigation, a large number of imaging studies performed after more than 4000 procedures of liver RFA during the past 10-year period were reviewed, and various radiologic manifestations of the RFA zone were compiled. Herein, the basic principles of RFA, as well as the histopathologic features of coagulation necrosis of the liver, are catalogued to provide a more complete understanding of such changes. Through this review, the reader will become more familiar with the usual and unusual radiologic findings of coagulation necrosis induced by RFA in the liver. This increased familiarity will not only facilitate the daily practice of radiology but also deepen understanding of the therapeutic modality of RFA. © RSNA, 2011.

Optimization of direct current-enhanced radiofrequency ablation: an ex vivo study.

PubMed

Tanaka, Toshihiro; Isfort, Peter; Bruners, Philipp; Penzkofer, Tobias; Kichikawa, Kimihiko; Schmitz-Rode, Thomas; Mahnken, Andreas H

2010-10-01

The purpose of this study was to investigate the optimal setting for radiofrequency (RF) ablation combined with direct electrical current (DC) ablation in ex vivo bovine liver. An electrical circuit combining a commercially available RF ablation system with DC was developed. The negative electrode of a rectifier that provides DC was connected to a 3-cm multitined expandable RF probe. A 100-mH inductor was used to prevent electrical leakage from the RF generator. DC was applied for 15 min and followed by RF ablation in freshly excised bovine livers. Electric current was measured by an ammeter. Coagulation volume, ablation duration, and mean amperage were assessed for various DC voltages (no DC, 2.2, 4.5, and 9.0 V) and different RF ablation protocols (stepwise increase from 40 to 80 W, 40 W fixed, and 80 W fixed). Results were compared using Kruskal-Wallis and Mann-Whitney U test. Applying DC with 4.5 or 9.0 V, in combination with 40 W fixed or a stepwise increase of RF energy, resulted in significantly increased zone of ablation size compared with 2.2 V or no DC (P = 0.009). At 4.5 V DC, the stepwise increase of RF energy resulted in the same necrosis size as a 40 W fixed protocol (26.6 +/- 3.9 vs. 26.5 +/- 4.0 ml), but ablation duration was significantly decreased (296 +/- 85 s vs. 423 +/- 104 s; P = 0.028). Mean amperage was significantly lower at 4.5 V compared with 9.0 V (P = 0.028). Combining a stepwise increase of RF energy with a DC voltage of 4.5 V is most appropriate to increase coagulation volume and to minimize procedure time.

Optimization of Direct Current-Enhanced Radiofrequency Ablation: An Ex Vivo Study

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

Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp; Isfort, Peter; Bruners, Philipp

2010-10-15

The purpose of this study was to investigate the optimal setting for radiofrequency (RF) ablation combined with direct electrical current (DC) ablation in ex vivo bovine liver. An electrical circuit combining a commercially available RF ablation system with DC was developed. The negative electrode of a rectifier that provides DC was connected to a 3-cm multitined expandable RF probe. A 100-mH inductor was used to prevent electrical leakage from the RF generator. DC was applied for 15 min and followed by RF ablation in freshly excised bovine livers. Electric current was measured by an ammeter. Coagulation volume, ablation duration, andmore » mean amperage were assessed for various DC voltages (no DC, 2.2, 4.5, and 9.0 V) and different RF ablation protocols (stepwise increase from 40 to 80 W, 40 W fixed, and 80 W fixed). Results were compared using Kruskal-Wallis and Mann-Whitney U test. Applying DC with 4.5 or 9.0 V, in combination with 40 W fixed or a stepwise increase of RF energy, resulted in significantly increased zone of ablation size compared with 2.2 V or no DC (P = 0.009). At 4.5 V DC, the stepwise increase of RF energy resulted in the same necrosis size as a 40 W fixed protocol (26.6 {+-} 3.9 vs. 26.5 {+-} 4.0 ml), but ablation duration was significantly decreased (296 {+-} 85 s vs. 423 {+-} 104 s; P = 0.028). Mean amperage was significantly lower at 4.5 V compared with 9.0 V (P = 0.028). Combining a stepwise increase of RF energy with a DC voltage of 4.5 V is most appropriate to increase coagulation volume and to minimize procedure time.« less

Microwave ablation with multiple simultaneously powered small-gauge triaxial antennas: results from an in vivo swine liver model.

PubMed

Brace, Christopher L; Laeseke, Paul F; Sampson, Lisa A; Frey, Tina M; van der Weide, Daniel W; Lee, Fred T

2007-07-01

To prospectively investigate the ability of a single generator to power multiple small-diameter antennas and create large zones of ablation in an in vivo swine liver model. Thirteen female domestic swine (mean weight, 70 kg) were used for the study as approved by the animal care and use committee. A single generator was used to simultaneously power three triaxial antennas at 55 W per antenna for 10 minutes in three groups: a control group where antennas were spaced to eliminate ablation zone overlap (n=6; 18 individual zones of ablation) and experimental groups where antennas were spaced 2.5 cm (n=7) or 3.0 cm (n=5) apart. Animals were euthanized after ablation, and ablation zones were sectioned and measured. A mixed linear model was used to test for differences in size and circularity among groups. Mean (+/-standard deviation) cross-sectional areas of multiple-antenna zones of ablation at 2.5- and 3.0-cm spacing (26.6 cm(2) +/- 9.7 and 32.2 cm(2) +/- 8.1, respectively) were significantly larger than individual ablation zones created with single antennas (6.76 cm(2) +/- 2.8, P<.001) and were 31% (2.5-cm spacing group: multiple antenna mean area, 26.6 cm(2); 3 x single antenna mean area, 20.28 cm(2)) to 59% (3.0-cm spacing group: multiple antenna mean area, 32.2 cm(2); 3 x single antenna mean area, 20.28 cm(2)) larger than 3 times the mean area of the single-antenna zones. Zones of ablation were found to be very circular, and vessels as large as 1.1 cm were completely coagulated with multiple antennas. A single generator may effectively deliver microwave power to multiple antennas. Large volumes of tissue may be ablated and large vessels coagulated with multiple-antenna ablation in the same time as single-antenna ablation. (c) RSNA, 2007.

The anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban or rivaroxaban.

PubMed

Brendel, L C; Dobler, F; Hessling, G; Michel, J; Braun, S L; Steinsiek, A L; Groha, P; Eckl, R; Deisenhofer, I; Hyseni, A; Roest, M; Ott, I; Steppich, B

2017-09-01

Measuring the anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban and rivaroxaban is challenging, since the activated coagulation time (ACT) does not seem to reflect the true anticoagulant activity of these drugs. We therefore evaluated coagulation properties of apixaban and rivaroxaban during RFA by different coagulation assays to better monitor periprocedural hemostasis. The study included 90 patients (61 ± 12 years) with atrial fibrillation who underwent RFA procedures. Patients received 20 mg rivaroxaban (n = 73) once or 5 mg apixaban (n = 17) twice daily 4 weeks prior to the procedure. During RFA, unfractionated heparin i.v. was given to maintain an ACT of 250-300 s. Blood samples were taken before and 10, 60, and 360 min after heparin administration. Heparin displayed a lower anti-Xa activity in rivaroxaban-treated patients compared to apixaban-treated patients. In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin than in rivaroxaban/heparin patients. This discordant coagulative state measured in vitro had no clinical impact in terms of bleeding or thromboembolic complications. We found different biochemical responses to rivaroxaban/heparin and apixaban/heparin during RFA. Precaution is necessary when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement.

Considerations for theoretical modeling of thermal ablation with catheter-based ultrasonic sources: implications for treatment planning, monitoring and control

PubMed Central

Prakash, Punit; Diederich, Chris J.

2012-01-01

Purpose To determine the impact of including dynamic changes in tissue physical properties during heating on feedback controlled thermal ablation with catheter-based ultrasound. Additionally, we compared impact several indicators of thermal damage on predicted extents of ablation zones for planning and monitoring ablations with this modality. Methods A 3D model of ultrasound ablation with interstitial and transurethral applicators incorporating temperature based feedback control was used to simulate thermal ablations in prostate and liver tissue. We investigated five coupled models of heat dependent changes in tissue acoustic attenuation/absorption and blood perfusion of varying degrees of complexity.. Dimensions of the ablation zone were computed using temperature, thermal dose, and Arrhenius thermal damage indicators of coagulative necrosis. A comparison of the predictions by each of these models was illustrated on a patient-specific anatomy in the treatment planning setting. Results Models including dynamic changes in blood perfusion and acoustic attenuation as a function of thermal dose/damage predicted near-identical ablation zone volumes (maximum variation < 2.5%). Accounting for dynamic acoustic attenuation appeared to play a critical role in estimating ablation zone size, as models using constant values for acoustic attenuation predicted ablation zone volumes up to 50% larger or 47% smaller in liver and prostate tissue, respectively. Thermal dose (t43 ≥ 240min) and thermal damage (Ω ≥ 4.6) thresholds for coagulative necrosis are in good agreement for all heating durations, temperature thresholds in the range of 54 °C for short (< 5 min) duration ablations and 50 °C for long (15 min) ablations may serve as surrogates for determination of the outer treatment boundary. Conclusions Accounting for dynamic changes in acoustic attenuation/absorption appeared to play a critical role in predicted extents of ablation zones. For typical 5—15 min ablations with this modality, thermal dose and Arrhenius damage measures of ablation zone dimensions are in good agreement, while appropriately selected temperature thresholds provide a computationally cheaper surrogate. PMID:22235787

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver.

PubMed

Petrusca, Lorena; Viallon, Magalie; Breguet, Romain; Terraz, Sylvain; Manasseh, Gibran; Auboiroux, Vincent; Goget, Thomas; Baboi, Loredana; Gross, Patrick; Sekins, K Michael; Becker, Christoph D; Salomir, Rares

2014-01-16

Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. At the end of the procedure, no ultrasound indication of the marker's presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Experimental validation of this new ballistic marker method was performed for liver MRgHIFU ablation, free of any side effects (e.g. no edema around the marker, no infection, no bleeding). The study suggests that the absolute reference marker had ultrasound conspicuity below the detection threshold, was irreversible, MR-compatible and MR-detectable, while also being a well-established histology staining technique.

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver

PubMed Central

2014-01-01

Background Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. Methods The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. Results At the end of the procedure, no ultrasound indication of the marker’s presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Conclusions Experimental validation of this new ballistic marker method was performed for liver MRgHIFU ablation, free of any side effects (e.g. no edema around the marker, no infection, no bleeding). The study suggests that the absolute reference marker had ultrasound conspicuity below the detection threshold, was irreversible, MR-compatible and MR-detectable, while also being a well-established histology staining technique. PMID:24433332

Numerical simulation of RF catheter ablation for the treatment of arterial aneurysm.

PubMed

Guo, Xuemei; Nan, Qun; Qiao, Aike

2015-01-01

Considering the blood coagulation induced by the heating of radio frequency ablation (RFA) and the mechanism of aneurysm embolization, we proposed that RFA may be used to treat arterial aneurysm. But the safety of this method should be investigated. A finite element method (FEM) was used to simulate temperature and pressure distribution in aneurysm with different electrode position, electric field intensity and ablation time. When the electrode is in the middle of the artery aneurysm sac, temperature rose clearly in half side of artery aneurysm, which is not suitable for RFA. Temperature rose in the whole aneurysm when the electrode is under the artery aneurysm orifice, which is suitable for the ablation therapy. And in this way, the highest temperature was 69.585°C when power was 5.0 V/mm with 60 s. It can promote the coagulation and thrombosis generation in the aneurysm sac while the outside tissue temperature rises a little. Meanwhile, the pressure (10 Pa) at the top of aneurysm sac with electrode insertion is less than that (60 Pa) without electrode, so electrode implant may protect the aneurysm from rupture. The results can provide a theoretical basis for interventional treatment of aneurysm with RFA.

Microwave ablation of hepatocellular carcinoma

PubMed Central

Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

2015-01-01

Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s’, RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s’, showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

Microwave liver ablation: influence of hepatic vein size on heat-sink effect in a porcine model.

PubMed

Yu, Nam C; Raman, Steven S; Kim, Young Jun; Lassman, Charles; Chang, Xinlian; Lu, David S K

2008-07-01

To determine influence of hepatic vein size on perfusion-mediated attenuation in adjacent microwave thermal ablation. With approval of the institutional animal research committee, seven Yorkshire pigs underwent percutaneous (n = 2) or open (n = 5) microwave liver ablation under general anesthesia. In each, multiple ultrasound-guided, nonoverlapping thermal lesions were created within 1 cm of hepatic veins in a 5-10-minute ablation at 45 W. After euthanasia, the liver was harvested and sectioned at 0.5-cm intervals and the degree of perivascular coagulation attenuation was graded on histopathologic analysis. Correlation between venous size (small, < or =3 mm; medium, 3-6 mm; and large, >6 mm) and attenuation grade was performed with use of the Spearman rank test. In 63 of 103 sections (61%)--29 of 37 (78%) small, 27 of 48 (56%) medium, and seven of 18 (39%) large veins--the thermal injury extended to the vein wall around the entire circumference of the coagulation front without distortion of the ablation margin. In 40 of 103 sections (38.9%), varying degrees of concave distortion of perivenous ablation margins were noted, with significant correlation between vein size and heat-sink extent (P < .01). However, thermal injury extended to the vascular wall in all sections without complete circumferential sparing of liver tissue. Around two thrombosed veins, thermal lesions encased the vessels, producing paradoxically convex ablation margins. Although the heat-sink effect was significantly dependent on hepatic vein size, the majority of pathologic sections exhibited no or minimal effect. Further study is required to assess clinical implications.

CT-based investigation of the contraction of ex vivo tissue undergoing microwave thermal ablation

NASA Astrophysics Data System (ADS)

Lopresto, Vanni; Strigari, Lidia; Farina, Laura; Minosse, Silvia; Pinto, Rosanna; D'Alessio, Daniela; Cassano, Bartolomeo; Cavagnaro, Marta

2018-03-01

Treatment planning in microwave thermal ablation (MTA) requires the capability to predict and estimate the shape and dimension of the thermally coagulated zone obtainable following a clinical protocol. The ultimate result relies on the knowledge of the performance of the ablation device, as well as of the temperature-dependent structural modifications that the tissue undergoes during the treatment, because of the very high temperatures reached (up to 100 °C or higher). In this respect, tissue shrinkage plays an important role, since the dimension of the ablated tissue evaluated at the end of the MTA procedure (e.g. by way of CT imaging) could underestimate the actual treated tissue, leading to inaccurate assessment of the treatment outcome. In this study, CT imaging was used for real-time monitoring of tissue contraction during MTA experiments carried out in ex vivo bovine liver. Fiducial lead markers were positioned into the tissue in a 3D spatial grid around the MTA applicator. The spatial and temporal evolution of tissue contraction was imaged during the experiments, and analysed in terms of displacements of clusters of fiducial markers. The results obtained indicated that contraction is highly heterogeneous in the zone of ablation, depending both on the heating and on interactions with nearby tissue. In particular, tissue shrinkage appeared asymmetric with respect to the direction of insertion of the microwave applicator in the central area of carbonised tissue (about 30% and 19% along the radial and longitudinal directions, respectively), and isotropic in the region of coagulated (but not carbonised) tissue (about 11%). The total ablated volume was reduced by approximately 43% with respect to its pre-ablation value. Finally, temperature measurements displayed a correlation between temperature increment and temporal evolution of tissue contraction in the zone of ablation.

Potassium titanyl phosphate laser tissue ablation: development and experimental validation of a new numerical model.

PubMed

Elkhalil, Hossam; Akkin, Taner; Pearce, John; Bischof, John

2012-10-01

The photoselective vaporization of prostate (PVP) green light (532 nm) laser is increasingly being used as an alternative to the transurethral resection of prostate (TURP) for treatment of benign prostatic hyperplasia (BPH) in older patients and those who are poor surgical candidates. In order to achieve the goals of increased tissue removal volume (i.e., "ablation" in the engineering sense) and reduced collateral thermal damage during the PVP green light treatment, a two dimensional computational model for laser tissue ablation based on available parameters in the literature has been developed and compared to experiments. The model is based on the control volume finite difference and the enthalpy method with a mechanistically defined energy necessary to ablate (i.e., physically remove) a volume of tissue (i.e., energy of ablation E(ab)). The model was able to capture the general trends experimentally observed in terms of ablation and coagulation areas, their ratio (therapeutic index (TI)), and the ablation rate (AR) (mm(3)/s). The model and experiment were in good agreement at a smaller working distance (WD) (distance from the tissue in mm) and a larger scanning speed (SS) (laser scan speed in mm/s). However, the model and experiment deviated somewhat with a larger WD and a smaller SS; this is most likely due to optical shielding and heat diffusion in the laser scanning direction, which are neglected in the model. This model is a useful first step in the mechanistic prediction of PVP based BPH laser tissue ablation. Future modeling efforts should focus on optical shielding, heat diffusion in the laser scanning direction (i.e., including 3D effects), convective heat losses at the tissue boundary, and the dynamic optical, thermal, and coagulation properties of BPH tissue.

Experimental study on ablation of leiomyoma by combination high-intensity focused ultrasound and iodized oil in vitro.

PubMed

Liang, Zhi-Gang; Gao, Yi; Ren, Xiao-Yan; Sun, Cui; Gu, Heng-Fang; Mou, Meng; Xiao, Yan-Bing

2017-10-01

The aim of the current study was to investigate whether iodized oil (IO) enhances high-intensity focused ultrasound (HIFU) ablation of uterine leiomyoma and to determine the features of hyperechoic changes in the target region. Forty samples of uterine leiomyoma were randomly divided into an experimental group and a control group. In the experimental group, the leiomyoma was ablated by HIFU 30 min after 1 mL of iodized oil had been injected into the center of the myoma. The hyperechoic values and areas in the target region were observed by B-modal ultrasound after HIFU ablation. The samples were cut successively into slices and stained by triphenyltetrazolium chloride (TTC) solution within 1 h after HIFU ablation. The diameters of TTC-non-stained areas were measured and tissues in the borderline of the TTC-stained and -non-stained areas were observed pathologically. All procedures in the control group were the same as those in the experimental group except IO was replaced by physiological saline. The hyperechoic value in the target region in the experimental group was higher than that in the control group 4 min after HIFU ablation (P < 0.05). Hyperechoic areas in the target region as well as TTC-non-stained volumes in the experimental group were greater than those in the control group (P < 0.05). Routine pathologic observation showed that coagulation necrosis of leiomyoma occurred in the target region in both groups. IO causes coagulation necrosis, enlarges tissue damage, and postpones the attenuation of hyperechoic changes in the target region when HIFU ablation is carried out for leiomyoma in vitro. © 2017 Japan Society of Obstetrics and Gynecology.

Liver cancer: increased microwave delivery to ablation zone with cooled-shaft antenna--experimental and clinical studies.

PubMed

Kuang, Ming; Lu, Ming D; Xie, Xiao Y; Xu, Hui X; Mo, Li Q; Liu, Guang J; Xu, Zuo F; Zheng, Yan L; Liang, Jin Y

2007-03-01

To prospectively investigate whether the ablation zone induced with microwaves could be increased by delivering greater energy with a cooled-shaft antenna. All studies were animal care and ethics committee approved. Written informed consent was obtained from all patients. Microwave ablation was performed by using a cooled-shaft antenna in 48 ex vivo and 12 in vivo experiments with porcine livers. The coagulation diameters achieved in different microwave ablation parameter groups (60-90 W for 5-25 minutes) were compared. Ninety patients (78 men, 12 women; mean age, 53 years; age range, 20-82 years) with 133 0.8-8.0-cm (mean, 2.7 cm +/- 1.5 [standard deviation]) primary or metastatic liver cancers were treated with the same microwave ablation technique. Complete ablation (CA) and local tumor progression (LTP) rates were determined. Generalized estimating equations were used to compare differences in tumor size, ablation zone diameter, and CA and LTP rates between different patient subgroups. In the ex vivo livers, in vivo livers, and liver cancers, one application of microwave energy with 80 W for 25 minutes produced mean coagulation diameters of 5.6 x 7.4 cm, 3.5 x 5.9 cm, and 3.6 x 5.0 cm, respectively. Skin burn was not observed. CA rates in small (

Photothermal effect of infrared lasers on ex vivo lamb brain tissues

NASA Astrophysics Data System (ADS)

Özgürün, Baturay; Gülsoy, Murat

2018-02-01

Here, the most suitable infrared laser for a neurosurgery operation is suggested, among 1940-nm thulium fiber, 1470-nm diode, 1070-nm ytterbium fiber and 980-nm diode lasers. Cortical and subcortical ex-vivo lamb brain tissues are exposed to the laser light with the combinations of some laser parameters such as output power, energy density, operation mode (continuous and pulsed-modulated) and operation time. In this way, the greatest ablation efficiency associated with the best neurosurgical laser type can be defined. The research can be divided into two parts; pre-dosimetry and dosimetry studies. The former is used to determine safe operation zones for the dosimetry study by defining coagulation and carbonization onset times for each of the brain tissues. The latter is the main part of this research, and both tissues are exposed to laser irradiation with various energy density levels associated with the output power and operation time. In addition, photo-thermal effects are compared for two laser operation modes, and then coagulation and ablation diameters to calculate the ablation efficiency are measured under a light microscope. Consequently, results are compared graphically and statistically, and it is found that thulium and 1470-nm diode lasers can be utilized as subcortical and cortical tissue ablator devices, respectively.

Automatic alignment of pre- and post-interventional liver CT images for assessment of radiofrequency ablation

NASA Astrophysics Data System (ADS)

Rieder, Christian; Wirtz, Stefan; Strehlow, Jan; Zidowitz, Stephan; Bruners, Philipp; Isfort, Peter; Mahnken, Andreas H.; Peitgen, Heinz-Otto

2012-02-01

Image-guided radiofrequency ablation (RFA) is becoming a standard procedure for minimally invasive tumor treatment in clinical practice. To verify the treatment success of the therapy, reliable post-interventional assessment of the ablation zone (coagulation) is essential. Typically, pre- and post-interventional CT images have to be aligned to compare the shape, size, and position of tumor and coagulation zone. In this work, we present an automatic workflow for masking liver tissue, enabling a rigid registration algorithm to perform at least as accurate as experienced medical experts. To minimize the effect of global liver deformations, the registration is computed in a local region of interest around the pre-interventional lesion and post-interventional coagulation necrosis. A registration mask excluding lesions and neighboring organs is calculated to prevent the registration algorithm from matching both lesion shapes instead of the surrounding liver anatomy. As an initial registration step, the centers of gravity from both lesions are aligned automatically. The subsequent rigid registration method is based on the Local Cross Correlation (LCC) similarity measure and Newton-type optimization. To assess the accuracy of our method, 41 RFA cases are registered and compared with the manually aligned cases from four medical experts. Furthermore, the registration results are compared with ground truth transformations based on averaged anatomical landmark pairs. In the evaluation, we show that our method allows to automatic alignment of the data sets with equal accuracy as medical experts, but requiring significancy less time consumption and variability.

Thermal Ablation by High-Intensity-Focused Ultrasound Using a Toroid Transducer Increases the Coagulated Volume and Allows Coagulation Near Portal and Hepatic veins in Pigs

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

Melodelima, D.; N'Djin, W. A.; Parmentier, H.

2009-04-14

A new geometry of HIFU transducer is described to enlarge the coagulated volume. The geometry of the transducer was not spherical. The surface of the transducer was built based on a toroid geometry. The transducer was generated by the revolution of a circle about an axis lying in its plane. Eight emitters operating at a frequency of 3 MHz were diced out of a single toroid piezocomposite element. Each of the eight emitters was divided into 32 transducers. The focal zone is conical and located at 70 mm from the transducer. A 7.5 MHz ultrasound imaging probe is placed inmore » the centre of the device for guiding the treatment. Our long-term objective is to develop a device that can be used during surgery. In vivo trials have been performed on 13 pigs to demonstrate this new principle and to evaluate the vascular tolerance of the treatment. This new geometry combined with consecutive activation of the eight emitters around the toroid allows achieving a mean thermal ablation of 7.0{+-}2.5 cm3 in 40 seconds. All lesions were visible with high contrast on sonograms. The correlation between the size of lesions observed on sonograms and during gross examination was 92%. This allows the user to easily enlarge the coagulated volume by juxtaposing single lesions. The pigs tolerate the treatment well over the experimental period even when coagulation was produced through portal and/or hepatic veins.« less

Cavitation enhances coagulated size during pulsed high-intensity focussed ultrasound ablation in an isolated liver perfusion system.

PubMed

Zhao, Lu-Yan; Liu, Shan; Chen, Zong-Gui; Zou, Jian-Zhong; Wu, Feng

2016-11-24

To investigate whether cavitation enhances the degree of coagulation during pulsed high-intensity focussed ultrasound (HIFU) in an isolated liver perfusion system. Isolated liver was treated by pulsed HIFU or continuous-wave HIFU with different portal vein flow rates. The cavitation emission during exposure was recorded, and real-time ultrasound images were used to observe changes in the grey scale. The coagulation size was measured and calculated. HIFU treatment led to complete coagulation necrosis and total cell destruction in the target regions. Compared to exposure at a duty cycle (DC) of 100%, the mean volumes of lesions induced by 6 s exposure at DCs of 50% and 10% were significantly larger (P < .01) but were smaller at a DC of 5%. The necrosis volume was negatively related to the perfusion rate in the pulsed HIFU at a DC of 50% for exposure durations of 4 and 6 s, while the perfusion flow rate did not affect the necrosis volume for exposure durations of 1, 2 and 3 s. For increased perfusion flow rates, there was no significant decrease in the cavitation activity for the pulsed-HIFU (P > .05). For continuous-wave HIFU exposure, there was a significant decrease in the necrosis volume and cavitation activity for exposure times of 1, 2, 3, 4, and 6 s with increasing portal perfusion rates. Perfusion flow rates negatively influence cavitation activity and coagulation volume. Ablation is significantly enhanced during pulsed HIFU exposure compared with continuous-wave HIFU.

Investigation of the efficacy of ultrafast laser in large bowel excision

NASA Astrophysics Data System (ADS)

Mohanan, Syam Mohan P. C.; Beck, Rainer J.; Góra, Wojciech S.; Perry, Sarah L.; Shires, Mike; Jayne, David; Hand, Duncan P.; Shephard, Jonathan D.

2017-02-01

Local resection of early stage tumors in the large bowel via colonoscopy has been a widely accepted surgical modality for colon neoplasm treatment. The conventional electrocautery techniques used for the resection of neoplasia in the mucosal or submucosal layer of colon tissue has been shown to create obvious thermal necrosis to adjacent healthy tissues and lacks accuracy in resection. Ultrafast picosecond (ps) laser ablation using a wavelength of 1030 or 515 nm is a promising surgical tool to overcome the limitations seen with conventional surgical techniques. The purpose of this initial study is to analyze the depth of ablation or the extent of coagulation deployed by the laser as a function of pulse energy and fluence in an ex-vivo porcine model. Precise control of the depth of tissue removal is of paramount importance for bowel surgery where bowel perforation can lead to morbidity or mortality. Thus we investigate the regimes that are optimal for tissue resection and coagulation through plasma mediated ablation of healthy colon tissue. The ablated tissue samples were analyzed by standard histologic methods and a three dimensional optical profilometer technique. We demonstrate that ultrafast laser resection of colonic tissue can minimize the region of collateral thermal damage (<50 μm) with a controlled ablation depth. This surgical modality allows potentially easier removal of early stage lesions and has the capability to provide more control to the surgeon in comparison with a mechanical or electrocautery device.

Multipolar hepatic radiofrequency ablation using up to six applicators: preliminary results.

PubMed

Bruners, P; Schmitz-Rode, T; Günther, R W; Mahnken, A

2008-03-01

To evaluate the clinical feasibility and safety of hepatic radiofrequency (RF) ablation using a multipolar RF system permitting the simultaneous use of up to six electrodes. Ten patients (3 female, 7 male, mean age 61) suffering from 29 hepatic metastases (range: 1 - 5) of different tumors were treated with a modified multipolar RF system (CelonLab Power, Celon Medical Instruments, Teltow, Germany) operating four to six needle-shaped internally cooled RF applicators. The procedure duration, applied energy and generator output were recorded during the intervention. The treatment result and procedure-related complications were analyzed. The achieved coagulation volume was calculated on the basis of contrast-enhanced CT scans 24 hours after RF ablation. Complete tumor ablation was achieved in all cases as determined by the post-interventional lack of contrast enhancement in the target region using four applicators in five patients, five applicators in one patient and six applicators in four patients. A mean energy deposition of 353.9 +/- 176.2 kJ resulted in a mean coagulation volume of 115.9 +/- 79.5 cm (3). The mean procedure duration was 74.9 +/- 21.2 minutes. Four patients showed an intraabdominal hemorrhage which necessitated further interventional treatment (embolization; percutaneous histoacryl injection) in two patients. Multipolar RF ablation of hepatic metastasis with up to six applicators was clinically feasible. In our patient population it was associated with an increased risk of intraabdominal bleeding probably due to the multiple punctures associated with the use of multiple applicators.

High-intensity focused ultrasound ablation induced apoptosis in human hepatocellular carcinoma.

PubMed

Yi, Jiang; Wu, Liguo; Liu, Zhou; Zou, Haibo; Li, Ning; Chen, Heping; Liu, Jinheng; Li, Tao; Zhang, Gang

2014-01-01

To evaluate the effect of high-intensity ultrasound (HIFU) ablation on human hepatocellular carcinoma tissues and apoptotic proteins (bcl-2 and p-53). Patients with hepatocellular carcinoma at stage B were treated with HIFU ablation. Levels of bcl-2 and p53 protein and the apoptosis rate were evaluated both in the pre-treatment and post-treatment tissue specimens using immunochemistry and TUNEL methods, respectively. After HIFU ablation, p53 protein levels were significantly increased around the coagulation necrosis area, whereas, the level of bcl-2 was significantly decreased. More apoptosis cells were found post ablation compared with those in the pretreatment tissues. Additionally, no significant correlation was found between p53/bcl-2 levels and apoptotic index. HIFU ablation may exert promote the apoptosis of hepatocellular carcinoma cells and the effect has a closely association with the change of p53 and bcl-2 expression.

In vitro assessment of fiber sweeping speed during Q-switched 532-nm laser tissue ablation

NASA Astrophysics Data System (ADS)

Rajabhandharaks, Danop; Kang, Hyun Wook; Ko, Woo Jin; Stinson, Douglas; Choi, Benjamin

2011-03-01

Photoselective vaporization of the prostate (PVP) is considered a minimally invasive procedure to treat benign prostatic hyperplasia (BPH). During the PVP, the prostate gland is irradiated by the 532-nm laser and the fiber is swept and dragged along the urethra. In this study the speed of sweeping fiber during the PVP is being investigated. In vitro porcine kidney model was used (N=100) throughout the experiment. A Q-switched 532-nm laser, equipped with sidefiring 750-Um fiber, was employed and set to power levels of 120 and 180 W. The speed of fiber sweeping was the only variable in this study and varied at 0 (i.e. no sweeping), 0.5, 1.0, 1.5, and 2.0 sweep/s. Ablation rate, depth, and coagulation thickness were quantified. Based on the current settings, ablation rate decreased as sweeping speed increased and was maximized between 0 to 1.0 sweep/s for 120-W power level and between 0 to 0.5 sweep/s for 180-W power level. Ablation rate at 180 W was higher than that at 120 W, regardless of sweeping speed. Ablation depth at both 120 and 180 W was maximized at 0 sweep/s and decreased 35% at 0.5 sweep/s. The overall coagulation thickness was less than 1.5 mm and comparable from 0 to 1.5 sweep/s (0.8~0.9 mm) and increased at 2.0 sweep/s (~1.1 mm). This study demonstrated that tissue ablation performance was contingent upon sweeping speed and maximized at slow sweeping speed due to longer laser-tissue interaction time and larger area coverage by the 532-nm light.

Micro-fractional ablative skin resurfacing with two novel erbium laser systems.

PubMed

Dierickx, Christine C; Khatri, Khalil A; Tannous, Zeina S; Childs, James J; Cohen, Richard H; Erofeev, Andrei; Tabatadze, David; Yaroslavsky, Ilya V; Altshuler, Gregory B

2008-02-01

Fractional ablation offers the potential benefits of full-surface ablative skin resurfacing while minimizing adverse effects. The purpose of this study was to evaluate the safety, damage profile, and efficacy of erbium fractional lasers. Histology from animal and human skin as well as clinical evaluations were conducted with erbium YAG (2,940 nm) and erbium YSGG (2,790 nm) fractional lasers varying pulse width, microbeam (microb) energy, number of passes, and stacking of pulses. Single-pulse treatment parameters from 1 to 12 mJ per 50-70 microm diameter microbeam and 0.25-5 milliseconds pulse widths produced microcolumns of ablation with border coagulation of up to 100 microm width and 450 microm depth. Stacking of pulses generated deeper microcolumns. Clinical observations and in vivo histology demonstrate rapid re-epithelization and limited adverse side effects. Facial treatments were performed in the periorbital and perioral areas using 1-8 passes of single and stacked pulses. Treatments were well-tolerated and subjects could resume their normal routine in 4 days. A statistically significant reduction in wrinkle scores at 3 months was observed for both periorbital and perioral wrinkles using blinded grading. For periorbital treatments of four passes or more, over 90% had > or =1 score wrinkle reduction (0-9 scale) and 42% had > or =2. For perioral wrinkles, over 50% had substantial improvements (> or =2). The clinical observations and histology findings demonstrate that micro-fractional ablative treatment with 2,790 and 2,940 nm erbium lasers resulted in safe and effective wrinkle reduction with minimal patient downtime. The depth and width of the ablated microcolumns and varying extent of surrounding coagulation can be controlled and used to design new treatment procedures targeted for specific indications and areas such as moderate to severe rhytides and photodamaged skin.

Algorithm optimization for multitined radiofrequency ablation: comparative study in ex vivo and in vivo bovine liver.

PubMed

Appelbaum, Liat; Sosna, Jacob; Pearson, Robert; Perez, Sarah; Nissenbaum, Yizhak; Mertyna, Pawel; Libson, Eugene; Goldberg, S Nahum

2010-02-01

To prospectively optimize multistep algorithms for largest available multitined radiofrequency (RF) electrode system in ex vivo and in vivo tissues, to determine best energy parameters to achieve large predictable target sizes of coagulation, and to compare these algorithms with manufacturer's recommended algorithms. Institutional animal care and use committee approval was obtained for the in vivo portion of this study. Ablation (n = 473) was performed in ex vivo bovine liver; final tine extension was 5-7 cm. Variables in stepped-deployment RF algorithm were interrogated and included initial current ramping to 105 degrees C (1 degrees C/0.5-5.0 sec), the number of sequential tine extensions (2-7 cm), and duration of application (4-12 minutes) for final two to three tine extensions. Optimal parameters to achieve 5-7 cm of coagulation were compared with recommended algorithms. Optimal settings for 5- and 6-cm final tine extensions were confirmed in in vivo perfused bovine liver (n = 14). Multivariate analysis of variance and/or paired t tests were used. Mean RF ablation zones of 5.1 cm +/- 0.2 (standard deviation), 6.3 cm +/- 0.4, and 7 cm +/- 0.3 were achieved with 5-, 6-, and 7-cm final tine extensions in a mean of 19.5 min +/- 0.5, 27.9 min +/- 6, and 37.1 min +/- 2.3, respectively, at optimal settings. With these algorithms, size of ablation at 6- and 7-cm tine extension significantly increased from mean of 5.4 cm +/- 0.4 and 6.1 cm +/- 0.6 (manufacturer's algorithms) (P <.05, both comparisons); two recommended tine extensions were eliminated. In vivo confirmation produced mean diameter in specified time: 5.5 cm +/- 0.4 in 18.5 min +/- 0.5 (5-cm extensions) and 5.7 cm +/- 0.2 in 21.2 min +/- 0.6 (6-cm extensions). Large zones of coagulation of 5-7 cm can be created with optimized RF algorithms that help reduce number of tine extensions compared with manufacturer's recommendations. Such algorithms are likely to facilitate the utility of these devices for RF ablation of focal tumors in clinical practice. (c) RSNA, 2010.

Percutaneous radiofrequency ablation of lung tumors in a large animal model.

PubMed

Ahrar, Kamran; Price, Roger E; Wallace, Michael J; Madoff, David C; Gupta, Sanjay; Morello, Frank A; Wright, Kenneth C

2003-08-01

Percutaneous radiofrequency ablation (RFA) is accepted therapy for liver tumors in the appropriate clinical setting, but its use in lung neoplasms remains investigational. We undertook this study to evaluate the feasibility and immediate effectiveness of RFA for treatment of both solitary pulmonary nodules and clusters of lung tumors in a large animal model. Percutaneous RFA of 14 lung tumors in five dogs was performed under CT guidance. Animals were euthanatized 8-48 hours after the procedure. The lungs and adjacent structures were harvested for gross and histopathologic evaluation. Five solitary pulmonary nodules (range, 17-26 mm) and three clusters of three nodules each (range, 7-17 mm per nodule) were treated with RFA. All ablations were technically successful. Perilesional ground-glass opacity and small asymptomatic pneumothoraces (n = 4) were visualized during the RFA sessions. One dog developed a large pneumothorax treated with tube thoracostomy but was euthanatized 8 hours post-RFA for persistent pneumothorax and continued breathing difficulty. Follow-up CT 48 hours post-RFA revealed opacification of the whole lung segment. Gross and histopathologic evaluation showed complete thermal coagulation necrosis of all treated lesions without evidence of any viable tumor. The region of thermal coagulation necrosis typically extended to the lung surface. Small regions of pulmonary hemorrhage and congestion often surrounded the areas of coagulation necrosis. RFA can be used to treat both solitary pulmonary nodules and clusters of tumor nodules in the canine lung tumor model. This model may be useful for development of specific RFA protocols for human lung tumors.

Current role of lasers in the treatment of benign prostatic hyperplasia (BPH).

PubMed

Kuntz, Rainer M

2006-06-01

Evaluate the current role of lasers in the treatment of benign prostatic hyperplasia (BPH). The results of a MEDLINE search for randomised trials and case series of the last 5 yr and published review articles were analysed for the safety and efficacy of neodymium:yttrium aluminum garnet (Nd:YAG), potassium-titanyl-phosphate (KTP), and holmium (Ho):YAG laser prostatectomy. The analysis includes 12 reports on randomised clinical trials, 2 comparative studies, 10 review articles, and a total of >5000 patients. Laser treatment of BPH has evolved from coagulation to enucleation. Blood loss is significantly reduced compared with transurethral resection and open prostatectomy. Visual laser ablation of the prostate and interstitial laser coagulation cause coagulative necrosis with secondary ablation. Long postoperative catheterisation, unpredictable outcomes, and high reoperation rates have restricted the use of these techniques. Ablative/vaporising techniques have become popular again with the marketing of new high-powered 80-W KTP and 100-W Ho lasers. Vaporisation immediately removes obstructing tissue. Short-term results are promising, but large series, long-term results, and randomised trials are lacking. Holmium laser enucleation (HoLEP) allows whole lobes of the prostate to be removed, mimicking the action of the index finger in open prostatectomy. Prostates of all sizes can be operated on. It is at least as safe and effective as transurethral resection of the prostate and open prostatectomy, with significantly lower morbidity. It is the only laser procedure that provides a specimen for histologic evaluation. HoLEP appears to be a size-independent new "gold standard" in the surgical treatment of BPH.

A novel suction/coagulation integrated probe for achieving better hemostasis: development and clinical use.

PubMed

Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Yamamoto, Hirofumi; Mizushima, Tsunekazu; Mori, Masaki; Doki, Yuichiro; Nakajima, Kiyokazu

2018-06-01

Modern electrosurgical tools have a specific coagulation mode called "soft coagulation". However, soft coagulation has not been widely accepted for surgical operations. To optimize the soft coagulation environment, we developed a novel suction device integrated with an electrosurgical probe, called the "Suction ball coagulator" (SBC). In this study, we aimed to optimize the SBC design with a prototyping process involving a bench test and preclinical study; then, we aimed to demonstrate the feasibility, safety, and potential effectiveness of the SBC for laparoscopic surgery in clinical settings. SBC prototyping was performed with a bench test. Device optimization was performed in a preclinical study with a domestic swine bleeding model. Then, SBC was tested in a clinical setting during 17 clinical laparoscopic colorectal surgeries. In the bench tests, two tip hole sizes and patterns showed a good suction capacity. The preclinical study indicated the best tip shape for accuracy. In clinical use, no device-related adverse event was observed. Moreover, the SBC was feasible for prompt hemostasis and blunt dissections. In addition, SBC could evacuate vapors generated by tissue ablation using electroprobe during laparoscopic surgery. We successfully developed a novel, integrated suction/coagulation probe for hemostasis and commercialized it.

Renal ablation using magnetic resonance-guided high intensity focused ultrasound: Magnetic resonance imaging and histopathology assessment.

PubMed

Saeed, Maythem; Krug, Roland; Do, Loi; Hetts, Steven W; Wilson, Mark W

2016-03-28

To use magnetic resonance-guided high intensity focused ultrasound (MRg-HIFU), magnetic resonance imaging (MRI) and histopathology for noninvasively ablating, quantifying and characterizing ablated renal tissue. Six anesthetized/mechanically-ventilated pigs underwent single/double renal sonication (n = 24) using a 3T-MRg-HIFU (1.1 MHz frequency and 3000J-4400J energies). T2-weighted fast spin echo (T2-W), perfusion saturation recovery gradient echo and contrast enhanced (CE) T1-weighted (T1-W) sequences were used for treatment planning, temperature monitoring, lesion visualization, characterization and quantification, respectively. Histopathology was conducted in excised kidneys to quantify and characterize cellular and vascular changes. Paired Student's t-test was used and a P-value < 0.05 was considered statistically significant. Ablated renal parenchyma could not be differentiated from normal parenchyma on T2-W or non-CE T1-W sequences. Ablated renal lesions were visible as hypoenhanced regions on perfusion and CE T1-W MRI sequences, suggesting perfusion deficits and necrosis. Volumes of ablated parenchyma on CE T1-W images in vivo (0.12-0.36 cm(3) for single sonication 3000J, 0.50-0.84 cm(3), for double 3000J, 0.75-0.78 cm(3) for single 4400J and 0.12-2.65 cm(3) for double 4400J) and at postmortem (0.23-0.52 cm(3), 0.25-0.82 cm(3), 0.45-0.68 cm(3) and 0.29-1.80 cm(3), respectively) were comparable. The ablated volumes on 3000J and 4400J double sonication were significantly larger than single (P < 0.01), thus, the volume and depth of ablated tissue depends on the applied energy and number of sonication. Macroscopic and microscopic examinations confirmed the locations and presence of coagulation necrosis, vascular damage and interstitial hemorrhage, respectively. Contrast enhanced MRI provides assessment of MRg-HIFU renal ablation. Histopathology demonstrated coagulation necrosis, vascular damage and confirmed the volume of damage seen on MRI.

Systematic review of high-intensity focused ultrasound ablation in the treatment of breast cancer.

PubMed

Peek, M C L; Ahmed, M; Napoli, A; ten Haken, B; McWilliams, S; Usiskin, S I; Pinder, S E; van Hemelrijck, M; Douek, M

2015-07-01

A systematic review was undertaken to assess the clinical efficacy of non-invasive high-intensity focused ultrasound (HIFU) ablation in the treatment of breast cancer. MEDLINE/PubMed library databases were used to identify all studies published up to December 2013 that evaluated the role of HIFU ablation in the treatment of breast cancer. Studies were eligible if they were performed on patients with breast cancer and objectively recorded at least one clinical outcome measure of response (imaging, histopathological or cosmetic) to HIFU treatment. Nine studies fulfilled the inclusion criteria. The absence of tumour or residual tumour after treatment was reported for 95·8 per cent of patients (160 of 167). No residual tumour was found in 46·2 per cent (55 of 119; range 17-100 per cent), less than 10 per cent residual tumour in 29·4 per cent (35 of 119; range 0-53 per cent), and between 10 and 90 per cent residual tumour in 22·7 per cent (27 of 119; range 0-60 per cent). The most common complication associated with HIFU ablation was pain (40·1 per cent) and less frequently oedema (16·8 per cent), skin burn (4·2 per cent) and pectoralis major injury (3·6 per cent). MRI showed an absence of contrast enhancement after treatment in 82 per cent of patients (31 of 38; range 50-100 per cent), indicative of coagulative necrosis. Correlation of contrast enhancement on pretreatment and post-treatment MRI successfully predicted the presence of residual disease. HIFU treatment can induce coagulative necrosis in breast cancers. Complete ablation has not been reported consistently on histopathology and no imaging modality has been able confidently to predict the percentage of complete ablation. Consistent tumour and margin necrosis with reliable follow-up imaging are required before HIFU ablation can be evaluated within large, prospective clinical trials. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Primary malignant tumours of the bony pelvis: US-guided high intensity focused ultrasound ablation.

PubMed

Wang, Yang; Wang, Wei; Tang, Jie

2013-11-01

The aim of this review is to evaluate the value of ultrasound (US)-guided high intensity focused ultrasound (HIFU) ablation in the treatment of primary malignant tumours of the bony pelvis. Eleven patients with primary malignant tumours of the bony pelvis received US-guided HIFU ablation. The maximum tumour size ranged from 5.6 to 25.0 cm (median 10.5 cm). Treatment was curative in four patients and palliative in seven patients. During follow-up, the effectiveness of HIFU ablation was assessed by contrast-enhanced magnetic resonance (MR). Significant coagulative necrosis was obtained in all patients after scheduled HIFU ablations; the volume ablation ratio was 86.7% ± 12.5% (range 65-100%). Complete tumour necrosis was achieved in all patients receiving curative HIFU ablation. No major complications were encountered. No patients died of local tumour progression during follow-up. US-guided HIFU ablation may be a safe and effective minimally invasive technique for the local treatment of primary malignant tumours of the bony pelvis.

Monitoring of tissue optical properties during thermal coagulation of ex vivo tissues.

PubMed

Nagarajan, Vivek Krishna; Yu, Bing

2016-09-01

Real-time monitoring of tissue status during thermal ablation of tumors is critical to ensure complete destruction of tumor mass, while avoiding tissue charring and excessive damage to normal tissues. Currently, magnetic resonance thermometry (MRT), along with magnetic resonance imaging (MRI), is the most commonly used technique for monitoring and assessing thermal ablation process in soft tissues. MRT/MRI is very expensive, bulky, and often subject to motion artifacts. On the other hand, light propagation within tissue is sensitive to changes in tissue microstructure and physiology which could be used to directly quantify the extent of tissue damage. Furthermore, optical monitoring can be a portable, and cost-effective alternative for monitoring a thermal ablation process. The main objective of this study, is to establish a correlation between changes in tissue optical properties and the status of tissue coagulation/damage during heating of ex vivo tissues. A portable diffuse reflectance spectroscopy system and a side-firing fiber-optic probe were developed to study the absorption (μa (λ)), and reduced scattering coefficients (μ's (λ)) of native and coagulated ex vivo porcine, and chicken breast tissues. In the first experiment, both porcine and chicken breast tissues were heated at discrete temperature points between 24 and 140°C for 2 minutes. Diffuse reflectance spectra (430-630 nm) of native and coagulated tissues were recorded prior to, and post heating. In a second experiment, porcine tissue samples were heated at 70°C and diffuse reflectance spectra were recorded continuously during heating. The μa (λ) and μ's (λ) of the tissues were extracted from the measured diffuse reflectance spectra using an inverse Monte-Carlo model of diffuse reflectance. Tissue heating was stopped when the wavelength-averaged scattering plateaued. The wavelength-averaged optical properties, <μ's (λ)> and <μa (λ)>, for native porcine tissues (n = 66) at room temperature, were 5.4 ± 0.3 cm(-1) and 0.780 ± 0.008 cm(-1) (SD), respectively. The <μ's (λ)> and <μa (λ)> for native chicken breast tissues (n = 66) at room temperature, were 2.69 ± 0.08 cm(-1) and 0.29 ± 0.01 cm(-1) (SD), respectively. In the first experiment, the <μ's (λ)> of coagulated porcine and chicken breast tissue rose to 56.4 ± 3.6 cm(-1) at 68.7 ± 1.7°C (SD), and 52.8 ± 1 cm(-1) at 57.1 ± 1.5°C (SD), respectively. Correspondingly, the <μa (λ)> of coagulated porcine (140.6°C), and chicken breast tissues (130°C) were 0.75 ± 0.05 cm(-1) and 0.263 ± 0.004 cm(-1) (SD). For both tissues, charring was observed at temperatures above 80°C. During continuous monitoring of porcine tissue (with connective tissues) heating, the <μ's (λ)> started to rise rapidly from 13.7 ± 1.5 minutes and plateaued at 19 ± 2.5 (SD) minutes. The <μ's (λ)> plateaued at 11.7 ± 3 (SD) minutes for porcine tissue devoid of connective tissue between probe and tissue surface. No charring was observed during continuous monitoring of thermal ablation process. The changes in optical absorption and scattering properties can be continuously quantified, which could be used as a diagnostic biomarker for assessing tissue coagulation/damage during thermal ablation. Lasers Surg. Med. 48:686-694, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Microwave ablation devices for interventional oncology.

PubMed

Ward, Robert C; Healey, Terrance T; Dupuy, Damian E

2013-03-01

Microwave ablation is one of the several options in the ablation armamentarium for the treatment of malignancy, offering several potential benefits when compared with other ablation, radiation, surgical and medical treatment modalities. The basic microwave system consists of the generator, power distribution system and antennas. Often under image (computed tomography or ultrasound) guidance, a needle-like antenna is inserted percutaneously into the tumor, where local microwave electromagnetic radiation is emitted from the probe's active tip, producing frictional tissue heating, capable of causing cell death by coagulation necrosis. Half of the microwave ablation systems use a 915 MHz generator and the other half use a 2450 MHz generator. To date, there are no completed clinical trials comparing microwave devices head-to-head. Prospective comparisons of microwave technology with other treatment alternatives, as well as head-to-head comparison with each microwave device, is needed if this promising field will garner more widespread support and use in the oncology community.

[System continuity and energy distribution in laser-induced thermo therapy (LITT)].

PubMed

Pech, M; Werk, M; Beck, A; Stohlmann, A; Ricke, J

2002-06-01

Evaluation of the continuity and energy distribution of a laser system for laser-induced thermo therapy. For evaluation of the continuity of laser optical devices, laser generating units and optical fibers of three different manufactures (Dornier, Hüttinger, Somatex), we used the equipment to generate a laser beam of 25 Watt for 60 minutes. Measurements of the applied energy were done sequentially with two MY Test (Fa. Hüttinger) units. We also performed two in vitro ablations of animal liver tissue with different fiber optics [Mikrodom A 13-0540, Microflexx REF A 13-0561 (Hüttinger), Diffusor-Tip H-6111-T 3, Diffusor H-6111-T 4 (Dornier), Somaflex-Diffusor (Somatex)] over 20 minutes at- an energy flow of 25 J per second. We then evaluated the geometry of coagulation. The different equipment used for our tests showed differences of a maximum of 10 %. Some components did not work properly in certain configurations even though the manufacturer assured it would. We saw significant differences in the ablation characteristics of the different fiber optics, especially in axial and frontal directions. Knowledge of the different characteristics in energy distribution and ablation characteristics are an important factor in performing a successful laser-induced thermo therapy.

Software-assisted post-interventional assessment of radiofrequency ablation

NASA Astrophysics Data System (ADS)

Rieder, Christian; Geisler, Benjamin; Bruners, Philipp; Isfort, Peter; Na, Hong-Sik; Mahnken, Andreas H.; Hahn, Horst K.

2014-03-01

Radiofrequency ablation (RFA) is becoming a standard procedure for minimally invasive tumor treatment in clinical practice. Due to its common technical procedure, low complication rate, and low cost, RFA has become an alternative to surgical resection in the liver. To evaluate the therapy success of RFA, thorough follow-up imaging is essential. Conventionally, shape, size, and position of tumor and coagulation are visually compared in a side-by-side manner using pre- and post-interventional images. To objectify the verification of the treatment success, a novel software assistant allowing for fast and accurate comparison of tumor and coagulation is proposed. In this work, the clinical value of the proposed assessment software is evaluated. In a retrospective clinical study, 39 cases of hepatic tumor ablation are evaluated using the prototype software and conventional image comparison by four radiologists with different levels of experience. The cases are randomized and evaluated in two sessions to avoid any recall-bias. Self-confidence of correct diagnosis (local recurrence vs. no local recurrence) on a six-point scale is given for each case by the radiologists. Sensitivity, specificity, positive and negative predictive values as well as receiver operating curves are calculated for both methods. It is shown that the software-assisted method allows physicians to correctly identify local tumor recurrence with a higher percentage than the conventional method (sensitivity: 0.6 vs. 0.35), whereas the percentage of correctly identified successful ablations is slightly reduced (specificity: 0.83 vs. 0.89).

Pure Ethiodized Oil-based Transcatheter Ablative Therapy in Normal Rabbit Kidneys and Kidneys Inoculated with VX-2 Carcinoma

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

Konya, Andras, E-mail: akonya@mdanderson.org; Stephens, L. Clifton; Wright, Kenneth C.

2011-10-15

Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol-Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization andmore » coil placement followed 7 days later (group 2, n = 6) or 11-14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean {+-} standard deviation) 0.47 {+-} 0.03, 0.53 {+-} 0.02, and 0.56 {+-} 0.04 ml of pure Ethiodol, followed by 0.47 {+-} 0.05, 0.42 {+-} 0.03, and 0.38 {+-} 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.« less

ON THE COAGULATION AND SIZE DISTRIBUTION OF PRESSURE CONFINED CORES

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

Huang Xu; Zhou Tingtao; Lin, D. N. C., E-mail: xuhuang@princeton.edu

2013-05-20

Observations of the Pipe Nebula have led to the discovery of dense starless cores. The mass of most cores is too small for their self-gravity to hold them together. Instead, they are thought to be pressure confined. The observed dense cores' mass function (CMF) matches well with the initial mass function of stars in young clusters. Similar CMFs are observed in other star forming regions such as the Aquila Nebula, albeit with some dispersion. The shape of these CMF provides important clues to the competing physical processes which lead to star formation and its feedback on the interstellar media. Inmore » this paper, we investigate the dynamical origin of the mass function of starless cores which are confined by a warm, less dense medium. In order to follow the evolution of the CMF, we construct a numerical method to consider the coagulation between the cold cores and their ablation due to Kelvin-Helmholtz instability induced by their relative motion through the warm medium. We are able to reproduce the observed CMF among the starless cores in the Pipe Nebula. Our results indicate that in environment similar to the Pipe Nebula: (1) before the onset of their gravitational collapse, the mass distribution of the progenitor cores is similar to that of the young stars, (2) the observed CMF is a robust consequence of dynamical equilibrium between the coagulation and ablation of cores, and (3) a break in the slope of the CMF is due to the enhancement of collisional cross section and suppression of ablation for cores with masses larger than the cores' Bonnor-Ebert mass.« less

Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.

PubMed

van den Bijgaart, Renske J E; Eikelenboom, Dylan C; Hoogenboom, Martijn; Fütterer, Jurgen J; den Brok, Martijn H; Adema, Gosse J

2017-02-01

Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4 + and CD8 + T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.

From coagulation to enucleation: the use of lasers in surgery for benign prostatic hyperplasia.

PubMed

Wilson, Liam C; Gilling, Peter J

2005-09-01

The application of lasers for the treatment of benign prostatic hyperplasia has evolved over the past 15 years. Early-generation neodymium:yttrium aluminum garnet lasers were used to coagulate and ablate prostatic tissue, but significant postoperative irritative symptoms and high reoperation rates meant that this approach did not seriously challenge the status quo for long. Ablative techniques have recently become popular again with the marketing of the newer-generation, higher-power potassium titanyl phosphate and holmium lasers. Although short-term data are encouraging, there are no comparative trials of significant duration, so it is not yet possible to draw conclusions with regard to efficacy and durability. The holmium laser can also be used as an incisional and dissecting tool that allows resection or enucleation of whole lobes of the prostate, mimicking the action of the index finger in open prostatectomy. The safety, efficacy, durability and cost-effectiveness of the holmium laser have been shown in well-designed randomized controlled trials.

Focused US system for MR imaging-guided tumor ablation.

PubMed

Cline, H E; Hynynen, K; Watkins, R D; Adams, W J; Schenck, J F; Ettinger, R H; Freund, W R; Vetro, J P; Jolesz, F A

1995-03-01

To measure the performance characteristics of a focused ultrasound (US) system for magnetic resonance (MR) imaging-guided tumor ablation. The authors constructed a focused US system for MR imaging-guided tumor ablation. The location of the heated region and thermal dose were monitored with temperature-sensitive MR images obtained in phantoms and rabbit skeletal muscle after application of each sonic pulse. The region heated by the focused ultrasound beam was within 1 mm of that observed on temperature-sensitive fast gradient-echo MR images of in vivo rabbit skeletal muscle. Analysis of heat flow and the rate of coagulation necrosis provided an estimate of the size of the ablated region that was in agreement with experimental findings. MR imaging provides target definition and control for thermal therapy in regions of variable perfusion or in tissues that are not well characterized.

Automatic Tracking Algorithm in Coaxial Near-Infrared Laser Ablation Endoscope for Fetus Surgery

NASA Astrophysics Data System (ADS)

Hu, Yan; Yamanaka, Noriaki; Masamune, Ken

2014-07-01

This article reports a stable vessel object tracking method for the treatment of twin-to-twin transfusion syndrome based on our previous 2 DOF endoscope. During the treatment of laser coagulation, it is necessary to focus on the exact position of the target object, however it moves by the mother's respiratory motion and still remains a challenge to obtain and track the position precisely. In this article, an algorithm which uses features from accelerated segment test (FAST) to extract the features and optical flow as the object tracking method, is proposed to deal with above problem. Further, we experimentally simulate the movement due to the mother's respiration, and the results of position errors and similarity verify the effectiveness of the proposed tracking algorithm for laser ablation endoscopy in-vitro and under water considering two influential factors. At average, the errors are about 10 pixels and the similarity over 0.92 are obtained in the experiments.

Laser ablation of basal cell carcinomas guided by confocal microscopy

NASA Astrophysics Data System (ADS)

Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

2016-02-01

Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

Computational modelling of internally cooled wet (ICW) electrodes for radiofrequency ablation: impact of rehydration, thermal convection and electrical conductivity.

PubMed

Trujillo, Macarena; Bon, Jose; Berjano, Enrique

2017-09-01

(1) To analyse rehydration, thermal convection and increased electrical conductivity as the three phenomena which distinguish the performance of internally cooled electrodes (IC) and internally cooled wet (ICW) electrodes during radiofrequency ablation (RFA), (2) Implement a RFA computer model with an ICW which includes these phenomena and (3) Assess their relative influence on the thermal and electrical tissue response and on the coagulation zone size. A 12-min RFA in liver was modelled using an ICW electrode (17 G, 3 cm tip) by an impedance-control pulsing protocol with a constant current of 1.5 A. A model of an IC electrode was used to compare the ICW electrode performance and the computational results with the experimental results. Rehydration and increased electrical conductivity were responsible for an increase in coagulation zone size and a delay (or absence) in the occurrence of abrupt increases in electrical impedance (roll-off). While the increased electrical conductivity had a remarkable effect on enlarging the coagulation zone (an increase of 0.74 cm for differences in electrical conductivity of 0.31 S/m), rehydration considerably affected the delay in roll-off, which, in fact, was absent with a sufficiently high rehydration level. In contrast, thermal convection had an insignificant effect for the flow rates considered (0.05 and 1 mL/min). Computer results suggest that rehydration and increased electrical conductivity were mainly responsible for the absence of roll-off and increased size of the coagulation zone, respectively, and in combination allow the thermal and electrical performance of ICW electrodes to be modelled during RFA.

A cost-utility analysis of ablative therapy for Barrett’s esophagus

PubMed Central

Inadomi, John M.; Somsouk, Ma; Madanick, Ryan D.; Thomas, Jennifer P.; Shaheen, Nicholas J.

2009-01-01

Background & Aims Recommendations for patients with Barrett’s esophagus (BE) include endoscopic surveillance with esophagectomy for early-stage cancer, although new technologies to ablate dysplasia and metaplasia are available. This study compares the cost-utility of ablation with that of endoscopic surveillance strategies. Methods A decision analysis model was created to examine a population of patients with BE (mean age 50), with separate analyses for patients with no dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). Strategies compared were: no endoscopic surveillance; endoscopic surveillance with ablation for incident dysplasia; immediate ablation followed by endoscopic surveillance in all patients or limited to patients in whom metaplasia persisted, and esophagectomy. Ablation modalities modeled included radiofrequency, argon plasma coagulation, multipolar electrocoagulation and photodynamic therapy. Results Endoscopic ablation for patients with HGD could increase life expectancy by 3 quality-adjusted years at an incremental cost of < $6,000, compared with no intervention. Patients with LGD or no dysplasia can also be optimally managed with ablation, but continued surveillance after eradication of metaplasia is expensive. If ablation permanently eradicates at least 28% of LGD or 40% of non-dysplastic metaplasias, ablation would be preferred to surveillance. Conclusions Endoscopic ablation could be the preferred strategy for managing patients with BE with HGD. Ablation might also be preferred in subjects with LGD or no dysplasia, but the cost-effectiveness depends on the long-term effectiveness of ablation and whether surveillance endoscopy can be discontinued following successful ablation. As further post-ablation data become available, the optimal management strategy will be clarified. PMID:19272389

Stability and trapping of magnetic resonance imaging contrast agents during high-intensity focused ultrasound ablation therapy.

PubMed

Hijnen, Nicole M; Elevelt, Aaldert; Grüll, Holger

2013-07-01

The purpose of this study was to investigate the use of Gd-DTPA shortly before magnetic resonance guided high-intensity focused ultrasound MR-HIFU thermal ablation therapy with respect to dissociation, trapping, and long-term deposition of gadolinium (Gd) in the body. Magnetic resonance-HIFU ablation treatment was conducted in vivo on both rat muscle and subcutaneous tumor (9L glioma) using a clinical 3T MR-HIFU system equipped with a small-animal coil setup. A human equivalent dose of gadopentetate dimeglumine (Gd-DTPA) (0.6 mmol/kg of body weight) was injected via a tail vein catheter just before ablation (≤5 minutes). Potential trapping of the contrast agent in the ablated area was visualized through the acquisition of R1 maps of the target location before and after therapy. The animals were sacrificed 2 hours or 14 days after the injection (n = 4 per group, a total of 40 animals). Subsequently, the Gd content in the tissue and carcass was determined using inductively coupled plasma techniques to investigate the biodistribution. Temporal trapping of Gd-DTPA in the coagulated tissue was observed on the R1 maps acquired within 2 hours after the ablation, an effect confirmed by the inductively coupled plasma analysis (3 times more Gd was found in the treated muscle volume than in the control muscle tissue). Two weeks after the therapy, the absolute amount of Gd present in the coagulated tissue was low compared with the amount present in the kidneys 14 days after the injection (ablated muscle, 0.009% ± 0.002% ID/g; kidney, 0.144% ± 0.165% ID/g). There was no significant increase in Gd content in the principal target organs for translocated Gdions (liver, spleen, and bone) or in the entire carcasses between the HIFU- and sham-treated animals. Finally, an in vivo relaxivity of 4.6 mmols was found in the HIFU-ablated volume, indicating intact Gd-DTPA. Magnetic resonance-HIFU treatment does not induce the dissociation of Gd-DTPA. In small-tissue volumes, no significant effect on the long-term in vivo Gd retention was found. However, care must be taken with the use of proton resonance frequency shift-based MR thermometry for HIFU guidance in combination with Gd because the susceptibility artifact induced by Gd can severely influence treatment outcome.

Photoselective laser ablation of the prostate: a review of the current 2015 tissue ablation options.

PubMed

Tholomier, Côme; Valdivieso, Roger; Hueber, Pierre-Alain; Zorn, Kevin C

2015-10-01

Transurethral resection of the prostate (TURP) is still considered the gold standard to treat benign prostatic hyperplasia (BPH). However, photoselective vaporization of the prostate (PVP) has gained widespread acceptance as an alternative option requiring preoperative patient selection. Four laser systems are currently in use: holmium, thulium, diode and GreenLight. The goal of this article is to review the physics and the basics behind laser prostatectomies, as well as to present the most current literature concerning the results, advantages, disadvantages and international recommendations for each vaporization procedure. Holmium laser ablation of the prostate (HoLAP) and GreenLight photoselective vaporization of the prostate are an alternative to TURP for small to medium-sized prostates, providing equivalent efficacy and safety. GreenLight is also safe and effective in large-sized prostates and especially beneficial in anti-coagulated individuals compared to TURP. Thulium vaporization of the prostate (ThuVAP) and diode vaporization both require additional randomized trials and long term studies before conclusion is made, despite promising initial results. Diode vaporization provides the best hemostasis overall, but at the cost of increased complication and re-treatment rate, and thus is not recommended except in severely anti-coagulated patients. Laser vaporization is a safe and effective alternative to TURP in the treatment of benign prostatic hyperplasia (BPH) for carefully selected patients. However, further research is still needed to assess the durability of each technology.

Preliminary experimental study on splenic hemodynamics of radiofrequency ablation for the spleen.

PubMed

Baba, Yasutaka; Hayashi, Sadao; Nagasato, Kohei; Higashi, Michiyo; Yoshiura, Takashi

2017-08-01

To test the splenic blood flow change after radiofrequency ablation (RFA) of the spleen in a porcine experimental model. Six pigs underwent RFA of the spleen via laparotomy. During the procedure of RFA, clamping of splenic artery (one) and both splenic artery/vein (one) was also performed. Measurement of blood flow of both splenic artery (SA) and splenic vein (SV) with flow-wire at pre- and post-RFA of the spleen was also performed. Ablated splenic lesions were created as estimating ∼50% area of the spleen in all pigs. Resected specimens reveal not only the coagulated necrosis but also the congestion of the spleen. On the SA hemodynamics, maximum peak velocity (MPV) changed from 37 ± 7 to 24 ± 8 cm/s (normal), 11 to 10 cm/s (clamp of the SA), and 12 to 7.5 cm/s (clamp of both SA/SV), respectively. On the SV hemodynamic, MPV changed from 15 ± 5 to 13 ± 4 cm/s (normal), 17 to 15 cm/s (clamp of the SA), and 17 to 26 cm/s (clamp of both SA/SV), respectively. RFA of the spleen could induce coagulation necrosis and reduce the splenic arterial blood flow.

Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: Preventing vector clearance and preserving infectivity.

PubMed

Krutzke, L; Prill, J M; Engler, T; Schmidt, C Q; Xu, Z; Byrnes, A P; Simmet, T; Kreppel, F

2016-08-10

The biodistribution of adenovirus type 5 (Ad5) vector particles is heavily influenced by interaction of the particles with plasma proteins, including coagulation factor X (FX), which binds specifically to the major Ad5 capsid protein hexon. FX mediates hepatocyte transduction by intravenously-injected Ad5 vectors and shields vector particles from neutralization by natural antibodies and complement. In mice, mutant Ad5 vectors that are ablated for FX-binding become detargeted from hepatocytes, which is desirable for certain applications, but unfortunately such FX-nonbinding vectors also become sensitive to neutralization by mouse plasma proteins. To improve the properties of Ad5 vectors for systemic delivery, we developed a strategy to replace the natural FX shield by a site-specific chemical polyethylene glycol shield. Coupling of polyethylene glycol to a specific site in hexon hypervariable region 1 yielded vector particles that were protected from neutralization by natural antibodies and complement although they were unable to bind FX. These vector particles evaded macrophages in vitro and showed significantly improved pharmacokinetics and hepatocyte transduction in vivo. Thus, site-specific shielding of Ad5 vectors with polyethylene glycol rendered vectors FX-independent and greatly improved their properties for systemic gene therapy. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Pulsed and CW adjustable 1942 nm single-mode all-fiber Tm-doped fiber laser system for surgical laser soft tissue ablation applications.

PubMed

Huang, Yize; Jivraj, Jamil; Zhou, Jiaqi; Ramjist, Joel; Wong, Ronnie; Gu, Xijia; Yang, Victor X D

2016-07-25

A surgical laser soft tissue ablation system based on an adjustable 1942 nm single-mode all-fiber Tm-doped fiber laser operating in pulsed or CW mode with nitrogen assistance is demonstrated. Ex vivo ablation on soft tissue targets such as muscle (chicken breast) and spinal cord (porcine) with intact dura are performed at different ablation conditions to examine the relationship between the system parameters and ablation outcomes. The maximum laser average power is 14.4 W, and its maximum peak power is 133.1 W with 21.3 μJ pulse energy. The maximum CW power density is 2.33 × 10⁶ W/cm² and the maximum pulsed peak power density is 2.16 × 10⁷ W/cm². The system parameters examined include the average laser power in CW or pulsed operation mode, gain-switching frequency, total ablation exposure time, and the input gas flow rate. The ablation effects were measured by microscopy and optical coherence tomography (OCT) to evaluate the ablation depth, superficial heat-affected zone diameter (HAZD) and charring diameter (CD). Our results conclude that the system parameters can be tailored to meet different clinical requirements such as ablation for soft tissue cutting or thermal coagulation for future applications of hemostasis.

Bipolar Radiofrequency Facet Ablation of the Lumbar Facet Capsule: An Adjunct to Conventional Radiofrequency Ablation for Pain Management

PubMed Central

Palea, Ovidiu; Granville, Michelle

2017-01-01

Radiofrequency facet ablation (RFA) has been performed using the same technique for over 50 years. Except for variations in electrode size, tip shape, and change in radiofrequency (RF) stimulation parameters, using standard, pulsed, and cooled RF wavelengths, the target points have remained absolutely unchanged from the original work describing RFA for lumbar pain control. Degenerative changes in the facet joint and capsule are the primary location for the majority of lumbar segmental pathology and pain. Multiple studies show that the degenerated facet joint is richly innervated as a result of the inflammatory overgrowth of the synovium. The primary provocative clinical test to justify an RFA is to perform an injection with local anesthetic into the facet joint and the posterior capsule and confirm pain relief. However, after a positive response, the radiofrequency lesion is made not to the facet joint but to the more proximal fine nerve branches that innervate the joint. The accepted target points for the recurrent sensory branch ignore the characteristic rich innervation of the pathologic lumbar facet capsule and assume that lesioning of these recurrent branches is sufficient to denervate the painful pathologic facet joint. This report describes the additional targets and technical steps for further coagulation points along the posterior capsule of the lumbar facet joint and the physiologic studies of the advantage of the bipolar radiofrequency current in this location. Bipolar RF to the facet capsule is a simple, extra step that easily creates a large thermo-coagulated lesion in this capsule region of the pathologic facet joint. Early studies demonstrate bipolar RF to the facet capsule can provide long-term pain relief when used alone for specific localized facet joint pain, to coagulate lumbar facet cysts to prevent recurrence, and to get more extensive pain control by combining it with traditional lumbar RFA, especially when RFA is repeated. PMID:29119066

Bipolar Radiofrequency Facet Ablation of the Lumbar Facet Capsule: An Adjunct to Conventional Radiofrequency Ablation for Pain Management.

PubMed

Jacobson, Robert E; Palea, Ovidiu; Granville, Michelle

2017-09-01

Radiofrequency facet ablation (RFA) has been performed using the same technique for over 50 years. Except for variations in electrode size, tip shape, and change in radiofrequency (RF) stimulation parameters, using standard, pulsed, and cooled RF wavelengths, the target points have remained absolutely unchanged from the original work describing RFA for lumbar pain control. Degenerative changes in the facet joint and capsule are the primary location for the majority of lumbar segmental pathology and pain. Multiple studies show that the degenerated facet joint is richly innervated as a result of the inflammatory overgrowth of the synovium. The primary provocative clinical test to justify an RFA is to perform an injection with local anesthetic into the facet joint and the posterior capsule and confirm pain relief. However, after a positive response, the radiofrequency lesion is made not to the facet joint but to the more proximal fine nerve branches that innervate the joint. The accepted target points for the recurrent sensory branch ignore the characteristic rich innervation of the pathologic lumbar facet capsule and assume that lesioning of these recurrent branches is sufficient to denervate the painful pathologic facet joint. This report describes the additional targets and technical steps for further coagulation points along the posterior capsule of the lumbar facet joint and the physiologic studies of the advantage of the bipolar radiofrequency current in this location. Bipolar RF to the facet capsule is a simple, extra step that easily creates a large thermo-coagulated lesion in this capsule region of the pathologic facet joint. Early studies demonstrate bipolar RF to the facet capsule can provide long-term pain relief when used alone for specific localized facet joint pain, to coagulate lumbar facet cysts to prevent recurrence, and to get more extensive pain control by combining it with traditional lumbar RFA, especially when RFA is repeated.

Ex vivo human bile duct radiofrequency ablation with a bipolar catheter.

PubMed

Atar, Mustafa; Kadayifci, Abdurrahman; Daglilar, Ebubekir; Hagen, Catherine; Fernandez-Del Castillo, Carlos; Brugge, William R

2018-06-01

Management of the primary and secondary tumors of the bile ducts still remains as a major clinical challenge. Radiofrequency (RF) ablation (RFA) of these tumors is feasible but the effect of RF energy on the human common bile duct (CBD) and surrounding tissues has not been investigated. This pilot study aimed to determine the relationship between RF energy and the depth of ablation in the normal human CBD. The study was performed on fresh ex vivo human biliary-pancreatic tissue which had been resected for a pancreatic cyst or mass. The study was conducted within 15 min after resection. A bipolar Habib RFA catheter was placed into the middle of the intact CBD, and three different (5, 7, 10 W) power settings were applied over a 90-s period by an RF generator. Gross and histological examinations were performed. The depth of coagulation necrosis in CBD and the effect of RFA on CBD wall and surrounding pancreas tissue were determined by microscopic examination. The study included eight tissue samples. 5 W power was applied to three sites and RFA caused only focal epithelial necrosis limited to the CBD mucosa. 7 and 10 W were applied to five sites and coagulation necrosis occurred in all cases. Microscopically, necrosis was transmural, involved accessory bile duct glands, and extended to the surrounding pancreatic tissue in four of these cases. Macroscopically, RFA resulted in circumferential white-yellowish color change extending approximately 2 cm of the CBD. Bipolar RF energy application with 5 W resulted in limited ablation on CBD wall. However, 7 and 10 W generated tissue necrosis which extended through the CBD wall and into surrounding pancreas tissue. Endoscopic biliary RFA is an effective technique for local biliary tissue ablation but the use of high energy may injure surrounding tissue.

Interstitial laser prostatectomy

NASA Astrophysics Data System (ADS)

Johnson, Douglas E.; Cromeens, Douglas M.; Price, Roger E.

1994-05-01

Interstitial laser coagulation of the canine prostate using the Sharplan interstitial thermal therapy fiber (Model 25432) was performed in 9 adult dogs and the subsequent gross and histopathologic changes occurring in the prostate were studied at intervals ranging from 1 hour to 5 weeks. A large well-demarcated area of acute coagulative necrosis developed around each fiber tract which in turn was surrounded by a prominent narrow zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction developed within the coagulative areas within 24 hours and by 4 days, each prostatic lobe contained an irregular cavity which became lined by normal-appearing transitional epithelium and that by 5 weeks, communicated with the prostatic urethra. These changes, similar to those reported following transurethral visual laser ablation of the prostate, suggest that interstitial laser thermal therapy may provide an alternative means for treating selected patients suffering from prostatic enlargement.

Changes in optical properties during heating of ex vivo liver tissues

NASA Astrophysics Data System (ADS)

Nagarajan, Vivek Krishna; Gogineni, Venkateshwara R.; White, Sarah B.; Yu, Bing

2017-02-01

Thermal ablation is the use of heat to induce cell death through coagulative necrosis. Ideally, complete ablation of tumor cells with no damage to surrounding critical structures such as blood vessels, nerves or even organs is desired. Ablation monitoring techniques are often employed to ensure optimal tumor ablation. In thermal tissue ablation, tissue damage is known to be dependent on the temperature and time of exposure. Aptly, current methods for monitoring ablation rely profoundly on local tissue temperature and duration of heating to predict the degree of tissue damage. However, such methods do not take into account the microstructural and physiological changes in tissues as a result of thermocoagulation. Light propagation within biological tissues is known to be dependent on the tissue microstructure and physiology. During tissue denaturation, changes in tissue structure alter light propagations in tissue which could be used to directly assess the extent of thermal tissue damage. We report the use of a spectroscopic system for monitoring the tissue optical properties during heating of ex vivo liver tissues. We observed that during tissue denaturation, continuous changes in wavelength-averaged μa(λ) and μ's(λ) followed a sigmoidal trend and are correlated with damage predicted by Arrhenius model.

Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

PubMed

Heinz, Stefan; Braspenning, Joris

2015-01-01

An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

Magnetic Resonance Mediated Radiofrequency Ablation.

PubMed

Hue, Yik-Kiong; Guimaraes, Alexander R; Cohen, Ouri; Nevo, Erez; Roth, Abraham; Ackerman, Jerome L

2018-02-01

To introduce magnetic resonance mediated radiofrequency ablation (MR-RFA), in which the MRI scanner uniquely serves both diagnostic and therapeutic roles. In MR-RFA scanner-induced RF heating is channeled to the ablation site via a Larmor frequency RF pickup device and needle system, and controlled via the pulse sequence. MR-RFA was evaluated with simulation of electric and magnetic fields to predict the increase in local specific-absorption-rate (SAR). Temperature-time profiles were measured for different configurations of the device in agar phantoms and ex vivo bovine liver in a 1.5 T scanner. Temperature rise in MR-RFA was imaged using the proton resonance frequency method validated with fiber-optic thermometry. MR-RFA was performed on the livers of two healthy live pigs. Simulations indicated a near tenfold increase in SAR at the RFA needle tip. Temperature-time profiles depended significantly on the physical parameters of the device although both configurations tested yielded temperature increases sufficient for ablation. Resected livers from live ablations exhibited clear thermal lesions. MR-RFA holds potential for integrating RF ablation tumor therapy with MRI scanning. MR-RFA may add value to MRI with the addition of a potentially disposable ablation device, while retaining MRI's ability to provide real time procedure guidance and measurement of tissue temperature, perfusion, and coagulation.

Microwave ablation of the liver: a description of lesion evolution over time and an investigation of the heat sink effect.

PubMed

Bhardwaj, N; Dormer, J; Ahmad, F; Strickland, A D; Gravante, G; West, K; Dennison, A R; Lloyd, D M

2011-12-01

Microwave ablation has been successfully used to treat unresectable liver tumours for many years. However, despite its widespread use, there seems to be a relative paucity of experimental data regarding lesion evolution and the effects of any surrounding vasculature on ablation morphology. The aim of this study was to investigate the principal pathological changes in the liver following microwave ablation, in particular the heat sink effect. In addition we carefully reviewed the available literature to provide an overview of all relevant pathological studies. Microwave ablation was carried out on male rats at various distances from the hilum. Histological (H&E) and immunocytochemical (caspase 3) analyses of the lesion were performed at various time points; 0, 4, 24, 48  hours, 2 weeks and 1 month. A literature review was carried out using Medline, Embase and the Cochrane database to identify all relevant histological studies. The lesion underwent complete coagulative necrosis and was extremely regular at the ablation edge with no evidence of any influence from surrounding blood vessels at all time points. H&E and caspase 3 results were consistent and microwave caused little collateral damage outside the intended ablation zone. This study suggests that microwave ablation is extremely concise and is minimally affected by the heat sink effect. Comparative investigations with other treatment modalities are required.

Past, present, and future of endobronchial laser photoresection

PubMed Central

Khemasuwan, Danai; Wang, Ko-Pen

2015-01-01

Laser photoresection of central airway obstruction is a useful tool for an Interventional Pulmonologist (IP). Endobronchial therapy of the malignant airway obstruction is considered as a palliative measure or a bridge therapy to the definite treatment of cancer. Several ablative therapies such as electrocautery, argon plasma coagulation (APC), cryotherapy and laser photoresection exist in the armamentarium of IP to tackle such presentations. Besides Neodymium-Yttrium, Aluminum, Garnet (Nd:YAG) laser, there are several different types of laser that have been used by the pulmonologist with different coagulative and cutting properties. This chapter focuses on the historical perspective, current status, and potentials of lasers in the management of central airway lesions. PMID:26807285

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

PubMed

Oki, Eiji; Tokunaga, Shoji; Emi, Yasunori; Kusumoto, Tetsuya; Yamamoto, Manabu; Fukuzawa, Kengo; Takahashi, Ikuo; Ishigami, Sumiya; Tsuji, Akihito; Higashi, Hidefumi; Nakamura, Toshihiko; Saeki, Hiroshi; Shirabe, Ken; Kakeji, Yoshihiro; Sakai, Kenji; Baba, Hideo; Nishimaki, Tadashi; Natsugoe, Shoji; Maehara, Yoshihiko

2016-07-01

The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Microwave thermal ablation: Effects of tissue properties variations on predictive models for treatment planning.

PubMed

Lopresto, Vanni; Pinto, Rosanna; Farina, Laura; Cavagnaro, Marta

2017-08-01

Microwave thermal ablation (MTA) therapy for cancer treatments relies on the absorption of electromagnetic energy at microwave frequencies to induce a very high and localized temperature increase, which causes an irreversible thermal damage in the target zone. Treatment planning in MTA is based on experimental observations of ablation zones in ex vivo tissue, while predicting the treatment outcomes could be greatly improved by reliable numerical models. In this work, a fully dynamical simulation model is exploited to look at effects of temperature-dependent variations in the dielectric and thermal properties of the targeted tissue on the prediction of the temperature increase and the extension of the thermally coagulated zone. In particular, the influence of measurement uncertainty of tissue parameters on the numerical results is investigated. Numerical data were compared with data from MTA experiments performed on ex vivo bovine liver tissue at 2.45GHz, with a power of 60W applied for 10min. By including in the simulation model an uncertainty budget (CI=95%) of ±25% in the properties of the tissue due to inaccuracy of measurements, numerical results were achieved in the range of experimental data. Obtained results also showed that the specific heat especially influences the extension of the thermally coagulated zone, with an increase of 27% in length and 7% in diameter when a variation of -25% is considered with respect to the value of the reference simulation model. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

MoXy fiber with active cooling cap for bovine prostate vaporization with high power 200W 532 nm laser

NASA Astrophysics Data System (ADS)

Peng, Steven Y.; Kang, Hyun Wook; Pirzadeh, Homa; Stinson, Douglas

2011-03-01

A novel MoXyTM fiber delivery device with Active Cooling Cap (ACCTM) is designed to transmit up to 180W of 532 nm laser light to treat benign prostatic hyperplasia (BPH). Under such high power tissue ablation, effective cooling is key to maintaining fiber power transmission and ensuring the reliability of the fiber delivery device To handle high power and reduce fiber degradation, the MoXy fiber features a larger core size (750 micrometer) and an internal fluid channel to ensure better cooling of the fiber tip to prevent the cap from burning, detaching, or shattering during the BPH treatment. The internal cooling channel was created with a metal cap and tubing that surrounds the optical fiber. In this study MoXy fibers were used to investigate the effect of power levels of 120 and 200 W on in-vitro bovine prostate ablation using a 532 nm XPSTM laser system. For procedures requiring more than 100 kJ, the MoXy fiber at 200W removed tissue at twice the rate of the current HPS fiber at 120W. The fiber maintained a constant tissue vaporization rate during the entire tissue ablation process. The coagulation at 200W was about 20% thicker than at 120W. In conclusion, the new fibers at 200W doubled the tissue removal rate, maintained vaporization efficiency throughout delivery of 400kJ energy, and induced similar coagulation to the existing HPS fiber at 120W.

Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

PubMed Central

Weinstein, M J; Chute, L E

1984-01-01

We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity. Images PMID:6421875

A trucut biopsy needle for bipolar radiofrequency ablation of needle tract: a proof-of-concept experiment.

PubMed

Bruners, Philipp; Penzkofer, Tobias; Isfort, Peter; Pfeffer, Jochen; Schmitz-Rode, Thomas; Günther, Rolf W; Mahnken, Andreas H

2010-08-01

To develop a trucut biopsy needle featuring two electrodes that allow for bipolar radiofrequency (RF) coagulation of the puncture tract. We modified a 14-G trucut biopsy needle to contain two insulated electrodes and connected the device to an RF generator. Biopsies in ex vivo porcine liver and kidney were performed. The puncture tract was coagulated by using different RF energy settings (5 W, 10 W, 20 W). Tissue specimens were dissected along the puncture tract and the coagulation area was macroscopically evaluated. CT-guided in vivo liver and kidney biopsies were performed in two domestic pigs. Lengths of specimens were measured. Post-biopsy contrast-enhanced CT examinations were performed to rule out biopsy-related bleeding. Animals were euthanised and coagulation areas macroscopically explored. The mean diameters of the coagulated area around the ex vivo biopsy tract were 4.2 +/- 1.1 mm (5 W), 6.0 +/- 2.0 mm (10 W) and 5.2 +/- 0.51 mm (20 W) in liver and 5.0 +/- 0.7 mm (5 W), 6.6 +/- 0.9 (10 W) and 6.0 +/- 2.0 mm (20 W) in kidney. After biopsies CT revealed no bleeding. Mean maximum coagulation diameters were 10.1 +/- 4.6 mm (10 W) in liver and 6.0 +/- 2.5 mm (10 W) in kidney. Mean length of the specimens was 12.2 +/- 4.4 mm in kidney and 11.1 +/- 3.6 mm in liver tissue. Bipolar RF biopsy is a promising tool for tract coagulation after percutaneous biopsy.

The relation between temperature distribution for lung RFA and electromagnetic wave frequency dependence of electrical conductivity with changing a lung's internal air volumes.

PubMed

Yamazaki, Nozomu; Watanabe, Hiroki; Lu, Xiaowei; Isobe, Yosuke; Kobayashi, Yo; Miyashita, Tomoyuki; Fujie, Masakatsu G

2013-01-01

Radio frequency ablation (RFA) for lung cancer has increasingly been used over the past few years because it is a minimally invasive treatment. As a feature of RFA for lung cancer, lung contains air during operation. Air is low thermal and electrical conductivity. Therefore, RFA for this cancer has the advantage that only the cancer is coagulated, and it is difficult for operators to control the precise formation of coagulation lesion. In order to overcome this limitation, we previously proposed a model-based robotic ablation system using finite element method. Creating an accurate thermo physical model and constructing thermal control method were a challenging problem because the thermal properties of the organ are complex. In this study, we measured electromagnetic wave frequency dependence of lung's electrical conductivity that was based on lung's internal air volumes dependence with in vitro experiment. In addition, we validated the electromagnetic wave frequency dependence of lung's electrical conductivity using temperature distribution simulator. From the results of this study, it is confirmed that the electromagnetic wave frequency dependence of lung's electrical conductivity effects on heat generation of RFA.

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo.

PubMed

von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T; Wagner, Denisa D; Mackman, Nigel; Engelmann, Bernd; Massberg, Steffen

2012-04-09

Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features.

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

PubMed Central

von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A.; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T.; Wagner, Denisa D.; Mackman, Nigel; Engelmann, Bernd

2012-01-01

Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features. PMID:22451716

Effects of argon plasma coagulation on human stomach tissue: An ex vivo study.

PubMed

Gong, Eun Jeong; Ahn, Ji Yong; Jung, Hwoon-Yong; Park, Young Soo; Na, Hee Kyong; Jung, Kee Wook; Kim, Do Hoon; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho

2017-05-01

Argon plasma coagulation (APC) is a safe alternative treatment for gastrointestinal neoplasms and precancerous lesions. However, the extent of thermal damage after APC is difficult to predict. We investigated the effects of APC on human stomach tissue. Argon plasma coagulation was performed on 10 freshly resected human stomachs that were obtained after total gastrectomy. The effects on tissue were compared across power settings (40, 60, and 80 W), durations (5, 10, 15, 20, and 25 s), and between injection (submucosal injection of normal saline) and control (without injection) groups. Success was defined as complete mucosal necrosis without damaging the muscularis propria. Without submucosal injection, the incidence of damaging the muscularis propria increased as the power and duration increased. Tissue damage in the injection group was mostly confined to the submucosa, even when using the high-power setting. In the injection group, ablations at 40 W for 20 s, 60 W for 15 s, and 80 W for 15 or 20 s produced success rates ≥80%. In the control group, ablations at 60 W for 10 s, and 80 W for 5, or 10 s produced success rates ≥80%. The optimal energy levels to achieve complete mucosal and submucosal necrosis without damaging the muscularis propria were 800-1600 and 600-800 J in the injection and control groups, respectively. Application of APC produces good results with a low risk of perforation. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

The effect of pre-operative topical anaesthetic cream on the ablative width and coagulative depth of ablative fractional resurfacing laser.

PubMed

Punyaratabandhu, Preawphan; Wanitphakdeedecha, Rungsima; Pattanaprichakul, Penvadee; Sitthinamsuwan, Panitta; Phothong, Weeranut; Eimpunth, Sasima; Lohsiriwat, Visnu; Manuskiatti, Woraphong

2017-02-01

Topical anaesthetic cream (TAC) is commonly used as a pre-treatment of ablative fractional resurfacing (AFR) laser. Most of anaesthetic cream contains distilled water as major component. Therefore, pre-operative TAC may interfere the photothermal reaction in the skin treated with fractional carbon-dioxide (FCO 2 ) laser and fractional erbium-doped yttrium aluminium garnet (FEr:YAG) laser. The objective of the study was to compare the ablative width (AW) and coagulative depth (CD) of AFR laser with and without pre-treatment with TAC. Four Thai females who underwent abdominoplasty were included in the study. The excised skin of each subject was divided into four areas. TAC (eutectic mixture of local anaesthesia; EMLA) with 1-h occlusion was applied only on the first and second areas. The first and third areas were treated with FCO 2 at 15 mj and 5% density. The second and fourth areas were treated with FEr:YAG at 28 J/cm 2 and 5% density. Six biopsied specimens were obtained from each area. A total of 96 specimens (24 specimens from each area) were collected from four patients and examined randomly by two dermatopathologists. The ablative width and coagulative depth from each specimen were determined. In FCO 2 -treated specimens, the mean AW of the specimens that were pre-treated with TAC and control was 174.86 ± 24.57 and 188.52 ± 41.32 μm. The mean CD of the specimens that were pre-treated with TAC and control was 594.96 ± 111.72 and 520.03 ± 147.40 μm. There were no significant differences in AW and CD between both groups (p = 0.53 and p = 0.15). In FEr:YAG-treated specimens, the mean AW of the specimens that were pre-treated with TAC and control was 381.11 ± 48.02 and 423.65 ± 60.16 μm. The mean CD of the specimens that were pre-treated with TAC and control was 86.03 ± 29.44 and 71.59 ± 18.99 μm. There were no significant differences in AW and CD between both groups (p = 0.16 and p = 0.24). The pre-treatment with TAC provided no statistically difference from the control group on AW and CD of both FCO 2 and FEr:YAG laser irradiation. However, there was a tendency to have narrower AW and deeper CD of the areas that were pre-treated with TAC when comparing to that of the control.

Ho:YAG laser arthroscopy of the knee

NASA Astrophysics Data System (ADS)

Sisto, Domenick J.; Blazina, Martin E.; Hirsh, Linda C.

1994-09-01

The HO:YAG laser is a near-contact laser with a capacity to ablate or cut tissues. The ablation function allows the surgeon to remove meniscal tissue, lyse and resect adhesions, melt loose bodies, and dissolve inflamed synovium. The cutting function of the laser is utilized to perform a lateral release or resect torn menisci. The laser can also be utilized to drill holes in Grade IV chondromalacic lesions to initiate a healing response. The laser has been embraced by orthopaedic surgeons because of its shape and versatility. The tip is only 2 mm wide and can be delivered into the tight posterior compartments of the knee with no damaging contact with the articular surfaces. The laser coagulates as it works and bleeding is minimized. The laser can function both as a cutting and ablating tool. The laser can also drill holes into subchondral bone to, hopefully, initiate a healing response.

Coagulation Factor Tests

MedlinePlus

... your coagulation factors. Coagulation factors are known by Roman numerals (I, II VIII, etc.) or by name ( ... need this test if you have a family history of bleeding disorders. Most bleeding disorders are inherited . ...

Mucosal ablation in Barrett's esophagus.

PubMed

Walker, S J; Selvasekar, C R; Birbeck, N

2002-01-01

Barrett's esophagus is a prevalent, premalignant condition affecting the gastroesophageal junction and distal esophagus. Ablation plus antireflux therapy has recently been advocated to prevent the development of adenocarcinoma or to treat those unfit or unwilling to undergo esophagectomy. The present article, based on a search of Medline/ISI databases and cross-referencing of relevant articles, reviews the literature on this subject. A number of techniques have been used to remove the affected mucosa, including laser, electrocoagulation, argon plasma coagulation and photodynamic therapy but, as yet, none has been shown to be superior. Depending on the method used, ablation results in complete removal of Barrett's esophagus in approximately one third of patients and a partial response in nearly two-thirds. The resultant squamous mucosa is apparently 'normal' but may regress. To promote and maintain regeneration, antireflux therapy must be sufficient to reduce repetitive injury to the esophageal mucosa. Whether ablation reduces the cancer risk or delays its occurrence is unknown, though recent data suggests benefit. Complications are infrequent and usually mild. Regular follow-up endoscopy and deep biopsies continue to be necessary. Careful data from much larger populations with long-term follow-up is required before ablation reaches the stage of broad clinical application.

Sphere-enhanced microwave ablation (sMWA) versus bland microwave ablation (bMWA): technical parameters, specific CT 3D rendering and histopathology.

PubMed

Gockner, T L; Zelzer, S; Mokry, T; Gnutzmann, D; Bellemann, N; Mogler, C; Beierfuß, A; Köllensperger, E; Germann, G; Radeleff, B A; Stampfl, U; Kauczor, H U; Pereira, P L; Sommer, C M

2015-04-01

This study was designed to compare technical parameters during ablation as well as CT 3D rendering and histopathology of the ablation zone between sphere-enhanced microwave ablation (sMWA) and bland microwave ablation (bMWA). In six sheep-livers, 18 microwave ablations were performed with identical system presets (power output: 80 W, ablation time: 120 s). In three sheep, transarterial embolisation (TAE) was performed immediately before microwave ablation using spheres (diameter: 40 ± 10 μm) (sMWA). In the other three sheep, microwave ablation was performed without spheres embolisation (bMWA). Contrast-enhanced CT, sacrifice, and liver harvest followed immediately after microwave ablation. Study goals included technical parameters during ablation (resulting power output, ablation time), geometry of the ablation zone applying specific CT 3D rendering with a software prototype (short axis of the ablation zone, volume of the largest aligned ablation sphere within the ablation zone), and histopathology (hematoxylin-eosin, Masson Goldner and TUNEL). Resulting power output/ablation times were 78.7 ± 1.0 W/120 ± 0.0 s for bMWA and 78.4 ± 1.0 W/120 ± 0.0 s for sMWA (n.s., respectively). Short axis/volume were 23.7 ± 3.7 mm/7.0 ± 2.4 cm(3) for bMWA and 29.1 ± 3.4 mm/11.5 ± 3.9 cm(3) for sMWA (P < 0.01, respectively). Histopathology confirmed the signs of coagulation necrosis as well as early and irreversible cell death for bMWA and sMWA. For sMWA, spheres were detected within, at the rim, and outside of the ablation zone without conspicuous features. Specific CT 3D rendering identifies a larger ablation zone for sMWA compared with bMWA. The histopathological signs and the detectable amount of cell death are comparable for both groups. When comparing sMWA with bMWA, TAE has no effect on the technical parameters during ablation.

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

PubMed Central

Kang, Yoo Goo; Martin, Douglas J.; Marquez, Jose; Lewis, Jessica H.; Bontempo, Franklin A.; Shaw, Byers W.; Starzl, Thomas E.; Winter, Peter M.

2010-01-01

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30–60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors. PMID:3896028

Renal Artery Embolization Combined With Radiofrequency Ablation in a Porcine Kidney Model: Effect of Small and Narrowly Calibrated Microparticles as Embolization Material on Coagulation Diameter, Volume, and Shape

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

Sommer, C. M., E-mail: christof.sommer@med.uni-heidelberg.de; Kortes, N.; Zelzer, S.

2011-02-15

The purpose of this study was to evaluate the effect of renal artery embolization with small and narrowly calibrated microparticles on the coagulation diameter, volume, and shape of radiofrequency ablations (RFAs) in porcine kidneys. Forty-eight RFAs were performed in 24 kidneys of 12 pigs. In 6 animals, bilateral renal artery embolization was performed with small and narrowly calibrated microparticles. Upper and lower kidney poles were ablated with identical system parameters. Applying three-dimensional segmentation software, RFAs were segmented on registered 2 mm-thin macroscopic slices. Length, depth, width, volume{sub s}egmented, and volume{sub c}alculated were determined to describe the size of the RFAs.more » To evaluate the shape of the RFAs, depth-to-width ratio (perfect symmetry-to-lesion length was indicated by a ratio of 1), sphericity ratio (perfect sphere was indicated by a sphericity ratio of 1), eccentricity (perfect sphere was indicated by an eccentricity of 0), and circularity (perfect circle was indicated by a circularity of 1) were determined. Embolized compared with nonembolized RFAs showed significantly greater depth (23.4 {+-} 3.6 vs. 17.2 {+-} 1.8 mm; p < 0.001) and width (20.1 {+-} 2.9 vs. 12.6 {+-} 3.7 mm; p < 0.001); significantly larger volume{sub s}egmented (8.6 {+-} 3.2 vs. 3.0 {+-} 0.7 ml; p < 0.001) and volume{sub c}alculated (8.4 {+-} 3.0 ml vs. 3.3 {+-} 1.1 ml; p < 0.001); significantly lower depth-to-width (1.17 {+-} 0.10 vs. 1.48 {+-} 0.44; p < 0.05), sphericity (1.55 {+-} 0.44 vs. 1.96 {+-} 0.43; p < 0.01), and eccentricity (0.84 {+-} 0.61 vs. 1.73 {+-} 0.91; p < 0.01) ratios; and significantly greater circularity (0.62 {+-} 0.14 vs. 0.45 {+-} 0.16; p < 0.01). Renal artery embolization with small and narrowly calibrated microparticles affected the coagulation diameter, volume, and shape of RFAs in porcine kidneys. Embolized RFAs were significantly larger and more spherical compared with nonembolized RFAs.« less

Laser-induced thermotherapy: an in-situ ablation technique for the local treatment of irresectable colorectal liver metastases

NASA Astrophysics Data System (ADS)

Ritz, Joerg-Peter; Isbert, Christoph M.; Roggan, Andre; Wacker, Frank; Buhr, Heinz-Johannes; Germer, Christoph-Thomas

2000-11-01

Laser-induced thermotherapy (LITT) is a so called in-situ- ablation technique which is used for the treatment of liver tumors. Coagulation necrosis is induced by transmitting the laser irradiation via quartz fibers directly into the tumor tissue. LITT represents similarly to surgical liver resection a local treatment form for liver metastases. The Nd-YAG laser (1064 nm) was used. The application system was placed percutaneously under open MRI control. On-line monitoring was done with MRI for evaluation of the postoperative follow-up we performed MRI-controls every 3 months. A total of 20 patients were treated. Due to the irradiation plan performed preoperatively, the treated tumors could be completely ablated by hyperthermia in all procedures. Complications were pleural effusion in 7 patients and a bile fistula and subcapsulary liver hematoma in one patient each. Local control of tumor growth can be achieved in tumors having undergone complete hyperthermic ablation. An assessment of the method regarding a prognostic benefit is not yet possible due to the short follow-up period and the small patient population.

A coaxial slot antenna with frequency of 433 MHz for microwave ablation therapies: design, simulation, and experimental research.

PubMed

Jiang, Yingxu; Zhao, Jinzhe; Li, Weitao; Yang, Yamin; Liu, Jia; Qian, Zhiyu

2017-11-01

Investigation of the structures and properties of antennas is important in the design of microwave ablation (MWA) system. In this study, we studied the performance of the novel tri- and single-slot antennas with frequency of 433 MHz in ex vivo conditions. The dielectric properties of liver tissue under different thermal coagulation levels were explored, which was beneficial to evaluate ablation condition of tissue and simulate temperature field. Then, the performances of the antennas were analyzed by using numerical method based on finite element method (FEM). It indicated that the present antennas with frequency of 433 MHz could produce a gourd-shaped MWA area with a longer length. Compared to antenna with frequency of 2450 MHz, the designed single-slot antenna could obtain the larger MWA area. In addition, the multiple-point ablations and a larger MWA area could be achieved simultaneously by using the present tri-slot antenna. This study has a potential for the innovative design of MWA antenna for treatment of liver tumor with a large range and a long length.

[Gastric vascular lesions in cirrhosis: gastropathy and antral vascular ectasia].

PubMed

Casas, Meritxell; Calvet, Xavier; Vergara, Mercedes; Bella, Maria Rosa; Junquera, Félix; Martinez-Bauer, Eva; Campo, Rafael

2015-02-01

Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro

DTIC Science & Technology

2011-11-01

thrombasthenia.12 In trauma, when a blood vessel is injured, tissue factor on subendothelial pericytes is exposed and binds to endogenous FVII ...a more complex effect on coagulation than simply dilution of any single coagulation factor like FVII or fibrinogen (Fig. 1). It is interesting to note...ORIGINAL ARTICLE Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro Daniel N. Darlington, PhD, Angel

[Coagulation factor VII levels in uremic patients and theirs influence factors].

PubMed

Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

2004-12-01

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

High intensity focused ultrasound ablation of goat liver in vivo: Pathologic changes of portal vein and the "heat-sink" effect.

PubMed

Jiang, F; He, M; Liu, Y J; Wang, Z B; Zhang, L; Bai, J

2013-01-01

The purpose of this study was to evaluate pathological changes of the portal vein (PV) and the effects on main branches of the hepatic PV during HIFU (high-intensity focused ultrasound) sonication when liver tissue adjacent to the main branches of hepatic PV was ablated. Normal liver tissue at 0mm, 5mm, 10mm away from the hepatic portal vein in 50 healthy goats was ablated with magnetic resonance image-guided HIFU (MRgHIFU). MRI showed a non-perfusion region at the target area but did not show any significant changes of the PV immediately after HIFU. The histological examination 1 day after HIFU showed coagulative necrosis at the target area, revealed deep-dyed swelling collagen (CS) fibers and vessel wall fracture (VWF) in the PV adjacent to the target area; however, no CS or VWF was observed in the PV 1 week after HIFU ablation. The energy required to ablate the foci at 0mm was 21% more than that at 10mm from the PV (p<0.05); the energy needed to ablate foci 5mm away from the PV was 10% more than that at 10mm from the PV (p<0.05). We concluded that minor injury of the hepatic portal vein may occur when ablating the adjacent liver tissue, and the acoustic energy deposition is related to the distance to the portal vein. Copyright © 2012 Elsevier B.V. All rights reserved.

Biological and analytical variations of 16 parameters related to coagulation screening tests and the activity of coagulation factors.

PubMed

Chen, Qian; Shou, Weiling; Wu, Wei; Guo, Ye; Zhang, Yujuan; Huang, Chunmei; Cui, Wei

2015-04-01

To accurately estimate longitudinal changes in individuals, it is important to take into consideration the biological variability of the measurement. The few studies available on the biological variations of coagulation parameters are mostly outdated. We confirmed the published results using modern, fully automated methods. Furthermore, we added data for additional coagulation parameters. At 8:00 am, 12:00 pm, and 4:00 pm on days 1, 3, and 5, venous blood was collected from 31 healthy volunteers. A total of 16 parameters related to coagulation screening tests as well as the activity of coagulation factors were analyzed; these included prothrombin time, fibrinogen (Fbg), activated partial thromboplastin time, thrombin time, international normalized ratio, prothrombin time activity, activated partial thromboplastin time ratio, fibrin(-ogen) degradation products, as well as the activity of factor II, factor V, factor VII, factor VIII, factor IX, and factor X. All intraindividual coefficients of variation (CVI) values for the parameters of the screening tests (except Fbg) were less than 5%. Conversely, the CVI values for the activity of coagulation factors were all greater than 5%. In addition, we calculated the reference change value to determine whether a significant difference exists between two test results from the same individual. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Catheter-based high-intensity ultrasound for epicardial ablation of the left ventricle: device design and in vivo feasiblity

NASA Astrophysics Data System (ADS)

Salgaonkar, Vasant A.; Nazer, Babak; Jones, Peter D.; Tanaka, Yasuaki; Martin, Alastair; Ng, Bennett; Duggirala, Srikant; Diederich, Chris J.; Gerstenfeld, Edward P.

2015-03-01

The development and in vivo testing of a high-intensity ultrasound thermal ablation catheter for epicardial ablation of the left ventricle (LV) is presented. Scar tissue can occur in the mid-myocardial and epicardial space in patients with nonischemic cardiomyopathy and lead to ventricular tachycardia. Current ablation technology uses radiofrequency energy, which is limited epicardially by the presence of coronary vessels, phrenic nerves, and fat. Ultrasound energy can be precisely directed to deliver targeted deep epicardial ablation while sparing intervening epicardial nerve and vessels. The proof-of-concept ultrasound applicators were designed for sub-xyphoid access to the pericardial space through a steerable 14-Fr sheath. The catheter consists of two rectangular planar transducers, for therapy (6.4 MHz) and imaging (5 MHz), mounted at the tip of a 3.5-mm flexible nylon catheter coupled and encapsulated within a custom-shaped balloon for cooling. Thermal lesions were created in the LV in a swine (n = 10) model in vivo. The ultrasound applicator was positioned fluoroscopically. Its orientation and contact with the LV were verified using A-mode imaging and a radio-opaque marker. Ablations employed 60-s exposures at 15 - 30 W (electrical power). Histology indicated thermal coagulation and ablative lesions penetrating 8 - 12 mm into the left ventricle on lateral and anterior walls and along the left anterior descending artery. The transducer design enabled successful sparing from the epicardial surface to 2 - 4 mm of intervening ventricle tissue and epicardial fat. The feasibility of targeted epicardial ablation with catheter-based ultrasound was demonstrated.

The holmium laser in urology.

PubMed

Wollin, T A; Denstedt, J D

1998-02-01

To review the physics related to the holmium laser, its laser-tissue interactions, and its application to the treatment of urological diseases. The holmium: YAG laser is a solid-state, pulsed laser that emits light at 2100 nm. It combines the qualities of the carbon dioxide and neodymium:YAG lasers providing both tissue cutting and coagulation in a single device. Since the holmium wavelength can be transmitted down optical fibers, it is especially suited for endoscopic surgery. The authors provide a review of the literature as it relates to the holmium laser and its application to urology. The holmium wavelength is strongly absorbed by water. Tissue ablation occurs superficially, providing for precise incision with a thermal injury zone ranging from 0.5 to 1.0 mm. This level of coagulation is sufficient for adequate hemostasis. The most common urologic applications of the holmium laser that have been reported include incision of urethral and ureteral strictures; ablation of superficial transitional cell carcinoma; bladder neck incision and prostate resection; and lithotripsy of urinary calculi. The holmium: YAG laser is a multi-purpose, multi-specialty surgical laser. It has been shown to be safe and effective for multiple soft tissue applications and stone fragmentation. Its utilization in urology is anticipated to increase with time as a result of these features.

Thermal ablation of pancreatic cyst with a prototype endoscopic ultrasound capable radiofrequency needle device: A pilot feasibility study

PubMed Central

Moris, Maria; Atar, Mustafa; Kadayifci, Abdurrahman; Krishna, Murli; Librero, Ariston; Richie, Eugene; Brugge, William; Wallace, Michael B.

2017-01-01

Background and Objectives: Pancreatic cysts are evaluated by endoscopic ultrasound and fine needle aspiration (EUS). The only accepted treatment is pancreatectomy, which is associated with morbidity and mortality. This study evaluated the optimal thermal dosimetry of a novel radiofrequency ablation device using a standard electrosurgical unit in ex vivo cyst models. Methods: A modified EUS 22-gauge monopolar needle prototype with a tip electrode connected to a standard electrosurgical unit (Erbe USA, Marietta, GA, USA) was used to induce a subboiling point temperature. A cyst model was created using 2-cm sections of porcine small intestine ligated and filled with saline. After ablation, the cyst models were prepared for pathological evaluation. The epithelial layers were measured in at least two different sites with a micrometer and compared with the corresponding control sample. Results: Thirty-two cyst models were ablated with maximum temperatures of 50°C, 60°C, 90°C, and 97°C in 8, 11, 11, and 2 cysts, respectively. Longer ablation times were required to induce higher temperatures. A trend in the reduction in thickness of the measured layers was observed after exposure to higher temperatures. A temperature over 50°C was required for the ablation of the muscularis, submucosa, and villi, and over 60°C was required to ablate the mucosal crypts. Conclusions: In a preclinical model, a novel radiofrequency EUS-capable needle connected to a standard electrosurgical unit using standard low-voltage coagulation provided ablation in a temperature-dependent fashion with a threshold of at least 60°C and a safe cyst margin below 97°C. This potentially will allow low-cost, convenient cyst ablation. PMID:28440238

Sphere-Enhanced Microwave Ablation (sMWA) Versus Bland Microwave Ablation (bMWA): Technical Parameters, Specific CT 3D Rendering and Histopathology

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

Gockner, T. L., E-mail: theresa.gockner@med.uni-heidelberg.de; Zelzer, S., E-mail: s.zelzer@dkfz-heidelberg.de; Mokry, T., E-mail: theresa.mokry@med.uni-heidelberg.de

PurposeThis study was designed to compare technical parameters during ablation as well as CT 3D rendering and histopathology of the ablation zone between sphere-enhanced microwave ablation (sMWA) and bland microwave ablation (bMWA).MethodsIn six sheep-livers, 18 microwave ablations were performed with identical system presets (power output: 80 W, ablation time: 120 s). In three sheep, transarterial embolisation (TAE) was performed immediately before microwave ablation using spheres (diameter: 40 ± 10 μm) (sMWA). In the other three sheep, microwave ablation was performed without spheres embolisation (bMWA). Contrast-enhanced CT, sacrifice, and liver harvest followed immediately after microwave ablation. Study goals included technical parameters during ablation (resulting power output,more » ablation time), geometry of the ablation zone applying specific CT 3D rendering with a software prototype (short axis of the ablation zone, volume of the largest aligned ablation sphere within the ablation zone), and histopathology (hematoxylin-eosin, Masson Goldner and TUNEL).ResultsResulting power output/ablation times were 78.7 ± 1.0 W/120 ± 0.0 s for bMWA and 78.4 ± 1.0 W/120 ± 0.0 s for sMWA (n.s., respectively). Short axis/volume were 23.7 ± 3.7 mm/7.0 ± 2.4 cm{sup 3} for bMWA and 29.1 ± 3.4 mm/11.5 ± 3.9 cm{sup 3} for sMWA (P < 0.01, respectively). Histopathology confirmed the signs of coagulation necrosis as well as early and irreversible cell death for bMWA and sMWA. For sMWA, spheres were detected within, at the rim, and outside of the ablation zone without conspicuous features.ConclusionsSpecific CT 3D rendering identifies a larger ablation zone for sMWA compared with bMWA. The histopathological signs and the detectable amount of cell death are comparable for both groups. When comparing sMWA with bMWA, TAE has no effect on the technical parameters during ablation.« less

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

Competition of coagulation sink and source rate: New particle formation in the Pearl River Delta of China

NASA Astrophysics Data System (ADS)

Gong, Youguo; Hu, Min; Cheng, Yafang; Su, Hang; Yue, Dingli; Liu, Feng; Wiedensohler, A.; Wang, Zhibin; Kalesse, H.; Liu, Shang; Wu, Zhijun; Xiao, Kaitao; Mi, Puchun; Zhang, Yuanhang

The coagulation sink and its role in new particle formation are investigated based on data obtained during the PRIDE-PRD2004 campaign at Xinken of Pearl River Delta, China. Analysis of size distributions and mode contributions of the coagulation sink show that the observed higher load of accumulation mode particles impose a significant effect on the coagulation sink and result in higher coagulation sinks at Xinken despite of the lower total particle number compared with other areas. Hence it is concluded that the higher coagulation sink may depress the occurrence frequency of new particle formation events. The strategies targeting at controlling accumulation mode particles may have influences on the frequency of new particle formation events at this area. The factors affecting the coagulation sink are evaluated. The relatively lower ambient relative humidities may weaken the coagulation sink and facilitate the occurrence of new particle formation events during noontime, while the surmise of nucleation and growth involving organic matter may imply an actually higher coagulation sink than expected. These factors have a significant influence on the ultimate fate of the newly formed nuclei and new particle formation. A comparison of event and non-event days indicates that the coagulation sink is not the only decisive factor affecting new particle formation, other factors including the precursor vapors and photochemical activity are none the less important either. Competition of coagulation sink and high source rate leads to the occurrence of new particle formation events at Xinken.

The peculiar ultrasonographic and elastographic features of thyroid nodules after treatment with laser or radiofrequency: similarities and differences.

PubMed

Andrioli, Massimiliano; Valcavi, Roberto

2014-12-01

The aim of percutaneous thermal ablation with laser (LA) or radiofrequency (RFA) is to reduce the volume of benign thyroid nodules. Little is known about ultrasonographic and elastographic appearances of thyroid lesions after treatment. For the first time, we report in detail the main ultrasonographic and elastographic characteristics of thermally ablated nodules and their underlying similarities and differences. Both thermal treatments usually produce a marked hypoechoic area of coagulative necrosis. LA-treated lesions usually become highly heterogeneous due to the presence of cavitations and charring; they then evolve into hyperechoic scars. In RFA-treated nodules, instead, the necrotic area is more homogeneous but presents more irregular margins compared to those observed in LA-treated lesions. Regardless of the thermal method used, vascularity is typically reduced in all treated nodules and stiffness, evaluated with qualitative elastography, increases. In conclusion, ultrasonographic and elastographic appearances of the thermally ablated thyroid lesions differ slightly according to the adopted procedure. Furthermore, they are peculiar, changeable over time, and potentially misleading.

A two-scale model of radio-frequency electrosurgical tissue ablation

NASA Astrophysics Data System (ADS)

Karaki, Wafaa; Rahul; Lopez, Carlos A.; Borca-Tasciuc, Diana-Andra; De, Suvranu

2017-12-01

Radio-frequency electrosurgical procedures are widely used to simultaneously dissect and coagulate tissue. Experiments suggest that evaporation of cellular and intra-cellular water plays a significant role in the evolution of the temperature field at the tissue level, which is not adequately captured in a single scale energy balance equation. Here, we propose a two-scale model to study the effects of microscale phase change and heat dissipation in response to radiofrequency heating on the tissue level in electrosurgical ablation procedures. At the microscale, the conservation of mass along with thermodynamic and mechanical equilibrium is applied to obtain an equation-of-state relating vapor mass fraction to temperature and pressure. The evaporation losses are incorporated in the macro-level energy conservation and results are validated with mean experimental temperature distributions measured from electrosurgical ablation testing on ex vivo porcine liver at different power settings of the electrosurgical instrument. Model prediction of water loss and its effect on the temperature along with the effect of the mechanical properties on results are evaluated and discussed.

Evaluation of high intensity focused ultrasound ablation of prostate tumor with hyperpolarized 13C imaging biomarkers

NASA Astrophysics Data System (ADS)

Lee, Jessie E.; Diederich, Chris J.; Salgaonkar, Vasant A.; Bok, Robert; Taylor, Andrew G.; Kurhanewicz, John

2015-03-01

Real-time hyperpolarized (HP) 13C MR can be utilized during high-intensity focal ultrasound (HIFU) therapy to improve treatment delivery strategies, provide treatment verification, and thus reduce the need for more radical therapies for lowand intermediate-risk prostate cancers. The goal is to develop imaging biomarkers specific to thermal therapies of prostate cancer using HIFU, and to predict the success of thermal coagulation and identify tissues potentially sensitized to adjuvant treatment by sub-ablative hyperthermic heat doses. Mice with solid prostate tumors received HIFU treatment (5.6 MHz, 160W/cm2, 60 s), and the MR imaging follow-ups were performed on a wide-bore 14T microimaging system. 13C-labeled pyruvate and urea were used to monitor tumor metabolism and perfusion accordingly. After treatment, the ablated tumor tissue had a loss in metabolism and perfusion. In the regions receiving sub-ablative heat dose, a timedependent change in metabolism and perfusion was observed. The untreated regions behaved as a normal untreated TRAMP prostate tumor would. This promising preliminary study shows the potential of using 13C MR imaging as biomarkers of HIFU/thermal therapies.

Combination of microneedle radiofrequency (RF), fractional RF skin resurfacing and multi-source non-ablative skin tightening for minimal-downtime, full-face skin rejuvenation.

PubMed

Kaplan, Haim; Kaplan, Lilach

2016-12-01

In the recent years, there is a growth in demand for radiofrequency (RF)-based procedures to improve skin texture, laxity and contour. The new generation of systems allow non-invasive and fractional resurfacing treatments on one platform. The aim of this study was to evaluate the safety and efficacy of a new treatment protocol using a multisource RF, combining 3 different modalities in each patient: [1] non-ablative RF skin tightening, [2] fractional skin resurfacing, and [3] microneedling RF for non-ablative coagulation and collagen remodelling. 14 subjects were enrolled in this study using EndyMed PRO ™ platform. Each patient had 8 non-ablative treatments and 4 fractional treatments (fractional skin resurfacing and Intensif). The global aesthetic score was used to evaluate improvement. All patients had improvement in skin appearance. About 43% had excellent or very good improvement above 50%, 18% had good improvement between 25 and 50%, and the rest 39% had a mild improvement of < 25%. Downtime was minimal and no adverse effect was reported. Our data show significant improvement of skin texture, skin laxity and wrinkle reduction achieved using RF treatment platform.

Protein corona changes mediated by surface modification of amorphous silica nanoparticles suppress acute toxicity and activation of intrinsic coagulation cascade in mice

NASA Astrophysics Data System (ADS)

Yoshida, Tokuyuki; Yoshioka, Yasuo; Morishita, Yuki; Aoyama, Michihiko; Tochigi, Saeko; Hirai, Toshiro; Tanaka, Kota; Nagano, Kazuya; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Higashisaka, Kazuma; Tsutsumi, Yasuo

2015-06-01

Recently, nanomaterial-mediated biological effects have been shown to be governed by the interaction of nanomaterials with some kinds of proteins in biological fluids, and the physical characteristics of the nanomaterials determine the extent and type of their interactions with proteins. Here, we examined the relationships between the surface properties of amorphous silica nanoparticles with diameters of 70 nm (nSP70), their interactions with some proteins in biological fluids, and their toxicity in mice after intravenous administration. The surface modification of nSP70 with amino groups (nSP70-N) prevented acute lethality and abnormal activation of the coagulation cascade found in the nSP70-treated group of mice. Since our previous study showed that coagulation factor XII played a role in the nSP70-mediated abnormal activation of the coagulation cascade, we examined the interaction of nSP70 and nSP70-N with coagulation factor XII. Coagulation factor XII bonded to the surface of nSP70 to a greater extent than that observed for nSP70-N, and consequently more activation of coagulation factor XII was observed for nSP70 than for nSP70-N. Collectively, our results suggest that controlling the interaction of nSP70 with blood coagulation factor XII by modifying the surface properties would help to inhibit the nSP70-mediated abnormal activation of the blood coagulation cascade.

Radiofrequency ablation during continuous saline infusion can extend ablation margins

PubMed Central

Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

2013-01-01

AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area. METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment. RESULTS: No liquid infusion was 17.3 ± 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 ± 3.3 mL) than with 5% glucose (21.4 ± 2.2 mL), 50% glucose (16.5 ± 0.9 mL) or no liquid infusion (17.3 ± 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose. CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence. PMID:23483097

Destructive effect of HIFU on rabbit embedded endometrial carcinoma tissues and their vascularities

PubMed Central

Guan, Liming; Xu, Gang

2017-01-01

Objectives To evaluate damage effect of High-intensity focused ultrasound on early stage endometrial cancer tissues and their vascularities. Materials and Methods Rabbit endometrial cancer models were established via tumor blocks implantation for a prospective control study. Ultrasonic ablation efficacy was evaluated by pathologic and imaging changes. The target lesions of experimental rabbits before and after ultrasonic ablation were observed after autopsy. The slides were used for hematoxylin-eosin staining, elastic fiber staining and endothelial cell staining; the slides were observed by optical microscopy. One slide was observed by electron microscopy. Then the target lesions of experimental animals with ultrasonic ablation were observed by vascular imaging, one group was visualized by digital subtract angiography, one group was quantified by color Doppler flow imaging, and one group was detected by dye perfusion. SPSS 19.0 software was used for statistical analyses. Results Histological examination indicated that High-intensity focused ultrasound caused the tumor tissues and their vascularities coagulative necrosis. Tumor vascular structure components including elastic fiber, endothelial cells all were destroyed by ultrasonic ablation. Digital subtract angiography showed tumor vascular shadow were dismissed after ultrasonic ablation. After ultrasonic ablation, gray-scale of tumor nodules enhanced in ultrasonography, tumor peripheral and internal blood flow signals disappeared or significantly reduced in color Doppler flow imaging. Vascular perfusion performed after ultrasonic ablation, tumor vessels could not filled by dye liquid. Conclusion High-intensity focused ultrasound as a noninvasive method can destroy whole endometrial cancer cells and their supplying vascularities, which maybe an alternative approach of targeted therapy and new antiangiogenic strategy for endometrial cancer. PMID:28121624

Destructive effect of HIFU on rabbit embedded endometrial carcinoma tissues and their vascularities.

PubMed

Guan, Liming; Xu, Gang

2017-03-21

To evaluate damage effect of High-intensity focused ultrasound on early stage endometrial cancer tissues and their vascularities. Rabbit endometrial cancer models were established via tumor blocks implantation for a prospective control study. Ultrasonic ablation efficacy was evaluated by pathologic and imaging changes. The target lesions of experimental rabbits before and after ultrasonic ablation were observed after autopsy. The slides were used for hematoxylin-eosin staining, elastic fiber staining and endothelial cell staining; the slides were observed by optical microscopy. One slide was observed by electron microscopy. Then the target lesions of experimental animals with ultrasonic ablation were observed by vascular imaging, one group was visualized by digital subtract angiography, one group was quantified by color Doppler flow imaging, and one group was detected by dye perfusion.SPSS 19.0 software was used for statistical analyses. Histological examination indicated that High-intensity focused ultrasound caused the tumor tissues and their vascularities coagulative necrosis. Tumor vascular structure components including elastic fiber, endothelial cells all were destroyed by ultrasonic ablation. Digital subtract angiography showed tumor vascular shadow were dismissed after ultrasonic ablation. After ultrasonic ablation, gray-scale of tumor nodules enhanced in ultrasonography, tumor peripheral and internal blood flow signals disappeared or significantly reduced in color Doppler flow imaging. Vascular perfusion performed after ultrasonic ablation, tumor vessels could not filled by dye liquid. High-intensity focused ultrasound as a noninvasive method can destroy whole endometrial cancer cells and their supplying vascularities, which maybe an alternative approach of targeted therapy and new antiangiogenic strategy for endometrial cancer.

Percutaneous Radiofrequency Lung Ablation Combined with Transbronchial Saline Injection: An Experimental Study in Swine

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

Kawai, T., E-mail: t-kawai@hosp.yoka.hyogo.jp; Kaminou, T., E-mail: kaminout@grape.med.tottori-u.ac.jp; Sugiura, K.

2010-02-15

To evaluate the efficacy of radiofrequency lung ablation with transbronchial saline injection. The bilateral lungs of eight living swine were used. A 13-gauge bone biopsy needle was inserted percutaneously into the lung, and 1 ml of muscle paste was injected to create a tumor mimic. In total, 21 nodules were ablated. In the saline injection group (group A), radiofrequency ablation (RFA) was performed for 11 nodules after transbronchial saline injection under balloon occlusion with a 2-cm active single internally cooled electrode. In the control group (group B), conventional RFA was performed for 10 nodules as a control. The infused salinemore » liquid showed a wedge-shaped and homogeneous distribution surrounding a tumor mimic. All 21 RFAs were successfully completed. The total ablation time was significantly longer (13.4 {+-} 2.8 min vs. 8.9 {+-} 3.5 min; P = 0.0061) and the tissue impedance was significantly lower in group A compared with group B (73.1 {+-} 8.8 {Omega} vs. 100.6 {+-} 16.6 {Omega}; P = 0.0002). The temperature of the ablated area was not significantly different (69.4 {+-} 9.1{sup o}C vs. 66.0 {+-} 7.9{sup o}C; P = 0.4038). There was no significant difference of tumor mimic volume (769 {+-} 343 mm{sup 3} vs. 625 {+-} 191 mm{sup 3}; P = 0.2783). The volume of the coagulated area was significantly larger in group A than in group B (3886 {+-} 1247 mm{sup 3} vs. 2375 {+-} 1395 mm{sup 3}; P = 0.0221). Percutaneous radiofrequency lung ablation combined with transbronchial saline injection can create an extended area of ablation.« less

Radiofrequency Cauterization with Biopsy Introducer Needle

PubMed Central

Pritchard, William F.; Wray-Cahen, Diane; Karanian, John W.; Hilbert, Stephen; Wood, Bradford J.

2014-01-01

PURPOSE The principal risks of needle biopsy are hemorrhage and implantation of tumor cells in the needle tract. This study compared hemorrhage after liver and kidney biopsy with and without radiofrequency (RF) ablation of the needle tract. MATERIALS AND METHODS Biopsies of liver and kidney were performed in swine through introducer needles modified to allow RF ablation with the distal 2 cm of the needle. After each biopsy, randomization determined whether the site was to undergo RF ablation during withdrawal of the introducer needle. Temperature was measured with a thermistor stylet near the needle tip, with a target temperature of 70°C–100°C with RF ablation. Blood loss was measured as grams of blood absorbed in gauze at the puncture site for 2 minutes after needle withdrawal. Selected specimens were cut for gross examination. RESULTS RF ablation reduced bleeding compared with absence of RF ablation in liver and kidney (P < .01), with mean blood loss reduced 63% and 97%, respectively. Mean amounts of blood loss (±SD) in the liver in the RF and no-RF groups were 2.03 g ± 4.03 (CI, 0.53–3.54 g) and 5.50 g ± 5.58 (CI, 3.33–7.66 g), respectively. Mean amounts of blood loss in the kidney in the RF and no-RF groups were 0.26 g ± 0.32 (CI, −0.01 to 0.53 g) and 8.79 g ± 7.72 (CI, 2.34–15.24 g), respectively. With RF ablation, thermal coagulation of the tissue surrounding the needle tract was observed. CONCLUSION RF ablation of needle biopsy tracts reduced hemorrhage after biopsy in the liver and kidney and may reduce complications of hemorrhage as well as implantation of tumor cells in the tract. PMID:14963187

Differential roles of tissue factor and phosphatidylserine in activation of coagulation.

PubMed

Spronk, Henri M H; ten Cate, Hugo; van der Meijden, Paola E J

2014-05-01

It has been suggested that the main physiological trigger of coagulation, tissue factor, possesses limited procoagulant activity and occurs in an inactive or so-called encrypted state. For the conversion of encrypted into decrypted tissue factor with sufficient procoagulant activity, four distinct models have been proposed: 1; dimer formation, 2; lipid rafts, 3; disulfide bonds, and 4; phosphatidylserine exposure. Pro and cons can be given for each of these mechanisms of tissue factor encryption/decryption, however, it seems most likely that two or more mechanisms act together in activating the procoagulant activity. The exposure of phosphatidylserine in the outer layer of cell membranes supports coagulation through enhanced formation of the tenase (factors IXa, VIIIa and X) and prothrombinase (factors Xa, Va and prothrombin) complexes. The proposed role for phosphatidylserine in decryption of tissue factor could contribute to the correct orientation of the tissue factor - factor VII complex. Overall, the contribution of both tissue factor and phosphatidylserine to coagulation seems distinct with tissue factor being the physiological activator and phosphatidylserine the driving force of propagation of coagulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Laser-produced plasmas in medicine

NASA Astrophysics Data System (ADS)

Gitomer, S. J.; Jones, R. D.

The laser has found numerous applications in medicine, beginning with uses in ophthalmology in the 1960's. Today, lasers are used in tissue cutting, blood coagulation, photo-dynamic cancer therapy, arterial plaque removal, dental drilling, etc. Those areas of laser medicine are examined in which plasmas (ionized gases) are produced. In fact, the presence of a plasma is essential for the application at hand to succeed. Examples are examined for the plasmas produced in ophthalmology (e.g., lens membrane destruction following cataract surgery), in urology and gastroenterology (e.g., kidney and gall stone ablation and fragmentation) and in cardiology and vascular surgery (e.g., laser ablation and removal of fibro-fatty and calcified arterial plaque). Experimental data are presented along with some results from computer simulations of the phenomena. Comments on future directions in these areas are included.

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Infrared thermal measurements of laser soft tissue ablation as a function of air/water coolant for Nd:YAG and diode lasers

NASA Astrophysics Data System (ADS)

Gekelman, Diana; Yamamoto, Andrew; Oto, Marvin G.; White, Joel M.

2003-06-01

The purpose of this investigation was to measure the maximum temperature at the Nd:YAG and Diode lasers fiberoptic tips as a function of air/water coolant, during soft tissue ablation in pig jaws. A pulsed Nd:YAG laser (1064nm) and a Diode laser (800-830 nm) were used varying parameters of power, conditioning or not of the fiber tip, under 4 settings of air/water coolant. The maximum temperature at the fiber tip was measured using an infra-red camera and the interaction of the fiber with the porcine soft tissue was evaluated. A two-factor ANOVA was used for statistical analysis (p<=0.05). Nd:YAG laser interaction with soft tissues produced temperatures levels directly proportional to power increase, but the conditioning of the fiber tip did not influence the temperature rise. On the other hand, conditioning of the fiber tip did influence the temperature rise for Diode laser. The addition of air/water coolant, for both lasers, did not promote temperature rise consistent with cutting and coagulation of porcine soft tissue. Laser parameters affect the fiberoptic surface temperature, and the addition of air/water coolant significantly lowered surface temperature on the fiberoptic tip for all lasers and parameters tested.

Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases.

PubMed

Massberg, Steffen; Grahl, Lenka; von Bruehl, Marie-Luise; Manukyan, Davit; Pfeiler, Susanne; Goosmann, Christian; Brinkmann, Volker; Lorenz, Michael; Bidzhekov, Kiril; Khandagale, Avinash B; Konrad, Ildiko; Kennerknecht, Elisabeth; Reges, Katja; Holdenrieder, Stefan; Braun, Siegmund; Reinhardt, Christoph; Spannagl, Michael; Preissner, Klaus T; Engelmann, Bernd

2010-08-01

Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.

Effects of radiofrequency probe application on irrigation fluid temperature in the wrist joint.

PubMed

Sotereanos, Dean G; Darlis, Nickolaos A; Kokkalis, Zinon T; Zanaros, George; Altman, Gregory T; Miller, Mark Carl

2009-12-01

Radiofrequency (RF) probes used in wrist arthroscopy may raise joint fluid temperature, increasing the risk of capsular and ligamentous damage. The purposes of the current study were to measure joint fluid temperature during wrist arthroscopy with the use of RF probes, and to determine whether using an outlet portal will reduce the maximum temperature. We performed wrist arthroscopy on 8 cadaveric arms. Ablation and coagulation cycles using RF probe were performed at documented locations within the joint. This was done for 60-second intervals on both the radial and ulnar side of the wrist, to mimic clinical practice. We used 4 fiberoptic phosphorescent probes to measure temperature (radial, ulnar, inflow-tube, and outflow-tube probes) and measured joint fluid temperature with and without outflow. There was a significant difference between wrists with and without outflow when examining maximum ablation temperatures (p < .002). All specimens showed higher maximum and average ablation temperatures without outflow. Maximum joint temperatures, greater than 60 degrees C, were observed in only no-outflow conditions. In performing RF ablation during wrist arthroscopy, the use of an outlet portal reduces the joint fluid temperature. Without an outlet portal, maximum temperatures can exceed desirable levels when using ablation; such temperatures have the potential to damage adjacent tissues. It is useful to maintain adequate outflow when using the radiofrequency probes during wrist arthroscopy.

Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach.

PubMed

Talab, Saman Shafaat; McDougal, W Scott; Wu, Chin-Lee; Tabatabaei, Shahin

2014-08-01

This study aimed evaluate the safety and feasibility of endoscopic potassium titanyl phosphate (KTP) laser application in the management of patients with radiation-induced hemorrhagic cystitis (RHC). We retrospectively reviewed the records of 20 patients with RHC who underwent endoscopic KTP laser ablation of telangiectatic bladder vessels between October 2005 and January 2013. After initial cystoscopy, KTP laser was used to ablate the submucosal vasculature while preserving the overlying mucosa. The surgical outcome was evaluated by duration of hematuria-free interval, number of episodes of hematuria, and number of required medical and/or surgical interventions after initial treatment. Overall, 20 patients underwent 26 sessions of KTP laser ablation of bladder vessels. The procedure was able to stop bleeding 92% of the time and the average hematuria-free interval after ablation was 11.8 months, with a range of 1-37 months. In 13 patients (65%) hematuria resolved after 1 session of KTP laser treatment, whereas 5 patients (25%) required multiple sessions. Two patients (10%) with severe hematuria continued to have bleeding after laser treatment, which necessitated proximal diversion of urine with percutaneous nephrostomy tubes to control bleeding. This study suggests that KTP laser, with its unique photoselectivity property, is a safe, effective, and durable treatment with minimal side effects for ablation of submucosal bladder vessels in patients with RHC. Copyright © 2014 Elsevier Inc. All rights reserved.

In vivo histological evaluation of non-insulated microneedle radiofrequency applicator with novel fractionated pulse mode.

PubMed

Harth, Yoram; Frank, Ido

2013-12-01

Microneedle radiofrequency is a novel method that allows non-thermal penetration of the epidermis followed by RF coagulation in selected depth of the dermis surrounded by zone of non-coagulative volumetric heating. The first generation of Microneedle RF applicators used insulated needles. These treatments were limited by a few factors, including low volume of dermal heating, lack of effect in the papillary dermis and pinpoint bleeding during the treatment. The system tested in this study (EndyMed PRO, Intensif applicator, EndyMed Medical, Cesarea, Israel) utilizes special extra sharp tapered non-insulated microneedles and a special pulse mode, allowing full coagulation during treatment and higher effective volume of dermal heat. After Ethics Committee approval, one female pig (Type Large white X Landrace, 34 Kg) was chosen for the study. The animal was anesthetized using Ketamine, Xylazin and Isofluran. The EndyMed PRO, Intensif applicator (was used for treatment with different needle depth penetration (1 mm-3.5 mm) and in multiple energy settings. Six mm punch biopsies were harvested for histological analysis at the following time points: immediately after the treatment, 4 days after the treatment and 14 days after the treatment. H&E and Masson-Trichrome stains were processed. Visual inspection of the treated skin, immediately after the treatment, revealed arrays of pinpoint erythematous papules surrounded by undamaged epidermal tissue. Treatment field showed no sign of bleeding. Mild to moderate Erythema and Edema developed a few minutes after the treatment, varying according to the total energy delivered. The histologies taken 4-day after therapy showed in all energy settings, dry micro crusts over the treatment zones, with full healing of epidermis. In the 14-day specimens there was a replacement of the crusts/debris by a normal looking stratum corneum with complete healing of epidermis and dermis. The current in vivo study confirms that the EndyMed PRO Intensif applicator effective and predictable tool to create cylindrical micro zones of coagulation in the papillary and reticular dermis with minimal damage to the epidermis. The histologies taken 4 days and 14 days after treatment show rapid epidermal renewal with predictable volume of coagulation in dermis related to the length of the needle and the power used. Coagulation of capillaries during treatment allows a dry treatment field. The predictability of the effect and minimal downtime may offer a significant advantage over treatments with ablative fractional lasers of insulated RF microneedles.

Coagulation disorders in dogs with hepatic disease.

PubMed

Prins, M; Schellens, C J M M; van Leeuwen, M W; Rothuizen, J; Teske, E

2010-08-01

Liver disease has been associated with abnormalities in haemostasis. In this study, coagulation times, platelet counts, platelet activity parameters, activities of individual coagulation factors, D-dimers, antithrombin (AT) and protein C activity were measured in 42 dogs with histologically confirmed liver disease. Outcome was correlated with histological diagnosis. One or more coagulation abnormalities were present in 57% of dogs with hepatic disease. Activated partial thromboplastin time was significantly prolonged in dogs with chronic hepatitis (CH), with or without cirrhosis. Mean platelet numbers, AT and factor IX activity were significantly lower in dogs with CH plus cirrhosis, compared to dogs with other hepatopathies. D-dimers were not significantly increased in any group. Only three dogs, all with different histological diagnoses, satisfied the criteria for disseminated intravascular coagulation (DIC). Haemostatic abnormalities were primarily seen in dogs with cirrhosis and this may be due to reduced synthesis rather than increased consumption of coagulation factors. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

An updated concept of coagulation with clinical implications.

PubMed

Romney, Gregory; Glick, Michael

2009-05-01

Over the past century, a series of models have been put forth to explain the coagulation mechanism. The coagulation cascade/waterfall model has gained the most widespread acceptance. This model, however, has problems when it is used in different clinical scenarios. A more recently proposed cell-based model better describes the coagulation process in vivo and provides oral health care professionals (OHCPs) with a better understanding of the clinical implications of providing dental care to patients with potentially increased bleeding tendencies. The authors conducted a literature search using the PubMed database. They searched for key words including "coagulation," "hemostasis," "bleeding," "coagulation factors," "models," "prothrombin time," "activated partial thromboplastin time," "international normalized ratio," "anticoagulation therapy" and "hemophilia" separately and in combination. The coagulation cascade/waterfall model is insufficient to explain coagulation in vivo, predict a patient's bleeding tendency, or correlate clinical outcomes with specific laboratory screening tests such as prothrombin time, activated partial thromboplastin time and international normalized ratio. However, the cell-based model of coagulation that reflects the in vivo process of coagulation provides insight into the clinical ramifications of treating dental patients with specific coagulation factor deficiencies. Understanding the in vivo coagulation process will help OHCPs better predict a patient's bleeding tendency. In addition, applying the theoretical concept of the cell-based model of coagulation to commonly used laboratory screening tests for coagulation and bleeding will result in safer and more appropriate dental care.

Polymorphisms of the factor VII gene associated with the low activities of vitamin K-dependent coagulation factors in one-month-old infants.

PubMed

Ito, Koichi; Goto, Kenji; Sugiura, Tokio; Muramatsu, Kanji; Ando, Toshihiro; Maniwa, Hiroko; Yokoyama, Takao; Sugiyama, Kohachiro; Togari, Hajime

2007-01-01

Despite administration of vitamin K (VK), some infants show lower activity of VK-dependent coagulation factors and they could develop intracranial hemorrhage. For preventing VK deficiency bleeding (VKDB) in infants, oral administration of VK and a screening test for VK deficiency are carried out in Japan. For the screening, the total activity of VK-dependent coagulation factors is measured using a commercial product, Normotest. This study was undertaken to clarify the importance of the following genetic and environmental factors on the coagulation status in one-month-old infants: two polymorphisms in the factor VII gene, -323P0/10 (a 10-bp insertion in the promoter region at position -323) and R353Q (the replacement of arginine [R] with glutamine [Q] at residue 353) and sex, age, gestational age, birth weight, and feeding regimen. Two hundred Japanese infants (34.6 +/- 4.0 days old) were screened for VK-dependent coagulation activity with Normotest and were genotyped for the two polymorphisms. Among the subjects screened, 18 infants (9%) carried the P10 allele and 26 (13%) carried the R353Q allele. Multiple regression analysis showed that the 10-bp inserted (P10) allele or the Q allele was associated with the lower coagulation activities. The coagulation activities for the R/Q genotype were significantly lower than those for the R/R genotype and those for the P0/P10 genotype were significantly lower than those for the P0/P0 genotype. Therefore, infants who carry the P10 allele or the Q allele show lower activity of VK-dependent coagulation factors. These infants may have a higher risk of VKDB manifestation.

Evaluation of corneal ablation by an optical parametric oscillator (OPO) at 2.94 μm and an Er:YAG laser and comparison to ablation by a 193-nm excimer laser

NASA Astrophysics Data System (ADS)

Telfair, William B.; Hoffman, Hanna J.; Nordquist, Robert E.; Eiferman, Richard A.

1998-06-01

Purpose: This study first evaluated the corneal ablation characteristics of (1) an Nd:YAG pumped OPO (Optical Parametric Oscillator) at 2.94 microns and (2) a short pulse Er:YAG laser. Secondly, it compared the histopathology and surface quality of these ablations with (3) a 193 nm excimer laser. Finally, the healing characteristics over 4 months of cat eyes treated with the OPO were evaluated. Methods: Custom designed Nd:YAG/OPO and Er:YAG lasers were integrated with a new scanning delivery system to perform PRK myopic correction procedures. After initial ablation studies to determine ablation thresholds and rates, human cadaver eyes and in-vivo cat eyes were treated with (1) a 6.0 mm Dia, 30 micron deep PTK ablation and (2) a 6.0 mm Dia, -5.0 Diopter PRK ablation. Cadaver eyes were also treated with a 5.0 mm Dia, -5.0 Diopter LASIK ablation. Finally, cats were treated with the OPO in a 4 month healing study. Results: Ablation thresholds below 100 mJ/cm2 and ablation rates comparable to the excimer were demonstrated for both infrared systems. Light Microscopy (LM) showed no thermal damage for low fluence treatments, but noticeable thermal damage at higher fluences. SEM and TEM revealed morphologically similar surfaces for low fluence OPO and excimer samples with a smooth base and no evidence of collagen shrinkage. The Er:YAG and higher fluence OPO treated samples revealed more damage along with visible collagen coagulation and shrinkage in some cases. Healing was remarkably unremarkable. All eyes had a mild healing response with no stromal haze and showed topographic flattening. LM demonstrated nothing except a moderate increase in keratocyte activity in the upper third of the stroma. TEM confirmed this along with irregular basement membranes. Conclusions: A non- thermal ablation process called photospallation is demonstrated for the first time using short pulse infrared lasers yielding damage zones comparable to the excimer and healing which is also comparable to the excimer. Such Infrared sources are, therefore, potentially attractive competitors to the excimer to perform PRK and LASIK.

Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

PubMed

Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

2015-08-01

Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The Authors.

The Role of Therapeutic Endoscopy in Patients With Cirrhosis-Related Causes of Gastrointestinal Bleeding.

PubMed

Kezer, Camille A; Gupta, Neil

2018-06-09

This article aims to review current therapeutic endoscopic treatments available for the management of gastrointestinal bleeding related to cirrhosis. Endoscopic band ligation is an effective treatment for primary prophylaxis, acute bleeding, and secondary prophylaxis of esophageal varices as well as for acute bleeding and secondary prophylaxis of select gastric varices. Sclerotherapy is a treatment option for acute bleeding and secondary prophylaxis of esophageal varices when band ligation is technically difficult. Cyanoacrylate glue injection is an effective treatment for acute bleeding of gastric and ectopic varices. Argon plasma coagulation is first-line and radiofrequency ablation is second-line treatment for chronic bleeding secondary to gastric antral vascular ectasia. There are a variety of endoscopic treatment modalities for cirrhosis-related gastrointestinal bleeding, and the appropriate therapy depends on the location of the bleed, history or presence of acute bleeding, and risk factors for intervention-related adverse events.

Different Recovery Profiles of Coagulation Factors, Thrombin Generation, and Coagulation Function After Hemorrhagic Shock in Pigs

DTIC Science & Technology

2012-06-06

Different recovery profiles of coagulation factors, thrombin generation, and coagulation function after hemorrhagic shock in pigs Wenjun Z. Martini ...Defense. Address for reprints: Wenjun Z. Martini , PhD, The US Army Institute of Surgical Research, 3698 Chambers Pass, Ft. Sam Houston, San Antonio, TX...control number 1. REPORT DATE 01 SEP 2015 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Different recovery profiles of

MR-guided microwave ablation in hepatic tumours: initial results in clinical routine.

PubMed

Hoffmann, Rüdiger; Rempp, Hansjörg; Keßler, David-Emanuel; Weiß, Jakob; Pereira, Philippe L; Nikolaou, Konstantin; Clasen, Stephan

2017-04-01

Evaluation of the technical success, patient safety and technical effectiveness of magnetic resonance (MR)-guided microwave ablation of hepatic malignancies. Institutional review board approval and informed patient consent were obtained. Fifteen patients (59.8 years ± 9.5) with 18 hepatic malignancies (7 hepatocellular carcinomas, 11 metastases) underwent MR-guided microwave ablation using a 1.5-T MR system. Mean tumour size was 15.4 mm ± 7.7 (7-37 mm). Technical success and ablation zone diameters were assessed by post-ablative MR imaging. Technique effectiveness was assessed after 1 month. Complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). Mean follow-up was 5.8 months ± 2.6 (1-10 months). Technical success and technique effectiveness were achieved in all lesions. Lesions were treated using 2.5 ± 1.2 applicator positions. Mean energy and ablation duration per tumour were 37.6 kJ ± 21.7 (9-87 kJ) and 24.7 min ± 11.1 (7-49 min), respectively. Coagulation zone short- and long-axis diameters were 31.5 mm ± 10.5 (16-65 mm) and 52.7 mm ± 15.4 (27-94 mm), respectively. Two CTCAE-2-complications occurred (pneumothorax, pleural effusion). Seven patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed. Microwave ablation is feasible under near real-time MR guidance and provides effective treatment of hepatic malignancies in one session. • Planning, applicator placement and therapy monitoring are possible without using contrast enhancement • Energy transmission from the generator to the scanner room is safely possible • MR-guided microwave ablation provides effective treatment of hepatic malignancies in one session • Therapy monitoring is possible without applicator retraction from the ablation site.

Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies.

PubMed

Slatter, David A; Percy, Charles L; Allen-Redpath, Keith; Gajsiewicz, Joshua M; Brooks, Nick J; Clayton, Aled; Tyrrell, Victoria J; Rosas, Marcela; Lauder, Sarah N; Watson, Andrew; Dul, Maria; Garcia-Diaz, Yoel; Aldrovandi, Maceler; Heurich, Meike; Hall, Judith; Morrissey, James H; Lacroix-Desmazes, Sebastien; Delignat, Sandrine; Jenkins, P Vincent; Collins, Peter W; O'Donnell, Valerie B

2018-03-22

Hemostatic defects are treated using coagulation factors; however, clot formation also requires a procoagulant phospholipid (PL) surface. Here, we show that innate immune cell-derived enzymatically oxidized phospholipids (eoxPL) termed hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) restore hemostasis in human and murine conditions of pathological bleeding. HETE-PLs abolished blood loss in murine hemophilia A and enhanced coagulation in factor VIII- (FVIII-), FIX-, and FX-deficient human plasma . HETE-PLs were decreased in platelets from patients after cardiopulmonary bypass (CPB). To explore molecular mechanisms, the ability of eoxPL to stimulate individual isolated coagulation factor/cofactor complexes was tested in vitro. Extrinsic tenase (FVIIa/tissue factor [TF]), intrinsic tenase (FVIIIa/FIXa), and prothrombinase (FVa/FXa) all were enhanced by both HETE-PEs and HETE-PCs, suggesting a common mechanism involving the fatty acid moiety. In plasma, 9-, 15-, and 12-HETE-PLs were more effective than 5-, 11-, or 8-HETE-PLs, indicating positional isomer specificity. Coagulation was enhanced at lower lipid/factor ratios, consistent with a more concentrated area for protein binding. Surface plasmon resonance confirmed binding of FII and FX to HETE-PEs. HETE-PEs increased membrane curvature and thickness, but not surface charge or homogeneity, possibly suggesting increased accessibility to cations/factors. In summary, innate immune-derived eoxPL enhance calcium-dependent coagulation factor function, and their potential utility in bleeding disorders is proposed.

Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies

PubMed Central

Slatter, David A.; Percy, Charles L.; Allen-Redpath, Keith; Gajsiewicz, Joshua M.; Brooks, Nick J.; Tyrrell, Victoria J.; Lauder, Sarah N.; Watson, Andrew; Dul, Maria; Garcia-Diaz, Yoel; Aldrovandi, Maceler; Heurich, Meike; Hall, Judith; Lacroix-Desmazes, Sebastien; Delignat, Sandrine; Jenkins, P. Vincent; Collins, Peter W.; O’Donnell, Valerie B.

2018-01-01

Hemostatic defects are treated using coagulation factors; however, clot formation also requires a procoagulant phospholipid (PL) surface. Here, we show that innate immune cell–derived enzymatically oxidized phospholipids (eoxPL) termed hydroxyeicosatetraenoic acid–phospholipids (HETE-PLs) restore hemostasis in human and murine conditions of pathological bleeding. HETE-PLs abolished blood loss in murine hemophilia A and enhanced coagulation in factor VIII- (FVIII-), FIX-, and FX-deficient human plasma . HETE-PLs were decreased in platelets from patients after cardiopulmonary bypass (CPB). To explore molecular mechanisms, the ability of eoxPL to stimulate individual isolated coagulation factor/cofactor complexes was tested in vitro. Extrinsic tenase (FVIIa/tissue factor [TF]), intrinsic tenase (FVIIIa/FIXa), and prothrombinase (FVa/FXa) all were enhanced by both HETE-PEs and HETE-PCs, suggesting a common mechanism involving the fatty acid moiety. In plasma, 9-, 15-, and 12-HETE-PLs were more effective than 5-, 11-, or 8-HETE-PLs, indicating positional isomer specificity. Coagulation was enhanced at lower lipid/factor ratios, consistent with a more concentrated area for protein binding. Surface plasmon resonance confirmed binding of FII and FX to HETE-PEs. HETE-PEs increased membrane curvature and thickness, but not surface charge or homogeneity, possibly suggesting increased accessibility to cations/factors. In summary, innate immune-derived eoxPL enhance calcium-dependent coagulation factor function, and their potential utility in bleeding disorders is proposed. PMID:29563336

Laser-produced plasmas in medicine

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

Gitomer, S.J.; Jones, R.D.

The laser has found numerous applications in medicine, beginning with uses in ophthalmology in the 1960's. Today, lasers are used in tissue cutting, blood coagulation, photodynamic cancer therapy, arterial plaque removal, dental drilling, etc. In this paper the authors examine those areas of laser medicine in which plasmas (ionized gases) are produced. In fact, the presence of a plasma is essential for the application at hand to succeed. We consider examples of the plasmas produced in ophthalmology (e.g., lens membrane destruction following cataract surgery), in urology and gastroenterology (e.g., kidney and gall stone ablation and fragmentation), and in cardiology andmore » vascular surgery (e.g., laser ablation and removal of fibro-fatty and calcified arterial plaque). Experimental data are presented, along with some results from computer simulations of the phenomena. Comments on future directions in these areas are included.« less

Laser-produced plasmas in medicine

NASA Astrophysics Data System (ADS)

Gitomer, Steven J.; Jones, Roger D.

1990-06-01

The laser has found numerous applications in medicine, beginning with uses in ophthalmology in the 1960's. Today, lasers are used in tissue cutting, blood coagulation, photo-dynamic cancer therapy, arterial plaque removal, dental drilling, etc. In this paper, we examine those areas of laser medicine in which plasmas (ionized gases) are produced. In fact, the presence of a plasma is essential for the application at hand to succeed. We consider examples of the plasmas produced in ophthalmology (e.g. lens membrane destruction following cataract surgery), in urology and gastroenterology (e.g. kidney and gall stone ablation and fragmentation) and in cardiology and vascular surgery (e.g. laser ablation and removal of fibro-fatty and calcified arterial plaque). Experimental data are presented along with some results from computer simulations of the phenomena. Comments on future directions in these areas are included.

Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU) in Treatment of Symptomatic Uterine Myomas

PubMed Central

Filipowska, Justyna; Łoziński, Tomasz

2014-01-01

Summary Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) is a noninvasive technique for ablation therapy for uterine myomas, where focused ultrasound energy beam generates localized high temperature in the selected area and coagulates chosen tissue, leaving the skin and tissues in between unharmed. Magnetic resonance imaging enables accurate targeting for HIFU as well as temperature monitoring during treatment. MR guidance with 3D anatomical imaging provides reference data for treatment planning, while real-time temperature monitoring aids in controlling ablation process. This review provides basic information regarding methodology, clinical indications for this kind of treatment, expected outcome and patient management during MR-HIFU procedure. The aim of this work is to introduce a new, noninvasive treatment method for uterine leiomyomas and to present a comparison with other currently used methods. PMID:25469176

Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU) in Treatment of Symptomatic Uterine Myomas.

PubMed

Filipowska, Justyna; Loziński, Tomasz

2014-01-01

Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) is a noninvasive technique for ablation therapy for uterine myomas, where focused ultrasound energy beam generates localized high temperature in the selected area and coagulates chosen tissue, leaving the skin and tissues in between unharmed. Magnetic resonance imaging enables accurate targeting for HIFU as well as temperature monitoring during treatment. MR guidance with 3D anatomical imaging provides reference data for treatment planning, while real-time temperature monitoring aids in controlling ablation process. This review provides basic information regarding methodology, clinical indications for this kind of treatment, expected outcome and patient management during MR-HIFU procedure. The aim of this work is to introduce a new, noninvasive treatment method for uterine leiomyomas and to present a comparison with other currently used methods.

Treatment of cervical intraepithelial lesions.

PubMed

Castle, Philip E; Murokora, Dan; Perez, Carlos; Alvarez, Manuel; Quek, Swee Chong; Campbell, Christine

2017-07-01

Precancerous cervical lesions precede the development of invasive cervical cancer by 10-20 years, making cervical cancer preventable if these lesions are detected and effectively treated. Treatment has evolved in the last few decades and now includes ablative options that can be performed in lower-resource settings where surgical excision is not feasible or routinely available. Gas-based cryotherapy, which freezes cervical tissue to induce localized necrosis, is the most commonly used ablative treatment. However, its implementation in low-resource settings is difficult because the refrigerant gas can be difficult to procure and transport, and is expensive. New cryotherapy devices that do not require an external supply of gas appear promising. Thermal coagulation, which burns cervical tissue to induce necrosis, has become more widely available in the last few years owing to its portability and the feasibility of using battery-powered devices. These two ablative treatments successfully eradicate 75%-85% of high-grade cervical lesions and have minor adverse effects. © 2017 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

Combined microwave ablation and minimally invasive open decompression for the management of thoracic metastasis in breast cancer.

PubMed

Liu, Bin; Yuan, Zhenchao; Wei, Chang Yuan

2018-01-01

The incidence rate of thoracic metastasis from breast cancer is increasing. Microwave ablation is one type of clinical therapy used to treat metastatic spine disease, although it can cause protein denaturation and immediate cell death, and coagulative necrosis can occur. Minimally invasive open decompression is associated with lower rates of surgical complications in comparison to traditional open surgery. Therefore, it is an alternative therapeutic option for spinal metastases. This study aimed to assess the efficacy of microwave ablation with minimally invasive open decompression in the management of breast cancer patients with thoracic metastasis. This single-institution retrospective study investigated 23 cases of thoracic metastasis from breast cancer treated with combined microwave ablation and minimally invasive open decompression. Patients that presented with indications for surgery underwent surgical treatment. Data were collected for pain scores, the Frankel Grade classification system for acute spinal injury, the Karnofsky performance status (KPS) scale and complications due to treatment. Of the 23 patients included in this study, all were successfully treated with microwave ablation and minimal invasive open decompression using our metrics. Of those, 18 patients (78.3%) showed improvement in their KPS results while 5 (21.7%) had alleviation of KPS. All 23 patients showed improvement in their Frankel Grade, suggesting improved neurological function following surgery. Most of the patients reported pain relief. Postoperative complications occurred in 4 patients. Microwave ablation combined with minimally invasive open decompression therapy for breast cancer patients with thoracic metastatic tumors is an alternative treatment that maintains or improves functional outcome in comparison to open surgery.

Application of erbium: YAG laser in ocular ablation.

PubMed

Tsubota, K

1990-01-01

Recent developments in lasers have provided us the possibility of laser ocular surgery. The xenon, argon, neodymium:YAG and dye lasers have been successfully used in out-patient clinics. The excimer laser has been attracting researchers' interest in the new application of laser to cornea and lens. The erbium:YAG laser emits a 2.94-microns beam that can ablate the transparent ocular tissues such as lenses and corneas. The author has applied this laser to the cornea, lens, vitreous and other ocular tissues. The erbium:YAG laser beam was directed through a 1.5-meter-long, 200-microns-diameter fiberoptic guide. The radiant energy measured about 50 mJ at the end of the probe. The laser was emitted as a 400-microsecond pulse. Freshly enucleated rabbit eyes were used in this study. Laser burns were applied to the tissue surface at various energy settings. At minimal power, the tissues were coagulated by the erbium:YAG laser application. At a power of more than 636-954 mJ/mm2, tissue began to evaporate; the tissue loss was observed under a surgical light microscope. Corneal photoablation, lens ablation, iridotomy, trabeculotomy, cutting of the vitreous and retinal ablation were easily performed. Like the excimer laser, the erbium:YAG laser is a potential tool for ocular surgery.

Fetoscopic laser ablation of placental anastomoses in twin-twin transfusion syndrome using 'Solomon technique'.

PubMed

Ruano, R; Rodo, C; Peiro, J L; Shamshirsaz, A A; Haeri, S; Nomura, M L; Salustiano, E M A; de Andrade, K K; Sangi-Haghpeykar, H; Carreras, E; Belfort, M A

2013-10-01

To document perinatal outcomes following use of the 'Solomon technique' in the selective photocoagulation of placental anastomoses for severe twin-twin transfusion syndrome (TTTS). Between January 2010 and July 2012, data were collected from 102 consecutive monochorionic twin pregnancies complicated by severe TTTS that underwent fetoscopic laser ablation at four different centers. We compared outcomes between subjects that underwent selective laser coagulation using the Solomon technique (cases) and those that underwent selective laser coagulation without this procedure (controls). Of the 102 pregnancies examined, 26 (25.5%) underwent the Solomon technique and 76 (74.5%) did not. Of the 204 fetuses, 139 (68.1%) survived up to 30 days of age. At least one twin survived in 82 (80.4%) pregnancies and both twins survived in 57 (55.9%) pregnancies. When compared with the control group, the Solomon-technique group had a significantly higher survival rate for both twins (84.6 vs 46.1%; P < 0.01) and a higher overall neonatal survival rate (45/52 (86.5%) vs 94/152 (61.8%); P < 0.01). Use of the Solomon technique remained independently associated with dual twin survival (adjusted odds ratio (aOR), 11.35 (95% CI, 3.11-53.14); P = 0.0007) and overall neonatal survival rate (aOR, 4.65 (95% CI, 1.59-13.62); P = 0.005) on multivariable analysis. There were no cases of recurrent TTTS or twin anemia-polycythemia sequence (TAPS) in the Solomon-technique group. Use of the Solomon technique following selective laser coagulation of placental anastomoses appears to improve twin survival and may reduce the risk of recurrent TTTS and TAPS. Our data support the idea of performing a randomized controlled trial to evaluate the effectiveness of the Solomon technique. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Eradication of Barrett's mucosa with argon plasma coagulation and acid suppression: immediate and mid term results

PubMed Central

Van Laethem, J-L; Cremer, M; Peny, M; Delhaye, M; Deviere, J

1998-01-01

Background—Intestinal metaplastic mucosa in Barrett's oesophagus can be replaced by squamous epithelium after mucosal thermal ablation associated with acid suppression therapy. 
Aims—To assess whether restoration of squamous epithelium can be obtained after ablation of Barrett's oesophagus using argon plasma coagulation (APC) associated with proton pump inhibitor (PPI) therapy. 
Methods—Thirty one patients with Barrett's oesophagus received APC. Omeprazole (40 mg/day) was given from the first APC application to one month after completion of the treatment, then given symptomatically. Twenty four hour pH-metry was performed during endotherapy. 
Results—Complete re-epithelialisation was visualised at endoscopy in 25/31 patients (81%) after a mean number of 2.4 APC sessions (range 1-4). Only partial squamous re-epithelialisation was observed in three patients and three others had no eradication. At histological assessment, eradication of Barrett's oesophagus was only confirmed in 19/31 patients (61%) due to the presence of a few residual Barrett's glands under the new squamous epithelium. Complete eradication was related to a Barrett's oesophagus segment length of less than 4 cm and the absence of circumferential extension but not to the normalisation of oesophageal acid exposure under PPI therapy. Seventeen patients with apparently complete endoscopic and histological eradication of Barrett's oesophagus were re-evaluated at one year; eight (47%) disclosed relapsing islands of Barrett metaplasia despite continuous omeprazole therapy (10-40 mg/day). 
Conclusions—APC combined with 40 mg omeprazole daily can eradicate Barrett's mucosa with apparent squamous re-epithelialisation in the majority of patients even in the absence of normalisation of oesophageal acid exposure. However, one year after endotherapy for Barrett's oesophagus, relapse is frequent but limited in extent. 

 Keywords: Barrett's oesophagus; argon plasma coagulation; omeprazole; gastro-oesophageal reflux; Barrett's adenocarcinoma PMID:9824599

Coagulation management in trauma-associated coagulopathy: allogenic blood products versus coagulation factor concentrates in trauma care.

PubMed

Klages, Matthias; Zacharowski, Kai; Weber, Christian Friedrich

2016-04-01

Coagulation management by transfusion of allogenic blood products and coagulation factors are competing concepts in current trauma care. Rapid and adequate therapy of trauma-associated coagulopathy is crucial to survival of severely injured patients. Standard coagulation tests such as prothrombin time and activated partial thromboplastin time are commonly used, but these tests are inappropriate for monitoring and guiding therapy in trauma patients. Coagulation factor-based treatment showed promising results, but randomized trials have not yet been performed. In addition, viscoelastic tests are needed to guide therapy, although there is in fact limited evidence for these in tests in trauma care. Regarding transfusion therapy with allogenic blood products, plasma transfusion has been associated with improved survival in trauma patients following massive transfusion. In contrast, patients not requiring massive transfusion seem to be at risk for suffering complications with increasing volumes of plasma transfused. The collective of trauma patients is heterogeneous. Despite the lack of evidence, there are strong arguments for individualized patient treatment with coagulation factors for some indications and to abstain from the use of fresh frozen plasma. In patients with severe trauma and major bleeding, plasma, platelets, and red blood cells should be considered to be administered at a ratio of 1 : 1 : 1.

Development and Implementation of a Coagulation Factor Testing Method Utilizing Autoverification in a High-volume Clinical Reference Laboratory Environment

PubMed Central

Riley, Paul W.; Gallea, Benoit; Valcour, Andre

2017-01-01

Background: Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. Methods: The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Results: Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. Conclusions: To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process. PMID:28706751

Development and Implementation of a Coagulation Factor Testing Method Utilizing Autoverification in a High-volume Clinical Reference Laboratory Environment.

PubMed

Riley, Paul W; Gallea, Benoit; Valcour, Andre

2017-01-01

Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process.

Opposite effects of Agrimonia pilosa Ledeb aqueous extracts on blood coagulation function

PubMed Central

Yuan, Wufeng; Jiang, Lei; Wang, Huan

2017-01-01

Background Agrimonia pilosa Ledeb (APL) has showed anticoagulant and antithrombotic activities in some studies, whereas its actual effects on blood coagulation are still unclear. This study was designed to observe the in vitro effects of APL aqueous extracts on blood coagulation, as well as to investigate the underlying mechanisms. Methods Studies were divided into four groups: 0, 4, 20, and 80 g/L of APL aqueous extracts mixed with plasma or whole blood samples. Clotting time of whole blood, plasma coagulation tests, activities of plasma coagulation factors, plasma calcium ion, platelet aggregation test, and platelet fibrinogen receptor as well as the blood viscosity were measured. Results It was observed that the APL aqueous extracts in 4 g/L significantly prolonged the whole blood clotting time and activated partial thromboplastin time, shortened prothrombin time, decreased activities of coagulation factor VIII, IX and XI, and levels of platelet aggregation and fibrinogen receptor expression. However, coagulation factor VII activity, and blood viscosity were increased after the extracts treatment. And the effects of APL extracts were in a concentration-dependent manner (0–80 g/L). Conclusions The results suggest that APL aqueous extracts have a total anticoagulant activity, whereas they exhibit opposite effects of greater anticoagulant activity than pro-coagulant activity. PMID:28480193

Economic aspects of intraoperative coagulation management targeting higher fibrinogen concentrations during major craniosynostosis surgery.

PubMed

Haas, Thorsten; Spielmann, Nelly; Restin, Tanja; Schmidt, Alexander R; Schmugge, Markus; Cushing, Melissa M

2016-01-01

Results of a previously published study demonstrated a significant decrease in transfusion requirements and calculated blood loss for pediatric major craniosynostosis surgery, if a ROTEM(®) FIBTEM trigger of <13 mm (early substitution group) was applied as compared to a trigger of <8 mm (conventional group). The aim of this study was a posthoc analysis of the costs for this coagulation management. The total volume as well as the number of units or bags for all transfused blood products and coagulation factors were recorded for each case. The number of laboratory and point-of-care coagulation tests was also analyzed. Total blood product costs were calculated according to the local prices per unit. The total cost for all transfused/administered blood products/coagulation factors per patient was a median of 1023EUR (IQR 850EUR-1058EUR) in the early substitution group as compared to a median of 910EUR (IQR 719EUR-1351EUR) in the conventional group (P = 0.81). No difference in the number of coagulation tests performed was observed. In this study, the use of a higher fibrinogen trigger was not linked to a significant increase in total costs for transfused blood products and coagulation factors, and may offer an economically equivalent approach to coagulation management. © 2015 John Wiley & Sons Ltd.

The Research of Feasibility and Efficacy of Radiofrequency Ablation in Treating Uterine Fibroids

PubMed Central

Luo, Xin; Shu, Shan-rong; Ma, Xue-feng; Shuai, Han-lin

2015-01-01

Abstract To explore the feasibility and efficacy of radiofrequency ablation in treating uterine fibroids. Ninety patients with multiple uterine fibroids, who had undergone hysterectomy were included in the study. After the uterus was resected, the temperature of 60, 80, 100°C were adopted to ablate the in vitro fibroid with each temperature dealing with 30 patients. Simultaneously, 5 patients were included, whose in vivo fibroid were ablated with the temperature of 100°C before the fibroids were removed after laparotomy. After the fibroids were ablated, the smooth muscle in the ablated center (group A), the ablated edge (group B) and 1 cm away from the ablated edge (group C) were taken. Then, the samples were stained with hematoxylin and eosin (HE) to examine the histopathological changes, and immunohistochemistry was performed to detect the expression of estrogen receptor (ER) and progesterone receptor (PR). After radiofrequency ablation, the ablated lesions were round, toast tan, and dry on gross appearance. There were no obvious tissue carbonization and there were distinct boundary from periphery tissue. In vitro: On automated analysis, the average optical density of ER and PR in group A, B, and C was lower than the control group (P < 0.05), and which were gradually raised with the increased distance to electrode. In the same treatment group, ER optical density was gradually decreased with the increased temperature among 3 different groups. The PR optical density was decreased with the increased temperature under different temperatures in group A and group B, there was significant difference among groups (P < 0.05). But in group C, there was no difference in PR expression among the temperature of 60, 80, and 100°C (P > 0.05). In vivo: Compared with the control group, the average optical density of ER and PR were significantly different among group A, B, and C (P < 0.05), what's more, it was gradually raised with the increased distance to electrode. After radiofrequency ablation, the tissues displayed coagulative necrosis, and decreased ER and PR expression. Radiofrequency ablation may be considered a minimally invasive alternative for those women who wish to retain their reproductive potential. Eighty degree Celsius was expected to be the optimum temperature in radiofrequency ablation treatment of uterine fibroid. PMID:26632689

Workflow oriented software support for image guided radiofrequency ablation of focal liver malignancies

NASA Astrophysics Data System (ADS)

Weihusen, Andreas; Ritter, Felix; Kröger, Tim; Preusser, Tobias; Zidowitz, Stephan; Peitgen, Heinz-Otto

2007-03-01

Image guided radiofrequency (RF) ablation has taken a significant part in the clinical routine as a minimally invasive method for the treatment of focal liver malignancies. Medical imaging is used in all parts of the clinical workflow of an RF ablation, incorporating treatment planning, interventional targeting and result assessment. This paper describes a software application, which has been designed to support the RF ablation workflow under consideration of the requirements of clinical routine, such as easy user interaction and a high degree of robust and fast automatic procedures, in order to keep the physician from spending too much time at the computer. The application therefore provides a collection of specialized image processing and visualization methods for treatment planning and result assessment. The algorithms are adapted to CT as well as to MR imaging. The planning support contains semi-automatic methods for the segmentation of liver tumors and the surrounding vascular system as well as an interactive virtual positioning of RF applicators and a concluding numerical estimation of the achievable heat distribution. The assessment of the ablation result is supported by the segmentation of the coagulative necrosis and an interactive registration of pre- and post-interventional image data for the comparison of tumor and necrosis segmentation masks. An automatic quantification of surface distances is performed to verify the embedding of the tumor area into the thermal lesion area. The visualization methods support representations in the commonly used orthogonal 2D view as well as in 3D scenes.

In vitro assessment of fiber sweeping angle during Q-switched 532-nm laser tissue ablation

NASA Astrophysics Data System (ADS)

Rajabhandharaks, Danop; Kang, Hyun Wook; Ko, Woo Jin; Stinson, Douglas; Choi, Benjamin

2011-03-01

Photoselective vaporization of the prostate (PVP) has been widely used to treat benign prostatic hyperplasia (BPH). It is well regarded as a safe and minimally invasive procedure and an alternative to the gold standard transurethral resection of the prostate (TURP). Despite of its greatness, as well aware of, the operative procedure time during the PVP is still prolonged. Such attempts have been tried out in order to shorten the operative time and increase its efficacy. However, scientific study to investigate techniques used during the PVP is still lacking. The objective of this study is to investigate how sweeping angle might affect the PVP performance. Porcine kidneys acquired from a local grocery store were used (N=140). A Q-switched 532-nm GreenLight XPSTM (American Medical Systems, Inc., MN, USA), together with 750- μm core MoXyTM fiber, was set to have power levels of 120 W and 180 W. Treatment speed and sweeping speed were fixed at 2 mm/s and 0.5 sweep/s, respectively. Sweeping angles were varied from 0 (no sweeping motion) to 120 degree. Ablation rate, depth, and coagulation zone were measured and quantified. Tissue ablation rate was peaked at 15 and 30 degree for both 120- and 180-W power levels and dramatically decreased beyond 60 degree. At 180 W, ablation rate increased 20% at 30 degree compared to 0 degree. This study demonstrated that ablation rate could be maximized and was contingent upon sweeping angle.

In vitro thermal profile suitability assessment of acids and bases for thermochemical ablation: underlying principles.

PubMed

Freeman, Laura A; Anwer, Bilal; Brady, Ryan P; Smith, Benjamin C; Edelman, Theresa L; Misselt, Andrew J; Cressman, Erik N K

2010-03-01

To measure and compare temperature changes in a recently developed gel phantom for thermochemical ablation as a function of reagent strength and concentration with several acids and bases. Aliquots (0.5-1 mL) of hydrochloric acid or acetic acid and sodium hydroxide or aqueous ammonia were injected for 5 seconds into a hydrophobic gel phantom. Stepwise increments in concentration were used to survey the temperature changes caused by these reactions. Injections were performed in triplicate, measured with a thermocouple probe, and plotted as functions of concentration and time. Maximum temperatures were reached almost immediately in all cases, reaching 75 degrees C-110 degrees C at the higher concentrations. The highest temperatures were seen with hydrochloric acid and either base. More concentrated solutions of sodium hydroxide tended to mix incompletely, such that experiments at 9 M and higher were difficult to perform consistently. Higher concentrations for any reagent resulted in higher temperatures. Stronger acid and base combinations resulted in higher temperatures versus weak acid and base combinations at the same concentration. Maximum temperatures obtained are in a range known to cause tissue coagulation, and all combinations tested therefore appeared suitable for further investigation in thermochemical ablation. Because of the loss of the reaction chamber shape at higher concentrations of stronger agents, the phantom does not allow complete characterization under these circumstances. Adequate mixing of reagents to maximize heating potential and avoid systemic exposure to unreacted acid and base must be addressed if the method is to be safely employed in tissues. In addition, understanding factors that control lesion shape in a more realistic tissue model will be critical. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

Anxiety and depression in patients three months after myocardial infarction: Association with markers of coagulation and the relevance of age.

PubMed

Geiser, Franziska; Urbach, Anne Sarah; Harbrecht, Ursula; Conrad, Rupert; Pötzsch, Bernd; Amann, Nele; Kiesewetter, Katharina; Sieke, Alexandra; Wolffs, Kyra; Skowasch, Dirk

2017-08-01

Anxiety and depression are associated with an activation of coagulation and an impairment of fibrinolysis, which may contribute to the increased cardiovascular risk associated with the two disorders. However, very few studies have examined the impact of psychological distress on coagulation factors in coronary artery disease patients. The aim of this study was to assess the correlation between anxiety/depression and factors of coagulation and fibrinolysis in patients who had suffered an acute MI three months prior. In 148 patients, anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS) shortly after MI and three months later. At the second time of assessment, plasma levels of fibrinogen, factor VII, factor VIII, von Willebrand factor, prothrombin-fragment 1 and 2, tissue-plasminogen-activator, plasminogen activator inhibitor-1, D-dimer, and homocysteine were measured. In 32% of the patients, elevated levels of anxiety and depression were found three months after a MI. Multiple regression analyses showed that coagulation and fibrinolysis markers were not significantly associated with HADS anxiety and depression scores. We found that age, gender, BMI, and smoking status were significant predictors for haemostasis factors. A higher age was associated with a higher coagulability but lower anxiety levels. We measured parameters of coagulation and fibrinolysis in patients three months after MI and found no predictive value of HADS anxiety and depression scores shortly after MI or at the time of blood sampling. The effects of age on the relationship between anxiety and haemostasis should be further investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia.

PubMed

Pawlinski, Rafal; Pedersen, Brian; Schabbauer, Gernot; Tencati, Michael; Holscher, Todd; Boisvert, William; Andrade-Gordon, Patricia; Frank, Rolf Dario; Mackman, Nigel

2004-02-15

Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry.

PubMed

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.

Multiple roles of the coagulation protease cascade during virus infection.

PubMed

Antoniak, Silvio; Mackman, Nigel

2014-04-24

The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

Acute Coagulopathy of Trauma in the Rat

DTIC Science & Technology

2013-01-01

coagulation and include prothrombin complex con- centrate, recombinant activated FVII , tranexamic acid, and fibrinogen (13, 14). The degree of coagulopathy...extrinsic pathway using tissue factor to initiate coagulation as would be expected following tissue injury. Cytochalasin D (inhibit platelet function in...chalasin D. ! Angle was elevated, and clotting time was shortened, suggesting that coagulation factors were activated and adequate to support thrombin

Local ablative treatments for hepatocellular carcinoma: An updated review

PubMed Central

Facciorusso, Antonio; Serviddio, Gaetano; Muscatiello, Nicola

2016-01-01

Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety. Although survival outcomes are similar to percutaneous ethanol injection, the lower local recurrence rate stands for a wider application of RFA in hepato-oncology. Moreover, RFA seems to be even more cost-effective than liver resection for very early HCC (single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm. There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate, but more robust prospective data is still needed to validate these pivotal findings. Among other thermal treatments, microwave ablation (MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis. In comparison to RFA, MWA has several theoretical advantages such as a broader zone of active heating, higher temperatures within the targeted area in a shorter treatment time and the lack of heat-sink effect. The safety concerns raised on the risks of this procedure, due to the broader and less predictable necrosis areas, have been recently overcome. However, whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown. Other treatments, such as high-intensity focused ultrasound ablation, laser ablation, and cryoablation, are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in the next future. PMID:27867681

Holmium:YAG and erbium:YAG laser interaction with hard and soft tissue

NASA Astrophysics Data System (ADS)

Charlton, Andrew; Dickinson, Mark R.; King, Terence A.; Freemont, Anthony J.

1991-06-01

The holmium YAG and erbium YAG lasers operating at 2.1 micrometers and 2.9 micrometers respectively, are the subject of great interest for various medical applications. The interaction of both these pulsed lasers with biological tissue involves absorption of the radiation by water leading to rapid heating and ablation, however the different absorption coefficients at these two wavelengths give rise to different ablation efficiencies and haemostatic properties for the two lasers. It is this cut/seal ratio that determines for which medical applications each of these lasers is most suited. The lasers were used to produce incisions in various tissues by translating the tissue at fixed speed beneath a focused laser beam. The laser energy density was varied between 100 and 500 J/cm2 and the lasers were operated at 2 Hz. After irradiation the tissues were fixed in formalin, processed routinely into paraffin wax, sectioned at 5 micrometers and stained with haemotoxylin and eosin. This allowed the dimensions of the incisions to be measured, as well as the depth of coagulative denatured tissue surrounding each incision. In this way the cut/seal ratio was determined for both the holmium YAG and erbium YAG laser in a range of hard and soft tissues. Results show that the latent heat of ablation for the holmium YAG laser interacting with soft tissue varies between 20-50 kJ/cm3, almost an order of magnitude larger than with the erbium YAG laser. Furthermore, the depth of coagulative necrosis with holmium YAG extends 100-400 micrometers , compared with 10-30 micrometers for erbium YAG. The two interactions clearly lead to vastly different results suggesting that the holmium YAG laser is suitable for producing lesions in highly vascular tissue where haemostasis is important, whereas the erbium YAG laser is better suited to avascular tissue requiring large depths of incision.

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin...

Intraoperative microwave ablation of pulmonary malignancies with tumor permittivity feedback control: ablation and resection study in 10 consecutive patients.

PubMed

Wolf, Farrah J; Aswad, Bassam; Ng, Thomas; Dupuy, Damian E

2012-01-01

To determine histologic changes induced by microwave ablation (MWA) in patients with pulmonary malignancy by using an ablation system with tumor permittivity feedback control, enabling real-time modulation of energy power and frequency. Institutional review board approval and patient informed consent were obtained for this prospective HIPAA-complaint ablation and resection study. Between March 2009 and January 2010, 10 patients (four women, six men; mean age, 71 years; age range, 52-82 years) underwent intraoperative MWA of pulmonary malignancies. Power (10-32 W) and frequency (908-928 MHz) were continuously adjusted by the generator to maintain a temperature of 110°-120°C at the 14-gauge antenna tip for one 10-minute application. After testing for an air leak, tumors were resected surgically. Gross inspection, slicing, and hematoxylin-eosin (10 specimens) and nicotinamide adenine dinucleotide (six specimens) staining were performed. Tumors included adenocarcinomas (n = 5), squamous cell carcinomas (n = 3), and metastases from endometrial (n = 1) and colorectal (n = 1) primary carcinomas. Mean maximum tumor diameter was 2.4 cm (range, 0.9-5.0 cm), and mean maximum volume was 8.6 cm(3) (range, 0.5-52.7 cm(3)). One air leak was detected. Five of 10 specimens were grossly measurable, revealing a mean maximum ablation zone diameter of 4.8 cm (range, 3.0-6.5 cm) and a mean maximum ablation zone volume of 15.1 cm(3) (range, 7.3-25.1 cm(3)). At hematoxylin-eosin staining, coagulation necrosis was observed in all ablation zones, extended into the normal lung in nine of 10 specimens, and up to blood vessel walls without evidence of vessel (>4 mm) thrombosis. Nicotinamide adenine dinucleotide staining enabled confirmation of no viability within ablation zones extending into normal lung in five of six specimens. MWA with tumor permittivity feedback control results in cytotoxic intratumoral temperatures and extension of ablation zones into aerated peritumoral pulmonary parenchyma, possibly forming the equivalent of an oncologic resection margin. © RSNA, 2011.

Laser-produced plasmas in medicine

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

Gitomer, S.J.; Jones, R.D.

The laser has found numerous applications in medicine, beginning with uses in ophthalmology in the 1960's. Today, lasers are used in tissue cutting, blood coagulation, photo-dynamic cancer therapy, arterial plaque removal, dental drilling, etc. In this paper, we examine those areas of laser medicine in which plasmas (ionized gases) are produced. In fact, the presence of a plasma is essential for the application at hand to succeed. We consider examples of the plasmas produced in ophthalmology (e.g., lens membrane destruction following cataract surgery), in urology and gastroenterology (e.g., kidney and gall stone ablation and fragmentation) and in cardiology and vascularmore » surgery (e.g., laser ablation and removal of fibro-fatty and calcified arterial plaque). Experimental data are presented along with some results from computer simulations of the phenomena. Comments on future directions in these areas are included. 63 refs.« less

Surgical effects on soft tissue produced by a 405-nm violet diode laser in vivo

NASA Astrophysics Data System (ADS)

Miyazaki, H.; Kato, J.; Kawai, S.; Hatayama, H.; Uchida, K.; Otsuki, M.; Tagami, J.; Yokoo, S.

2011-12-01

This study evaluated the surgical performance of a 405-nm diode laser in vivo, using living rat liver tissue. Tissue was incised by irradiation with the laser at low output power ranging from 1 W (722 W/cm2) to 3 W (2165 W/cm2) on a manual control at a rate of 1 mm/s. As a control, incisions using a stainless scalpel were compared. Immediately after operation, the surface of the incisions was macroscopically observed and histopathologically evaluated by microscopy. Laser-ablated liver tissue was smooth with observable signs of remnant carbonization and easily acquired hemostasis. The thickness of the denatured layer increased in proportion to the output power; the coagulation layer did not thicken accordingly. Bleeding could not be stopped for tissues incised with the stainless scalpel. The 405-nm diode laser thus proved to be effective for ablating soft tissue with high hemostatic ability at low power.

Effect of platelet-derived β-thromboglobulins on coagulation.

PubMed

Egan, Karl; van Geffen, Johanna P; Ma, Hui; Kevane, Barry; Lennon, Aine; Allen, Seamus; Neary, Elaine; Parsons, Martin; Maguire, Patricia; Wynne, Kieran; O' Kennedy, Richard; Heemskerk, Johan W M; Áinle, Fionnuala Ní

2017-06-01

β-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C. In contrast, the effect of βTG on coagulation is unknown. Clotting times, thrombin generation, chromogenic clotting factor assays, and surface plasmon resonance (SPR) were used to assess the effect of purified βTG on coagulation. In normal pooled plasma, βTG shortened the lagtime and time to peak thrombin generation of tissue factor (TF)-dependent and TF-independent thrombin generation. In factor VIII and factor IX-deficient plasmas, βTG induced thrombin generation in the absence of a TF stimulus and in the presence of anti-TF and factor VIIa inhibitory antibodies. The procoagulant effect was not observed when thrombin generation was independent of factor X activation (supplementation of factor X-deficient plasma with factor Xa). Cleavage of a factor Xa-specific chromogenic substrate was observed when βTG was incubated with factor X, suggesting a direct interaction between βTG and factor X. Using SPR, βTG were found to bind to immobilised factor X in a dose dependent manner. βTG modulate coagulation in vitro via an interaction with factor X. Copyright © 2017 Elsevier Ltd. All rights reserved.

First collaborative experience with thulium laser ablation of localized upper urinary tract urothelial tumors using retrograde intra-renal surgery.

PubMed

Defidio, Lorenzo; De Dominicis, Mauro; Di Gianfrancesco, Luca; Fuchs, Gerhard; Patel, Anup

2011-09-01

Thulium laser ablation (TLA) outcomes with blinded performance evaluation after retrograde intra-renal surgical (RIRS) treatment of upper urinary tract transitional cell carcinomas (UUT-TCC). A UUT-TCC patient cohort undergoing RIRS-TLA by an international endoscopic surgical collaboration in a European center (April 2005-July 2009), underwent outcomes evaluation. All 4 surgeons were blinded and independently scored both TLA and Holmium:YAG laser ablation performance aspects annually using a Likert scoring system (0-10). All patients (n = 59, median age 66 years, 9 with solitary kidney) had complete UUT inspection. Presenting lesion(s) were intra-renal (n = 30, 51%), ureteral (n = 13, 22%), and combined (n = 16, 27%). Single-stage TLA sufficed in 81.4% (tumors < 1.5 cm). Significant recurrence free survival differences occurred according to primary tumor size >/< 1.5 cm and multi-focality, but location made no difference. Median Likert scores were i) fiber-tip stability --5.5/8.75, p = 0.016; ii) reduced bleeding--5/8.5, p = 0.004; iii)fiber-tip precision--5.5/8.5, p = 0.003; iv) mucosal perforation reduction--3.5/7.5, p = 0.001; v) ablation efficiency tumors < 1.5 cm--6/9, p = 0.017; tumors > 1.5 cm--6.75/6.75, p = 1, and vi) overall efficiency--6/7.5, p = 0.09, for Holmium:YAG and TLA, respectively. The Thulium laser delivered non-inferior recurrence free survival to RIRS-UUT-TCC Holmium:YAG laser ablation, but better median parameter performance scores in fiber-tip stability, precision, reduced bleeding and mucosal perforation reduction in expert ratings. Despite improved photothermal coagulation, and endo-visualization for tumors < 1.5 cm, both ablation and overall efficiency remained challenging for larger tumors with both existing laser technologies.

Analysis of aggregation of platelets in thrombosis

NASA Astrophysics Data System (ADS)

Ahuja, Suresh

Platelets are key players in thrombus formation by first rolling over collagen bound von Willebrand factor followed by formation of a stable interaction with collagen. The first adhered platelets bind additional platelets until the whole injury is sealed off by a platelet aggregate. The coagulation system stabilizes the formed platelet plug by creating a tight fibrin network, and then wound contraction takes place because of morphological changes in platelets. Coagulation takes place by platelet activation and aggregation mainly through fibrinogen polymerization into fibrin fibers. The process includes multiple factors, such as thrombin, plasmin, and local shear-rate which regulate and control the process. Coagulation can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by the exposure of a negatively charged. It is able to activate factor XII, using a complex reaction that includes prekallikrein and high-molecular-weight kininogen as cofactors.. Thrombin is the final enzyme that is needed to convert fibrinogen into fibrin. The extrinsic pathway starts with the exposure of tissue factor to the circulating blood, which is the major initiator of coagulation. There are several feedback loops that reinforce the coagulation cascade, resulting in large amounts of thrombin. It is dependent on the presence of pro-coagulant surfaces of cells expressing negatively charged phospholipids--which include phosphatidylserine (PS)--on their outer membrane. PS-bearing surfaces are able to increase the efficiency of the reactions by concentrating and co-localizing coagulation factors.. Aggregation of platelets are analyzed and compared to adhesion of platelet to erythrocyte and to endothelial cells. This abstract is replacing MAR16-2015-020003.

Monitoring and treatment of coagulation abnormalities in burn patients. an international survey on current practices

PubMed Central

Lavrentieva, A.; Depetris, N.; Kaimakamis, E.; Berardino, M.; Stella, M.

2016-01-01

Summary The magnitude of coagulation abnormalities, and the definition and treatment of coagulopathy in burn patients are inadequately understood and continue to be discussed in the literature. We aimed to analyse physicians’ views on monitoring and treating coagulation abnormalities in burn patients. A total of 350 questionnaires were distributed electronically to burn ICU physicians. Participation was voluntary and anonymous. Responses were analysed electronically and comparisons were made according to the region of the ICU or the specialty of the physician. Of the 350 questionnaires distributed, 55 (15.7%) were returned. The majority of burn specialists consider sepsis-induced coagulopathy to be the most frequent coagulopathy in burn patients, and 74.5% declare that they do not use any specific definition/scoring system in their department to detect coagulopathy. The majority of specialists (70.8%) use standard coagulation tests. The most frequent indications for plasma transfusion are massive bleeding (32.8%) and Disseminated Intravascular Coagulation syndrome treatment (20%). The main specific factors reported in our study are cryoprecipitate (23.2%) and fibrinogen concentrate (18.9%). 21.1% of respondents state that they do not use any specific coagulation factor substitution in burn patients. Specific coagulation factor substitution is not a routine practice. The low response rate precludes the generalization of our results. PMID:28149244

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry

PubMed Central

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Background: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. Objective: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Methods: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. Results: The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Conclusions: Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group. PMID:27858671

Optimization of Lyophilized Plasma for Use in Combat Casualties

DTIC Science & Technology

2013-01-21

SD. (Fib: fibrinogen, FII: Factor II, FV: Factor V, FVII : Factor VII, FVIII: Factor VIII, FIX: Factor IX, FX: Factor X, FXI: Factor XI, FXII...coagulation factor activity. Twenty swine were anesthetized and subjected to a validated model of polytrauma and hemorrhagic shock. They were...to assess inflammatory markers. Major Findings: 50%LP had higher electrolyte concentrations, osmolarity, and increased coagulation factor activity

The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

PubMed Central

Nickel, Katrin F.; Ronquist, Göran; Langer, Florian; Labberton, Linda; Fuchs, Tobias A.; Bokemeyer, Carsten; Sauter, Guido; Graefen, Markus; Mackman, Nigel; Stavrou, Evi X.; Ronquist, Gunnar

2015-01-01

Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies. PMID:26153520

Tm:fiber laser ablation with real-time temperature monitoring for minimizing collateral thermal damage: ex vivo dosimetry for ovine brain.

PubMed

Tunc, Burcu; Gulsoy, Murat

2013-01-01

The thermal damage of the surrounding tissue can be an unwanted result of continuous-wave laser irradiations. In order to propose an effective alternative to conventional surgical techniques, photothermal damage must be taken under control by a detailed dose study. Real-time temperature monitoring can be also an effective way to get rid of these negative effects. The aim of the present study is to investigate the potential of a new laser-thermoprobe, which consists of a continuous-wave 1,940-nm Tm:fiber laser and a thermocouple measurement system for brain surgery in an ex vivo study. A laser-thermoprobe was designed for using the near-by tissue temperature as a real-time reference for the applicator. Fresh lamb brain tissues were used for experiments. 320 laser shots were performed on both cortical and subcortical tissue. The relationship between laser parameters, temperature changes, and ablation (removal of tissue) efficiency was determined. The correlation between rate of temperature change and ablation efficiency was calculated. Laser-thermoprobe leads us to understand the basic laser-tissue interaction mechanism in a very cheap and easy way, without making a change in the experimental design. It was also shown that the ablation and coagulation (thermally irreversible damage) diameters could be predicted, and carbonization can be avoided by temperature monitoring. Copyright © 2013 Wiley Periodicals, Inc.

Versatility of erbium YAG laser: from fractional skin rejuvenation to full-field skin resurfacing.

PubMed

Holcomb, J David

2011-05-01

For the laser surgeon, the Er-YAG laser is an invaluable tool that delivers unsurpassed ablation efficiency, and with appropriate functionality (quasi long-pulse feature) provides sufficient tissue coagulation to remodel deep rhytids. As such, the 2940-nm wavelength is well suited for routine laser skin rejuvenation in full-field, fractional, and point-beam modes with additional benefits, including applicability to diverse skin types, short healing times, and a low likelihood of energy-related complications. Copyright © 2011 Elsevier Inc. All rights reserved.

In Vitro Assessment of Nanoparticle Effects on Blood Coagulation.

PubMed

Potter, Timothy M; Rodriguez, Jamie C; Neun, Barry W; Ilinskaya, Anna N; Cedrone, Edward; Dobrovolskaia, Marina A

2018-01-01

Blood clotting is a complex process which involves both cellular and biochemical components. The key cellular players in the blood clotting process are thrombocytes or platelets. Other cells, including leukocytes and endothelial cells, contribute to clotting by expressing the so-called pro-coagulant activity (PCA) complex on their surface. The biochemical component of blood clotting is represented by the plasma coagulation cascade, which includes plasma proteins also known as coagulation factors. The coordinated interaction between platelets, leukocytes, endothelial cells, and plasma coagulation factors is necessary for maintaining hemostasis and for preventing excessive bleeding. Undesirable activation of all or some of these components may lead to pathological blood coagulation and life-threatening conditions such as consumptive coagulopathy or disseminated intravascular coagulation (DIC). In contrast, unintended inhibition of the coagulation pathways may lead to hemorrhage. Thrombogenicity is the property of a test material to induce blood coagulation by affecting one or more elements of the clotting process. Anticoagulant activity refers to the property of a test material to inhibit coagulation. The tendency to cause platelet aggregation, perturb plasma coagulation, and induce leukocyte PCA can serve as an in vitro measure of a nanomaterial's likelihood to be pro- or anticoagulant in vivo. This chapter describes three procedures for in vitro analyses of platelet aggregation, plasma coagulation time, and activation of leukocyte PCA. Platelet aggregation and plasma coagulation procedures have been described earlier. The revision here includes updated details about nanoparticle sample preparation, selection of nanoparticle concentration for the in vitro study, and updated details about assay controls. The chapter is expanded to describe a method for the leukocyte PCA analysis and case studies demonstrating the performance of these in vitro assays.

The effect of CO2 laser treatment on skin tissue.

PubMed

Baleg, Sana Mohammed Anayb; Bidin, Noriah; Suan, Lau Pik; Ahmad, Muhammad Fakarruddin Sidi; Krishnan, Ganesan; Johari, Abd Rahman; Hamid, Asma

2015-09-01

The aim of this study was to evaluate the effects of multiple pulses on the depth of injury caused by CO2 laser in an in vivo rat model. A 10 600-nm CO2 laser was applied to rat skin, with one side of the rat dorsal skin being exposed, leaving the other side as a control. All of the various laser pulses tested led to gradual loss of epidermal thickness as well as a dramatic increase in thermal damage depth. Collagen coagulation was most effective with ten pulses of CO2 laser, while the strength of irradiated skin tissue increased as the influence of the laser increased. Fundamental laser-skin interaction effects were studied using a CO2 laser. The photodamaged areas obtained from laser interaction were recorded via couple charge device video camera and analyzed via ImageJ software. Photodamage induced by CO2 laser is due to photothermal effects, which involve burning and vaporizing mechanisms to ablate the epidermis layer. The burning area literally expands and penetrates deep into the dermis layer, subsequently causing collagen coagulation. This fundamental study shows in detail the effect of CO2 laser interaction with skin. The CO2 attributed severe burning, producing deep coagulation, and induced strength to treated skin. © 2015 Wiley Periodicals, Inc.

Reduced plasma levels of coagulation factors in relation to prostate cancer.

PubMed

Beecken, Wolf-Dietrich; Bentas, Wassilios; Engels, Knut; Glienke, Wolfgang; Urbschat, Anja; Jonas, Dietger; Binder, Jochen; Scharrer, Inge

2002-10-01

Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Copyright 2002 Wiley-Liss, Inc.

Normal Hemostatic Profiles and Coagulation Factors in Healthy Free-Living Florida Manatees ( Trichechus manatus latirostris).

PubMed

Barratclough, Ashley; Floyd, Ruth Francis; Conner, Bobbi; Reep, Roger; Ball, Ray; Stacy, Nicole

2016-10-01

Hemostatic disorders presumptively play an important role in the pathophysiology of several important disease conditions in the Florida manatee ( Trichechus manatus latirostris). Prior to pursuing such clinical implications, it is essential to establish normal hemostatic profiles in clinically healthy animals. During annual health assessments of free-living manatees organized by the US Geological Survey, blood samples were collected from 12 healthy animals from the Atlantic coast and 28 from the Gulf of Mexico coast of Florida, with body lengths of 210-324 cm. The following analyses were performed on citrated plasma: prothrombin (PT), partial thromboplastin time (PTT), and concentrations of fibrinogen, D-dimers, and coagulation factors VII, VIII, IX, X, XI, and XII. Compared to other mammalian species, manatees had short PT (9.2±1.5 s) and PTT (10.7±0.5 s), fibrinogen was 369±78.7 mg/dL, antithrombin III was 132±11%, and D-dimer was 142±122 ng/mL. Baseline concentrations for the listed coagulation factors were established. When comparing coagulation factors between locations, Atlantic coast manatees had significantly higher factors VIII, IX, and X than did Gulf Coast manatees. This finding may reflect differences in water salinity, diet, or genetics. There were no differences in coagulation factors when among sexes and sizes. These baselines for hemostatic profiles and coagulation factors in healthy free-living manatees lay the foundation for diagnosis and future research of hemostatic disorders and contribute to understanding their role in the pathophysiology of manatees affected by various diseases.

Current oncologic applications of radiofrequency ablation therapies

PubMed Central

Shah, Dhruvil R; Green, Sari; Elliot, Angelina; McGahan, John P; Khatri, Vijay P

2013-01-01

Radiofrequency ablation (RFA) uses high frequency alternating current to heat a volume of tissue around a needle electrode to induce focal coagulative necrosis with minimal injury to surrounding tissues. RFA can be performed via an open, laparoscopic, or image guided percutaneous approach and be performed under general or local anesthesia. Advances in delivery mechanisms, electrode designs, and higher power generators have increased the maximum volume that can be ablated, while maximizing oncological outcomes. In general, RFA is used to control local tumor growth, prevent recurrence, palliate symptoms, and improve survival in a subset of patients that are not candidates for surgical resection. It’s equivalence to surgical resection has yet to be proven in large randomized control trials. Currently, the use of RFA has been well described as a primary or adjuvant treatment modality of limited but unresectable hepatocellular carcinoma, liver metastasis, especially colorectal cancer metastases, primary lung tumors, renal cell carcinoma, boney metastasis and osteoid osteomas. The role of RFA in the primary treatment of early stage breast cancer is still evolving. This review will discuss the general features of RFA and outline its role in commonly encountered solid tumors. PMID:23671734

Combination of high-intensity focused ultrasound irradiation and hydroxyapatite nanoparticle injection to injure normal goat liver tissue in vivo without costal bone incision.

PubMed

Liu, L; Xiao, Z; Xiao, Y; Wang, Z; Li, F; Li, M; Peng, X

2014-10-20

The aims of this study were to evaluate the in vivo safety of intravenous nano-hydroxyapatite (nano-HA), to explore how nano-HA might influence the effects of high-intensity focused ultrasound (HIFU) on normal liver tissue, and to investigate whether intravenous nano-HA could enhance HIFU for hepatocellular carcinoma ablation in a goat model. The present study, for the first time, indicated that the delivery of abundant nano-HA into the body over short periods of time could be assembled by the hepatic reticuloendothelial system, subsequently leading to a rapid rise of ultrasound-induced overheating, and ultimately resulting in enlargement of the coagulation necrotic area for ablated hepatocellular carcinoma in goats both in vivo and ex vivo. On the other hand, therapeutic doses of nano-HA were much lower than the lethal dose, and consequently presented transient and mild abnormalities of hepatic enzymes and renal function during the first 24 h after nano-HA injection. These results suggested that the combined application of nano-HA and HIFU is potentially a more effective alternative option compared to surgery for hepatocellular carcinoma local ablation in a safe and feasible manner.

Endoscopic management of chronic radiation proctitis

PubMed Central

Rustagi, Tarun; Mashimo, Hiroshi

2011-01-01

Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications. This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis. PMID:22147960

Endoscopic management of chronic radiation proctitis.

PubMed

Rustagi, Tarun; Mashimo, Hiroshi

2011-11-07

Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications. This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis.

Pathological effects of lung radiofrequency ablation that contribute to pneumothorax, using a porcine model.

PubMed

Izaaryene, Jean; Cohen, Frederic; Souteyrand, Philippe; Rolland, Pierre-Henri; Vidal, Vincent; Bartoli, Jean-Michel; Secq, Veronique; Gaubert, Jean-Yves

2017-11-01

The incidence of pneumothorax is 7 times higher after lung radiofrequency ablation (RFA) than after lung biopsy. The reasons for such a difference have never been objectified. The histopathologic changes in lung tissue are well-studied and established for RF in the ablation zone. However, it has not been previously described what the nature of thermal injury might be along the shaft of the RF electrode as it traverses through normal lung tissue to reach the ablation zone. The purpose of this study was to determine the changes occurring around the RF needle along the pathway between the ablated zone and the pleura. In 3 anaesthetised and ventilated swine, 6 RFA procedures (right and left lungs) were performed using a 14-gauge unipolar multi-tined retractable 3 cm radiofrequency LeVeen probe with a coaxial introducer positioned under CT fluoroscopic guidance. In compliance with literature guidelines, we implemented a gradually increasing thermo-ablation protocol using a RF generator. Helical CT images were acquired pre- and post-RFA procedure to detect and evaluate pneumothorax. Four percutaneous 19-gauge lung biopsies were also performed on the fourth swine under CT guidance. Swine were sacrificed for lung ex vivo examinations, scanning electron microscopy (SEM) and pathological analysis. Three severe (over 50 ml) pneumothorax were detected after RFA. In each one of them, pathological examination revealed a fistulous tract between ablation zone and pleura. No fistulous tract was observed after biopsies. In the 3 cases of severe pneumothorax, the tract was wide open and clearly visible on post procedure CT images and SEM examinations. The RFA tract differed from the needle biopsy tract. The histological changes that are usually found in the ablated zone were observed in the RFA tract's wall and were related to thermal lesions. These modifications caused the creation of a coagulated pulmonary parenchyma rim between the thermo-ablation zone and the pleural space. The structural properties of the damage can explain why the RFA tract is remains patent after needle withdrawal. Our study demonstrates for the first time that the changes around the RF needle are the same as in the ablated zone. The damage could create fistulous tracts along the needle path between thermo-ablation zone and pleural space. These fistulas could certainly be responsible for severe pneumothorax that occurs in many patients treated with lung RFA.

Photoactive dye-enhanced tissue ablation for endoscopic laser prostatectomy.

PubMed

Ahn, Minwoo; Hau, Nguyen Trung; Van Phuc, Nguyen; Oh, Junghwan; Kang, Hyun Wook

2014-11-01

Laser light has been widely used as a surgical tool to treat benign prostate hyperplasia (BPH) over 20 years. Recently, application of high laser power up to 200 W was often reported to swiftly remove a large amount of prostatic tissue. The purpose of this study was to validate the feasibility of photoactive dye injection to enhance light absorption and eventually to facilitate tissue vaporization with low laser power. Chicken breast tissue was selected as a target tissue due to minimal optical absorption at the visible wavelength. Four biocompatible photoactive dyes, including amaranth (AR), black dye (BD), hemoglobin powder (HP), and endoscopic marker (EM), were selected and tested in vitro with a customized 532 nm laser system with radiant exposure ranging from 0.9 to 3.9 J/cm(2) . Light absorbance and ablation threshold were measured with UV-Vis spectrometer and Probit analysis, respectively, and compared to feature the function of the injected dyes. Ablation performance with dye-injection was evaluated in light of radiant exposure, dye concentration, and number of injection. Higher light absorption by injected dyes led to lower ablation threshold as well as more efficient tissue removal in the order of AR, BD, HP, and EM. Regardless of the injected dyes, ablation efficiency principally increased with radiant exposure, dye concentration, and number of injection. Among the dyes, AR created the highest ablation rate of 44.2 ± 0.2 µm/pulse due to higher absorbance and lower ablation threshold. High aspect ratios up to 7.1 ± 0.4 entailed saturation behavior in the tissue ablation injected with AR and BD, possibly resulting from plume shielding and increased scattering due to coagulation. Preliminary tests on canine prostate with a hydraulic injection system demonstrated that 80 W with dye injection yielded comparable ablation efficiency to 120 W with no injection, indicating 33% reduced laser power with almost equivalent performance. Due to efficient coupling of optical energy, pre-injection of photoactive dyes promoted the degree of tissue removal during laser irradiation. Further studies will investigate spatial distribution of dyes and optimal injecting pressure to govern the extent of dye-assisted ablation in a predictable manner. In-depth comprehension on photoactive dye-enhanced tissue ablation can help accomplish efficient and safe laser vaporization for BPH with low power application. © 2014 Wiley Periodicals, Inc.

Comparison of functional aspects of the coagulation cascade in human and sea turtle plasmas.

PubMed

Soslau, Gerald; Wallace, Bryan; Vicente, Catherine; Goldenberg, Seth J; Tupis, Todd; Spotila, James; George, Robert; Paladino, Frank; Whitaker, Brent; Violetta, Gary; Piedra, Rotney

2004-08-01

Functional hemostatic pathways are critical for the survival of all vertebrates and have been evolving for more than 400 million years. The overwhelming majority of studies of hemostasis in vertebrates have focused on mammals with very sparse attention paid to reptiles. There have been virtually no studies of the coagulation pathway in sea turtles whose ancestors date back to the Jurassic period. Sea turtles are often exposed to rapidly altered environmental conditions during diving periods. This may reduce their blood pH during prolonged hypoxic dives. This report demonstrates that five species of turtles possess only one branch of the mammalian coagulation pathway, the extrinsic pathway. Mixing studies of turtle plasmas with human factor-deficient plasmas indicate that the intrinsic pathway factors VIII and IX are present in turtle plasma. These two factors may play a significant role in supporting the extrinsic pathway by feedback loops. The intrinsic factors, XI and XII are not detected which would account for the inability of reagents to induce coagulation via the intrinsic pathway in vitro. The analysis of two turtle factors, factor II (prothrombin) and factor X, demonstrates that they are antigenically/functionally similar to the corresponding human factors. The turtle coagulation pathway responds differentially to both pH and temperature relative to each turtle species and relative to human samples. The coagulation time (prothrombin time) increases as the temperature decreases between 37 and 15 degrees C. The increased time follows a linear relationship, with similar slopes for loggerhead, Kemps ridley and hawksbill turtles as well as for human samples. Leatherback turtle samples show a dramatic nonlinear increased time below 23 degrees C, and green turtle sample responses were similar but less dramatic. All samples also showed increased prothrombin times as the pH decreased from 7.8 to 6.4, except for three turtle species. The prothrombin times decreased, to varying extents, in a linear fashion relative to reduced pH with the rate of change greatest in leatherbacks>green>loggerhead turtles. All studies were conducted with reagents developed for human samples which would impact on the quantitative results with the turtle samples, but are not likely to alter the qualitative results. These comparative studies of the coagulation pathway in sea turtles and humans could enhance our knowledge of structure/function relationships and evolution of coagulation factors.

Percutaneous transhepatic cholangiography and intraductal radiofrequency ablation combined with biliary stent placement for malignant biliary obstruction.

PubMed

Li, Teng-Fei; Huang, Guo-Hao; Li, Zhen; Hao, Chang-Fu; Ren, Jian-Zhuang; Duan, Xu-Hua; Zhang, Kai; Chen, Chen; Han, Xin-Wei; Jiao, De-Chao; Zhang, Meng-Fan; Wang, Yan-Li

2015-05-01

To determine the safety and feasibility of percutaneous transhepatic cholangiography (PTC) and intraductal radiofrequency (RF) ablation combined with biliary stent placement for malignant biliary obstruction. Data from patients with unresectable malignant biliary obstruction who underwent PTC, intraductal RF ablation, and biliary stent placement (n = 12) or PTC and biliary stent placement only (control group; n = 14) were reviewed. Postoperative complications, jaundice remission, and stent patency were assessed. All procedures were successful. No severe complications (eg, biliary bleeding, perforation) occurred. Two experimental group patients developed cholangitis, which resolved with conservative treatment. The 1-week jaundice remission and 3-month stent patency rates were similar in both groups, but the 6-month stent patency rate was higher in the experimental group (P < .05). In the experimental group, one death occurred as a result of gastrointestinal hemorrhage (unrelated to stent placement) by 3 months, and there were two cases of recurrent jaundice by 6 months. The latter two patients underwent repeat PTC, ablation, and stent placement. In the control group, one death occurred as a result of hepatic failure caused by progressive jaundice at 3 months, and another death resulted from disseminated intravascular coagulation caused by jaundice recurrence at 138 days after stent placement. In addition, seven patients developed jaundice recurrence (50-151 d after stent placement). PTC and repeat stent placement were performed in these patients. Percutaneous transhepatic cholangiography and intraductal RF ablation combined with biliary stent placement for malignant biliary obstruction is safe and feasible and effectively prolongs stent patency time. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Injectable PLGA/Fe3O4 implants carrying cisplatin for synergistic magnetic hyperthermal ablation of rabbit VX2 tumor.

PubMed

Yang, Yang; Wang, Fengjuan; Zheng, Kaiyuan; Deng, Liming; Yang, Lu; Zhang, Nan; Xu, Chunyan; Ran, Haitao; Wang, Zhaoxia; Wang, Zhigang; Zheng, Yuanyi

2017-01-01

Magnetic hyperthermia ablation has attracted wide attention in tumor therapy for its minimal invasion. Although the chemo-hyperthermal synergism has been proven to be effective in subcutaneously xenografted tumors of nude mice in our previous experiment, the occurrence of residual tumors due to incomplete ablation is more common in relatively larger and deeper-seated tumors in anti-tumor therapy. Thus, a larger tumor and larger animal model are needed for further study of the therapeutic efficacy. In this study, we tested the efficiency of this newly developed technique using a rabbit tumor model. Furthermore, we chose cisplatin (DDP), which has been confirmed with high efficiency in enhancing hyperthermia therapy as the chemotherapeutic drug for the synergistic magnetic hyperthermal ablation therapy of tumors. In vitro studies demonstrated that developed DDP-loaded magnetic implants (DDP/PLGA-Fe3O4) have great heating efficacy and the drug release can be significantly boosted by an external alternating magnetic field (AMF). In vivo studies showed that the phase-transitional DDP/PLGA-Fe3O4 materials that are ultrasound (US) and computerized tomography (CT) visible can be well confined in the tumor tissues after injection. When exposed to AMF, efficient hyperthermia was induced, which led to the cancer cells' coagulative necrosis and accelerating release of the drug to kill residual tumors. Furthermore, an activated anti-tumor immune system can promote apoptosis of tumor cells. In conclusion, the DDP/PLGA-Fe3O4 implants can be used efficiently for the combined chemotherapy and magnetic-hyperthermia ablation of rabbit tumors.

Focal Hydrothermal Ablation: Preliminary Investigation of a New Concept

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

Roy, Sumit, E-mail: sumit.roy@online.no

2013-08-01

PurposeTo determine whether focal tissue ablation is possible with interstitial instillation of steam.MethodsFresh swine livers were used. Through a 20 gauge needle, steam was instilled every 5 s, 3 (n = 5), 6 (n = 5), 9 (n = 5), or 12 (n = 5 + 5) times in a liver lobe. The ablated zones were sectioned parallel (n = 20) or perpendicular (n = 5) to the needle track. The longitudinal long and short axis diameters, or transverse long and short axis diameters of areas with discoloration on macroscopic examination, were measured. The experiment was repeated in vivo onmore » a pig. Steam instillation was performed once every 5 s for 5 min in the liver (n = 3) and in muscle (n = 4), and temperature changes at three neighboring sites were monitored. Long and short axis diameters of the discolored areas were measured.ResultsA well-defined area of discoloration was invariably present at the site of steam instillation. The median longitudinal long axis diameter were 2.0, 2.5, 2.5, and 3.5 cm for 3, 6, 9, and 12 steam instillations in vitro, while median short axis diameters were 1.0, 1.5, 1.5, and 1.5 cm, respectively. Six attempts at ablation in vivo could be successfully completed. The long axis diameters of the ablated zones in the liver were 7.0 and 8.0 cm, while in muscle it ranged from 5.5 to 7.0 cm.ConclusionInstillation of steam in the liver in vitro and in vivo, and in muscle in vivo rapidly leads to circumscribed zones of coagulation necrosis.« less

Visualization of risk structures for interactive planning of image guided radiofrequency ablation of liver tumors

NASA Astrophysics Data System (ADS)

Rieder, Christian; Schwier, Michael; Weihusen, Andreas; Zidowitz, Stephan; Peitgen, Heinz-Otto

2009-02-01

Image guided radiofrequency ablation (RFA) is becoming a standard procedure as a minimally invasive method for tumor treatment in the clinical routine. The visualization of pathological tissue and potential risk structures like vessels or important organs gives essential support in image guided pre-interventional RFA planning. In this work our aim is to present novel visualization techniques for interactive RFA planning to support the physician with spatial information of pathological structures as well as the finding of trajectories without harming vitally important tissue. Furthermore, we illustrate three-dimensional applicator models of different manufactures combined with corresponding ablation areas in homogenous tissue, as specified by the manufacturers, to enhance the estimated amount of cell destruction caused by ablation. The visualization techniques are embedded in a workflow oriented application, designed for the use in the clinical routine. To allow a high-quality volume rendering we integrated a visualization method using the fuzzy c-means algorithm. This method automatically defines a transfer function for volume visualization of vessels without the need of a segmentation mask. However, insufficient visualization results of the displayed vessels caused by low data quality can be improved using local vessel segmentation in the vicinity of the lesion. We also provide an interactive segmentation technique of liver tumors for the volumetric measurement and for the visualization of pathological tissue combined with anatomical structures. In order to support coagulation estimation with respect to the heat-sink effect of the cooling blood flow which decreases thermal ablation, a numerical simulation of the heat distribution is provided.

Congenital combined deficiency of coagulation factors: a study of seven patients.

PubMed

Naderi, Majid; Tabibian, Shadi; Hosseini, Maryam Sadat; Alizadeh, Shaban; Hosseini, Soudabeh; Shamsizadeh, Morteza; Dorgalaleh, Akbar

2015-01-01

Combined deficiency of coagulation factors is considered as an extremely rare bleeding disorder (RBD) inherited in an autosomal recessive pattern. This disorder is more likely to occur in regions with a high rate of consanguineous marriages or in restricted communities. Sistan and Baluchistan, a province in southeast of Iran with a high rate of consanguinity, is a clear model of such regions with a very high prevalence of recessively inherited disorders. The aim of this study was to report the frequency of combined factor deficiency in this province. This descriptive study was conducted on 358 patients with RBD. Demographic information and medical history of each patient were recorded, and the patients were examined by a physician. Routine screening tests were carried out for all patients, and further coagulation tests including coagulation factor activity and antigen assays were subsequently performed for all suspected patients. Among 358 patients, four were found to be affected with combined factor (F)V and FVIII deficiency (F5F8D). In addition, one patient with combined deficiency of FVII-FXIII, one with combined FVII-FX and one with combined FVIII-FIX deficiency were identified. In Sistan and Baluchistan Province, coinheritance of recessively inherited disorders like combined coagulation factor deficiencies was surprisingly higher than expected.

[Factor XIII-guided treatment algorithm reduces blood transfusion in burn surgery].

PubMed

Carneiro, João Miguel Gonçalves Valadares de Morais; Alves, Joana; Conde, Patrícia; Xambre, Fátima; Almeida, Emanuel; Marques, Céline; Luís, Mariana; Godinho, Ana Maria Mano Garção; Fernandez-Llimos, Fernando

Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM ® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10g.dL -1 and the other blood products by routine coagulation and ROTEM ® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Factor XI and XII as antithrombotic targets.

PubMed

Müller, Felicitas; Gailani, David; Renné, Thomas

2011-09-01

Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.

Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion: A case report.

PubMed

Kim, Ji Hong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon; Shin, Yong Un

2018-04-01

Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden, painless visual loss and optic disc edema. NAION occurs mainly in the presence of cardiovascular disease and hypercoagulability, mainly in patients over 50 years of age. We experienced a case of NAION associated with central retinal vein occlusion (CRVO) in a young man with no underlying disease. A 46-year-old man was referred to our clinic following a sudden loss of vision in his right eye. The patient exhibited no underlying disease and reported no ongoing medication. Significant visual loss and visual disturbance of the right eye were observed. The pupil of the right eye was enlarged and an afferent pupillary defect was observed. On fundus examination, retinal hemorrhage was observed in the peripheral retina; macular edema was observed in optical coherence tomography analysis. However, optic disc edema was not evident. No abnormal findings were found in routine blood tests for hypercoagulability. After 3 days of steroid intravenous injection, macular edema disappeared and visual acuity was improved, but optic disc edema began to appear. One week later, optic disc edema was evident and visual acuity was significantly reduced; thus, the patient was diagnosed with NAION. In fluorescein angiography, peripheral retinal ischemia was observed, suggesting that CRVO was complicated. Blood tests, including analysis of coagulation factors, were performed again, showing that coagulation factors IX and XI were increased. Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion. Systemic steroids were administered. One month later, optic disc edema and retinal hemorrhage gradually diminished and eventually disappeared; however, visual acuity did not recover. In young patients without underlying disease, cases of NAION require careful screening for coagulation disorders. Even if there is no abnormality in the test for routine coagulation status, it may be necessary to confirm a coagulation defect through an additional coagulation factor assay.

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

Crocetti, Laura, E-mail: l.crocetti@med.unipi.it; Lencioni, Riccardo; Bozzi, Elena

The purpose of this study was to investigate the feasibility and safety of lung radiofrequency (RF) ablation by using low-perfusion-rate, expandable, multitined electrodes in an in vivo animal model. Ten New Zealand White rabbits underwent RF ablation using low-perfusion-rate, expandable, multitined electrodes (Starburst Talon; RITA Medical Systems, Mountain View, CA) and a 200-W RF generator. The electrode was positioned under fluoroscopy guidance and a single percutaneous RF ablation was performed. Saline perfusate was doped with nonionic iodinated contrast agent to render it visible on computed tomography (CT). The pump infused the saline doped with contrast agent into the lateral tinesmore » at a rate of 0.1ml/min. The planned ablation was of 3 min, with the hooks deployed to 2 cm at a target temperature of 105{sup o}C. An immediate posttreatment CT scan documented the distribution of the doped saline and the presence of immediate complications. The animals were monitored for delayed complications and sacrificed within 72 h (n = 4), 2 weeks (n = 3), or 4 weeks (n = 3). Assessment of ablation zone and adjacent structures was done at autopsy. Major complications consisted of pneumothorax requiring drainage (n = 2) and skin burn (n = 1). Immediately after the procedure the area of ablation was depicted at CT as a round, well-demarcated area, homogeneously opacified by iodinated contrast medium (mean size, 2.3 {+-} 0.8 cm). The presence of a sharply demarcated area of coagulation necrosis (mean size, 2.1 {+-} 0.4 cm) without severe damage to adjacent structures was confirmed at autopsy. In one case, euthanized at 4 weeks, in whom pneumothorax and pleural effusion were depicted, pleural fibrinous adhesions were demonstrated at autopsy. In conclusion, lung RF ablation performed in an in vivo animal model using low-perfusion-rate, expandable, multitined electrodes is feasible and safe. No severe damage to adjacent structures was demonstrated.« less

Feasibility of MRI-guided Focused Ultrasound as Organ-Sparing Treatment for Testicular Cancer

NASA Astrophysics Data System (ADS)

Staruch, Robert; Curiel, Laura; Chopra, Rajiv; Hynynen, Kullervo

2009-04-01

High cure rates for testicular cancer have prompted interest in organ-sparing surgery for patients with bilateral disease or single testis. Focused ultrasound (FUS) ablation could offer a noninvasive approach to organ-sparing surgery. The objective of this study was to determine the feasibility of using MR thermometry to guide organ-sparing focused ultrasound surgery in the testis. The testes of anesthetized rabbits were sonicated in several discrete locations using a single-element focused transducer operating at 2.787MHz. Focal heating was visualized with MR thermometry, using a measured PRF thermal coefficient of -0.0089±0.0003 ppm/° C. Sonications at 3.5-14 acoustic watts applied for 30 seconds produced maximum temperature elevations of 10-80° C, with coagulation verified by histology. Coagulation of precise volumes in the testicle is feasible with MRI-guided focused ultrasound. Variability in peak temperature for given sonication parameters suggests the need for online temperature feedback control.

Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

PubMed

Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

2012-01-01

Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

Upregulation of the Coagulation Factor VII Gene during Glucose Deprivation Is Mediated by Activating Transcription Factor 4

PubMed Central

Cronin, Katherine R.; Mangan, Thomas P.; Carew, Josephine A.

2012-01-01

Background Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Methodology/Principal Findings Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/− SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/−15% to 188+/−27% and 100+/−8.8% to 176.3+/−17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Conclusions/Significance Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress. PMID:22848420

Current status of laser applications in urology

NASA Astrophysics Data System (ADS)

Knipper, Ansgar; Thomas, Stephen; Durek, C.; Jocham, Dieter

1993-05-01

The overall development of laser use in urology is recessing. The reasons are the refinement of methods of radical surgery and the continuing development of alternative technologies involving electric current. Taking the cost factor into account, are lasers still opportune in medicine? The answer is definitely yes. Cost reduction in medical practice without quality loss is only possible with effective methods of minimally invasive surgery. Continuing investigation of cutting, welding, coagulating and ablating instruments is justified. Competition of lasers to other technologies can only be beneficial to the cause. But where are the highlights of laser applications? The unsurpassed utilization of optical properties of lasers lie in the concept of photodynamic therapies and in optical feedback mechanisms for laser applications. The combination of lasers with three dimensional visualization of the treatment area by ultrasound (TULIP-procedure for benign prostatic hyperplasia) is a novel approach in laser application. The further development of these treatment modalities will reveal the true benefit of laser technology in urological applications.

[Endothelial microparticles (EMP) in physiology and pathology].

PubMed

Sierko, Ewa; Sokół, Monika; Wojtukiewicz, Marek Z

2015-08-18

Endothelial microparticles (EMP) are released from endothelial cells (ECs) in the process of activation and/or apoptosis. They harbor adhesive molecules, enzymes, receptors and cytoplasmic structures and express a wide range of various constitutive antigens, typical for ECs, at their surface. Under physiological conditions the concentration of EMP in the blood is clinically insignificant. However, it was reported that under pathological conditions EMP concentration in the blood might slightly increase and contribute to blood coagulation, angiogenesis and inflammation. It has been shown that EMP directly and indirectly contribute to the activation of blood coagulation. Endothelial microparticles directly participate in blood coagulation through their surface tissue factor (TF) - a major initiator of blood coagulation. Furthermore, EMP exhibit procoagulant potential via expression of negatively charged phospholipids at their surface, which may promote assembly of coagulation enzymes (TF/VII, tenases and prothrombinase complexes), leading to thrombus formation. In addition, they provide a binding surface for coagulation factors: IXa, VIII, Va and IIa. Moreover, it is possible that EMP transfer TF from TF-bearing EMP to activated platelets and monocytes by binding them through adhesion molecules. Also, EMP express von Willebrand factor, which may facilitate platelet aggregation. Apart from their procoagulant properties, it was demonstrated that EMP may express adhesive molecules and metalloproteinases (MMP-2, MMP-9) at their surface and release growth factors, which may contribute to angiogenesis. Additionally, surface presence of C3 and C4 - components of the classical pathway - suggests pro-inflammatory properties of these structures. This article contains a summary of available data on the biology and pathophysiology of endothelial microparticles and their potential role in blood coagulation, angiogenesis and inflammation.

Fractional ablative and nonablative radiofrequency for skin resurfacing and rejuvenation of Thai patients.

PubMed

Thanasarnaksorn, Wilai; Siramangkhalanon, Vorapot; Duncan, Diane Irvine; Belenky, Inna

2018-04-01

Fractional radiofrequency (RF) technology is often the preferable skin resurfacing treatment, especially among Asian patients. Second generation fractional RF technology has exclusive capability to produce separate biological responses (ablation, coagulation, or a combination of both) with 3 distinguished penetration depth programs. The aim of this study was to evaluate the efficacy and safety of a fractional RF handpiece such as this, on the Thai population. Fifty-five Thai patients were treated with a fractional RF handpiece. The clinical assessment included a pain score, satisfaction survey, physician assessment, a combined patient and physician's assessment of skin condition, and clinical photographic assessments. The wound healing response was evaluated according to 5-time points: immediately after applying a pulse, post 24 hours, post 7 days, post 1 month and post 8 weeks. The obtained patient satisfaction score was "very satisfied" among 74% of the patients, post 3 sessions. Positive correlation was found between patient satisfaction and the physician's assessment. The skin condition assessment showed an increase from an average of 4.2 to 7.9. All treated symptoms improved after each treatment and the clinical outcome lasted at least up to 3-5 months. No significant adverse events were recorded. The in vivo prospective study showed a dose-related response in the deepness of the coagulation injury. In addition, there was evidence for a progressive healing process beginning shortly after exposure and completed within a week. This study clinically and histologically supports the efficacy of fractional RF handpiece in question with a high safety profile. © 2017 Wiley Periodicals, Inc.

Laser-induced thermotherapy: intra- and extralesionary recurrence after incomplete destruction of experimental liver metastasis.

PubMed

Isbert, C; Roggan, A; Ritz, J P; Müller, G; Buhr, H J; Lehmann, K S; Germer, C T

2001-11-01

The aim of this study was to determine the energy (J/mm3 tumor volume) and temperature required for a complete laser-induced thermotherapy (LITT) of experimental liver tumors, and to find out causes and areas of local recurrence followed by incomplete treatment. In VX-2 tumor-bearing rabbits LITT was performed using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (1064 nm) with a diffuser-tip applicator and a temperature feedback system. The animals were randomized into four groups (n = 20) that differed in the target temperature at the tumor border as follows: 45 degrees C, 50 degrees C, 55 degrees C and 60 degrees C. The target temperature was held for 10 min constant. Histologic examination (hematoxylin and eosin [H and E], nicotinamide adenine dinucleotide phosphate [NADPH]-dehydrogenase) was performed at 0 h, 24 h, 96 h, and 14 days after LITT. The pretreatment tumor volume of 2191 +/- 61 mm3 was the same for all groups (p > 0.05). Energy up to target temperature and total energy required, lesion size, and the rate of incomplete tumor ablation (recurrences) are listed below (ap < 0.05, Kruskal-Wallis test). Histologically, two forms of local recurrences could be differentiated intralesionary and extralesionary. To achieve complete in situ ablation under the given conditions, it is necessary to apply laser energy of 3 J/mm3 tumor volume. A minimum temperature of 60 degrees C on the tumor border presumed an application of 10 min. Recurrence was found outside the coagulation zone (extralesionary) and in high vascularized areas within the coagulation zone (intralesionary).

Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein Bim up-regulation

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

Borensztajn, Keren S.; Bijlsma, Maarten F.; Groot, Angelique P.

2007-07-15

Coagulation Factor (F)Xa is a serine protease that plays a crucial role during blood coagulation by converting prothrombin into active thrombin. Recently, however, it emerged that besides this role in coagulation, FXa induces intracellular signaling leading to different cellular effects. Here, we show that coagulation factor (F)Xa drives tumor cells of epithelial origin, but not endothelial cells or monocytes, into apoptosis, whereas it even enhances fibroblast survival. FXa signals through the protease activated receptor (PAR)-1 to activate extracellular-signal regulated kinase (ERK) 1/2 and p38. This activation is associated with phosphorylation of the transcription factor CREB, and in tumor cells withmore » up-regulation of the BH3-only pro-apoptotic protein Bim, leading to caspase-3 cleavage, the main hallmark of apoptosis. Transfection of tumor cells with dominant negative forms of CREB or siRNA for either PAR-1, Bim, ERK1 and/or p38 inhibited the pro-apoptotic effect of FXa. In fibroblasts, FXa-induced PAR-1 activation leads to down-regulation of Bim and pre-treatment with PAR-1 or Bim siRNA abolishes proliferation. We thus provide evidence that beyond its role in blood coagulation, FXa plays a key role in cellular processes in which Bim is the central player in determining cell survival.« less

Hepatic dysfunction contributes to coagulation disturbances in patients undergoing whole body hyperthermia by use of extracorporeal circulation.

PubMed

Worel, Nina; Knöbl, Paul; Karanikas, Georgios; Fuchs, Eva-Maria; Bojic, Andja; Brodowicz, Thomas; Jilma, Petra; Zielinski, Christoph C; Köstler, Wolfgang J; Locker, Gottfried J

2014-09-01

This phase I study was performed to evaluate coagulation alterations during extracorporeal circulation (ECC) induced whole body hyperthermia (WBHT) in 12 patients with advanced soft tissue sarcomas. To distinguish between effects of normothermic ECC and ECC-WBHT, blood samples were drawn at different time points: at baseline, after 30 min on normothermic ECC, at the end of the heating period, and 24 h and 7 days thereafter. Standard coagulation tests, coagulation factors, thrombelastography,platelets and reticulated platelets, liver enzymes, and scintigraphic platelet imaging were performed. Normothermic ECC resulted in coagulation alterations most likely due to systemic anticoagulation. Induction of hyperthermia caused thrombocytopenia, increased fibrin degradation products,prolonged clotting times, alteration in coagulation factors, and increased liver enzymes. The majority of these effects was most pronounced 24 h after ECC-WBHT. In addition, late liver sequestration of platelets was demonstrated in scintigraphic imaging at that time point. Temporal correlation between hemostatic alterations and elevation in liver enzymes leads to the assumption that liver impairment might play a crucial role in coagulation disturbances observed during ECC-WBHT and thereafter, thus strongly supported by liver sequestration of platelets.Therefore a close monitoring of hepatic derived coagulation alterations in patients undergoing extracorporeal whole body hypothermia is warranted.

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

PubMed

Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

2016-06-23

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

Overview of the coagulation system.

PubMed

Palta, Sanjeev; Saroa, Richa; Palta, Anshu

2014-09-01

Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms 'coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same.

Overview of the coagulation system

PubMed Central

Palta, Sanjeev; Saroa, Richa; Palta, Anshu

2014-01-01

Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms ‘coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same. PMID:25535411

Bipolar radiofrequency ablation of liver metastases during laparotomy. First clinical experiences with a new multipolar ablation concept.

PubMed

Ritz, Joerg-Peter; Lehmann, Kai S; Reissfelder, Christoph; Albrecht, Thomas; Frericks, Bernd; Zurbuchen, Urte; Buhr, Heinz J

2006-01-01

Radiofrequency ablation (RFA) is a promising method for local treatment of liver malignancies. Currently available systems for radiofrequency ablation use monopolar current, which carries the risk of uncontrolled electrical current paths, collateral damages and limited effectiveness. To overcome this problem, we used a newly developed internally cooled bipolar application system in patients with irresectable liver metastases undergoing laparotomy. The aim of this study was to clinically evaluate the safety, feasibility and effectiveness of this new system with a novel multipolar application concept. Patients with a maximum of five liver metastases having a maximum diameter of 5 cm underwent laparotomy and abdominal exploration to control resectability. In cases of irresectability, RFA with the newly developed bipolar application system was performed. Treatment was carried out under ultrasound guidance. Depending on tumour size, shape and location, up to three applicators were simultaneously inserted in or closely around the tumour, never exceeding a maximum probe distance of 3 cm. In the multipolar ablation concept, the current runs alternating between all possible pairs of consecutively activated electrodes with up to 15 possible electrode combinations. Post-operative follow-up was evaluated by CT or MRI controls 24-48 h after RFA and every 3 months. In a total of six patients (four male, two female; 61-68 years), ten metastases (1.0-5.5 cm) were treated with a total of 14 RF applications. In four metastases three probes were used, and in another four and two metastases, two and one probes were used, respectively. During a mean ablation time of 18.8 min (10-31), a mean energy of 48.8 kJ (12-116) for each metastases was applied. No procedure-related complications occurred. The patients were released from the hospital between 7 and 12 days post-intervention (median 9 days). The post-interventional control showed complete tumour ablation in all cases. Bipolar radiofrequency using the novel multipolar ablation concept permits a safe and effective therapy for the induction of large volumes of coagulation in the local treatment of liver metastases.

Tissue ablation accelerated by peripheral scanning mode with high-intensity focused ultrasound: a study on isolated porcine liver perfusion.

PubMed

Bu, Rui; Yin, Li; Yang, Han; Wang, Qi; Wu, Feng; Zou, Jian Zhong

2013-08-01

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p < 0.01). This study revealed that the complete peripheral necrosis barrier within the target tissues can defined using linear-scanned HIFU in an isolated porcine liver perfusion model. Additionally, the flow rate in the major hepatic vessels may play an important role in the use of the peripheral ablation mode, and this novel mode of ablation may enhance the therapeutic efficacy and tolerability of the treatment of large tumors using HIFU ablation. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

PubMed

Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

2018-06-01

 Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

[Influencing factors and mechanism of arsenic removal during the aluminum coagulation process].

PubMed

Chen, Gui-Xia; Hu, Cheng-Zhi; Zhu, Ling-Feng; Tong, Hua-Qing

2013-04-01

Aluminum coagulants are widely used in arsenic (As) removal during the drinking water treatment process. Aluminium chloride (AlCl3) and polyaluminium chloride (PACl) which contains high content of Al13 were used as coagulants. The effects of aluminum species, pH, humic acid (HA) and coexisting anions on arsenic removal were investigated. Results showed that AlCl3 and PACl were almost ineffective in As(II) removal while the As(V) removal efficiency reached almost 100%. pH was an important influencing factor on the arsenic removal efficiency, because pH influenced the distribution of aluminum species during the coagulation process. The efficiency of arsenic removal by aluminum coagulants was positively correlated with the content of Al13 species. HA and some coexisting anions showed negative impact on arsenic removal because of the competitive adsorption. The negative influence of HA was more pronounced at low coagulant dosages. PO4(3-) and F(-) showed marked influence during arsenic removal, but there was no obvious influence when SiO3(2-), CO3(2-) and SO4(2-) coexisted. The present study would be helpful to direct arsenic removal by enhanced coagulation during the drinking water treatment.

EXTRINSIC COAGULATION BLOCKADE ATTENUATES LUNG INJURY AND PROINFLAMMATORY CYTOKINE RELEASE AFTER INTRATRACHEAL LIPOPOLYSACCHARIDE

EPA Science Inventory

Initiation of coagulation by tissue factor (TF) is a potentially powerful regulator of local inflammatory responses. We hypothesized that blockade of TF-factor VIIa (FVIIa) complex would decrease lung inflammation and proinflammatory cytokine release after tracheal instillation o...

Effects of alum coagulation on speciation and distribution of trihalomethanes (THMs) and haloacetic acids (HAAs).

PubMed

Gang, Dianchen; Clevenger, Thomas E; Banerji, Shankha K

2005-01-01

The impacts of alum coagulation on the distribution of disinfection by-products (DBPs), trihalomethanes (THMs), and haloacetic acids (HAAs) were evaluated under controlled chlorination conditions using four surface waters. Among the nine HAAs found in waters, dihaloacetic acids (X2AAs) have been found to be the dominant species in all of the raw and alum treated waters. Alum coagulation tends to remove more monohaloacetic acids (XAAs) and trihaloacetic acids (X3AAs) precursors than that of dihaloacetic acids (X2AAs). Alum coagulation treated water had a lower HAA9/TTHM ratio compared with that of the raw water. The increase of THM bromine incorporation factors (BIFalpha) value of alum treated water was statistically significant in comparison with the raw water. On average, BIFalpha increased by 54% after the alum coagulation process in these four different waters. This indicated that THM speciations shifted in favor of the more brominated compounds. However, alum coagulation treatment process had less effect on HAA bromi ne incorporation factors (BIFbeta)than it did on BIFalpha. Bromine incorporation factor (BIF) values decreased with time in the THM and HAA formation processes, especially within the first 10 h of the reaction time. This suggested that brominated THMs or HAAs formed faster than the chlorinated species in the initial period.

HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

PubMed Central

Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

2010-01-01

Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

PubMed Central

Takahashi, Kazue; Chang, Wei-Chuan; Takahashi, Minoru; Pavlov, Vasile; Ishida, Yumi; La Bonte, Laura; Shi, Lei; Fujita, Teizo; Stahl, Gregory L.; Van Cott, Elizabeth M.

2010-01-01

The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases. PMID:20399528

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

3D Myocardial Elastography In Vivo.

PubMed

Papadacci, Clement; Bunting, Ethan A; Wan, Elaine Y; Nauleau, Pierre; Konofagou, Elisa E

2017-02-01

Strain evaluation is of major interest in clinical cardiology as it can quantify the cardiac function. Myocardial elastography, a radio-frequency (RF)-based cross-correlation method, has been developed to evaluate the local strain distribution in the heart in vivo. However, inhomogeneities such as RF ablation lesions or infarction require a three-dimensional approach to be measured accurately. In addition, acquisitions at high volume rate are essential to evaluate the cardiac strain in three dimensions. Conventional focused transmit schemes using 2D matrix arrays, trade off sufficient volume rate for beam density or sector size to image rapid moving structure such as the heart, which lowers accuracy and precision in the strain estimation. In this study, we developed 3D myocardial elastography at high volume rates using diverging wave transmits to evaluate the local axial strain distribution in three dimensions in three open-chest canines before and after radio-frequency ablation. Acquisitions were performed with a 2.5 MHz 2D matrix array fully programmable used to emit 2000 diverging waves at 2000 volumes/s. Incremental displacements and strains enabled the visualization of rapid events during the QRS complex along with the different phases of the cardiac cycle in entire volumes. Cumulative displacement and strain volumes depict high contrast between non-ablated and ablated myocardium at the lesion location, mapping the tissue coagulation. 3D myocardial strain elastography could thus become an important technique to measure the regional strain distribution in three dimensions in humans.

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

PubMed

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2015-12-01

Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time

PubMed Central

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2015-01-01

Objectives: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro. PMID:26998384

Pilot testing of dissolved air flotation (DAF) in a highly effective coagulation-flocculation integrated (FRD) system.

PubMed

Wang, Yili; Guo, Jinlong; Tang, Hongxiao

2002-01-01

Factors of pretreatment coagulation/flocculation units were studied using raw water of low temperature and low turbidity. Aluminum sulfate (AS) and selected polyaluminium chlorides (PACls) were all effective in the DAF process when used under favorable conditions of coagulant addition, coagulation, flocculation and flotation units. Compared with the AS coagulant, PACls, at lower dosage, could give the same effective performance even with shorter coagulation/flocculation time or lower recycle ratio during the treatment of cold water. This is attributed to the higher-charged polymeric Al species, and the lower hydrophilic and more compact flocculated flocs of PACl coagulant. Based on results of pilot experiments, the goal of FRD system can be achieved by combining a DAF heterocoagulation reactor with PACl coagulant (F), an efficient flocculation reactor (R), as well as an economical auto-dosing system (D).

Histological evaluation of vertical laser channels from ablative fractional resurfacing: an ex vivo pig skin model.

PubMed

Skovbølling Haak, Christina; Illes, Monica; Paasch, Uwe; Hædersdal, Merete

2011-07-01

Ablative fractional resurfacing (AFR) represents a new treatment potential for various skin conditions and new laser devices are being introduced. It is important to gain information about the impact of laser settings on the dimensions of the created laser channels for obtaining a safe and efficient treatment outcome. The aim of this study was to establish a standard model to document the histological tissue damage profiles after AFR and to test a new laser device at diverse settings. Ex vivo abdominal pig skin was treated with a MedArt 620, prototype fractional carbon dioxide (CO(2)) laser (Medart, Hvidovre, Denmark) delivering single microbeams (MB) with a spot size of 165 μm. By using a constant pulse duration of 2 ms, intensities of 1-18 W, single and 2-4 stacked pulses, energies were delivered in a range from 2-144 mJ/MB. Histological evaluations included 3-4 high-quality histological measurements for each laser setting (n = 28). AFR created cone-shaped laser channels. Ablation depths varied from reaching the superficial dermis (2 mJ, median 41 μm) to approaching the subcutaneous fat (144 mJ, median 1,943 μm) and correlated to the applied energy levels in an approximate linear relation (r(2) = 0.84, p < 0.001). The dermal ablation width increased slightly within the energy range of 4-144 mJ (median 163 μm). The thickness of the coagulation zone reached a plateau around 65 μm at energies levels above 16 mJ. The calculated volumes of ablated tissue increased with increasing energies. We suggest this ex vivo pig skin model to characterize AFR laser channels histologically.

MR-guided focused ultrasound: a potentially disruptive technology.

PubMed

Bradley, William G

2009-07-01

A disruptive technology is a technological innovation that overturns the existing dominant technologies in a market. Magnetic resonance (MR)-guided focused ultrasound (MRgFUS) is a noninvasive procedure based on the combination of real-time MR anatomic guidance, MR thermometry, and high-intensity focused ultrasound. Several hundred transducer elements become convergent at a point under MR guidance, leading to heating and coagulation necrosis. Outside the focal point, there is no significant heating. There is no need to break the skin for procedures in the body or to perform a craniotomy for procedures in the brain. This lack of invasiveness is what makes MRgFUS so disruptive compared with surgery. At present, MRgFUS has been used for the ablation of uterine fibroids, breast tumors, painful bony metastases, and liver tumors. In the brain, it has been used for the ablation of glioblastomas and for functional neurosurgery. Phantom and animal studies suggest future applications for prostate cancer and acute stroke treatment.

Ablation of dermal and mucosal lesions with a new CO2 laser application system

NASA Astrophysics Data System (ADS)

Jovanovic, Sergije; Sedlmaier, Benedikt W.; Fuehrer, Ariane

1997-05-01

Laser treatment of skin changes has become common practice in recent years. The high absorption of the wavelength of the carbon-dioxide laser (10600 nm) is responsible for its low penetration depth in biological tissue. Shortening the exposure time minimizes thermic side effects such as carbonization and coagulation. This effect can be achieved with the SilkTouchTM scanner 767, since the focused laser beam is moved over a defined area by rapidly rotating mirrors. This enables controlled and reliable removal of certain dermal lesions, particularly hypertrophic scars, scars after common acne, wrinkles, rhinophyma and benign neoplasms like verruca vulgaris. Cosmetically favorable reepithelialization of the lasered surfaces results within a very short period of time. Benign mucosal changes of the upper aerodigestive tract can also be treated. Ablation is less traumatic for papillomas, fibromas, hyperplasias in the area of Waldeyer's tonsillar ring and certain laryngotracheal pathologies. Clinical examples demonstrate the advantages of this new mode of application.

Diagnosis and treatment of superficial esophageal cancer.

PubMed

Barret, Maximilien; Prat, Frédéric

2018-01-01

Endoscopy allows for the screening, early diagnosis, treatment and follow up of superficial esophageal cancer. Endoscopic submucosal dissection has become the gold standard for the resection of superficial squamous cell neoplasia. Combinations of endoscopic mucosal resection and radiofrequency ablation are the mainstay of the management of Barrett's associated neoplasia. However, protruded, non-lifting or large lesions may be better managed by endoscopic submucosal dissection. Novel ablation tools, such as argon plasma coagulation with submucosal lifting and cryoablation balloons, are being developed for the treatment of residual Barrett's esophagus, since iatrogenic strictures still hamper the development of extensive circumferential resections in the esophagus. Optimal surveillance modalities after endoscopic resection are still to be determined. The assessment of the risk of lymph-node metastases, as well as of the need for additional treatments based on qualitative and quantitative histological criteria, balanced to the patient's condition, requires a dedicated multidisciplinary team decision process. The need for trained endoscopists, expert pathologists and surgeons, and specialized multidisciplinary meetings underlines the role of expert centers in the management of superficial esophageal cancer.

Porcine intact and wounded skin responses to atmospheric nonthermal plasma.

PubMed

Wu, Andrew S; Kalghatgi, Sameer; Dobrynin, Danil; Sensenig, Rachel; Cerchar, Ekaternia; Podolsky, Erica; Dulaimi, Essel; Paff, Michelle; Wasko, Kimberly; Arjunan, Krishna Priya; Garcia, Kristin; Fridman, Gregory; Balasubramanian, Manjula; Ownbey, Robert; Barbee, Kenneth A; Fridman, Alexander; Friedman, Gary; Joshi, Suresh G; Brooks, Ari D

2013-01-01

Thermal plasma is a valued tool in surgery for its coagulative and ablative properties. We suggested through in vitro studies that nonthermal plasma can sterilize tissues, inactive pathogens, promote coagulation, and potentiate wound healing. The present research was undertaken to study acute toxicity in porcine skin tissues. We demonstrate that floating electrode-discharge barrier discharge (FE-DBD) nonthermal plasma is electrically safe to apply to living organisms for short periods. We investigated the effects of FE-DBD plasma on Yorkshire pigs on intact and wounded skin immediately after treatment or 24h posttreatment. Macroscopic or microscopic histological changes were identified using histological and immunohistochemical techniques. The changes were classified into four groups for intact skin: normal features, minimal changes or congestive changes, epidermal layer damage, and full burn and into three groups for wounded skin: normal, clot or scab, and full burn-like features. Immunohistochemical staining for laminin layer integrity showed compromise over time. A marker for double-stranded DNA breaks, γ-H2AX, increased over plasma-exposure time. These findings identified a threshold for plasma exposure of up to 900s at low power and <120s at high power. Nonthermal FE-DBD plasma can be considered safe for future studies of external use under these threshold conditions for evaluation of sterilization, coagulation, and wound healing. Copyright © 2013 Elsevier Inc. All rights reserved.

The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

PubMed Central

Wheeler, Allison P.; Gailani, David

2016-01-01

Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI and IX – the classical intrinsic pathway of coagulation. It is well recognized that this series of proteolytic reactions is not an accurate model for hemostasis in vivo, as factor XII deficiency does not cause abnormal bleeding, and fXI deficiency causes a relatively mild propensity to bleed excessively with injury. Despite their limited roles in hemostasis, there is mounting evidence that fXI and fXII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a relatively small effect on hemostasis. In this chapter the contributions of components of the intrinsic pathway to thrombosis in animal models and humans are discussed, and results of early clinical trials of drugs targeting factors IX, XI and XII are presented. PMID:27637310

Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

PubMed

Shustova, Olga N; Antonova, Olga A; Golubeva, Nina V; Khaspekova, Svetlana G; Yakushkin, Vladimir V; Aksuk, Svetlana A; Alchinova, Irina B; Karganov, Mikhail Y; Mazurov, Alexey V

2017-07-01

: Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

PubMed

Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

2009-11-14

To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (P<0.05) during the regeneration phase compared with D0. Among these 5 factors, factor IX and factor XI showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in plasma activity for both factors were consistent with our RT-PCR findings. In contrast, the plasma activities of the other coagulation factors (fibrinogen, factors V, VII, XIII, and VWF) were not significantly reduced, despite the reduction in the liver mRNA levels. Unlike the other factors, FX showed a temporal increase in its plasma activity, with significant increases (P<0.05) detected at D1. Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions.

Nakagami-m parametric imaging for characterization of thermal coagulation and cavitation erosion induced by HIFU.

PubMed

Han, Meng; Wang, Na; Guo, Shifang; Chang, Nan; Lu, Shukuan; Wan, Mingxi

2018-07-01

Nowadays, both thermal and mechanical ablation techniques of HIFU associated with cavitation have been developed for noninvasive treatment. A specific challenge for the successful clinical implementation of HIFU is to achieve real-time imaging for the evaluation and determination of therapy outcomes such as necrosis or homogenization. Ultrasound Nakagami-m parametric imaging highlights the degrading shadowing effects of bubbles and can be used for tissue characterization. The aim of this study is to investigate the performance of Nakagami-m parametric imaging for evaluating and differentiating thermal coagulation and cavitation erosion induced by HIFU. Lesions were induced in basic bovine serum albumin (BSA) phantoms and ex vivo porcine livers using a 1.6 MHz single-element transducer. Thermal and mechanical lesions induced by two types of HIFU sequences respectively were evaluated using Nakagami-m parametric imaging and ultrasound B-mode imaging. The lesion sizes estimated using Nakagami-m parametric imaging technique were all closer to the actual sizes than those of B-mode imaging. The p-value obtained from the t-test between the mean m values of thermal coagulation and cavitation erosion was smaller than 0.05, demonstrating that the m values of thermal lesions were significantly different from that of mechanical lesions, which was confirmed by ex vivo experiments and histologic examination showed that different changes result from HIFU exposure, one of tissue dehydration resulting from the thermal effect, and the other of tissue homogenate resulting from mechanical effect. This study demonstrated that Nakagami-m parametric imaging is a potential real-time imaging technique for evaluating and differentiating thermal coagulation and cavitation erosion. Copyright © 2018 Elsevier B.V. All rights reserved.

Fire and ice: percutaneous ablative therapies and cement injection in management of metastatic disease of the spine.

PubMed

Munk, Peter L; Murphy, Kieran J; Gangi, Afshin; Liu, David M

2011-04-01

Oncology intervention is actively moving beyond simple bone cement injection. Archimedes taught us that a volume displaces its volume. Where does the tumor we displace with our cement injection go? It is no longer acceptable that we displace tumor into the venous system with our cement injections. We must kill the tumor first. Different image-guided percutaneous techniques can be used for treatment in patients with primary or secondary bone tumors. Curative ablation can be applied for the treatment of specific benign or in selected cases of malignant localized spinal tumors. Pain palliation therapy of primary and secondary bone tumors can be achieved with safe, fast, effective, and tolerable percutaneous methods. Ablation (chemical, thermal, mechanical), cavitation (radiofrequency ionization), and consolidation (cementoplasty) techniques can be used separately or in combination. Each technique has its indications, with both advantages and drawbacks. To prevent pathological fractures, a consolidation is necessary. In spinal or acetabular tumors, a percutaneous cementoplasty should be associated with cryoablation to avoid a compression fracture. The cement is injected after complete thawing of the ice ball or the day after the cryotherapy. A syndrome of multiorgan failure, severe coagulopathy, and disseminated intravascular coagulation following hepatic cryoablation has been described and is referred to as the cryoshock phenomenon. © Thieme Medical Publishers.

A successful treatment for hepatocellular carcinoma with Osler-Rendu-Weber disease using radiofrequency ablation under laparoscopy.

PubMed

Takaoka, Yoshinari; Morimoto, Naoki; Miura, Kouichi; Nomoto, Hiroaki; Murayama, Kozue; Hirosawa, Takuya; Watanabe, Shunji; Fujieda, Takeshi; Ttsukui, Mamiko; Kawata, Hirotoshi; Niki, Toshiro; Isoda, Norio; Iijima, Makoto; Yamamoto, Hironori

2018-06-16

Hepatocellular carcinoma (HCC) can be difficult to diagnose and treat in patients with Osler-Rendu-Weber disease due to vascular malformation and regenerative nodular hyperplasia. In addition, percutaneous liver puncture should be avoided for the diagnosis and treatment as the procedure carries a high risk of bleeding. We herein report the successful treatment of HCC in a patient with Osler-Rendu-Weber disease using radiofrequency ablation (RFA) under laparoscopy. A 71-year-old man with Osler-Rendu-Weber disease was admitted to our hospital for the treatment of HCC. He also had chronic hepatitis C virus infection. The arterioportal shunts in the liver were detected by computed tomography (CT) and angiography. A tumor 20 mm in size was detected as a defected-lesion in the hepatic segment IV during the portal phase by CT. RFA under laparoscopy was performed for the curative treatment for HCC, with sufficient ablation obtained. Although the blood gushed out from the needle tract at the end of the procedure, complete hemostasis was achieved promptly using coagulation forceps. The post-operative course was favorable. Thus, laparoscopic RFA is a useful treatment modality for HCC in patients with Osler-Rendu-Weber disease, as a hemostasis device can be used with direct visualization.

An exploratory factor analysis of inflammatory and coagulation markers associated with femoral artery atherosclerosis in the San Diego Population Study.

PubMed

Egnot, Natalie Suder; Barinas-Mitchell, Emma; Criqui, Michael H; Allison, Matthew A; Ix, Joachim H; Jenny, Nancy S; Wassel, Christina L

2018-04-01

Several biomarkers of inflammation and coagulation have been implicated in lower extremity atherosclerosis. We utilized an exploratory factor analysis (EFA) to identify distinct factors derived from circulating inflammatory and coagulation biomarkers then examined the associations of these factors with measures of lower extremity subclinical atherosclerosis, including the ankle-brachial index (ABI), common and superficial femoral intima-media thickness (IMT), and atherosclerotic plaque presence, burden, and characteristics. The San Diego Population Study (SDPS) is a prospective, community-living, multi-ethnic cohort of 1103 men and women averaged age 70. Regression analysis was used to assess cross-sectional associations between the identified groupings of biomarkers (factors) and the ABI and femoral artery atherosclerosis measurements. Two biomarker factors emerged from the factor analysis. Factor 1 consisting of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen was significantly associated with higher odds (OR = 1.99, p < 0.01) of a borderline ABI value (0.91-0.99), while Factor 2 containing D-dimer and pentraxin (PTX)-3 was significantly associated with higher common femoral artery (CFA) IMT (β = 0.23, p < 0.01) and lower ABI (β = -0.03, p < 0.01). Two groupings of biomarkers were identified via EFA of seven circulating biomarkers of inflammation and coagulation. These distinct groups are differentially associated with markers of lower extremity subclinical atherosclerosis. Our findings suggest that high inflammatory and coagulation burden were better markers of more severe lower-extremity disease as indicated by low ABI rather than early atherosclerotic lesion development in the femoral artery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Complement Activation Alters Platelet Function

DTIC Science & Technology

2015-12-01

haemostatic and coagulation properties of platelets. 15. SUBJECT TERMS Platelets, Complement, Trauma, Tissue Damage 16. SECURITY CLASSIFICATION... coagulation , there is mounting evidence that they may also be important in the development and progression of inflammatory processes (Coppinger et al...receptor-ligand interactions and/or through exposure to cytokines including IL-6, other acute-phase reactants, and pro- coagulant factors such as thrombin

[Open laser surgery on the locomotor apparatus].

PubMed

Gerber, B E; al-Khodairy, A T; Morscher, E; Hefti, F

1996-02-01

The first applications of laser in surgery of the locomotor apparatus in the early 1980s used the haemostatic properties of laser to diminish the amount of substitution of coagulation factors in haemophiliac patients. Only since the early 1990s has a device been available in corporating the pulsed holmium:YAG laser which works in a fluid medium without relevant side effects. Apart from haemostasis, the cutting function and tissue ablation, together with the thermal shrinking effect, are exploited in arthroscopy and percutaneous disc decompression. Now that the biophysical mechanisms of action have been elucidated, nothing stands in the way of the use of infrared lasers in open surgery of the locomotor apparatus in some indications. In a prospective clinical study we included 30 consecutive patients who underwent open laser surgery from November 1992 to August 1994, for the following indications: the sparing haemostatic tissue ablation was used for synovectomy or for bony resection in osteophytes and osteochondromas of different locations, an osteoid osteoma and a painful sacral hyperplasia in the presence of incomplete sacral meningomyelocele. With bleeding eliminated, the shaping was much easier. The non-ablative shrinking produced less tissue loss and a stabilizing strengthening of tissue at the margins of soft tissue resections, e.g. in jumper's knee, tennis elbow and Achilles tendon cysts. All laser functions that are useful in open surgery have also been used in sequestered disc herniations that are inaccessible a percutaneous procedure and, in spinal decompression, for remodelling of the posterior spine contour. An analgesic effect of laser limited the postoperative administration of analgesic drugs to an average of 3 days. No complications related to the laser treatment were observed. At follow-up 12-21 months after operation, 25 of the 30 patients in this heterogeneous population showed complete or near-total healing of the operated pathological finding, and a further 3 patients showed significant improvement. To what extent these very encouraging results will persist will be shown by long-term observation.

Multiple response optimization of the coagulation process for upgrading the quality of effluent from municipal wastewater treatment plant

NASA Astrophysics Data System (ADS)

Li, Na; Hu, Yi; Lu, Yong-Ze; Zeng, Raymond J.; Sheng, Guo-Ping

2016-05-01

To meet the high quality standard of receiving water, the coagulation process using polyferric chloride (PFC) was used to further improve the water quality of effluent from wastewater treatment plants. Uniform design (UD) coupled with response surface methodology (RSM) was adopted to assess the effects of the main influence factors: coagulant dosage, pH and basicity, on the removal of total organic carbon (TOC), NH4+-N and PO43--P. A desirability function approach was used to effectively optimize the coagulation process for the comprehensive removal of TOC, NH4+-N and PO43--P to upgrade the effluent quality in practical application. The optimized operating conditions were: dosage 28 mg/L, pH 8.5 and basicity 0.001. The corresponding removal efficiencies for TOC, NH4+-N and PO43--P were 77.2%, 94.6% and 20.8%, respectively. More importantly, the effluent quality could upgrade to surface water Class V of China through coagulation under optimal region. In addition, grey relational analysis (GRA) prioritized these three factors as: pH > basicity > dosage (for TOC), basicity > dosage > pH (for NH4+-N), pH > dosage > basicity (for PO43--P), which would help identify the most important factor to control the treatment efficiency of various effluent quality indexes by PFC coagulation.

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

Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

PubMed

Mallik, Suman; Prasad, Ramesh; Bhattacharya, Anindita; Sen, Prosenjit

2018-05-10

Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

PubMed Central

Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

2016-01-01

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

Application of Cox model in coagulation function in patients with primary liver cancer.

PubMed

Guo, Xuan; Chen, Mingwei; Ding, Li; Zhao, Shan; Wang, Yuefei; Kang, Qinjiong; Liu, Yi

2011-01-01

To analyze the distribution of coagulation parameters in patients with primary liver cancer; explore the relationship between clinical staging, survival, and coagulation parameters by using Coxproportional hazard model; and provide a parameter for clinical management and prognosis. Coagulation parameters were evaluated in 228 patients with primary liver cancer, 52 patients with common liver disease, and 52 normal healthy controls. The relationship between primary livercancer staging and coagulation parameters wasanalyzed. Follow-up examinations were performed. The Cox proportional hazard model was used to analyze the relationship between coagulationparameters and survival. The changes in the coagulation parameters in patients with primary liver cancer were significantly different from those in normal controls. The effect of the disease on coagulation function became more obvious as the severity of liver cancer increased (p<0.05). The levels of D-dimer, fibrinogen degradation products (FDP), fibrinogen (FIB), and platelets (PLT) were negatively correlated with the long-term survival of patients with advanced liver cancer. The stages of primary liver cancer are associated with coagulation parameters. Coagulation parameters are related to survival and risk factors. Monitoring of coagulation parameters may help ensure better surveillance and treatment for liver cancer patients.

Testing of Intravenous Hemostatic Agents in a Novel Swine Model of Bleeding: Preliminary Results With FXa-PCPs

DTIC Science & Technology

2005-08-01

proceeds through a prothrombinase complex (prothrombin, factor Va, calcium, and phospholipid). Thrombin is the final product in the coagulation cascade...we report preliminary data on the efficacy of mixtures of highly purified blood coagulation factors (FVIIa and FXa) and phospholipids vesicles (PCPS...testing. Further study of these drugs for the use of traumatic hemorrhage is not warranted. 15. SUBJECT TERMS Recombinant Factor VI~a, factor Xa

The Potential Role of Recombinant Activated Factor VIIa (rFVIIa) in Military Pre-Hospital Setting

DTIC Science & Technology

2004-09-01

coagulation factors and platelets by crystalloids, colloids, or blood products The severity of dilutional coagulopathy is determined by both volume and...RTO-MP-HFM-109 3 - 1 The Potential Role of Recombinant Activated Factor VIIa (rFVIIa) in Military Pre-Hospital Setting LTC (ret.) Uri...decrease mortality from exsanguinations. Recombinant factor VIIa (rFVIIa) has been shown to overcome a variety of coagulation and platelet disorders

Establishment of the 2nd Korean national biological reference standard for blood coagulation factor VIII:C concentrate.

PubMed

Lee, Naery; Seo, Ji Suk; Kim, Jae Ok; Ban, Sang Ja

2017-05-01

Since the 1st Korean national biological reference standard for factor (F)VIII concentrate, established in 2001, has shown declining potency, we conducted this study to replace this standard with a 2nd Korean national biological reference standard for blood coagulation FVIII concentrate. The candidate materials for the 2nd standard were prepared in 8000 vials with 10 IU/ml of target potency, according to the approved manufacturing process of blood coagulation Factor VIII:C Monoclonal Antibody-purified, Freeze-dried Human Blood Coagulation Factor VIII:C. Potency was evaluated by one-stage clotting and chromogenic methods and the stability was confirmed to meet the specifications during a period of 73 months. Since the potencies obtained by the two methods differed significantly (P < 0.015), the values were determined separately according to the geometric means (8.9 and 7.4 IU/vial, respectively). The geometric coefficients of interlaboratory variability were 3.4% and 7.6% by the one-stage clotting and chromogenic assays, respectively. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

[Hereditary heterozygous factor VII deficiency in patients undergoing surgery : Clinical relevance].

PubMed

Woehrle, D; Martinez, M; Bolliger, D

2016-10-01

A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients. In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015. In addition, by searching the literature, we identified publications reporting patients with FVII deficiency undergoing surgical procedures without perioperative substitution. We identified 22 patients undergoing 46 surgical procedures, resulting in a prevalence of 1:1500-2000. Coagulation factor concentrates were administered during the perioperative period in 15 procedures (33 %), whereas in the other 31 procedures (66 %), FVII deficiency was not substituted. No postoperative bleeding or thromboembolic events were reported. In addition, we found no differences in pre- and postoperative hemoglobin and coagulation parameters, with the exception of an improved postoperative INR value in the substituted group. In the literature review, we identified five publications, including 125 patients with FVII deficiency, undergoing 213 surgical procedures with no perioperative substitution. Preoperative substitution using coagulation factor concentrates does not seem to be mandatory in patients with an FVII level ≥15 %. For decision-making on preoperative substitution, patient history of an increased tendency to bleed may be more important than the FVII level or increased INR value.

Incidence and Risk Factors for Liver Abscess After Thermal Ablation of Liver Neoplasm

PubMed Central

Su, Xiu-Feng; Li, Na; Chen, Xu-Fang; Zhang, Lei; Yan, Ming

2016-01-01

Background Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most frequently used thermal ablation methods for the treatment of liver cancer. Liver abscess is a common and severe complication of thermal ablation treatment. Objectives The objective of this study was to determine the incidence and risk factors of liver abscess formation after thermal ablation of liver cancer. Materials and Methods The clinical data of 423 patients who underwent 691 thermal ablation procedures for liver cancer were collected in order to retrospectively analyze the basic characteristics, incidence, and risk factors associated with liver abscess formation. Patients with multiple risk factors for liver abscess formation were enrolled in a risk factor group, and patients with no risk factors were enrolled in a control group. The chi-square test and multiple logistic regression analysis were used to analyze the relationship between the occurrence of liver abscesses and potential risk factors. Results Two hundred and eight patients underwent 385 RFA procedures, and 185 patients underwent 306 MWA procedures. The total incidence of liver abscesses was 1.7%, while the rates in the RFA group (1.8%) and MWA groups (1.6%) were similar (P > 0.05). The rates of liver abscesses in patients who had child-pugh class B and class C cirrhosis (P = 0.0486), biliary tract disease (P = 0.0305), diabetes mellitus (P = 0.0344), and porta hepatis tumors (P = 0.0123) were 4.0%, 6.7%, 6.5%, and 13.0%, respectively. There was a statistically significant difference between these four groups and the control group (all P < 0.05). The incidence of liver abscesses in the combined ablation and percutaneous ethanol injection (PEI) group (P = 0.0026) was significantly lower than that of the ablation group (P < 0.05). Conclusions The incidence of liver abscesses after liver cancer thermal ablation is low. Child-Pugh Class B and Class C cirrhosis, biliary tract disease, diabetes mellitus, and porta hepatis tumors are four significant risk factors. Combined ablation and PEI reduces the rate of liver abscesses. PMID:27642345

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

PubMed

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-12-15

Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer.

PubMed

Kanda, Mitsuro; Tanaka, Chie; Kobayashi, Daisuke; Mizuno, Akira; Tanaka, Yuri; Takami, Hideki; Iwata, Naoki; Hayashi, Masamichi; Niwa, Yukiko; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Murotani, Kenta; Fujiwara, Michitaka; Kodera, Yasuhiro

2017-02-01

Systemic hemostasis and thrombosis activation has been implicated in tumor progression and metastasis. This study aimed to investigate the use of coagulation factors as a novel prediction method for postoperative outcomes after curative gastrectomy in patients with stage II/III gastric cancer (GC). Overall, 126 patients with stage II/III GC who underwent gastrectomy between May 2003 and February 2016 were eligible for inclusion in the study. We retrospectively evaluated the predictive value of preoperative platelet count and plasma fibrinogen and d-dimer levels, and coagulation score (0: fibrinogen and d-dimer both below upper limits; 1: either fibrinogen or d-dimer over upper limits; 2: both fibrinogen and d-dimer over upper limits) for short- and long-term outcomes. Postoperative complications were significantly more frequent in patients with elevated preoperative d-dimer levels compared with those with normal d-dimer levels (26 vs. 10 %; p = 0.032). The prevalence of postoperative complications showed a stepwise increase in proportion to the coagulation score. Patients with a coagulation score of 2 had significantly larger tumors (p = 0.013) and significantly greater intraoperative blood loss (p = 0.004) than those who scored 0 or 1. Coagulation score showed the highest values distinguished high-risk patients in overall and disease-free survival, and a coagulation score of 2 was an independent prognostic factor for recurrence. Patients with a coagulation score of 2 experienced a significantly higher prevalence of liver metastasis as an initial recurrence than those who scored 0 or 1 (p = 0.019). The coagulation score is a simple and promising predictor for postoperative complications and recurrence after gastrectomy in stage II/III GC patients.

Theoretical comparison of two interstitial ultrasound applicators designed to induce cylindrical zones of tissue ablation.

PubMed

Lafon, C; Chavrier, F; Prat, F; Chapelon, J Y; Cathignol, D

1999-05-01

Although interstitial techniques are invasive, they are still the first-line therapeutic modalities for certain types of tumour. They are mainly relevant to tumours that are either inoperable or located so deep that access is complicated. Of the various types of radiation that can be delivered by the interstitial route, ultrasound is the most suitable for deep heating. The study compares the efficacy of two types of applicator with respect to their ability to induce cylindrical zones of coagulation necrosis. The transducer of the first applicator is tubular, whereas the second is plane and can rotate around its axis. Both have an external diameter of 4 mm, are fitted with surface cooling systems and operate at 10.7 MHz and 14 W.cm-2. Comparison involves mathematical modelling of ablated tissue in the targeted area by resolving the bioheat transfer equation (BHTE) using an algorithm based on finite differences. The BHTE gives a temperature value from which the thermal dose can be determined. It is shown that tissue ablation by tubular transducers is slow, and, in consequence, perfusion disturbs the heating pattern: in vivo, irradiation with a tubular transducer lasting 1081 s would be required to ablate a tissue mass with a radius of 8 mm. The corresponding period using a rotating plane transducer with 20 firing angles is only 618 s. The mean exposure time of each shot lasts 31 +/- 7 s. Therefore perfusion would have much less impact in the case of therapy administered using a plane transducer than that using a tubular one.

Hybrid laparoscopic and robotic ultrasound-guided radiofrequency ablation-assisted clampless partial nephrectomy.

PubMed

Nadler, Robert B; Perry, Kent T; Smith, Norm D

2009-07-01

To describe a clampless approach made possible by creating an avascular plane of tissue with radiofrequency ablation. Laparoscopic partial nephrectomy is slowly gaining acceptance as a method to treat small (<4 cm) and select moderate (<7 cm) renal masses. The intricacies of laparoscopic suturing, which result in prolonged warm ischemia times, have delayed the widespread acceptance of this technique among urologists. Laparoscopic suturing to close the collecting system was done using the da Vinci robot. An avascular plane of tissue from coagulation necrosis was achieved with the Habib 4X radiofrequency ablation device and the Rita 1500X generator. Typically, we used a power setting of 50 W but have found settings as low as 25 W necessary to provide hemostasis for larger vessels. The tumor was then sharply excised with a negative margin using robotic scissors and electrocautery to facilitate tissue cutting. Retrograde injection of methylthioninium chloride and saline through an externalized ureteral catheter allowed for precise sutured closure of the collecting system. FloSeal and BioGlue were then applied, making surgical bolsters or parenchymal sutures unnecessary. Intraoperative histologic evaluation of the surgical margin and repeat resection of the tumor bed was possible because the renal hilum was not clamped, and no warm ischemia was used. This technique, which combines the improving technologies of robotic surgery, intraoperative laparoscopic ultrasonography, and radiofrequency ablation, might make more surgeons comfortable with the intricacies of laparoscopic suturing and eliminate prolonged warm ischemia times. Overall, this method should result in more patients being able to undergo minimally invasive laparoscopic partial nephrectomy.

OCT analysis of microneedle and Er:YAG surface ablation for enhanced transdermal delivery of hyperosmotic agents for optical skin clearing

NASA Astrophysics Data System (ADS)

Stumpp, Oliver F.; Welch, A. J.; Gill, Harvinder S.; Prausnitz, Mark R.

2004-07-01

The purpose of this study is to investigate the feasibility of using microneedles in comparison to Er:YAG skin surface laser ablation as a means to modify the epidermis of in-vitro hamster skin to facilitate delivery of topically applied hyper-osmotics such as glycerol into the skin to achieve optical skin clearing. This allows to temporarily reduce scattering of light in otherwise turbid tissues with potential applications pertaining to non-invasive optical imaging techniques such as optical coherence tomography (OCT) or therapeutic applications like laser blood vessel coagulation to treat port wine stains in skin. A portable, battery powered Er:YAG laser (Lasette) manufactured by Cell Robotics Inc. was used to produce holes in the stratum corneum and epidermis using individual 400 μs pulses causing localized ablation. Following each laser pulse the tissue was mechanically translated by 1 mm before another pulse was delivered. As an alternative method to the use of an expensive laser source requiring some kind of light scanning mechanism to treat larger skin areas efficiently, microneedles were investigated. They do not require an energy supply, are also pain-free and can be manufactured into arrays allowing treatment of larger skin areas. A single application forms micron scale holes in the stratum corneum through which topically applied skin clearing agents such as glycerol can penetrate into the tissue. In this feasibility study individual microneedles were used to manually induce holes in the skin each spaced approximately 1 mm apart from the other. Upon such epidermal modification by either technique, glycerol was then applied to the tissue surface and amplitude OCT measurements monitored changes of the optical properties of the tissue over time. Due to the geometry of the microneedle used in this study the cross sectional area of each hole in the epidermis was about 68% smaller than the comparable ablation site caused by an individual laser pulse. Results indicate enhanced skin clearing rates due to the induced holes in the stratum corneum in both cases by a factor of 5 to 8. Due to the larger area of laser ablation in comparison to the holes caused by microneedles, overall skin clearing rates are higher with the laser. However, localized data analysis near holes produced by either technique yields comparable results which show an increase in the clearing rate of up to 10 to 13 times over intact skin without any holes.

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.

Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats.

PubMed

Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki

2010-08-01

Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation. Thrombus formation was initiated by FeCl(3)-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle. TAK-442 (3mg/kg, po), aspirin (100mg/kg, po) or clopidogrel (3mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment. These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings. (c) 2010 Elsevier Ltd. All rights reserved.

Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

PubMed

Hoemann, Caroline D; Marchand, Catherine; Rivard, Georges-Etienne; El-Gabalawy, Hani; Poubelle, Patrice E

2017-11-01

Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B 4 (LTB 4 ) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB 4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB 4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB 4 , a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

PubMed

Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

2011-10-01

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

Chronic radiation proctopathy: A practical review of endoscopic treatment.

PubMed

Lenz, Luciano; Rohr, Rachel; Nakao, Frank; Libera, Ermelindo; Ferrari, Angelo

2016-02-27

Chronic radiation proctopathy (CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbid-mortality. Endoscopy has a role in the diagnosis, staging and treatment of this disease. Currently available endoscopic modalities are formalin, potassium titanyl phosphate laser, neodymium:yttrium-aluminum-garnet laser, argon laser, bipolar electrocoagulation (BiCAP), heater probe, band ligation, cryotherapy, radiofrequency ablation and argon plasma coagulation (APC). Among these options, APC is the most promising.

Ways of Noninvasive Facial Skin Tightening and Fat Reduction.

PubMed

Fritz, Klaus; Salavastru, Carmen

2016-06-01

For skin tightening, ablative and nonablative lasers have been used with various parameters full or fractionated. Currently, other energy-based technologies have been developed such as radiofrequency (RF) from mono- to multipolar, microneedling RF, and high-intensity focused ultrasound. They heat up the tissue to a clinical endpoint. Temperatures above 42°C stimulate fibroblasts to produce more collagen and some technologies produce small coagulation points that allow to shrink and to tighten the tissue with less downtime or side effects. Alternative treatments not based on heat can be chemical peels from light to deep and microneedling without RF. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Plasmodium falciparum-infected erythrocytes induce Tissue Factor expression in endothelial cells and support the assembly of multimolecular coagulation complexes

PubMed Central

Francischetti, Ivo MB; Seydel, Karl B; Monteiro, Robson Q; Whitten, Richard O; Erexson, Cindy R; Noronha, Almério LL; Ostera, Graciela R.; Kamiza, Steve B; Molyneux, Malcolm E; Ward, Jerrold M; Taylor, Terrie E

2010-01-01

Summary Background Plasmodium falciparum malaria infects 300–500 million people every year causing 1–2 million deaths annually. Evidence of a coagulation disorder, activation of endothelial cells (EC) and increase in inflammatory cytokines are often present in malaria. Objectives We have asked whether parasitized red blood cells (pRBC) interaction with EC induces Tissue Factor expression in vitro and in vivo. The potential of phosphatidylserine-containing pRBC to support the assembly of blood coagulation complexes was also investigated. Results We demonstrate that mature forms of pRBC induce functional expression of tissue factor (TF) by endothelial cells (EC) in vitro with productive assembly of the extrinsic Xnase complex and initiation of the coagulation cascade. Late stage pRBC also support the prothrombinase and intrinsic Xnase complex formation in vitro, and may function as activated platelets in the amplification phase of the blood coagulation. Notably, postmortem brain sections obtained from P. falciparum-infected children who died from Cerebral Malaria and other causes display a consistent staining for TF in the EC. Conclusions These findings place TF expression by endothelium and the amplification of the coagulation cascade by pRBC and/or activated platelets as potentially critical steps in the pathogenesis of malaria. Furthermore, it may allow investigators to test other therapeutic alternatives targeting TF or modulators of EC function in the treatment of malaria and/or its complications. PMID:17002660

No effect of isolated long-term supine immobilization or profound prolonged hypoxia on blood coagulation.

PubMed

Venemans-Jellema, A; Schreijer, A J M; Le Cessie, S; Emmerich, J; Rosendaal, F R; Cannegieter, S C

2014-06-01

Long-distance air travel is associated with an increased risk of venous thrombosis. The most obvious factor that can explain air travel-related thrombosis is prolonged seated immobilization. In addition, hypobaric hypoxia has been shown to affect coagulation, and the lowered atmospheric pressures present in the cabin during the flight may therefore play an etiologic role. Because immobilization and hypoxic conditions are usually present simultaneously in airplanes or hypobaric chambers, their separate effects on the coagulation system or on thrombosis risk have not been studied extensively. To investigate the separate effects of long-term immobilization and profound prolonged hypoxia on blood coagulation. We performed two studies in collaboration with European Space Agency/European Space Research and Technology Centre. In the first study, 24 healthy, non-smoking, adult women underwent 60 days of -6° head-down bed rest. In the second study, we took blood samples from 25 healthy men who participated during their stay in the Concordia station in Antarctica, where, due to the atmospheric conditions, continuous severe hypobaric hypoxia is present. In both studies, we measured markers of blood coagulation at baseline and at several time points during the exposures. We observed no increase in coagulation markers during immobilization or in the hypobaric environment, compared with baseline measurements. Our results indicate that neither immobilization nor hypoxia per se affects blood coagulation. These results implicate that a combination of risk factors is necessary to induce the coagulation system during air travel. © 2014 International Society on Thrombosis and Haemostasis.

New models of hemostasis.

PubMed

McMichael, Maureen

2012-05-01

Hemostasis is an essential protective mechanism that depends on a delicate balance of procoagulant and anticoagulant processes. The waterfall/cascade models of coagulation are useful for understanding several essential steps of coagulation in vitro. These have resulted in the creation of the plasma-based tests used commonly and the ability to identify deficiencies in the extrinsic, intrinsic, and common pathways of coagulation. The model was also essential in elucidating the role of several of the inhibitors of coagulation and is currently used to demonstrate coagulation as it occurs in plasma in a static environment that is devoid of endothelial interactions. The intrinsic pathway originally described by these models does not appear to be essential for in vivo hemostasis but may play a role in pathologic thrombosis. The waterfall/cascade models' lack of cellular elements sets the stage for the cell-based model of coagulation. The cell-based model of blood coagulation, which includes the varied, complicated network of factors necessary for appropriate in vivo coagulation to occur, was the next step in the evolution of our understanding of coagulation. Recently, researchers have focused on real-time, in vivo models of hemostasis and this research reveals unexpected phenomena. Copyright © 2012 Elsevier Inc. All rights reserved.

The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro

PubMed Central

Golderman, Valery; Shavit-Stein, Efrat; Tamarin, Ilia; Rosman, Yossi; Shrot, Shai; Rosenberg, Nurit

2016-01-01

Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain. PMID:27689805

Risk factors associated with short-term outcome and development of perioperative complications in dogs undergoing surgery because of gastric dilatation-volvulus: 166 cases (1992-2003).

PubMed

Beck, Jennifer J; Staatz, Andrew J; Pelsue, Davyd H; Kudnig, Simon T; MacPhail, Catriona M; Seim, Howard B; Monnet, Eric

2006-12-15

To evaluate risk factors associated with death and development of perioperative complications in dogs undergoing surgery for treatment of gastric dilatation-volvulus (GDV). Retrospective case series. 166 dogs. Records of dogs with confirmed GDV that underwent surgery were reviewed. Logistic regression was performed to identify factors associated with development of complications (ie, hypotension, arrhythmias, gastric necrosis necessitating gastrectomy, disseminated intravascular coagulation, peritonitis, sepsis, postoperative dilatation, postoperative vomiting, and incisional problems) and with short-term outcome (ie, died vs survived to the time of suture removal). Short-term mortality rate was 16.2% (27/166). Risk factors significantly associated with death prior to suture removal were clinical signs for > 6 hours prior to examination, combined splenectomy and partial gastrectomy, hypotension at any time during hospitalization, peritonitis, sepsis, and disseminated intravascular coagulation. Partial gastrectomy was not a significant risk factor for death but was for peritonitis, disseminated intravascular coagulation, sepsis, and arrhythmias. Age, gastrectomy, and disseminated intravascular coagulation were risk factors for development of hypotension. Use of a synthetic colloid or hypertonic saline solution was associated with a significantly decreased risk of hypotension. Results suggest that the prognosis for dogs undergoing surgery because of GDV is good but that certain factors are associated with an increased risk that dogs will develop perioperative complications or die.

Coagulation Management in Jersey Calves: An ex vivo Study.

PubMed

Gröning, Sabine; Maas, Judith; van Geul, Svenja; Rossaint, Rolf; Steinseifer, Ulrich; Grottke, Oliver

2017-01-01

Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood. © 2017 S. Karger AG, Basel.

Analysis of rhG-CSF-effects on platelets by in vitro bleeding test and transcranial Doppler ultrasound examination.

PubMed

Söhngen, D; Wienen, S; Siebler, M; Boogen, C; Scheid, C; Schulz, A; Kobbe, G; Diehl, V; Heyll, A

1998-12-01

Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen.

Bimodal electric tissue ablation (BETA): a study on ablation size when the anode is placed on the peritoneum and the liver.

PubMed

Tiong, Leong U; Finnie, John W; Field, John B; Maddern, Guy J

2012-07-01

In bimodal electric tissue ablation (BETA), the cathode of the DC circuit is attached to the radiofrequency (RF) electrode to increase the surrounding tissue hydration. This will delay tissue desiccation and allowing the ablation process to continue for a longer period of time before "roll-off" occurs, resulting in larger ablations compared with standard radiofrequency ablation (RFA). Previous research showed that attaching the anode to the skin using electrosurgical grounding pads would reduce the efficacy of BETA because of the high electrical resistivity of the skin. This study investigated the ablation size produced when the anode was attached to the peritoneum (BETA-peritoneum) and the liver (BETA-liver) respectively. The anode of the DC circuit in BETA was attached to the peritoneum and the liver in a pig model using ECG dots. In BETA, 9 V of DC was provided for 10 min, after which the radiofrequency generator were switched on and both electrical circuits allowed to run concurrently until "roll-off." The size of ablations produced was compared to when the anode attached to the skin (BETA-skin) and standard RFA, respectively. The sites of anode placement were examined for local tissue injury. The transverse diameters in BETA-peritoneum and BETA-liver were significantly larger compared with BETA-skin and standard RFA, respectively (P < 0.001). The axial diameter in the BETA-peritoneum and BETA-liver groups were also larger compared with the BETA-skin and RFA groups, although the differences did not reach statistical significance (P = 0.09). Hematoxylin and eosin (H and E) examination of the peritoneum and the liver where the anode was attached showed coagulation necrosis involving the superficial epithelium and the liver capsule, respectively. BETA can be used to treat larger liver tumors more effectively and may reduce the tumor recurrence rates compared with standard RFA. The efficacy of BETA depends on ensuring good electrical conductivity between the cathode and the anode of the DC circuit. Research so far has shown that BETA works best when the anode is placed deep to the skin as the stratum corneum consisted of a layer of a-nucleated cells, which have high electrical resistivity. The liver could be the ideal location to place the anode as it has excellent electrical conductivity, therefore ensuring maximum tissue hydration around the cathode to produce the largest ablations possible. Copyright © 2012 Elsevier Inc. All rights reserved.

Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model.

PubMed Central

O'Brien, D P; Giles, A R; Tate, K M; Vehar, G A

1988-01-01

The bleeding disorder of hemophilia A currently treated by replacement therapy of the missing coagulation factor, factor VIII, is frequently complicated by the development of neutralizing antibodies. The therapeutic potential of attenuated forms of the lipid-associated glycoprotein tissue factor, a known initiator of coagulation, was investigated as a factor VIII-by-passing activity. The protein moiety of tissue factor (Apo-TF) was partially purified and exhibited minimal procoagulant activity before relipidation in vitro. In pilot studies, Apo-TF injection into rabbits previously anticoagulated with an antibody to factor VIII was found to have a procoagulant effect. The efficacy of the material was further demonstrated when injection of Apo-TF in hemophilic dogs resulted in a normalization of the cuticle bleeding time. Little or no change in the blood parameters associated with disseminated intravascular coagulation was observed at lower doses, although mild to moderate effects were seen at higher doses. These data suggest a novel role for Apo-TF preparations as a potential therapeutic agent for hemophiliacs with antibodies to factor VIII once the potential thrombogenicity of such materials is evaluated. Images PMID:3134399

Tissue factor-dependent coagulation activation by heme: A thromboelastometry study.

PubMed

de Souza, Gleice Regina; Hounkpe, Bidossessi Wilfried; Fiusa, Maiara Marx Luz; Colella, Marina Pereira; Annichino-Bizzacchi, Joyce M; Traina, Fabiola; Costa, Fernando Ferreira; De Paula, Erich Vinicius

2017-01-01

Heme has been characterized as potent trigger of inflammation. In hemostasis, although heme has been shown to both induce and inhibit different compartments of hemostasis, its net effect on the hemostatic balance, and the biological relevance of these effects remain to be determined. Herein we evaluated the effect of heme on hemostasis using a global assay able to generate clinically relevant data in several other complex hemostatic diseases. Citrated whole blood samples from healthy participants were stimulated by heme or vehicle and incubated for 4h at 37°C. Rotational thromboelastometry was immediately performed. The participation of tissue factor in coagulation activation was evaluated using inhibitory antibody. Heme was able of inducing ex vivo coagulation activation in whole blood, affecting predominantly parameters associated with the initial phases of clot formation. This activation effect was at least partially dependent on hematopoietic tissue factor, since the effects of heme were partially abrogated by the inhibition of human tissue factor. In conclusion, using a global hemostasis assay, our study confirmed that heme is able to activate coagulation in whole blood, in a tissue factor-dependent way. These findings could explain the disturbance in hemostatic balance observed in conditions associated with the release of heme such as sickle cell disease.

Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.

PubMed

Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido

2008-04-01

Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.

[Interventional radiology for bone metastases].

PubMed

Iannessi, Antoine; Garnon, Julien; Cormier, Évelyne; Clarencon, Frédéric; Chiras, Jacques

2013-11-01

The management of bone metastases requires a multidisciplinary staff to include systemic and local treatments like radiotherapy, surgery or interventional radiology (IR). Patients are often fragile. Imaging allows safe guidance to create "mini-invasive" procedures under adequate anesthesia. Patients' selection is important. If the goal is pain relief, cementoplasty provides a very effective bone consolidation and pain control. Simple and low-risk, vertebroplasty is the technique of choice in case of lytic bone metastases with spinal fracture risk or after failure of analgesic radiotherapy. If the medical project is curative, the tumor ablation procedures are realised through thermic or embolic techniques. After 60°C, the heat induces a coagulative necrose. Under -20°C, the cold leads to destroy the tissues. The major advantage of the cryotherapy is the predictibility of the ablation zone due to the well-visualized ice ball on perprocedural images. This technique is much more adapted to spare the nervous structures closed to the metastasis. The development of these new techniques of IR will treat bone metastases earlier, sometimes asymptomatic and thus improves the quality of life in patients with bone metastases.

Management algorithms for cervical cancer screening and precancer treatment for resource-limited settings.

PubMed

Basu, Partha; Meheus, Filip; Chami, Youssef; Hariprasad, Roopa; Zhao, Fanghui; Sankaranarayanan, Rengaswamy

2017-07-01

Management algorithms for screen-positive women in cervical cancer prevention programs have undergone substantial changes in recent years. The WHO strongly recommends human papillomavirus (HPV) testing for primary screening, if affordable, or if not, then visual inspection with acetic acid (VIA), and promotes treatment directly following screening through the screen-and-treat approach (one or two clinic visits). While VIA-positive women can be offered immediate ablative treatment based on certain eligibility criteria, HPV-positive women need to undergo subsequent VIA to determine their eligibility. Simpler ablative methods of treatment such as cryotherapy and thermal coagulation have been demonstrated to be effective and to have excellent safety profiles, and these have become integral parts of new management algorithms. The challenges faced by low-resource countries are many and include, from the management perspective, identifying an affordable point-of-care HPV detection test, minimizing over-treatment, and installing an effective information system to ensure high compliance to treatment and follow-up. © 2017 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

Diagnosis and treatment of superficial esophageal cancer

PubMed Central

Barret, Maximilien; Prat, Frédéric

2018-01-01

Endoscopy allows for the screening, early diagnosis, treatment and follow up of superficial esophageal cancer. Endoscopic submucosal dissection has become the gold standard for the resection of superficial squamous cell neoplasia. Combinations of endoscopic mucosal resection and radiofrequency ablation are the mainstay of the management of Barrett’s associated neoplasia. However, protruded, non-lifting or large lesions may be better managed by endoscopic submucosal dissection. Novel ablation tools, such as argon plasma coagulation with submucosal lifting and cryoablation balloons, are being developed for the treatment of residual Barrett’s esophagus, since iatrogenic strictures still hamper the development of extensive circumferential resections in the esophagus. Optimal surveillance modalities after endoscopic resection are still to be determined. The assessment of the risk of lymph-node metastases, as well as of the need for additional treatments based on qualitative and quantitative histological criteria, balanced to the patient’s condition, requires a dedicated multidisciplinary team decision process. The need for trained endoscopists, expert pathologists and surgeons, and specialized multidisciplinary meetings underlines the role of expert centers in the management of superficial esophageal cancer. PMID:29720850

[Lasers in dentistry. Part B--Interaction with biological tissues and the effect on the soft tissues of the oral cavity, the hard tissues of the tooth and the dental pulp].

PubMed

Moshonov, J; Stabholz, A; Leopold, Y; Rosenberg, I; Stabholz, A

2001-10-01

The interaction of laser energy with target tissue is mainly determined by two non operator-dependent factors: the specific wavelength of the laser and the optical properties of the target tissues. Power density, energy density, pulse repetition rate, pulse duration and the mode of energy transferring to the tissue are dictated by the clinician. Combination of these factors enables to control optimal response for the clinical application. Four responses are described when the laser beam hits the target tissue: reflection, absorption, transmission and scattering. Three main mechanisms of interaction between the laser and the biological tissues exist: photothermic, photoacoustic and photochemical. The effect of lasers on the soft tissues of the oral cavity is based on transformation of light energy into thermal energy which, in turn heats the target tissue to produce the desirable effect. In comparison to the scalpel used in surgical procedures, the laser beam is characterized by tissue natural sterility and by minimum bleeding during the surgical procedures due to blood vessels welding. The various effects achieved by the temperature elevation during the laser application on the soft tissue are: I. coagulation and hemostasis II. tissue sterilization III. tissue welding IV. incision and excision V. ablation and vaporization Ablation and melting are the two basic modalities by which the effect of lasers on the hard tissues of the tooth is produced. When discussing the effect of laser on dental hard tissues, the energy absorption in the hydroxyapatite plays a major role in addition to its absorption in water. When laser energy is absorbed in the water of the hard tissues, a rapid volume expansion of the evaporating water occurs as a result of a substantial temperature elevation in the interaction site. Microexplosions are produced causing hard tissue disintegration. If pulp temperatures are raised beyond 5 degrees C level, damage to the dental pulp is irreversible. Histologically, after laser ablation, presence of odontoblastic nuclei is important. Consistency and composition of the intracellular tissue is another factor influencing cell viability. If heat is intensive and exists for an extended time, the consistency of the intracellular ground substance may not be preserved. Accordingly, the application of excessive energy densities has been shown to result in significant damage to pulp tissue and in particular to odontoblasts. Studies showed that the use of Er:YAG laser to treat dental hard tissues is both safe and effective for caries removal, cavity preparation and enamel etching.

Contact Activation of Blood Plasma and Factor XII by Ion-exchange Resins

PubMed Central

Yeh, Chyi-Huey Josh; Dimachkie, Ziad O.; Golas, Avantika; Cheng, Alice; Parhi, Purnendu; Vogler, Erwin A.

2011-01-01

Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quarternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles ( FXII→surfaceactivatorFXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean-glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion-exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade. PMID:21982294

Coagulation Imbalance and Neurocognitive Functioning in Older HIV+ Adults on Suppressive Antiretroviral Therapy

PubMed Central

Montoya, Jessica l.; Iudicello, Jennifer; Oppenheim, Hannah A.; Fazeli, Pariya l.; Potter, Michael; MA, Qing; Mills, Paul J.; Ellis, Ronald J.; Grant, Igor; Letendre, Scott l.; Moore, David J.

2017-01-01

Objectives To compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. Design Cross-sectional study of 66 antiretroviral therapy-treated virally suppressed HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. Methods Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive neuropsychological battery. Plasma biomarkers associated with procoagulation (fibrinogen, p-selectin, tissue factor, and von Willebrand factor), anticoagulation (antithrombin, protein C, and thrombomodulin), fibrinolysis (d-dimer, plasminogen activator inhibitor-1, and plasminogen) were collected. Multivariable linear regression was used to test the interaction of HIV and coagulation on neurocognitive functioning. Results Most participants were male (78.0%) and non-Hispanic white (73.0%) with a mean age of 57.8 years. Among HIV-infected participants, mean estimated duration of HIV infection was 19.4 years and median current CD4+ cell count was 654 cells/mm3. Levels of soluble biomarkers of procoagulation, anticoagulation, and fibrinolysis were comparable between the HIV serostatus groups. Coagulation and HIV had an interacting effect on neurocognitive functioning, such that greater coagulation imbalance was associated with poorer neurocognitive functioning among the HIV-infected participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers. Conclusions Elevated levels of procoagulants may exert a particularly detrimental effect on neurocognitive functioning among older HIV-infected persons. A better understanding of the specific role of coagulation in the etiology of HIV-associated neurocognitive disorders may lead to treatments aimed at reducing coagulopathy, thereby improving neurocognitive outcomes. PMID:28099190

Coagulation imbalance and neurocognitive functioning in older HIV-positive adults on suppressive antiretroviral therapy.

PubMed

Montoya, Jessica L; Iudicello, Jennifer; Oppenheim, Hannah A; Fazeli, Pariya L; Potter, Michael; Ma, Qing; Mills, Paul J; Ellis, Ronald J; Grant, Igor; Letendre, Scott L; Moore, David J

2017-03-27

The aim of this study was to compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. A cross-sectional study of 66 antiretroviral therapy treated, virally suppressed, HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well validated comprehensive neuropsychological battery. Plasma biomarkers associated with procoagulation (fibrinogen, p-selectin, tissue factor and von Willebrand factor), anticoagulation (antithrombin, protein C and thrombomodulin), fibrinolysis (d-dimer, plasminogen activator inhibitor-1 and plasminogen) were collected. Multivariable linear regression was used to test the interaction of HIV and coagulation on neurocognitive functioning. Most participants were male (78.0%) and non-Hispanic white (73.0%) with a mean age of 57.8 years. Among HIV-infected participants, mean estimated duration of HIV infection was 19.4 years and median current CD4 cell count was 654 cells/μl. Levels of soluble biomarkers of procoagulation, anticoagulation and fibrinolysis were comparable between the HIV serostatus groups. Coagulation and HIV had an interacting effect on neurocognitive functioning, such that greater coagulation imbalance was associated with poorer neurocognitive functioning among the HIV-infected participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers. Elevated levels of procoagulants may exert a particularly detrimental effect on neurocognitive functioning among older HIV-infected persons. A better understanding of the specific role of coagulation in the cause of HIV-associated neurocognitive disorders may lead to treatments aimed at reducing coagulopathy, thereby improving neurocognitive outcomes.

Influence of spatial and temporal spot distribution on the ocular surface quality and maximum ablation depth after photoablation with a 1050 Hz excimer laser system.

PubMed

Mrochen, Michael; Schelling, Urs; Wuellner, Christian; Donitzky, Christof

2009-02-01

To investigate the effect of temporal and spatial distributions of laser spots (scan sequences) on the corneal surface quality after ablation and the maximum ablation of a given refractive correction after photoablation with a high-repetition-rate scanning-spot laser. IROC AG, Zurich, Switzerland, and WaveLight AG, Erlangen, Germany. Bovine corneas and poly(methyl methacrylate) (PMMA) plates were photoablated using a 1050 Hz excimer laser prototype for corneal laser surgery. Four temporal and spatial spot distributions (scan sequences) with different temporal overlapping factors were created for 3 myopic, 3 hyperopic, and 3 phototherapeutic keratectomy ablation profiles. Surface quality and maximum ablation depth were measured using a surface profiling system. The surface quality factor increased (rough surfaces) as the amount of temporal overlapping in the scan sequence and the amount of correction increased. The rise in surface quality factor was less for bovine corneas than for PMMA. The scan sequence might cause systematic substructures at the surface of the ablated material depending on the overlapping factor. The maximum ablation varied within the scan sequence. The temporal and spatial distribution of the laser spots (scan sequence) during a corneal laser procedure affected the surface quality and maximum ablation depth of the ablation profile. Corneal laser surgery could theoretically benefit from smaller spot sizes and higher repetition rates. The temporal and spatial spot distributions are relevant to achieving these aims.

Imaging of blood plasma coagulation at supported lipid membranes.

PubMed

Faxälv, Lars; Hume, Jasmin; Kasemo, Bengt; Svedhem, Sofia

2011-12-15

The blood coagulation system relies on lipid membrane constituents to act as regulators of the coagulation process upon vascular trauma, and in particular the 2D configuration of the lipid membranes is known to efficiently catalyze enzymatic activity of blood coagulation factors. This work demonstrates a new application of a recently developed methodology to study blood coagulation at lipid membrane interfaces with the use of imaging technology. Lipid membranes with varied net charges were formed on silica supports by systematically using different combinations of lipids where neutral phosphocholine (PC) lipids were mixed with phospholipids having either positively charged ethylphosphocholine (EPC), or negatively charged phosphatidylserine (PS) headgroups. Coagulation imaging demonstrated that negatively charged SiO(2) and membrane surfaces exposing PS (obtained from liposomes containing 30% of PS) had coagulation times which were significantly shorter than those for plain PC membranes and EPC exposing membrane surfaces (obtained from liposomes containing 30% of EPC). Coagulation times decreased non-linearly with increasing negative surface charge for lipid membranes. A threshold value for shorter coagulation times was observed below a PS content of ∼6%. We conclude that the lipid membranes on solid support studied with the imaging setup as presented in this study offers a flexible and non-expensive solution for coagulation studies at biological membranes. It will be interesting to extend the present study towards examining coagulation on more complex lipid-based model systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Intrapleural fluid infusion for MR-guided high-intensity focused ultrasound ablation in the liver dome.

PubMed

Wijlemans, Joost W; de Greef, Martijn; Schubert, Gerald; Moonen, Chrit T W; van den Bosch, Maurice A A J; Ries, Mario

2014-12-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of tumors in the liver dome is challenging because of the presence of air in the costophrenic angle. In this study, we used a porcine liver model and a clinical MR-HIFU system to assess the feasibility and safety of using intrapleural fluid infusion (IPI) to create an acoustic window for MR-HIFU ablation in the liver dome. Healthy adult Dalland land pigs (n = 6) under general anesthesia were used with animal committee approval. Degassed saline (200-800 mL) was infused into the intrapleural space under ultrasound guidance. A clinical 1.5-T MR-HIFU system was used to perform sonications (4-mm treatment cells, 300-450 W, 20-30 seconds) in the liver dome under real-time MR thermometry. An intercostal firing technique was used to prevent rib heating in one experiment. Technical success was defined as a temperature increase (>10°C) in the target area. After termination, the animal was examined for thermal damage to liver, diaphragm, pleura, lung, or intercostal muscle. An acoustic window was established in all animals. A temperature increase in the target area was achieved in all animals (max. 47°C-67°C). MR thermometry showed no heating outside the target area. Intercostal firing effectively reduced rib heating (55°C vs. 42°C). Postmortem examination revealed no unwanted thermal damage. One complication occurred, in the first experiment, because of an ill-suited needle (displacement of the needle). The results indicate that IPI may be used safely to assist MR-HIFU ablation of tumors in the liver dome. For reliable tissue coagulation, IPI must be combined with an intercostal sonication technique. Considering the proportion of patients with tumors in the liver dome, IPI widens the applicability of MR-HIFU ablation for liver tumors considerably. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Short and medium term outcomes after rollerball endometrial ablation for menorrhagia.

PubMed

Fraser, I S; Angsuwathana, S; Mahmoud, F; Yezerski, S

1993-04-05

To review prospectively the intraoperative, short and medium term outcomes of patients treated by rollerball endometrial ablation during the learning curve for this relatively new procedure. Seventy-seven women with menorrhagia (71 with dysfunctional bleeding; six with additional small intramural myomas) underwent hysteroscopic rollerball endometrial ablation by coagulation diathermy during 1.5% glycine irrigation, after a two-month period of hormonal suppression. OPERATIVE AND SHORT-TERM EFFECTS: These were recorded at operation and six-week follow-up. No serious short-term complications were recorded. Objective measurement of intraoperative blood loss was always less than 20 mL. One woman experienced uterine perforation with a narrow cervical dilator which did not interfere with the ablation, and two patients had mild postoperative uterine infections. One patient experienced persistent postoperative pain. MEDIUM-TERM OUTCOME: This was recorded at each visit, or by telephone, and confirmed by questionnaire at one year. Twenty-five per cent achieved complete amenorrhoea, 29% staining only, 30% light periods, 10% "normal" or erratic periods and 6% were unchanged. Five patients underwent a second ablation, and three of these later underwent hysterectomy. Measured menstrual blood loss fell from 104 +/- 19 mL (mean +/- standard error of mean) to 1.7 +/- 1.1 mL at six months in 18 women. Other menstrual symptoms were also often dramatically reduced. Of those women with dysmenorrhoea, 33% were cured and 43% markedly improved; of those with midcycle pain, 28% were cured and 53% markedly improved; of those with significant premenstrual symptoms, 13% were cured, 47% markedly improved, 11% unchanged, and 6% were worse. This new procedure is a safe and effective treatment for menorrhagia caused by dysfunctional uterine bleeding, with impressive ancillary benefits for dysmenorrhoea, midcycle pain and premenstrual tension. It is often called minimally invasive surgery, but it must be recognised that it is not minor surgery.

Fish as bioreactors: transgene expression of human coagulation factor VII in fish embryos.

PubMed

Hwang, Gyulin; Müller, Ferenc; Rahman, M Aziz; Williams, Darren W; Murdock, Paul J; Pasi, K John; Goldspink, Geoffrey; Farahmand, Hamid; Maclean, Norman

2004-01-01

A plasmid containing human coagulation factor VII (hFVII) complementary DNA regulated by a cytomegalovirus promoter was microinjected into fertilized eggs of zebrafish, African catfish, and tilapia. The active form of hFVll was detected in the fish embryos by various assays. This positive expression of human therapeutic protein in fish embryos demonstrates the possibility of exploitation of transgenic fish as bioreactors.

Nanoparticles and the blood coagulation system. Part II: safety concerns

PubMed Central

Ilinskaya, Anna N; Dobrovolskaia, Marina A

2014-01-01

Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a desirable interface between this system and engineered nanomaterials was assessed in part I, which was published in the May 2013 issue of Nanomedicine. Unwanted pro- and anti-coagulant properties of nanoparticles represent significant concerns in the field of nanomedicine, and often hamper the development and transition into the clinic of many promising engineered nanocarriers. This part will focus on the undesirable effects of engineered nanomaterials on the blood coagulation system. We will discuss the relationship between the physicochemical properties of nanoparticles (e.g., size, charge and hydrophobicity) that determine their negative effects on the blood coagulation system in order to understand how manipulation of these properties can help to overcome unwanted side effects. PMID:23730696

High-intensity focused ultrasound ablation of thyroid nodules: first human feasibility study.

PubMed

Esnault, Olivier; Franc, Brigitte; Ménégaux, Fabrice; Rouxel, Agnès; De Kerviler, Eric; Bourrier, Pierre; Lacoste, François; Chapelon, Jean-Yves; Leenhardt, Laurence

2011-09-01

Thyroid surgery is common, but complications may occur. High-intensity focused ultrasound (HIFU) is a minimally invasive alternative to surgery. We hypothesized that an optimized HIFU device could be safe and effective for ablating benign thyroid nodules without affecting neighboring structures. In this open, single-center feasibility study, 25 patients were treated with HIFU with real-time ultrasound imaging 2 weeks before a scheduled thyroidectomy for multinodular goiter. Thyroid ultrasonography imaging, thyroid function, were evaluated before and after treatment. Adverse events were carefully recorded. Each patient received HIFU for one thyroid nodule, solid or mixed, with mean diameter ≥8 mm, and no suspicion of malignancy. The HIFU device was progressively adjusted with stepwise testing. The energy level for ablation ranged from 35 to 94 J/pulse for different groups of patients. One pathologist examined all removed thyroids. Three patients discontinued treatment due to pain or skin microblister. Among the remaining 22 patients, 16 showed significant changes by ultrasound. Macroscopic and histological examinations showed that all lesions were confined to the targeted nodule without affecting neighboring structures. At pathological analysis, the extent of nodule destruction ranged from 2% to 80%. Five out of 22 patients had over 20% pathological lesions unmistakably attributed to HIFU. Seventeen cases had putative lesions including nonspecific necrosis, hemorrhage, nodule detachment, cavitations, and cysts. Among these 17 cases, 12 had both ultrasound changes and cavitation at histology that may be expected for an HIFU effect. In the last three patients ablated at the highest energy level, significant ultrasound changes and complete coagulative necrosis were observed in 80%, 78%, and 58% of the targeted area, respectively. There were no major complications of ablation. This study showed the potential efficacy of HIFU for human thyroid nodule ablation. Lesions were clearly visible by histology and ultrasound after high energy treatments, and safety and tolerability were good. We identified a power threshold for optimal necrosis of the target thyroid tissue. Further studies are ongoing to assess nodule changes at longer follow-up times.

Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

PubMed

de Moerloose, P; Schved, J-F; Nugent, D

2016-07-01

Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

Radiofrequency Thermal Ablation: Increase in Lesion Diameter with Continuous Acetic Acid Infusion

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

Lubienski, Andreas; Duex, Markus; Lubienski, Katrin

Purpose. To evaluate the influence of continuous infusion of acetic acid 50% during radiofrequency ablation (RFA) on the size of the thermal lesion produced. Methods. Radiofrequency (RF) was applied to excised bovine liver by using an expandable needle electrode with 10 retractable tines (LeVeen Needle Electrode, RadioTherapeutics, Sunnyvale, CA) connected to a commercially available RF generator (RF 2000, RadioTherapeutics, Sunnyvale, CA). Experiments were performed using three different treatment modalities: RF only (n = 15), RF with continuous saline 0.9% infusion (n = 15), and RF with continuous acetic acid 50% infusion (n = 15). RF duration, power output, tissue impedance,more » and time to a rapid rise in impedance were recorded. The ablated lesions were evaluated both macroscopically and histologically. Results. The ablated lesions appeared as spherical or ellipsoid, well-demarcated pale areas with a surrounding brown rim with both RF only and RF plus saline 0.9% infusion. In contrast, thermolesions generated with RF in combination with acetic acid 50% infusion were irregular in shape and the central portion was jelly-like. Mean diameter of the coagulation necrosis was 22.3 {+-} 2.1 mm (RF only), 29.2 {+-} 4.8 mm (RF + saline 0.9%) and 30.7 {+-} 5.7 mm (RF + acetic acid 50%), with a significant increase in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Time to a rapid rise in impedance was significantly prolonged in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Conclusions. A combination of RF plus acetic acid 50% infusion is able to generate larger thermolesions than RF only or RF combined with saline 0.9% infusion.« less

Prostate thermal therapy with catheter-based ultrasound devices and MR thermal monitoring

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Nau, Will H.; Kinsey, Adam; Ross, Tony; Wootton, Jeff; Juang, Titania; Butts-Pauly, Kim; Ricke, Viola; Liu, Erin H.; Chen, Jing; Bouley, Donna M.; Van den Bosch, Maurice; Sommer, Graham

2007-02-01

Four types of transurethral applicators were devised for thermal ablation of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns; planar and curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate the heating technology and develop treatment control strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature and thermal dose in multiple slices through the target volume. Sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation and modulated dwell time can conform thermal ablation to selected regions. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with directional devices can be used to effectively ablate the posterior peripheral zone of the gland while protecting the rectum. The MR derived 52 °C and lethal thermal dose contours (t 43=240 min) allowed for real-time control of the applicators and effectively defined the extent of thermal damage. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast and precise thermal ablation of prostate, with potential for treatment of cancer or BPH.

On coagulation mechanisms of charged nanoparticles produced by combustion of hydrocarbon and metallized fuels

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

Savel'ev, A. M.; Starik, A. M.

2009-02-15

The contributions of van der Waals, Coulomb, and polarization interactions between nanometersized particles to the particle coagulation rate in both free-molecular and continuum regimes are analyzed for particle charges of various magnitudes and signs. Analytical expressions are obtained for the coagulation rate constant between particles whose interaction in the free-molecular regime is described by a singular potential. It is shown that van der Waals and polarization forces significantly increase the coagulation rate between a neutral and a charged particle (by a factor of up to 10) and can even suppress the Coulomb repulsion between like-charged particles of widely different sizes.

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.

Activation of blood coagulation in cancer: implications for tumour progression

PubMed Central

Lima, Luize G.; Monteiro, Robson Q.

2013-01-01

Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies. PMID:23889169

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.

Influential factors of formation kinetics of flocs produced by water treatment coagulants.

PubMed

Wu, Chunde; Wang, Lin; Hu, Bing; Ye, Jian

2013-05-01

The growth rate and size of floc formation is of great importance in water treatment especially in coagulation process. The floc formation kinetics and the coagulation efficiency of synthetic water were investigated by using an on-line continuous optical photometric dispersion analyze and the analysis of water quality. Experimental conditions such as alum dosage, pH value for coagulation, stirring intensity and initial turbidity were extensively examined. The photometric dispersion analyze results showed that coagulation of kaolin suspensions with two coagulants (alum and polyaluminium chloride) could be taken as a two-phase process: slow and rapid growth periods. Operating conditions with higher coagulant doses, appropriate pH and average shear rate might be particularly advantageous. The rate of overall floc growth was mainly determined by a combination of hydraulic and water quality conditions such as pH and turbidity. The measurement of zeta potential indicates that polyaluminium chloride exhibited higher charge-neutralizing ability than alum and achieved lower turbidities than alum for equivalent Al dosages. Under the same operating conditions, the alum showed a higher grow rate, but with smaller floc size.

Initial Resuscitation with Plasma and Other Blood Components Reduced Bleeding Compared to Hetastarch in Anesthetized Swine with Uncontrolled Splenic Hemorrhage

DTIC Science & Technology

2011-04-01

products and Hextend. The fluid with the highest amount of coagulation factors , FFP resulted in the lowest blood loss. The FFP treatment had the highest...compared to humans and have higher concentrations of many of the clotting factors (FV, FVII , FVIII, F IX, and FXII).44 Although we have confirmed the higher...utilizing plasma early in treatment is to prevent dilution of remaining coagulation factors or reverse the coagulopathy that has been observed in

Effects of In Vitro Hemodilution, Hypothermia and rFVIIa Addition on Coagulation in Human Blood

DTIC Science & Technology

2012-03-30

primary fluids used by many trauma units and the US Army for pre-hospital resuscitation [17]. HX, a hetastarch-based product in a balanced electro...and has been associated with dilution of coagulation factors and hypothermia. Recombinant activated Factor VII (rFVIIa) has been used, often as a...of rFVIIa results in an enhancement of thrombin generation on the platelet surface at the site of injury independent of the presence of Factor VIII

Therapeutic Correction of Thrombin Generation in Dilution-Induced Coagulopathy: Computational Analysis Based on a Data Set of Healthy Subjects

DTIC Science & Technology

2012-01-01

Factor VIIa tended to primarily impact clotting time, thrombin peak time, and maximum slope of the thrombin curve, whereas in the case of PCC- FVII ...constituents of existing PCCs are the four coagulation factors (F) II (prothrombin), FVII , FIX, and FX.3 Notably, FVII inhibits thrombin generation by...proposed PCC composition (coagulation factors [F] II, IX, and X and the anticoagulant antithrombin), designated PCC-AT, was compared with that of

Risk Factors for Bile Duct Injury After Percutaneous Thermal Ablation of Malignant Liver Tumors: A Retrospective Case-Control Study.

PubMed

Lin, Man-Xia; Ye, Jie-Yi; Tian, Wen-Shuo; Xu, Ming; Zhuang, Bo-Wen; Lu, Ming-De; Xie, Xiao-Yan; Kuang, Ming

2017-04-01

Bile duct injury after ablation of malignant liver tumors (MLTs) was not unusual and should be avoided. However, few studies have focused on evaluating the risk factors for intrahepatic bile duct injury. To evaluate the risk factors for intrahepatic bile duct injury after ablation of MLTs and to evaluate the minimum safe distance for ablating tumors abutting bile ducts. Sixty-five patients with intrahepatic bile duct injury after ablation of MLTs, and 65 controls were recruited. Risk factors for intrahepatic bile duct injury were analyzed. Tumor location was recorded as ≤5 mm (group A), 5-10 mm (group B), and >10 mm (group C) from the right/left main duct or segmental bile duct. Ascites history (P < 0.001), TACE treatment history (P = 0.025), intrahepatic bile duct dilatation before ablation (P < 0.001), and tumor location (P = 0.000) were identified as significant risk factors for intrahepatic bile duct injury. Significant differences in the risk of intrahepatic bile duct injury were found between groups B and C (P = 0.000), but not between groups A and B (P = 0.751). Ascites history (P = 0.002) and tumor location (P < 0.001) were independent predictors with the OR (95 % confidence interval) of 39.31(3.95-391.69) and 16.56 (5.87-46.71), respectively. Bile duct injury after ablation of MLTs was the result of local treatment-related factors combined with the patients' general condition. The minimum safe distance for ablation of tumor abutting a bile duct was 10 mm.

Laser prostatectomy with side-firing Albarran bridge

NASA Astrophysics Data System (ADS)

Mattioli, Stefano

1996-01-01

Laser ablation of the prostatic tissue or laser prostatectomy, is used as an alternative method to traditional endoscopic resection of the prostate (TURP). Recently, there have been reports of transurethral coagulation of the prostate using various sidefiring laser systems. These devices can be classified into two groups: one that uses total internal reflection, and one that has a gold-plated metal reflecting mirror. We have developed a new Albarran bridge with these characteristics in order to minimize the restrictions presented by the other delivery systems. Laser coagulation of the prostate has been performed using a conventional bare fiber passed through a sidefiring Albarran bridge containing a distal gold-plated reflector with a deflecting mechanism. The complete device passes through a 21 F. rigid cystourethroscope. The system and the fiber can be used for several dozen treatments. Transurethral laser coagulation was performed on 65 patients for obstructive symptoms caused by begnin prostatic hyperplasia. The dosimetry was 1000 J per 1cc of prostatic tissue at 60 W for 60 seconds. Successful results were obtained in 55 patients (85%). A significant reduction in obstructive symptoms from a mean AUA-6 Symptom Score of 21.2 preoperatively to 9.1 at 3 months and 7.6 at 6 months was associated with an increase in the peak urine flow rate from 6.1 mL/sec preoperatively to 13.1 mL/sec at 3 months and 15.7 mL/sec at 6 months. The residual urine volume averaged 190 mL preoperatively and 365 mL at 6 months. Transurethral laser coagulation of the prostate represents a useful alternative to transurethral resection, especially in high-risk patients with an enlarged median lobe or a small prostate. Treatment is bloodless and, with the aid of the modified Albarran bridge, can be performed with standard urological instrumentation and conventional Nd:YAG laser system. The new Albarran bridge also can reduce the cost of laser treatment.

Effects of Er:YAG laser irradiation on human cartilage

NASA Astrophysics Data System (ADS)

Glinkowski, Wojciech; Brzozowska, Malgorzata; Ciszek, Bogdan; Rowinski, Jan; Strek, Wieslaw

1996-03-01

Irradiation of the hyaline or fibrous cartilage excised from the body of a human cadaver with Er:YAG laser beam, single pulse with a dose of 1 J, produces a crater with a depth of approximately 500 micrometers and a diameter varying from 5 to 300 micrometers. Histological examination has revealed that the laser-made craters were surrounded by a thin rim (2-10 micrometer) of charred and coagulated tissue. No damage was observed in the cartilage surrounding the rim. The presence of sharp demarcation between the tissue areas ablated by laser energy and the undamaged areas argues for the potential usefulness of the Er:YAG laser in surgery of cartilages.

Soluble Proteins Form Film by the Treatment of Low Temperature Plasma

NASA Astrophysics Data System (ADS)

Ikehara, Sanae; Sakakita, Hajime; Ishikawa, Kenji; Akimoto, Yoshihiro; Nakanishi, Hayao; Shimizu, Nobuyuki; Hori, Masaru; Ikehara, Yuzuru

2015-09-01

It has been pointed out that low temperature plasma in atmosphere was feasible to use for hemostasis without heat injury. Indeed, earlier studies demonstrated that low temperature plasma played an important role to stimulate platelets to aggregate and turned on the proteolytic activities of coagulation factors, resulting in the acceleration of the natural blood coagulation process. On the other hands, our developed equips could immediately form clots upon the contact with plasma flair, while the histological appearance was different from natural coagulation. Based on these findings in formed clots, we sought to determine if plasma flair supplied by our devices was capable of forming film using a series of soluble proteins Following plasma treatment, films were formed from bovine serum albumin, and the other plasma proteins at physiological concentration. Analysis of trans-electron microscope demonstrated that plasma treatment generated small protein particles and made them fuse to be larger aggregations The combined results demonstrated that plasma are capable of aggregating soluble proteins and that platelets and coagulation factors are not necessary for plasma induced blood coagulation. Supported in part by Grants-in-Aid for Scientific Research on Priority Area (21590454, 24590498, and 24108006 to Y. I.).

Risk factors for disseminated intravascular coagulation in patients with lung cancer.

PubMed

Nakano, Kentaro; Sugiyama, Kumiya; Satoh, Hideyuki; Shiromori, Sadaaki; Sugitate, Kei; Arifuku, Hajime; Yoshida, Naruo; Watanabe, Hiroyoshi; Tokita, Shingo; Wakayama, Tomoshige; Tatewaki, Masamitsu; Souma, Ryosuke; Koyama, Kenya; Hirata, Hirokuni; Fukushima, Yasutsugu

2018-05-31

The mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non-lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer. Twenty-six patients with progressive, inoperable stage IIB or higher lung cancer (20 men, 6 women; mean age 71 years; 11 Adeno, 10 squamous cell carcinoma, and 5 small cell carcinoma) and five healthy volunteers without respiratory disease (3 men, 2 women; mean age 72 years) were enrolled in the study. Blood samples were collected at lung cancer diagnosis, before treatment. White blood cell count, platelet count, serum C-reactive protein, fibrin/fibrinogen degradation products, fibrinogen, thrombin-antithrombin complex, and D-dimer levels differed significantly between lung cancer patients and the control group, but not among the pathologic types of lung cancer. Thrombomodulin levels were significantly higher in patients with Adeno and squamous cell carcinoma than in those with small cell carcinoma (P < 0.05 and P < 0.01, respectively). Antithrombin levels were significantly lower in patients with squamous cell carcinoma than in those with Adeno (P < 0.05). Coagulation disorders may develop secondary to chronic inflammation in patients with progressive lung cancer. DIC in lung cancer may be attributed to changes in anticoagulation factors, such as thrombomodulin and antithrombin, but not in other coagulation factors. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Isolation and partial purification of anticoagulant fractions from the venom of the Iranian snake Echis carinatus.

PubMed

Babaie, Mahdi; Zolfagharian, Hossein; Salmanizadeh, Hossein; Mirakabadi, Abbas Zare; Alizadeh, Hafezeh

2013-01-01

Many snake venoms comprise different factors, which can either promote or inhibit the blood coagulation pathway. Coagulation disorders and hemorrhage belong to the most prominent features of bites of the many vipers. A number of these factors interact with components of the human blood coagulation. This study is focused on the effect of Echis carinatus snake venom on blood coagulation pathway. Anticoagulant factors were purified from the Iranian Echis carinatus venom by two steps: gel filtration (Sephadex G-75) and ion-exchange (DEAE-Sephadex) chromatography, in order to study the anticoagulant effect of crude venom and their fractions. The prothrombin time was estimated on human plasma for each fraction. Our results showed that protrombin time value was increase from 13.4 s to 170 s for F2C and to 280 s for F2D. Our study showed that these fractions of the venom delay the prothrombine time and thus can be considered as anticoagulant factors. They were shown to exhibit proteolytic activity. The molecular weights of these anticoagulants (F2C, F2D) were estimated by SDS/PAGE electrophoresis. F2C comprises two protein bands with molecular weights of 50 and 79 kDa and F2D a single band with a molecular weight of 42 kDa.

A Joint Model for Vitamin K-Dependent Clotting Factors and Anticoagulation Proteins.

PubMed

Ooi, Qing Xi; Wright, Daniel F B; Tait, R Campbell; Isbister, Geoffrey K; Duffull, Stephen B

2017-12-01

Warfarin acts by inhibiting the reduction of vitamin K (VK) to its active form, thereby decreasing the production of VK-dependent coagulation proteins. The aim of this research is to develop a joint model for the VK-dependent clotting factors II, VII, IX and X, and the anticoagulation proteins, proteins C and S, during warfarin initiation. Data from 18 patients with atrial fibrillation who had warfarin therapy initiated were available for analysis. Nine blood samples were collected from each subject at baseline, and at 1-5, 8, 15 and 29 days after warfarin initiation and assayed for factors II, VII, IX and X, and proteins C and S. Warfarin concentration-time data were not available. The coagulation proteins data were modelled in a stepwise manner using NONMEM ® Version 7.2. In the first stage, each of the coagulation proteins was modelled independently using a kinetic-pharmacodynamic model. In the subsequent step, the six kinetic-pharmacodynamic models were combined into a single joint model. One patient was administered VK and was excluded from the analysis. Each kinetic-pharmacodynamic model consisted of two parts: (1) a common one-compartment pharmacokinetic model with first-order absorption and elimination for warfarin; and (2) an inhibitory E max model linked to a turnover model for coagulation proteins. In the joint model, an unexpected pharmacodynamic lag was identified and the estimated degradation half-life of VK-dependent coagulation proteins were in agreement with previously published values. The model provided an adequate fit to the observed data. The joint model represents the first work to quantify the influence of warfarin on all six VK-dependent coagulation proteins simultaneously. Future work will expand the model to predict the influence of exogenously administered VK on the time course of clotting factor concentrations after warfarin overdose and during perioperative warfarin reversal procedures.

Development of a microplate coagulation assay for Factor V in human plasma.

PubMed

Tilley, Derek; Levit, Irina; Samis, John A

2011-06-28

Factor V (FV) in its activated form, FVa, is a critical regulator of thrombin generation during fibrin clot formation. There is a need of a simple, fast, and inexpensive microplate-based coagulation assay to measure the functional activity of FV in human plasma. The objective of this study was to develop a microplate-based assay that measures FV coagulation activity during clot formation in human plasma, which is currently not available. The FV assay requires a kinetic microplate reader to measure the change in absorbance at 405nm during fibrin formation in human plasma. The FV assay accurately measures the time, initial rate, and extent of fibrin clot formation in human plasma. The FV microplate assay is simple, fast, economical, sensitive to approx 24-80pM, and multiple samples may be analyzed simultaneously. All the required materials are commercially available. Standard curves of time or initial rate of fibrin clot formation vs FV activity in the 1-stage assay (Without activation by thrombin) may be used to measure FV activity in samples of human plasma. The assay was used to demonstrate that in nine patients with disseminated intravascular coagulation (DIC), the FV 1-stage, 2-stage (With activation by thrombin), and total (2-stage activity - 1-stage activity) activities were decreased, on average, by approximately 54%, 44%, and 42%, respectively, from prolonged clot times when compared to normal pooled human reference plasma (NHP). The results indicate that the FV in the DIC patient plasmas supported both a delayed and slower rate of fibrin clot formation compared with NHP; however, the extent of fibrin clot formation in the DIC patients remained largely unchanged from that observed with NHP. The FV microplate assay may be easily adapted to measure the activity of any coagulation factor using the appropriate factor-deficient plasma and clot initiating reagent. The microplate assay will find use in both research and clinical laboratories to provide measurement of the functional coagulation activity of FV in human plasma.

Pneumothorax as a complication of percutaneous radiofrequency ablation for lung neoplasms.

PubMed

Yamagami, Takuji; Kato, Takeharu; Hirota, Tatsuya; Yoshimatsu, Rika; Matsumoto, Tomohiro; Nishimura, Tsunehiko

2006-10-01

The present study was performed to determine the frequency of the complication of pneumothorax after radiofrequency (RF) ablation for lung neoplasms and risk factors affecting such pneumothoraces. The study was based on 129 consecutive sessions of percutaneous RF ablation of lung neoplasms under real-time computed tomographic fluoroscopic guidance performed in a single institution between May 2003 and November 2005 in 41 patients (17 women, 24 men; mean age, 63 years; age range, 29-82 y). Correlation was determined between the incidence of pneumothorax after RF ablation and multiple factors: sex, age, presence of emphysema, lesion size, lesion depth, contact of tumor with pleura, number of punctures, maximum power of RF generator, period of ablation, tissue temperature at the end of the RF ablation session, and patient position during the procedure. Management of each case of iatrogenic pneumothorax was reviewed. Pneumothorax after RF ablation occurred in 38 of 129 RF ablation sessions (29.5%). Fourteen of the 38 cases were treated by manual aspiration, and 24 were simply observed. In five cases (3.9%), chest tube placement was required as therapy for pneumothorax. The risk of pneumothorax was significantly increased in patients with pulmonary emphysema. The frequency of pneumothorax after RF ablation in our experience is similar to the frequency of pneumothorax after lung biopsy reported in the literature. Various conditions for RF ablation did not influence the incidence of pneumothorax. Emphysema was the only individual factor that correlated significantly with the development of iatrogenic pneumothorax.

How Frequency of Electrosurgical Current and Electrode Size Affect the Depth of Electrocoagulation.

PubMed

Taheri, Arash; Mansoori, Parisa; Bahrami, Naeim; Alinia, Hossein; Watkins, Casey E; Feldman, Steven R

2016-02-01

Many factors affect the depth of electrocoagulation. To evaluate the effect of current frequency and electrode size on the depth of electrocoagulation. In this in vitro study, 4 cylindrical electrodes (2, 2.3, 3, and 4 mm) were used to apply 3 electrosurgical currents (0.4, 1.5, and 3 MHz) to bovine liver. Each electrode was placed at different points on the surface of the liver, and energy at various levels and frequencies was delivered to the tissue. Subsequently, cross-sections of the liver were analyzed. Coagulation started at the periphery of the electrode-tissue contact area. With higher energy levels, coagulation spreads to involve the remainder of the contact area. Neither the frequency nor the electrode size had any effect on this coagulation pattern. The frequency of the current also did not show any relation with depth of coagulation; however, there was a direct correlation between the size of the electrode and the depth of coagulation. Larger-tip electrodes provided deeper coagulation compared with finer-tip electrodes.

Life-threatening urethral hemorrhage after placement of a Foley catheter in a patient with uroseptic disseminated intravascular coagulation due to chronic urinary retention induced by untreated benign prostatic hyperplasia.

PubMed

Ikegami, Yukihiro; Yoshida, Keisuke; Imaizumi, Tsuyoshi; Isosu, Tsuyoshi; Kurosawa, Shin; Murakawa, Masahiro

2016-10-01

A 77-year-old man with severe septic disseminated intravascular coagulation following urinary infection was transported to our hospital. He had developed urinary retention induced by untreated prostatic hyperplasia. Immediate drainage with a Foley catheter was successfully carried out, but the hematuria progressed to life-threatening hemorrhage. Complete hemostasis was impossible by surgical treatment because the tissue around the prostatic urethra was very fragile and hemorrhagic. Organized treatments (continuous hemodiafiltration combined with polymyxin-B immobilized fiber column hemoperfusion and systemic treatment with antibiotics and coagulation factors) were commenced soon after the operation. The patient eventually recovered from the septic disseminated intravascular coagulation. This case report illustrates the risk of placement of Foley catheters in patients with severe septic disseminated intravascular coagulation.

Chronic sleep deprivation markedly reduces coagulation factor VII expression

PubMed Central

Pinotti, Mirko; Bertolucci, Cristiano; Frigato, Elena; Branchini, Alessio; Cavallari, Nicola; Baba, Kenkichi; Contreras-Alcantara, Susana; Ehlen, J. Christopher; Bernardi, Francesco; Paul, Ketema N.; Tosini, Gianluca

2010-01-01

Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (−30.5%) the thrombin generation potential in plasma evaluated upon extrinsic (TF/FVIIa pathway) but not intrinsic activation of coagulation. This variation was consistent with a decrease (−49.8%) in the plasma activity levels of factor VII (FVII), the crucial physiologicalal trigger of coagulation, which was even more pronounced at the liver mRNA level (−85.7%). The recovery in normal sleep conditions for three days completely restored thrombin generation and FVII activity in plasma. For the first time, we demonstrate that chronic sleep deprivation on its own reduces, in a reversible manner, the FVII expression levels, thus influencing the TF/FVIIa activation pathway efficiency. PMID:20418241

Factors affecting tumor ablation during high intensity focused ultrasound treatment.

PubMed

Hassanuddin, Aizan; Choi, Jun-Ho; Seo, Dong-Wan; Ryu, Choong Heon; Kim, Su-Hui; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2014-07-01

High intensity focused ultrasound (HIFU) utilizes a targeted extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We used an in vitro model to examine the effects of bone, metallic stents, plastic stents, metal plates, and cyst-like lesions on HIFU treatment. HIFU was delivered to the phantom models implanted with foreign bodies, and the location, shape, and size of the ablated zones were evaluated. Bone and metallic plates reflected the ultrasound beam, shifting the ablation zone from the focal zone to the prefocal area. In the phantoms containing metal stent, plastic stent, and cyst, most of the ablative energy was reflected to the prefocal area by the surface, with the remainder penetrating through the phantom. The area of the ablated margins was significantly larger in size and volume than the intended focal ablation zone. During HIFU therapy, artificial or anatomical barriers could affect the direction of the ultrasound beams, shifting the ablation zone from the focal area to a prefocal site with a larger than expected ablation zone. These factors should be considered prior to HIFU treatment for pancreatic tumors because they could limit ablation success, in addition to causing complications.

Hemostasis in Overt and Subclinical Hyperthyroidism

PubMed Central

Ordookhani, Arash; Burman, Kenneth D.

2017-01-01

Context There are contradictory results on the effect of hyperthyroidism on hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). The present review focuses on hemostatic changes in overt and subclinical hyperthyroidism. Methods A systematic literature search was conducted employing MEDLINE database. The following words were used for the search: Hyperthyroidism; thyrotoxicosis; Graves disease; goiter, nodular; hemostasis; blood coagulation factors; blood coagulation disorders; venous thromboembolism; bleeding; fibrinolysis. The articles that were related to hyperthyroidism and hemostasis are used in this manuscript. Results Hyperthyroidism, either overt or subclinical, renders a hypercoagulable state, although there are several studies with contradictory findings in the literature. Hypercoagulability may be caused by an increase in the level of various coagulation factors such as factor (F) VIII, FX, FIX, von Willebrand F (vWF), and fibrinogen, while hypofibrinolysis by changes in coagulation parameters such as a decrease in plasmin and plasmin activator or an increase in α2-antiplasmin, plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor Conclusions Although many reports are in favor of a hypercoagulable state in overt hyperthyroidism but this finding at the biochemical level and its clinical implication, on the occurrence of VTE, has yet to be confirmed. PMID:29201071

Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype

PubMed Central

Capote, Joana; Martinez, Leonel; Vetrone, Sylvia; Barton, Elisabeth R.; Sweeney, H. Lee; Miceli, M. Carrie

2016-01-01

In the degenerative disease Duchenne muscular dystrophy, inflammatory cells enter muscles in response to repetitive muscle damage. Immune factors are required for muscle regeneration, but chronic inflammation creates a profibrotic milieu that exacerbates disease progression. Osteopontin (OPN) is an immunomodulator highly expressed in dystrophic muscles. Ablation of OPN correlates with reduced fibrosis and improved muscle strength as well as reduced natural killer T (NKT) cell counts. Here, we demonstrate that the improved dystrophic phenotype observed with OPN ablation does not result from reductions in NKT cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. These changes are associated with increased expression of pro-regenerative factors insulin-like growth factor 1, leukemia inhibitory factor, and urokinase-type plasminogen activator. Furthermore, altered macrophage polarization correlated with increases in muscle weight and muscle fiber diameter, resulting in long-term improvements in muscle strength and function in mdx mice. These findings suggest that OPN ablation promotes muscle repair via macrophage secretion of pro-myogenic growth factors. PMID:27091452

Factor XI as a target for antithrombotic therapy

PubMed Central

Bane, Charles E.; Gailani, David

2014-01-01

Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

Autotransfusion from experimental hemothorax: levels of coagulation factors.

PubMed

Napoli, V M; Symbas, P J; Vroon, D H; Symbas, P N

1987-03-01

The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.

Anticoagulation by factor Xa inhibitors.

PubMed

Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

2010-08-01

Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

Selective nanoparticle-directed photothermal ablation of the canine prostate

NASA Astrophysics Data System (ADS)

Schwartz, Jon A.; Price, Roger E.; Gill-Sharp, Kelly L.; Sang, Krystina L.; Khorchani, Jennifer D.; Payne, J. Donald; Goodwin, Bradford S.

2011-03-01

This study adapted AuroLase® Therapy, previously reported for the treatment of brain tumors, to the treatment of prostate disease by 1) using normal canine prostate in vivo, directly injected with a solution of nanoparticles as a proxy for prostate tumor and, 2) developing an appropriate laser dosimetry for prostate which is which is subablative in native prostate while simultaneously producing photothermal coagulation in prostate tissue containing therapeutic nanoshells. Healthy, mixed-breed hound dogs were given surgical laparotomies during which nanoshells were injected directly into one or both prostate hemispheres. Laser energy was delivered percutaneously to the parenchyma of the prostate along 1-5 longitudinal tracts via a liquid-cooled optical fiber catheter terminated with a 1-cm isotropic diffuser after which the incision was closed and sutured using standard surgical techniques. The photothermal lesions were permitted to resolve for up to 8 days, after which each animal was euthanized, necropsied, and the prostate taken for histopathological analysis. We developed a laser dosimetry which is sub- to marginally ablative in native prostate and simultaneously ablative of prostate tissue containing nanoshells which would indicate a viable means of treating tumors of the prostate which are known from other studies to accumulate nanoshells. Secondly, we determined that multiple laser treatments of nanoshell-containing prostate tissue could be accomplished while sparing the urethra and prostate capsule thermal damage. Finally, we determined that the extent of damage zone radii correlate positively with nanoshell concentration, and negatively to the length of time between nanoshell injection and laser treatment.

Optoacoustic monitoring of cutting efficiency and thermal damage during laser ablation.

PubMed

Bay, Erwin; Douplik, Alexandre; Razansky, Daniel

2014-05-01

Successful laser surgery is characterized by a precise cut and effective hemostasis with minimal collateral thermal damage to the adjacent tissues. Consequently, the surgeon needs to control several parameters, such as power, pulse repetition rate, and velocity of movements. In this study we propose utilizing optoacoustics for providing the necessary real-time feedback of cutting efficiency and collateral thermal damage. Laser ablation was performed on a bovine meat slab using a Q-switched Nd-YAG laser (532 nm, 4 kHz, 18 W). Due to the short pulse duration of 7.6 ns, the same laser has also been used for generation of optoacoustic signals. Both the shockwaves, generated due to tissue removal, as well as the normal optoacoustic responses from the surrounding tissue were detected using a single broadband piezoelectric transducer. It has been observed that the rapid reduction in the shockwave amplitude occurs as more material is being removed, indicating decrease in cutting efficiency, whereas gradual decrease in the optoacoustic signal likely corresponds to coagulation around the ablation crater. Further heating of the surrounding tissue leads to carbonization accompanied by a significant shift in the optoacoustic spectra. Our results hold promise for real-time monitoring of cutting efficiency and collateral thermal damage during laser surgery. In practice, this could eventually facilitate development of automatic cut-off mechanisms that will guarantee an optimal tradeoff between cutting and heating while avoiding severe thermal damage to the surrounding tissues.

An in vitro analysis of the effect of acidosis on coagulation in chronic disease states - a thromboelastograph study.

PubMed

White, Hayden; Bird, Robert; Sosnowski, Kellie; Jones, Mark

2016-06-01

Thrombosis is a complication of many chronic illnesses. Chronic obstructive pulmonary disease (COPD) and diabetes mellitus are common medical conditions frequently associated with a hypercoagulable state. Acidaemia has been shown to reduce coagulation. COPD and diabetes mellitus during acute deterioration can present with a severe acidaemia. The impact of this acidaemia on coagulation is poorly studied. Patients presenting with a diagnosis of diabetic ketoacidosis or type II respiratory failure from COPD and a pH of less than 7.2 were included in our study. A coagulation screen and a thromboelastograph (TEG) were performed on admission and 24 hours later. The mean pH on admission was 7.07 and mean base excess was -16.3. The activated partial thromboplastin time was associated with pH change but remained within the normal range (26-41 s). All other coagulation and TEG parameters failed to show evidence of association (p>0.05). In the two models of non-haemorrhagic acidosis investigated, coagulation was not altered by the changes in pH. More work is needed to understand the complex relationship between factors affecting coagulation in individual disease processes. © 2016 Royal College of Physicians.

Neonatal Plasma Transfusion: An Evidence-Based Review.

PubMed

Keir, Amy K; Stanworth, Simon J

2016-10-01

Several clinical scenarios for plasma transfusion are repeatedly identified in audits, including treatment of bleeding in association with laboratory evidence of coagulopathy, correction of disseminated intravascular coagulation, prevention of intraventricular hemorrhage, management of critically ill neonates (eg, during sepsis or as a volume expander), or correction of markers of prolonged coagulation in the absence of bleeding. The findings of at least one national audit of transfusion practice indicated that almost half of plasma transfusions are given to neonates with abnormal coagulation values with no evidence of active bleeding, despite the limited evidence base to support the effectiveness of this practice. Plasma transfusions to neonates should be considered in the clinical context of bleeding (eg, vitamin K dependent), disseminated intravascular coagulation, and very rare inherited deficiencies of coagulation factors. There seems to be no role for prophylactic plasma to prevent intraventricular hemorrhage or for use as a volume expander. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigating the characteristic strength of flocs formed from crude and purified Hibiscus extracts in water treatment.

PubMed

Jones, Alfred Ndahi; Bridgeman, John

2016-10-15

The growth, breakage and re-growth of flocs formed using crude and purified seed extracts of Okra (OK), Sabdariffa (SB) and Kenaf (KE) as coagulants and coagulant aids was assessed. The results showed floc size increased from 300 μm when aluminium sulphate (AS) was used as a coagulant to between 696 μm and 722 μm with the addition of 50 mg/l of OK, KE and SB crude samples as coagulant aids. Similarly, an increase in floc size was observed when each of the purified proteins was used as coagulant aid at doses of between 0.123 and 0.74 mg/l. The largest floc sizes of 741 μm, 460 μm and 571 μm were obtained with a 0.123 mg/l dose of purified Okra protein (POP), purified Sabdariffa (PSP) and purified Kenaf (PKP) respectively. Further coagulant aid addition from 0.123 to 0.74 mg/l resulted in a decrease in floc size and strength in POP and PSP. However, an increase in floc strength and reduced d50 size was observed in PKP at a dose of 0.74 mg/l. Flocs produced when using purified and crude extract samples as coagulant aids exhibited high recovery factors and strength. However, flocs exhibited greater recovery post-breakage when the extracts were used as a primary coagulant. It was observed that the combination of purified proteins and AS improved floc size, strength and recovery factors. Therefore, the applications of Hibiscus seeds in either crude or purified form increases floc growth, strength, recoverability and can also reduce the cost associated with the import of AS in developing countries. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

PubMed

Tang, Mariann; Fenger-Eriksen, Christian; Wierup, Per; Greisen, Jacob; Ingerslev, Jørgen; Hjortdal, Vibeke; Sørensen, Benny

2017-06-01

Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes

PubMed Central

Oehmcke, Sonja; Westman, Johannes; Malmström, Johan; Mörgelin, Matthias; Olin, Anders I.; Kreikemeyer, Bernd; Herwald, Heiko

2013-01-01

Previous studies have shown that stimulation of whole blood or peripheral blood mononuclear cells with bacterial virulence factors results in the sequestration of pro-coagulant microvesicles (MVs). These particles explore their clotting activity via the extrinsic and intrinsic pathway of coagulation; however, their pathophysiological role in infectious diseases remains enigmatic. Here we describe that the interaction of pro-coagulant MVs with bacteria of the species Streptococcus pyogenes is part of the early immune response to the invading pathogen. As shown by negative staining electron microscopy and clotting assays, pro-coagulant MVs bind in the presence of plasma to the bacterial surface. Fibrinogen was identified as a linker that, through binding to the M1 protein of S. pyogenes, allows the opsonization of the bacteria by MVs. Surface plasmon resonance analysis revealed a strong interaction between pro-coagulant MVs and fibrinogen with a KD value in the nanomolar range. When performing a mass-spectrometry-based strategy to determine the protein quantity, a significant up-regulation of the fibrinogen-binding integrins CD18 and CD11b on pro-coagulant MVs was recorded. Finally we show that plasma clots induced by pro-coagulant MVs are able to prevent bacterial dissemination and possess antimicrobial activity. These findings were confirmed by in vivo experiments, as local treatment with pro-coagulant MVs dampens bacterial spreading to other organs and improved survival in an invasive streptococcal mouse model of infection. Taken together, our data implicate that pro-coagulant MVs play an important role in the early response of the innate immune system in infectious diseases. PMID:23935504

Evaluation of Consequences of Dust Positioned in Southwest of Iran on Coagulant Factors

PubMed Central

Saeb, Keivan; Sarizade, Gholamreza; Khodadi, Mohammad; Biazar, Esmaeil

2013-01-01

Background: Various regions in Iran, especially the Khuzestan Province, have been covered by dust and dirt during the past two years due to environmental changes in the Middle East. We sought to evaluate the effect of these pollutants on the coagulant factors of people residing in Abadan and Khoramshahr, two major cities of Khuzestan Province. Methods: One hundred twenty-nine healthy individuals were enrolled into this study, and their prothrombin time as well as fibrinogen, platelet, and Factor VIII levels were measured before and after climate changes. Results: After climate changes, the mean prothrombin time decreased, while the fibrinogen, platelet, and Factor VIII levels rose. Conclusion: The results of this study suggest that the pollutants deployed in the Middle East can affect prothrombin time as well as fibrinogen, platelet, and Factor VII levels considerably and increase coagulant state. The pollutants can, consequently, increase the risk of cardiovascular diseases. It seems that cooperation at government levels between Iran and its neighboring countries is required to reverse desertification and avoid inaccurate usage of subterranean water resources so as to lessen air pollution. PMID:23825886

The fibrinogen/CRP ratio as a new parameter for the diagnosis of disseminated intravascular coagulation in patients with HELLP syndrome and as a predictive factor for neonatal outcome.

PubMed

Windsperger, Karin; Lehner, Rainer

2013-02-01

The aim of this study was to determine if the fibrinogen/C-reactive protein (CRP) ratio could be used in obstetrics as a predictor for a disseminated intravascular coagulation. One hundred eleven patients with hemolysis, elevated liver enzymes, and low platelet count syndrome at the Department of Obstetrics and Fetomaternal Medicine (General Hospital, Vienna, Austria) were selected and divided into 2 groups (overt disseminated intravascular coagulation, no overt disseminated intravascular coagulation). The classical parameters and the fibrinogen/CRP ratio were compared. The analysis was carried out using IBM SPSS statistical package (SPSS, Inc, Cary, NC). The fibrinogen/CRP ratio showed significant differences. The receiver-operating characteristic analysis showed for the ratio (area under the curve, 0.74) significantly better discriminative power than for fibrinogen (area under curve, 0.59). The odds ratio for the fibrinogen/CRP ratio was 7.04. Finally, significant correlations between the ratio and the neonatal outcome were found. We suggest the implementation of the fibrinogen/CRP ratio within patients with hemolysis, elevated liver enzymes, and low platelet count syndrome as a diagnostic and prognostic factor for the occurrence of disseminated intravascular coagulation. Copyright © 2013 Mosby, Inc. 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.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.

PubMed

Ordookhani, Arash; Burman, Kenneth D

2017-04-01

There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders

PubMed Central

Ordookhani, Arash; Burman, Kenneth D.

2017-01-01

Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Results Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Conclusions Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted. PMID:29026409

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

PubMed

Lee, D; Nayak, S; Martin, S W; Heatherington, A C; Vicini, P; Hua, F

2016-12-01

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. Background Prothrombin fragment 1 + 2 (F 1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F 1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F 1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F 1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F 1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F 1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. © 2016 International Society on Thrombosis and Haemostasis.

Carbon Dioxide Laser Ablation of Basal Cell Carcinoma with Visual Guidance by Reflectance Confocal Microscopy: A Proof of Principle Pilot Study

PubMed Central

Hibler, B.P.; Sierra, H.; Cordova, M.; Phillips, W.; Rajadhyaksha, M.; Nehal, K.S.; Rossi, A.M.

2016-01-01

Background Laser ablation is an alternative, non-surgical treatment modality for low-risk basal cell carcinoma (BCC); however, lack of confirmative tumour destruction or residual tumour presence has been a limiting factor to adoption. Reflectance confocal microscopy (RCM) provides non-invasive, cellular-level resolution imaging of the skin and is capable of identifying tumour. Objective To evaluate the use of RCM to guide carbon dioxide (CO2) laser ablation of BCC, confirm destruction, and correlate findings with histology. Methods RCM was used pre-ablation to evaluate for features of BCC. Ablation was performed with a CO2 laser, and the response rapidly assessed using handheld RCM to evaluate for residual tumour. Confirmative pathology was used to verify confocal imaging. Results RCM imaging identified tumour pre-ablation with features not identified on normal, surrounding skin. Post-ablation, RCM documented complete removal of tumour in six cases and residual tumour in two. Histologic examination identified the ablated area and confirmed clearance of tumour in the six aforementioned cases and corroborated confocal findings for residual tumour in the other two cases. Conclusions We report successful treatment of superficial and nodular BCC using CO2 laser ablation augmented by RCM imaging for pre-ablation guidance and verification of tumour removal post-ablation. Akin to complete circumferential and deep margin control techniques, using RCM helps to map peripheral and deep BCC margins to hone in on areas exhibiting persistent tumour after ablation. CO2 laser ablation visually guided by RCM can help circumvent previously cited limiting factors of laser ablation for tumour destruction by providing cellular-level resolution imaging of tumour and margin assessment in between each laser pass and post-ablation. PMID:26800657

Comparison of a novel high-power blue diode laser (λ=442 nm) with Ho:YAG (λ=2100 nm), Tm fiber (λ=1940 nm), and KTP (λ=532 nm) lasers for soft tissue ablation

NASA Astrophysics Data System (ADS)

Vinnichenko, Victoriya; Kovalenko, Anastasiya; Arkhipova, Valeriya; Yaroslavsky, Ilya; Altshuler, Gregory; Gapontsev, Valentin

2018-02-01

Three lasers were directly compared, including the Ho:YAG laser (λ = 2100 nm), Tm fiber laser (λ = 1940 nm) operating in 3 different modes (CW, regular pulse, and super pulse), and blue diode laser (λ = 442 nm) for vaporization and coagulation efficiency for treating blood-rich soft tissues, ex vivo, in a porcine kidney model at quasi-contact cutting in water. In addition, experimental results were compared with published data on performance of KTP laser (λ = 532 nm) at similar experimental settings (Power = 60 W and cutting speed = 2 mm/s). Tm fiber laser in pulsed mode and blue laser produced highest vaporization rates of 3.7 and 3.4 mm3/s, respectively. Tm fiber laser (in both CW and pulsed modes) also produced the largest coagulation zone among the laser sources tested. A carbonization zone was observed for Tm fiber laser in CW and pulsed modes, as well as for the blue diode laser. Tm fiber laser in super-pulse mode and Ho:YAG laser both resulted in irregular coagulation zones without carbonization. Comparison with known data for KTP laser revealed that tissue effects of the blue laser are similar to that of the KTP laser. These results suggest that the combination of the two lasers (Tm fiber and blue diode) in one system may achieve high cutting efficiency and optimal coagulation for hemostasis during surgical treatment. Ex vivo testing of the combined system revealed feasibility of this approach. The combination of the CW Tm fiber laser (120W) and the blue diode laser (60W) emitting through a combination tip were compared with CW 120 W Tm fiber laser alone and 120 W Ho:YAG laser. Vaporization rates measured 34, 28, and 6 mm3/s, and coagulation zones measured 0.6, 1.3, and 1.7 mm, respectively. A carbonization zone was only observed with CW Tm fiber laser. The vaporization rate of combined CW Tm fiber laser / blue diode laser was comparable to published data for KTP laser for equivalent total power. Thus, high-power blue diode laser, Tm fiber laser, and their combination may provide an alternative to conventional Ho:YAG and KTP lasers for applications in urology and other surgical fields.

MR-guided conformal heating of canine prostate using interstitial applicators

NASA Astrophysics Data System (ADS)

Nau, William H.; Diederich, Chris J.; Ross, Anthony; Butts, R. K.; Rieke, Viola; Bouley, Donna; Gill, Harchi; Daniel, Bruce; Sommer, Graham

2003-06-01

MRI compatible, multi-element ultrasound applicators were fabricated using cylindrical piezoceramic transducers sectored to 180 degrees to provide angular directional heating. The applicators were designed to be inserted into standard 13 or 14 gage brachytherapy catheters integrated with water-cooling. Two applicators were inserted transperinealy into the posterior region of a canine prostate. Power output ranged from 5-15 W per element during the 15 minute heating period. Phase-sensitive gradient-recalled MR imaging was used to monitor the treatment in real-time on a 0.5 Tesla MRT system. Gadolinium-enhanced T1 weighted images and diffusion-weighted images were obtained to view the regions which had been ablated during the heating procedure. Upon euthanasia, the prostate was removed, axially sectioned, and stained with TTC to reveal any regions of remaining viable tissue. Results from this study indicated a large volume of ablated tissue within the prostate which was highly correlated to the regions in the T1-weighted and diffusion-weighted images which had decreased intensity, and to the 52C contour displayed in the images obtained during the treatment. This study demonstrates the ability to control thermal coagulation within a targeted tissue volume while protecting surrounding tissue from thermal damage.

Prenatal Therapy of Large Placental Chorioangiomas: Case Report and Review of the Literature

PubMed Central

Hosseinzadeh, Pardis; Shamshirsaz, Alireza A.; Javadian, Pouya; Espinoza, Jimmy; Gandhi, Manisha; Ruano, Rodrigo; Cass, Darrell L.; Olutoye, Oluyinka A.; Belfort, Michael A.

2015-01-01

Objective To review techniques and outcomes of different prenatal treatments for large placental chorioangiomas. Study Design Presentation of a case of laparoscopic-assisted laser coagulation and a systematic review of the literature for articles related to intervention for placental chorioangioma. Results A total of 37 cases of definitive (n = 23) and supportive therapy (n = 14) were evaluated, including one case treated in our center. Approximately 35% of the patients had a spontaneous preterm delivery in definitive treatment group versus 36% in the supportive group. The infant survival rates were 65 and 71% in the two groups, respectively. We further compared the two types of laser ablation (fetoscopic [n = 10] and interstitial [n = 4]). Approximately 30% of the patients in the fetoscopic and 25% in interstitial group, had a spontaneous preterm delivery. Survival rates were 60 and 100% in fetoscopic and interstitial groups, respectively. Conclusion Laser ablation and embolization of chorioangiomas via minimally invasive approach may prevent or reverse fetal hydrops due to high cardiac states. However, further studies are needed to refine the appropriate selection criteria that will justify the risk of this invasive in utero therapy for chorioangiomas. PMID:26495184

Canine transurethral laser prostatectomy using a rotational technique

NASA Astrophysics Data System (ADS)

Cromeens, Douglas M.; Johnson, Douglas E.

1995-05-01

Conventional radical prostatectomy in the dog has historically been attended by unacceptably high incidence of urinary incontinence (80 - 100%). Ablation of the prostate can be accomplished in the dog by transurethral irradiation of the prostate with the Nd:YAG laser and a laterally deflecting fiber. Exposure has ranged between 40 and 60 watts for 60 seconds at 4 fixed locations. Although prostatectomies performed with the above described technique offers significant advantage over conventional prostatectomies, the high power density at each location can result in small submucosal explosions (`popcorn effect') that increase the potential for bleeding and rupture of the prostatic capsule. We describe a new technique in which the energy is applied continuously by a laser fiber rotating around a central point. Delivering 40 watts of Nd:YAG energy for 4 minutes using a new angle-delivery device (UrotekTM), we produced results comparable to those of other previously reported techniques in the canine model with two added advantages: (1) a more even application of heat resulting in no `popcorn' effect and (2) a more reliably predictable area of coagulative necrosis within a given axial plane. This technique should provide additional safety for the veterinary surgeon performing visual laser ablation of the prostate in the dog.

Vitamin K: from coagulation to calcification.

PubMed

Paakkari, Ilari

Vitamin K is not only essential for the synthesis of coagulation factors in the liver, but it also strengthens the bones and prevents calcification of the arteries. These effects are mediated through the same mechanism, i.e. carboxylation of Gla target proteins. The discovery of novel Gla proteins that are not associated with blood coagulation or calcium metabolism indicates that vitamin K has additional effects in the pancreas and the central nervous system, for example. As dietary supplements, vitamin K1 of plant origin and vitamins K2 of bacterial origin may exert different effects.

Use of combined coagulation-adsorption process as pretreatment of landfill leachate

PubMed Central

2013-01-01

Landfill leachate is an important pollution factor resulting from municipal landfill sites. Physical and chemical processes are the better option for pretreatment or full treatment of landfill leachate. This article presents a combination of pre-treatment method (coagulation and adsorption) for leachate collected from municipal solid waste open dumping site. Physico chemical characteristics of stabilized and fresh leachate were examined. Coagulation process was examined by using alum and ferric chloride. A low cost adsorbent, fly ash was used for adsorption studies. Coagulation studies were carried out for fresh and stabilized leachate. Adsorption studies have been conducted for alum pre-treated stabilized leachate. Effect of coagulant dose, adsorbent dose, pH and contact time were carried out. The effective optimum coagulant dosages were 0.6 g/L and 0.7 g/L for alum and ferric chloride respectively for stabilized leachate and incase of fresh leachate 0.8 g/L and 0.6 g/L for alum and ferric chloride respectively. For the alum pretreated stabilized leachate, the maximum COD removal is 28% using fly ash adsorbent with equilibrium time of 210 min and optimum dose of 6 g/L. Overall COD removal efficiency of 82% was obtained by coagulation using alum and adsorption using fly ash for stabilized leachate. The results obtained showed that combined coagulation and adsorption process can be used effectively for stabilized leachate treatment. PMID:23517661

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

PubMed

Reddel, C J; Allen, J D; Ehteda, A; Taylor, R; Chen, V M Y; Curnow, J L; Kritharides, L; Robertson, G

2017-03-01

Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a hypercoagulable state, which is partly attributable to IL-6 release by the tumor. The findings support the importance of the coagulation state in cancer cachexia and the clinical utility of anti-inflammatory interventions. © 2017 International Society on Thrombosis and Haemostasis.

Four-dimensional optoacoustic temperature mapping in laser-induced thermotherapy

NASA Astrophysics Data System (ADS)

Oyaga Landa, Francisco Javier; Deán-Ben, Xosé Luís.; Sroka, Ronald; Razansky, Daniel

2018-02-01

Photoablative laser therapy is in common use for selective destruction of malignant masses, vascular and brain abnormalities. Tissue ablation and coagulation are irreversible processes occurring shortly after crossing a certain thermal exposure threshold. As a result, accurate mapping of the temperature field is essential for optimizing the outcome of these clinical interventions. Here we demonstrate four-dimensional optoacoustic temperature mapping of the entire photoablated region. Accuracy of the method is investigated in tissue-mimicking phantom experiments. Deviations of the volumetric optoacoustic temperature readings provided at 40ms intervals remained below 10% for temperature elevations above 3°C, as validated by simultaneous thermocouple measurements. The excellent spatio-temporal resolution of the new temperature monitoring approach aims at improving safety and efficacy of laser-based photothermal procedures.

Mapping of thermal injury in biologic tissues using quantitative pathologic techniques

NASA Astrophysics Data System (ADS)

Thomsen, Sharon L.

1999-05-01

Qualitative and quantitative pathologic techniques can be used for (1) mapping of thermal injury, (2) comparisons lesion sizes and configurations for different instruments or heating sources and (3) comparisons of treatment effects. Concentric zones of thermal damage form around a single volume heat source. The boundaries between some of these zones are distinct and measurable. Depending on the energy deposition, heating times and tissue type, the zones can include the following beginning at the hotter center and progressing to the cooler periphery: (1) tissue ablation, (2) carbonization, (3) tissue water vaporization, (4) structural protein denaturation (thermal coagulation), (5) vital enzyme protein denaturation, (6) cell membrane disruption, (7) hemorrhage, hemostasis and hyperhemia, (8) tissue necrosis and (9) wound organization and healing.

Comparison of laser- and RF-based interstitial coagulation systems for the treatment of liver tumors (Invited Paper)

NASA Astrophysics Data System (ADS)

de Jager, Arjan A.; van Trier, Bart N.; Veenendaal, Liesbeth M.; van Hillegersberg, Richard; Verdaasdonk, Rudolf M.

2005-04-01

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Surgical treatments, including hepatic resection and liver transplantation are considered as the most effective treatment of HCC. However, less than 20% of HCC patients can be treated surgically because of: multi-focal diseases, proximity of tumor to key vascular or biliary structures and inadequate functional hepatic reserve related coexistent cirrhosis. In this unfortunate groups of patients various palliative treatments modalities are being performed to extend the time of survival and quality of life. These techniques include trans-catheter arterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and Interstitial Thermal Therapy: laser-induced interstitial thermotherapy (LITT) and radio-frequency ablation (RFA).

Abnormal factor VIII coagulant antigen in patients with renal dysfunction and in those with disseminated intravascular coagulation.

PubMed Central

Weinstein, M J; Chute, L E; Schmitt, G W; Hamburger, R H; Bauer, K A; Troll, J H; Janson, P; Deykin, D

1985-01-01

Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments. Images PMID:3932466

Pleural Puncture that Excludes the Ablation Zone Decreases the Risk of Pneumothorax after Percutaneous Microwave Ablation in Porcine Lung

PubMed Central

Lee, Kyungmouk Steve; Takaki, Haruyuki; Yarmohammadi, Hooman; Srimathveeravalli, Govindarajan; Luchins, Kerith; Monette, Sébastien; Nair, Sreejit; Kishore, Sirish; Erinjeri, Joseph P.

2017-01-01

Purpose To test the hypothesis that the geometry of probe placement with respect to the pleural puncture site affects the risk of pneumothorax after microwave (MW) ablation in the lung. Materials and Methods Computed tomography–guided MW ablation of the lung was performed in 8 swine under general anesthesia and mechanical ventilation. The orientation of the 17-gauge probe was either perpendicular (90°) or parallel (< 30°) with respect to the pleural puncture site, and the ablation power was 30 W or 65 W for 5 minutes. After MW ablation, swine were euthanized, and histopathologic changes were assessed. Frequency and factors affecting pneumothorax were evaluated by multivariate analysis. Results Among 62 lung MW ablations, 13 (21%) pneumothoraces occurred. No statistically significant difference was noted in the rate of pneumothorax between the perpendicular and the parallel orientations of the probe (31% vs 14%; odds ratio [OR], 2.8; P = .11). The pneumothorax rate was equal for 65-W and 30-W ablation powers (21% and 21%; OR, 1.0; P = .94). Under multivariate analysis, 2 factors were independent positive predictors of pneumothorax: ablation zone inclusive of pleural insertion point (OR, 7.7; P = .02) and time since intubation (hours) (OR, 2.7; P = .02). Conclusions Geometries where the pleural puncture site excluded the ablation zone decreased pneumothorax in swine undergoing MW ablation in the lung. Treatment planning to ensure that the pleural puncture site excludes the subsequent ablation zone may reduce the rate of pneumothorax in patients undergoing MW ablation in the lung. PMID:25753501

Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

PubMed

Mast, Alan E

2016-01-01

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

Prevalence of nucleic acid sequences specific for human parvoviruses, hepatitis A and hepatitis E viruses in coagulation factor concentrates.

PubMed

Modrow, S; Wenzel, J J; Schimanski, S; Schwarzbeck, J; Rothe, U; Oldenburg, J; Jilg, W; Eis-Hübinger, A M

2011-05-01

Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2×10(1) and 1.3×10(3) genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Factor XII (Hageman factor) deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Sepsis-Induced Coagulation in the Baboon Lung Is Associated with Decreased Tissue Factor Pathway Inhibitor

PubMed Central

Tang, Haiwang; Ivanciu, Lacramioara; Popescu, Narcis; Peer, Glenn; Hack, Erik; Lupu, Cristina; Taylor, Fletcher B.; Lupu, Florea

2007-01-01

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis. PMID:17640967

Differences in coagulation among Asians and Caucasians and the implication for reconstructive microsurgery.

PubMed

Singhal, Dhruv; Smorodinsky, Emmanuil; Guo, Lifei

2011-01-01

Microvascular reconstructive surgery has seen a revival with the introduction of muscle-sparing perforator flaps. Recognition of potential ethnic differences in coagulation profiles would be important to a microvascular surgeon. Based on clinical observations, we hypothesize that Asian patients have a less thrombogenic coagulation profile than Caucasians. An extensive retrospective review was performed. The annual incidence of venous thromboembolism in the United States is generally accepted to range from 70 to 120 events per 100,000 people versus 16 to 17 events per 100,000 persons in Asia. Autopsy analysis of pulmonary embolism incidence was noted to be 15% in North Americans and less than 1% in Asian populations. Thromboelastography analysis of Asian and Caucasian patients undergoing cholecystectomy revealed different hemostatic mechanisms. Comparison of Asians and Caucasians undergoing the Fontan procedure revealed significantly lower postoperative factor levels in Asians than Caucasians. Baseline comparison of factor and serum levels revealed Asians with the least thrombogenic profiles compared with other ethnic groups. Asians and Caucasians demonstrate different baseline rates of deep vein thrombosis and pulmonary embolism, different hemostatic responses to surgery, and different baseline levels of clotting factors. Further study may lead to better pre-, intra-, and postoperative care of the free flap patient based on their ethnic coagulation profile. © Thieme Medical Publishers.

Increased thromboplastic potential in diabetes: a multifactorial phenomenon.

PubMed

Landgraf-Leurs, M M; Ladik, T; Smolka, B; Bock, T; Schramm, W; Spannagl, M; Landgraf, R

1987-07-01

Coagulation parameters, platelet aggregation, and thromboxane production as well as metabolic parameters were measured in 31 diabetic patients, 12 without and 19 with clinically manifest late complications, and in 14 healthy control subjects. Spontaneous in vitro aggregation as well as ADP, collagen, and arachidonic acid induced aggregation were higher in both groups of diabetic patients, without an increase in thromboxane B2 production. In diabetic patients with late complications an increase in fibrinogen, fibrinogen cyanogen bromide peptide, factor VIII related antigen, C1-esterase inhibitor, and antithrombin III was observed in comparison to healthy subjects. Fibrinogen, C1-esterase inhibitor, and factor VIII related antigen were already elevated in diabetic patients without clinically manifest late vascular complications. No strict correlations were found between serum glucose, glycosylated hemoglobin, and glycosylated albumin, on the one hand, and coagulation promoting or inhibiting factors, aggregation or thromboxane B2 production, on the other, in either control or diabetic subjects. Also no correlations existed between the coagulation parameters and the aggregation results. In vitro incubation of pooled normal plasma with different glucose concentrations had no influence on the methods by which the coagulation parameters were measured. These data indicate that rather early in the diabetic state many changes take place in different phases of the thrombostatic process, all resulting in an increased hemostatic diathesis.

Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

PubMed

De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele

2017-10-12

Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

Hemostatic abnormalities in Noonan syndrome.

PubMed

Artoni, Andrea; Selicorni, Angelo; Passamonti, Serena M; Lecchi, Anna; Bucciarelli, Paolo; Cerutti, Marta; Cianci, Paola; Gianniello, Francesca; Martinelli, Ida

2014-05-01

A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score <2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K-dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P < .01 for all aggregating agents). Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients. Copyright © 2014 by the American Academy of Pediatrics.

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.

Development of a microplate coagulation assay for Factor V in human plasma

PubMed Central

2011-01-01

Background Factor V (FV) in its activated form, FVa, is a critical regulator of thrombin generation during fibrin clot formation. There is a need of a simple, fast, and inexpensive microplate-based coagulation assay to measure the functional activity of FV in human plasma. The objective of this study was to develop a microplate-based assay that measures FV coagulation activity during clot formation in human plasma, which is currently not available. Methods The FV assay requires a kinetic microplate reader to measure the change in absorbance at 405nm during fibrin formation in human plasma. The FV assay accurately measures the time, initial rate, and extent of fibrin clot formation in human plasma. Results The FV microplate assay is simple, fast, economical, sensitive to approx 24-80pM, and multiple samples may be analyzed simultaneously. All the required materials are commercially available. Standard curves of time or initial rate of fibrin clot formation vs FV activity in the 1-stage assay (Without activation by thrombin) may be used to measure FV activity in samples of human plasma. The assay was used to demonstrate that in nine patients with disseminated intravascular coagulation (DIC), the FV 1-stage, 2-stage (With activation by thrombin), and total (2-stage activity - 1-stage activity) activities were decreased, on average, by approximately 54%, 44%, and 42%, respectively, from prolonged clot times when compared to normal pooled human reference plasma (NHP). The results indicate that the FV in the DIC patient plasmas supported both a delayed and slower rate of fibrin clot formation compared with NHP; however, the extent of fibrin clot formation in the DIC patients remained largely unchanged from that observed with NHP. Conclusions The FV microplate assay may be easily adapted to measure the activity of any coagulation factor using the appropriate factor-deficient plasma and clot initiating reagent. The microplate assay will find use in both research and clinical laboratories to provide measurement of the functional coagulation activity of FV in human plasma. PMID:21711555

Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.

PubMed

Yamamoto, Tomohiro; Wolf, Hans-Gerd; Sinzobahamvya, Nicodème; Asfour, Boulos; Hraska, Victor; Schindler, Ehrenfried

2015-08-01

In open heart surgery, heparinization is commonly neutralized using an empirical heparin:protamine ratio ranging between 1:1 and 1:1.5. However, these ratios may result in protamine overdose that should be avoided for its negative side effects on the coagulation system. This study aimed to indicate the appropriate treatment for prolonged activated clotting time (ACT) after protamine administration following cardiopulmonary bypass (CPB) in pediatric open heart surgery by investigating the underlying reasons for it. Twenty-seven children (<10 kg) undergoing open heart surgery were included. Heparin was administered only before CPB (400 IU/kg) and in the pump priming volume for CPB (2,000 IU) and was neutralized by 1:1 protamine after CPB. The blood heparin concentration was measured using anti-Xa assay. ACT and blood concentrations of heparin, coagulation factors, thrombin-antithrombin complex, and prothrombin fragment 1 + 2 were assessed. A rotational thromboelastometry (ROTEM; Tem International GmbH, München, Bayern, Germany) was used to confirm the coagulation status and residual heparin after protamine administration. Anti-Xa assay showed that there is no residual heparin in the blood after 1:1 protamine administration. Nevertheless, ACT (128.89 ± 3.09 seconds before heparin administration) remained prolonged (177.14 ± 5.43 seconds at 10 minutes after protamine, 182.00 ± 5.90 seconds at 30 minutes after protamine). The blood concentrations of coagulation factors were significantly lower than those before heparin administration (p < 0.01). The low FIBTEM MCF of ROTEM (4.43 ± 0.32 mm) at 10 minutes after protamine indicated low fibrinogen concentration. Prolonged ACT after heparin neutralization by 1:1 protamine administration does not necessarily indicate residual heparin, but low blood concentrations of coagulation factors should be considered as a reason as well. Accordingly, supply of coagulation factors instead of additional protamine should be considered. Georg Thieme Verlag KG Stuttgart · New York.

Studies on a family with combined functional deficiencies of vitamin K-dependent coagulation factors.

PubMed Central

Goldsmith, G H; Pence, R E; Ratnoff, O D; Adelstein, D J; Furie, B

1982-01-01

Two siblings with m ild hemorrhagic symptoms had combined functional deficiencies of vitamin K-dependent clotting factors. Prothrombin (0.18-0.20 U/ml) and Stuart factor (Factor X, 0.18-0.20 U/ml) and Stuart factor (Factor X, 0.18-0.20 U/ml) were most severely affected. Antigenic amounts of affected coagulation factors were normal and normal generation of thrombin activity occurred in the patients' plasmas after treatment with nonophysiologic activators that do not require calcium for prothrombin activation. Hepatobilary disease, malabsorptive disorders, and plasma warfarin were not present. Both parents had normal levels of all coagulation factors. The patients' plasmas contained prothrombin that reacted both with antibody directed against des-gamma-carboxyprothrombin and native prothrombin. Crossed immunoelectrophoresis of patients' plasmas and studies of partially purified patient prothrombin suggested the presence of a relatively homogeneous species of dysfunctional prothrombin, distinct from the heterologous species found in the plasma of warfarin-treated persons. These studies are most consistent with a posttranslational defect in hepatic carboxylation of vitamin K-dependent factors. This kindred uniquely possesses an autosomal recessive disorder of vitamin K-dependent factor formation that causes production of an apparently homogeneous species of dysfunctional prothrombin; the functional deficiencies in clotting factors are totally corrected by oral or parenteral administration of vitamin K1. Images PMID:7085873

Visual servoing for a US-guided therapeutic HIFU system by coagulated lesion tracking: a phantom study.

PubMed

Seo, Joonho; Koizumi, Norihiro; Funamoto, Takakazu; Sugita, Naohiko; Yoshinaka, Kiyoshi; Nomiya, Akira; Homma, Yukio; Matsumoto, Yoichiro; Mitsuishi, Mamoru

2011-06-01

Applying ultrasound (US)-guided high-intensity focused ultrasound (HIFU) therapy for kidney tumours is currently very difficult, due to the unclearly observed tumour area and renal motion induced by human respiration. In this research, we propose new methods by which to track the indistinct tumour area and to compensate the respiratory tumour motion for US-guided HIFU treatment. For tracking indistinct tumour areas, we detect the US speckle change created by HIFU irradiation. In other words, HIFU thermal ablation can coagulate tissue in the tumour area and an intraoperatively created coagulated lesion (CL) is used as a spatial landmark for US visual tracking. Specifically, the condensation algorithm was applied to robust and real-time CL speckle pattern tracking in the sequence of US images. Moreover, biplanar US imaging was used to locate the three-dimensional position of the CL, and a three-actuator system drives the end-effector to compensate for the motion. Finally, we tested the proposed method by using a newly devised phantom model that enables both visual tracking and a thermal response by HIFU irradiation. In the experiment, after generation of the CL in the phantom kidney, the end-effector successfully synchronized with the phantom motion, which was modelled by the captured motion data for the human kidney. The accuracy of the motion compensation was evaluated by the error between the end-effector and the respiratory motion, the RMS error of which was approximately 2 mm. This research shows that a HIFU-induced CL provides a very good landmark for target motion tracking. By using the CL tracking method, target motion compensation can be realized in the US-guided robotic HIFU system. Copyright © 2011 John Wiley & Sons, Ltd.

Correction factor for ablation algorithms used in corneal refractive surgery with gaussian-profile beams

NASA Astrophysics Data System (ADS)

Jimenez, Jose Ramón; González Anera, Rosario; Jiménez del Barco, Luis; Hita, Enrique; Pérez-Ocón, Francisco

2005-01-01

We provide a correction factor to be added in ablation algorithms when a Gaussian beam is used in photorefractive laser surgery. This factor, which quantifies the effect of pulse overlapping, depends on beam radius and spot size. We also deduce the expected post-surgical corneal radius and asphericity when considering this factor. Data on 141 eyes operated on LASIK (laser in situ keratomileusis) with a Gaussian profile show that the discrepancy between experimental and expected data on corneal power is significantly lower when using the correction factor. For an effective improvement of post-surgical visual quality, this factor should be applied in ablation algorithms that do not consider the effects of pulse overlapping with a Gaussian beam.

Current status of lasers in soft tissue dental surgery.

PubMed

Pick, R M; Colvard, M D

1993-07-01

The aims of this paper are to briefly describe laser physics, the types of lasers currently available for use on soft tissues focusing primarily on CO2 and Nd:YAG laser energies, the histological effects of lasers on oral tissues, laser safety, the clinical applications of lasers on oral soft tissues, and future directions. Of the two types of lasers currently available for dental applications, both the CO2 and Nd:YAG lasers can be used for frenectomies, ablation of lesions, incisional and excisional biopsies, gingivectomies, gingivoplasties, soft tissue tuberosity reductions, operculum removal, coagulation of graft donor sites, and certain crown lengthening procedures. The advantages of lasers include a relatively bloodless surgical and post-surgical course, minimal swelling and scarring, coagulation, vaporization, and cutting, minimal or no suturing, reduction in surgical time, and, in a majority of cases, much less or no post-surgical pain. CO2 lasers, compared to Nd:YAG are faster for most procedures, with less depth of tissue penetration and a well-documented history. There have been recent reports on the use of the Nd:YAG laser for periodontal scaling, gingival curettage, and root desensitization, but further research needs to be conducted. Both the CO2 and the Nd:YAG laser have limited use in conventional flap therapy.

Methotrexate-loaded PLGA nanobubbles for ultrasound imaging and Synergistic Targeted therapy of residual tumor during HIFU ablation.

PubMed

Zhang, Xuemei; Zheng, Yuanyi; Wang, Zhigang; Huang, Shuai; Chen, Yu; Jiang, Wei; Zhang, Hua; Ding, Mingxia; Li, Qingshu; Xiao, Xiaoqiu; Luo, Xin; Wang, Zhibiao; Qi, Hongbo

2014-06-01

High intensity focused ultrasound (HIFU) has attracted the great attention in tumor ablation due to its non-invasive, efficient and economic features. However, HIFU ablation has its intrinsic limitations for removing the residual tumor cells, thus the tumor recurrence and metastasis cannot be avoided in this case. Herein, we developed a multifunctional targeted poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs), which not only function as an efficient ultrasound contrast agent for tumor imaging, but also a targeted anticancer drug carrier and excellent synergistic agent for enhancing the therapeutic efficiency of HIFU ablation. Methotrexate (MTX)-loaded NBs were synthesized and filled with perfluorocarbon gas subsequently using a facile but general double emulsion evaporation method. The active tumor-targeting monoclonal anti-HLA-G antibodies (mAbHLA-G) were further conjugated onto the surface of nanobubbles. The mAbHLA-G/MTX/PLGA NBs could enhance the ultrasound imaging both in vitro and in vivo, and the targeting efficiency to HLA-G overexpressing JEG-3 cells has been demonstrated. The elaborately designed mAbHLA-G/MTX/PLGA NBs can specifically target to the tumor cells both in vitro and in vivo, and their blood circulation time in vivo was much longer than non-targeted MTX/PLGA NBs. Further therapeutic evaluations showed that the targeted NBs as a synergistic agent can significantly improve the efficiency of HIFU ablation by changing the acoustic environment, and the focused ultrasound can promote the on-demand MTX release both in vitro and in vivo. The in vivo histopathology test and immunohistochemical analysis showed that the mAbHLA-G/MTX/PLGA NBs plus HIFU group presented most serious coagulative necrosis, the lowest proliferation index and the highest apoptotic index. Therefore, the successful introduction of targeted mAbHLA-G/MTX/PLGA NBs provides an excellent platform for the highly efficient, imaging-guided and non-invasive HIFU synergistic therapy of cancer with the supplementary functions of killing residual tumor cells and preventing tumor recurrence/metastasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tissue ablation after 120W greenlight laser vaporization and bipolar plasma vaporization of the prostate: a comparison using transrectal three-dimensional ultrasound volumetry

NASA Astrophysics Data System (ADS)

Kranzbühler, Benedikt; Gross, Oliver; Fankhauser, Christian D.; Hefermehl, Lukas J.; Poyet, Cédric; Largo, Remo; Müntener, Michael; Seifert, Hans-Helge; Zimmermann, Matthias; Sulser, Tullio; Müller, Alexander; Hermanns, Thomas

2012-02-01

Introduction and objectives: Greenlight laser vaporization (LV) of the prostate is characterized by simultaneous vaporization and coagulation of prostatic tissue resulting in tissue ablation together with excellent hemostasis during the procedure. It has been reported that bipolar plasma vaporization (BPV) of the prostate might be an alternative for LV. So far, it has not been shown that BPV is as effective as LV in terms of tissue ablation or hemostasis. We performed transrectal three-dimensional ultrasound investigations to compare the efficiency of tissue ablation between LV and BPV. Methods: Between 11.2009 and 5.2011, 50 patients underwent pure BPV in our institution. These patients were matched with regard to the pre-operative prostate volume to 50 LV patients from our existing 3D-volumetry-database. Transrectal 3D ultrasound and planimetric volumetry of the prostate were performed pre-operatively, after catheter removal, 6 weeks and 6 months. Results: Median pre-operative prostate volume was not significantly different between the two groups (45.3ml vs. 45.4ml; p=1.0). After catheter removal, median absolute volume reduction (BPV 12.4ml, LV 6.55ml) as well as relative volume reduction (27.8% vs. 16.4%) were significantly higher in the BPV group (p<0.001). After six weeks (42.9% vs. 33.3%) and six months (47.2% vs. 39.7%), relative volume reduction remained significantly higher in the BPV group (p<0.001). Absolute volume reduction was non-significantly higher in the BPV group after six weeks (18.4ml, 13.8ml; p=0.051) and six months (20.8ml, 18ml; p=0.3). Clinical outcome parameters improved significantly in both groups without relevant differences between the groups. Conclusions: Both vaporization techniques result in efficient tissue ablation with initial prostatic swelling. BPV seems to be superior due to a higher relative volume reduction. This difference had no clinical impact after a follow-up of 6M.

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study

PubMed Central

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log(des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment. PMID:28458303

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

PubMed

Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

2017-01-01

Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

PubMed

Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

2017-06-01

During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation of systemic coagulation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Effects of anti-aggregant, anti-inflammatory and anti-coagulant drug consumption on the preparation and therapeutic potential of plasma rich in growth factors (PRGF).

PubMed

Anitua, Eduardo; Troya, María; Zalduendo, Mar; Orive, Gorka

2015-02-01

The prevalence and incidence of trauma-related injuries, coronary heart disease and other chronic diseases increase dramatically with age. This population sector is therefore a regular consumer of different types of drugs that may affect platelet aggregation and the coagulation cascade. We have evaluated whether the consumption of acetylsalicylic acid, acenocoumarol, glucosamine sulfate and chondroitin sulfate, and therefore their presence in blood, could interfere with the preparation and biological outcomes of plasma rich in growth factors (PRGF). Clotting time, clot retraction and platelet activation of PRGF was evaluated. PRGF growth factor content and the release of different biomolecules by tendon fibroblasts were also quantified, as well as cell proliferation and cell migration. The preparation and biological potential of PRGF is not affected by the intake of the evaluated drugs, and solely its angiogenic potential and its capacity to induce HA and fibronectin synthesis, is reduced in patients taking anti-coagulants.

[Use of thrombelastography to guide posttraumatic hemostatic therapy: More coagulation factor concentrates and less allogenic blood transfusion?

PubMed

David, J S; Imhoff, E; Parat, S; Augey, L; Geay-Baillat, M-O; Incagnoli, P; Tazarourte, K

2016-11-01

Viscoelastic technics are used for 10 years and include the ROTEM ® and the TEG ® . These devices that exploit the viscoelastic properties of the clotting blood, allow a rapid and global analysis of the haemostatic process taking into account all the process interfering with haemostasis such as inflammation. It has been shown that the use of these technics in clinical situations such as trauma, postpartum haemorrhage, gastrointestinal bleeding or cardiac surgery may reduce the need for blood product, the cost and perhaps may improve the outcome of the patients. Thanks to a rapid identification of the underlying coagulation deficit, these technics facilitate decision-making during acute care and help to guide the treatment, particularly with coagulation factor's concentrate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Near fatal spontaneous intraperitoneal bleeding: A rare manifestation in a congenital factor X deficiency carrier.

PubMed

Vinod, K V; Hitha, B; Kaaviya, R; Dutta, T K

2015-03-01

Congenital factor X (FX) deficiency is a rare coagulation disorder of autosomal recessive inheritance, characterized by bleeding of variable severity. Bleeding severity generally correlates with the level of FX functional activity and severe bleeding usually occurs in moderate and severe deficiency, when FX coagulant activity is <5%. FX activity above 10% is infrequently associated with severe bleeding. Here we report the rare occurrence of life-threatening massive spontaneous intraperitoneal bleeding with hypovolemic shock, resulting from spontaneous rupture of an ovarian luteal cyst in a 25-year-old FX deficiency carrier woman, with a FX activity of 26%. She was managed successfully conservatively, with fresh frozen plasma and packed red blood cell transfusions and she showed gradual improvement. The case is being reported to discuss the diagnosis and management of this rare inherited coagulation disorder.

The influence of prophylactic factor VIII in severe hemophilia A

PubMed Central

Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

2013-01-01

Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from <1% to 22%. Thrombin generation (maximum level and rate) in both empirical and computational systems increased as the level of fVIII increased. FXIII activation rates also increased as the fVIII level increased. Upon suppression of fVIII, thrombin generation became comparable in both systems. Plasma composition analysis showed a negative correlation between bleeding history and computational thrombin generation in the absence of fVIII. Conclusion Residual prophylactic fVIII directly causes an increase in thrombin generation and fibrin cross-linking in individuals with clinically severe hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

Haemostatic monitoring during postpartum haemorrhage and implications for management

PubMed Central

Solomon, C.; Collis, R. E.; Collins, P. W.

2012-01-01

Summary Postpartum haemorrhage (PPH) is a major risk factor for maternal morbidity and mortality. PPH has numerous causative factors, which makes its occurrence and severity difficult to predict. Underlying haemostatic imbalances such as consumptive and dilutional coagulopathies may develop during PPH, and can exacerbate bleeding and lead to progression to severe PPH. Monitoring coagulation status in patients with PPH may be crucial for effective haemostatic management, goal-directed therapy, and improved outcomes. However, current PPH management guidelines do not account for the altered baseline coagulation status observed in pregnant patients, and the appropriate transfusion triggers to use in PPH are unknown, due to a lack of high-quality studies specific to this area. In this review, we consider the evidence for the use of standard laboratory-based coagulation tests and point-of-care viscoelastic coagulation monitoring in PPH. Many laboratory-based tests are unsuitable for emergency use due to their long turnaround times, so have limited value for the management of PPH. Emerging evidence suggests that viscoelastic monitoring, using thrombelastography- or thromboelastometry-based tests, may be useful for rapid assessment and for guiding haemostatic therapy during PPH. However, further studies are needed to define the ranges of reference values that should be considered ‘normal’ in this setting. Improving awareness of the correct application and interpretation of viscoelastic coagulation monitoring techniques may be critical in realizing their emergency diagnostic potential. PMID:23075633

Coagulation under flow: the influence of flow-mediated transport on the initiation and inhibition of coagulation.

PubMed

Fogelson, Aaron L; Tania, Nessy

2005-01-01

A mathematical model of intravascular coagulation is presented; it encompasses the biochemistry of the tissue factor pathway, platelet activation and deposition on the subendothelium, and flow- and diffusion-mediated transport of coagulation proteins and platelets. Simulation experiments carried out with the model indicate the predominant role played by the physical processes of platelet deposition and flow-mediated removal of enzymes in inhibiting coagulation in the vicinity of vascular injury. Sufficiently rapid production of factors IXa and Xa by the TF:VIIa complex can overcome this inhibition and lead to formation of significant amounts of the tenase complex on the surface of activated platelets and, as a consequence, to substantial thrombin production. Chemical inhibitors are seen to play almost no (TFPI) or little (AT-III and APC) role in determining whether substantial thrombin production will occur. The role of APC is limited by the necessity for diffusion of thrombin from the site of injury to nearby endothelial cells to form the thrombomodulin-thrombin complex and for diffusion in the reverse direction of the APC made by this complex. TFPI plays an insignificant part in inhibiting the TF:VIIa complex under the conditions studied whether its action involves sequential binding of TFPI to Xa and then TFPI:Xa to TF:VIIa, or direct binding of TFPI to Xa already bound to the TF:VIIa complex. Copyright 2005 S. Karger AG, Basel.

Optimum coagulant forecasting by modeling jar test experiments using ANNs

NASA Astrophysics Data System (ADS)

Haghiri, Sadaf; Daghighi, Amin; Moharramzadeh, Sina

2018-01-01

Currently, the proper utilization of water treatment plants and optimizing their use is of particular importance. Coagulation and flocculation in water treatment are the common ways through which the use of coagulants leads to instability of particles and the formation of larger and heavier particles, resulting in improvement of sedimentation and filtration processes. Determination of the optimum dose of such a coagulant is of particular significance. A high dose, in addition to adding costs, can cause the sediment to remain in the filtrate, a dangerous condition according to the standards, while a sub-adequate dose of coagulants can result in the reducing the required quality and acceptable performance of the coagulation process. Although jar tests are used for testing coagulants, such experiments face many constraints with respect to evaluating the results produced by sudden changes in input water because of their significant costs, long time requirements, and complex relationships among the many factors (turbidity, temperature, pH, alkalinity, etc.) that can influence the efficiency of coagulant and test results. Modeling can be used to overcome these limitations; in this research study, an artificial neural network (ANN) multi-layer perceptron (MLP) with one hidden layer has been used for modeling the jar test to determine the dosage level of used coagulant in water treatment processes. The data contained in this research have been obtained from the drinking water treatment plant located in Ardabil province in Iran. To evaluate the performance of the model, the mean squared error (MSE) and correlation coefficient (R2) parameters have been used. The obtained values are within an acceptable range that demonstrates the high accuracy of the models with respect to the estimation of water-quality characteristics and the optimal dosages of coagulants; so using these models will allow operators to not only reduce costs and time taken to perform experimental jar tests but also to predict a proper dosage for coagulant amounts and to project the quality of the output water under real conditions.

Chemical coagulation-based processes for trace organic contaminant removal: current state and future potential.

PubMed

Alexander, Jonathan T; Hai, Faisal I; Al-Aboud, Turki M

2012-11-30

Trace organic contaminants have become an increasing cause of concern for governments and water authorities as they attempt to respond to the potential challenges posed by climate change by implementing sustainable water cycle management practices. The augmentation of potable water supplies through indirect potable water reuse is one such method currently being employed. Given the uncertainty surrounding the potential human health impacts of prolonged ingestion of trace organic contaminants, it is vital that effective and sustainable treatment methods are utilized. The purpose of this article is to provide a comprehensive literature review of the performance of the chemical coagulation process in removing trace organic contaminants from water. This study evaluated the removal data collated from recent research relating to various trace organic contaminants during the coagulation process. It was observed that there is limited research data relating to the removal of trace organic contaminants using coagulation. The findings of this study suggest that there is a gap in the current research investigating the potential of new types of coagulants and exploring coagulation-based hybrid processes to remove trace organic contaminants from water. The data analysed in this study regarding removal efficiency suggests that, even for the significantly hydrophobic compounds, hydrophobicity is not the sole factor governing removal of trace organic contaminants by coagulation. This has important implications in that the usual practice of screening coagulants based on turbidity (suspended solid) removal proves inadequate in the case of trace organic contaminant removal. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quality control in the development of coagulation factor concentrates.

PubMed

Snape, T J

1987-01-01

Limitation of process change is a major factor contributing to assurance of quality in pharmaceutical manufacturing. This is particularly true in the manufacture of coagulation factor concentrates, for which presumptive testing for poorly defined product characteristics is an integral feature of finished product quality control. The development of new or modified preparations requires that this comfortable position be abandoned, and that the effect on finished product characteristics of changes to individual process steps (and components) be assessed. The degree of confidence in the safety and efficacy of the new product will be determined by, amongst other things, the complexity of the process alteration and the extent to which the results of finished product tests can be considered predictive. The introduction of a heat-treatment step for inactivation of potential viral contaminants in coagulation factor concentrates presents a significant challenge in both respects, quite independent of any consideration of assessment of the effectiveness of the viral inactivation step. These interactions are illustrated by some of the problems encountered with terminal dry heat-treatment (72 h. at 80 degrees C) of factor VIII and prothrombin complex concentrates manufactured by the Blood Products Laboratory.

Functional assembly of intrinsic coagulation proteases on monocytes and platelets. Comparison between cofactor activities induced by thrombin and factor Xa

PubMed Central

1992-01-01

Generation of coagulation factor Xa by the intrinsic pathway protease complex is essential for normal activation of the coagulation cascade in vivo. Monocytes and platelets provide membrane sites for assembly of components of this protease complex, factors IXa and VIII. Under biologically relevant conditions, expression of functional activity by this complex is associated with activation of factor VIII to VIIIa. In the present studies, autocatalytic regulatory pathways operating on monocyte and platelet membranes were investigated by comparing the cofactor function of thrombin-activated factor VIII to that of factor Xa-activated factor VIII. Reciprocal functional titrations with purified human factor VIII and factor IXa were performed at fixed concentrations of human monocytes, CaCl2, factor X, and either factor IXa or factor VIII. Factor VIII was preactivated with either thrombin or factor Xa, and reactions were initiated by addition of factor X. Rates of factor X activation were measured using chromogenic substrate specific for factor Xa. The K1/2 values, i.e., concentration of factor VIIIa at which rates were half maximal, were 0.96 nM with thrombin- activated factor VIII and 1.1 nM with factor Xa-activated factor VIII. These values are close to factor VIII concentration in plasma. The Vsat, i.e., rates at saturating concentrations of factor VIII, were 33.3 and 13.6 nM factor Xa/min, respectively. The K1/2 and Vsat values obtained in titrations with factor IXa were not significantly different from those obtained with factor VIII. In titrations with factor X, the values of Michaelis-Menten coefficients (Km) were 31.7 nM with thrombin- activated factor VIII, and 14.2 nM with factor Xa-activated factor VIII. Maximal rates were 23.4 and 4.9 nM factor Xa/min, respectively. The apparent catalytic efficiency was similar with either form of factor VIIIa. Kinetic profiles obtained with platelets as a source of membrane were comparable to those obtained with monocytes. These kinetic profiles are consistent with a 1:1 stoichiometry for the functional interaction between cofactor and enzyme on the surface of monocytes and platelets. Taken together, these results indicate that autocatalytic pathways connecting the extrinsic, intrinsic, and common coagulation pathways can operate efficiently on the monocyte membrane. PMID:1613461

Non-ablative fractional resurfacing of surgical and post-traumatic scars.

PubMed

Vasily, David B; Cerino, Mary E; Ziselman, Ethel M; Zeina, S Tannous

2009-11-01

Non-ablative, fractional lasers generate microscopic columns of coagulated tissue through the epidermis and dermis to evoke a wound healing response. In this study, the authors examined the efficacy and safety of the non-ablative 1540 nm erbium:glass fractional laser in the treatment of surgical and post-traumatic scars. Clinical studies were conducted on a range of surgical and post-traumatic scars with a 1540 nm erbium:glass fractional laser varying energy, pulse widths, treatment passes, and number of treatments. A histological study was conducted on a postsurgical scar to follow the time course of healing post-treatment and the impact of the fractional treatment on normalization of scar tissue, as compared to baseline histology of the scar. Histologic findings demonstrated rapid re-epithelialization of the epidermis within 72 hours of treatment. Remodeling of scar tissue with renewal and reorganization of collagen fibers in the dermis was noted two weeks post-treatment. Clinical subjects, with Fitzpatrick skin types II-V, received three to seven treatments with microbeam energies up to 60 mJ/pb and five passes. Relative to baseline, 73% of treated scars improved 50% or more and 43% improved 75% or more. Side effects included mild swelling (95% of subjects), erythema (94%) and purpura (5%), which all resolved within two to three days. Downtime was minimal-to-none for all subjects. These data illustrate the safety and efficacy of the 1540 nm erbium:glass fractional laser in the treatment of surgical and post-traumatic scars. Practitioners can vary energy and microbeam density in order to tailor the treatment to reflect the individual scar characteristics.

The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function: a systematic review.

PubMed

Frieben, Ryan W; Lin, Hao-Cheng; Hinh, Peter P; Berardinelli, Francesco; Canfield, Steven E; Wang, Run

2010-07-01

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia (BPH) on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy (TUMT), transurethral needle ablation of the prostate (TUNA), transurethral ethanol ablation of the prostate (TEAP) and high-intensity frequency ultrasound (HIFU), in comparison with traditional transurethral resection of the prostate (TURP) or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction (EjD) is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies (> 33.6%). TUMT, TUNA and neodymium:yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP.

The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function: a systematic review

PubMed Central

Frieben, Ryan W.; Lin, Hao-Cheng; Hinh, Peter P.; Berardinelli, Francesco; Canfield, Steven E.; Wang, Run

2010-01-01

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia (BPH) on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy (TUMT), transurethral needle ablation of the prostate (TUNA), transurethral ethanol ablation of the prostate (TEAP) and high-intensity frequency ultrasound (HIFU), in comparison with traditional transurethral resection of the prostate (TURP) or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction (EjD) is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies (> 33.6%). TUMT, TUNA and neodymium:yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP. PMID:20473318

Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation.

PubMed

Chiu, Bill; Melin-Aldana, Hector; Superina, Riccardo A

2007-10-01

A 3-year-old girl developed extrahepatic portal vein obstruction (EHPVO) after a liver transplant. She had sequelae of portal hypertension that required another transplantation. The circumstances allowed for comparison of liver-dependent coagulation factor production between the second donor liver and the explanted liver with EHPVO. Liver samples from the explanted first graft and the second transplant were obtained. Fresh tissue was used to perform reverse transcription-polymerase chain reaction with primers against factors V, VII, as well as VIII, protein C, and paraffin-embedded sections for hepatocyte proliferation using Ki-67 antibody as well as for apoptosis using TUNEL assay. The transcription of factor VII and that of protein C were decreased in the explant as compared with the newly transplanted liver (factor VII, 77% of the donor; protein C, 88% of the donor). The transcription of factor V and that of factor VIII were unchanged. The explant had a greater percentage of proliferating hepatocytes than the new organ (0.85% +/- 0.75% vs 0.11% +/- 0.21%). The percentage of apoptotic cells was similar between the 2 livers (0.09% +/- 0.13% vs 0.09% +/- 0.13%). Idiopathic EHPVO is associated with a reduction in liver-dependent coagulation factor transcription and an increase in hepatocyte proliferation. Portal blood flow deprivation alters hepatic homeostasis and initiates mechanisms that attempt to restore liver-dependent coagulation factors.

Quality of Clotting Factor Activity in Fresh Frozen Plasma at Thaw with a Microwave System and after Storage at 4 degrees C for 48 Hours.

PubMed

Kuta, Piotr; Hauck-Dlimi, Barbara; Strobel, Julian; Zimmermann, Robert; Eckstein, Reinhold

2016-01-01

Uncontrolled hemorrhage in polytrauma patients usually results in rapid need of blood products. Despite the shorter thawing times of microwave devices for heating fresh frozen plasma (FFP), their use has remained controversial, and just a few laboratory analyses have been published on this topic. The aim of this study was to analyse the quality of clotting factors immediately after thawing FFP with a microwave device and after 48-hour post thaw storage at 4 degrees C. 24 FFP units of all four ABO blood groups (six of each blood group) were thawed with a Transfusio-therm 2000 and later stored at 4 degrees C for 48 hours. Samples were drawn aseptically and investigated on various clotting factors and protein proteases (fibrinogen, antithrombin, FII, FV, FVII, FVIII, FIX, FX, FXI, FXIII, vWF antigen and activity, protein S, and protein C) using standard coagulation and chromogenic assays immediately after thawing and again after a 48-hour storage period at 4 degrees C. All units were tested for both anaerobic and aerobic microbial contamination using standard operating procedures immediately after thawing. After thawing, all coagulation factors and protein protease activities were within normal ranges. Blood group O individuals had approximately 25% lower plasma levels of vWF antigen and activity. After a 48-hour storage period at 4 degrees C, FVIII and FIX activities declined significantly in all blood groups, whereas the remaining clotting factors remained comparably stable. Immediately after rapid thawing using a microwave system, all FFP units contained adequate coagulation factor activities to maintain hemostatic activity at the time of product thaw. The post thaw refrigerated storage caused an anticipated decrease in factor VIII and IX activities, but retained normal coagulation factor levels of many plasma proteins. Therefore we conclude that the Transfusio-therm 2000 has no clinically significant influence on the activity of clotting factors and plasma proteases in FFP units.

Improvement of ablative margins by the intraoperative use of CEUS-CT/MR image fusion in hepatocellular carcinoma.

PubMed

Li, Kai; Su, Zhong-Zhen; Xu, Er-Jiao; Ju, Jin-Xiu; Meng, Xiao-Chun; Zheng, Rong-Qin

2016-04-18

To assess whether intraoperative use of contrast-enhanced ultrasound (CEUS)-CT/MR image fusion can accurately evaluate ablative margin (AM) and guide supplementary ablation to improve AM after hepatocellular carcinoma (HCC) ablation. Ninety-eight patients with 126 HCCs designated to undergo thermal ablation treatment were enrolled in this prospective study. CEUS-CT/MR image fusion was performed intraoperatively to evaluate whether 5-mm AM was covered by the ablative area. If possible, supplementary ablation was applied at the site of inadequate AM. The CEUS image quality, the time used for CEUS-CT/MR image fusion and the success rate of image fusion were recorded. Local tumor progression (LTP) was observed during follow-up. Clinical factors including AM were examined to identify risk factors for LTP. The success rate of image fusion was 96.2% (126/131), and the duration required for image fusion was 4.9 ± 2.0 (3-13) min. The CEUS image quality was good in 36.1% (53/147) and medium in 63.9% (94/147) of the cases. By supplementary ablation, 21.8% (12/55) of lesions with inadequate AMs became adequate AMs. During follow-up, there were 5 LTPs in lesions with inadequate AMs and 1 LTP in lesions with adequate AMs. Multivariate analysis showed that AM was the only independent risk factor for LTP (hazard ratio, 9.167; 95% confidence interval, 1.070-78.571; p = 0.043). CEUS-CT/MR image fusion is feasible for intraoperative use and can serve as an accurate method to evaluate AMs and guide supplementary ablation to lower inadequate AMs.

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.

Principles of dielectric blood coagulometry as a comprehensive coagulation test.

PubMed

Hayashi, Yoshihito; Brun, Marc-Aurèle; Machida, Kenzo; Nagasawa, Masayuki

2015-10-06

Dielectric blood coagulometry (DBCM) is intended to support hemostasis management by providing comprehensive information on blood coagulation from automated, time-dependent measurements of whole blood dielectric spectra. We discuss the relationship between the series of blood coagulation reactions, especially the aggregation and deformation of erythrocytes, and the dielectric response with the help of clot structure electron microscope observations. Dielectric response to the spontaneous coagulation after recalcification presented three distinct phases that correspond to (P1) rouleau formation before the onset of clotting, (P2) erythrocyte aggregation and reconstitution of aggregates accompanying early fibrin formation, and (P3) erythrocyte shape transformation and/or structure changes within aggregates after the stable fibrin network is formed and platelet contraction occurs. Disappearance of the second phase was observed upon addition of tissue factor and ellagic acid for activation of extrinsic and intrinsic pathways, respectively, which is attributable to accelerated thrombin generation. A series of control experiments revealed that the amplitude and/or quickness of dielectric response reflect platelet function, fibrin polymerization, fibrinolysis activity, and heparin activity. Therefore, DBCM sensitively measures blood coagulation via erythrocytes aggregation and shape changes and their impact on the dielectric permittivity, making possible the development of the battery of assays needed for comprehensive coagulation testing.

Tolerance of high-intensity focused ultrasound ablation in patients with hepatocellular carcinoma.

PubMed

Cheung, Tan To; Chu, Ferdinand S K; Jenkins, Caroline R; Tsang, Dickson S F; Chok, Kenneth S H; Chan, Albert C Y; Yau, Thomas C C; Chan, See Ching; Poon, Ronnie T P; Lo, Chung Mau; Fan, Sheung Tat

2012-10-01

High-intensity focused ultrasound (HIFU) ablation is a relatively new, noninvasive way of ablation for treating hepatocellular carcinoma (HCC). Emerging evidence has shown that it is effective for the treatment of HCC, even in patients with poor liver function. There is currently no data on the safety limit of HIFU ablation in patients with cirrhosis. However, this information is vital for the selection of appropriate patients for the procedure. We analyzed HCC patients who had undergone HIFU ablation and determined the lower limit of liver function and other patient factors with which HCC patients can tolerate this treatment modality. Preoperative variables of 100 patients who underwent HIFU ablation for HCC were analyzed to identify the risk factors in HIFU intolerance in terms of stress-induced complications. Factors that may contribute to postablation complications were compared. Thirteen (13 %) patients developed a total of 18 complications. Morbidity was mainly due to skin and subcutaneous tissue injuries (n = 9). Five patients had first-degree skin burn, one had second-degree skin burn, and three had third-degree skin burn. Four complications were grade 3a in the Clavien classification and 14 were below this grade. Univariate analysis showed that age (p = 0.022) was the only independent factor in HIFU intolerance. HIFU ablation is generally well tolerated in HCC patients with cirrhosis. It is safe for Child-Pugh A and B patients and selected Child-Pugh C patients. With this new modality, HCC patients who were deemed unsalvageable by other surgical means in the past because of simultaneous Child-Pugh B or C disease now have a new hope.

Imaging analyses of coagulation-dependent initiation of fibrinolysis on activated platelets and its modification by thrombin-activatable fibrinolysis inhibitor.

PubMed

Brzoska, Tomasz; Suzuki, Yuko; Sano, Hideto; Suzuki, Seiichirou; Tomczyk, Martyna; Tanaka, Hiroki; Urano, Tetsumei

2017-04-03

Using intravital confocal microscopy, we observed previously that the process of platelet phosphatidylserine (PS) exposure, fibrin formation and lysine binding site-dependent plasminogen (plg) accumulation took place only in the centre of thrombi, not at their periphery. These findings prompted us to analyse the spatiotemporal regulatory mechanisms underlying coagulation and fibrinolysis. We analysed the fibrin network formation and the subsequent lysis in an in vitro experiment using diluted platelet-rich plasma supplemented with fluorescently labelled coagulation and fibrinolytic factors, using confocal laser scanning microscopy. The structure of the fibrin network formed by supplemented tissue factor was uneven and denser at the sites of coagulation initiation regions (CIRs) on PS-exposed platelets. When tissue-type plasminogen activator (tPA; 7.5 nM) was supplemented, labelled plg (50 nM) as well as tPA accumulated at CIRs, from where fibrinolysis started and gradually expanded to the peripheries. The lysis time at CIRs and their peripheries (50 µm from the CIR) were 27.9 ± 6.6 and 44.4 ± 9.7 minutes (mean ± SD, n=50 from five independent experiments) after the addition of tissue factor, respectively. Recombinant human soluble thrombomodulin (TMα; 2.0 nM) attenuated the CIR-dependent plg accumulation and strongly delayed fibrinolysis at CIRs. A carboxypeptidase inhibitor dose-dependently enhanced the CIR-dependent fibrinolysis initiation, and at 20 µM it completely abrogated the TMα-induced delay of fibrinolysis. Our findings are the first to directly present crosstalk between coagulation and fibrinolysis, which takes place on activated platelets' surface and is further controlled by thrombin-activatable fibrinolysis inhibitor (TAFI).

Factor II deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Factor X deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Factor VII deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

ANALYSIS OF FACTORS AFFECTING OUTCOME OF ULTRASOUND-GUIDED RADIOFREQUENCY HEAT ABLATION FOR TREATMENT OF PRIMARY HYPERPARATHYROIDISM IN DOGS.

PubMed

Bucy, Daniel; Pollard, Rachel; Nelson, Richard

2017-01-01

Radiofrequency (RF) parathyroid ablation is a noninvasive treatment for hyperparathyroidism in dogs. There are no published data assessing factors associated with RF parathyroid ablation success or failure in order to guide patient selection and improve outcome. The purpose of this retrospective analytical study was to determine whether imaging findings, biochemical data, or concurrent diseases were associated with RF heat ablation treatment failure. For inclusion in the study, dogs must have had a clinical diagnosis of primary hyperparathyroidism, undergone cervical ultrasound and RF ablation of abnormal parathyroid tissue, and must have had at least 3 months of follow-up information available following the date of ultrasound-guided parathyroid ablation. Dogs were grouped based on those with recurrent or persistent hypercalcemia and those without recurrent or persistent hypercalcemia following therapy. Parathyroid nodule size, thyroid lobe size, nodule location, and presence of concurrent disease were recorded. Recurrence of hypercalcemia occurred in 9/32 dogs that had ablation of abnormal parathyroid tissue (28%) and one patient had persistent hypercalcemia (3%) following parathyroid ablation. Nodule width (P = 0.036), height (P = 0.028), and largest cross-sectional area (P = 0.023) were larger in dogs that had recurrent or persistent hypercalcemia following ablation. Hypothyroidism was more common in dogs with recurrent disease (P = 0.044). Radiofrequency ablation was successful in 22/32 (69%) dogs. Larger parathyroid nodule size and/or concurrent hypothyroidism were associated with treatment failure in dogs that underwent ultrasound-guided RF parathyroid nodule ablation. © 2016 American College of Veterinary Radiology.

Anticoagulation beyond direct thrombin and factor Xa inhibitors: indications for targeting the intrinsic pathway?

PubMed

van Montfoort, Maurits L; Meijers, Joost C M

2013-08-01

Antithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. In terms of effectiveness, these drugs are comparable to the currently available anticoagulants; however, they are still associated with issues such as bleeding, reversal of the drug and complicated laboratory monitoring. Vitamin K antagonists, heparin, direct thrombin and factor Xa inhibitors have in common that they target key proteins of the haemostatic system. In an attempt to overcome these difficulties we investigated whether the intrinsic coagulation factors (VIII, IX, XI, XII, prekallikrein and high-molecular-weight kininogen) are superior targets for anticoagulation. We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.

Functional Consequences of Mannose and Asialoglycoprotein Receptor Ablation*

PubMed Central

Mi, Yiling; Coonce, Marcy; Fiete, Dorothy; Steirer, Lindsay; Dveksler, Gabriela; Townsend, R. Reid; Baenziger, Jacques U.

2016-01-01

The mannose receptor (ManR, Mrc1) and asialoglycoprotein receptor (ASGR, Asgr1 and Asgr2) are highly abundant endocytic receptors expressed by sinusoidal endothelial cells and parenchymal cells in the liver, respectively. We genetically manipulated either receptor individually or in combination, revealing phenotypic changes in female and male mice associated with changes in circulating levels of many glycoproteins. Both receptors rise and fall in response to progesterone during pregnancy. Thirty percent of Asgr2−/− and 65% of Mrc1−/−Asgr2−/− mice are unable to initiate parturition at the end of pregnancy, whereas Mrc1−/− mice initiate normally. Twenty five percent of Mrc1−/−Asgr2−/− male mice develop priapism when mating due to thrombosis of the penile vein, but neither Mrc1−/− nor Asgr2−/− mice do so. The half-life for luteinizing hormone (LH) clearance increases in Mrc1−/− and Mrc1−/−Asgr2−/− mice but not in Asgr2−/− mice; however, LH and testosterone are elevated in all three knockouts. The ManR clears LH thus regulating testosterone production, whereas the ASGR appears to mediate clearance of an unidentified glycoprotein that increases LH levels. More than 40 circulating glycoproteins are elevated >3.0-fold in pregnant Mrc1−/−Asgr2−/− mice. Pregnancy-specific glycoprotein 23, undetectable in WT mice (<50 ng/ml plasma), reaches levels of 1–10 mg/ml in the plasma of Mrc1−/−Asgr2−/− and Asgr2−/− mice, indicating it is cleared by the ASGR. Elevation of multiple coagulation factors in Mrc1−/−Asgr2−/− mice may account for priapism seen in males. These male and female phenotypic changes underscore the key roles of the ManR and ASGR in controlling circulating levels of numerous glycoproteins critical for regulating reproductive hormones and blood coagulation. PMID:27405760

TREATMENT OF LANDFILL LEACHATE BY COUPLING COAGULATION-FLOCCULATION OR OZONATION TO GRANULAR ACTIVATED CARBON ADSORPTION.

PubMed

Oloibiri, Violet; Ufomba, Innocent; Chys, Michael; Audenaert, Wim; Demeestere, Kristof; Van Hulle, Stijn W H

2015-01-01

A major concern for landfilling facilities is the treatment of their leachate. To optimize organic matter removal from this leachate, the combination of two or more techniques is preferred in order to meet stringent effluent standards. In our study, coagulation-flocculation and ozonation are compared as pre- treatment steps for stabilized landfill leachate prior to granular activated carbon (GAC) adsorption. The efficiency of the pre treatment techniques is evaluated using COD and UVA254 measurements. For coagulation- flocculation, different chemicals are compared and optimal dosages are determined. After this, iron (III) chloride is selected for subsequent adsorption studies due to its high percentage of COD and UVA254 removal and good sludge settle-ability. Our finding show that ozonation as a single treatment is effective in reducing COD in landfill leachate by 66% compared to coagulation flocculation (33%). Meanwhile, coagulation performs better in UVA254 reduction than ozonation. Subsequent GAC adsorption of ozonated effluent, coagulated effluent and untreated leachate resulted in 77%, 53% and 8% total COD removal respectively (after 6 bed volumes). The effect of the pre-treatment techniques on GAC adsorption properties is evaluated experimentally and mathematically using Thomas and Yoon-Nelson models. Mathematical modelling of the experimental GAC adsorption data shows that ozonation increases the adsorption capacity and break through time with a factor of 2.5 compared to coagulation-flocculation.

Stability of colloidal gold and determination of the Hamaker constant

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

Demirci, S.; Enuestuen, B.V.; Turkevich, J.

1978-12-14

Previous computation of stability factors of colloidal gold from coagulation data was found to be in systematic error due to an underestimation of the particle concentration by electron microscopy. A new experimental technique was developed for determination of this concentration. Stability factors were recalculated from the previous data using the correct concentration. While most of the previously reported conclusions remain unchanged, the absolute rate of fast coagulation is found to agree with that predicted by the theory. A value of the Hamaker constant was determined from the corrected data.

6-Methylsulfinylhexyl isothiocyanate modulates endothelial cell function and suppresses leukocyte adhesion.

PubMed

Okamoto, Takayuki; Akita, Nobuyuki; Nagai, Masashi; Hayashi, Tatsuya; Suzuki, Koji

2014-01-01

6-Methylsulfinylhexyl isothiocyanate (6-MSITC) is an active compound in wasabi (Wasabia japonica Matsum.), which is one of the most popular spices in Japan. 6-MSITC suppresses lipopolysaccharide-induced macrophage activation, arachidonic- or adenosine diphosphate-induced platelet activation, and tumor cell proliferation. These data indicate that 6-MSITC has several biological activities involving anti-inflammatory, anti-coagulant, and anti-apoptosis properties. Endothelial cells (ECs) maintain vascular homeostasis and play crucial roles in crosstalk between blood coagulation and vascular inflammation. In this study, we determined the anti-coagulant and anti-inflammatory effects of 6-MSITC on human umbilical vein endothelial cells (HUVECs). 6-MSITC slightly reduced tissue factor expression, but did not alter von Willebrand factor release in activated HUVECs. 6-MSITC modulated the generation of activated protein C, which is essential for negative regulation of blood coagulation, on normal ECs. In addition, 6-MSITC reduced tumor necrosis factor-α (TNF-α)-induced interleukin-6 and monocyte chemoattractant protein-1 expression. 6-MSITC markedly attenuated TNF-α-induced adhesion of human monoblast U937 cells to HUVECs and reduced vascular cell adhesion molecule-1 and E-selectin mRNA expression in activated ECs. These results showed that 6-MSITC modulates EC function and suppresses cell adhesion. This study provides new insight into the mechanism of the anti-inflammatory effect of 6-MSITC, suggesting that 6-MSITC has therapeutic potential as a treatment for vasculitis and vascular inflammation.

IgMk paraprotein from gammopathy patient can bind to cardiolipin and interfere with coagulation assay: a case report.

PubMed

Wu, Xin-Yao; Yin, Yu-Feng; Teng, Jia-Lin; Zhang, Li-Wei; Yang, Cheng-de

2017-06-23

The monoclonal gammopathies are a group of plasma-cell proliferative disorders characterized by the secretion of monoclonal immunoglobulin (M protein or paraprotein). Some rare cases have revealed the specific affinity of paraprotein as autoantibody. Here we report a patient with monoclonal gammopathy of undetermined significance (MGUS) accompanied by a remarkable increase of anticardiolipin antibody (aCL) and an extensively decreased coagulation factor activity, however, without any clinical signs of antiphospholipid syndrome (APS) and bleeding. Our further investigation indicated that IgMκ paraprotein of this patient possessed an antibody activity against phospholipids so as to bind to cardiolipin and interfere with coagulation assay in vitro. This case might be indicative that an abnormality of coagulation tests, disturbed by IgMκ paraprotein, does not predict a risk of bleeding in this patient.

Antithrombin, an Important Inhibitor in Blood Clots.

PubMed

Zhu, Ying; Cong, Qing-Wei; Liu, Yue; Wan, Chun-Ling; Yu, Tao; He, Guang; He, Lin; Cai, Lei; Chou, Kuo-Chen

2016-01-01

Blood coagulation is healthy and lifesaving because it can stop bleeding. It can, however, be a troublemaker as well, causing serious medical problems including heart attack and stroke. Body has complex blood coagulation cascade to modulate the blood clots. In the environment of plasma, the blood coagulation cascade is regulated by antithrombin, which is deemed one of the most important serine protease inhibitors. It inhibits thrombin; it can inhibit factors IXa and Xa as well. Interestingly, its inhibitory ability will be significantly increased with the existence of heparin. In this minireview paper, we are to summarize the structural features of antithrombin, as well as its heparin binding modes and anti-coagulation mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to find more effective approaches or compounds to modulate the antithrombin.

Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population.

PubMed

Barillari, Giovanni; Fabbro, Elisabetta; Pasca, Samantha; Bigotto, Enrico

2009-06-01

Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P < 0.05) for tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein, factor VII and factor XI; conversely for factor VIII, factor IX, factor XII, antithrombin III and fibrinogen, the results gave a difference statistically significant (P < 0.01). In patients with DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.

Principal component analysis to assess the efficiency and mechanism for enhanced coagulation of natural algae-laden water using a novel dual coagulant system.

PubMed

Ou, Hua-Se; Wei, Chao-Hai; Deng, Yang; Gao, Nai-Yun; Ren, Yuan; Hu, Yun

2014-02-01

A novel dual coagulant system of polyaluminum chloride sulfate (PACS) and polydiallyldimethylammonium chloride (PDADMAC) was used to treat natural algae-laden water from Meiliang Gulf, Lake Taihu. PACS (Aln(OH)mCl3n-m-2k(SO4)k) has a mass ratio of 10 %, a SO4 (2-)/Al3 (+) mole ratio of 0.0664, and an OH/Al mole ratio of 2. The PDADMAC ([C8H16NCl]m) has a MW which ranges from 5 × 10(5) to 20 × 10(5) Da. The variations of contaminants in water samples during treatments were estimated in the form of principal component analysis (PCA) factor scores and conventional variables (turbidity, DOC, etc.). Parallel factor analysis determined four chromophoric dissolved organic matters (CDOM) components, and PCA identified four integrated principle factors. PCA factor 1 had significant correlations with chlorophyll-a (r=0.718), protein-like CDOM C1 (0.689), and C2 (0.756). Factor 2 correlated with UV254 (0.672), humic-like CDOM component C3 (0.716), and C4 (0.758). Factors 3 and 4 had correlations with NH3-N (0.748) and T-P (0.769), respectively. The variations of PCA factors scores revealed that PACS contributed less aluminum dissolution than PAC to obtain equivalent removal efficiency of contaminants. This might be due to the high cationic charge and pre-hydrolyzation of PACS. Compared with PACS coagulation (20 mg L(-1)), the removal of PCA factors 1, 2, and 4 increased 45, 33, and 12 %, respectively, in combined PACS-PDADMAC treatment (0.8 mg L(-1) +20 mg L(-1)). Since PAC contained more Al (0.053 g/1 g) than PACS (0.028 g/1 g), the results indicated that PACS contributed less Al dissolution into the water to obtain equivalent removal efficiency.

Factor Xa Activation of Factor V is of Paramount Importance in Initiating the Coagulation System: Lessons from a Tick Salivary Protein

PubMed Central

Schuijt, Tim J.; Bakhtiari, Kamran; Daffre, Sirlei; DePonte, Kathleen; Wielders, Simone J.H.; Marquart, J. Arnoud; Hovius, Joppe W.; van der Poll, Tom; Fikrig, Erol; Bunce, Matthew W.; Camire, Rodney M.; Nicolaes, Gerry A.F.; Meijers, Joost C.M.; van 't Veer, Cornelis

2013-01-01

Background Generation of active procoagulant cofactor FVa and its subsequent association with the enzyme FXa to form the prothrombinase complex is a pivotal initial event in blood coagulation and has been the subject of investigative effort, speculation and controversy. The current paradigm assumes that FV activation is initiated by limited proteolysis by traces of (meizo) thrombin. Methods and Results Recombinant tick salivary protein TIX-5 was produced and anticoagulant properties were studied using plasma, whole blood and purified systems. Here we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B-domain of FV and show that FXa activation of FV is pivotal for plasma and blood clotting. In line, tick feeding is impaired on TIX-5 immune rabbits displaying the in vivo importance of TIX-5. Conclusions Our data elucidate a unique molecular mechanism by which ticks inhibit the host's coagulation system. Based on our data we propose a revised blood coagulation scheme wherein direct FXa-mediated FV activation occurs in the initiation phase during which thrombin-mediated FV activation is restrained by fibrinogen and inhibitors. PMID:23817575

Polyacrylamide grafted cellulose as an eco-friendly flocculant: Key factors optimization of flocculation to surfactant effluent.

PubMed

Zhu, Hangcheng; Zhang, Yong; Yang, Xiaogang; Shao, Lan; Zhang, Xiumei; Yao, Juming

2016-01-01

The discharge of effluents from surfactant manufacturers is giving rise to increasingly serious environmental problems. In order to develop the eco-friendly flocculation materials to achieve effective removal of pollutants from the surfactant effluents, the bamboo pulp cellulose from Phyllostachys heterocycla is employed as the skeleton material to synthesize an eco-friendly bamboo pulp cellulose-g-polyacrylamide (BPC-g-PAM) for flocculation. The BPC-g-PAM is used with the metal ions as the coagulant to treat the effluent from a surfactant manufacturer. The response surface methodology coupled with Box-behnken design is employed to optimize the key factors of coagulation-flocculation. The results show that the combination of Fe(3+) with BPC-g-PAM achieves the best coagulation-flocculation performance like, the fast treatment time, minimum coagulant and BPC-g-PAM dosages compared with the other two combinations of Al(3+) with BPC-g-PAM and Ca(2+) with BPC-g-PAM. Therefore, the combination of Fe(3+) with BPC-g-PAM is expected to promote its application for the pollution control in the surfactant manufacturers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.

PubMed

Ferreira, Cláudia N; Carvalho, Maria G; Reis, Helton J; Gomes, Karina B; Sousa, Marinez O; Palotás, András

2014-05-01

Dyslipidemia is one of the pathognomonic elements of athero-genesis, as well as cerebro- and cardio-vascular disease (CCVD). Hemostatic factors are also involved in athero-sclerosis and ischemic changes, however their relationship with disrupted lipid homeostasis is not well characterized. The aim of this study was to determine the coagulation state of dyslipidemic patients and to evaluate their association with CCVD risk factors. Biochemical and hematological parameters, as well as neuro-psychiatric profile of 109 dyslipidemic subjects and 107 normo-lipidic healthy volunteers were assessed. Serum bio-marker levels and cognitive performance generally did not differ in the groups, but prothrombin fragment 1+2 (F1+2) and D-dimer concentrations were markedly higher among women. Hyper-coagulability was not associated with dyslipidemia, but was correlated with the female gender, which might pose an increased thromboembolic risk in asymptomatic women.

CO2 laser therapy of rhinophyma

NASA Astrophysics Data System (ADS)

Voigt, Peggy; Jovanovic, Sergije; Sedlmaier, Benedikt W.

2000-06-01

Laser treatment of skin changes has become common practice in recent years. High absorption of the CO2 laser wavelength in water is responsible for its low penetration dpt in biological tissue. Shortening the tissue exposure time minimizes thermic side effects of laser radiation such as carbonization and coagulation. This can be achieved with scanner systems that move the focused laser beam over a defined area by microprocessor-controlled rapidly rotating mirrors. This enables controlled and reliable removal of certain dermal lesions, particularly hypertrophic scars, scars after common acne, wrinkles and rhinophyma. Laser ablation of rhinophyma is a stress-minimizing procedure for the surgeon and the patient, since it is nearly bloodless and can be performed under local anaesthesia. Cosmetically favorable reepithelization of the lasered surfaces is achieved within a very short period of time.

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.

[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.

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.

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

PubMed

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk

PubMed Central

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease. PMID:26057532

Coagulation activation by MC28 fibrosarcoma cells facilitates lung tumor formation.

PubMed

Amirkhosravi, M; Francis, J L

1995-01-01

Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia and the risk factors for postoperative recurrence

PubMed Central

Li, Chunli; Jia, Libo; Wang, Zhenzhou; Niu, Ling; An, Xinjiang

2018-01-01

The present study investigated the therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia (SVT), and explored the risk factors for postoperative recurrence. A total of 312 patients with pediatric SVT were selected in the Affiliated Children's Hospital of Xuzhou Medical University from April, 2011 to March, 2017. All the patients were subjected to radiofrequency ablation, and clinical data were retrospectively analyzed. Tilt table test was performed before and after treatment, and heart rate, systolic and diastolic blood pressure before and after treatment were compared. Plasma levels of D-dimer (D-D), platelet α-granule membrane protein (GMP-140) and thrombin-antithrombin III complex (TAT) were detected by enzyme-linked immunosorbent assay before treatment, immediately after radiofrequency oblation, and at 1, 3 and 7 days after treatment. Treatment outcomes were compared between the atrioventricular reentrant tachycardia (AVRT) and atrioventricular nodal reentrant tachycardia (AVNRT) groups. Risk factors for postoperative recurrence were analyzed. Supine position heart rate after treatment was not significantly different from that before treatment (P>0.05), while the upright position heart rate was significantly increased after treatment (P<0.05). Systolic pressures of the supine and upright positions were significantly reduced after treatment compared with the levels before (P<0.05), but no significant differences were found in diastolic blood pressure of supine and the upright position (P>0.05). No significant difference in radiofrequency ablation rate, recurrence rate and incidence of complications were found between the AVRT and AVNRT groups (P>0.05). After radiofrequency, the levels of D-D, GMP-140 and TAT ablation showed an upward trend, but decreased at day 7 to reach preoperative levels. Logistic regression analysis revealed that residual slow pathway (OR=6.718, P=0.005) and inaccurate targeting (OR=2.815, P=0.007) were independent risk factors for postoperative recurrence (P<0.05). Although radiofrequency ablation can damage the cardiac vagal nerve, resulting in an increase in the heart rate after ablation during the course of the tilt table test and changed hemagglutination state within one week after ablation, those changes returned to normal after one week. The efficacy of radiofrequency ablation in the treatment of pediatric SVT is clear, and recurrence rate is low. Residual slow pathway and inaccurate targeting were independent risk factors for postoperative recurrence. PMID:29725383

Therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia and the risk factors for postoperative recurrence.

PubMed

Li, Chunli; Jia, Libo; Wang, Zhenzhou; Niu, Ling; An, Xinjiang

2018-05-01

The present study investigated the therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia (SVT), and explored the risk factors for postoperative recurrence. A total of 312 patients with pediatric SVT were selected in the Affiliated Children's Hospital of Xuzhou Medical University from April, 2011 to March, 2017. All the patients were subjected to radiofrequency ablation, and clinical data were retrospectively analyzed. Tilt table test was performed before and after treatment, and heart rate, systolic and diastolic blood pressure before and after treatment were compared. Plasma levels of D-dimer (D-D), platelet α-granule membrane protein (GMP-140) and thrombin-antithrombin III complex (TAT) were detected by enzyme-linked immunosorbent assay before treatment, immediately after radiofrequency oblation, and at 1, 3 and 7 days after treatment. Treatment outcomes were compared between the atrioventricular reentrant tachycardia (AVRT) and atrioventricular nodal reentrant tachycardia (AVNRT) groups. Risk factors for postoperative recurrence were analyzed. Supine position heart rate after treatment was not significantly different from that before treatment (P>0.05), while the upright position heart rate was significantly increased after treatment (P<0.05). Systolic pressures of the supine and upright positions were significantly reduced after treatment compared with the levels before (P<0.05), but no significant differences were found in diastolic blood pressure of supine and the upright position (P>0.05). No significant difference in radiofrequency ablation rate, recurrence rate and incidence of complications were found between the AVRT and AVNRT groups (P>0.05). After radiofrequency, the levels of D-D, GMP-140 and TAT ablation showed an upward trend, but decreased at day 7 to reach preoperative levels. Logistic regression analysis revealed that residual slow pathway (OR=6.718, P=0.005) and inaccurate targeting (OR=2.815, P=0.007) were independent risk factors for postoperative recurrence (P<0.05). Although radiofrequency ablation can damage the cardiac vagal nerve, resulting in an increase in the heart rate after ablation during the course of the tilt table test and changed hemagglutination state within one week after ablation, those changes returned to normal after one week. The efficacy of radiofrequency ablation in the treatment of pediatric SVT is clear, and recurrence rate is low. Residual slow pathway and inaccurate targeting were independent risk factors for postoperative recurrence.

Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

PubMed

Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

2016-01-01

Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

PubMed

De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

2015-01-01

Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII.

Hard tissue ablation with a spray-assisted mid-IR laser

NASA Astrophysics Data System (ADS)

Kang, H. W.; Rizoiu, I.; Welch, A. J.

2007-12-01

The objective of this study was to understand the dominant mechanism(s) for dental enamel ablation with the application of water spray. A free-running Er,Cr:YSGG (yttrium, scandium, gallium, garnet) laser was used to ablate human enamel tissue at various radiant exposures. During dental ablation, distilled water was sprayed on the sample surface, and these results were compared to ablation without a spray (dry ablation). In order to identify dominant ablation mechanisms, transient acoustic waves were compared to ablation thresholds and the volume of material removed. The ablation profile and depth were measured using optical coherence tomography (OCT). Irregular surface modification, charring and peripheral cracks were associated with dry ablation, whereas craters for spray samples were relatively clean without thermal damage. In spite of a 60% higher ablation threshold for spray associated irradiations owing to water absorption, acoustic peak pressures were six times higher and ablation volume was up to a factor of 2 larger compared to dry ablation. The enhanced pressure and ablation performance of the spray-assisted process was the result of rapid water vaporization, material ejection with recoil stress, interstitial water explosion and possibly liquid-jet formation. With water cooling and abrasive/disruptive mechanical effects, the spray ablation can be a safe and efficient modality for dental treatment.

Holmium: yttrium aluminum garnet laser-assisted endoscopic sinus surgery: laboratory experience.

PubMed

Shapshay, S M; Rebeiz, E E; Bohigian, R K; Hybels, R L; Aretz, H T; Pankratov, M M

1991-02-01

Endoscopic sinus surgery has gained wide acceptance since its introduction into the United States. Complex sinus anatomy and troublesome bleeding have been associated with complications, which vary in severity from synechia to blindness and leakage of cerebrospinal fluid. Endoscopic sinus surgery using a holmium: yttrium aluminum garnet pulsed solid-state laser oscillating at 2.1 microns with fiberoptic delivery was performed in the laboratory, and the results were compared with those of conventional endoscopic sinus surgery. Three beagle dogs, six human cadaver heads, and one calf head were used in the in vivo and in vitro studies to evaluate the bone ablation, tissue coagulation, and hemostatic properties of the holmium: yttrium aluminum garnet laser. Modified endoscopic telescopes for sinus surgery, a newly developed handpiece for fiberoptic delivery, and other surgical instruments were used. The results indicate that the holmium: yttrium aluminum garnet laser and new delivery instrumentation provide good hemostasis and controlled soft-tissue ablation and bone removal. The access to all sinuses in the human cadaver model was very good. The canine in vivo study showed delayed but complete healing on the laser-treated side. Clinical evaluation of the holmium: yttrium aluminum garnet laser is warranted to increase the precision and safety of endoscopic sinus surgery.

Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation

PubMed Central

1994-01-01

Cells of monocytic lineage can initiate extravascular fibrin deposition via expression of blood coagulation mediators. This report is about experiments on three mechanisms with the potential to modulate monocyte- initiated coagulation. Monocyte procoagulant activity was examined as a function of lipid cofactor, protein cofactor, and specific inhibitor expression during short-term culture in vitro. Lipid cofactor activity was measured as the initial rate of factor X activation by intrinsic- pathway components, the assembly of which depends on this cofactor. Lipid cofactor activity levels changed by < 30% during 48-h culture. Protein cofactor, i.e., tissue factor (TF) antigen was measured by enzyme immunoassay. It increased from 461 pg/ml to a maximum value of 3,550 pg/ml at 24 h and remained at 70% of this value. Specific TF activity, measured as factor VII-dependent factor X activation rate, decreased from 54 to 18 nM FXa/min between 24 and 48 h. TF activity did not correlate well with either lipid cofactor or TF protein levels. In contrast, the decrease in TF activity coincided in time with maximal expression of tissue factor pathway inhibitor (TFPI) mRNA, which was determined using reverse transcriptase polymerase chain reaction (RT- PCR), and with maximal TFPI protein levels measured by immunoassay. The number of mRNA copies coding for TFPI and TF in freshly isolated blood monocytes were 46 and 20 copies/cells, respectively. These values increased to 220 and 63 copies/cell during short-term cell culture in the presence of endotoxin. Results demonstrate concomitant expression by monocytes of genes coding for both the essential protein cofactor and the specific inhibitor of the extrinsic coagulation pathway. Together with functional and antigenic analyses, they also imply that the initiation of blood clotting by extravascular monocyte/macrophages can be modulated locally by TFPI independently of plasma sources of the inhibitor. PMID:8195712

Coagulation Profile as a Risk Factor for 30-Day Morbidity and Mortality Following Posterior Lumbar Fusion.

PubMed

Bronheim, Rachel S; Oermann, Eric K; Cho, Samuel K; Caridi, John M

2017-06-15

A retrospective cohort study. The aim of this study was to identify associations between abnormal coagulation profile and postoperative morbidity and mortality in patients undergoing posterior lumbar fusion (PLF). The literature suggests that abnormal coagulation profile is associated with postoperative complications, notably the need for blood transfusion. However, there is little research that directly addresses the influence of coagulation profile on postoperative complications following PLF. The American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP) was utilized to identify patients undergoing PLF between 2006 and 2013. Nine thousand two hundred ninety-five patients met inclusion criteria. Multivariate analysis was utilized to identify associations between abnormal coagulation profile and postoperative complications. Low platelet count was an independent risk factor for organ space surgical site infections (SSIs) [odds ratio (OR) = 6.0, P < 0.001], ventilation >48 hours (OR = 4.5, P = 0.002), Acute renal failure (OR = 5.8, P = 0.007), transfusion (OR = 1.6, P < 0.001), sepsis (OR = 2.2, P = 0.037), reoperation (OR = 2.5, P = 0.001), and death (OR = 3.7, P = 0.049). High partial thromboplastin time (PTT) was an independent risk factor for ventilation >48 hours (OR = 5.6, P = 0.002), cerebrovascular accident (CVA)/stroke with neurological deficit (OR = 5.1, P = 0.011), cardiac arrest (OR = 5.4, P = 0.030), transfusion (OR = 1.5, P = 0.020), and death (OR = 4.5, P = 0.050). High International Normalized Ration (INR) was an independent risk factor for pneumonia (OR = 8.7, P = 0.001), pulmonary embolism (OR = 5.6, P = 0.021), deep venous thrombosis/Thrombophlebitis (OR = 4.8, P = 0.011), septic shock (OR = 8.4, P = 0.048), and death (OR = 9.8, P = 0.034). Bleeding disorder was an independent risk factor for organ space SSI (OR = 5.4, P = 0.01), pneumonia (OR = 3.0, P = 0.023), and sepsis (OR = 4.4, P < 0.001). Abnormal coagulation profile was an independent predictor of morbidity and mortality in patients undergoing PLF. As such, it should be considered in preoperative optimization and risk stratification.

Molecular cloning, characterization and expression analysis of coagulation factor VII gene in grass carp (Ctenopharyngodon idella).

PubMed

Liu, Qiaolin; Xu, Baohong; Xiao, Tiaoyi; Su, Jianming; Zhong, Lei

2013-08-01

Coagulation factor VII has been studied in several species but, to date, not in grass carp (Ctenopharyngodon idella), a commercially important freshwater fish found in China. In this study, the full-length cDNA of grass carp coagulation factor VII (GcCFVII) was cloned using a RACE-Ready cDNA Kit, grass carp were challenged with a hemorrhagic virus, and temporal expression profiles of GcCFVII in the thymus, gills, liver, spleen, and head kidney were examined at 0 h, 24 h, 48 h, 72 h, 96 h, and 138 h using fluorescence quantitative PCR. The results showed the 1480 bp GcCFVII to contain three conservative motifs: Gla, EGF-CA, and Tryp-SPc, similar to other species. Phylogenetic analysis showed the evolution of GcCFVII gene to be consistent with the evolution of the species. After viral challenge, GcCFVII expression in five tissues of grass carp showed different patterns of fluctuation. These results provide a solid basis for further investigation of GcCFVII and its relationship with grass carp hemorrhage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Physiotherapy, rehabilitation and sports in countries with limited replacement coagulation factor supply.

PubMed

Buzzard, B M

2007-09-01

It is well documented that physiotherapy and rehabilitation benefit people with haemophilia by strengthening the key muscle groups and protecting joints from the adverse effects of repeated haemorrhages. Rehabilitation, in conjunction with the availability of replacement coagulation factor products, has revolutionized approaches to the management of patients with haemophilia in developed countries and has led to a substantial decrease in both the morbidity and mortality rates among the haemophilic population. Modern treatment approaches have also enabled persons with haemophilia to participate in sporting activities along with their peers; however, these improvements in care have not been achieved in developing nations, where health-care resources and facilities are scarce and the supply of coagulation factor products is limited. This article attempts to address the following questions about the management of haemophilic patients in developing countries: Can physiotherapy, rehabilitation and sports prevent disabilities and preserve independence? Is participation in sports activities possible in developing countries? Do countries differ with regard to guidelines for participation in sports? Should we be encouraging participation in sports or allowing patients with haemophilia to do as they choose?

Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids.

PubMed

Tholstrup, T; Marckmann, P; Jespersen, J; Sandström, B

1994-02-01

The effect of fats high in individual, prevalent saturated dietary fatty acids on lipoproteins and hemostatic variables in young healthy subjects was evaluated in a randomized strictly controlled metabolic feeding study. Three experimental diets: shea butter (S; 42% stearic acid), palm oil (P; 43% palmitic palmitic acid), and palm-kernel oil with high-oleic sunflower oil (ML; 10% myristic acid, 30% lauric acid) were served to 15 men for 3 wk each, separated by washout periods. Diet S compared with diet P resulted in significant reduction in plasma cholesterol (22%) LDL cholesterol (26%), apolipoprotein B (18%), HDL cholesterol (12%), apolipoprotein A-I (13%), and a 13% lower factor VII coagulant activity (P = 0.001). Similar differences were observed between diets S and ML. In conclusion, intake of shea butter high in stearic acid favorably affects blood lipids and factor VII coagulant activity in young men, compared with fats high in saturated fatty acids with 12-16 carbons.

Confinement regulates complex biochemical networks: initiation of blood clotting by "diffusion acting".

PubMed

Shen, Feng; Pompano, Rebecca R; Kastrup, Christian J; Ismagilov, Rustem F

2009-10-21

This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da(2), was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as "diffusion acting", which is distinct from "diffusion sensing". The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological "on" and "off" processes that are controlled by thresholds.

The Loss of Homeostasis in Hemostasis: New Approaches in Treating and Understanding Acute Disseminated Intravascular Coagulation in Critically Ill Patients*

PubMed Central

Abrams, Charles S.

2012-01-01

Abstract Disseminated intravascular coagulation (DIC) profoundly increases the morbidity and mortality of patients who have sepsis. Both laboratory and clinical research advanced the understanding of the biology and pathophysiology of DIC. This, in turn, gave rise to improved therapies and patient outcomes. Beginning with a stimulus causing disruption of vascular integrity, cytokines and chemokines cause activation of systemic coagulation and inflammation. Seemingly paradoxically, the interplay between coagulation and inflammation also inhibits endogenous anticoagulants, fibrinolytics, and antiinflammatory pathways. The earliest documented and best‐studied microbial cause of DIC is the lipopolysaccharide endotoxin of Gram‐negative bacteria. Extensive microvascular thrombi emerge in the systemic vasculature due to dysregulation of coagulation. The result of this unrestrained, widespread small vessel thromboses multiorgan system failure. Consumption of platelets and coagulation factors during this process can lead to an elevated risk of hemorrhage. The management of these patients with simultaneous hemorrhage and thrombosis is complex and challenging. Definitive treatment of DIC, and attenuation of end‐organ damage, requires control of the inciting cause. Currently, activated protein C is the only approved therapy in the United States for sepsis complicated by DIC. Further research is needed in this area to improve clinical outcomes for patients with sepsis. Clin Trans Sci 2012; Volume 5: 85–92 PMID:22376264

Coagulation Abnormalities of Sickle Cell Disease: Relationship with Clinical Outcomes and the Effect of Disease Modifying Therapies

PubMed Central

Noubouossie, Denis; Key, Nigel S.; Ataga, Kenneth I.

2015-01-01

Sickle cell disease (SCD) is a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multi-factorial, with contributions from ischemia-reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle RBC phosphatidylserine expression. Recent studies in animal models suggest that activation of coagulation may contribute to the pathogenesis of SCD, but the data on the contribution of coagulation and platelet activation to SCD-related complications in humans are limited. Clinical trials of new generations of anticoagulants and antiplatelet agents, using a variety of clinical endpoints are warranted. PMID:26776344

Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

PubMed Central

Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

2017-01-01

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

Role of plasma kallikrein in diabetes and metabolism.

PubMed

Feener, E P; Zhou, Q; Fickweiler, W

2013-09-01

Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.

Repeated Radiofrequency Ablation Combined With Ablated Lesion Elimination and Transarterial Chemoembolization Improves the Outcome of Solitary Huge Hepatocellular Carcinomas 10 cm or Larger

PubMed Central

Ke, Shan; Gao, Jun; Kong, Jian; Ding, Xue-Mei; Niu, Hai-Gang; Xin, Zong-Hai; Ning, Chun-Min; Guo, Shi-Gang; Li, Xiao-Long; Zhang, Long; Dong, Yong-Hong; Sun, Wen-Bing

2016-01-01

Abstract This study investigated the effectiveness of a new strategy, repeated radiofrequency (RF) ablation combined with ablated lesion elimination following transarterial chemoembolization (TACE)/transarterial embolization (TAE), for solitary huge hepatocellular carcinoma (SHHCC) 10 cm or larger. From July 2008 to October 2015, 39 consecutive patients with SHHCC were screened. Of these, 12 were treated with TACE/TAE and repeated RF ablation (TACE/TAE + RF ablation group) and the remaining 27 patients were treated with the aforementioned new strategy (new strategy group). Local tumor progression (LTP)-free survival, intrahepatic distant recurrence (IDR)-free survival, and overall survival (OS) rates were obtained using the Kaplan–Meier method. Univariate and multivariate analyses were performed on several clinicopathological variables to identify factors affecting long-term outcome and intrahepatic recurrence. Correlation analysis was also performed. The 1-, 2-, and 3-year LTP-free survival rates and OS rates were significantly higher in the new strategy group than in the TACE/TAE + RF ablation group (82.9% vs 58.3%, 73.9% vs 29.2%, 18.5% vs 9.7%, P = 0.002; 92.0% vs 75.0%, 84.0% vs 33.3%, 32.7% vs 16.7%, P = 0.025). However, there was no significant difference between the 2 groups in the 1-, 2-, and 3-year IDR-free survival rates (P = 0.108). Using univariate analysis, alpha-fetoprotein (AFP > 200 ng/mL), ablative margin (AM > 1.0 cm), and well-differentiated cells were found to be significant factors for predicting LTP, IDR, and OS. Surgical elimination was found to be a significant factor only for predicting OS. In multivariate analyses, AFP (>200 ng/mL), AM (>1.0 cm), and well-differentiated cells were found to be significant independent factors linked to LTP, IDR, and OS. Correlation analysis indicated that AM > 1.0 cm was strongly associated with surgical elimination (P < 0.001, correlation coefficient = 0.877). For patients with SHHCC who were initially excluded from surgery, the new strategy including repeated RF ablation combined with ablated lesion elimination following TACE/TAE should now be considered as an alternative treatment. PMID:27100425

High-powered microwave ablation of larger hepatocellular carcinoma: evaluation of recurrence rate and factors related to recurrence.

PubMed

Zhang, N N; Lu, W; Cheng, X J; Liu, J Y; Zhou, Y H; Li, F

2015-11-01

To evaluate the safety and efficacy of high-powered (80-100 W) percutaneous microwave ablation (MWA) at a frequency of 2450±10 MHz for treating larger hepatocellular carcinoma (HCC) and to predict the risk factors of local recurrence after high-powered MWA. The study was approved by the Institutional Review Board, and informed consent was waived because of the retrospective study design. Forty-five patients with a total of 60 lesions received high-power (80-100 W) MWA at a frequency of 2450±10 MHz through a percutaneous approach that was guided by ultrasound. Of the 60 lesions with a maximum tumour measuring 3-8 cm, 46 lesions were 3-5 cm and 14 were 5-8 cm. The complete ablation rates, local recurrence rates, complications, and short-term survival were analysed. Ten possible risk factors for local recurrence were analysed. The complete ablation rates were 82.61% for the first ablation and 100% for the second ablation for 3-5 cm lesions. The complete ablation rates were 64.29% (82.61% versus 64.29%, p=0.037) for the first ablation and 85.71% (100% versus 85.71%, p=0.055) for the second ablation for 5-8 cm lesions. Local recurrence was observed in 11 out of the 45 (24.44%) successfully treated patients. The 1-year and 2-year survival rates were 95.56% (43/45) and 86.67% (39/45), respectively. No procedure-related mortality was observed and no major bleeding, liver rupture, or liver abscesses occurred. Univariate analysis showed that a positive correlation existed between the number of lesions (p=0.022), proximity to the risk area (p=0.001), pre-ablation alpha-fetoprotein (AFP) levels (p=0.025), hepatitis B virus (HBV)-DNA replication (p=0.027) and local recurrence. Multivariate analysis identified HBV-DNA (p=0.031) and proximity to the risk area (p=0.039) as the independent prognosis factors causing postoperative HCC local recurrence. High-powered MWA of larger hepatocellular carcinomas appears to be a safe and effective treatment. HBV-DNA and proximity to the risk area appear to be independent predictors of local tumour recurrence. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The role of protease-activated receptors PAR-1 and PAR-2 in the repair of 16HBE 14o(-) epithelial cell monolayers in vitro.

PubMed

Ewen, D; Clarke, S L; Smith, J R; Berger, C; Salmon, G; Trevethick, M; Shute, J K

2010-03-01

We recently reported that repair following mechanical wounding of epithelial cell layers in vitro is dependent on fibrin formation and the activity of locally expressed coagulation cascade proteins. Serine proteases of the coagulation cascade are an important group of protease-activated receptor (PAR) activators and PAR-1 to 4 are expressed by the normal bronchial epithelium. We tested the hypothesis that activation of PAR-1 and PAR-2 by coagulation cascade proteases stimulates epithelial repair via effects on fibrin formation. Using mechanically wounded 16HBE 14o(-) epithelial cell layers in culture, we investigated the effect of PAR-1 and PAR-2 agonist peptides, control partially scrambled peptides and PAR-neutralizing antibodies on the rate of repair and fibrin formation. Coagulation factors in culture supernatants were measured by immunoblot. RT-PCR was used to investigate PAR-1, PAR-2 and PGE2 receptor (EP-1 to EP-4) expression in this model and qRT-PCR to quantify responses to wounding. Additionally, we investigated the effect of exogenously added factor Xa (FXa) and neutrophil elastase and the influence of PGE2 and indomethacin on the repair response. PAR-1 and PAR-2 peptide agonists stimulated the rate of repair and enhanced the formation of a fibrin provisional matrix to support the repair process. Conversely, PAR-neutralizing antibodies inhibited repair. Under serum-free culture conditions, 16HBE 14o(-) cells expressed EP-2 and EP-3, but not EP-1 or EP-4, receptors. Wounding induced an increased expression of EP-3 but did not alter EP-2, PAR-1 or PAR-2 expression. In the absence of PAR agonists, there was no evidence for a role for PGE2 in fibrin formation or the repair process. Indomethacin attenuated fibrin formation in wounded cultures only in the presence of the PAR-2 peptide. FXa stimulated epithelial repair while neutrophil elastase reduced the levels of coagulation factors and inhibited repair. Locally expressed serine proteases of the coagulation cascade activate PAR-1 and PAR-2 to enhance fibrin formation and bronchial epithelial repair.

Laser-assisted delivery of topical methotrexate - in vitro investigations.

PubMed

Taudorf, Elisabeth Hjardem

2016-06-01

Ablative fractional lasers (AFXL) are increasingly used to treat dermatological disorders and to facilitate laser-assisted topical drug delivery. In this thesis, laser-tissue interactions generated by stacked pulses with a miniaturized low-power 2,940 nm AFXL were characterized (study I). Knowledge of the correlation between laser parameters and tissue effects was used to deliver methotrexate (MTX) topically through microscopic ablation zones (MAZs) of precise dimensions. MTX is a well-known chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects, and topical delivery is thus of potential benefit. The impact of MAZ depth (study II) and transport kinetics (study III) on MTX deposition in skin as well as transdermal permeation was determined in vitro. Quantitative analyses of dermal and transdermal MTX concentrations were performed by high performance liquid chromatography (HPLC) (study II & III), while qualitative analyses of MTX biodistribution in skin were illustrated and semi-quantified by fluorescence microscopy (study II & III) and desorption electro spray mass spectrometry imaging (DESI-MSI) (study III). Laser-tissue interactions generated by AFXL: AFXL-exposure generated a variety of MAZ-dimensions. MAZ depth increased linearly with the logarithm of total energy delivered by stacked pulses, but was also affected by variations in power, pulse energy, pulse duration, and pulse repetition rate. Coagulation zones lining MAZs increased linearly with the applied total energy, while MAZ width increased linearly with the logarithm of stacked pulses. Results were gathered in a mathematical model estimating relations between laser parameters and specific MAZ dimensions. Impact of MAZ depth on AFXL-assisted topical MTX delivery: Pretreatment by AFXL facilitated topical MTX delivery to all skin layers. Deeper MAZs increased total MTX deposition in skin compared to superficial MAZs and altered the intradermal biodistribution profile towards maximum accumulation in deeper skin layers. Biodistribution of MTX occurred throughout the skin without being compromised by coagulation zones of varying thickness. The ratio of skin deposition versus transdermal permeation was constant, regardless of MAZ depth. Impact of transport kinetics on AFXL-assisted topical MTX delivery: MTX accumulated rapidly in AFXL-processed skin. MTX was detectable in mid-dermis after 15 min. and saturated the skin after 7 h at a ten-fold increased MTX-concentration compared to intact skin. Transdermal permeation stayed below 1.5% of applied MTX before skin saturation, and increased afterwards up to 8.0% at 24h. MTX distributed radially into the coagulation zone within 15 min of application and could be detected in surrounding skin at 1.5 h. Upon skin saturation, MTX had distributed in an entire mid-dermal skin section. In conclusion, adjusting laser parameters and application time may enable targeted treatments of dermatological disorders and potentially pose a future alternative to systemic MTX in selected dermatological disorders.

Coagulation removal of humic acid-stabilized carbon nanotubes from water by PACl: influences of hydraulic condition and water chemistry.

PubMed

Ma, Si; Liu, Changli; Yang, Kun; Lin, Daohui

2012-11-15

Discharged carbon nanotubes (CNTs) can adsorb the widely-distributed humic acid (HA) in aquatic environments and thus be stabilized. HA-stabilized CNTs can find their way into and challenge the potable water treatment system. This study investigated the efficiency of coagulation and sedimentation techniques in the removal of the HA-stabilized multi-walled carbon nanotubes (MWCNTs) using polyaluminum chloride (PACl) as a coagulant, with a focus on the effects of hydraulic conditions and water chemistry. Stirring speeds in the mixing and reacting stages were gradually changed to examine the effect of the hydraulic conditions on the removal rate. The stirring speed in the reacting stage affected floc formation and thereby had a greater impact on the removal rate than the stirring speed in the mixing stage. Water chemistry factors such as pH and ionic strength had a significant effect on the stability of MWCNT suspension and the removal efficiency. Low pH (4-7) was favorable for saving the coagulant and maintaining high removal efficiency. High ionic strength facilitated the destabilization of the HA-stabilized MWCNTs and thereby lowered the required PACl dosage for the coagulation. However, excessively high ionic strength (higher than the critical coagulation concentration) decreased the maximum removal rate, probably by inhibiting ionic activity of PACl hydrolyzate in water. These results are expected to shed light on the potential improvement of coagulation removal of aqueous stabilized MWCNTs in water treatment systems. Copyright © 2012 Elsevier B.V. All rights reserved.

[Effects on phenol removal in the process of enhanced coagulation by manganese dioxide formed in situ].

PubMed

Zhang, Li-Zhu; Chen, Xiao-Dong; Ma, Jun; Yu, Min; Li, Xin

2011-10-01

Phenol was selected as a model compound. Factors, such as Ca2+, tannic acid, dose of kaolinite, dose of manganese dioxide formed in situ and pH, were invested on phenol removal in the process of enhanced coagulation by manganese dioxide formed in situ. Results showed that the addition of Ca2+ is beneficial for phenol removal. In the range of Ca2+ varied from 0 to 1.0 mmol x L(-1), the efficiency of phenol removal was enhanced more than 10%. Tannic acid can enhance phenol removal significantly when they are coexisted in water. As tannic acid was added to 10 mg x L(-1), phenol removal can be increased about 30% and 50% in the process of coagulation by AlCl3 and enhanced coagulation by manganese dioxide formed in situ, respectively. The dose of coagulant can be reduced in the process of enhanced coagulation with the addition of manganese dioxide formed in situ. The point of 1 mg x L(-1) manganese dioxide formed in situ linked with 30 mg x L(-1) AlCl3 can have the same phenol removal efficiency as the addition of 50 mg x L(-1) AlCl3. In the range of pH varied from 5 to 9, phenol can be removed with the high efficiency in the process of enhanced coagulation by manganese dioxide formed in situ. While under the strong acid condition and strong basic condition, phenol has lower removal efficiency.

Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

PubMed

Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

2010-05-01

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

Measurement of the coagulation dynamics of bovine liver using the modified microscopic Beer-Lambert law.

PubMed

Terenji, Albert; Willmann, Stefan; Osterholz, Jens; Hering, Peter; Schwarzmaier, Hans-Joachim

2005-06-01

During heating, the optical properties of biological tissues change with the coagulation state. In this study, we propose a technique, which uses these changes to monitor the coagulation process during laser-induced interstitial thermotherapy (LITT). Untreated and coagulated (water bath, temperatures between 35 degrees C and 90 degrees C for 20 minutes.) samples of bovine liver tissue were examined using a Nd:YAG (lambda = 1064 nm) frequency-domain reflectance spectrometer. We determined the time integrated intensities (I(DC)) and the phase shifts (Phi) of the photon density waves after migration through the tissue. From these measured quantities, the time of flight (TOF) of the photons and the absorption coefficients of the samples were derived using the modified microscopic Beer-Lambert law. The absorption coefficients of the liver samples decreased significantly with the temperature in the range between 50 degrees C and 70 degrees C. At the same time, the TOF of the investigated photos was found increased indicating an increased scattering. The coagulation dynamics could be well described using the Arrhenius formalism with the activation energy of 106 kJ/mol and the frequency factor of 1.59 x 10(13)/second. Frequency-domain reflectance spectroscopy in combination with the modified microscopic Beer-Lambert (MBL) is suitable to measure heat induced changes in the absorption and scattering properties of bovine liver in vitro. The technique may be used to monitor the coagulation dynamics during local thermo-coagulation in vivo. Copyright 2005 Wiley-Liss, Inc.

Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

PubMed

de Jong, Hanna K; Parry, Chris M; van der Vaart, Thomas W; Kager, Liesbeth M; van den Ende, Stannie J; Maude, Rapeephan R; Wijedoru, Lalith; Ghose, Aniruddha; Hassan, Mohammed U; Hossain, Mohammed A; Dondorp, Arjan M; Baker, Steve; Faiz, M Abul; Meijers, Joost C M; Wiersinga, W Joost

2018-05-07

Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

RF-ablation in periventricular heterotopia-related epilepsy.

PubMed

Cossu, Massimo; Mirandola, Laura; Tassi, Laura

2018-05-01

Drug-resistant focal epilepsy is a common occurrence in patients with gray matter nodular heterotopia (NH), and surgical treatment is often considered in these cases. NH-related epileptogenicity is sustained by complex networks, which may involve the nodules and extralesional cortex in various combinations. Therefore, invasive EEG is usually required to identify the structures involved in seizure generation. It has been reported that surgery may be effective in cases with unilateral lesions, whereas bilateral cases are not optimal candidates for surgical success. Furthermore, violation of cortical and subcortical structures for approaching deep-seated nodules may result in neurological deficits. For these reasons, selective stereotactic ablation with radiofrequency thermocoagulation (RFTC) has been proposed as an alternative option in these patients. In particular, RFTC may be performed by using the same recording intracerebral electrodes implanted for stereo-electro-encephalo-graphy (SEEG) monitoring, with the advantage of a reliable electro-clinical guide. Excellent results on seizures have been initially reported following coagulation of single, unilateral NH. Subsequent experience has indicated that, basing on the evidence of SEEG recording, promising results may be obtained also in more extended unilateral and bilateral cases. In more complex cases, coagulation of both the nodules and of the involved extralesional cortical structures is often required. In a recently reported series, 67% of patients experienced sustained seizure freedom after the procedure. However, post RFTC seizure outcome in complex cases (NH plus other malformations of cortical development) is not as good as in other patterns of NH. RFTC, especially if guided by SEEG evaluation, should be considered as a first-line treatment option in NH-related epilepsy. Satisfactory results may be obtained also in cases not amenable to traditional surgery. The procedure is safe and does not prevent eventual resective surgery in case of failure in seizure control. For these reasons, in patients undergoing SEEG evaluation, electrode arrangement should be planned with the aim to cover as extensively as possible the heterotopic and extralesional areas, which will presumably be the targets of RFTC. Copyright © 2017 Elsevier B.V. All rights reserved.

Short communication: Prediction of milk coagulation and acidity traits in Mediterranean buffalo milk using Fourier-transform mid-infrared spectroscopy.

PubMed

Manuelian, C L; Visentin, G; Boselli, C; Giangolini, G; Cassandro, M; De Marchi, M

2017-09-01

Milk coagulation and acidity traits are important factors to inform the cheesemaking process. Those traits have been deeply studied in bovine milk, whereas scarce information is available for buffalo milk. However, the dairy industry is interested in a method to determine milk coagulation and acidity features quickly and in a cost-effective manner, which could be provided by Fourier-transform mid-infrared (FT-MIR) spectroscopy. The aim of this study was to evaluate the potential of FT-MIR to predict coagulation and acidity traits of Mediterranean buffalo milk. A total of 654 records from 36 herds located in central Italy with information on milk yield, somatic cell score, milk chemical composition, milk acidity [pH, titratable acidity (TA)], and milk coagulation properties (rennet coagulation time, curd firming time, and curd firmness) were available for statistical analysis. Reference measures of milk acidity and coagulation properties were matched with milk spectral information, and FT-MIR prediction models were built using partial least squares regression. The data set was divided into a calibration set (75%) and a validation set (25%). The capacity of FT-MIR spectroscopy to correctly classify milk samples based on their renneting ability was evaluated by a canonical discriminant analysis. Average values for milk coagulation traits were 13.32 min, 3.24 min, and 39.27 mm for rennet coagulation time, curd firming time, and curd firmness, respectively. Milk acidity traits averaged 6.66 (pH) and 7.22 Soxhlet-Henkel degrees/100 mL (TA). All milk coagulation and acidity traits, except for pH, had high variability (17 to 46%). Prediction models of coagulation traits were moderately to scarcely accurate, whereas the coefficients of determination of external validation were 0.76 and 0.66 for pH and TA, respectively. Canonical discriminant analysis indicated that information on milk coagulating ability is present in the MIR spectra, and the model correctly classified as noncoagulating the 91.57 and 67.86% of milk samples in the calibration and validation sets, respectively. In conclusion, our results can be relevant to the dairy industry to classify buffalo milk samples before processing. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Coagulation Profile as a Risk Factor for 30-day Morbidity Following Cervical Laminectomy and Fusion.

PubMed

Bronheim, Rachel S; Oermann, Eric K; Cho, Samuel K; Caridi, John M

2018-02-15

Retrospective analysis of prospectively collected data. The aim of this study was to determine the ability of abnormal coagulation profile to predict adverse events following posterior cervical laminectomy and fusion (PCLF). PCLF is an increasingly common procedure used to treat a variety of traumatic and degenerative spinal conditions. Abnormal coagulation profile is associated with postoperative adverse events, including blood transfusion. There is a paucity of literature that specifically addresses the relationship between coagulation profile and complications following PCLF. ACS-NSQIP was utilized to identify patients undergoing PCLF between 2006 and 2013. A total of 3546 patients met inclusion criteria. Multivariate analysis was utilized to identify associations between abnormal coagulation profile and postoperative complications. Membership in the low-platelet cohort was an independent risk factor for myocardial infarction (Odds Ratio (OR) = 5.4 [1.0, 29.1], P = 0.049) and bleeding transfusion (OR = 2.0 [1.2, 3.4], P = 0.011). Membership in the high international normalized ratio group was an independent risk factor for pneumonia (OR = 6.3 [2.5, 16.1], P < 0.001), ventilation >48 hours (OR = 6.5 [2.3, 18.4], P < 0.001), organ space surgical site infection (OR = 11.1 [2.1, 57.3], P = 0.004), urinary tract infection (OR = 3.0 [1.2, 8.0], P = 0.024), bleeding transfusion (OR = 6.0 [3.4, 10.7], P < 0.001), sepsis (OR = 5.1 [1.6, 16.4], P = 0.006), and septic shock (OR = 6.8 [1.7, 27.4], P = 0.007). Membership in the bleeding disorders cohort was an independent predictor of unplanned intubation (OR = 3.2 [1.1, 9.5], P = 0.041), pneumonia (OR = 2.9 [1.2, 7.2], P = 0.023), ventilation >48 hours (OR = 4.8 [1.9, 12.4], P = 0.001), cerebrovascular accident/stroke with neurological deficit (OR = 24.8 [2.9, 210.6], P = 0.003), bleeding transfusion (OR = 2.1 [1.1, 4.1], P = 0.032), reoperation (OR = 3.6 [1.4, 9.3], P = 0.008), and sepsis (OR = 3.4 [1.1, 10.4], P = 0.031). This is the first large study to document abnormal coagulation profile as an independent predictor of outcomes following PCLF. Abnormal coagulation profile represents a predictor of complications that can be medically mitigated, and is therefore a valuable parameter to assess preoperatively. Coagulation profile should continue to play a role in targeting patients for risk stratification, preoperative optimization, and quality improvement initiatives. 3.

Femtosecond laser for cavity preparation in enamel and dentin: ablation efficiency related factors.

PubMed

Chen, H; Li, H; Sun, Yc; Wang, Y; Lü, Pj

2016-02-11

To study the effects of laser fluence (laser energy density), scanning line spacing and ablation depth on the efficiency of a femtosecond laser for three-dimensional ablation of enamel and dentin. A diode-pumped, thin-disk femtosecond laser (wavelength 1025 nm, pulse width 400 fs) was used for the ablation of enamel and dentin. The laser spot was guided in a series of overlapping parallel lines on enamel and dentin surfaces to form a three-dimensional cavity. The depth and volume of the ablated cavity was then measured under a 3D measurement microscope to determine the ablation efficiency. Different values of fluence, scanning line spacing and ablation depth were used to assess the effects of each variable on ablation efficiency. Ablation efficiencies for enamel and dentin were maximized at different laser fluences and number of scanning lines and decreased with increases in laser fluence or with increases in scanning line spacing beyond spot diameter or with increases in ablation depth. Laser fluence, scanning line spacing and ablation depth all significantly affected femtosecond laser ablation efficiency. Use of a reasonable control for each of these parameters will improve future clinical application.

[Molecular genetic analysis for a pedigree with severe hereditary coagulation factor VII deficiency].

PubMed

Ding, Qiu-lan; Wang, Hong-li; Wang, Xue-feng; Wang, Ming-shan; Fu, Qi-hua; Wu, Wen-man; Hu, Yi-qun; Wang, Zhen-yi

2003-10-01

To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree. The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production. Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation. Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.

The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

PubMed

Smadja, David M; Susen, Sophie; Rauch, Antoine; Cholley, Bernard; Latrémouille, Christian; Duveau, Daniel; Zilberstein, Luca; Méléard, Denis; Boughenou, Marie-Fazia; Belle, Eric Van; Gaussem, Pascale; Capel, Antoine; Jansen, Piet; Carpentier, Alain

2017-10-01

To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). Preclinical study SETTING: Single-center biosurgical research laboratory. Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. Surgical implantation of TAH through a mid-sternotomy approach. Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Real-time Focused Ultrasound Surgery (FUS) Monitoring Using Harmonic Motion Imaging (HMI)

NASA Astrophysics Data System (ADS)

Maleke, Caroline; Konofagou, Elisa E.

2009-04-01

Monitoring changes in tissue mechanical properties to optimally control thermal exposure is important in thermal therapies. The amplitude-modulated (AM) harmonic motion imaging (HMI) for focused ultrasound (HMIFU) technique is a radiation force technique, which has the capability of tracking tissue stiffness during application of an oscillatory force. The feasibility of HMIFU for assessing mechanical tissue properties has been previously demonstrated. In this paper, a confocal transducer, combining a 4.5 MHz FUS transducer and a 3.3 MHz phased array imaging transducer, was used. The FUS transducer was driven by AM wave at 15 Hz with an acoustic intensity (Ispta) was equal to 1050 W/cm2. A lowpass digital filter was used to remove the spectrum of the higher power beam prior to displacement estimation. The resulting axial tissue displacement was estimated using 1D cross-correlation with a correlation window of 2 mm and a 92.5% overlap. A thermocouple was also used to measure the temperature near the ablated region. 2D HMI-images from six-bovine-liver specimens indicated the onset of coagulation necrosis through changes in amplitude displacement after coagulation due to its simultaneous probing and heating capability. The HMI technique can thus be used to monitor temperature-related stiffness changes of tissues during thermal therapies in real-time, i.e., without interrupting or modifying the treatment protocol.

Argon plasma coagulation of gastric inlet patches for the treatment of globus sensation: it is an effective therapy in the long term.

PubMed

Klare, P; Meining, A; von Delius, S; Wolf, P; Konukiewitz, B; Schmid, R M; Bajbouj, M

2013-01-01

To determine the long-term effect of argon plasma coagulation (APC) of gastric inlet patches in the cervical esophagus for patients suffering from globus sensation. We intended to follow up all patients between 2004 and 2011 (n = 49) who received argon plasma ablation of gastric inlet patches for globus sensation at our clinic. Symptoms were assessed by a visual analogue scale (VAS) in 31 of 49 patients. Follow-up endoscopy of the upper gastrointestinal tract was performed to confirm residual or relapsed cervical inlet patches. After a median period of 27 months, APC was assessed as a successful therapy in 23 of 31 patients (74%). VAS scores decreased significantly from 7.6 to 4.0 in the long term. Twenty-two of 31 patients were willing to undergo follow-up endoscopy. Endoscopy revealed recurrent/residual gastric inlet patches after APC in 11 of 22 cases. These patients suffered from a significant relapse of symptoms in the postinterventional period (p < 0.001). This retrospective study indicates that APC of gastric inlet patches for the treatment of globus sensation might be a sufficient therapy option. Recurrences or residual heterotopic gastric mucosa are possible and seem to be associated with a relapse of symptoms. Therefore, endoscopic follow-up and retreatment might be necessary if globus sensation is not sufficiently eliminated. © 2013 S. Karger AG, Basel.

Incisional effects of 1940 nm thulium fiber laser on oral soft tissues

NASA Astrophysics Data System (ADS)

Güney, Melike; Tunç, Burcu; Gülsoy, Murat

2013-02-01

Lasers of different wavelengths are being used in oral surgery for incision and excision purposes with minimal bleeding and pain. Among these wavelengths, those close to 2μ yield more desirable results on oral soft tissue due to their strong absorption by water. The emission of 1940 nm Thulium fiber laser is well absorbed by water which makes it a promising tool for oral soft tissue surgery. This study was conducted to investigate the potential of thulium fiber laser as an incisional and excisional oral surgical tool. Ovine tongue has been used as the target tissue due to its similarities to human oral tissues. Laser light obtained from a 1940 nm Thulium fiber laser was applied in contact mode onto ovine tongue completely submerged in saline solution in vitro, via a 600)μm fiber moved with a velocity of 0.5 mm /s to form incisions. There were a total of 9 groups determined by the power (2,5-3- 3,5 W), and number of passes (1-3-5). The samples were stained with HE for microscopic evaluation of depth of ablation and extent of coagulation. The depth of incisions produced with 1940 nm Thulium fiber laser increased with increasing power and number of passes, however an increase in the width of the coagulation zone was also observed.

Real-time Focused Ultrasound Surgery (FUS) Monitoring Using Harmonic Motion Imaging (HMI)

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

Maleke, Caroline; Konofagou, Elisa E.; Department of Radiology, Columbia University, New York, NY

2009-04-14

Monitoring changes in tissue mechanical properties to optimally control thermal exposure is important in thermal therapies. The amplitude-modulated (AM) harmonic motion imaging (HMI) for focused ultrasound (HMIFU) technique is a radiation force technique, which has the capability of tracking tissue stiffness during application of an oscillatory force. The feasibility of HMIFU for assessing mechanical tissue properties has been previously demonstrated. In this paper, a confocal transducer, combining a 4.5 MHz FUS transducer and a 3.3 MHz phased array imaging transducer, was used. The FUS transducer was driven by AM wave at 15 Hz with an acoustic intensity (I{sub spta}) wasmore » equal to 1050 W/cm{sup 2}. A lowpass digital filter was used to remove the spectrum of the higher power beam prior to displacement estimation. The resulting axial tissue displacement was estimated using 1D cross-correlation with a correlation window of 2 mm and a 92.5% overlap. A thermocouple was also used to measure the temperature near the ablated region. 2D HMI-images from six-bovine-liver specimens indicated the onset of coagulation necrosis through changes in amplitude displacement after coagulation due to its simultaneous probing and heating capability. The HMI technique can thus be used to monitor temperature-related stiffness changes of tissues during thermal therapies in real-time, i.e., without interrupting or modifying the treatment protocol.« less

Long-term effect of argon plasma coagulation (APC) in the treatment of gastric antral vascular ectasia (GAVE).

PubMed

Naga, Mazen; Esmat, Serag; Naguib, Mohamed; Sedrak, Heba

2011-03-01

Gastric antral vascular ectasia (GAVE) is a distinct vascular abnormality, mainly involving the gastric antrum. It is a rare but well-known cause of occult gastrointestinal bleeding. Various endoscopic treatment modalities have been tried in this condition. The aim of the study is to show the long-term effect of argon plasma coagulation (APC) on GAVE. Twenty-nine patients with endoscopically proved GAVE were enrolled in the study. Clinical assessment of GAVE patients, haemoglobin (Hb) level and transfused blood units were recorded after APC using 60-80-W power setting. A second session was done 1month after the therapeutic procedure to ensure complete ablation of all lesions. The documented Hb levels and number of blood units transfused 3months after APC were recorded. At endoscopy, all patients had the classic type of GAVE. The mean Hb level increased from 7.5±1.7gdl(-1) before APC to 10.2±0.8gdl(-1) after APC (p value <0.001). The transfusion requirements significantly decreased to 0.2±0.5units/patient (p value <0.001). Endoscopic APC is a safe, effective and inexpensive modality in treating GAVE and could be an alternative to the currently available endoscopic methods. Copyright © 2011 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

PubMed Central

Kumar, Gaurav; Moussa, Marwan; Wang, Yuanguo; Rozenblum, Nir; Galun, Eithan; Goldberg, S. Nahum

2016-01-01

Purpose To elucidate how hepatic radiofrequency (RF) ablation affects distant extrahepatic tumor growth by means of two key molecular pathways. Materials and Methods Rats were used in this institutional animal care and use committee–approved study. First, the effect of hepatic RF ablation on distant subcutaneous in situ R3230 and MATBIII breast tumors was evaluated. Animals were randomly assigned to standardized RF ablation, sham procedure, or no treatment. Tumor growth rate was measured for 3½ to 7 days. Then, tissue was harvested for Ki-67 proliferative indexes and CD34 microvascular density. Second, hepatic RF ablation was performed for hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and c-Met receptor expression measurement in periablational rim, serum, and distant tumor 24 hours to 7 days after ablation. Third, hepatic RF ablation was combined with either a c-Met inhibitor (PHA-665752) or VEGF receptor inhibitor (semaxanib) and compared with sham or drug alone arms to assess distant tumor growth and growth factor levels. Finally, hepatic RF ablation was performed in rats with c-Met–negative R3230 tumors for comparison with the native c-Met–positive line. Tumor size and immunohistochemical quantification at day 0 and at sacrifice were compared with analysis of variance and the two-tailed Student t test. Tumor growth curves before and after treatment were analyzed with linear regression analysis to determine mean slopes of pre- and posttreatment growth curves on a per-tumor basis and were compared with analysis of variance and paired two-tailed t tests. Results After RF ablation of normal liver, distant R3230 tumors were substantially larger at 7 days compared with tumors treated with the sham procedure and untreated tumors, with higher growth rates and tumor cell proliferation. Similar findings were observed in MATBIII tumors. Hepatic RF ablation predominantly increased periablational and serum HGF and downstream distant tumor VEGF levels. Compared with RF ablation alone, RF ablation combined with adjuvant PHA-665752 or semaxanib reduced distant tumor growth, proliferation, and microvascular density. For c-Met–negative tumors, hepatic RF ablation did not increase distant tumor growth, proliferation, or microvascular density compared with sham treatment. Conclusion RF ablation of normal liver can stimulate distant subcutaneous tumor growth mediated by HGF/c-Met pathway and VEGF activation. This effect was not observed in c-Met–negative tumors and can be blocked with adjuvant c-Met and VEGF inhibitors. © RSNA, 2015 PMID:26418615

Ablation of dentin by irradiation of violet diode laser

NASA Astrophysics Data System (ADS)

Hatayama, H.; Kato, J.; Akashi, G.; Hirai, Y.; Inoue, A.

2006-02-01

Several lasers have been used for clinical treatment in dentistry. Among them, diode lasers are attractive because of their compactness compared with other laser sources. Near-infrared diode lasers have been practically used for cutting soft tissues. Because they penetrate deep to soft tissues, they cause sufficiently thick coagulation layer. However, they aren't suitable for removal of carious dentin because absorption by components in dentin is low. Recently, a violet diode laser with a wavelength of 405nm has been developed. It will be effective for cavity preparation because dentin contains about 20% of collagen whose absorption coefficient at a violet wavelength is larger than that at a near-infrared wavelength. In this paper, we examined cutting performance of the violet diode laser for dentin. To our knowledge, there have been no previous reports on application of a violet laser to dentin ablation. Bovine teeth were irradiated by continuous wave violet diode laser with output powers in a range from 0.4W to 2.4W. The beam diameter on the sample was about 270μm and an irradiation time was one second. We obtained the crater ablated at more than an output power of 0.8W. The depth of crater ranged from 20μm at 0.8W to 90μm at 2.4W. Furthermore, the beam spot with an output power of 1.7W was scanned at a speed of 1mm/second corresponding to movement of a dentist's hand in clinical treatment. Grooves with the depth of more than 50μm were also obtained. From these findings, the violet diode laser has good potential for cavity preparation. Therefore, the violet diode laser may become an effective tool for cavity preparation.

Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding

PubMed Central

Weiner, Joseph Paul; Wong, Andrew Thomas; Schwartz, David; Martinez, Manuel; Aytaman, Ayse; Schreiber, David

2016-01-01

Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient’s symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases. PMID:27610010

Comparative study of conventional US, contrast enhanced US and enhanced MR for the follow-up of prostatic radiofrequency ablation.

PubMed

Feng, Chao; Hu, Bin; Hu, Bing; Chen, Lei; Li, Jia; Huang, Jin

2017-06-01

The aim of the present study was to evaluate and compare the effectiveness of different imaging methods during follow-up of prostatic radiofrequency ablation. Prostatic radiofrequency ablation (RFA) was performed in 20 healthy beagle dogs. Various imaging examinations were used to monitor the results of RFA, including conventional ultrasound (US), contrast enhanced ultrasound (CEUS) and enhanced magnetic resonance (MR). Imaging exams were performed at five phases: Immediately following RFA, one week later, one month later, three months later and six months later. The morphology for each imaging test and histological results were recorded and compared in each phase. Based on the actual results from autopsy, the accuracy of those imaging exams was evaluated. The canine prostate gland demonstrated typical coagulative necrosis immediately following RFA. The lesion would develop into stable cyst if no other complications occurred within the six-month follow-up. Regarding the RFA lesion volume measurement and the reflection of pathological changes, conventional US was not able to accurately measure the volume of RFA lesion and missed many more details concerning the RFA-treated area than CEUS and MR during the three months. The results from CEUS exhibited comparable accuracy to those from enhanced MR at each phase. However, there were no significant differences in the results from US, CEUS and MR at six months, which may contribute to the complete formation of lesion cyst. In the early phase, conventional US was not sufficient for evaluating the efficacy of RFA. Enhanced US and MR provided clear images and accurate information. However, CEUS has the advantage of being more economical, using more convenient equipment and faster scanning, thus identifying it as the more feasible choice. Furthermore, no notable advantages were observed among any image examinations in the long-term follow-up.

High-intensity focused ultrasound for ex vivo kidney tissue ablation: influence of generator power and pulse duration.

PubMed

Häcker, Axel; Köhrmann, Kai Uwe; Knoll, Thomas; Langbein, Sigrun; Steidler, Annette; Kraut, Oliver; Marlinghaus, Ernst; Alken, Peter; Michel, Maurice Stephan

2004-11-01

The therapeutic application of noninvasive tissue ablation by high-intensity focused ultrasound (HIFU) requires precise physical definition of the focal size and determination of control parameters. The objective of this study was to measure the extent of ex-vivo porcine kidney tissue ablation at variable generator parameters and to identify parameters to control lesion size. The ultrasound waves generated by a cylindrical piezoceramic element (1.04 MHz) were focused at a depth of 100 mm using a parabolic reflector (diameter 100 mm). A needle hydrophone was used to measure the field distribution of the sound pressure. The morphology and extent of tissue necrosis were examined at generator powers of up to 400 W (P(el)) and single pulse durations of as long as 8 seconds. The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (-6 dB). A sharp demarcation between coagulation necrosis and intact tissue was observed. Lesion size was controlled by both the variation of generator power and the pulse duration. At a constant pulse duration of 2 seconds, a generator power of 100 W remained below the threshold doses for inducing a reproducible lesion. An increase in power to as high as 400 W induced lesions with average dimensions of as much as 11.2 x 3 mm. At constant total energy (generator power x pulse duration), lesion size increased at higher generator power. This ultrasound generator can induce defined and reproducible necrosis in ex-vivo kidney tissue. Lesion size can be controlled by adjusting the generator power and pulse duration. Generator power, in particular, turned out to be a suitable control parameter for obtaining a lesion of a defined size.

Plasmapheresis in severe septic shock with disseminated intravascular coagulation.

PubMed

Zilow, E P; Selle, B; Zilow, G

1994-01-01

An 18-year-old female with CNS relapse of acute lymphoblastic leukemia after previous complete remission of the disease underwent chemotherapy. Due to the therapy she suffered from profound suppression of bone marrow with consecutive thrombocytopenia and leukopenia. Despite prophylactic treatment, severe septicemia occurred with septic shock, hemolysis and disseminated intravascular coagulation (DIC). As the clinical course became uncontrollable by means of conventional therapy, including broad-spectrum antibiotics, substitution of fresh frozen plasma, antithrombin III and heparin therapy, plasma exchange was used as a rescue therapy. This method succeeded in effective replacement of clotting factors and normalization of coagulation, in removal of fibrinogen degradation products and probably of toxins and shock mediators. The patient recovered from shock.

Proteins, Platelets, and Blood Coagulation at Biomaterial Interfaces

PubMed Central

Xu, Li-Chong; Bauer, James; Siedlecki, Christopher A.

2015-01-01

Blood coagulation and platelet adhesion remain major impediments to the use of biomaterials in implantable medical devices. There is still significant controversy and question in the field regarding the role that surfaces play in this process. This manuscript addresses this topic area and reports on state of the art in the field. Particular emphasis is placed on the subject of surface engineering and surface measurements that allow for control and observation of surface-mediated biological responses in blood and test solutions. Appropriate use of surface texturing and chemical patterning methodologies allow for reduction of both blood coagulation and platelet adhesion, and new methods of surface interrogation at high resolution allow for measurement of the relevant biological factors. PMID:25448722

Evaluation of pain during high-intensity focused ultrasound ablation of benign thyroid nodules.

PubMed

Lang, Brian H H; Woo, Yu-Cho; Chiu, Keith Wan-Hang

2018-06-01

To assess severity and factors of pain during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules. 128 patients who underwent a HIFU ablation for a benign thyroid nodule were analysed. All patients received a bolus of intravenous pethidine and diazepam before treatment. After treatment, patients were asked to rate their overall pain experience on a visual analogue scale (0-100) (0 = no pain; 100 = worse possible pain) during treatment, 2 h after treatment and the following morning. Binary logistic regression was performed to evaluate associated factors for pain including patient demographics, nodule size, body mass index (BMI) and treatment parameters. At T1, median (range) pain score was 65.0 (0.00-100.00). Only 16 (12.5 %) patients had a pain score of zero. In multivariate analysis, only lower BMI (OR 1.265, 95 % CI 1.102-1.452, p=0.001) and longer nodule diameter (OR 1.462, 95 % CI 1.071-1.996, p=0.017) were independent factors for pain score at T1 ≤ 65.0. A moderate to severe amount of pain was reported during ablation of benign thyroid nodules in over 50 % of patients. Patients' BMI and length of nodule diameter were independent variables for pain during HIFU ablation. • Pain was moderate to severe during HIFU ablation of thyroid nodules. • Only one in eight patients reported no pain during ablation. • Level of energy per pulse did not affect pain. • Patients with lower BMI and larger nodules had less pain.

Treatment tailoring for factor V deficient patients and perioperative management using global hemostatic coagulation assays.

PubMed

Levy-Mendelovich, Sarina; Barg, Assaf Arie; Rosenberg, Nurit; Avishai, Einat; Luboshitz, Jacob; Misgav, Mudi; Kenet, Gili; Livnat, Tami

2018-07-01

Congenital factor V deficiency (FVD) is a rare bleeding disorder with an estimated incidence of 1 in 1000,000 in the general population. Since the common coagulation tests do not correlate with the bleeding tendency there is an unmet need to predict FVD patients' bleeding hazard prior to surgical interventions. To optimize treatment prior to surgical interventions, using global coagulation assays, thrombin generation (TG) and rotating thromboelastogram (ROTEM). Our cohort included 5 patients with FVD, 4 severe and one mild. Two of them underwent TG and ROTEM prior to surgical interventions, including ex vivo spiking assays using bypass agents and platelets spiking. All five patients exhibited prolonged PT and PTT, non-dependent on their bleeding tendency. Patient 1, who demonstrated severe bleeding phenotype, underwent surgery treated by combination of APCC (FEIBA) and platelet transfusion. Therapy was guided by global tests (TG as well as ROTEM) results. During the pre and post-operative period neither excessive bleeding nor any thrombosis was noted. In contrast, TG and ROTEM analysis of patient 4 has lead us to perform the surgery without any blood products' support. Indeed, the patient did not encounter any bleeding. Global coagulation assays may be useful ancillary tools guiding treatment decisions in FVD patients undergoing surgical procedures. Copyright © 2018 Elsevier Inc. All rights reserved.

Response surface methodology investigation into the interactions between arsenic and humic acid in water during the coagulation process.

PubMed

Watson, Malcolm Alexander; Tubić, Aleksandra; Agbaba, Jasmina; Nikić, Jasmina; Maletić, Snežana; Molnar Jazić, Jelena; Dalmacija, Božo

2016-07-15

Interactions between arsenic and natural organic matter (NOM) are key limiting factors during the optimisation of drinking water treatment when significant amounts of both must be removed. This work uses Response Surface Methodology (RSM) to investigate how they interact during their simultaneous removal by iron chloride coagulation, using humic acid (HA) as a model NOM substance. Using a three factor Box-Behnken experimental design, As and HA removals were modelled, as well as a combined removal response. ANOVA results showed the significance of the coagulant dose for all three responses. At high initial arsenic concentrations (200μg/l), As removal was significantly hindered by the presence of HA. In contrast, the HA removal response was found to be largely independent of the initial As concentration, with the optimum coagulant dose increasing at increasing HA concentrations. The combined response was similar to the HA removal response, and the interactions evident are most interesting in terms of optimising treatment processes during the preparation of drinking water, highlighting the importance of utilizing RSM for such investigations. The combined response model was successfully validated with two different groundwaters used for drinking water supply in the Republic of Serbia, showing excellent agreement under similar experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

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

Gillams, Alice, E-mail: alliesorting@gmail.com; Khan, Zahid; Osborn, Peter

2013-06-15

Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, andmore » factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.« less

Increased circulating procoagulant and anticoagulant factors as TF and TFPI according to severity or infecting serotypes in human dengue infection.

PubMed

Leal de Azeredo, Elzinandes; Solórzano, Victor Edgar Fiestas; de Oliveira, Débora Batista; Marinho, Cintia Ferreira; de Souza, Luiz José; da Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de-Oliveira-Pinto, Luzia Maria

2017-01-01

Tissue Factor (TF) is the initiator of coagulation and Tissue Factor Inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Circulating levels of TF and TFPI were quantified in dengue patients and the relationships with disease severity and infecting serotype analysed. A significant decrease in TF and TPFI plasma levels was observed in mild DF patients compared with severe dengue. Furthermore, both factors were associated with haemorrhagic manifestations. Finally, TF levels were significantly increased in DENV-1/2 infected patients as compared with DENV-4. These findings suggest that activation of TF-pathway is an important component of DENV -related coagulation disorders. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Identification and Mechanistic Analysis of a Novel Tick-Derived Inhibitor of Thrombin

PubMed Central

Jablonka, Willy; Kotsyfakis, Michalis; Mizurini, Daniella M.; Monteiro, Robson Q.; Lukszo, Jan; Drake, Steven K.; Ribeiro, José M. C.; Andersen, John F.

2015-01-01

A group of peptides from the salivary gland of the tick Hyalomma marginatum rufipes, a vector of Crimean Congo hemorrhagic fever show weak similarity to the madanins, a group of thrombin-inhibitory peptides from a second tick species, Haemaphysalis longicornis. We have evaluated the anti-serine protease activity of one of these H. marginatum peptides that has been given the name hyalomin-1. Hyalomin-1 was found to be a selective inhibitor of thrombin, blocking coagulation of plasma and inhibiting S2238 hydrolysis in a competitive manner with an inhibition constant (Ki) of 12 nM at an ionic strength of 150 mM. It also blocks the thrombin-mediated activation of coagulation factor XI, thrombin-mediated platelet aggregation, and the activation of coagulation factor V by thrombin. Hyalomin-1 is cleaved at a canonical thrombin cleavage site but the cleaved products do not inhibit coagulation. However, the C-terminal cleavage product showed non-competitive inhibition of S2238 hydrolysis. A peptide combining the N-terminal parts of the molecule with the cleavage region did not interact strongly with thrombin, but a 24-residue fragment containing the cleavage region and the C-terminal fragment inhibited the enzyme in a competitive manner and also inhibited coagulation of plasma. These results suggest that the peptide acts by binding to the active site as well as exosite I or the autolysis loop of thrombin. Injection of 2.5 mg/kg of hyalomin-1 increased arterial occlusion time in a mouse model of thrombosis, suggesting this peptide could be a candidate for clinical use as an antithrombotic. PMID:26244557

From Laser Desorption to Laser Ablation of Biopolymers

NASA Astrophysics Data System (ADS)

Franz, Hillenkamp

1998-03-01

For selected indications laser ablation and cutting of biological tissues is clinical practice. Preferentially lasers with emission wavelengths in the far UV and the mid IR are used, for which tissue absorption is very high. Morphologically the ablation sites look surprisingly similar for the two wavelength ranges, despite of the very different prim y putative interaction mechanisms. Ablation depth as a function of fluence follows a sigmoidal curve. Even factors below the nominal ablation threshold superficial layers of material get removed from the surface. This is the fluence range for Matrix-Assisted Laser Desorption/Ionization (MALDI). Evidence will be presented which suggest that strong similarities exist between the desorption and ablation processes both for UV- as well as for IR-wavelengths.

Phrenic nerve injury after radiofrequency ablation of lung tumors: retrospective evaluation of the incidence and risk factors.

PubMed

Matsui, Yusuke; Hiraki, Takao; Gobara, Hideo; Uka, Mayu; Masaoka, Yoshihisa; Tada, Akihiro; Toyooka, Shinichi; Mitsuhashi, Toshiharu; Mimura, Hidefumi; Kanazawa, Susumu

2012-06-01

To retrospectively investigate the incidence of and risk factors for phrenic nerve injury after radiofrequency (RF) ablation of lung tumors. The study included 814 RF ablation procedures of lung tumors. To evaluate the development of phrenic nerve injury, chest radiographs obtained before and after the procedure were examined. Phrenic nerve injury was assumed to have developed if the diaphragmatic level was elevated after the procedure. To identify risk factors for phrenic nerve injury, multiple variables were compared between cases of phrenic nerve injury and randomly selected controls by using univariate analyses. Multivariate analysis was then performed to identify independent risk factors. Evaluation of phrenic nerve injury from chest radiographs was possible after 786 procedures. Evidence of phrenic nerve injury developed after 10 cases (1.3%). Univariate analysis revealed that larger tumor size (≥ 20 mm; P = .014), proximity of the phrenic nerve to the tumor (< 10 mm; P < .001), the use of larger electrodes (array diameter or noninsulated tip length ≥ 3 cm; P = .001), and higher maximum power applied during ablation (≥ 100 W; P < .001) were significantly associated with the development of phrenic nerve injury. Multivariate analysis demonstrated that the proximity of the phrenic nerve to the tumor (< 10 mm; P < .001) was a significant independent risk factor. The incidence of phrenic nerve injury after RF ablation was 1.3%. The proximity of the phrenic nerve to the tumor was an independent risk factor for phrenic nerve injury. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

[Haplotype Analysis of Coagulation Factor VII Gene in a Patient with Congenital Coagulation Factor VII Deficiency with Heterozygous p.Arg337Cys Mutation and o.Aro413Gin Polymorphism..

PubMed

Suzuki, Keijiro; Yoshioka, Tomoko; Obara, Takehiro; Suwabe, Akira

2016-05-01

Congenital coagulation factor VII (FVII) deficiency is a rare hemorrhagic disease with an autosomal reces- sive inheritance pattern. We analyzed coagulation factor VII gene (F7) of a patient with FVII deficiency and used expression studies to investigate the effect of a missense mutation on FVII secretion. The proband, a 69-year-old Japanese woman, had a history of postpartum bleeding and excessive bleeding after dental extrac- tion. She was found to have mildly increased PT-INR (1.17) before an ophthalmic operation. FVII activity and antigen were reduced (29.0% and 32.8%). Suspecting that the proband was FVII deficient, we analyzed F7 of the patient. Sequence analysis revealed that the patient was heterozygous for a point mutation (p.Arg337Cys) in the catalytic domain and polymorphisms: the decanucleotide insertion at the promoter re- gion, dimorphism (c.525C >T) in exon 5, and p.Arg413Gln in exon 8. Haplotype analysis clarified that p.Arg337Cys was located on the p.Arg413 allele (Ml allele). The other allele had the p.Arg413Gln polymor- phism(M2 allele) which is known to produce less FVII. Expression studies revealed that p.Arg337Cys causes impairment of FVII secretion. Insufficient secretion of FVII arising from both the p.Arg337Cys/M1 allele and the p.Arg337/M2 allele might lower the FVII level of this patient(<50%). The FVII level in a heterozygous FVII deficient patient might be influenced by F7 polymorphisms on the normal allele. There- fore, genetic analyses are important for the diagnosis of heterozygous FVII deficiency.

Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial

PubMed Central

Nemeth, Banne; Scheres, Luuk J J; Lijfering, Willem M

2015-01-01

Objective To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. Design Crossover trial. Setting Main meeting room of Leiden University’s Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. Participants 24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. Main outcome measures The primary outcome measures were markers, or “fear factors” of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. Results All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. Conclusion Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration ClinicalTrials.gov NCT02601053. PMID:26673787

21 CFR 864.7290 - Factor deficiency test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene). (b) Classification. Class II (performance standards). [45 FR 60613...

Clinical risk factors to predict deep venous thrombosis post-endovenous laser ablation of saphenous veins.

PubMed

Chi, Y-W; Woods, T C

2014-04-01

Endovenous laser ablation of saphenous veins is an alternative in treating symptomatic varicose veins. Deep venous thrombosis (DVT) has been reported in up to 7.7% of patients undergoing such procedure. We sought to establish clinical risk factors that predict DVT post-endovenous laser ablation. Patients who underwent endovenous laser ablation were prospectively followed. Clinical data and post-interventional duplex ultrasound were analysed. A P value <0.05 was accepted as representing a significant difference. From 2007 to 2008, 360 consecutive patients were followed. Nineteen DVTs were found on follow-up ultrasound. Eighteen cases involved either the saphenofemoral or saphenopopliteal junctions; only one case involved the deep venous system. Age >66 (P = 0.007), female gender (P = 0.048) and prior history of superficial thrombophlebitis (SVT) (P = 0.002) were associated with increased risk of DVT postprocedure. Age >66, female gender and history of SVT were significant predictors of DVT post-endovenous laser ablation of saphenous veins.

Successful synthesis of active human coagulation factor VII by co-expression of mammalian gamma-glutamyl carboxylase and modification of vit.K cycle in Drosophila Schneider S2 cells.

PubMed

Nagahashi, Kotomi; Umemura, Kazuo; Kanayama, Naohiro; Iwaki, Takayuki

2017-04-01

Mammalian gamma-glutamyl carboxylase and reduced vitamin K are indispensable for synthesis of mature mammalian vitamin K dependent proteins including some of blood coagulation factors (factors II, VII, IX, and X). It was well known that Drosophila melanogaster expressed gamma-glutamyl carboxylase and possessed a vit.K cycle although native substrates for them have not been identified yet. Despite the potential capability of gamma carboxylation in D. melanogaster derived cells such as S2 cells, Drosophila gamma-glutamyl carboxylase failed to gamma carboxylate a peptide fused to the human coagulation factor IX propeptide. Thus, it had been believed that the Drosophila system was not adequate to synthesize mammalian vit.K dependent proteins. Indeed, we previously attempted to synthesize biologically active factor VII in S2 cells although we were not able to obtain it. However, recently, a successful transient expression of biologically active human factor IX from S2 cells was reported. In the present study, several expression vectors which enable expressing mammalian GGCX, VKORC1, and/or PDIA2 along with F7 were developed. S2 cells transfected with pMKA85, pMAK86, and pMAK219 successfully synthesized active FVII. Thus, mammalian GGCX was indispensable to synthesize active FVII while mammalian VKORC1 and PDIA2 were not critical but supportive factors for S2 cells.

Numerical models of cell death in RF ablation with monopolar and bipolar probes

NASA Astrophysics Data System (ADS)

Bright, Benjamin M.; Pearce, John A.

2013-02-01

Radio frequency (RF) is used clinically to treat unresectible tumors. Finite element modeling has proven useful in treatment planning and applicator design. Typically isotherms in the middle 50s °C have been used as the parameter of assessment in these models. We compare and contrast isotherms for multiple known Arrhenius thermal damage predictors including collagen denaturation, vascular disruption, liver coagulation and cell death. Models for RITA probe geometries are included in the study. Comparison to isotherms is sensible when the activation time is held constant, but varies considerably when heating times vary. The purpose of this paper is to demonstrate the importance of looking at specific processes and keeping track of the methods used to derive the Arrhenius coefficients in order to study the extremely complex cell death processes due to thermal therapies.

The fractional laser-induced coagulation zone characterized over time by laser scanning confocal microscopy-A proof of concept study.

PubMed

Banzhaf, Christina A; Lin, Lynlee L; Dang, Nhung; Freeman, Michael; Haedersdal, Merete; Prow, Tarl W

2018-01-01

Ablative fractional laser (AFXL) is an acknowledged technique to increase uptake of topical agents in skin. Micro thermal ablation zones (MAZs) consist of ablated vertical channels surrounded by a coagulation zone (CZ). Laser scanning confocal microscopy (LSCM) images individual MAZs at 733 nm (reflectance confocal microscopy (RCM)). Further, LSCM can image sodium fluorescein (NaF) fluorescence with 488 nm excitation (fluorescence confocal microcopy (FCM)), a small hydrophilic test molecule (370 MW, log P -1.52), which may simulate uptake, bio-distribution and kinetics of small hydrophilic drugs. To explore LSCM for combined investigations of CZ thickness and uptake, bio-distribution and kinetics of NaF in AFXL-exposed skin. Excised human abdominal skin samples were exposed to AFXL (15 mJ/microbeam, 2% density) and NaF gel (1000 μg/ml, 10 μl/cm2) in six repetitions, including untreated control samples. CZ thickness and spatiotemporal fluorescence intensities (FI) were quantified up to four hours after NaF application by RCM and FCM. Test sites were scanned to a depth of 200 μm, quantifying thickness of skin compartments (stratum corneum, epidermis, upper dermis), individual CZ thicknesses and FI in CZ and surrounding skin. RCM images established skin morphology to a depth of 200 μm. The CZ thickness measurements were feasible to a depth of 50 μm, and remained unchanged over time at 50 μm (P > 0.5). FI were detected to a depth of 160 μm and remained constant in CZ up to four hours after NaF application (15 minutes: 79 AU (73-92 AU), 60 minutes: 72 AU (58-82 AU), four hours: 78 AU (71-90 AU), P > 0.1). In surrounding skin, FI increased significantly over time, but remained lower than FI in CZ (15 minutes: 21 AU (17-22 AU), 60 minutes: 21 AU (19-26 AU), four hours: 42 (31- 48 AU), P = 0.03). AFXL-processed skin generated higher FI compared to non-laser processed skin in epidermis and upper dermis at 60 minutes and four hours (P = 0.03). By LSCM, assessment of the AFXL-induced CZ thickness was feasible to a depth of 50 μm, and assessment of FI from a small hydrophilic test molecule, NaF in CZ and surrounding skin feasible to a depth of 160 μm. Lasers Surg. Med. 50:70-77, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation*

PubMed Central

Alvarez-Flores, Miryam Paola; Furlin, Daniel; Ramos, Oscar H. P.; Balan, Andrea; Konno, Katsuhiro; Chudzinski-Tavassi, Ana Marisa

2011-01-01

Envenoming by the contact of human skin with Lonomia obliqua caterpillars promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy. Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of L. obliqua that is probably partially responsible for the observed syndrome because it activates factor X and is recognized by an effective antilonomic serum. Here we unveil the proteolytic activity of Losac and demonstrate the feasibility of its recombinant production. On the other hand, Losac has no homology to known proteases, but it can be inhibited by PMSF, a serine protease inhibitor. Instead, it shows closer homology to members of the hemolin family of proteins, a group of cell adhesion molecules. The recombinant protein (rLosac) shortened the coagulation time of normal and deficient plasmas, whereas it was ineffective in factor X-deficient plasma unless reconstituted with this protein. rLosac was able to activate factor X in a dose- and time-dependent manner but not γ-carboxyglutamic acid domainless factor X. Moreover, phospholipids and calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or fibrinogen, indicating its specificity for blood coagulation activation. Linear double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics. Cleavage of factor X by rLosac resulted in fragments that are compatible with those generated by RVV-X (a well known factor X activator). Together, our results validate Losac as the first protein from the hemolin family exhibiting procoagulant activity through selective proteolysis on coagulation factor X. PMID:21177860

Confinement Regulates Complex Biochemical Networks: Initiation of Blood Clotting by “Diffusion Acting”

PubMed Central

Shen, Feng; Pompano, Rebecca R.; Kastrup, Christian J.; Ismagilov, Rustem F.

2009-01-01

Abstract This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da2, was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as “diffusion acting”, which is distinct from “diffusion sensing”. The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological “on” and “off” processes that are controlled by thresholds. PMID:19843446

A case control study on the structural equation model of the mechanism of coagulation and fibrinolysis imbalance in chronic schistosomiasis.

PubMed

Le, Aiping; Zhang, Lunli; Liu, Wei; Li, Xiaopeng; Ren, Jianwei; Ning, An

2017-02-01

A structural equation model was used for verification with chronic schistosomiasis to investigate the coagulation-anticoagulation system imbalance and to deduce the mechanism of D-dimer (D-D) level elevation in patients with advanced schistosome hepatic disease. We detected the plasma levels of tissue-type fiber plasminogen activator (tPA), urokinase type plasminogen activator (uPA), plasmin-antiplasmin complex (PAP), plasminogen (PLG), antithrombin (AT), plasminogen activator inhibitor 1 (PAI1), D-D, factor VIII: C (FVIII:C), antithrombin-III (AT-III), PLG, protein S (PS), and protein C (PC) in the healthy people as control (69), patients with chronic schistosomiasis (150) or advanced chronic schistosomiasis (90). FVIII, PAP, D-D, tPA, and uPA plasma levels were significantly higher in the chronic group than in the control group and were also significantly higher in the advanced group. However, AT-III, PC, PS, AT, PLG, and PAI1 plasma levels in the advanced and chronic groups were significantly lower than those in the control group. With progression of disease in patients with schistosomiasis japonica, a hypercoagulable state is induced by the coagulation-anticoagulation imbalance, eventually leading to patients with high levels of D-D. Furthermore, we established a structural equation model path of a "chronic schistosomiasis disease stage-(coagulation-anticoagulation-fibrinolysis)-D-D." By using analysis of moment structures (AMOS), it was shown that the chronic schistosomiasis stage was positively related to factor VIII and had negative correlation with AT-III; a good positive correlation with PAP, tPA, and uPA; and a good negative correlation with PLG and PAI1. In addition, our results show that the path coefficient of anticoagulation-fibrinolysis system to the chronic stage of schistosomiasis or D-D levels was significantly higher than that of the coagulation system. In conclusion, the coagulation and fibrinolysis imbalance in patients with chronic schistosomiasis, especially with advanced schistosomiasis, is due to the progression of disease stages.

Tissue factor expression by endothelial cells in sickle cell anemia.

PubMed

Solovey, A; Gui, L; Key, N S; Hebbel, R P

1998-05-01

The role of the vascular endothelium in activation of the coagulation system, a fundamental homeostatic mechanism of mammalian biology, is uncertain because there is little evidence indicating that endothelial cells in vivo express tissue factor (TF), the system's triggering mechanism. As a surrogate for vessel wall endothelium, we examined circulating endothelial cells (CEC) from normals and patients with sickle cell anemia, a disease associated with activation of coagulation. We find that sickle CEC abnormally express TF antigen (expressed as percent CEC that are TF-positive), with 66+/-13% positive in sickle patients in steady-state, 83+/-19% positive in sickle patients presenting with acute vasoocclusive episodes, and only 10+/-13% positive in normal controls. Repeated samplings confirmed this impression that TF expression is greater when sickle patients develop acute vasoocclusive episodes. Sickle CEC are also positive for TF mRNA, with excellent concurrence between antigen and mRNA expression. The TF expressed on the antigen-positive CEC is functional, as demonstrated by a binding assay for Factor VIIa and a chromogenic assay sensitive to generation of Factor Xa. By establishing that endothelial cells in vivo can express TF, these data imply that the vast endothelial surface area does provide an important pathophysiologic trigger for coagulation activation.

Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure

NASA Astrophysics Data System (ADS)

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Matsuyama, Keigo; Nakazato, Yasutaro; Arimori, Akihiro; Isobe, Masaaki; Tochigi, Saeko; Kondoh, Sayuri; Hirai, Toshiro; Akase, Takanori; Yamashita, Takuya; Yamashita, Kohei; Yoshida, Tokuyuki; Nagano, Kazuya; Abe, Yasuhiro; Yoshioka, Yasuo; Kamada, Haruhiko; Imazawa, Takayoshi; Itoh, Norio; Kondoh, Masuo; Yagi, Kiyohito; Mayumi, Tadanori; Tsunoda, Shin-ichi; Tsutsumi, Yasuo

2012-02-01

We previously reported that well-dispersed amorphous nanosilicas with particle size 70 nm (nSP70) penetrate skin and produce systemic exposure after topical application. These findings underscore the need to examine biological effects after systemic exposure to nanosilicas. The present study was designed to examine the biological effects. BALB/c mice were intravenously injected with amorphous nanosilicas of sizes 70, 100, 300, 1000 nm and then assessed for survival, blood biochemistry, and coagulation. As a result, injection of nSP70 caused fatal toxicity, liver damage, and platelet depletion, suggesting that nSP70 caused consumptive coagulopathy. Additionally, nSP70 exerts procoagulant activity in vitro associated with an increase in specific surface area, which increases as diameter reduces. In contrast, nSP70-mediated procoagulant activity was absent in factor XII-deficient plasma. Collectively, we revealed that interaction between nSP70 and intrinsic coagulation factors such as factor XII, were deeply related to nSP70-induced harmful effects. In other words, it is suggested that if interaction between nSP70 and coagulation factors can be suppressed, nSP70-induced harmful effects may be avoided. These results would provide useful information for ensuring the safety of nanomaterials (NMs) and open new frontiers in biological fields by the use of NMs.

Edible bird’s nest attenuates procoagulation effects of high-fat diet in rats

PubMed Central

Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Hou, Zhiping

2015-01-01

Edible bird’s nest (EBN) is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD-) induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipoprotein (oxLDL), adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count) were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia. PMID:26251574

Complement component 5 promotes lethal thrombosis

PubMed Central

Mizuno, Tomohiro; Yoshioka, Kengo; Mizuno, Masashi; Shimizu, Mie; Nagano, Fumihiko; Okuda, Tomoyuki; Tsuboi, Naotake; Maruyama, Shoichi; Nagamatsu, Tadashi; Imai, Masaki

2017-01-01

Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. PMID:28205538

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

PubMed

Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur

2012-01-01

Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

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

Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay

PubMed Central

Tilley, Derek; Levit, Irina; Samis, John A.

2012-01-01

In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase 1, 2. Manual FV assays have been described 3, 4, but they are time consuming and subjective. Automated FV assays have been reported 5-7, but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput 8, 9. Microplate assays have been reported for clot lysis 10, platelet aggregation 11, and coagulation Factors 12, but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma. This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405nm during fibrin formation in human plasma (Figure 1) 13. The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity). Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections 14. DIC is associated with a poor prognosis and increases mortality above the pre-existing pathology 15. The assay was used to show that in 9 patients with DIC, the FV 1-stage, 2-stage, and total activities were decreased, on average, by 54%, 44%, and 42%, respectively, compared with normal pooled human reference plasma (NHP). The FV microplate assay is easily adaptable to measure the activity of any coagulation factor. This assay will increase our understanding of FV biochemistry through a more accurate and complete measurement of its activity in research and clinical settings. This information will positively impact healthcare environments through earlier diagnosis and development of more effective treatments for coagulation disorders, such as DIC. PMID:22987015

Measurement of factor v activity in human plasma using a microplate coagulation assay.

PubMed

Tilley, Derek; Levit, Irina; Samis, John A

2012-09-09

In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase (1, 2). Manual FV assays have been described (3, 4), but they are time consuming and subjective. Automated FV assays have been reported (5-7), but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput (8, 9). Microplate assays have been reported for clot lysis (10), platelet aggregation (11), and coagulation Factors (12), but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma. This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405 nm during fibrin formation in human plasma (Figure 1) (13). The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80 pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity). Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections (14). DIC is associated with a poor prognosis and increases mortality above the pre-existing pathology (15). The assay was used to show that in 9 patients with DIC, the FV 1-stage, 2-stage, and total activities were decreased, on average, by 54%, 44%, and 42%, respectively, compared with normal pooled human reference plasma (NHP). The FV microplate assay is easily adaptable to measure the activity of any coagulation factor. This assay will increase our understanding of FV biochemistry through a more accurate and complete measurement of its activity in research and clinical settings. This information will positively impact healthcare environments through earlier diagnosis and development of more effective treatments for coagulation disorders, such as DIC.

Purification and Autoactivation Method for Recombinant Coagulation Factor VII.

PubMed

Granovski, Vladimir; Freitas, Marcela C C; Abreu-Neto, Mario Soares; Covas, Dimas T

2018-01-01

Recombinant coagulation factor VII is a very important and complex protein employed for treatment of hemophiliac patients (hemophilia A/B) who develop inhibitors antibodies to conventional treatments (FVIII and FIX). The rFVII is a glycosylated molecule and circulates in plasma as zymogen of 50 kDa. When activated the molecule is cleaved to 20-30 kDa and has a half-life of about 3 h, needing to be processed fast and efficiently until freeze-drying. Here, we describe a very simple and fast purification sequence for rFVII using affinity FVII Select resin and a dialysis system that can be easily scaled up.

Increased coagulation and fibrinolytic potential of solvent-detergent plasma: a comparative study between Omniplasma and fresh frozen plasma.

PubMed

van Beers, J J B C; van Egmond, L T; Wetzels, R J H; Verhezen, P W M; Beckers, E A M; van Oerle, R; Spronk, H M H; Straat, R J M H E; Henskens, Y M C

2016-07-01

In this study, differences in levels of proteins involved in coagulation and fibrinolysis were compared between fresh frozen (quarantine plasma) and Omniplasma. Furthermore, thawing conditions and plasma stability after thawing were studied. 10 Omniplasma and 10 quarantine plasma units were used to study different procoagulation, anticoagulation and fibrinolytic parameters. Analysis took place at different time-points during plasma storage at 2-6°C. At baseline, significant reduced levels of factor V, free protein S, α2-antiplasmin and tPA-induced ROTEM lysis time were observed in Omniplasma as compared to quarantine plasma. Moreover, thrombin generation, IXa-AT complex levels and factor XIa were significantly increased in Omniplasma. The majority of the parameters studied remained stable in Omniplasma 48 h after thawing, with the exception of factor VIII (decrease) and IXa-AT (increase). Our results suggest an increased coagulation potential, presumingly as a result of contact activation during the production process and also, an increased fibrinolytic potential in Omniplasma. The stability of Omniplasma, based upon the different parameters studied, is comparable to Q-plasma. A maximum post-thawing time of 48 hfor Omniplasma can be suggested. © 2016 International Society of Blood Transfusion.

A Comparison of Blood Factor XII Autoactivation in Buffer, Protein Cocktail, Serum, and Plasma Solutions

PubMed Central

Golas, Avantika; Yeh, Chyi-Huey Josh; Pitakjakpipop, Harit; Siedlecki, Christopher A.; Vogler, Erwin A.

2012-01-01

Activation of blood plasma coagulation in vitro by contact with material surfaces is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. The only plausible explanation consistent with current understanding of coagulation-cascade biochemistry is that procoagulant stimulus arising from the activation complex of the intrinsic pathway is dependent on activator surface area. And yet, it is herein shown that activation of the blood zymogen factor XII (Hageman factor, FXII) dissolved in buffer, protein cocktail, heat-denatured serum, and FXI deficient plasma does not exhibit activator surface-area dependence. Instead, a highly-variable burst of procoagulant-enzyme yield is measured that exhibits no measurable kinetics, sensitivity to mixing, or solution-temperature dependence. Thus, FXII activation in both buffer and protein-containing solutions does not exhibit characteristics of a biochemical reaction but rather appears to be a “mechanochemical” reaction induced by FXII molecule interactions with hydrophilic activator particles that do not formally adsorb blood proteins from solution. Results of this study strongly suggest that activator surface-area dependence observed in contact activation of plasma coagulation does not solely arise at the FXII activation step of the intrinsic pathway. PMID:23117212

Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging.

PubMed

Liu, Heng; Chen, Xiao; Xue, Wei; Chu, Chengchao; Liu, Yu; Tong, Haipeng; Du, Xuesong; Xie, Tian; Liu, Gang; Zhang, Weiguo

The highly infiltrative and invasive nature of glioma cells often leads to blurred tumor margins, resulting in incomplete tumor resection and tumor recurrence. Accurate detection and precise delineation of glioma help in preoperative delineation, surgical planning and survival prediction. In this study, recombinant epidermal growth factor-like domain-1, derived from human coagulation factor VII, was conjugated to iron oxide nanoparticles (IONPs) for targeted glioma magnetic resonance (MR) imaging. The synthesized EGF1-EGFP-IONPs exhibited excellent targeting ability toward tissue factor (TF)-positive U87MG cells and human umbilical vein endothelial cells in vitro, and demonstrated persistent and efficient MR contrast enhancement up to 12 h for preclinical glioma models with high targeting specificity in vivo. They hold great potential for clinical translation and developing targeted theranostics against brain glioma.

Positive Selection during the Evolution of the Blood Coagulation Factors in the Context of Their Disease-Causing Mutations

PubMed Central

Rallapalli, Pavithra M.; Orengo, Christine A.; Studer, Romain A.; Perkins, Stephen J.

2014-01-01

Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining hemostasis. The 11 human coagulation factors (FG, FII–FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Ma. Human FVIII, FIX, and FXI are associated with thousands of disease-causing mutations. Here, we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during vertebrate evolution, and compared these with human mutations in FVIII, FIX, and FXI. Positive selection was identified for fibrinogen (FG), FIII, FVIII, FIX, and FX in the mammalian Primates and Laurasiatheria and the Sauropsida (reptiles and birds). This showed that the coagulation system in vertebrates was under strong selective pressures, perhaps to adapt against blood-invading pathogens. The comparison of these results with disease-causing mutations reported in FVIII, FIX, and FXI showed that the number of disease-causing mutations, and the probability of positive selection were inversely related to each other. It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations. In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing. A residue-by-residue comparison of the FVIII, FIX, and FXI sequence alignments confirmed this. This improved understanding of evolutionary changes in FVIII, FIX, and FXI provided greater insight into disease-causing mutations, and better assessments of the codon sites that may be mutated in applications of gene therapy. PMID:25158795

Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma.

PubMed

Schmidt, David E; Halmin, Märit; Wikman, Agneta; Östlund, Anders; Ågren, Anna

2017-10-01

Massive traumatic haemorrhage is aggravated through the development of trauma-induced coagulopathy, which is managed by plasma transfusion and/or fibrinogen concentrate administration. It is yet unclear whether these treatments are equally potent in ensuring adequate haemostasis, and whether additional factor XIII (FXIII) administration provides further benefits. In this study, we compared ROTEM whole blood coagulation profiles after experimental massive transfusion with different transfusion regimens in an in vitro model of dilution- and transfusion-related coagulopathy. Healthy donor blood was mixed 1 + 1 with six different transfusion regimens. Each regimen contained RBC, platelet concentrate, and either fresh frozen plasma (FFP) or Ringer's acetate (RA). The regimens were further augmented through addition of a low- or medium-dose fibrinogen concentrate and FXIII. Transfusion with FFP alone was insufficient to maintain tissue-factor activated clot strength, coincidental with a deficiency in fibrin-based clot strength. Fibrinogen concentrate conserved, but did not improve coagulation kinetics and overall clot strength. Only combination therapy with FFP and low-dose fibrinogen concentrate improved both coagulation kinetics and fibrin-based clot strength. Administration of FXIII did not result in an improvement of clot strength. In conclusion, combination therapy with both FFP and low-dose fibrinogen concentrate improved clotting time and produced firm clots, representing a possible preferred first-line regimen to manage trauma-induced coagulopathy when RBC and platelets are also transfused. Further research is required to identify optimal first-line transfusion fluids for massive traumatic haemorrhage.

The first EGF domain of coagulation factor IX attenuates cell adhesion and induces apoptosis.

PubMed

Ishikawa, Tomomi; Kitano, Hisataka; Mamiya, Atsushi; Kokubun, Shinichiro; Hidai, Chiaki

2016-07-01

Coagulation factor IX (FIX) is an essential plasma protein for blood coagulation. The first epidermal growth factor (EGF) motif of FIX (EGF-F9) has been reported to attenuate cell adhesion to the extracellular matrix (ECM). The purpose of the present study was to determine the effects of this motif on cell adhesion and apoptosis. Treatment with a recombinant EGF-F9 attenuated cell adhesion to the ECM within 10 min. De-adhesion assays with native FIX recombinant FIX deletion mutant proteins suggested that the de-adhesion activity of EGF-F9 requires the same process of FIX activation as that which occurs for coagulation activity. The recombinant EGF-F9 increased lactate dehydrogenase (LDH) activity release into the medium and increased the number of cells stained with annexin V and activated caspase-3, by 8.8- and 2.7-fold respectively, indicating that EGF-F9 induced apoptosis. Activated caspase-3 increased very rapidly after only 5 min of administration of recombinant EGF-F9. Treatment with EGF-F9 increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), but not that of phosphorylated MAPK 44/42 or c-Jun N-terminal kinase (JNK). Inhibitors of caspase-3 suppressed the release of LDH. Caspase-3 inhibitors also suppressed the attenuation of cell adhesion and phosphorylation of p38 MAPK by EGF-F9. Our data indicated that EGF-F9 activated signals for apoptosis and induced de-adhesion in a caspase-3 dependent manner. © 2016 The Author(s).

Telangiectatic Matting is Associated with Hypersensitivity and a Bleeding Tendency.

PubMed

Kadam, Pooja; Lim, Jerrick; Paver, Ian; Connor, David E; Parsi, Kurosh

2018-04-01

The aim was to investigate the pathogenesis of telangiectatic matting (TM) and identify possible risk factors. This study had two parts. The clinical records of consecutive patients were retrospectively analysed to identify risk factors for TM. In the second part, the haemostatic and coagulation profile of the subset of patients with TM were analysed and compared with controls using standard coagulation tests, platelet function and a global assay of coagulation (rotational thromboelastometry, ROTEM). In 352 consecutive patients presenting to a phlebology practice, 25 patients had TM (7.1%). All 25 patients were female with the median age of 45 (27-57) years. A comprehensive medical history was taken. Among 27 possible risk factors assessed, statistically significant associations included recurrent epistaxis, easy bruising, hypersensitivity (eczema, hives, hay fever, and rhinitis), previous treatment with sclerotherapy or endovenous laser for lower limb veins, and a family history of telangiectasias. Variables not associated with TM included oral contraceptive intake, hormone replacement therapy, and age. The haemostatic and coagulation profile of 12 patients (6 male and 6 female) with TM did not differ significantly from those without TM. TM is associated with both hypersensitivity and a bleeding tendency. This study revealed no significant increase in the incidence of haemostatic abnormalities in patients with TM compared with the control group. Given the significant association with hypersensitivity disorders, the underlying mast cell hyper-reactivity may contribute to both hypersensitivity and a bleeding tendency and predispose patients to TM. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Alteration of Antithrombin III and D-dimer Levels in Clinically Localized Prostate Cancer

PubMed Central

Ko, Dong Woo; Park, Juhyun; Kim, In Sung; Doo, Seung Hwan; Yoon, Cheol Yong; Park, Hongzoo; Lee, Won Ki; Kim, Dae Sung; Jeong, Seong Jin; Byun, Seok-Soo; Lee, Sang Eun

2010-01-01

Purpose We performed a comparative analysis of the plasma levels of antithrombin (AT) III, plasminogen, fibrinogen, and D-dimer among patients with and without clinically localized prostate cancer to investigate the clinical significance of the coagulation profile in prostate cancer. Materials and Methods A prospective study was performed in which plasma levels of AT III, plasminogen, fibrinogen, and D-dimer were assessed in patients before they underwent prostate biopsy. According to the results of the biopsy, the patients were categorized into the cancer group or the control group. Levels of the four coagulation factors were then compared between the cancer and control groups. Also, levels of the four coagulation factors were correlated with tumor stage and grade in the cancer group. Results The cancer group had significantly lower levels of AT III activity and higher plasma D-dimer levels than did the control group (p=0.007 and p=0.018, respectively). Within the cancer group, no significant differences were observed in the levels of AT III, plasminogen, fibrinogen, or D-dimer between those with a pathological Gleason score of ≥7 and otherwise. Regarding pathologic stage of prostate cancer, the subjects with organ-confined disease and those with extraprostatic extension of a tumor demonstrated no significant differences in the preoperative levels of the four coagulation factors analyzed. Conclusions Our results suggest that plasma levels of AT III and D-dimer are altered in patients with prostate cancer. Further study is needed to elucidate the underlying mechanism and clinical significances of such a phenomenon among patients with clinically localized prostate cancer. PMID:20414406

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

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

Schechter, Melissa E.; Andrade, Bruno B.; He, Tianyu

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. Thus, a better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidencemore » of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.« less

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

DOE PAGES

Schechter, Melissa E.; Andrade, Bruno B.; He, Tianyu; ...

2017-08-30

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. Thus, a better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidencemore » of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.« less