L-Asparaginase lowers plasma antithrombin and mannan-binding-lectin levels: Impact on thrombotic and infectious events in children with acute lymphoblastic leukemia.

PubMed

Merlen, Clémence; Bonnefoy, Arnaud; Wagner, Eric; Dedeken, Laurence; Leclerc, Jean-Marie; Laverdière, Caroline; Rivard, Georges-Etienne

2015-08-01

L-asparaginase, a key therapeutic agent in the management of patients with acute lymphoblastic leukemia (ALL), dramatically impairs hepatic protein synthesis. We investigated the effects of prolonged exposure to L-asparaginase on antithrombin (AT), fibrinogen and mannan-binding-lectin (MBL) levels, and on the occurrence of thrombotic events (TE) and febrile neutropenia episodes (FN) in pediatric patients. Protein levels were measured in 97 children during 30 weeks of chemotherapy with L-asparaginase and up to 1 year following remission. TE and FN episodes were recorded during this period. Median AT level decreased from 0.96 IU/mL prior to treatment (range: 0.69-1.38) to 0.55 IU/mL (0.37-0.76) during therapy. Fibrinogen and MBL decreased from 3.18 g/L (1.29-7.28) and 1,177 ng/mL (57-5,343) to 1.56 g/L (0.84-2.13) and 193 ng/mL (57-544), respectively. All three proteins had recovered 1-4 weeks after L-asparaginase cessation. TE were reported in 22 (23%) patients. Of these, 11 occurred after a median of 10 administrations of L-asparaginase. Fifty-one FN were associated with infections, of which 36 occurred during treatment with L-asparaginase. Patients with low levels of MBL at diagnosis were at higher risk of FN associated with infections (RR = 1.59, 95%CI: 1.026-2.474). Both AT and MBL decreases were moderately correlated with fibrinogen (r = 0.51 and 0.58, respectively). Children with ALL are exposed to significant decrease in AT, fibrinogen and MBL levels, and concomitant increased risk of thrombosis and FN with infection during L-asparaginase treatment. Measuring plasma levels of these liver-derived proteins could help predict the occurrence of adverse events. © 2015 Wiley Periodicals, Inc.

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy.

PubMed

Wayhs, Sâmia Yasin; Wottrich, Joise; Uggeri, Douglas Prestes; Dias, Fernando Suparregui

2013-01-01

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and evere liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure management and treatment success.

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy

PubMed Central

Wayhs, Sâmia Yasin; Wottrich, Joise; Uggeri, Douglas Prestes; Dias, Fernando Suparregui

2013-01-01

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and severe liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure appropriate management and treatment success. PMID:23917984

Clustering of ABCB1 and CYP2C19 Genetic Variants Predicts Risk of Major Bleeding and Thrombotic Events in Elderly Patients with Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel.

PubMed

Galeazzi, Roberta; Olivieri, Fabiola; Spazzafumo, Liana; Rose, Giuseppina; Montesanto, Alberto; Giovagnetti, Simona; Cecchini, Sara; Malatesta, Gelsomina; Di Pillo, Raffaele; Antonicelli, Roberto

2018-06-23

The clinical efficacy of clopidogrel in secondary prevention of vascular events is hampered by marked inter-patient variability in drug response, which partially depends on genetic make-up. The aim of this pilot prospective study was to evaluate 12-month cardiovascular outcomes in elderly patients with acute coronary syndrome (ACS) receiving dual antiplatelet therapy (aspirin and clopidogrel) according to the clustering of CYP2C19 and ABCB1 genetic variants. Participants were 100 consecutive ACS patients who were genotyped for CYP2C19 (G681A and C-806T) and ABCB1 (C3435T) polymorphisms, which affect clopidogrel metabolism and bioavailability, using PCR-restriction fragment length polymorphism. They were then grouped as poor, extensive and ultra-rapid metabolisers based on the combination of CYP2C19 loss-of-function (CYP2C19*2) and gain-of-function (CYP2C19*17) alleles and ABCB1 alleles. The predictive value of each phenotype for acute vascular events was estimated based on 12-month cardiovascular outcomes. The poor metabolisers were at an increased risk of thrombotic events (OR 1.26; 95% CI 1.099-1.45; χ 2  = 5.676; p = 0.027), whereas the ultra-rapid metabolisers had a 1.31-fold increased risk of bleeding events compared with the poor and extensive metabolisers (OR 1.31; 95% CI 1.033-1.67; χ 2  = 5.676; p = 0.048). Logistic regression model, including age, sex, BMI and smoking habit, confirmed the differential risk of major events in low and ultra-rapid metabolisers. Our findings suggest that ACS patients classified as 'poor or ultra-rapid' metabolisers based on CYP2C19 and ABCB1 genotypes should receive alternative antiplatelet therapies to clopidogrel.

A rare combination of thrombotic thrombocytopenic purpura and antiphospholipid syndrome.

PubMed

Viner, Maya; Murakhovskaya, Irina

2017-07-01

: Thrombocytopenia, in the setting of microangiopathic hemolytic anemia and thrombotic events, is characteristic of both thrombotic thrombocytopenic purpura and primary antiphospholipid syndrome. Clinically, it is difficult to distinguish between these two syndromes. We present a 41-year-old woman with chronic, relapsing thrombotic thrombocytopenic purpura in the presence of antiphospholipid antibodies. She had clinical manifestations of antiphospholipid syndrome without meeting laboratory criteria of the Sydney classification system. In the literature, there have only been nine cases of thrombotic thrombocytopenic purpura associated with primary antiphospholipid syndrome. Seven of the nine cases suffered from one or multiple strokes, a common feature in antiphospholipid syndrome, but an uncommon finding in thrombotic thrombocytopenic purpura. We introduce the possibility of an association between thrombotic thrombocytopenic purpura and the presence of antiphospholipid antibodies. Systematic testing of ADAMTS13 activity and anti-ADAMTS13 antibodies in patients who present with neurological symptoms and thrombocytopenia, in the presence of antiphospholipid antibodies, may help with the diagnosis of the rare thrombotic thrombocytopenic purpura-antiphospholipid syndrome combination.

Experimental acute thrombotic stroke in baboons

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

Del Zoppo, G.J.; Copeland, B.R.; Harker, L.A.

1986-11-01

To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9more » cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8.« less

Thrombotic microangiopathy associated with Valproic acid toxicity.

PubMed

Hebert, Sean A; Bohan, Timothy P; Erikson, Christian L; Swinford, Rita D

2017-08-03

Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA. We present the first case of a patient meeting clinical criteria for DI-TMA following admission for valproic acid toxicity. An adolescent male with difficult to control epilepsy was admitted for impaired hepatic function while on valproic acid therapy. On the third hospital day, he developed severe metabolic lactic acidosis and multiorgan failure, prompting transfer to the pediatric intensive care unit. Progressive anemia and thrombocytopenia instigated an evaluation for thrombotic microangiopathy, where confirmed by concomitant hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and concurrent oliguric acute kidney injury. Thrombotic thrombocytopenic purpura was less likely with adequate ADAMTS13. Discontinuing valproic acid reversed the anemia, thrombocytopenia, and normalized the LDH and haptoglobin, supporting a drug-induced cause for the TMA. To the best of our knowledge, this is the first report of drug-induced TMA from valproic acid toxicity.

Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report.

PubMed

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Unlu, Serkan; Ertem, Kadir; Nizam, Ilknur

2014-08-01

Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in multiple organ systems, which becomes manifest with microangiopathic hemolytic anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13 activity leads to an excess of high molecular weight von Willebrand factor multimers in plasma, leading to platelet aggregation and diffuse intravascular thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic lesions occurring in TTP leads to ischemia and convulsion. Depending on the properties of the bony tissue, fractures are divided into three groups as traumatic, pathological, and stress fractures. A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as cancer, infections, inherited bone disorders, or a bone cyst. We herein report a case with a pathologic fracture due to convulsion secondary to thrombotic thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia and convulsion, as in our patient and pathological fractures presented in our case report may occur as a result of severe muscle contractions associated with convulsive activity. Thrombotic thrombocytopenic pupura is a disease that involves many organ systems and thus may have a very wide spectrum of clinical presentations. Copyright © 2014. Published by Elsevier Ltd.

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura.

PubMed

Cao, Wenjing; Pham, Huy P; Williams, Lance A; McDaniel, Jenny; Siniard, Rance C; Lorenz, Robin G; Marques, Marisa B; Zheng, X Long

2016-11-01

Acquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme-linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (P<0.0001). The plasma levels of HNP1-3 correlated with the levels of plasma complement fragment Bb (rho=0.48, P=0.0004) and serum lactate dehydrogenase (rho=0.28, P=0.04); in addition, the plasma levels of Bb correlated with iC3b (rho=0.55, P<0.0001), sC5b-9 (rho=0.63, P<0.0001), serum creatinine (rho=0.42, p=0.0011), and lactate dehydrogenase (rho=0.40, P=0.0034), respectively. Moreover, the plasma levels of iC3b and sC5b-9 were correlated (rho=0.72, P<0.0001), despite no statistically significant difference of the two markers between thrombotic thrombocytopenic purpura patients and the control. We conclude that innate immunity, i.e. neutrophil and complement activation via the alternative pathway, may play a role in the pathogenesis of acute autoimmune thrombotic thrombocytopenic purpura, and a therapy targeted at these pathways may be considered in a subset of these patients. Copyright© Ferrata Storti Foundation.

Opportunities for improvement in anti-thrombotic therapy and other strategies for the management of acute coronary syndromes: Insights from EPICOR, an international study of current practice patterns.

PubMed

Bueno, Héctor; Sinnaeve, Peter; Annemans, Lieven; Danchin, Nicolas; Licour, Muriel; Medina, Jesús; Pocock, Stuart; Sánchez-Covisa, Joaquín; Storey, Robert F; Jukema, J Wouter; Zeymer, Uwe; Van de Werf, Frans

2016-02-01

To describe international patterns and opportunities for improvement of pre- and in-hospital care of patients hospitalized for acute coronary syndromes (ACS), with special focus on anti-thrombotic therapy. EPICOR (long-tErm follow-uP of anti-thrombotic management patterns In acute CORonary syndrome patients), an international, cohort study, which enrolled 10,568 consecutive ACS survivors from 555 hospitals in 20 countries across Europe and Latin America (September 2010 to March 2011), prospectively registered detailed information on pre- and in-hospital management. Globally, 4738 (44.8%) were attended before hospitalization, 4241 (40.1%) had an ECG, 2119 (20%) received anti-platelet therapy and 101 STEMI patients (2%) fibrinolysis. In-hospital, 7944 patients (75.2%) received dual anti-platelet therapy, most often with clopidogrel (69.7%), and less with prasugrel (5.4%); 1705 (16.1%) had triple anti-platelet therapy, and 849 (8%) single anti-platelet therapy. STEMI patients more often received pre-hospital anti-thrombotics, and prasugrel, GP IIb/IIIa inhibitors and UFH in-hospital (all p < 0.001). More NSTE-ACS patients received clopidogrel, single anti-platelet therapy, and fondaparinux (all p < 0.001). As many as 33% of ACS patients were medically managed. A significant decreasing gradient was found between Northern, Southern and Eastern Europe and Latin America in use of more potent patterns of anti-platelet therapy, reperfusion therapy and invasive strategy. This large international study shows room for improvement in use of anti-thrombotic drugs and other strategies for optimal management of ACS, including pre-hospital ECG and anti-thrombotic therapy. Regional practice differences not based on evidence or conditioned by economic constraints should be reduced. © The European Society of Cardiology 2015.

Procoagulant activity of extracellular vesicles as a potential biomarker for risk of thrombosis and DIC in patients with acute leukaemia.

PubMed

Gheldof, Damien; Haguet, Hélène; Dogné, Jean-Michel; Bouvy, Céline; Graux, Carlos; George, Fabienne; Sonet, Anne; Chatelain, Christian; Chatelain, Bernard; Mullier, François

2017-02-01

Haemostatic complication is common for patients with hematologic malignancies. Recent studies suggest that the procoagulant activity (PCA) of extracellular vesicles (EV) may play a major role in venous thromboembolism and disseminated intravascular coagulation (DIC) in acute leukaemia. To study the impact of EVs from leukaemic patients on thrombin generation and to assess EV-PCA as a potential biomarker for thrombotic complications in patients with acute leukaemia. Blood samples from a cohort of patients with newly diagnosed acute leukaemia were obtained before treatment (D-0), 3 and 7 days after treatment (D-3 and D-7). Extracellular vesicles were isolated and concentrated by ultracentrifugation. EV-PCA was assessed by thrombin generation assay, and EV-associated tissue factor activity was measured using a commercial bio-immunoassay (Zymuphen MP-TF®). Of the 53 patients, 6 had increased EV-PCA at D-0 and 4 had a thrombotic event. Patients without thrombotic events (n = 47) had no elevated EV-PCA. One patient had increased EVs with procoagulant activity at D-3 and developed a DIC at D-5. This patient had no increased EVs-related tissue factor activity from D-0 to D-7 (<2 pg/ml). Eight patients had increased EVs with tissue factor activity (>2 pg/ml), of these, four had a thrombosis and two had haemorrhages. Procoagulant activity of extracellular vesicles could have a predictive value in excluding the risk of thrombotic events. Our findings also suggest a possible association between thrombotic events and EV-PCA.

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

Thrombotic thrombocytopenic purpura

MedlinePlus

... medlineplus.gov/ency/article/000552.htm Thrombotic thrombocytopenic purpura To use the sharing features on this page, please enable JavaScript. Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that causes blood ...

Current insights into thrombotic microangiopathies: Thrombotic thrombocytopenic purpura and pregnancy.

PubMed

von Auer, Charis; von Krogh, Anne-Sophie; Kremer Hovinga, Johanna A; Lämmle, Bernhard

2015-02-01

The complex relation between thrombotic thrombocytopenic purpura (TTP) and pregnancy is concisely reviewed. Pregnancy is a very strong trigger for acute disease manifestation in patients with hereditary TTP caused by double heterozygous or homozygous mutations of ADAMTS13 (ADisintegrin And Metalloprotease with ThromboSpondin type 1 domains, no. 13). In several affected women disease onset during their first pregnancy leads to the diagnosis of hereditary TTP. Without plasma treatment mother and especially fetus are at high risk of dying. The relapse risk during a next pregnancy is almost 100% but regular plasma transfusion starting in early pregnancy will prevent acute TTP flare-up and may result in successful pregnancy outcome. Pregnancy may also constitute a mild risk factor for the onset of acute acquired TTP caused by autoantibody-mediated severe ADAMTS13 deficiency. Women having survived acute acquired TTP may not be at very high risk of TTP relapse during an ensuing next pregnancy but seem to have an elevated risk of preeclampsia. Monitoring of ADAMTS13 activity and inhibitor titre during pregnancy may help to guide management and to avoid disease recurrence. Finally, TTP needs to be distinguished from the much more frequent hypertensive pregnancy complications, preeclampsia and especially HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet count) syndrome. © 2015 Elsevier Ltd. All rights reserved.

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

PubMed

Thompson, Douglas D; Murray, Gordon D; Candelise, Livia; Chen, Zhengming; Sandercock, Peter A G; Whiteley, William N

2015-10-01

Aspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage. We aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient. We used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk. Ischemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53-0·59) and haemorrhagic events (0·57, 0·52-0·64), though well between patients with and without poor functional outcome (0·77, 0

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study.

PubMed

Riva, Nicoletta; Ageno, Walter; Poli, Daniela; Testa, Sophie; Rupoli, Serena; Santoro, Rita; Lerede, Teresa; Piana, Antonietta; Carpenedo, Monica; Nicolini, Alberto; Ferrini, Piera Maria; Martini, Giuliana; Mangione, Catello; Contino, Laura; Bonfanti, Carlo; Gresele, Paolo; Tosetto, Alberto

2015-01-01

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups.

Reduction of factor XII in antiphospholipid antibody-positive patients with thrombotic events in the rheumatology clinic.

PubMed

Takeishi, M; Mimori, A; Nakajima, K; Mimura, T; Suzuki, T

2003-02-01

Although rheumatological diagnosis often includes an assessment of antiphospholipid (aPL) antibodies, the significance of other prothrombotic factors has not been established in thrombotic patients who are not afflicted with either arteriosclerosis or vasculitis syndrome. We have observed both the presence of antiphospholipid antibodies and a reduction of factor XII in such patients. Our results identified both lupus anticoagulant-positive (50%) and anticardiolipin antibody-positive (58%) patients. In addition, 83% of patients showed factor XII antigen level reduction. Furthermore, 70% of aPL-positive thrombotic patients showed factor XII antigen level reduction. Only two cases had antiphospholipid antibody alone, and 4/12 showed just factor XII antigen reduction. Recently, it has been reported that the presence of antiphospholipid antibodies induces factor XII reduction, and that anti-factor XII autoantibody can be detected in thrombotic patients. However, our results indicate that there are smaller factor XII reductions in non-thrombotic controls who are positive for antiphospholipid antibodies. Furthermore, anti-factor XII autoantibody was not detected in patients with decreased factor XII levels. Kindred research suggested that in two patients there was a genetic component to factor XII reduction. We concluded that the presence of both antiphospholipid antibodies and reduced serum factor XII was observed in most thrombotic patients from our rheumatology clinic. It is therefore possible to consider that the coexistence of these prothrombotic factors can contribute to the onset of thrombosis.

Trichinella Nativa Outbreak With Rare Thrombotic Complications Associated With Meat From a Black Bear Hunted in Northern Ontario.

PubMed

Dalcin, Daniel; Zarlenga, Dante S; Larter, Nicholas C; Hoberg, Eric; Boucher, Daniel A; Merrifield, Samuel; Lau, Rachel; Ralevski, Filip; Cheema, Karamjit; Schwartz, Kevin L; Boggild, Andrea K

2017-05-15

Although trichinellosis is known to cause thrombotic disease, serious thrombotic events are rare and have not been previously associated with Trichinella nativa infection. Patient interviews and medical chart reviews were conducted on 10 men who became ill following consumption of a common source of black bear meat. Trichinella serology on patient sera as well as polymerase chain reaction (PCR) and larval identification of the meat samples was conducted. All 10 exposed individuals developed an acute illness clinically compatible with trichinellosis, characterized by fever, abdominal pain, and diarrhea, along with eosinophilia ranging from 0.9 × 109/L to 6.1 × 109/L. Within 2 weeks of the diarrheal illness, systemic symptoms developed in all exposed individuals characterized by fever, myalgia, periorbital edema, and fatigue. ST-elevation myocardial infarction and sinus venous tract thrombosis occurred as a complication of trichinellosis in 2 patients. Acute serology was nonreactive in all patients, though convalescent serology was reactive in 6 of 8 (75%) patients for whom sera was available. Multiplex PCR identified T. nativa from the bear meat, and was corroborated by microscopic larval identification. We report a 100% attack rate of T. nativa from bear meat among those who were exposed, and demonstrate that this species can cause serious thrombotic complications of trichinellosis in humans. Education of hunters and the public regarding the importance of proper preparation of wild game prior to ingestion is warranted. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Statins but Not Aspirin Reduce Thrombotic Risk Assessed by Thrombin Generation in Diabetic Patients without Cardiovascular Events: The RATIONAL Trial

PubMed Central

Macchia, Alejandro; Laffaye, Nicolás; Comignani, Pablo D.; Cornejo Pucci, Elena; Igarzabal, Cecilia; Scazziota, Alejandra S.; Herrera, Lourdes; Mariani, Javier A.; Bragagnolo, Julio C.; Catalano, Hugo; Tognoni, Gianni; Nicolucci, Antonio

2012-01-01

Background The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events. Methodology/Principal Findings Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent. Conclusions/Significance While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. Trial Registration ClinicalTrials.gov NCT00793754 PMID:22470429

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study

PubMed Central

Riva, Nicoletta; Ageno, Walter; Poli, Daniela; Testa, Sophie; Rupoli, Serena; Santoro, Rita; Lerede, Teresa; Piana, Antonietta; Carpenedo, Monica; Nicolini, Alberto; Ferrini, Piera Maria; Martini, Giuliana; Mangione, Catello; Contino, Laura; Bonfanti, Carlo; Gresele, Paolo; Tosetto, Alberto

2015-01-01

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups. PMID:26508913

[Clopidogrel induced thrombotic thrombocytopenic purpura].

PubMed

Karkowski, L; Wolf, M; Lescampf, J; Coppérré, B; Veyradier, A; Ninet, J; Hot, A

2011-12-01

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. Drug-induced TTP is uncommon and we report a TTP associated with the use of clopidogrel. We report a 50-year-old man who presented with acute myocardial infarction and received clopidogrel therapy. He developed acute TTP ten days after clopidogrel onset. Imputability of the drug was demonstrated during a reintroduction test. Deficiency of ADAMTS 13 was confirmed and autoantibodies against ADAMTS 13 were detected. Complete remission was obtained after 24 plasma exchange sessions and adjunction of corticosteroids. Drug-induced TTP are probably immunologic, as was demonstrated in our patient. Clinicians should be aware of this possible uncommon adverse effect of clopidogrel because prompt therapy is imperative for life saving. Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Long-term low-molecular-weight heparin and the post-thrombotic syndrome: a systematic review.

PubMed

Hull, Russell D; Liang, Jane; Townshend, Grace

2011-08-01

Post-thrombotic syndrome causes considerable morbidity. The Home-LITE study showed a lower incidence of post-thrombotic syndrome and venous ulcers after 3 months of treating deep vein thrombosis with the low-molecular-weight heparin tinzaparin versus oral anticoagulation. This systematic review examined whether long-term treatment of deep vein thrombosis using low-molecular-weight heparin, rather than oral anticoagulation, reduces development of post-thrombotic syndrome. We identified 9 articles comparing treatment of deep vein thrombosis using long-term low-molecular-weight heparin with any comparator, which reported outcomes relevant to the post-thrombotic syndrome assessed ≥ 3 months post-deep vein thrombosis. Pooled analysis of 2 studies yielded an 87% risk reduction with low-molecular-weight heparin in the incidence of venous ulcers at ≥ 3 months (P = .019). One study showed an overall odds ratio of 0.77 (P = .001) favoring low-molecular-weight heparin for the presence of 8 patient-reported post-thrombotic syndrome signs and symptoms. Pooled analysis of 5 studies showed a risk ratio for low-molecular-weight heparin versus oral anticoagulation of 0.66 (P < .0001) for complete recanalization of thrombosed veins. These results support the lower incidence of post-thrombotic syndrome and venous ulcers observed in Home-LITE. Long-term treatment with low-molecular-weight heparin rather than oral anticoagulation after a deep vein thrombosis may reduce or prevent development of signs and symptoms associated with post-thrombotic syndrome. Post-thrombotic syndrome and associated acute ulcers may develop more rapidly after deep vein thrombosis than previously recognized. Copyright © 2011 Elsevier Inc. All rights reserved.

Stroke in thrombotic thrombocytopenic purpura induced by thyrotoxicosis: a case report.

PubMed

Bellante, Flavio; Redondo Saez, Patricia; Springael, Cecile; Dethy, Sophie

2014-07-01

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease involving the platelet aggregation and resulting in hemolytic anemia, thrombocytopenia, and microvascular occlusion. Although frequent neurologic features are headache and confusion, focal deficit is described in 30% of the cases. There are a lot of causes inducing thrombotic thrombocytopenic, but reports are lacking when associated with Grave disease. We describe the case of a 51-year-old Caucasian woman presenting a 24-hour story of sudden onset of dysarthria and left superior limb palsy. Four months before, she developed severe hyperthyroidism associated with petechiae, hemolytic anemia, thrombocytopenia, and schistocytes at blood film examination. Relapse of TTP in association with Grave disease was diagnosed. There are few reports describing association between Grave disease and TTP with only mild neurologic involvement. We described, to our knowledge, the first case of acute ischemic stroke secondary to thrombotic thrombocytopenic induced by thyrotoxicosis. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

PubMed

Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

2015-10-01

Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCAM-1 levels were higher in SLE patients (P < 0.05). Considering three groups of SLE patients depending on ADAMTS13 activity (>60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy.

PubMed

Mariotte, Eric; Azoulay, Elie; Galicier, Lionel; Rondeau, Eric; Zouiti, Fouzia; Boisseau, Pierre; Poullin, Pascale; de Maistre, Emmanuel; Provôt, François; Delmas, Yahsou; Perez, Pierre; Benhamou, Ygal; Stepanian, Alain; Coppo, Paul; Veyradier, Agnès

2016-05-01

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; activity <10%). We aimed to investigate the association between mechanisms for ADAMTS13 deficiency and the epidemiology and pathophysiology of thrombotic thrombocytopenic purpura at initial presentation. Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686. We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials

PubMed Central

Whiteley, William N; Adams, Harold P; Bath, Philip MW; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter AG

2013-01-01

Summary Background Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. Methods We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome “dead or dependent” in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Findings Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59–0·67) and for haemorrhagic events was 0·60 (0·55–0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. Interpretation There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials.

PubMed

Whiteley, William N; Adams, Harold P; Bath, Philip M W; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter A G

2013-06-01

Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome "dead or dependent" in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59-0·67) and for haemorrhagic events was 0·60 (0·55-0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

PubMed

Tamez, Hector; Généreux, Philip; Yeh, Robert W; Amin, Amit P; Fan, Weihong; White, Harvey D; Kirtane, Ajay J; Stone, Gregg W; Gibson, C Michael; Harrington, Robert A; Bhatt, Deepak L; Pinto, Duane S

2018-05-04

Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI. © 2018 Wiley Periodicals, Inc.

Trichinella nativa outbreak with rare thrombotic complications associated with meat from a black bear hunted in Northern Ontario

USDA-ARS?s Scientific Manuscript database

Although trichinellosis is known to cause thrombotic disease, serious thrombotic events are rare and have previously not been shown to be associated with Trichinella nativa. Patient interviews and medical chart reviews were conducted on ten men who became ill following consumption of a common source...

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

PubMed

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

2017-03-10

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

A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study.

PubMed

Mitchell, Lesley G; Andrew, Maureen; Hanna, Kim; Abshire, Thomas; Halton, Jacqueline; Anderson, Ron; Cherrick, Irene; Desai, Sunil; Mahoney, Donald; McCuster, Patricia; Wu, John; Dahl, Gary; Chait, Peter; de Veber, Gabrielle; Lee, Kyong-Jin; Mikulis, David; Ginsberg, Jeffrey; Way, Cliford

2003-01-15

Thrombotic events (TEs) are serious secondary complications in children with acute lymphoblastic leukemia (ALL) who receive L-asparaginase (ASP) therapy; however, the prevalence of TEs has not been established. The primary objective of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study was to determine the prevalence of TEs. The secondary objective was to detect any association of TEs with the presence of congenital or acquired prothrombotic disorders. Children with ALL were screened for TEs at the end of ASP treatment using bilateral venograms, ultrasound, magnetic resonance imaging, and echocardiography. Symptomatic TEs were confirmed by appropriate radiographic tests. All tests were read by a blinded central adjudication committee. Twenty-two of 60 children had TEs, a prevalence of 36.7% (95% confidence interval, 24.4-48.8%). TEs were located in the sinovenous system of the brain in 1 patient, the right atrium in 3 patients, and the upper central venous system in 19 patients. TEs detected by venography resulted in 1) 25-100% occlusion, with 1 in 3 patients showing occlusion of > 75% of the greatest vessel dimension, and 2) the presence of collaterals in 60% of patients, with 40% categorized as major. No children with TEs were positive for factor V Leiden or prothrombin gene 20201A, and four of eight children with antiphospholipid antibodies had a TE. The prevalence of TEs is exceedingly high in this population, and it is likely that the extent of occlusion is likely clinically significant. No trend was seen toward an association between TEs and the presence of congenital prothrombotic disorders. A trend was seen toward an association between TEs and antiphospholipid antibodies. Carefully designed clinical trials of primary prophylaxis for the prevention of TEs are required in this patient population. Copyright 2003 American Cancer Society

Low ADAMTS-13 in plavix induced thrombotic thrombocytopenic purpura.

PubMed

Cao, Long Bao; Jones, Christopher; Movahed, Assad

2013-04-16

Thrombotic thrombocytopenia purpura (TTP) was first described in 1924 as a "pathologic alteration of the microvasculature, with detachment or swelling of the endothelium, amorphous material in the sub-endothelial space, and luminal platelet aggregation leading to compromise of the microcirculation". Ticlopidine induced TTP has been highly associated with autoimmune induced reduction in ADAMTS-13 activity. These findings, to a lesser extent, have also been found in clopidogrel induced TTP. We report a case of clopidogrel associated TTP in a patient that presented with acute stroke, renal failure, and non-ST elevation myocardial infarction.

Secondary thrombotic microangiopathy in two patients with Philadelphia-positive hematological malignancies treated with imatinib mesylate.

PubMed

Ojeda-Uribe, Mario; Merieau, Sylvain; Guillon, Marie; Aujoulat, Olivier; Hinschberger, Olivier; Eisenmann, Jean-Claude; Kenizou, David; Debliquis, Agathe; Veyradier, Agnès; Chantrel, François

2016-04-01

Drug-mediated thrombotic microangiopathy may cause life-threatening medical emergencies. Novel targeted therapies have dramatically changed the prognosis of a number of oncological diseases. Tyrosine kinase inhibitors of the Breakpoint Cluster Region-Abelson (BCR-ABL) oncoprotein are used in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Imatinib mesylate, which was the first anti-BCR-ABL tyrosine kinase inhibitor, has demonstrated a high tolerance profile and efficacy in these patients for many years. Good results have also been observed in patients with gastrointestinal stromal tumors. In this study, we describe two patients with Philadelphia chromosome-positive hematological malignancies who presented with secondary thrombotic microangiopathy that was most likely linked to the use of imatinib. Other potential causes of thrombotic microangiopathy were discarded, and the predisposing role of some comorbidities and potential short or long-term drug-drug interactions was assessed. The clinical and biological data were more indicative of atypical secondary hemolytic uremic syndrome in one of the cases and of secondary thrombotic microangiopathy with renal and cardiac impairment in the other, which is also categorized as secondary hemolytic uremic syndrome. The outcome was favorable after imatinib discontinuation and the treatment of severe cardiac and renal failures. © The Author(s) 2015.

Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

ClinicalTrials.gov

2018-02-12

Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.

PubMed

Mörtzell, M; Berlin, G; Nilsson, T; Axelsson, C G; Efvergren, M; Audzijoni, J; Griskevicius, A; Ptak, J; Blaha, M; Tomsova, H; Liumbruno, G M; Centoni, P; Newman, E; Eloot, S; Dhondt, A; Tomaz, J; Witt, V; Rock, G; Stegmayr, B

2011-10-01

Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034). Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact

Case report: a 70-year-old man with undiagnosed factor VII deficiency presented with acute ischemic stroke.

PubMed

Ip, Hing-Lung; Chan, Anne Yin-Yan; Ng, Kit-Chung; Soo, Yannie Oi-Yan; Wong, Lawrence Ka-Sing

2013-11-01

Factor VII deficiency is an uncommon coagulation disorder that patient usually presents with bleeding diathesis, but thrombotic event has been reported. We report a case of unusual clinical presentation in a patient with undiagnosed factor VII deficiency who presented with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Dental treatment in the era of new anti-thrombotic agents.

PubMed

Sahar-Helft, Sharonit; Chackartchi, Tali; Polak, David; Findler, Mordechai

2018-06-01

In recent years, there have been dramatic changes in anti-thrombotic treatment as a result of new anti-thrombotic agents, as well as changes in the indications for their use. As a consequence, dentists are encountering larger numbers of patients who are undergoing anti-thrombotic treatment and who have increased risk for bleeding. The current paper aims to review the literature regarding up-to-date anti-thrombotic treatment and provide information regarding their implications on dentistry. An online search was performed of the literature published between 2000 and 2016. Articles dealing with evidence-based clinical guidelines for anti-thrombotic treatments, as well as literature reporting the use of anti-thrombotic medications were included. The manuscripts were screened according to their relevance to dentistry as well as their treatment protocol guidelines. In total, 5,539 publications were identified: 56 of 554 evidence-based clinical guidelines were found that dealt with treatment protocols with anti-thrombotic agents; and 132 of 5,539 articles describe direct anti-thrombotic medications. Dental treatment includes a risk for bleeding. As a result of the increasing number of patients taking new-generation anti-thrombotic drugs, dentists must be up to date regarding the implications of such drugs on dental treatment as well as the practical means to achieve haemostasis. © 2017 FDI World Dental Federation.

[Fatal thrombotic microangiopathy in the mother and fetus].

PubMed

Udvardy, M; Telek, B; Kiss, A; Flóra Nagy, M; Mikó, T; Rák, K

1990-04-14

The appearance of thrombotic microangiopathy (thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome) could have been documented in a 23 years old pregnant woman, who had been treated previously for immune-thrombocytolytic purpura. The disturbing anamnestic data caused significant delay in correct diagnosis and in starting of fresh-frozen plasma therapy, so the woman and her fetus (in utero) had been died. The specific histological microangiopathic lesions could have been well documented by the autopsy of the mother, however no such alterations could have been detected in the fetus and placenta. This latter intriguing observation might be remarkable in the evaluation of several concepts dealing with the aetiopathogenesis of thrombotic microangiopathy. The short review of literature of thrombotic microangiopathy in pregnancy and puerperial period is also given.

Venous thrombotic events in hospitalized children and adolescents with inflammatory bowel disease.

PubMed

Nylund, Cade M; Goudie, Anthony; Garza, Jose M; Crouch, Gary; Denson, Lee A

2013-05-01

Adults with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events (TEs). We sought to evaluate the risk for TE in children and adolescents with IBD using a large population database. The triennial Healthcare Cost and Utilization Project Kids' Inpatient Database was used in a retrospective cohort study of hospitalized children in the United States across 1997, 2000, 2003, 2006, and 2009. Billing codes were used to identify discharges with Crohn disease, ulcerative colitis, pulmonary embolism, deep vein thrombosis, thrombophlebitis, thrombosis of intracranial venous sinus, Budd-Chiari syndrome, and portal vein thrombosis. A logistic regression model was fitted to quantify the increased risk of TE in children with IBD, while adjusting for other risk factors of thrombosis. The total weighted number of pediatric discharges was 7,448,292, and 68,394 (0.92%) were identified with IBD. The incidence of any TE in a hospitalized child or adolescent with IBD was 117.9/10,000 with a relative risk (95% confidence interval) of 2.36 (2.15-2.58). The adjusted odds ratio for any TE in a patient with IBD without surgery was 1.22 (1.08-1.36). Risk factors for TE among patients with IBD include older age, central venous catheter, parenteral nutrition, and an identified hypercoagulable condition. There is an increasing trend of TE in both the IBD and non-IBD patients. Hospitalized children and adolescents with IBD are at increased risk for TE. Conservative methods of TE prevention including hydration, mobilization, or pneumatic devices should be considered in hospitalized patients with IBD.

Anagrelide reduces thrombotic risk in essential thrombocythaemia vs. hydroxyurea plus aspirin.

PubMed

Dombi, Péter; Illés, Árpád; Demeter, Judit; Homor, Lajos; Simon, Zsofia; Karadi, Eva; Udvardy, Miklos; Egyed, Miklos

2017-02-01

To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA). A questionnaire was developed using 2008 WHO diagnostic criteria, and thrombotic risk factors were stratified according to Landolfi criteria. Through questionnaire completion, clinicians at Hungarian haematological centres entered data into the Hungarian MPN Registry on patients with myeloproliferative neoplasms. Based on ET registry data, TEs in anagrelide-treated patients (n = 139) were compared with HU + ASA-treated patients (n = 141). Patients were followed up for (median) 6 yr. TEs were reported in significantly fewer anagrelide-treated patients versus HU + ASA (15.1% versus 49.6%; P < 0.001). Numbers of major arterial and major venous events were similar between the groups, although there were over fivefold more minor arterial and minor venous events in the HU + ASA group (P < 0.001). While median age at diagnosis was older and length of follow-up shorter in the HU + ASA group (P < 0.05), this did not influence TE incidence; medication and TE before diagnosis only influenced TE incidence. Anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous TEs versus HU + ASA over 6 yr. Risk of TE after diagnosis was significantly increased if the patient had TE before diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

FcγRIIa ligation induces platelet hypersensitivity to thrombotic stimuli.

PubMed

Berlacher, Mark D; Vieth, Joshua A; Heflin, Brittany C; Gay, Steven R; Antczak, Adam J; Tasma, Brian E; Boardman, Holly J; Singh, Navinderjit; Montel, Angela H; Kahaleh, M Bashar; Worth, Randall G

2013-01-01

Platelets are known for their important role in hemostasis, however their significance in other functions, including inflammation and infection, are becoming more apparent. Patients with systemic lupus erythematosus (SLE) are known to have circulating IgG complexes in their blood and are highly susceptible to thrombotic events. Because platelets express a single receptor for IgG, we tested the hypothesis that ligation of this receptor (FcγRIIa) induces platelet hypersensitivity to thrombotic stimuli. Platelets from SLE patients were considerably more sensitive to thrombin compared to healthy volunteers, and this correlated with elevated levels of surface IgG on SLE platelets. To test whether FcγRIIa ligation stimulated thrombin hypersensitivity, platelets from healthy volunteers were incubated with buffer or heat-aggregated IgG, then stimulated with increasing concentrations of thrombin. Interestingly, heat-aggregated IgG-stimulated platelets, but not buffer-treated platelets, were hypersensitive to thrombin, and hypersensitivity was blocked by an anti-FcγRIIa monoclonal antibody (mAb). Thrombin hypersensitivity was not due to changes in thrombin receptor expression (GPIbα or PAR1) but is dependent on activation of shared signaling molecules. These observations suggest that ligation of platelet FcγRIIa by IgG complexes induces a hypersensitive state whereby small changes in thrombotic stimuli may result in platelet activation and subsequent vascular complications such as transient ischemic attacks or stroke. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Thrombotic microangiopathy in adults].

PubMed

Barrientos, Gonzalo J; Michelangelo, Hernán

2006-01-01

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.

Child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency: a cohort study of the French national registry for thrombotic microangiopathy.

PubMed

Joly, Bérangère S; Stepanian, Alain; Leblanc, Thierry; Hajage, David; Chambost, Hervé; Harambat, Jérôme; Fouyssac, Fanny; Guigonis, Vincent; Leverger, Guy; Ulinski, Tim; Kwon, Thérésa; Loirat, Chantal; Coppo, Paul; Veyradier, Agnès

2016-11-01

Thrombotic thrombocytopenic purpura is a rare thrombotic microangiopathy, related to a severe ADAMTS13 deficiency (a disintegrin and metalloprotease with thromboSpondin type 1 repeats, member 13; activity <10% of normal). Childhood-onset thrombotic thrombocytopenic purpura is very rare and initially often misdiagnosed, especially when ADAMTS13 deficiency is acquired (ie, not linked to inherited mutations of the ADAMTS13 gene). We aimed to investigate initial presentation, management, and outcome of acquired thrombotic thrombocytopenic purpura in children. Between Jan 1, 2000, and Dec 31, 2015, we studied a cohort of patients with child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura included in the French national registry for thrombotic microangiopathies at presentation and during follow up. The inclusion criteria were: first episode before age 18 years; ADAMTS13 activity less than 10% of normal at presentation; positive anti-ADAMTS13 autoantibodies during an episode, or a recovery of ADAMTS13 activity in remission, or both. ADAMTS13 activity and anti-ADAMTS13 autoantibodies were investigated by a central laboratory, and medical records were extensively reviewed to collect clinical and biological features with a standardised form. This study is registered with ClinicalTrials.gov, number NCT00426686. We enrolled 973 patients with childhood-onset thrombotic microangiopathy, of whom 74 had a severe ADAMTS13 deficiency (activity <10%) at presentation. 24 patients had an inherited thrombotic thrombocytopenic purpura also known as Upshaw-Schulman syndrome and five did not have follow-up data available, thus 45 children had acquired thrombotic thrombocytopenic purpura and were included in our database at presentation. 25 (56%) patients had idiopathic disease and 20 (44%) had miscellaneous associated clinical conditions. At diagnosis, median age was 13 years (IQR 7-16, range 4 months-17 years), with a sex ratio of 2·5 girls to 1 boy. Anti-ADAMTS13

Pegylated bovine carboxyhaemoglobin utilisation in a thrombotic thrombocytopenic purpura patient.

PubMed

Sam, C; Desai, P; Laber, D; Patel, A; Visweshwar, N; Jaglal, M

2017-08-01

To determine if pegylated bovine carboxyhaemoglobin can be utilised in a thrombotic thrombocytopenic purpura (TTP) patient. TTP is a condition characterized by thrombotic microangiopathy and has a high mortality rate when left untreated. Therapeutic plasma exchange is well established as the most effective and evidence-based treatment of TTP. The ability to administer plasma exchange therapy is limited in Jehovah's Witnesses who decline blood products due to religious beliefs. Pegylated bovine carboxyhaemoglobin is a novel oxygen transfer agent in development for the management of complications of ischaemia due to acute anaemia. Treatment was well tolerated, with grade 1 paresthesia of the right face and arm 1 h after the first infusion of Sanguinate, which spontaneously resolved and did not recur, and grade 1 cardiac troponin elevation after receiving the medication (with peak at 0·079 ng mL -1 ), but further workup with electrocardiogram and echocardiogram was unremarkable. By discharge on day 19, the patient's haemoglobin increased to 8·8 g dL -1 and platelet count to 221 000. We report the first case of TTP in a Jehovah's Witness that was successfully managed with the use of pegylated bovine carboxyhaemoglobin as an adjunct medication. © 2017 British Blood Transfusion Society.

Can rotational thromboelastometry predict thrombotic complications in reconstructive microsurgery?

PubMed

Kolbenschlag, Jonas; Daigeler, Adrien; Lauer, Sarah; Wittenberg, Gerhard; Fischer, Sebastian; Kapalschinski, Nicolai; Lehnhardt, Marcus; Goertz, Ole

2014-05-01

Thrombotic occlusion of the microvascular pedicle is the major reason for flap loss. Thus, identifying patients who are at risk for such events is paramount. Rotational thromboelastometry (RTE) is widely used to detect coagulopathy and hypercoagulable states. The aim of our study was to assess its diagnostic value in reconstructive microsurgery. In all 181 patients undergoing free tissue transfer at our department between February 2010 and November 2011 preoperative RTE was performed. In addition, coagulation values as well as patient's demographic data, cause and localization of defect, type of flap and surgical revisions were recorded. The majority of patients was male (59.6%) with traumatic (59.7%) defects located on the lower extremity (60.3%). ALT was the most often used flap (35.9%). Preoperatively, 36.5% of patients had a hypercoagulable RTE (higher than physiological RTE values; intrinsic (ICPT) or extrinsic (ECPT) mean clot firmness (MCF) >72mm or functional fibrinogen (ICF) MCF >25mm). A total of 28 primary thrombosis of the microvascular pedicle occurred, 11 of those in-patients with a hypercoagulable state. Total flap loss rate because ofthrombosis was 7.7% (n = 14). Both a hypercoagulable RTE assay and a functional fibrinogen to platelet ratio (FPR) of >43 (MCF value of ICF divided by the MCF value of ICPT) were significant predictors of thrombotic flap loss when performing multivariate binary logistic regression, co-factoring for age, sex, and comorbidities (p = 0.036 and 0.003, respectively). RTE seems to be able to identify patients that are prone to thrombotic complications and might be used as a screening tool. Copyright © 2013 Wiley Periodicals, Inc.

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

PubMed

Hinojosa, C A; Olivares-Cruz, S; Laparra-Escareno, H; Sanchez-Castro, S; Tamayo-Garcia, B; Anaya-Ayala, J E

2016-12-02

Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only

The Lectin Pathway in Thrombotic Conditions-A Systematic Review.

PubMed

Larsen, Julie Brogaard; Hvas, Christine Lodberg; Hvas, Anne-Mette

2018-06-04

The lectin pathway of the complement system can activate the coagulation system in vitro, but the role of the lectin pathway in haemostatic activation and thrombosis in vivo is not clear. We performed a systematic review of the existing literature on associations between the lectin pathway and arterial and venous thrombosis, in accordance with the Assessing the Methodological Quality of Systematic Reviews guidelines. PubMed and Embase were searched from January 1990 to March 2017. We included original studies on human study populations investigating associations between the lectin pathway (protein serum levels, genotype or gene expression) and thrombotic conditions or laboratory coagulation markers. Exclusion criteria were case studies including fewer than five cases, conference abstracts or any other language than English. In total, 43 studies were included which investigated associations between the lectin pathway and cardiovascular thrombotic events (CVEs) ( n  = 22), ischaemic stroke ( n  = 9), CVE and stroke ( n  = 1) and other conditions (systemic lupus erythematosus [ n  = 6], sepsis-related coagulopathy [ n  = 3], pulmonary embolism [ n  = 1], asparaginase treatment [ n  = 1]). Studies on the lectin pathway and CVE risk reported discrepant results, as both high and low mannose-binding lectin (MBL) serum levels were found to correlate with increased CVE risk. In ischaemic stroke patients, occurrence of stroke as well as increased stroke severity and poor outcome were consistently associated with high serum MBL. For other thromboembolic conditions, only few studies were identified. In conclusion, lectin pathway activation may negatively influence outcome after ischaemic stroke and possibly contribute to CVE risk. Further research is warranted to elucidate the role of the lectin pathway in other thrombotic conditions. Schattauer GmbH Stuttgart.

Cumulative Review of Thrombotic Microangiopathy, Thrombotic Thrombocytopenic Purpura, and Hemolytic Uremic Syndrome Reports with Subcutaneous Interferon β-1a.

PubMed

Ben-Amor, Ali-Frédéric; Trochanov, Anton; Fischer, Tanya Z

2015-05-01

Rare cases of thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), have been reported with interferon β products. We performed a cumulative review of TMA cases recorded in a Global Safety Database for patients with multiple sclerosis who received subcutaneous interferon β-1a treatment. Search criteria were: all reported cases, serious and non-serious, from all sources (including non-health care professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or company. Data lock was May 3, 2014, with additional analysis of cases reported between August 1, 2014-November 30, 2014. Ninety-one patient cases (76.9% female) with 105 events were retrieved. Time to onset varied from 2 months to 14 years, and in 31.9% of patients the event occurred within 2 years of treatment initiation. Seven patients had a fatal outcome (five were secondary to other causes and two reported insufficient information). Forty-four patients recovered, 32 patients had not recovered at the time of the report, and in eight cases outcome was either not reported or unknown. Treatment was discontinued in 84.6% (77/91) of patients. In 67% (61/91) of patients, the reporter suspected a causal association between treatment and TMA/TTP-HUS. Risk factors and/or confounding factors were present in 45.1% (41/91) of patients. Early prodromal syndrome or specific patterns were not detected, although 54.9% (50/91) of cases contained insufficient information. Overall reporting rate of TMA/TTP-HUS was estimated as 7.2 per 100,000 patient-years. Reporting rates for human serum album (HSA)-containing and HSA-free formulations were 5.72 and 7.68 per 100,000 patient-years, respectively. No new signal relating specifically to increased frequency of TMA/TTP-HUS with HSA-free subcutaneous interferon β-1a was detected and no additional risk mitigation measures are required regarding the different

Outcome of severe adult thrombotic microangiopathies in the intensive care unit.

PubMed

Pene, Frédéric; Vigneau, Cécile; Auburtin, Marc; Moreau, Delphine; Zahar, Jean-Ralph; Coste, Joël; Heshmati, Farhad; Mira, Jean-Paul

2005-01-01

Thrombotic microangiopathies, namely thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, are uncommon microvascular occlusive diseases. Despite the dramatic improvement in the outcome by exogenous plasma supply, either through plasma infusion or through plasma exchange, patients frequently require support in the intensive care unit. In the present study, we evaluated the outcome of a large cohort of patients with severe thrombotic microangiopathies. A retrospective multicenter study from January 1998 to June 2001. Fourteen French university hospital medical intensive care units. Sixty three adult patients with severe thrombotic microangiopathies. Of the 63 patients, 19 had a clinical presentation of thrombotic thrombocytopenic purpura, 18 had hemolytic uremic syndrome and 26 had combined neurologic and renal failures. Infections were the main etiology associated with thrombotic microangiopathies. The mortality rate was 35%. Of the survivors, all achieved complete remission. Whereas neurologic failure assessed through the Glasgow coma scale was an independent predictor of mortality [HR=0.845 (CI 95%: 0.759-0.940), P=0.002], renal impairment did not appear to be an adverse prognostic factor. The use of plasma exchange was independently associated with survival [HR=0.269 (CI 95%: 0.104-0.691), P=0.006]. Thrombotic microangiopathies with severe organ dysfunctions leading to hospitalization in the intensive care unit are associated with high mortality. Neurologic impairment appears to be the main adverse prognostic factor correlated to mortality, and the study confirms the importance of plasma exchange in the treatment of high-risk patients.

Thrombotic complications of implanted central venous access devices: prospective evaluation.

PubMed

Labourey, Jean-Luc; Lacroix, Philippe; Genet, Dominique; Gobeaux, François; Martin, Jean; Venat-Bouvet, Laurence; Lavau-Denes, Sandrine; Maubon, Antoine; Tubiana-Mathieu, Nicole

2004-05-01

Implanted venous access devices (IVAD) are routinely used in oncologic patients. Thrombotic complication is a source of morbidity. During one year 246 patients with different solid neoplastic diseases received IVAD for chemotherapy administration. Two hundred forty-nine IVAD were placed percutaneously or by surgical cutdown. IVAD were flushed immediately after implantation with 3-5 mL of heparinized saline (100 U/mL). No monthly flush was required. A prospective evaluation of thrombotic complications was realised. in event of catheter dysfunction and/or clinical symptoms of phlebitis, a catheter opacification and/or a Doppler ultrasonography were performed. Twenty-three catheter dysfunctions were noted, corresponding to 13 catheter occlusions. Twelve patients presented clinical symptoms of phlebitis. Eleven venous thrombosis were diagnosed in this group; 10 by echo-Doppler and one by scanography. A unvaried statistic analysis using Fisher's test was performed to detect risk factors. Two factors were identified: the position of catheter tip above T4 (p < 0.001) and mediastinal or cervical lymph nodes larger than 6 cm (p < 0.001). The first increased the risk of catheter occlusion and the second increased the risk of phlebitis.

Evaluation of Plasma Platelet Microparticles in Thrombotic Thrombocytopenic Purpura.

PubMed

Tahmasbi, Leila; Karimi, Mehran; Kafiabadi, Sedigheh Amini; Nikougoftar, Mahin; Haghpanah, Sezaneh; Ranjbaran, Reza; Moghadam, Mohamad

2017-01-01

Platelet microparticles (PMPs) have a procoagulant activity about 50-100 times greater than active platelets due to high expression of negatively charged phospholipids on their surfaces. In this study, we evaluated microparticle immunophenotyping and also plasma PMPs level in patients with Thrombotic Thrombocytopenic Purpura (TTP) in Southern Iran. We had two study groups: 15 TTP patients and 15 healthy control group and PMPs from platelet concentrate (PC) at the 5 th day of storage. Microparticles were prepared in two steps, by low and high centrifugation followed by size confirmation via 'Dynamic Light Scattering (DLS)' Zetasizer. Immunophenotyping of PMPs was done via flow cytometry, using a FACS Calibur flow cytometer (BD, USA). PMPs counts were obtained using Partec-cyflow and Polysciences Microbeads (1 micron in diameter). Results were analyzed using FlowJo 7.6 (Treestar, USA) and Partec FlowMax software. Our results showed that the majority of microparticles in TTP patients and normal individuals were PMPs and also demonstrated that the plasma PMPs level in TTP patients was higher than the normal control group ( P -value<0.001). It seems that elevated PMPs level in TTP patients could be related to thrombotic events. Nevertheless, more studies are needed to confirm these results. © 2017 by the Association of Clinical Scientists, Inc.

Acute disseminated melioidosis giving rise to pneumonia and renal abscesses complicated with thrombotic thrombocytopenic purpura in a post partum woman: a case report.

PubMed

Wijewickrama, Piyumi Sachindra Alwis; Weerakoon, Rohini

2017-11-29

Melioidosis is an established endemic infection in Sri Lanka, caused by Burkholderia pseudomallei, a gram negative bacterium distributed in saprophytes in soil and surface water. Main mode of transmission is via percutaneous inoculation. Pneumonia is the most common presentation in acute disease. We report a 33 year old previously healthy Sinhalese female with an occupational exposure to surface water in paddy fields, who was on postpartum day 6 following an uncomplicated pregnancy and delivery via an elective caesarian section. She presented with a 1 day history of breathlessness, preceded by a brief episode of fever. She had occasional right side coarse crackles and pitting oedema of both lower limbs. Shortly after admission, she developed type one respiratory failure needing invasive mechanical ventilation. Initial chest x-ray revealed slight obliteration of right medial diaphragmatic border while echocardiogram revealed moderate pulmonary hypertension. Computed tomography pulmonary angiogram excluded a pulmonary embolism, but revealed bilateral multi-lobar consolidation. Abdominal computed tomography demonstrated bilateral pyelonephritis with renal abscesses. As initial cultures were inconclusive, melioidosis antibody levels were done due to high degree of suspicion, which was found to be positive with a titer of 1:2560. A diagnosis of melioidosis was made based on the suggestive clinical picture, exposure history and the highly positive antibody level. She developed left side focal seizures together with thrombocytopenia and microangiopathic haemolytic anemia, suggestive of thrombotic thrombocytopenic purpura. Magnetic resonance imaging of brain was negative for cerebral abscesses but revealed extensive minute haemorrhagic foci throughout the cerebrum. Thus, the final diagnosis was acute melioidosis causing pneumonia and renal abscesses, complicated with thrombotic thrombocytopenic purpura and sepsis. She demonstrated dramatic response to high dose meropenem

Prothrombin complex concentrate and fatal thrombotic adverse events: A complication to keep in mind.

PubMed

Tabet, Rabih; Shammaa, Youssef; Karam, Boutros; Yacoub, Harout; Lafferty, James

2018-05-13

Thromboembolic events such as deep vein thrombosis and pulmonary embolism are well-known complications that can occur after prothrombin complex concentrate therapy. However, acute myocardial infarction is a very rare but potentially life-threatening complication that was exclusively described in patients with bleeding disorders who received chronic and recurrent concentrate infusions. We report the case of a 70 year-old male patient with cholangiocarcinoma who was admitted to our hospital with worsening fatigue and weakness. His stay was complicated by uncontrolled bleeding secondary to rivaroxaban use and advanced liver disease. By the end of the prothrombin complex concentrate infusion used to reverse his coagulopathy, patient developed ST-segment elevation myocardial infarction with cardiogenic shock and passed away. This is the first reported case of acute myocardial infarction that occurs in a patient without hemophilia and after the first prothrombin complex concentrate infusion.

Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura.

PubMed

Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

2015-10-01

Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64-15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59-27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications.

Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

PubMed Central

Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

2015-01-01

Abstract Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.

PubMed

Sun, Yu-Yo; Morozov, Yury M; Yang, Dianer; Li, Yikun; Dunn, R Scott; Rakic, Pasko; Chan, Pak H; Abe, Koji; Lindquist, Diana M; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h post-tHI--significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼ 80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation.

Synergy of Combined tPA-Edaravone Therapy in Experimental Thrombotic Stroke

PubMed Central

Sun, Yu-Yo; Morozov, Yury M.; Yang, Dianer; Li, Yikun; Dunn, R. Scott; Rakic, Pasko; Chan, Pak H.; Abe, Koji; Lindquist, Diana M.; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h – but not at 4 h post-tHI – significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation. PMID:24911517

Future therapeutic directions for factor Xa inhibition in the prophylaxis and treatment of thrombotic disorders.

PubMed

Turpie, Alexander G G

2003-11-15

The targeted mechanism of factor Xa inhibition has been studied extensively, initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic surgical setting. Future therapeutic directions for selective factor Xa inhibition in the management of other thrombotic diseases are discussed. Thromboembolic diseases can occur in the venous or arterial sides of the circulatory system. Factor Xa inhibition is a targeted approach to anticoagulation that resulted from significant advances in our understanding of the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied extensively in the orthopedic surgical setting for the prophylaxis of VTE. Current investigations that are under way or completed evaluate the efficacy and safety of fondaparinux for the management of various thrombotic diseases. The future development of fondaparinux resides primarily in three therapeutic areas: prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes. For the prevention of VTE, fondaparinux has been studied as extended prophylaxis following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal surgical patients (PEGASUS and APOLLO), and for use in medical patients (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was investigated in phase 2 studies for the treatment of acute coronary syndromes, including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina (PENTUA). Encouraging data from these trials are the basis for phase 3 programs in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic clinical programs for fondaparinux in the management of thrombosis support the concept that targeted inhibition of coagulation is an effective advance in antithrombotic therapy.

Overweight individuals are at increased risk for thrombotic thrombocytopenic purpura.

PubMed

Nicol, Kathleen K; Shelton, Brent J; Knovich, Mary Ann; Owen, John

2003-11-01

Our understanding of the pathophysiology of thrombotic thrombocytopenic purpura, TTP, has increased dramatically in the past few years with the identification of the role of ADAMTS13. Nonetheless, risk factors for the development of acute TTP are few. Informally, obesity was felt to be common in patients with TTP and so a formal study was undertaken to further define this association. We report our data in 105 patients with classical TTP as defined by thrombocytopenia and microangiopathic hemolytic anemia. We found that marked obesity is a previously unrecognized risk factor with an associated odds ratio of 7.6. Interestingly, despite this increased risk, obesity might well be associated with lower mortality, although this did not reach statistical significance. Copyright 2003 Wiley-Liss, Inc.

[Research Progress on Role of Inflammasome in Development of Thrombotic Diseases -Review].

PubMed

Wang, Jin-Xia; Liu, Ai-Fei; Li, Fang-Lin; Chen, Yi-Jian

2017-08-01

Inflammasome is a group of polyprotein complexes located in the cytoplasm, its activation can induce the maturation and release of proinflammatory cytokines IL-1β and IL-18, and promote the early atherosclerosis. In the recent years, it is found that the inflammasome is activated in thrombotic deseases, moveover, the activated inflammasome and its activation induced cytokines promote the occurrence and development of thrombolic deseases, and show the unfavaourable effect on prognosis. With further exploration on the mechanisms of thrombotic diseases, the relationship between the inflammasome and thrombotic diseases increasingly become a hot spot of research. This review focuses on the action mechanisms of inflammasome in thrombotic diseases.

Stressful events and coping related to acute and sub-acute whiplash-associated disorders.

PubMed

Pettersson, Susanne; Bring, Annika; Åsenlöf, Pernilla

2017-03-01

Purpose To describe daily stressors affecting and coping strategies employed by individuals with whiplash-associated disorders (WAD) immediately to one month (acute) and three to four months (sub-acute) after injury events using a daily coping assessment. Levels of pain, anxiety, depressed mood and activity are also compared between phases. Method A descriptive prospective design with a content analysis approach was used. Participants completed daily coping assessments for one week during both acute and sub-acute phases. Main measure was whiplash-associated disorders-daily coping assessment (WAD-DCA). Results Nine participants used words describing recovery in the sub-acute phase; 31 described stressful events during both phases. Most frequently reported stressors were related to "symptoms", "emotions" and "occupations/studies". These were equally reported during both phases. Cognitive coping strategies were employed more often during the sub-acute phase (p = 0.008). The only behavioral strategy that increased in prevalence over time was the "relaxed" strategy (p = 0.001). Anxiety levels declined over time (p = 0.022). Conclusion The reported stressors were largely uniform across both acute and sub-acute phases; however, the use of cognitive coping strategies increased over time. The WAD-DCA captures individual stressors and coping strategies employed during a vulnerable phase of rehabilitation and can thus provide information that is useful to clinical practice. Implications for rehabilitation The WAD-DCA provides valuable information for clinical practice when employed during early phases of whiplash-associated disorder development. Reported stressors during the acute and sub-acute phases are essentially the same, whereas cognitive coping strategies grow in prevalence over time. Tailored treatments in early phases of whip-lash associated disorders may benefit from strategies aimed at matching patient-specific stressors with contextually adapted coping

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

PubMed

Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S; Stearns-Kurosawa, D J; Kurosawa, Shinichiro

2013-08-01

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

A single-center prospective study on the safety of plasma exchange procedures using a double-viral-inactivated and prion-reduced solvent/detergent fresh-frozen plasma as the replacement fluid in the treatment of thrombotic microangiopathy.

PubMed

Vendramin, Chiara; McGuckin, Siobhan; Alwan, Ferras; Westwood, John-Paul; Thomas, Mari; Scully, Marie

2017-01-01

Patients presenting with acute episodes of thrombotic microangiopathies (TMAs) require urgent access to plasma exchange (PEX). OctaplasLG, a solvent/detergent fresh-frozen plasma product that has undergone viral inactivation and prion reduction step, has been used in our institution since 2013, replacing Octaplas. We prospectively reviewed 981 PEX procedures where OctaplasLG was the replacement fluid in 90 patients admitted acutely with a TMA presentation within our institution from January 1, 2013, to December 31, 2015. We recorded citrate toxicities, plasma reactions, viral transfer, complications related to central venous catheter, and venous thrombotic events (VTEs). Citrate toxicities were 5.4%, plasma reactions were 2%, and all were classified as Grade 1 or 2. VTE had an incidence of 12.2%, although 50% of the episodes occurred in early remission when patients were not receiving PEX. No line insertions complications were recorded. Line-associated infections were 2.2%. Hepatitis B and C serology and human immunodeficiency virus (HIV) were checked on admission. There were four patients who may have had passive transient transfer of hepatitis B antibodies from pooled plasma. No hepatitis C or HIV viral transfer was documented after treatment and no seroconversion was detected after treatment. Our data have demonstrated that the incidence of complications during PEX is low and using OctaplasLG is comparable to the low incidence of reactions. No cases of anaphylaxis, transfusion-related acute lung injury, or fatal plasma reactions were seen. There was no evidence of viral transmission or seroconversion after treatment. © 2016 AABB.

Life after acquired thrombotic thrombocytopenic purpura: morbidity, mortality, and risks during pregnancy.

PubMed

Vesely, S K

2015-06-01

Patients who have recovered from their acute episode of acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) were once thought to have complete recovery except for risk of relapse. Data from previous publications from the Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry are summarized. Patients have decreased cognitive function and increased prevalence of hypertension, systemic lupus erythematosus, major depression, and albuminuria as compared to the expected values from the US population. The proportion of patients that died during the follow-up period was greater than expected based on the US population reference population. Among women who had a pregnancy following recovery from TTP, relapse during pregnancy or postpartum is uncommon, but the occurrence of preeclampsia may be increased. Thirteen of 16 pregnancies in these women resulted in healthy children. Increased morbidity and mortality in TTP patients following recovery suggest that TTP may be more of a chronic disorder than a disorder with acute episodes and complete recovery. © 2015 International Society on Thrombosis and Haemostasis.

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

PubMed

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

2016-12-31

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

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

PubMed Central

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

2016-01-01

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

Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis.

PubMed

Bolaños-Meade, J; Keung, Y K; López-Arvizu, C; Florendo, R; Cobos, E

1999-12-01

The combination of sickle cell disease crisis and thrombotic thrombocytopenic purpura has been described only a few times. Here we present the case of a patient with a hemolytic crisis due to sickle cell disease complicated by thrombotic thrombocytopenic purpura. We also review the cases previously reported and compare and contrast them, highlighting diagnostic challenges.

Nonbacterial thrombotic endocarditis presenting as intracerebral hemorrhage.

PubMed

Wigger, Olivier; Windecker, Stephan; Bloechlinger, Stefan

2016-12-01

Nonbacterial thrombotic endocarditis is a rare cause of valvular heart disease, most commonly associated with advanced malignancy. The morbidity of this kind of endocarditis lies in its tendency to embolize, while the valve function is usually preserved. The central nervous system is the most common site of embolization, leading to ischemic stroke. We report a case of nonbacterial thrombotic endocarditis complicated by intracerebral hemorrhage as the first manifestation of adenocarcinoma of the lung. The endocarditis led to severe aortic regurgitation. In view of the advanced stage of lung cancer, the patient refused further therapy. He passed away 3 weeks after first diagnosis of the adenocarcinoma.

Clinical correlates of acute pulmonary events in children and adolescents with sickle cell disease*

PubMed Central

Paul, Rabindra; Minniti, Caterina P.; Nouraie, Mehdi; Luchtman-Jones, Lori; Campbell, Andrew; Rana, Sohail; Onyekwere, Onyinye; Darbari, Deepika S.; Ajayi, Olaid; Arteta, Manuel; Ensing, Gregory; Sable, Craig; Dham, Niti; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

2013-01-01

Objectives We aimed to identify risk factors for acute pulmonary events in children and adolescents in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study. Methods Patients with hemoglobin SS (n=376) and other sickle cell genotypes (n=127) aged 3-20 years were studied at four centers in a cross-sectional manner. A sub-group (n=293) was followed for a median of 21 months (range 9-35). Results A patient-reported history of one or more acute pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in 195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By logistic regression, history of acute pulmonary events was independently associated with patient-reported history of asthma (p<0.0001), older age (p=0.001), >3 severe pain episodes in the preceding 12 months (p=0.002), higher tricuspid regurgitation velocity (TRV) (p=0.028), and higher white blood cell (WBC) count (p=0.043) among hemoglobin SS patients. History of acute pulmonary events was associated with >3 severe pain episodes (p=0.009) among patients with other genotypes. During follow-up, 43 patients (15%) had at least one new ACS episode including 11 without a baseline history of acute pulmonary events. History of acute pulmonary events (odds ratio 5.4; p<0.0001) and younger age (odds ratio 0.9; p=0.010) were independently associated with developing a new episode during follow-up. Conclusions Asthma history, frequent pain and higher values for TRV and WBC count were independently associated with history of acute pulmonary events in hemoglobin SS patients and frequent pain was associated in those with other genotypes. Measures to reduce pain episodes and control asthma may help to decrease the incidence of acute pulmonary events in SCD. PMID:23560516

High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation.

PubMed

Holy, Erik W; Besler, Christian; Reiner, Martin F; Camici, Giovanni G; Manz, Jasmin; Beer, Jürg H; Lüscher, Thomas F; Landmesser, Ulf; Tanner, Felix C

2014-11-01

Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

Auricular chondritis and thrombotic microangiopathy: an unusual combination revealing systemic lupus erythematosus.

PubMed

Bellon, Nathalia; Anguel, Nadia; Vandendries, Christophe; Goujard, Cecile; Lambotte, Olivier

2013-07-01

Thrombotic microangiopathy is a severe disorder, which is a cause of stroke in young patients. Etiologic investigations are mandatory to diagnose underlying disease. Systemic lupus erythematosus is one of the diseases, which can be associated with thrombotic microangiopathy. Although lupus diagnosis is usually easy, relying on characteristic clinical manifestations, rare symptoms can be misinterpreted. We report here a case of polychondritis, which was the first manifestation of a lupus-associated thrombotic microangiopathy. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

PubMed Central

Lever, Michael; George, Peter M.; Elmslie, Jane L.; Atkinson, Wendy; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

2012-01-01

Background Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. Methods Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. Principal Findings The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). Conclusions Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk. PMID:22649561

Worrying About Terrorism and Other Acute Environmental Health Hazard Events

PubMed Central

Babcock-Dunning, Lauren

2012-01-01

Objectives. To better understand why some people worry more about terrorism compared with others, we measured how much US residents worried about a terrorist event in their area and examined the association of their fears with their concerns about acute and chronic hazards and other correlates. Methods. In 2008 (n = 600) and 2010 (n = 651), we performed a random-digit dialing national landline telephone survey. We asked about worries about terrorism and 5 other environmental health hazard issues. We also collected demographic and socioeconomic data. Results. Only 15% worried “a great deal” about a terrorist event in their area and 18% to 33% were greatly concerned about other environmental issues. Fear about acute hazard events was a stronger predictor of a great deal of concern about terrorism than were age, race/ethnicity, gender, educational achievement, and other correlates. Conclusions. Those who worried most about acute environmental health hazard events were most likely to worry about terrorism. Also, those who were older, poorer, Blacks, or Latinos, or who lived in populous urban areas felt they were most vulnerable to terrorist attacks. We recommend methods to involve US citizens as part of disaster planning. PMID:22397346

Worrying about terrorism and other acute environmental health hazard events.

PubMed

Greenberg, Michael; Babcock-Dunning, Lauren

2012-04-01

To better understand why some people worry more about terrorism compared with others, we measured how much US residents worried about a terrorist event in their area and examined the association of their fears with their concerns about acute and chronic hazards and other correlates. In 2008 (n = 600) and 2010 (n = 651), we performed a random-digit dialing national landline telephone survey. We asked about worries about terrorism and 5 other environmental health hazard issues. We also collected demographic and socioeconomic data. Only 15% worried "a great deal" about a terrorist event in their area and 18% to 33% were greatly concerned about other environmental issues. Fear about acute hazard events was a stronger predictor of a great deal of concern about terrorism than were age, race/ethnicity, gender, educational achievement, and other correlates. Those who worried most about acute environmental health hazard events were most likely to worry about terrorism. Also, those who were older, poorer, Blacks, or Latinos, or who lived in populous urban areas felt they were most vulnerable to terrorist attacks. We recommend methods to involve US citizens as part of disaster planning.

Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

PubMed

Ivanes, Fabrice; Susen, Sophie; Mouquet, Frédéric; Pigny, Pascal; Cuilleret, François; Sautière, Karine; Collet, Jean-Philippe; Beygui, Farzin; Hennache, Bernadette; Ennezat, Pierre Vladimir; Juthier, Françis; Richard, Florence; Dallongeville, Jean; Hillaert, Marieke A; Doevendans, Pieter A; Jude, Brigitte; Bertrand, Michel; Montalescot, Gilles; Van Belle, Eric

2012-01-01

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). Our results

PREVALENCE OF POST-THROMBOTIC SYNDROME AFTER CARDIAC CATHETERIZATION

PubMed Central

Luceri, Michael J.; Tala, Joana A.; Weismann, Constance G.; Silva, Cicero T.; Faustino, E. Vincent S.

2015-01-01

BACKGROUND As the survival of children with cardiac disease increases, chronic complications of deep venous thrombosis from cardiac catheterization, particularly post-thrombotic syndrome, may be important to monitor for and treat, if needed. We aimed to determine the prevalence of this syndrome in children who underwent cardiac catheterization. PROCEDURE We conducted a cross-sectional study of children <18 years old at least 1 year from first catheterization through the femoral vein. We used the Manco-Johnson instrument, the only tool validated in children, to diagnose post-thrombotic syndrome. We defined the syndrome as a score ≥1. It was considered physically and functionally significant if the score was ≥1 in both physical and functional domains of the instrument. We also conducted ultrasonography to assess for thrombosis and valvular insufficiency. RESULTS We enrolled 62 children with a median age of 4 months during catheterization and a median of 5.4 years since catheterization. A total of 40 children had post-thrombotic syndrome (prevalence: 64.5%; 95% confidence interval: 51.3%–76.3%), the majority of which were mild. Presence of cyanotic congenital heart disease, total number of catheterizations, use of antithrombotic agents at any time after the first catheterization, age at first catheterization, or time since first catheterization was not associated with the syndrome. A total of 7 children (prevalence: 11.3%; 95% confidence interval: 3.2%–19.4%) had physically and functionally significant syndrome. None of the children had abnormalities on ultrasonography at the time of enrollment. CONCLUSIONS Post-thrombotic syndrome is a common complication after cardiac catheterization. Manifestations are usually mild and unlikely to require treatment. PMID:25663038

CFD-based Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms

NASA Astrophysics Data System (ADS)

Sengupta, Dibyendu; Kung, Ethan; Kahn, Andrew; Burns, Jane; Marsden, Alison

2012-11-01

Coronary aneurysms occur in 25% of untreated Kawasaki Disease (KD) patients and put patients at increased risk for myocardial infarction and sudden death. Clinical guidelines recommend using aneurysm diameter >8 mm as the arbitrary criterion for treating with anti-coagulation therapy. This study uses patient-specific modeling to non-invasively determine hemodynamic parameters and quantify thrombotic risk. Anatomic models were constructed from CT angiographic image data from 5 KD aneurysm patients and one normal control. CFD simulations were performed to obtain hemodynamic data including WSS and particle residence times (PRT). Thrombosis was clinically observed in 4/9 aneurysmal coronaries. Thrombosed vessels required twice as many cardiac cycles (mean 8.2 vs. 4.2) for particles to exit, and had lower mean WSS (1.3 compared to 2.8 dynes/cm2) compared to vessels with non-thrombosed aneurysms of similar max diameter. 1 KD patient in the cohort with acute thrombosis had diameter < 8 mm. Regions of low WSS and high PRT predicted by simulations correlated with regions of subsequent thrombus formation. Thrombotic risk stratification for KD aneurysms may be improved by incorporating both hemodynamic and geometric quantities. Current clinical guidelines to assess patient risk based only on aneurysm diameter may be misleading. Further prospective study is warranted to evaluate the utility of patient-specific modeling in risk stratifying KD patients with coronary aneurysms. NIH R21.

Acute cor pulmonale due to pulmonary tumour thrombotic microangiopathy from renal cell carcinoma.

PubMed

Story, Maria; Kwon, Sook Kyung; Robinson, Robert; Fortis, Spyridon

2017-06-28

We report the case of a previously healthy man who presented with subacute dyspnoea after a long drive. He developed hypoxic respiratory failure, thought secondary to a massive pulmonary embolism and was treated with tissue plasminogen activator but died in the hospital despite aggressive medical measures. Autopsy revealed pulmonary tumour thrombotic microangiopathy (PTTM) from papillary renal cell carcinoma. PTTM is a rare clinicopathological syndrome that clinically results in symptoms of dyspnoea and right heart failure. Pathologically, a localised paraneoplastic process evolves from tumour microemboli in the pulmonary arterioles, resulting in fibrocellular proliferation and narrowing of the vessels, causing subacute right heart failure. To our knowledge, this is the first case of PTTM due to papillary renal cell carcinoma. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Disaster metrics: quantification of acute medical disasters in trauma-related multiple casualty events through modeling of the Acute Medical Severity Index.

PubMed

Bayram, Jamil D; Zuabi, Shawki

2012-04-01

The interaction between the acute medical consequences of a Multiple Casualty Event (MCE) and the total medical capacity of the community affected determines if the event amounts to an acute medical disaster. There is a need for a comprehensive quantitative model in MCE that would account for both prehospital and hospital-based acute medical systems, leading to the quantification of acute medical disasters. Such a proposed model needs to be flexible enough in its application to accommodate a priori estimation as part of the decision-making process and a posteriori evaluation for total quality management purposes. The concept proposed by de Boer et al in 1989, along with the disaster metrics quantitative models proposed by Bayram et al on hospital surge capacity and prehospital medical response, were used as theoretical frameworks for a new comprehensive model, taking into account both prehospital and hospital systems, in order to quantify acute medical disasters. A quantitative model called the Acute Medical Severity Index (AMSI) was developed. AMSI is the proportion of the Acute Medical Burden (AMB) resulting from the event, compared to the Total Medical Capacity (TMC) of the community affected; AMSI = AMB/TMC. In this model, AMB is defined as the sum of critical (T1) and moderate (T2) casualties caused by the event, while TMC is a function of the Total Hospital Capacity (THC) and the medical rescue factor (R) accounting for the hospital-based and prehospital medical systems, respectively. Qualitatively, the authors define acute medical disaster as "a state after any type of Multiple Casualty Event where the Acute Medical Burden (AMB) exceeds the Total Medical Capacity (TMC) of the community affected." Quantitatively, an acute medical disaster has an AMSI value of more than one (AMB / TMC > 1). An acute medical incident has an AMSI value of less than one, without the need for medical surge. An acute medical emergency has an AMSI value of less than one with

Overwork accelerates thrombotic reaction: implications for the pathogenesis of Karoshi.

PubMed

Otsui, Kazunori; Yamamoto, Junichiro; Inoue, Nobutaka

2018-02-01

Work-related stressors are potential causes of cardiovascular diseases (CVDs) and stroke; however, the pathophysiological mechanisms by which occupational stress induces and exacerbates CVDs remain unclear. The global thrombosis test (GTT) is a novel in vitro assay for evaluating both thrombotic reactions and subsequent thrombolysis. The time required to form an occlusive thrombus with the GTT, called as the occlusion time (OT), and the time to lyse the thrombus, the lysis time (LT), are markers of thrombotic and thrombolytic reactions, respectively. We investigated the impact of work-related stress on the thrombotic and thrombolytic reactions in 46 healthy medical residents. Off-duty or on-duty blood samples were collected on the mornings of non-work days or after the night duty on the emergent room respectively. The duration of sleep was significantly shorter during night duty than during off-duty nights [2.25 (1.0, 3.0) h vs. 6.0 (5.0, 7.0) h; p < 0.001]. Baseline OT was 310.3 (260.9, 437.7) s. whereas the on-duty OT was significantly shortened [284.2 (230.5, 355.8) s; p < 0.01]. LT was significantly prolonged during overwork conditions compared with off-duty conditions [1547 (1346, 1908) s vs. 1470 (1219, 1692) s; p < 0.05]. Overwork accelerates the thrombotic reactions. These reactions might explain the pathogenesis of overwork-related CVDs. The GTT is a good tool for evaluating of the level of fatigue.

Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura

PubMed Central

Rakhmanina, Natella; Wong, Edward CC; Davis, Jeremiah C; Ray, Patricio E

2014-01-01

HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression. PMID:25429351

Acute Kidney Injury in Pregnancy-specific Disorders.

PubMed

Prakash, J; Ganiger, V C

2017-01-01

The incidence of acute kidney injury in pregnancy (P-AKI) has declined significantly over the last three decades in developing countries. However, it is still associated with significant fetomaternal mortality and morbidity. The diagnosis of P-AKI is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate (GFR) are not validated in this population. The incidence of P-AKI with respect to total AKI cases has decreased in the last three decades from 25% in 1980s to 9% in 2000s at our centre. During the first trimester of gestation, AKI develops most often due to septic abortion or hyperemesis gravidarum. Septic abortion related AKI with respect to total AKI decreased from 9% to 5% in our study. Prevention of unwanted pregnancy and avoidance of septic abortion are keys to eliminate abortion associated AKI in early pregnancy. However, we have not seen AKI on account of hyperemesis gravidarum over a period of 33 years at our center. In the third trimester, the differential diagnosis of AKI in association with pregnancy specific conditions namely preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies of pregnancy (P-TMA) is more challenging, because these 3 conditions share several clinical features of thrombotic microangiopathy which makes the diagnosis very difficult on clinical grounds. It is imperative to distinguish these conditions to make appropriate therapeutic decisions. Typically, AFLP and HELLP syndrome improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for pregnancy associated thrombotic microangioathies (P-TMA). We observed that preclampsia/eclampsia is the most common cause of AKI in late third trimester and postpartum periods followed by puerperal sepsis and postpartum hemorrhage. Pregnancy-associated thrombotic microangiopathies (aHUS/TTP) and AFLP are rare causes of AKI during pregnancy in developing countries.

Acute Kidney Injury in Pregnancy-specific Disorders

PubMed Central

Prakash, J.; Ganiger, V. C.

2017-01-01

The incidence of acute kidney injury in pregnancy (P-AKI) has declined significantly over the last three decades in developing countries. However, it is still associated with significant fetomaternal mortality and morbidity. The diagnosis of P-AKI is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate (GFR) are not validated in this population. The incidence of P-AKI with respect to total AKI cases has decreased in the last three decades from 25% in 1980s to 9% in 2000s at our centre. During the first trimester of gestation, AKI develops most often due to septic abortion or hyperemesis gravidarum. Septic abortion related AKI with respect to total AKI decreased from 9% to 5% in our study. Prevention of unwanted pregnancy and avoidance of septic abortion are keys to eliminate abortion associated AKI in early pregnancy. However, we have not seen AKI on account of hyperemesis gravidarum over a period of 33 years at our center. In the third trimester, the differential diagnosis of AKI in association with pregnancy specific conditions namely preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies of pregnancy (P-TMA) is more challenging, because these 3 conditions share several clinical features of thrombotic microangiopathy which makes the diagnosis very difficult on clinical grounds. It is imperative to distinguish these conditions to make appropriate therapeutic decisions. Typically, AFLP and HELLP syndrome improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for pregnancy associated thrombotic microangioathies (P-TMA). We observed that preclampsia/eclampsia is the most common cause of AKI in late third trimester and postpartum periods followed by puerperal sepsis and postpartum hemorrhage. Pregnancy-associated thrombotic microangiopathies (aHUS/TTP) and AFLP are rare causes of AKI during pregnancy in developing countries. PMID:28761227

Defining the Thrombotic Risk in Patients with Myeloproliferative Neoplasms

PubMed Central

Vianello, Fabrizio; Battisti, Anna; Cella, Giuseppe; Marchetti, Marina; Falanga, Anna

2011-01-01

Polycythemia vera (PV) and essential thrombocythemia (ET) are two Philadelphia-negative myeloproliferative neoplasms (MPN) associated with an acquired mutation in the JAK2 tyrosine kinase gene. There is a rare incidence of progression to myelofibrosis and myeloid metaplasia in both disorders, which may or may not precede transformation to acute myeloid leukemia, but thrombosis is the main cause of morbidity and mortality. The pathophysiology of thrombosis in patients with MPN is complex. Traditionally, abnormalities of platelet number and function have been claimed as the main players, but increased dynamic interactions between platelets, leukocytes, and the endothelium do probably represent a fundamental interplay in generating a thrombophilic state. In addition, endothelial dysfunction, a well-known risk factor for vascular disease, may play a role in the thrombotic risk of patients with PV and ET. The identification of plasma markers translating the hemostatic imbalance in patients with PV and ET would be extremely helpful in order to define the subgroup of patients with a significant clinical risk of thrombosis. PMID:21623459

[Thrombotic skin gangrene: A rare extra-intestinal manifestation of ulcerative colitis].

PubMed

Aounallah, A; Ghariani Fetoui, N; Ghariani, N; Korbi, M; Mokni, S; Boussofara, L; Saidi, W; Ksiaa, M; Ben Jazia, I; Guerfala, M; Sriha, B; Belajouza, C; Denguezli, M; Nouira, R

2017-02-01

Thrombotic cutaneous gangrene is a rare extra-intestinal manifestation of ulcerative colitis with a severe prognosis. A 35-year-old woman with a 7-year history of ulcerative colitis presented with extensive ecchymotic lesions that began a few hours earlier. On examination, she was febrile with multiple necrotic lesions. Skin biopsy showed multiple microthrombi in the dermal vessels. A diagnosis of thrombotic cutaneous gangrene was established. The patient was treated with heparin and systemic corticosteroids. The majority of cutaneous lesions showed improvement after 1 month. Thrombophlebitis of the left lower limb occurred subsequently. Thrombotic cutaneous gangrene is attributed to microvascular thrombosis, which arises from the hypercoagulability observed in ulcerative colitis. Complete blood and coagulation tests must be performed and early anticoagulation with heparin must be considered in order to prevent the progression of cutaneous infarction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Stressful life events and acute kidney injury in intensive and semi-intensive care unities.

PubMed

Diniz, Denise Para; Marques, Daniella Aparecida; Blay, Sérgio Luis; Schor, Nestor

2012-03-01

Several studies point out that pathophysiological changes related to stress may influence renal function and are associated with disease onset and evolution. However, we have not found any studies about the influence of stress on renal function and acute kidney injury. To evaluate the association between stressful life events and acute kidney injury diagnosis, specifying the most stressful classes of events for these patients in the past 12 months. Case-control study. The study was carried out at Hospital São Paulo, in Universidade Federal de São Paulo and at Hospital dos Servidores do Estado de São Paulo, in Brazil. Patients with acute kidney injury and no chronic disease, admitted to the intensive or semi-intensive care units were included. Controls included patients in the same intensive care units with other acute diseases, except for the acute kidney injury, and also with no chronic disease. Out of the 579 patients initially identified, 475 answered to the Social Readjustment Rating Scale (SRRS) questionnaire and 398 were paired by age and gender (199 cases and 199 controls). The rate of stressful life events was statistically similar between cases and controls. The logistic regression analysis to detect associated effects of the independent variables to the stressful events showed that: increasing age and economic classes A and B in one of the hospitals (Hospital São Paulo - UNIFESP) increased the chance of a stressful life event (SLE). This study did not show association between the Acute Kidney Injury Group with a higher frequency of stressful life events, but that old age, higher income, and type of clinical center were associated.

Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial.

PubMed

Cornel, Jan H; Lopes, Renato D; James, Stefan; Stevens, Susanna R; Neely, Megan L; Liaw, Danny; Miller, Julie; Mohan, Puneet; Amerena, John; Raev, Dimitar; Huo, Yong; Urina-Triana, Miguel; Gallegos Cazorla, Alex; Vinereanu, Dragos; Fridrich, Viliam; Harrington, Robert A; Wallentin, Lars; Alexander, John H

2015-04-01

Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in

[Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

PubMed

García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

2009-02-01

Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk.

PubMed

Lee, Jee-Soo; Gu, JaYoon; Park, Hee Sue; Yoo, Hyun Ju; Kim, Hyun Kyung

2017-05-01

Highly specific assays for measuring antiphospholipid antibodies (aPLs) are required for accurate assessment of thrombotic risk. aPLs against β2-glycoprotein I domain I (anti-β2GPIdI) and against prothrombin complexed with phosphatidylserine (anti-PS/PT) have been recently identified as being associated with a hypercoagulable state. This study evaluated the synergism between anti-β2GPIdI and anti-PS/PT for predicting thrombotic events. A total of 180 patients with clinical suspicion of hypercoagulability were evaluated. The plasma levels of lupus anticoagulant (LA) and antibodies against anticardiolipin (anti-CL) (IgG and IgM), β2GPI (IgG and IgM), PS/PT (IgG and IgM), and β2GPI dI (IgG) were measured. IgG anti-β2GPIdI and LA were highly associated with thrombosis. Mean values and positivity rates of IgG anti-β2GPI dI and IgG anti-PS/PT were significantly higher in the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+) than in the other groups. Interestingly, the thrombotic risk [odds ratio (OR) 24.400, 95% confidence interval (CI) 1.976-63.273, p<0.001] of the newly defined triple positive group (LA+, IgG anti-CL+, IgG anti-β2GPIdI+; OR 11.182, 95% CI 1.976-63.273, p=0.006) was more than twice that of the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+). Double positivity for IgG anti-PS/PT and IgG anti-β2GPI also indicated significant thrombotic risk (OR 7.467, 95% CI 2.350-23.729, p=0.001). Furthermore, the thrombotic risk associated with double positivity for IgG anti-PS/PT and IgG anti-β2GPIdI was markedly elevated (OR 33.654, 95% CI 6.322-179.141, p<0.001). Our data suggest that simultaneous measurement of IgG anti-β2GPIdI and IgG anti-PS/PT may improve clinical decision-making for aPL-positive patients.

How We Identify and Manage Patients with Inadequately Controlled Polycythemia Vera.

PubMed

Reiter, Andreas; Harrison, Claire

2016-10-01

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by an overactive Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway through mutations in JAK2 exons 12 or 14 (JAK2 V617F). The dominant clinical characteristics include erythrocytosis (with or without leukocytosis/thrombocytosis), thrombotic events, and symptoms. Increased risk of mortality is mainly caused by thrombotic events and progression to post-polycythemia vera myelofibrosis (PPV-MF) or secondary acute myeloid leukemia (sAML). The most important prognostic factors include age and a history of thrombotic events, although recent evidence has indicated that leukocytosis and additional cytogenetic aberrations may also be of significant prognostic value. First-line therapies include aspirin and phlebotomies, which significantly reduce the incidence of thrombotic events and prolong survival. Cytoreductive treatment with hydroxyurea (approved) and conventional or pegylated interferon-α (effective, but not approved in many countries) is initiated for high-risk or inadequately controlled disease, e.g., uncontrolled hematocrit, leukocytosis, thrombocytosis, thrombotic events, splenomegaly, or symptoms. However, some patients may not receive initial benefit from first-line therapy or may become resistant or intolerant in due course. Although second-line treatment options are limited, clinical trials have shown the efficacy of ruxolitinib toward improving blood counts, enlarged spleen, and symptoms and potentially reducing thrombotic events. Identification of patients with uncontrolled PV is important for clinical care, as such patients have a high risk of complications, and future studies with JAK inhibitors or other agents alone or in combination are needed to test their potential to reduce rates of thrombotic events and transformation to PPV-MF or sAML.

Understanding Smoking after Acute Illness: An Application of the Sentinel Event Method

PubMed Central

Abar, Beau; Bock, Beth; Chapman, Gretchen; Boudreaux, Edwin D.

2016-01-01

The Sentinel Event Theory provides a stepwise approach for building models to understand how negative events can spark health behavior change. This study tested a preliminary model using the Sentinel Events Method in a sample (N = 300) of smokers who sought care for acute cardiac symptoms. Patients completed measures on: smoking-related causal attribution, perceived severity of the acute illness event, illness-related fear, and intentions to quit smoking. Patients were followed up one week after the health event and a 7 day time line follow back (TLFB) was completed to determine abstinence from tobacco. Structural equation models were performed using average predictor scale scores at baseline, as well as three different time anchors for ratings of illness severity and illness-related fear. Quit intentions, actual illness severity, and age were consistent, positive, independent predictors of 7 day point prevalence abstinence. Additional research on the influences of perceptions and emotional reactions is warranted. PMID:25563437

Eligibility for medical thromboprophylaxis based on risk-factor weights, and clinical thrombotic event rates.

PubMed

Millar, J Alasdair; Lett, Joanne E; Bagley, Leonard J; Densie, Ian K

2012-04-16

To measure eligibility for medical thromboprophylaxis using two Australasian guidelines - the Australia and New Zealand Working Party Guidelines [WPG] and the National Health and Medical Research Council Guidelines [NHMRCG]) - and proposed new guidelines based on risk-factor weights; and to measure the incidence of clinical venous thromboembolism (VTE) events in medical patients ("ensuing VTE"). Prospective case-note audit in an acute medical ward of Southland Hospital, a regional hospital in Invercargill, New Zealand, among all 595 patients who were discharged consecutively from 21 November 2010 to 7 March 2011. Of these, 245 were excluded on clinical grounds or because they were under the care of the authors. The primary outcome was eligibility for prophylaxis under each guideline. Secondary outcomes included incidence of ensuing VTEs, use of thromboprophylaxis, drug acquisition costs with each guideline, and bedside practicability of a guideline based on risk-factor weights. Nineteen per cent of patients were eligible under the new guidelines, compared with 80%, 88% and 36% under the WPG and two interpetations of the NHMRCG, respectively. One patient had an ensuing VTE. The new guideline had lower drug acquisition costs and was suitable for bedside use. Clinical VTE events are rare in medical patients, and medical VTE thromboprophylaxis needs to be more focused. The new guideline has performance characteristics th@satisfy this need.

[Thrombotic Microangiopathies].

PubMed

Schubert, Jörg; Dechant, Michael

2018-06-01

Thrombotic microangiopathies are almost devastating diseases leading to death at high frequency if untreated. They consist of at least five distinct entities, TTP, HUS, aHUS, TMA due to drug interference, systemic disease or post therapy TMA. Around 10 years ago there was only one established therapeutic approach as plasmapheresis. Meanwhile, there are new drugs been licensed or within licensing process. Patients with atypical HUS can be treated successfully by the Complement inhibitor Eculizumab. In addition, there is a new inhibitor of von-Willebrand-Polymerisation available. Caplacizumab provides a significantly better remission and decrease in TMA-related death. For therapy associated TMA as VOD/SOS Defibrotide could be established within a phase III study to significantly improve outcomes. In order to select these new medical approaches individual diagnostic parameters need to be established in order to rapidly distinguish between the TMA entities and start targeted therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

PubMed

Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

2015-11-01

Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4). © 2015 Wiley Periodicals, Inc.

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2015-09-16

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. This is an update of the review first published in 2013. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) ((CENTRAL) 2015, Issue 8). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two review authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review there is currently insufficient evidence to determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2013-04-30

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review it is not possible to support the use of rutosides in the prevention of PTS. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

JAK2 V617F, MPL, and CALR mutations in essential thrombocythaemia and major thrombotic complications: a single-institute retrospective analysis.

PubMed

Pósfai, Éva; Marton, Imelda; Király, Péter Attila; Kotosz, Balázs; Kiss-László, Zsuzsanna; Széll, Márta; Borbényi, Zita

2015-07-01

Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000), red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p = 0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.

Influenza-associated thrombotic microangiopathies.

PubMed

Bitzan, Martin; Zieg, Jakub

2017-09-07

Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity <10%. Median age was 15 years (range 0.5-68 years), two thirds were male. Oligoanuria was documented in 81% and neurological involvement in 40% of patients. Serum C3 was reduced in 5 out of 14 patients (36%); Coombs test was negative in 7 out of 7 and elevated fibrin/fibrinogen degradation products were documented in 6 out of 8 patients. Pathogenic complement gene mutations were found in 7 out of 8 patients tested (C3, MCP, or MCP combined with CFB or clusterin). Twenty out of 24 patients recovered completely, but 3 died (12%). Ten of the surviving patients underwent plasma exchange (PLEX) therapy, 5 plasma infusions. Influenza-mediated HUS or TTP is rare. A sizable proportion of tested patients demonstrated mutations associated with alternative pathway of complement dysregulation that was uncovered by this infection. Further research is warranted targeting the roles of viral neuraminidase, enhanced virus-induced complement activation and/or ADAMTS13 antibodies, and rational treatment approaches.

Safety of Pregnancy After Cerebral Venous Thrombosis: Results of the ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis)-2 PREGNANCY Study.

PubMed

Aguiar de Sousa, Diana; Canhão, Patrícia; Crassard, Isabelle; Coutinho, Jonathan; Arauz, Antonio; Conforto, Adriana; Béjot, Yannick; Giroud, Maurice; Ferro, José M

2017-11-01

Pregnancy is associated with increased risk of venous thrombotic events, including cerebral venous thrombosis. We aimed to study the complications and outcome of subsequent pregnancies in women with previous cerebral venous thrombosis. Follow-up study of women with acute cerebral venous thrombosis at childbearing age included in a previously described cohort (International Study of Cerebral Vein and Dural Sinus Thrombosis). Patients were interviewed by local neurologists to assess rate of venous thrombotic events, pregnancy outcomes, and antithrombotic prophylaxis during subsequent pregnancies. A total of 119 women were included, with a median follow-up of 14 years. Eighty-two new pregnancies occurred in 47 women. In 83% (68 of 82), some form of antithrombotic prophylaxis was given during at least 1 trimester of pregnancy or puerperium. Venous thrombotic events occurred in 3 pregnancies, including 1 recurrent cerebral venous thrombosis. Two of the 3 women were on prophylactic low-molecular-weight heparin at the time of the event. Outcomes of pregnancies were 51 full-term newborns, 9 preterm births, 2 stillbirths, and 20 abortions (14 spontaneous). In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent. © 2017 American Heart Association, Inc.

Thrombotic thrombocytopenic purpura possibly triggered by Graves’ disease

PubMed Central

Chitnis, Saurabh D; Mene-Afejuku, Tuoyo O; Aujla, Amandeep; Shady, Ahmed; Gil, Gaby S; Cativo, Eder Hans; Popescu-Martinez, Andrea

2017-01-01

Abstract Thrombotic thrombocytopenic purpura (TTP) is a part of a spectrum of thrombotic microangiopathy syndromes which are mainly characterized by platelet aggregation causing microangiopathic hemolytic anemia, thrombocytopenia and microvascular occlusion. In literature, very few cases expressing a direct association between pre-existing Grave’s disease and TTP have been described. A 37-year-old African–American woman with past medical history of Grave’s disease and polysubstance abuse who presented with complaints of dyspnoea at rest and chest pain was diagnosed to have TTP on further evaluation. Patient also showed severely elevated thyroid hormones and suppressed thyroid stimulating hormone levels indicating severe thyrotoxicosis. Initiation of prompt management of TTP and thyrotoxicosis led to a favorable patient outcome. In conclusion, patients presenting with thyrotoxicosis, thrombocytopenia and microangioapthic hemolytic anemia without an alternative cause should be treated and screened for TTP due to the high fatality associated with untreated or untimely detection of this disease. PMID:29744115

Acute Kidney Injury in Pregnancy.

PubMed

Jim, Belinda; Garovic, Vesna D

2017-07-01

Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. In difficult and rare cases, a renal biopsy may need to be considered for the exact diagnosis and to facilitate appropriate treatment, but the risks and benefits need to be carefully weighed. The use of eculizumab for the treatment of atypical HUS has demonstrated efficacy in early case reports. Non-pregnancy related causes such as volume depletion and pyelonephritis require early and aggressive resuscitative as well as antibiotic measures respectively. We will discuss in this review the various etiologies of AKI in pregnancy, current diagnostic approaches, and the latest treatment strategies. Given the recent trends of increasing maternal age at the time of pregnancy, and the availability of modern reproductive methods increase the risks of AKI in pregnancy in the coming years. Copyright © 2017 Elsevier Inc. All rights reserved.

Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model.

PubMed

Kuijpers, M J E; Gilio, K; Reitsma, S; Nergiz-Unal, R; Prinzen, L; Heeneman, S; Lutgens, E; van Zandvoort, M A M J; Nieswandt, B; Egbrink, M G A Oude; Heemskerk, J W M

2009-01-01

Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe(-/-) mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo.

Association of Antihypertensive Medication Adherence With Healthcare Use and Medicaid Expenditures for Acute Cardiovascular Events.

PubMed

Yang, Zhuo; Howard, David H; Will, Julie; Loustalot, Fleetwood; Ritchey, Matthew; Roy, Kakoli

2016-05-01

We assessed the impact of antihypertensive medication (AHM) adherence on the incidence and associated Medicaid costs of acute cardiovascular disease (CVD) events among Medicaid beneficiaries. The study cohort (n=59,037) consists of nonelderly adults continuously enrolled (36 mo and above) in a Medicaid fee-for-service program. AHM adherence was calculated using the medication possession ratio (MPR) and stratified to low (MPR<60%), moderate (60%≤MPR<80%), and high (MPR≥80%) levels. We used a proportional hazard model to estimate risk for acute CVD events and generalized linear models to estimate Medicaid per-patient-per-year costs. Low and moderate adherence subgroups had about 1.8 and 1.4 times higher risk of acute CVD events, compared with high adherence subgroup. By adherence level, Medicaid per-patient per-year costs for (1) CVD-related emergency department visits and hospitalizations were $661 (low), $479 (moderate), and $343 (high) and (2) AHMs were $430 (low), $604 (moderate), and $664 (high). Costs for CVD events and AHMs combined were similar across adherence subgroups. Lower adherence to AHM was associated with progressively higher CVD risk. The increase in medication cost from higher AHM adherence was offset solely by reduced Medicaid spending on acute CVD events.

Does the circadian pattern for acute cardiac events presentation vary with fasting?

PubMed

Al Suwaidi, J; Bener, A; Gehani, A A; Behair, S; Al Mohanadi, D; Salam, A; Al Binali, H A

2006-01-01

Over one billion Muslims fast worldwide during the month of Ramadan. The impact of fasting on circadian presentation with acute cardiac events is unknown. To determine if fasting has any effect on the circadian presentation of acute cardiac events. A prospective study in a general hospital. Patients with acute coronary events were divided into two groups based on the history of fasting. Information about age, gender, cardiovascular risk factor profiles and outcome was collected. The relationship of time of presentation of initial symptoms with fasting was evaluated using Student's t-test, Mann-Whitney U-test and chi2 analysis. Of the 1019 patients hospitalized during the study period, 162 were fasting. Although, fasting patients were more likely to present to the emergency department in the time periods 5-6 AM (10.5% vs 6.3%) and 11 PM (11.1% vs 7.1%) and were less likely to present in the time periods 1-2 PM (3.7% vs 7.2%) and 5-6 PM (3.7% vs 7.0%); these differences were not statistically significant. Fasting patients were less likely to have their symptoms start between 5 and 8 AM (11.1% vs 19.4%) and more likely to have symptoms between 5 and 6 PM (11.1% vs 6.0%) and 3 and 4 AM (11.1% vs 6.9%). These differences for time of initial symptoms were statistically significant (P=0.002). Exogenous factors associated with fasting, namely, the changes in food intake and/or sleep timings, affect the circadian rhythm and influence the timing of presentation of acute coronary events.

Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors

PubMed Central

Goldenberg, Neil A.; Donadini, Marco P.; Kahn, Susan R.; Crowther, Mark; Kenet, Gili; Nowak-Göttl, Ulrike; Manco-Johnson, Marilyn J.

2010-01-01

Background Post-thrombotic syndrome is a manifestation of chronic venous insufficiency following deep venous thrombosis. This systematic review was conducted to critically evaluate pediatric evidence on frequency of occurrence, validity of outcome measures, and prognostic indicators of post-thrombotic syndrome. Design and Methods A comprehensive literature search of original reports revealed 19 eligible studies, totaling 977 patients with upper/lower extremity deep venous thrombosis. Calculated weighted mean frequency of post-thrombotic syndrome was 26% (95% confidence interval: 23–28%) overall, and differed significantly by prospective/non-prospective analysis and use/non-use of a standardized outcome measure. Results Standardized post-thrombotic syndrome outcome measures included an adaptation of the Villalta scale, the Clinical-Etiologic-Anatomic-Pathologic classification, and the Manco-Johnson instrument. Data on validity were reported only for the Manco-Johnson instrument. No publications on post-thrombotic syndrome-related quality of life outcomes were identified. Candidate prognostic factors for post-thrombotic syndrome in prospective studies included use/non-use of thrombolysis and plasma levels of factor VIII activity and D-dimer. Conclusions Given that affected children must endure chronic sequelae for many decades, it is imperative that future collaborative pediatric prospective cohort studies and trials assess as key objectives and outcomes the incidence, severity, prognostic indicators, and health impact of post-thrombotic syndrome, using validated measures. PMID:20595095

Identifying youth at risk for difficulties following a traumatic event: pre-event factors are associated with acute symptomatology.

PubMed

Goslin, Megan C; Stover, Carla Smith; Berkowitz, Steven; Marans, Steven

2013-08-01

This study examined factors related to children's acute symptoms following a potentially traumatic event (PTE) to more clearly identify domains that should be included in screenings of youth exposed to a PTE. In particular, the authors examined whether trauma category (i.e., sexual abuse/disclosure of abuse, intentionally perpetrated traumas other than sexual abuse, and unintentional traumas) was related to symptoms after controlling for other relevant factors. Participants were 112 youth presenting for clinical evaluation within a month of a PTE and their nonoffending caregivers. Using data from baseline assessments collected as part of a randomized controlled trial of a secondary prevention program, the following factors were tested in 3 hierarchical regression models: index PTE category, history of traumatic exposure, preindex event functioning, and parenting behaviors. Prior trauma exposure, preindex event functioning, and hostile parenting were uniquely related to children's symptoms in the acute posttraumatic period after controlling for time since the event and child age, but trauma category was not. Implications for identifying and referring children at high risk for poor outcomes in the early aftermath of a PTE are discussed. An exclusive focus on the event is insufficient and more comprehensive understanding of the child and family is required. Copyright © 2013 International Society for Traumatic Stress Studies.

A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER.

PubMed

Hunt, Ryan; Yalamanoglu, Ayla; Tumlin, James; Schiller, Tal; Baek, Jin Hyen; Wu, Andrew; Fogo, Agnes B; Yang, Haichun; Wong, Edward; Miller, Peter; Buehler, Paul W; Kimchi-Sarfaty, Chava

2017-02-16

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

Early blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial (SCAST).

PubMed

Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M; Berge, Eivind

2016-08-01

Early blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was dependent on the timing of treatment. Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular event (vascular death, nonfatal stroke or nonfatal myocardial infarction) during the first 6 months. The modified Rankin Scale (mRS) score following a vascular event was used to categorize vascular events in order of severity: no event (n = 1798), minor (mRS 0-2, n = 59), moderately severe (mRS 3-4, n = 57) and major event (mRS 5-6, n = 115). We used ordinal logistic regression for analysis and adjusted for predefined prognostic variables. Candesartan had no overall effect on vascular events (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among the patients treated within 6 h, the adjusted common odds ratio for vascular events was 0.37, 95% confidence interval 0.16-0.84, P = 0.02, and there was no heterogeneity of effect between ischaemic and haemorrhagic strokes. Ordinal analysis of vascular events showed no overall effect of candesartan in the subacute phase of stroke. The effect of treatment given within 6 h of stroke onset appears promising, and will be addressed in ongoing trials. Ordinal analysis of vascular events is feasible and can be used in future trials.

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

PubMed

İlgen, U; Yayla, M E; Ateş, A; Okatan, İ E; Yurteri, E U; Torgutalp, M; Keleşoğlu, A B D; Turgay, T M; Kınıklı, G

2018-04-01

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome

PubMed Central

Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-01-01

Abstract Rationale: The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. Patient concerns: We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Diagnoses: Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. Intervetions: The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Outcomes: Clinical improvement ensued. At follow-up the patient is well. Lessons: The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities. PMID:29642153

Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome.

PubMed

Braun, Oscar Ö; Bico, Besim; Chaudhry, Uzma; Wagner, Henrik; Koul, Sasha; Tydén, Patrik; Scherstén, Fredrik; Jovinge, Stefan; Svensson, Peter J; Gustav Smith, J; van der Pals, Jesper

2015-01-01

Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS). We identified all ACS patients on DT upon discharge from Helsingborg Hospital and Skåne University Hospital in Malmö and Lund, Sweden, during 2013. Patients on DT were compared with historical controls discharged with TT. Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for three months. In total, 107 DT patients were identified and compared with 159 controls on TT. Mean HAS-BLED bleeding risk score and duration of treatment were similar between the groups (HAS-BLED 2.2+/-0.8 vs 2.2+/-1.0 units, p=NS; duration 2.7+/-0.8 vs 2.5+/-0.9months, p=NS; DT vs TT). The incidence of spontaneous major bleeding was similar between the groups, as was a composite of all thrombotic events, i.e. peripheral embolism, stroke/TIA and acute coronary syndrome (bleeding 8/106 (7.5%) vs 11/157 (7.0%), p=NS; thrombosis 5/106 (4.7%) vs 5/157 (3.2%), p=NS; DT vs TT). Rates of thrombotic and bleeding events were similar in patients with TT and patients with ticagrelor and warfarin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Design and rationale of the ANALYZE ST study: a prospective, nonrandomized, multicenter ST monitoring study to detect acute coronary syndrome events in implantable cardioverter-defibrillator patients.

PubMed

Gibson, C Michael; Krucoff, Mitchell; Kirtane, Ajay J; Rao, Sunil V; Mackall, Judith A; Matthews, Ray; Saba, Samir; Waksman, Ron; Holmes, David

2014-10-01

In the setting of ST-segment elevation myocardial infarction, timely restoration of normal blood flow is associated with improved myocardial salvage and survival. Despite improvements in door-to-needle and door-to-balloon times, there remains an unmet need with respect to improved symptom-to-door times. A prior report of an implanted device to monitor ST-segment deviation demonstrated very short times to reperfusion among patients with an acute coronary syndrome (ACS) with documented thrombotic occlusion. The goal of the ANALYZE ST study is to evaluate the safety and effectiveness of a novel ST-segment monitoring feature using an existing implantable cardioverter-defibrillator (ICD) among patients with known coronary artery disease. The ANALYZE ST study is a prospective, nonrandomized, multicenter, pivotal Investigational Device Exemption study enrolling 5,228 patients with newly implanted ICD systems for standard clinical indications who also have a documented history of coronary artery disease. Patients will be monitored for 48 months, during which effectiveness of the device for the purpose of early detection of cardiac injury will be evaluated by analyzing the sensitivity of the ST monitoring feature to identify clinical ACS events. In addition, the safety of the ST monitoring feature will be evaluated through the assessment of the percentage of patients for which monitoring produces a false-positive event over the course of 12 months. The ANALYZE ST trial is testing the hypothesis that the ST monitoring feature in the Fortify ST ICD system (St. Jude Medical, Inc., St. Paul, MN) (or other ICD systems with the ST monitoring feature) will accurately identify patients with clinical ACS events. Copyright © 2014 Mosby, Inc. All rights reserved.

Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura

PubMed Central

Jiang, Yang; McIntosh, Jennifer J.; Reese, Jessica A.; Deford, Cassandra C.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; Terrell, Deirdra R.; Vesely, Sara K.; Knudtson, Eric J.

2014-01-01

Pregnancy may precipitate acute episodes of thrombotic thrombocytopenic purpura (TTP), but pregnancy outcomes in women who have recovered from acquired TTP are not well documented. We analyzed pregnancy outcomes following recovery from TTP associated with acquired, severe ADAMTS13 deficiency (ADAMTS13 activity <10%) in women enrolled in the Oklahoma TTP-HUS Registry from 1995 to 2012. We also systematically searched for published reports on outcomes of pregnancies following recovery from TTP associated with acquired, severe ADAMTS13 deficiency. Ten women in the Oklahoma Registry had 16 subsequent pregnancies from 1999 to 2013. Two women had recurrent TTP, which occurred 9 and 29 days postpartum. Five of 16 pregnancies (31%, 95% confidence interval, 11%-59%) in 3 women were complicated by preeclampsia, a frequency greater than US population estimates (2.1%-3.2%). Thirteen (81%) pregnancies resulted in normal children. The literature search identified 382 articles. Only 6 articles reported pregnancies in women who had recovered from TTP associated with acquired, severe ADAMTS13 deficiency, describing 10 pregnancies in 8 women. TTP recurred in 6 pregnancies. Conclusions: With prospective complete follow-up, recurrent TTP complicating subsequent pregnancies in Oklahoma patients is uncommon, but the occurrence of preeclampsia may be increased. Most pregnancies following recovery from TTP in Oklahoma patients result in normal children. PMID:24398329

Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool.

PubMed

Avila, M L; Brandão, L R; Williams, S; Ward, L C; Montoya, M I; Stinson, J; Kiss, A; Lara-Corrales, I; Feldman, B M

2016-08-01

Our goal was to conduct the item generation and piloting phases of a new discriminative and evaluative tool for pediatric post-thrombotic syndrome. We followed a formative model for the development of the tool, focusing on the signs/symptoms (items) that define post-thrombotic syndrome. For item generation, pediatric thrombosis experts and subjects diagnosed with extremity post-thrombotic syndrome during childhood nominated items. In the piloting phase, items were cross-sectionally measured in children with limb deep vein thrombosis to examine item performance. Twenty-three experts and 16 subjects listed 34 items, which were then measured in 140 subjects with previous diagnosis of limb deep vein thrombosis (70 upper extremity and 70 lower extremity). The items with strongest correlation with post-thrombotic syndrome severity and largest area under the curve were pain (in older children), paresthesia, and swollen limb for the upper extremity group, and pain (in older children), tired limb, heaviness, tightness and paresthesia for the lower extremity group. The diagnostic properties of the items and their correlations with post-thrombotic syndrome severity varied according to the assessed venous territory. The information gathered in this study will help experts decide which item should be considered for inclusion in the new tool. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diagnosis and management of acquired thrombotic thrombocytopenic purpura in southeast China: a single center experience of 60 cases.

PubMed

Zhou, Xinping; Ye, Xingnong; Ren, Yanling; Mei, Chen; Ma, Liya; Huang, Jiansong; Xu, Weilai; Wei, Juying; Ye, Li; Mai, Wenyuan; Qian, Wenbin; Meng, Haitao; Jin, Jie; Tong, Hongyan

2016-12-01

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected in 10 years in a single center in southeast China. A total of 60 patients diagnosed with acute acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients, 52 patients presented with their first episodes, and eight patients had two or more episodes. The median age at presentation was 49 (range, 17 to 78) years with a female predominance (male:female ratio, 1:1.60). ADAMTS 13 activity were analyzed in 43 patients, among whom 33 (76.7%) patients had a baseline level of < 5%. Mortality was 30%. Plasma exchange (PEX) was performed in 62 of 69 (89.9%) episodes. Corticosteroids were administered in 54 of 69 (78.3%) episodes. Other immunosuppressants (e.g., vincristine, cyclosporine, and cyclosporin) were used in 7 of 69 (10.1%) episodes. Rituximab was documented in 4 patients with refractory/relapsed TTP for 5 episodes, showing encouraging results. In conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the mainstay of the therapy, and rituximab can be used in relapsed/refractory disease.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

PubMed Central

Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post-thrombotic

Self-perception of aging and acute medical events in chronically institutionalized middle-aged and older persons with schizophrenia.

PubMed

Cheng, Sheung-Tak; Yip, Leona C Y; Jim, Olivia T T; Hui, Anna N N

2012-09-01

To examine the relationship between self-perceptions of aging and acute medical events in chronically institutionalized middle-aged and older persons with schizophrenia. Participants were 83 persons with schizophrenia (30% women; mean age = 58.48, SD = 8.14) residing in a long-stay care home, who were without organic mental disorders, mental retardation, serious audiovisual impairment, and serious cognitive and physical impairment. They received assessments in body mass index, functional health, and global mental status, and responded to measures of self-perception of aging at baseline. Acute events that required medical attention were recorded for the next 3 months. 8% of the participants had acute medical events. Bivariate analysis suggested that number of comorbid medical conditions, mobility, Mini-Mental State Examination, and negative self-perception of aging were predictive of acute medical events. However, multivariate analysis (logistic regression) showed that only mobility (OR = 0.78, p = 0.04) and negative self-perception of aging (OR = 3.38, p = 0.02) had independent effects on acute medical events, with the latter being the stronger predictor. Positive aging self-perception, body mass index, and smoking were unrelated to medical events. Physical vulnerabilities may not be sufficient to explain the development of acute medical events in late-life schizophrenia. How individuals perceive their aging process, which is expected to regulate health behavior and help-seeking, may be an even more important factor. Further research should investigate whether such self-perceptions, which are probably rooted in stereotypes about aging socialized early in life, are modifiable in this population. Copyright © 2011 John Wiley & Sons, Ltd.

Defining the genetics of thrombotic microangiopathies.

PubMed

Vieira-Martins, Paula; El Sissy, Carine; Bordereau, Pauline; Gruber, Aurelia; Rosain, Jeremie; Fremeaux-Bacchi, Veronique

2016-04-01

The spectrum of the thrombotic microangiopathies (TMA) encompasses a heterogeneous group of disorders with hereditary and acquired forms. Endothelial cell injury in the microvasculature is common to all TMAs, whatever the pathophysiological process. In this review we describe genetic mutations characteristic of certain TMAs and review their contributions to disease. Recent identification of novel pathologic mutations has been enabled by exome studies. The monogenic forms of TMA are more frequently caused by recessive alterations in von Willebrand factor cleaving protease ADAMST13, leading to congenital thrombotic thrombocytopenic purpura, or cobalamine C and DGKE genes, leading to an atypical hemolytic-uremic syndrome (aHUS)-like TMA. aHUS, whether idiopathic or linked to a known complement amplifying condition, is a TMA that primarily affects kidney function. It often results from a combination of an underlying genetic susceptibility with environmental factors activating the alternative complement pathway. Pathogenic variants in at least five complement genes coding for complement factor H (CFH) complement factor I (CFI), MCP (CD46), C3 and complement factor B (CFB) have been demonstrated to increase the risk of developing aHUS, but several more genes have been implicated. A new challenge is to separate disease-associated genetic variants from the broader background of variants or polymorphisms present in all human genomes that are rare, potentially functional, but may or may not be pathogenic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

PubMed

Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

2017-01-01

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

Numerical Simulation of Thrombotic Occlusion in Tortuous Arterioles

PubMed Central

Feng, Zhi-Gang; Cortina, Miguel; Chesnutt, Jennifer KW; Han, Hai-Chao

2017-01-01

Tortuous microvessels alter blood flow and stimulate thrombosis but the physical mechanisms are poorly understood. Both tortuous microvessels and abnormally large platelets are seen in diabetic patients. Thus, the objective of this study was to determine the physical effects of arteriole tortuosity and platelet size on the microscale processes of thrombotic occlusion in microvessels. A new lattice-Boltzmann method-based discrete element model was developed to simulate the fluid flow field with fluid-platelet coupling, platelet interactions, thrombus formation, and thrombotic occlusion in tortuous arterioles. Our results show that vessel tortuosity creates high shear stress zones that activate platelets and stimulate thrombus formation. The growth rate depends on the level of tortuosity and the pressure and flow boundary conditions. Once thrombi began to form, platelet collisions with thrombi and subsequent activations were more important than tortuosity level. Thrombus growth narrowed the channel and reduced the flow rate. Larger platelet size leads to quicker decrease of flow rate due to larger thrombi that occluded the arteriole. This study elucidated the important roles that tortuosity and platelet size play in thrombus formation and occlusion in arterioles. PMID:29327739

Early versus delayed, provisional eptifibatide in acute coronary syndromes.

PubMed

Giugliano, Robert P; White, Jennifer A; Bode, Christoph; Armstrong, Paul W; Montalescot, Gilles; Lewis, Basil S; van 't Hof, Arnoud; Berdan, Lisa G; Lee, Kerry L; Strony, John T; Hildemann, Steven; Veltri, Enrico; Van de Werf, Frans; Braunwald, Eugene; Harrington, Robert A; Califf, Robert M; Newby, L Kristin

2009-05-21

Glycoprotein IIb/IIIa inhibitors are indicated in patients with acute coronary syndromes who are undergoing an invasive procedure. The optimal timing of the initiation of such therapy is unknown. We compared a strategy of early, routine administration of eptifibatide with delayed, provisional administration in 9492 patients who had acute coronary syndromes without ST-segment elevation and who were assigned to an invasive strategy. Patients were randomly assigned to receive either early eptifibatide (two boluses, each containing 180 microg per kilogram of body weight, administered 10 minutes apart, and a standard infusion > or = 12 hours before angiography) or a matching placebo infusion with provisional use of eptifibatide after angiography (delayed eptifibatide). The primary efficacy end point was a composite of death, myocardial infarction, recurrent ischemia requiring urgent revascularization, or the occurrence of a thrombotic complication during percutaneous coronary intervention that required bolus therapy opposite to the initial study-group assignment ("thrombotic bailout") at 96 hours. The key secondary end point was a composite of death or myocardial infarction within the first 30 days. Key safety end points were bleeding and the need for transfusion within the first 120 hours after randomization. The primary end point occurred in 9.3% of patients in the early-eptifibatide group and in 10.0% in the delayed-eptifibatide group (odds ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.23). At 30 days, the rate of death or myocardial infarction was 11.2% in the early-eptifibatide group, as compared with 12.3% in the delayed-eptifibatide group (odds ratio, 0.89; 95% CI, 0.79 to 1.01; P=0.08). Patients in the early-eptifibatide group had significantly higher rates of bleeding and red-cell transfusion. There was no significant difference between the two groups in rates of severe bleeding or nonhemorrhagic serious adverse events. In patients who had acute

[Evaluation of the antithrombotic strategy in low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis].

PubMed

Aceves-Velázquez, Eduardo; Vieyra-Herrera, Gerardo; Rodríguez-Chávez, Laura; Herrera-Alarcón, Valentín

2017-07-16

According to current guidelines, in patients without additional risk factors who have undergone aortic valve replacement with a bioprosthesis, anticoagulation in the first 3 months after surgery is still a matter of debate. According to current evidence, aspirin in low doses is a reasonable alternative to vitamin K antagonists (VKA). A comparison is made between the incidence of thrombotic and haemorrhagic complications in patients with low thrombotic risk who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico. The hypothesis: aspirin as monotherapy has a beneficial effect compared to VKA. The studied patients were the low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico from 2011 to 2015. The groups studied were: aspirin only, VKA only, and the combination of VKA plus aspirin. The patients were retrospectively followed-up for 12 months, and the thrombotic and haemorrhagic complications were documented. Of the 231 patients included in the study, only one patient in the VKA only group presented with a haemorrhagic complication. No thrombotic complications were observed. In the present study no thrombotic complications were observed in patients who did not receive anticoagulation in the first 3 months after an aortic valve replacement with a bioprosthesis after a follow up period of 12 months. This suggests that the use of aspirin only is safe during this period. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus.

PubMed

Male, Christoph; Foulon, Denise; Hoogendoorn, Hugh; Vegh, Patricia; Silverman, Earl; David, Michèle; Mitchell, Lesley

2005-12-15

Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti-beta2-glycoprotein-I (anti-beta2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti-beta2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti-beta2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.

Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

PubMed

Male, C; Mitchell, L; Julian, J; Vegh, P; Joshua, P; Adams, M; David, M; Andrew, M E

2001-02-15

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)

Development and Validation of a Practical Two-Step Prediction Model and Clinical Risk Score for Post-Thrombotic Syndrome.

PubMed

Amin, Elham E; van Kuijk, Sander M J; Joore, Manuela A; Prandoni, Paolo; Cate, Hugo Ten; Cate-Hoek, Arina J Ten

2018-06-04

 Post-thrombotic syndrome (PTS) is a common chronic consequence of deep vein thrombosis that affects the quality of life and is associated with substantial costs. In clinical practice, it is not possible to predict the individual patient risk. We develop and validate a practical two-step prediction tool for PTS in the acute and sub-acute phase of deep vein thrombosis.  Multivariable regression modelling with data from two prospective cohorts in which 479 (derivation) and 1,107 (validation) consecutive patients with objectively confirmed deep vein thrombosis of the leg, from thrombosis outpatient clinic of Maastricht University Medical Centre, the Netherlands (derivation) and Padua University hospital in Italy (validation), were included. PTS was defined as a Villalta score of ≥ 5 at least 6 months after acute thrombosis.  Variables in the baseline model in the acute phase were: age, body mass index, sex, varicose veins, history of venous thrombosis, smoking status, provoked thrombosis and thrombus location. For the secondary model, the additional variable was residual vein obstruction. Optimism-corrected area under the receiver operating characteristic curves (AUCs) were 0.71 for the baseline model and 0.60 for the secondary model. Calibration plots showed well-calibrated predictions. External validation of the derived clinical risk scores was successful: AUC, 0.66 (95% confidence interval [CI], 0.63-0.70) and 0.64 (95% CI, 0.60-0.69).  Individual risk for PTS in the acute phase of deep vein thrombosis can be predicted based on readily accessible baseline clinical and demographic characteristics. The individual risk in the sub-acute phase can be predicted with limited additional clinical characteristics. Schattauer GmbH Stuttgart.

Allopurinol use and the risk of acute cardiovascular events in patients with gout and diabetes.

PubMed

Singh, Jasvinder A; Ramachandaran, Rekha; Yu, Shaohua; Curtis, Jeffrey R

2017-03-14

Few studies, if any, have examined cardiovascular outcomes in patients with diabetes and gout. Both diabetes and gout are risk factors for cardiovascular disease. The objective of this study was to examine the effect of allopurinol on the risk of incident acute cardiovascular events in patients with gout and diabetes. We used the 2007-2010 Multi-Payer Claims Database (MPCD) that linked health plan data from national commercial and governmental insurances, representing beneficiaries with United Healthcare, Medicare, or Medicaid coverage. In patients with gout and diabetes, we assessed the current allopurinol use, defined as a new filled prescription for allopurinol, as the main predictor of interest. Our outcome of interest was the occurrence of the first Incident hospitalized myocardial infarction (MI) or stroke (composite acute cardiovascular event), after which observations were censored. We employed multivariable-adjusted Cox proportional hazards models that simultaneously adjusted for patient demographics, cardiovascular risk factors and other medical comorbidities. We calculated hazard ratios [HR] (95% confidence intervals [CI]) for incident composite (MI or stroke) acute cardiovascular events. We performed sensitivity analyses that additionally adjusted for the presence of immune diseases and colchicine use, as potential confounders. There were 2,053,185 person days (5621.3 person years) of current allopurinol use and 1,671,583 person days (4576.5 person years) of prior allopurinol use. There were 158 incident MIs or strokes in current and 151 in prior allopurinol users, respectively. Compared to previous allopurinol users, current allopurinol users had significantly lower adjusted hazard of incident acute cardiovascular events (incident stroke or MI), with an HR of 0.67 (95% CI, 0.53, 0.84). Sensitivity analyses, additionally adjusted for immune diseases or colchicine use, confirmed this association. Current allopurinol use protected against the occurrence

Population-based study of blood biomarkers in prediction of sub-acute recurrent stroke

PubMed Central

Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Silver, Louise E; Rothwell, Peter M

2017-01-01

Background and purpose Risk of recurrent stroke is high in the first few weeks after TIA or stroke and clinic risk prediction tools have only limited accuracy, particularly after the hyper-acute phase. Previous studies of the predictive value of biomarkers have been small, been done in selected populations and have not concentrated on the acute phase or on intensively treated populations. We aimed to determine the predictive value of a panel of blood biomarkers in intensively treated patients early after TIA and stroke. Methods We studied 14 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in early TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were related to 90-day risk of recurrent stroke as Hazard Ratio (95%CI) per decile increase, adjusted for age and sex. Results Among 1292 eligible patients there were 53 recurrent ischaemic strokes within 90 days. There were moderate correlations (r>0.40; p<0001) between the inflammatory biomarkers and between the cell damage and thrombotic subsets. However, associations with risk of early recurrent stroke were weak, with significant associations limited to Interleukin-6 (HR=1.12, 1.01-1.24; p=0.035) and C-reactive protein (1.16, 1.02-1.30; p=0.019). When stratified by type of presenting event, P-selectin predicted stroke after TIA (1.31, 1.03-1.66; p=0.028) and C-reactive protein predicted stroke after stroke (1.16, 1.01-1.34; p=0.042). These associations remained after fully adjusting for other vascular risk factors. Conclusion In the largest study to date, we found very limited predictive utility for early recurrent stroke for a panel of inflammatory, thrombotic and cell damage biomarkers. PMID:25158774

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome: Case report.

PubMed

Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-04-01

The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Clinical improvement ensued. At follow-up the patient is well. The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities.

[The revolution of monoclonal antibodies in the treatment of thrombotic microangiopathy].

PubMed

Sauvètre, G; Grange, S; Froissart, A; Veyradier, A; Coppo, P; Benhamou, Y

2015-05-01

Thrombotic microangiopathies (TMA) define a syndrome characterized by the association of microangiopathic haemolytic anaemia with schistocytes, peripheral thrombocytopenia, and organ injury of variable severity. Thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uremic syndrome (HUS) are the main forms of TMA. Recent advances in the pathophysiology of those two diseases, which include in HUS the identification of a deregulation of the alternative complement pathway, and in TTP a severe deficiency in ADAMTS-13, allowed to develop specific, pathophysiology-based therapies. Therefore, rituximab and eculizumab tends to be increasingly used, and there is an urgent need to define consensual modes of administration at the international level, as well as common definitions of response evaluation and follow-up explorations. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Predictors for the development of post-thrombotic syndrome in patients with primary lower limb deep venous thrombosis: A case-control study.

PubMed

Siddiqui, Nadeem A; Sophie, Ziad; Zafar, Farhan; Soares, Delvene; Naz, Iram

2017-02-01

Introduction Post-thrombotic syndrome is a common and debilitating sequelae of lower limb deep venous thrombosis. Very little awareness is present about the risk factors and about the diagnosis, prevention, and treatment of this condition. Objective The objective of this study is to identify the predictors of post-thrombotic syndrome after lower limb deep venous thrombosis. Materials and methods A case-control study was conducted on all adult patients who were admitted with lower limb deep venous thrombosis at our institution from January 2005 to June 2012. These patients were scheduled for a research clinic visit, which included informed consent, data collection, and physical examination. Patients found to have post-thrombotic syndrome served as cases and those without post-thrombotic syndrome served as controls. Villalta scoring system was used to diagnose the post-thrombotic syndrome and then to assess the severity of the condition in both the groups. Cox regression risk factor analysis was performed to identify the predictors of post-thrombotic syndrome. Results Out of the 125 patients examined, 49 were found to have post-thrombotic syndrome. Risk factors found to be significant were body mass index of more than 35 kg/m 2 ( n = 13, p = 0.003), history of immobilization ( n = 19, p = 0.003), one or more hypercoagable disorders ( n = 32, p = 0.02), iliofemoral deep venous thrombosis ( n = 18, p = 0.001), complete obstruction on ultrasound ( n = 26, p = 0.016), unstable range of international normalized ratio ( n = 23, p = 0.041) and non-compliance for the use of compressions stockings ( n = 14, p = 0.001). On multivariate analysis, one or more hypercoagable disorder, iliofemoral deep venous thrombosis, and non-compliance to the use of compression stockings were found to be independent risk factors for the development of post-thrombotic syndrome. Conclusion One or more hypercoagable disorders, iliofemoral

New directions for pharmacotherapy in the treatment of acute coronary syndrome.

PubMed

Adamski, Piotr; Adamska, Urszula; Ostrowska, Małgorzata; Koziński, Marek; Kubica, Jacek

2016-12-01

Acute coronary syndromes (ACS) are one of the leading causes of death worldwide. Several landmark trials, followed by a widespread introduction of new agents, have significantly improved ACS outcomes in recent years. However, despite the use of contemporary therapy, a substantial number of ACS patients continue to suffer from cardiovascular events. Areas covered: The aim of this review was to summarize available data on innovative drugs and pharmacological strategies that have potential to amend the current ACS therapy. We present the results of recent large clinical trials, as well as insights from ongoing phase III and phase IV studies, exploring the value of new strategies for the improvement of outcomes in ACS. Expert opinion: More potent platelet inhibition, more profound lipid reduction and possibly anti-inflammatory action are considered to have potential to further reduce the rates of adverse cardiovascular and thrombotic events in ACS patients. 'Hit fast, hit hard' approach regarding novel antiplatelet and lipid-lowering therapy seems attractive, but it has to be considered that these strategies may be associated with increased adverse events rate. Introduction of cangrelor and ezetimibe, and potentially future recognition of proprotein convertase subtilisin/kexin type 9 antibodies, are likely to alter the landscape of ACS pharmacotherapy.

Possible green tea-induced thrombotic thrombocytopenic purpura.

PubMed

Liatsos, George D; Moulakakis, Antonios; Ketikoglou, Ioannis; Klonari, Stella

2010-04-01

A case of a patient who developed thrombotic thrombocytopenic purpura (TTP) after consuming a weight-loss product containing green tea is reported. A 38-year-old, 68-kg Caucasian woman arrived at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. She had no symptoms of infection and denied illegal drug use. Her medical history included hypothyroidism, for which she was treated with levothyroxine 150 microg daily for the past four years. She reported that she had been using a green tea preparation for the two months before admission to lose body weight. The daily preparation contained 200 mg of green tea extract 5:1, equivalent to 1 g of natural green tea. On clinical examination, the patient appeared acutely ill and was afebrile, with pallor, petechiae, and purpura of the extremities. Laboratory test results at the time of admission revealed that the patient had anemia and marked thrombocytopenia. A peripheral blood smear demonstrated a feature of microangiopathic hemolytic anemia. Immunoglobulin G autoantibodies against ADAM metallopeptidase with thrombospondin type 1 motif, 13 were detected. On hospital day 3, the patient appeared confused and exhibited aphasia that was initially transient but then recurrent. Brain computerized tomography did not exhibit focal pathology. Over the next few days, her neurologic symptoms subsided and her platelet count and hematocrit value gradually increased. Plasmapheresis was performed (12 procedures). Corticosteroid treatment was also initiated. After 20 days of hospitalization, the patient was discharged. A 38-year-old woman developed TTP after consuming a weight-loss product containing green tea extract for two months.

[Thrombosis and post-thrombotic syndrome as a consequence of an accident].

PubMed

Wahl, U; Hirsch, T

2015-10-01

Phlebothromboses represent alarming complications in accident victims since they can cause fatal pulmonary embolisms. More than half of those affected also develop post-thrombotic syndrome in the course of the illness. In addition to making clinical assessments, the traumatologist should also have fundamental knowledge about diagnostic methods and be familiar with interpreting internal findings. Colour-coded duplex sonography plays a central role in diagnosing thrombosis and in assessing functional limitations. Further information can be gathered from various phlebological procedures. The expert evaluation of the immediate, as well as the long-term consequences of an accident frequently require leg swelling to be classified. It is not uncommon for post-thrombotic syndrome to be diagnosed for the first time during this process. An additional vascular appraisal is often required. An appreciation of social-medical and insurance-related aspects means a high degree of responsibility is placed on the expert.

77 FR 21982 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-12

...] Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS...: Cardiovascular and Renal Drugs Advisory Committee. General Function of the Committee: To provide advice and...., to reduce the risk of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS...

Group A beta-haemolytic streptococcal acute chest event in a child with sickle cell anaemia.

PubMed

Suara, R O

2001-06-01

Acute chest syndrome is a major cause of death and hospitalisation in children with sickle cell anaemia. It is often initiated by an infection, particularly pneumonia. Microbial agents previously not associated with acute chest syndrome are becoming increasingly important. Group A beta-haemolytic Streptococcus (GABHS) is thought to be an uncommon cause of pneumonia in children with sickle cell anaemia. We report a 15-year-old African-American girl who presented with an acute chest event characterised by fever, cough, chest pain, shortness of breath, right upper abdominal quadrant pain, jaundice and otitis media. Chest radiograph showed multi-lobar pneumonia with left pleural effusion. Group A beta-haemolytic Streptococcus was isolated from culture of pleural and middle ear fluids. She responded to therapy that included antibiotics, exchange blood transfusion, oxygen, thoracotomy chest tube drainage and decortication. In a child with sickle cell anaemia presenting with fever and an acute chest event, pneumonia should be considered and GABHS recognised as a possible aetiological agent. In addition, a chest X-ray should be obtained and antibiotics against agents causing community-acquired pneumonia instituted.

The relationship of platelet reactivity to the occurrence of post-stenting ischemic events: emergence of a new cardiovascular risk factor.

PubMed

Gurbel, Paul A

2006-01-01

The reactivity of platelets to agonists plays a central role in the genesis of thrombosis following percutaneous coronary intervention (PCI) and spontaneous plaque rupture. Antiplatelet therapy has reduced the occurrence of thrombotic events following PCI, including myocardial infarction and stent thrombosis. Because the platelet is a fundamental component in the generation of an arterial thrombus and the stimulus for thrombosis is marked in PCI, it is logical to predict that patients with superior platelet inhibition would have the best outcomes with respect to ischemic events post PCI. However, until recently there was little information linking measurements of high ex vivo platelet reactivity to the occurrence of ischemic events. An emerging body of data, mostly from small studies, supports the pivotal link between periprocedural platelet physiology and increased risk of adverse thrombotic events. This review explores the available information linking platelet reactivity during and after PCI to the occurrence of adverse events, including myocardial infarction, recurrent ischemia within 6 months, and stent thrombosis.

Trousseau's syndrome in a patient with advanced stage gastric cancer.

PubMed

Chien, Tai-Long; Rau, Kung-Ming; Chung, Wen-Jung; Tai, Wei-Chen; Wang, Shih-Ho; Chiu, Yi-Chun; Wu, Keng-Liang; Chou, Yeh-Pin; Wu, Chia-Che; Chen, Yen-Hao; Chuah, Seng-Kee

2015-09-14

Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau's syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered.

Disentangling the effect of illness perceptions on health status in people with type 2 diabetes after an acute coronary event.

PubMed

Vos, Rimke Cathelijne; Kasteleyn, Marise Jeannine; Heijmans, Monique Johanna; de Leeuw, Elke; Schellevis, François Georges; Rijken, Mieke; Rutten, Guy Emile

2018-03-02

Chronically ill patients such as people with type 2 diabetes develop perceptions of their illness, which will influence their coping behaviour. Perceptions are formed once a health threat has been recognised. Many people with type 2 diabetes suffer from multimorbidity, for example the combination with cardiovascular disease. Perceptions of one illness may influence perceptions of the other condition. The aim of the current study was to evaluate the effect of an intervention in type 2 diabetes patients with a first acute coronary event on change in illness perceptions and whether this mediates the intervention effect on health status. The current study is a secondary data analysis of a RCT. Two hundred one participants were randomised (1:1 ratio) to the intervention (n = 101, three home visits) or control group (n = 100). Outcome variables were diabetes and acute coronary event perceptions, assessed with the two separate Brief Illness Perceptions Questionnaires (BIPQs); and health status (Euroqol Visual Analog Scale (EQ-VAS)). The intervention effect was analysed using ANCOVA. Linear regression analyses were used to assess whether illness perceptions mediated the intervention effect on health status. A positive intervention effect was found on the BIPQ diabetes items coherence and treatment control (F = 8.19, p = 0.005; F = 14.01, p < 0.001). No intervention effect was found on the other BIPQ diabetes items consequence, personal control, identity, illness concern and emotional representation. Regarding the acute coronary event, a positive intervention effect on treatment control was found (F = 7.81, p = 0.006). No intervention effect was found on the other items of the acute coronary event BIPQ. Better diabetes coherence was associated with improved health status, whereas perceiving more treatment control was not. The mediating effect of the diabetes perception 'coherence' on health status was not significant. Targeting illness

Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/β+-thalassemia patient: a rare and challenging condition.

PubMed

Vlachaki, Efthymia; Agapidou, Aleka; Neokleous, Nikolaos; Adamidou, Despoina; Vetsiou, Evaggelia; Boura, Panagiota

2014-10-01

The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/β(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/β(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Endovascular treatment of post-thrombotic and non-thrombotic iliofemoral venous outflow obstructions with self-expanding nitinol stents.

PubMed

Stuck, Anna K; Reich, Thomas; Engelberger, Rolf P; Sebastian, Tim; Kucher, Nils

2018-06-01

The aim of the study was to investigate venous patency and clinical outcomes for endovascular treatment of iliofemoral venous obstruction in patients with post-thrombotic syndrome (PTS) and non-thrombotic iliac vein lesion (NIVL) with dedicated self-expanding nitinol stents. Data were collected from the prospective Swiss Venous Stent Registry, enrolling consecutive patients with a standardized follow-up procedure since January 2008. Patency was evaluated by duplex sonography and clinical outcome by various scores including the Villalta score at baseline, three, six, and 12 months, and then annually after endovascular therapy. Overall, 93 patients (64 PTS, 29 NIVL) were analysed. Mean follow-up time was 20 ± 16 (range 3-70) months. A total of 11 (12 %) patients had a stent occlusion, all of which occurred in the PTS group, and 13 (14 %) patients had a symptomatic stent stenosis. Primary patency was 79 % (95 % CI 68-87 %) at 12 months and 72 % (95 % CI 59-82 %) at 24 months. In PTS patients, primary patency at 12 months was 75 % (95 % CI 61-84 %) vs. 89 % (95 % CI 63-97 %) in NIVL patients (p = 0.10). Secondary patency at 24 months was 94 % (95 % CI 84-98 %) in PTS and 100 % in NIVL, p = 0.19). Overall, 62 (67 %) patients were free from PTS at the latest follow-up with a Villalta score < 5 points. Predictive factors for the loss of primary patency were stents placed below the inguinal ligament (OR 2.59, 95 % CI, 0.99-6.84, p = 0.05). In symptomatic patients with chronic iliofemoral vein obstruction, endovascular therapy with self-expanding nitinol stents was associated with favourable patency rates and clinical improvement in the majority of patients.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

PubMed

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

2017-08-04

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

Venous thrombotic events are not increased in patients with rheumatoid arthritis treated with anti‑TNF therapy: results from the British Society for Rheumatology Biologics Register

PubMed Central

Davies, Rebecca; Galloway, James B; Watson, Kath D; Lunt, Mark; Symmons, Deborah P M; Hyrich, Kimme L

2011-01-01

Objectives Past studies have reported conflicting rates of venous thrombotic events (VTEs) in rheumatoid arthritis (RA). The current study aimed to compare (1) the rates of VTEs in patients with RA treated with anti-tumour necrosis factor (anti-TNF) therapy versus those treated with non-biological disease-modifying antirheumatic drugs (nbDMARDs) alone and (2) the rates between each individual anti-TNF agent and nbDMARDs. Methods Using data from the British Society for Rheumatology Biologics Register, a national prospective observational cohort study of biological safety in patients with RA, the authors compared the incidence of VTEs between 11 881 anti-TNF- and 3673 nbDMARD-treated patients. Analysis was limited to the first VTE per person. HRs were calculated using Cox modelling. Adjustment was made for potential confounders including surgery performed during follow-up. Results A total of 196 first VTEs were reported (151 anti-TNF, 45 nbDMARD). Overall there was no difference in the rates of VTEs between anti-TNF- and nbDMARD-treated patients (adjusted HR 0.8 (95% CI 0.5 to 1.5)). The risk was similar across all anti-TNF agents. Rates of postoperative VTEs did not significantly differ between groups. Conclusions These data suggest that anti-TNF therapy is not associated with an increased risk of VTEs in RA patients. PMID:21784722

Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study.

PubMed

Rozen, Laurence; Noubouossie, Denis; Dedeken, Laurence; Huybrechts, Sophie; Lê, Phu Quoc; Ferster, Alina; Demulder, Anne

2017-02-01

Asparaginase (Asp) and corticosteroid (CS) treatment in patients with acute lymphoblastic leukaemia (ALL) is associated with an increased risk of thrombotic events. Characterization of global haemostatic phenotypes of patients with ALL during Asp therapy. Thrombin generation (TG) was monitored in platelet-poor plasma of 56 children treated for a B lineage ALL (36 with native, 20 with PEG Asp) using 1 pM tissue factor and 4 μM phospholipids, with and without thrombomodulin. Protein C activity (PC), free protein S (PS), antithrombin (AT) and fibrinogen levels were also measured. Elevated endogenous thrombin potential (ETP) and peak of TG were noted at diagnosis, throughout the Induction phase and Late Intensification but was significantly less for PEG than for native Asp (P < 0.001), while age, sex, type of corticosteroid during Induction and molecular response had no significant effect. The reduction of ETP after addition of thrombomodulin was significantly lower in ALL children compared with that in controls, suggesting impairment in PS/PC pathway. Three patients experienced thrombosis: two treated with native and one with PEG Asp. The two patients with native Asp had, at the time of thrombosis, a prothrombotic profile. Treatment with Asp, in combination with CS, enhances TG in children with ALL, more significantly with native than PEG Asp, which is present early at diagnosis, persists during Induction and reappears during Late Intensification. This is consistent with the high incidence of thrombotic events described during these phases of therapy. The less pronounced effect of PEG Asp remains to be elucidated. © 2016 Wiley Periodicals, Inc.

The effect of acute microgravity on mechanically-induced membrane damage and membrane-membrane fusion events

NASA Technical Reports Server (NTRS)

Clarke, M. S.; Vanderburg, C. R.; Feeback, D. L.; McIntire, L. V. (Principal Investigator)

2001-01-01

Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". Both membrane rupture and membrane resealing events mediated by membrane-membrane fusion characterize this response. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

The Effect of Acute Microgravity on Mechanically-Induced Membrane Damage and Membrane-Membrane Fusion Events

NASA Technical Reports Server (NTRS)

Clarke, Mark, S. F.; Vanderburg, Charles R.; Feedback, Daniel L.

2001-01-01

Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". This response is characterized by both membrane rupture and membrane resealing events mediated by membrane-membrane fusion. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

Elevated leukocyte count and adverse hospital events in patients with acute coronary syndromes: findings from the Global Registry of Acute Coronary Events (GRACE).

PubMed

Furman, Mark I; Gore, Joel M; Anderson, Fredrick A; Budaj, Andrzej; Goodman, Shaun G; Avezum, Avaro; López-Sendón, José; Klein, Werner; Mukherjee, Debabrata; Eagle, Kim A; Dabbous, Omar H; Goldberg, Robert J

2004-01-01

To examine the association between elevated leukocyte count and hospital mortality and heart failure in patients enrolled in the multinational, observational Global Registry of Acute Coronary Events (GRACE). Elevated leukocyte count is associated with adverse hospital outcomes in patients presenting with acute myocardial infarction (AMI). The association of this prognostic factor with hospital mortality and heart failure in patients with other acute coronary syndromes (ACS) is unclear. We examined the association between admission leukocyte count and hospital mortality and heart failure in 8269 patients presenting with an ACS. This association was examined separately in patients with ST-segment elevation AMI, non-ST-segment elevation AMI, and unstable angina. Leukocyte count was divided into 4 mutually exclusive groups (Q): Q1 <6000, Q2 = 6000-9999, Q3 = 10,000-11,999, Q4 >12,000. Multiple logistic regression analysis was performed to examine the association between elevated leukocyte count and hospital events while accounting for the simultaneous effect of several potentially confounding variables. Increasing leukocyte count was significantly associated with hospital death (adjusted odds ratio [OR] 2.8, 95% CI 2.1-3.6 for Q4 compared to Q2 [normal range]) and heart failure (OR 2.7, 95% CI 2.2-3.4) for patients presenting with ACS. This association was seen in patients with ST-segment elevation AMI (OR for hospital death 3.2, 95% CI 2.1-4.7; OR for heart failure 2.4, 95% CI 1.8-3.3), non-ST-segment elevation AMI (OR for hospital death 1.9, 95% CI 1.2-3.0; OR for heart failure 1.7, 95% CI 1.1-2.5), or unstable angina (OR for hospital death 2.8, 95% CI 1.4-5.5; OR for heart failure 2.0, 95% CI 0.9-4.4). In men and women of all ages with the spectrum of ACS, initial leukocyte count is an independent predictor of hospital death and the development of heart failure.

Risk factors for acute adverse events during ultrasound-guided central venous cannulation in the emergency department.

PubMed

Theodoro, Daniel; Krauss, Missy; Kollef, Marin; Evanoff, Bradley

2010-10-01

Ultrasound (US) greatly facilitates cannulation of the internal jugular vein. Despite the ability to visualize the needle and anatomy, adverse events still occur. The authors hypothesized that the technique has limitations among certain patients and clinical scenarios. The purpose of this study was to identify characteristics of adverse events surrounding US-guided central venous cannulation (CVC). The authors assembled a prospective observational cohort of emergency department (ED) patients undergoing consecutive internal jugular CVC with US. The primary outcome of interest was a composite of acute mechanical adverse events including hematoma, arterial cannulation, pneumothorax, and unsuccessful placement. Physicians performing the CVC recorded anatomical site, reason for insertion, and acute complications. The patients with catheters were followed until the catheters were removed based on radiographic evidence or hospital nursing records. ED charts and pharmacy records contributed variables of interest. A self-reported online survey provided physician experience information. Logistic regression was used to calculate the odds of an adverse outcome.   Physicians attempted 289 CVCs on 282 patients. An adverse outcome occurred in 57 attempts (19.7%, 95% confidence interval [CI] = 15.5 to 24.7), the most common being 31 unsuccessful placements (11%, 95% CI = 7.7 to 14.8). Patients with a history of end-stage renal disease (odds ratio [OR] = 3.54, 95% CI = 1.59 to 7.89), and central lines placed by operators with intermediate experience (OR = 2.26, 95% CI = 1.19 to 4.32), were most likely to encounter adverse events. Previously cited predictors such as body mass index (BMI), coagulopathy, and pulmonary hyperinflation were not significant in our final model. Acute adverse events occurred in approximately one-fifth of US-guided internal jugular central line attempts. The study identified both patient (history of end-stage renal disease) and physician (intermediate

BK polyomavirus encephalitis in a patient with thrombotic microangiopathy after an allogeneic hematopoietic stem cell transplant.

PubMed

Jun, Jae-Bum; Choi, Yunsuk; Kim, Hawk; Lee, Sun Ho; Jeong, Joseph; Jung, Jiwon

2016-12-01

To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with transplant-associated thrombotic microangiopathy has been reported in an hematopoietic stem cell transplantation (HCT) recipient. We report the case of an HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and intravenous immunoglobulin without improvement in mental status. Early suspicion of BKPyV encephalitis in an HCT recipient presenting with altered mental status and hemorrhagic cystitis is important. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Using discrete event computer simulation to improve patient flow in a Ghanaian acute care hospital.

PubMed

Best, Allyson M; Dixon, Cinnamon A; Kelton, W David; Lindsell, Christopher J; Ward, Michael J

2014-08-01

Crowding and limited resources have increased the strain on acute care facilities and emergency departments worldwide. These problems are particularly prevalent in developing countries. Discrete event simulation is a computer-based tool that can be used to estimate how changes to complex health care delivery systems such as emergency departments will affect operational performance. Using this modality, our objective was to identify operational interventions that could potentially improve patient throughput of one acute care setting in a developing country. We developed a simulation model of acute care at a district level hospital in Ghana to test the effects of resource-neutral (eg, modified staff start times and roles) and resource-additional (eg, increased staff) operational interventions on patient throughput. Previously captured deidentified time-and-motion data from 487 acute care patients were used to develop and test the model. The primary outcome was the modeled effect of interventions on patient length of stay (LOS). The base-case (no change) scenario had a mean LOS of 292 minutes (95% confidence interval [CI], 291-293). In isolation, adding staffing, changing staff roles, and varying shift times did not affect overall patient LOS. Specifically, adding 2 registration workers, history takers, and physicians resulted in a 23.8-minute (95% CI, 22.3-25.3) LOS decrease. However, when shift start times were coordinated with patient arrival patterns, potential mean LOS was decreased by 96 minutes (95% CI, 94-98), and with the simultaneous combination of staff roles (registration and history taking), there was an overall mean LOS reduction of 152 minutes (95% CI, 150-154). Resource-neutral interventions identified through discrete event simulation modeling have the potential to improve acute care throughput in this Ghanaian municipal hospital. Discrete event simulation offers another approach to identifying potentially effective interventions to improve patient

Prasugrel (Effient) vs. clopidogrel (Plavix).

PubMed

2009-09-07

The FDA has approved prasugrel (Effient--Lilly/Daiichi Sankyo), an oral antiplatelet drug, for use with aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndromes (ACS) being managed with percutaneous coronary intervention (PCI).1 It will compete with clopidogrel (Plavix) for such use.

Swine Model of Thrombotic Caval Occlusion Created by Autologous Thrombus Injection with Assistance of Intra-caval Net Knitting

PubMed Central

Shi, Wan-Yin; Wu, Shuang; Hu, Lan-Yue; Liu, Chang-Jian; Gu, Jian-Ping

2015-01-01

To evaluate the feasibility of a swine model of thrombotic inferior vena cava (IVC) occlusion (IVCO) created by autologous thrombus injection with assistance of intra-caval net knitting. Sixteen pigs were included and divided into two groups: Group A (n = 10), IVCO model created by knitting a caval net followed by autologous thrombus injection; Group B (n = 6), control model created by knitting a net and normal saline injection. Venography was performed to assess each model and the associated thrombotic occlusion. The vessels were examined histologically to analyse the pathological changes postoperatively. IVCO model was successfully created in 10 animals in Group A (100%). Immediate venography showed extensive clot burden in the IVC. Postoperative venography revealed partial caval occlusion at 7 days, and complete occlusion coupled with collateral vessels at 14 days. Histologically, Group A animals had significantly greater venous wall thickening, with CD163-positive and CD3-positive cell infiltration. Recanalization channels were observed at the margins of the thrombus. By contrast, no thrombotic occlusion of the IVC was observed in Group B. The thrombotic IVCO model can be reliably established in swine. The inflammatory reaction may contribute to the caval thrombus propagation following occlusion. PMID:26680253

Risk factors, management and primary prevention of thrombotic complications related to the use of central venous catheters.

PubMed

Linnemann, Birgit; Lindhoff-Last, Edelgard

2012-09-01

An adequate vascular access is of importance for the treatment of patients with cancer and complex illnesses in the intensive, perioperative or palliative care setting. Deep vein thrombosis and thrombotic occlusion are the most common complications attributed to central venous catheters in short-term and, especially, in long-term use. In this review we will focus on the risk factors, management and prevention strategies of catheter-related thrombosis and occlusion. Due to the lack of randomised controlled trials, there is still controversy about the optimal treatment of catheter-related thrombotic complications, and therapy has been widely adopted using the evidence concerning lower extremity deep vein thrombosis. Given the increasing use of central venous catheters in patients that require long-term intravenous therapy, the problem of upper extremity deep venous thrombosis can be expected to increase in the future. We provide data for establishing a more uniform strategy for preventing, diagnosing and treating catheter-related thrombotic complications.

[Platelet aggregation and antiplatelet agents in acute coronary syndromes].

PubMed

Collet, Jean-Philippe; Choussat, Rémi; Montalescot, Gilles

2004-03-01

Antiplatelet agents are the cornerstone therapy of acute coronary syndromes. In the setting of ST elevation myocardial infarction, antiplatelet therapy prevent the prothrombotic effect of reperfusion therapy including thrombolysis and primary percutaneous coronary intervention. In non ST-elevation acute coronary syndromes, antiplatelet therapy prevent s complete coronary thrombotic occlusion and therefore the occurrence of ST elevation myocardial infarction. Antiplatelet agent benefit is related to the patient's risk profile. It is well established that combined antiplatelet therapy is the most effective in high risk patients. Several important issues have to be faced including the identification of non responders, dose adjustment and the management of temporary interruption of antiplatelet agents in stable coronary artery disease patients.

[Acute myocardial infarction after wasp sting without anaphylactic reaction].

PubMed

Bongo, Angelo Sante; Fornaro, Gianluigi; Sansa, Mara; Macciò, Sergio; Rognoni, Andrea

2005-03-01

Bites of hymenopterans (bees, wasps and hornets) are very frequent phenomena that can stir up allergical reactions in venom-susceptible patients but that seldom provoke acute myocardial infarction. In the literature we can find case reports of myocardial infarction after bites of hymenopterans, and preceded by an allergic reaction (sometimes with angiographic evidence of undamaged coronary arteries). The pathophysiological determinant seems to be related to the chemical composition of hymenopterans venom, basically made up by vasoactive and thrombogenic substances able to create vasospasm and coronary thrombosis. Our report refers to a 65-year-old male patient without prior cardiological and allergic events who, bitten by a sharm of three bees, complains of an acute large anterior myocardial infarction with angiographic evidence of thrombotic lesion of the proximal left anterior descending artery treated with direct stenting with procedural success, without showing allergical symptoms. The pathophysiological determinant seems to be related to the release of vasoactive amines and thrombogenic substances contained into the hymenopterans venom, the former able to produce vasospasm, the latter able to create diffuse thrombosis. The use of adrenaline itself to counteract the possible systemic allergic reaction appears to advise against the treatment of patients with cardiological symptoms or coronary artery disease and because of its strong vasoactive activity (it leads, in fact, to vasoconstriction) and thrombogenic effects.

Registry on acute cardiovascular events during endurance running races: the prospective RACE Paris registry.

PubMed

Gerardin, Benoît; Collet, Jean-Philippe; Mustafic, Hazrije; Bellemain-Appaix, Anne; Benamer, Hakim; Monsegu, Jacques; Teiger, Emmanuel; Livarek, Bernard; Jaffry, Murielle; Lamhaut, Lionel; Fleischel, Catherine; Aubry, Pierre

2016-08-21

Long distance running races are associated with a low risk of life-threatening events much often attributed to hypertrophic cardiomyopathy. However, retrospective analyses of aetiology lack consistency. Incidence and aetiology of life-threatening/fatal events were assessed in long distance races in the prospective Registre des Accidents Cardiaques lors des courses d'Endurance (RACE Paris Registry) from October 2006 to September 2012. Characteristics of life-threatening/fatal events were analysed by interviewing survivors and reviewing medical records including post-mortem data of each case. Seventeen life-threatening events were identified of 511 880 runners of which two were fatal. The vast majority were cardiovascular events (13/17) occurring in experienced male runners [mean (±SD) age 43 ± 10 years], with infrequent cardiovascular risk factors, atypical warning symptoms prior to the race or negative treadmill test when performed. Acute myocardial ischaemia was the predominant aetiology (8 of 13) and led to immediate myocardial revascularization. All cases with initial shockable rhythm survived. There was no difference in event rate according to marathons vs. half-marathons and events were clustered at the end of the race. A meta-analysis of all available studies including the RACE Paris registry (n = 6) demonstrated a low prevalence of life-threatening events (0.75/100 000) and that presentation with non-shockable rhythm [OR = 29.9; 95% CI (4.0-222.5), P = 0.001] or non-ischaemic aetiology [OR = 6.4; 95% CI (1.4-28.8), P = 0.015] were associated with case-fatality. Life-threatening/fatal events during long distance races are rare, most often unpredictable and mainly due to acute myocardial ischaemia. Presentation with non-shockable rhythm and non-ischaemic aetiology are the major determinant of case fatality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Degree of fusiform dilatation of the proximal descending aorta in type B acute aortic dissection can predict late aortic events.

PubMed

Marui, Akira; Mochizuki, Takaaki; Koyama, Tadaaki; Mitsui, Norimasa

2007-11-01

Predicting the risk factors for late aortic events in patients with type B acute aortic dissection without complications may help to determine a therapeutic strategy for this disorder. We investigated whether late aortic events in type B acute aortic dissection can be predicted accurately by an index that expresses the degree of fusiform dilatation of the proximal descending aorta during the acute phase; this index can be calculated as follows: (maximum diameter of the proximal descending aorta)/(diameter of the distal aortic arch + diameter of the descending aorta at the pulmonary artery level). Patients with type B acute aortic dissection without complications (n = 141) were retrospectively analyzed to determine the predictors of late aortic events; these include aortic dilatation, rupture, refractory pain, organ ischemia, rapid aortic enlargement, and rapid enlargement of ulcer-like projections. The fusiform index in patients with late aortic events (0.59) was higher than that in patients without late aortic events (0.53, P < .01). Patients with a higher fusiform index exhibited aortic dilatation earlier than those with a lower fusiform index. By multivariate analysis, we conclude that the predominant independent predictors of late aortic events were a maximum aortic diameter of 40 mm or more, a patent false lumen, and a fusiform index of 0.64 or more (hazard ratios, 3.18, 2.64, and 2.73, respectively). The values of actuarial freedom from aortic events for patients with all 3 predictors at 1, 5, and 10 years were 22%, 17%, and 8%, respectively, whereas the values in those without these predictors were 97%, 94%, and 90%, respectively. The degree of fusiform dilatation of the proximal descending aorta, a patent false lumen, and a large aortic diameter can be predominant predictors of late aortic events in patients with type B acute aortic dissection. Patients with these predictors should be recommended to undergo early interventions (surgery or stent

Withdrawal of statins increases event rates in patients with acute coronary syndromes.

PubMed

Heeschen, Christopher; Hamm, Christian W; Laufs, Ulrich; Snapinn, Steven; Böhm, Michael; White, Harvey D

2002-03-26

HMG-CoA Reductase Inhibitors (statins) reduce cardiac event rates in patients with stable coronary heart disease. Withdrawal of chronic statin treatment during acute coronary syndromes may impair vascular function independent of lipid-lowering effects and thus increase cardiac event rate. We investigated the effects of statins on the cardiac event rate in 1616 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study who had coronary artery disease and chest pain in the previous 24 hours. We recorded death and nonfatal myocardial infarction during the 30-day follow-up. Baseline clinical characteristics did not differ among 1249 patients without statin therapy, 379 patients with continued statin therapy, and 86 patients with discontinued statin therapy after hospitalization. Statin therapy was associated with a reduced event rate at 30-day follow-up compared with patients without statins (adjusted hazard ratio, 0.49 [95% CI, 0.21 to 0.86]; P=0.004). If the statin therapy was withdrawn after admission, cardiac risk increased compared with patients who continued to receive statins (2.93 [95% CI, 1.64 to 6.27]; P=0.005) and tended to be higher compared with patients who never received statins (1.69 [95% CI, 0.92 to 3.56]; P=0.15). This was related to an increased event rate during the first week after onset of symptoms and was independent of cholesterol levels. In a multivariate model, troponin T elevation (P=0.005), ST changes (P=0.02), and continuation of statin therapy (P=0.008) were the only independent predictors of patient outcome. Statin pretreatment in patients with acute coronary syndromes is associated with improved clinical outcome. However, discontinuation of statins after onset of symptoms completely abrogates this beneficial effect.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies

PubMed Central

Masci, Paul P.; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A.; Gobe, Glenda C.

2017-01-01

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic. PMID:28777290

Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review.

PubMed

Franchini, Massimo; Lippi, Giuseppe; Targher, Giovanni

2011-08-01

A kaleidoscope of coagulation disorders have been reported in patients with thyroid dysfunctions. Globally, these disorders involve both primary and secondary hemostasis and range from subclinical laboratory abnormalities to, more rarely, life-threatening hemorrhages or thrombotic events. While overt hypothyroidism appears to be associated with a bleeding tendency, hyperthyroidism emerged to have an increased risk of thrombotic events. In particular, a number of case reports have documented acute venous thrombosis complications in patients with overt hyperthyroidism, especially at cerebral sites. Nevertheless, further observational and intervention studies might be needed to provide a more definitive information on the clinical relevance of this association, along with the potential implication for prevention and treatment of coagulation-fibrinolytic abnormalities in patients with thyroid dysfunction.

Rutosides for treatment of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2015-09-16

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. This is an update of the review first published in 2013. To determine the effectiveness (improvement or deterioration in symptoms) and safety of rutosides for treatment of post-thrombotic syndrome (PTS) in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) (CENTRAL (2015, Issue 8)). Clinical trials databases were searched for details of ongoing and unpublished studies. Two review authors (JM and DNK) independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two review authors (JM and SEY) extracted information from the trials. Disagreements were resolved by discussion. Data were extracted using designated data extraction forms. The Cochrane risk of bias tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post-thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of deep venous thrombosis or pulmonary embolism, compliance with therapy, and adverse effects. All of the

[Gemcitabine-induced thrombotic microangiopathy: Can we improve screening and treatment?

PubMed

Charmetant, Xavier; Jolivot, Anne; Fournier, Thomas; Puthet, Jean-Charles; Cassier, Philippe; Lemoine, Sandrine; Juillard, Laurent

2017-06-01

Thrombotic microangiopathy is a rare but severe complication of treatment with gemcitabine. Its prevalence increases because gemcitabine's indications are growing. We report four cases, which presented with common clinical and biological manifestations, i.e. high blood pressure, proteinuria and increasing plasmatic creatinine level. However, severity was not similar, hemodialysis was inconstant. There is no consensus on treatment for this condition. Stopping gemcitabine is essential. Treatment was dispensed considering the severity of the presentation: plasma exchange therapy of variable outcome, and eculizumab, which was efficient when used. It's important to note that this syndrome includes common and frequent signs in patients receiving chemotherapies. But they must encourage the research of most specific signs, such as hypertension, mechanic hemolysis signs, proteinuria or hematuria, in order to recognize thrombotic microangiopathy as early as possible to treat it precociously, and to prevent additional gemcitabine injections. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Metabolic syndrome and the risk of adverse cardiovascular events after an acute coronary syndrome.

PubMed

Cavallari, Ilaria; Cannon, Christopher P; Braunwald, Eugene; Goodrich, Erica L; Im, KyungAh; Lukas, Mary Ann; O'Donoghue, Michelle L

2018-05-01

Background The incremental prognostic value of assessing the metabolic syndrome has been disputed. Little is known regarding its prognostic value in patients after an acute coronary syndrome. Design and methods The presence of metabolic syndrome (2005 International Diabetes Federation) was assessed at baseline in SOLID-TIMI 52, a trial of patients within 30 days of acute coronary syndrome (median follow-up 2.5 years). The primary endpoint was major coronary events (coronary heart disease death, myocardial infarction or urgent coronary revascularization). Results At baseline, 61.6% ( n = 7537) of patients met the definition of metabolic syndrome, 34.7% (n = 4247) had diabetes and 29.3% had both ( n = 3584). The presence of metabolic syndrome was associated with increased risk of major coronary events (adjusted hazard ratio (adjHR) 1.29, p < 0.0001) and recurrent myocardial infarction (adjHR 1.30, p < 0.0001). Of the individual components of the definition, only diabetes (adjHR 1.48, p < 0.0001) or impaired fasting glucose (adjHR 1.21, p = 0.002) and hypertension (adjHR 1.46, p < 0.0001) were associated with the risk of major coronary events. In patients without diabetes, metabolic syndrome was numerically but not significantly associated with the risk of major coronary events (adjHR 1.13, p = 0.06). Conversely, diabetes was a strong independent predictor of major coronary events in the absence of metabolic syndrome (adjHR 1.57, p < 0.0001). The presence of both diabetes and metabolic syndrome identified patients at highest risk of adverse outcomes but the incremental value of metabolic syndrome was not significant relative to diabetes alone (adjHR 1.07, p = 0.54). Conclusions After acute coronary syndrome, diabetes is a strong and independent predictor of adverse outcomes. Assessment of the metabolic syndrome provides only marginal incremental value once the presence or absence of diabetes is established.

Acute gouty arthritis complicated with acute ST elevation myocardial infarction is independently associated with short- and long-term adverse non-fatal cardiac events.

PubMed

Liu, Kuan-Liang; Lee, Hsin-Fu; Chou, Shing-Hsien; Lin, Yen-Chen; Lin, Chia-Pin; Wang, Chun-Li; Chang, Chi-Jen; Hsu, Lung-An

2014-01-01

Large epidemiologic studies have associated gouty arthritis with the risk of coronary heart disease. However, there has been a lack of information regarding the outcomes for patients who have gout attacks during hospitalization for acute myocardial infarction. We reviewed the data of 444 consecutive patients who were admitted to our hospital between 2005 and 2008 due to acute ST elevation myocardial infarction (STEMI). The clinical outcomes were compared between patients with gout attack and those without. Of the 444, 48 patients with acute STEMI developed acute gouty arthritis during hospitalization. The multivariate analysis identified prior history of gout and estimated glomerular filtration rate as independent risk factors of gout attack for patients with acute STEMI (odds ratio (OR) 21.02, 95 % CI 2.96-149.26, p = 0.002; OR 0.92, 95 % CI 0.86-0.99, p = 0.035, respectively). The in-hospital mortality and duration of hospital stay did not differ significantly between the gouty group and the non-gouty group (controls). During a mean follow-up of 49 ± 28 months, all-cause mortality and stroke were similar for both groups. Multivariate Cox regression showed that gout attack was independently associated with short- and long-term adverse non-fatal cardiac events (hazard ratio (HR) 1.88, 95 % CI 1.09-3.24, p = 0.024; HR 1.82, 95 % CI 1.09-3.03, p = 0.022, respectively). Gout attack among patients hospitalized due to acute STEMI was independently associated with short-term and long-term rates of adverse non-fatal cardiac events.

Impact of tornadoes on hospital admissions for acute cardiovascular events.

PubMed

Silva-Palacios, Federico; Casanegra, Ana Isabel; Shapiro, Alan; Phan, Minh; Hawkins, Beau; Li, Ji; Stoner, Julie; Tafur, Alfonso

2015-11-01

There is a paucity of data describing cardiovascular events after tornado outbreaks. We proposed to study the effects of tornadoes on the incidence of cardiovascular events at a tertiary care institution. Hospital admission records from a single center situated in a tornado-prone area three months before and after a 2013 tornado outbreak were abstracted. To control for seasonal variation, we also abstracted data from the same period of the prior year (control). Hospital admissions for cardiovascular events (CVEs) including acute myocardial infarction, stroke and venous thromboembolism (VTE) were summated by zip codes, and compared by time period. There were 22,607 admissions analyzed, of which 6,705 (30%), 7,980 (35%), and 7,922 (35%) were during the pre-tornado, post-tornado, and control time frames, respectively. There were 344 CVE in the controls, 317 CVE in pre-tornado and 364 CVEs in post tornado periods. There was no difference in the prevalence of CVE during the post-tornado season compared with the control (PPR=1.05 95% CI: 0.91 to 1.21, p=0.50) or the pre-tornado season (PPR=0.96, 95% CI: 0.83 to 1.21, p=0.63). In conclusion, tornado outbreaks did not increase the prevalence of cardiovascular events. In contrast to the effect of hurricanes, implementation of a healthcare policy change directed toward the early treatment and prevention of cardiovascular events after tornadoes does not seem warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of tornadoes on hospital admissions for acute cardiovascular events

PubMed Central

Silva-Palacios, Federico; Casanegra, Ana Isabel; Shapiro, Alan; Phan, Minh; Hawkins, Beau; Li, Ji; Stoner, Julie; Tafur, Alfonso

2016-01-01

Background There is a paucity of data describing cardiovascular events after tornado outbreaks. We proposed to study the effects of tornadoes on the incidence of cardiovascular events at a tertiary care institution. Population and methods Hospital admission records from a single center situated in a tornado-prone area three months before and after a 2013 tornado outbreak were abstracted. To control for seasonal variation, we also abstracted data from the same period of the prior year (control). Hospital admissions for cardiovascular events (CVEs) including acute myocardial infarction, stroke and venous thromboembolism (VTE) were summated by zip codes, and compared by time period. Results There were 22,607 admissions analyzed, of which 6,705 (30%), 7,980 (35%), and 7,922 (35%) were during the pre-tornado, post-tornado, and control time frames, respectively. There were 344 CVE in the controls, 317 CVE in pre-tornado and 364 CVEs in post tornado periods. There was no difference in the prevalence of CVE during the post-tornado season compared with the control (PPR = 1.05 95% CI: 0.91 to 1.21, p = 0.50) or the pre-tornado season (PPR= 0.96, 95% CI: 0.83 to 1.21, p = 0.63). Conclusion In conclusion, tornado outbreaks did not increase the prevalence of cardiovascular events. In contrast to the effect of hurricanes, implementation of a healthcare policy change directed toward the early treatment and prevention of cardiovascular events after tornadoes does not seem warranted. PMID:26388119

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA L II): relationship between vascular events and the use of hormone replacement therapy in postmenopausal women.

PubMed

Fernández, Mónica; Calvo-Alén, Jaime; Bertoli, Ana M; Bastian, Holly M; Fessler, Barri J; McGwin, Gerald; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S

2007-10-01

To examine the influence of hormone replacement therapy (HRT) in the occurrence of vascular arterial and venous thrombotic events in postmenopausal women with systemic lupus erythematosus (SLE). SLE women aged > or =16 years, disease duration < or =5 years from LUMINA, a multiethnic, longitudinal outcome study, were included. Menopause was defined at disease onset as the presence of amenorrhea >6 months and/or oophorectomy, and/or increased follicle stimulating hormone values, and/or HRT use regardless of the presence or absence of climacteric symptoms (hot flashes). Patients were divided into HRT ever users and nonusers. Patients with positive antiphospholipid antibodies (n = 9) or vascular arterial events (n = 1) occurring before HRT use were excluded. The occurrence of vascular arterial and venous thrombotic events was compared between HRT users and HRT nonusers and its role examined by logistic regression after adjusting for "confounding by indication" using propensity score or logistic regression analyses. Seventy-two postmenopausal women, 32 (44%) HRT users and 40 (56%) HRT nonusers, were studied. HRT use was associated with fewer vascular arterial but not venous thrombotic events (P = 0.021) in the univariable analyses. However, after adjusting for the propensity score, HRT use was no longer significant (P = 0.064). Comparable results were obtained by logistic regression. HRT use was not associated with the occurrence of vascular arterial events in the LUMINA patients. HRT use in women with SLE should be individualized, but our data suggest its use may be safe if antiphospholipid antibodies are not present or vascular arterial events have not previously occurred.

Acute Coronary Syndrome in Indian Subcontinent Patients Residing in the Middle East: Results From Gulf Registry of Acute Coronary Events II.

PubMed

Panduranga, Prashanth; Sulaiman, Kadhim J; Al-Zakwani, Ibrahim; Alhabib, Khalid F; Hersi, Ahmad; Suwaidi, Jassim Al; Alsheikh-Ali, Alawi A; Almahmeed, Wael; Saif, Shukri Al; Al-Faleh, Hussam; Al-Lawati, Jawad; Asaad, Nidal; Al-Motarreb, Ahmed; Amin, Haitham

2015-10-01

We compared baseline characteristics, clinical presentation, and in-hospital outcomes between Middle Eastern Arabs and Indian subcontinent patients presenting with acute coronary syndrome (ACS). Of the 7930 patients enrolled in Gulf Registry of Acute Coronary Events II (RACE II), 23% (n = 1669) were from the Indian subcontinent. The Indian subcontinent patients, in comparison with the Middle Eastern Arabs, were younger (49 vs 60 years; P < .001), more were males (96% vs 80%; P < .001), had lower proportion of higher Global Registry of Acute Coronary Events risk score (8% vs 27%; P < .001), and less likely to be associated with diabetes (34% vs 42%; P < .001), hypertension (36% vs 51%; P < .001), and hyperlipidemia (29% vs 39%; P < .001) but more likely to be smokers (55% vs 29%; P < .001). After multivariable adjustment, the Middle Eastern Arabs were less likely to be associated with in-hospital congestive heart failure (odds ratio [OR], 0.65; 95% confidence interval [CI]: 0.50-0.86; P = .003) but more likely to be associated with recurrent ischemia (OR 1.33; 95% CI: 1.03-1.71; P = .026) when compared to the Indian subcontinent patients. Despite the baseline differences, there were largely no significant differences in in-hospital outcomes between the Indians and the Middle Eastern Arabs. © The Author(s) 2014.

Prognostic Implications of Dual Platelet Reactivity Testing in Acute Coronary Syndrome.

PubMed

de Carvalho, Leonardo P; Fong, Alan; Troughton, Richard; Yan, Bryan P; Chin, Chee-Tang; Poh, Sock-Cheng; Mejin, Melissa; Huang, Nancy; Seneviratna, Aruni; Lee, Chi-Hang; Low, Adrian F; Tan, Huay-Cheem; Chan, Siew-Pang; Frampton, Christopher; Richards, A Mark; Chan, Mark Y

2018-02-01

Studies on platelet reactivity (PR) testing commonly test PR only after percutaneous coronary intervention (PCI) has been performed. There are few data on pre- and post-PCI testing. Data on simultaneous testing of aspirin and adenosine diphosphate antagonist response are conflicting. We investigated the prognostic value of combined serial assessments of high on-aspirin PR (HASPR) and high on-adenosine diphosphate receptor antagonist PR (HADPR) in patients with acute coronary syndrome (ACS). HASPR and HADPR were assessed in 928 ACS patients before (initial test) and 24 hours after (final test) coronary angiography, with or without revascularization. Patients with HASPR on the initial test, compared with those without, had significantly higher intraprocedural thrombotic events (IPTE) (8.6 vs. 1.2%, p  ≤ 0.001) and higher 30-day major adverse cardiovascular and cerebrovascular events (MACCE; 5.2 vs. 2.3%, p  = 0.05), but not 12-month MACCE (13.0 vs. 15.1%, p  = 0.50). Patients with initial HADPR, compared with those without, had significantly higher IPTE (4.4 vs. 0.9%, p  = 0.004), but not 30-day (3.5 vs. 2.3%, p  = 0.32) or 12-month MACCE (14.0 vs. 12.5%, p  = 0.54). The c-statistic of the Global Registry of Acute Coronary Events (GRACE) score alone, GRACE score + ASPR test and GRACE score + ADPR test for discriminating 30-day MACCE was 0.649, 0.803 and 0.757, respectively. Final ADPR was associated with 30-day MACCE among patients with intermediate-to-high GRACE score (adjusted odds ratio [OR]: 4.50, 95% confidence interval [CI]: 1.14-17.66), but not low GRACE score (adjusted OR: 1.19, 95% CI: 0.13-10.79). In conclusion, both HASPR and HADPR predict ischaemic events in ACS. This predictive utility is time-dependent and risk-dependent. Schattauer GmbH Stuttgart.

Infective and thrombotic complications of central venous catheters in patients with hematological malignancy: prospective evaluation of nontunneled devices.

PubMed

Worth, Leon J; Seymour, John F; Slavin, Monica A

2009-07-01

Central venous catheter (CVC)-related bloodstream infection (CR-BSI) is a significant complication in hematology patients. A range of CVC devices may be used, and risks for the development of complications are not uniform. The objectives of this study were to determine the natural history and rate of CVC-related complications and risk factors for CR-BSI and to compare device-specific complications in a hematology population. An observational cohort of patients with hematologic malignancy was prospectively studied following CVC insertion. Participants were reviewed until a CVC-related complication necessitated device removal, completion of therapy, death, or defined end-of-study date. The National Nosocomial Infection Surveillance definition for CR-BSI was used. Overall and device-specific rates of infective and noninfective complications were calculated and potential risk factors were captured. One hundred six CVCs (75 peripherally inserted central venous catheters [PICCs], 31 nontunneled CVCs) were evaluated in 66 patients, over 2,399 CVC days. Thrombosis occurred in 16 cases (15.1%), exit-site infection in two (1.9%), and CR-BSI in 18 (7.5 per 1,000 CVC days). No significant differences were found when complication rates in PICC and nontunneled devices were compared. An underlying diagnosis of acute myeloid leukemia was negatively associated with CR-BSI (odds ratio (OR) 0.14, p = 0.046), and a previous diagnosis of fungal infection was associated with infection (OR 22.82, p = 0.031). CR-BSI rates in our hematology population are comparable to prior reports. A low rate of exit-site infection and high proportion of thrombotic complications were observed. No significant differences in thrombotic or infective complications were evident when PICC and nontunneled devices were compared. PICC devices are a practical and safe option for management of hematology patients.

Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid β-protein precursor abolishes its anti-thrombotic properties in vivo.

PubMed

Xu, Feng; Davis, Judianne; Hoos, Michael; Van Nostrand, William E

2017-07-01

Kunitz proteinase inhibitor (KPI) domain-containing forms of the amyloid β-protein precursor (AβPP) inhibit cerebral thrombosis. KPI domain-lacking forms of AβPP are abundant in brain. Regions of AβPP other than the KPI domain may also be involved with regulating cerebral thrombosis. To determine the contribution of the KPI domain to the overall function of AβPP in regulating cerebral thrombosis we generated a reactive center mutant that was devoid of anti-thrombotic activity and studied its anti-thrombotic function in vitro and in vivo. To determine the extent of KPI function of AβPP in regulating cerebral thrombosis we generated a recombinant reactive center KPI R13I mutant devoid of anti-thrombotic activity. The anti-proteolytic and anti-coagulant properties of wild-type and R13I mutant KPI were investigated in vitro. Cerebral thrombosis of wild-type, AβPP knock out and AβPP/KPI R13I mutant mice was evaluated in experimental models of carotid artery thrombosis and intracerebral hemorrhage. Recombinant mutant KPI R13I domain was ineffective in the inhibition of pro-thrombotic proteinases and did not inhibit the clotting of plasma in vitro. AβPP/KPI R13I mutant mice were similarly deficient as AβPP knock out mice in regulating cerebral thrombosis in experimental models of carotid artery thrombosis and intracerebral hemorrhage. We demonstrate that the anti-thrombotic function of AβPP primarily resides in the KPI activity of the protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Autoimmune conditions are associated with perioperative thrombotic complications in liver transplant recipients: A UNOS database analysis.

PubMed

Bezinover, Dmitri; Iskandarani, Khaled; Chinchilli, Vernon; McQuillan, Patrick; Saner, Fuat; Kadry, Zakiyah; Riley, Thomas R; Janicki, Piotr K

2016-05-21

End stage liver disease (ESLD) is associated with significant thrombotic complications. In this study, we attempted to determine if patients with ESLD, due to oncologic or autoimmune diseases, are susceptible to thrombosis to a greater extent than patients with ESLD due to other causes. In this retrospective study, we analyzed the UNOS database to determine the incidence of thrombotic complications in orthotopic liver transplant (OLT) recipients with autoimmune and oncologic conditions. Between 2000 and 2012, 65,646 OLTs were performed. We found 4,247 cases of preoperative portal vein thrombosis (PVT) and 1,233 cases of postoperative vascular thrombosis (VT) leading to graft failure. Statistical evaluation demonstrated that patients with either hepatocellular carcinoma (HCC) or autoimmune hepatitis (AIC) had a higher incidence of PVT (p = 0.05 and 0.03 respectively). Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and AIC had a higher incidence of postoperative VT associated with graft failure (p < 0.0001, p < 0.0001, p = 0.05 respectively). Patients with preoperative PVT had a higher incidence of postoperative VT (p < 0.0001). Multivariable logistic regression demonstrated that patients with AIC, and BMI ≥40, having had a transjugular intrahepatic portosystemic shunt, and those with diabetes mellitus were more likely to have preoperative PVT: odds ratio (OR)(1.36, 1.19, 1.78, 1.22 respectively). Patients with PSC, PBC, AIC, BMI ≤18, or with a preoperative PVT were more likely to have a postoperative VT: OR (1.93, 2.09, 1.64, 1.60, and 2.01, respectively). Despite the limited number of variables available in the UNOS database potentially related to thrombotic complications, this analysis demonstrates a clear association between autoimmune causes of ESLD and perioperative thrombotic complications. Perioperative management of patients at risk should include strategies to reduce the potential for these

[Testing system design and analysis for the execution units of anti-thrombotic device].

PubMed

Li, Zhelong; Cui, Haipo; Shang, Kun; Liao, Yuehua; Zhou, Xun

2015-02-01

In an anti-thrombotic pressure circulatory device, relays and solenoid valves serve as core execution units. Thus the therapeutic efficacy and patient safety of the device will directly depend on their performance. A new type of testing system for relays and solenoid valves used in the anti-thrombotic device has been developed, which can test action response time and fatigue performance of relay and solenoid valve. PC, data acquisition card and test platform are used in this testing system based on human-computer interaction testing modules. The testing objectives are realized by using the virtual instrument technology, the high-speed data acquisition technology and reasonable software design. The two sets of the system made by relay and solenoid valve are tested. The results proved the universality and reliability of the testing system so that these relays and solenoid valves could be accurately used in the antithrombotic pressure circulatory equipment. The newly-developed testing system has a bright future in the aspects of promotion and application prospect.

Acute neurovascular events in cancer patients receiving anti-vascular endothelial growth factor agents: Clinical experience in Paris University Hospitals.

PubMed

Tlemsani, Camille; Mir, Olivier; Psimaras, Dimitri; Vano, Yann-Alexandre; Ducreux, Michel; Escudier, Bernard; Rousseau, Benoit; Loirat, Delphine; Ceccaldi, Bernard; André, Thierry; Goldwasser, François; Ricard, Damien

2016-10-01

Despite the increasing and broadening use of agents targeting the vascular endothelial growth factor (VEGF) pathway, little is known on their acute neurovascular toxicities. This retrospective, multi-centre study examined the characteristics of patients with solid tumours who experienced an ischaemic or haemorrhagic stroke, a transient ischaemic accident (TIA) or a posterior reversible encephalopathy syndrome (PRES) while under anti-VEGF and until 8 weeks after termination of treatment and evaluated their management in our institutions from 2004 to 2014. Patients with newly diagnosed or progressive cerebral metastases at the time of the acute neurovascular event were excluded. Thirty-four patients (55.9% men) were identified, and experienced either ischaemic stroke (n = 18), PRES (n = 9), TIA (n = 6) or haemorrhagic stroke (n = 1). At initiation of anti-VEGF agents, 64.7% of patients had previous cardiovascular risk factors, and 52.9% had hypertension. Eight patients (23.5%) had received cerebral radiotherapy, five of which concomitantly to anti-VEGF treatment. Six (17%) patients died in the 8 weeks following the acute neurovascular event, and only 55.9% recovered their initial neurological status. Overall, 1-year and 2-year survival rates after the acute neurovascular event were 67.9% and 50%, respectively. When anti-VEGF agents were reintroduced (n = 6), severe vascular toxicity recurred in two patients. Neurovascular events under VEGF treatments are potentially severe, and the management of comorbid conditions has to be improved. A prospective collection of data and standardised management of such events is therefore being structured in our institutions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Complete resolution of transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease by defibrotide and plasma exchange.

PubMed

Beşişik, Sevgi Kalayoğlu; Oztürk, Gülistan Bahat; Calişkan, Yaşar; Sargin, Deniz

2005-03-01

Transplantation-associated thrombotic microangiopathy has been associated with significantly reduced survival following allogeneic bone marrow transplantation. We describe here the course of Transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease, and response to plasma exchange therapy. A 19-year-old male patient underwent hematopoietic stem cell transplantation (HSCT) from his HLA-matched brother for lymphoblastic lymphoma in the first complete remission. Transplantation-associated thrombotic microangiopathy was diagnosed 17 days after transplantation. At that time, neurological abnormalities were not present. Cyclosporin A (CsA) was discontinued. Hematological stabilization was recorded. On day +20, abdominal distention, painful hepatomegaly and ascites complicated the clinical picture. With a high hepatic venous pressure gradient (18mmH20), veno-occlusive disease of the liver was diagnosed and defibrotide was started, which resulted in a dramatic cessation of pain and increase in urinary output. However, transplantation-associated thrombotic microangiopathy-related symptoms progressed and plasma exchange was instituted, which resulted in worsening of veno-occlusive disease symptoms. He was referred to the Intensive Care Unit due to respiratory compromise and was intubated. Plasma exchange was continued in order after hemofiltration. In three days, fever resolved, hemofiltration could be stopped, and ventilator dependence ended. After 19 aphereses, serum LDH level returned to normal and schistocytes were minimal on microscopic examination of the blood film. Platelet count increase was more gradual. Plasma exchange was discontinued. On the 40th day of defibrotide, all symptoms related with veno-occlusive disease were resolved and defibrotide was stopped. We think that our case is important to establish the relation and management strategy of these two small vessel complications of HSCT.

Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders.

PubMed

Ferluga, Janez; Kouser, Lubna; Murugaiah, Valarmathy; Sim, Robert B; Kishore, Uday

2017-04-01

Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part. These include systemic lupus erythematosus, rheumatoid arthritis, atypical haemolytic uremic syndrome, anti-phospholipid syndrome and age-related macular degeneration. Such diseases are generally complex - multigenic and heterogeneous in their symptoms and predisposition/susceptibility. They usually need to be triggered by vascular trauma, drugs or infection and non-complement genetic factors also play a part. Underlying events seem to include decline in peripheral regulatory T cells, dendritic cell, and B cell tolerance, associated with alterations in lymphoid organ microenvironment. Factor H is an abundant protein, synthesised in many cell types, and its reported binding to many different ligands, even if not of high affinity, may influence a large number of molecular interactions, together with the accepted role of Factor H within the complement system. Factor H is involved in mesenchymal stem cell mediated tolerance and also contributes to self-tolerance by augmenting iC3b production and opsonisation of apoptotic cells for their silent dendritic cell engulfment via complement receptor CR3, which mediates anti-inflammatory-tolerogenic effects in the apoptotic cell context. There may be co-operation with other phagocytic receptors, such as complement C1q receptors, and the Tim glycoprotein family, which specifically bind phosphatidylserine expressed on the apoptotic cell surface. Factor H is able to discriminate between self and

Using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey to Predict the Occurrence of Short-Term Coronary Heart Disease Events in Women.

PubMed

McSweeney, Jean C; Cleves, Mario A; Fischer, Ellen P; Pettey, Christina M; Beasley, Brittany

Few instruments capture symptoms that predict cardiac events in the short-term. This study examines the ability of the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey to predict acute cardiac events within 3 months of administration and to identify the prodromal symptoms most associated with short-term risk in women without known coronary heart disease. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered to 1,097 women referred to a cardiologist for initial coronary heart disease evaluation. Logistic regression models were used to examine prodromal symptoms individually and in combination to identify the subset of symptoms most predictive of an event within 3 months. Fifty-one women had an early cardiac event. In bivariate analyses, 4 of 30 prodromal symptoms were significantly associated with event occurrence within 90 days. In adjusted analyses, women reporting arm pain or discomfort and unusual fatigue were more likely (OR, 4.67; 95% CI, 2.08-10.48) to have a cardiac event than women reporting neither. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey may assist in predicting short-term coronary heart disease events in women without known coronary heart disease. Copyright © 2017 Jacobs Institute of Women's Health. All rights reserved.

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials.

PubMed

Hesse, Kerrick; Fulton, Rachael L; Abdul-Rahim, Azmil H; Lees, Kennedy R

2014-09-01

Adverse events (AE) in trial populations present a major burden to researchers and patients, yet most events are unrelated to investigational treatment. We aimed to develop a coherent list of expected AEs, whose incidence can be predicted by patient characteristics that will inform future trials and perhaps general poststroke care. We analyzed raw AE data from patients participating in acute ischemic stroke trials. We identified events that occurred with a lower 99% confidence bound greater than nil. Among these, we applied receiver operating characteristic principles to select the fewest types of events that together represented the greatest number of reports. Using ordinal logistic regression, we modeled the incidence of these events as a function of patient age, sex, baseline National Institutes of Health Stroke Scale, and multimorbidity status, defining P<0.05 as statistically significant. We analyzed 5775 placebo-treated patients, reporting 21 217 AEs. Among 756 types of AEs, 132 accounted for 82.7%, of which 80% began within 10 days after stroke. Right hemisphere (odds ratio [OR], 1.67), increasing baseline National Institutes of Health Stroke Scale (OR, 1.11), multimorbidity status (OR, 1.09 per disease), patient age (OR, 1.01 per year), height (OR, 1.01 per centimeter), diastolic blood pressure (OR, 0.99 per mm Hg), and smoking (OR, 0.82) were independently associated with developing more AEs but together explained only 13% of the variation. A list of 132 expected AEs after acute ischemic stroke may be used to simplify interpretation and reporting of complications. AEs can be modestly predicted by patient characteristics, facilitating stratification of patients by risk for poststroke complications. © 2014 American Heart Association, Inc.

Outcomes in the treatment of thrombotic thrombocytopenic purpura with splenectomy: a retrospective cohort study.

PubMed

Outschoorn, Ubaldo Martinez; Ferber, Andres

2006-12-01

The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE), but the role of splenectomy is still undefined. The records of all patients with TTP at a single center over a 20-year period were retrospectively reviewed. Response to plasma exchange was determined. The outcome of patients treated with splenectomy in the setting of TTP was evaluated. Sixty-one patients had been treated for TTP. Thirty-nine patients (64%) achieved complete remission (CR) with PE, nineteen (31%) of these achieving sustained CR and seventeen (28%) with relapsed TTP. Twenty patients (33%) had PE refractory TTP and two patients (3%) had PE dependent TTP. During this time period, 10 patients (16%) underwent splenectomy, four patients (7%) for PE dependent TTP, three (5%) for relapsed TTP, and three (5%) for refractory TTP. All of the patients achieved CR after splenectomy. Two patients who had undergone splenectomy had subsequent relapses, both with previously relapsed TTP. In relapsed patients the relapse rate after splenectomy was 0.27 events per patient year compared to 0.6 events per patient year before splenectomy. Median follow-up after splenectomy was 19 months (range 0.13-90 months). In conclusion, relapses in TTP can be managed successfully with additional PE or with splenectomy. PE dependent or refractory TTP can be successfully treated with splenectomy.

Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.

PubMed

Schwartz, G G; Olsson, A G; Ezekowitz, M D; Ganz, P; Oliver, M F; Waters, D; Zeiher, A; Chaitman, B R; Leslie, S; Stern, T

2001-04-04

Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12

Predictors of thrombotic complications and mass effect exacerbation after pipeline embolization: The significance of adenosine diphosphate inhibition, fluoroscopy time, and aneurysm size.

PubMed

Raychev, Radoslav; Tateshima, Satoshi; Vinuela, Fernando; Sayre, Jim; Jahan, Reza; Gonzalez, Nestor; Szeder, Viktor; Duckwiler, Gary

2016-02-01

The mechanisms leading to delayed rupture, distal emboli and intraparenchymal hemorrhage in relation to pipeline embolization device (PED) placement remain debatable and poorly understood. The aim of this study was to identify clinical and procedural predictors of these perioperative complications. We conducted a retrospective review of consecutive patients who underwent PED placement. We utilized a non-commercial platelet aggregation method measuring adenosine diphosphate (ADP)% inhibition for evaluation of clopidogrel response. To our knowledge, this is the first study to test ADP in neurovascular procedures. Multivariable regression analysis was used to identify the strongest predictor of three separate outcomes: (1) thrombotic complications, (2) hemorrhagic complications, and (3) aneurysm mass effect exacerbation Permanent complication-related morbidity and mortality at 3 months was 6% (3/48). No specific predictors of hemorrhagic complications were identified. In the univariate analysis, the strongest predictors of thrombotic complications were: ADP% inhibition<49 (p=0.01), aneurysm size (p=0.04) and fluoroscopy time (p=0.002). In the final multivariate analysis, among all baseline variables, fluoroscopy time exceeding 52 min was the only factor associated with thrombotic complications (p=0.007). Aneurysm size≥18 mm was the single predictor of mass effect exacerbation (p=0.039). Procedural complexity, reflected by fluoroscopy time, is the strongest predictor of thrombotic complications in this study. ADP% inhibition is a reliable method of testing clopidogrel response in neurovascular procedures and values of <50% may predict thrombotic complications. Interval mass effect exacerbation after PED placement may be anticipated in large aneurysms exceeding 18 mm. © The Author(s) 2015.

Catastrophic antiphospholipid antibody syndrome presenting as acute vascular occlusion in a young female patient.

PubMed

Alonso, Joaquín Valle; Del Pozo, Francisco Javier Fonseca; Álvarez, Manuel Vaquero; Pedraza, Jorge; Aguayo, Miguel Angel; Sanchez, Almudena

Acquired thrombotic and thromboembolic disorders may be presented initially with symptoms and signs of acute ischaemia or organ dysfunction that will lead many of these patients to seek care in the emergency department. We report a case of a 19-year-old female patient who developed catastrophic antiphospholipid syndrome (CAPS syndrome or Asherson syndrome) 6 weeks post stillbirth with an initial presentation of acute vascular occlusion. The patient was immediately operated and anticoagulated with significant improvement. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.

PubMed

Lavikainen, Piia; Helin-Salmivaara, Arja; Eerola, Mervi; Fang, Gang; Hartikainen, Juha; Huupponen, Risto; Korhonen, Maarit Jaana

2016-06-03

Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Retrospective cohort study. Finnish healthcare registers. Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect. Published by the BMJ Publishing

Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

PubMed

Pezzini, Alessandro; Grassi, Mario; Lodigiani, Corrado; Patella, Rosalba; Gandolfo, Carlo; Zini, Andrea; Delodovici, Maria Luisa; Paciaroni, Maurizio; Del Sette, Massimo; Toriello, Antonella; Musolino, Rossella; Calabrò, Rocco Salvatore; Bovi, Paolo; Adami, Alessandro; Silvestrelli, Giorgio; Sessa, Maria; Cavallini, Anna; Marcheselli, Simona; Bonifati, Domenico Marco; Checcarelli, Nicoletta; Tancredi, Lucia; Chiti, Alberto; Del Zotto, Elisabetta; Spalloni, Alessandra; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Giacalone, Giacomo; Ferrazzi, Paola; Poli, Loris; Morotti, Andrea; Rasura, Maurizia; Simone, Anna Maria; Gamba, Massimo; Cerrato, Paolo; Micieli, Giuseppe; Melis, Maurizio; Massucco, Davide; De Giuli, Valeria; Iacoviello, Licia; Padovani, Alessandro

2014-04-22

Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65). Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.

Acute myocardial infarction in a young male wrestler: A case report

PubMed Central

Poorzand, Hoorak; Jafarzadeh Esfehani, Reza; Hosseinzadeh, Peyman; Vojdanparast, Mohammad

2015-01-01

BACKGROUND Anabolic steroids have been widely used in recent years. It could adversely affect the cardiovascular system. Non-traditional risk factors for coronary heart diseases (CHDs) have raised great concern. CASE REPORT A young bodybuilder was presented with crushing retrosternal chest pain, excessive diaphoresis, and vomiting. The symptoms began during wrestling. The patient did not have a history of traditional cardiovascular risk factors. He was using large quantities of nutritional and bodybuilding supplements with multiple intramuscular injections of dexamethasone during past 6 months. The electrocardiography (ECG) revealed ST-segment elevation in the precordial, I and aVL leads consistent with acute extensive myocardial infarction (MI). Lipid profile, cardiac troponin, and creatine phosphokinase-MB (CPK-MB) was abnormal. Transthoracic echocardiography (TTE) revealed mild left ventricular (LV) enlargement and reduced global systolic dysfunction with regional wall akinesia. The patient received thrombolytic therapy which was resulted in symptomatic relief and resolution in ST-T changes. Significant smoke was seen in LV cavity without clot formation on the discharge day. About 1 week later, large fresh clots were seen in the apex. He was admitted again, and the burden of clots was reduced significantly after initiation of oral warfarin. Other laboratory tests were as follows: High-sensitivity C-reactive protein (CRP): 25.9 mg/dl, homocysteine: 26.2 µmol/l. The patient was discharged with specific medication. Clots were disappeared after 6 weeks of warfarin therapy. Later, the patient was evaluated again, and there was not any symptom and LV clots. CONCLUSION Hyperhomocysteinemia could be induced by steroid abuse and may cause atherosclerotic and thrombotic effects in healthy athletes. We suggest clinicians to take a careful history of young athletes presented with MI or thrombotic events and also pay special attention to their homocysteine levels in their

In vitro efficacy of pro- and anticoagulant strategies in compensated and acutely ill patients with cirrhosis.

PubMed

Lisman, Ton; Kleiss, Simone; Patel, Vishal C; Fisher, Caleb; Adelmeijer, Jelle; Bos, Sarah; Singanayagam, Arjuna; Stoy, Sidsel Hyldgaard; Shawcross, Debbie L; Bernal, William

2018-05-16

A simultaneous decline in pro- and anticoagulant drivers in patients with liver diseases results in a 'rebalanced' hemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro- and antihemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound hemostatic changes. We tested the effects in vitro of the addition of clinically relevant doses of commonly used pro- and antihemostatic strategies in plasma from healthy individuals (n=30) and patients with compensated (n=18) and acutely decompensated cirrhosis (n=18), and acute-on-chronic liver failure (n=10). We used thrombin generation tests and fibrin clot permeability assays to assess potency of various approaches. Fresh frozen plasma and recombinant factor VIIa modestly increased thrombin generation (10-20%). Prothrombin complex concentrate increased thrombin generation 2-fold in controls and 2-4-fold in patients. Clot permeability decreased after addition of fibrinogen concentrate by 51% in controls and by 50-60% in patients. Low molecular weight heparin decreased thrombin generation by 18% in controls and by 23-54% in patients. Similarly, dabigatran decreased thrombin generation by 33% in controls and by 47-100% in patients. In contrast, rivaroxaban decreased thrombin generation by 55% in controls, but only by 11-38% in patients. These in vitro data suggest little prohemostatic effect of fresh frozen plasma and recombinant factor VIIa in acutely ill cirrhotics, whereas prothrombin complex concentrate and fibrinogen concentrate clearly improved hemostasis. Furthermore, our data suggest the requirement for dose-adjustments of commonly used anticoagulants in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Diagnosis and management of thrombotic thrombocytopenic purpura (TTP) in Australia: findings from the first 5 years of the Australian TTP/thrombotic microangiopathy registry.

PubMed

Blombery, P; Kivivali, L; Pepperell, D; McQuilten, Z; Engelbrecht, S; Polizzotto, M N; Phillips, L E; Wood, E; Cohney, S

2016-01-01

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA). In 2009, the Australian TTP/TMA registry was established to collect data on patients presenting with TTP/TMA throughout Australia. To summarise information on the diagnosis and management of patients with TTP collected in the first 5 years (2009-2014) of the Australian TTP registry. Registry data from June 2009 to October 2014 were reviewed. Fifty-seven patients were identified with TTP (defined as ADAMTS13 activity <10%), accounting for 72 clinical episodes. ADAMTS13 inhibitor testing was performed in nine out of 57 patients (16%), reflecting the limited availability of accredited testing facilities. Sixty-seven out of 72 episodes were treated with therapeutic plasma exchange (PEx) using cryodepleted plasma (40% of episodes), fresh frozen plasma (36%) or a mixture (22%). Median exposure to plasma products was 55.9 L. PEx was commenced ≥2 days from stated diagnosis in 15% of episodes. Adverse reactions to PEx were common with documented allergic reactions (including life threatening) in 21% of episodes. Adjunctive immunosuppression was documented in 76% of episodes (corticosteroid 71% and rituximab 39%). Platelet transfusion was administered in 15% of episodes. Data from the Australian TTP/TMA registry suggest a heterogenous approach to the diagnosis and management of TTP in Australia over the assessed period. These observations highlight areas for improvement and standardisation of practice, including comprehensive diagnostic testing, more immediate access to PEx and a more uniform approach to adjunctive immunosuppression and supportive care. © 2015 Royal Australasian College of Physicians.

Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease

PubMed Central

Fanaroff, Alexander C.; Roe, Matthew T.

2018-01-01

Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with apirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase, aspirin impairs gastric mucosal protective mechanisms. Prior trials have shown that up to 15–20% of patients developed gastrointestinal symptoms with aspirin monotherapy and roughly 1% of patients per year had a clinically significant bleeding event, including 1 in 1000 patients who suffered an intracranial or fatal bleed. These risks have been shown to be compounded for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), who are also treated with other anti-thrombotic agents during the acute care/procedural period, as well as for an extended time period afterwards. Given observations of substantial increases in bleeding rates from many prior long-term clinical trials that have evaluated aspirin together with other oral platelet inhibitors or oral anti-coagulants, the focus of contemporary research has pivoted towards tailored anti-thrombotic regimens that attempt to either shorten the duration of exposure to aspirin or replace aspirin with an alternative anti-thrombotic agent. While these shifts are occurring, the safety profile of aspirin when used for the secondary prevention treatment of patients with established cardiovascular disease deserves further consideration. PMID:27028617

The Acute Risks of Exercise in Apparently Healthy Adults and Relevance for Prevention of Cardiovascular Events.

PubMed

Goodman, Jack M; Burr, Jamie F; Banks, Laura; Thomas, Scott G

2016-04-01

Increased physical activity (PA) is associated with improved quality of life and reductions in cardiovascular (CV) morbidity and all-cause mortality in the general population in a dose-response manner. However, PA acutely increases the risk of adverse CV event or sudden cardiac death (SCD) above levels expected at rest. We review the likelihood of adverse CV events related to exercise in apparently healthy adults and strategies for prevention, and contextualize our understanding of the long-term risk reduction conferred from PA. A systematic review of the literature was performed using electronic databases; additional hand-picked relevant articles from reference lists and additional sources were included after the search. The incidence of adverse CV events in adults is extremely low during and immediately after PA of varying types and intensities and is significantly lower in those with long-standing PA experience. The risk of SCD and nonfatal events during and immediately after PA remains extremely low (well below 0.01 per 10,000 participant hours); increasing age and PA intensity are associated with greater risk. In most cases of exercise-related SCD, occult CV disease is present and SCD is typically the first clinical event. Exercise acutely increases the risk of adverse CV events, with greater risk associated with vigorous intensity. The risks of an adverse CV event during and immediately after exercise are outweighed by the health benefits of vigorous exercise performed regularly. A key challenge remains the identification of occult structural heart disease and inheritable conditions that increase the chances of lethal arrhythmias during exercise. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-12-16

Psoriasis patients exhibit an increased risk of atherothrombotic events, including myocardial infarction and stroke. Clinical evidence suggests that psoriasis patients with early onset and more severe disease have the highest risk for these co-morbidities, perhaps due to the extent of body surface involvement, subsequent levels of systemic inflammation, or chronicity of disease. We sought to determine whether acute or chronic skin-specific inflammation was sufficient to promote thrombosis. We used two experimental mouse models of skin-specific inflammation generated in either an acute (topical Aldara application onto wild-type C57Bl/6 mice for 5 days) or chronic (a genetically engineered K5-IL-17C mouse model of psoriasiform skin inflammation) manner. Arterial thrombosis was induced using carotid artery photochemical injury (Rose Bengal-green light laser) and carotid artery diameters were measured post-clot formation. We also examined measures of clot formation including prothrombin (PT) and activated partial thromboplastin time (aPTT). Skin inflammation was examined histologically and we profiled plasma-derived lipids. The number of skin-draining lymph-node (SDLN) and splenic derived CD11b(+)Ly6C(high) pro-inflammatory monocytes and CD11b(+)Ly6G(+) neutrophils was quantified using multi-color flow cytometry. Mice treated with topical Aldara for 5 days had similar carotid artery thrombotic occlusion times to mice treated with vehicle cream (32.2 ± 3.0 vs. 31.4 ± 2.5 min, p = 0.97); in contrast, K5-IL-17C mice had accelerated occlusion times compared to littermate controls (15.7 ± 2.1 vs. 26.5 ± 3.5 min, p < 0.01) while carotid artery diameters were similar between all mice. Acanthosis, a surrogate measure of inflammation, was increased in both Aldara-treated and K5-IL-17C mice compared to their respective controls. Monocytosis, defined as elevated SDLN and/or splenic CD11b(+)Ly6C(high) cells, was significantly increased in both Aldara-treated (SDLN: 3.8-fold, p

CYP2C19 activity and cardiovascular risk factors in patients with an acute coronary syndrome.

PubMed

Martínez-Quintana, Efrén; Rodríguez-González, Fayna; Medina-Gil, José María; Garay-Sánchez, Paloma; Tugores, Antonio

2017-09-20

CYP2C19 is a major isoform of cytochrome P450 that metabolizes a number of drugs and is involved in the glucocorticoids synthesis. CYP2C19 polymorphisms have been associated with the genetic risk for type 2 diabetes. Five hundred and three patients with an acute coronary event were studied to assess the association between the CYP2C19 activity (CYP2C19*2, CYP2C19*3 and CYP2C19*17 variants) and the type of acute coronary syndrome, cardiovascular risk factors (arterial systemic hypertension, diabetes mellitus, dyslipidemia and smoking), analytical parameters and the extent and severity of coronary atherosclerosis. Genotype distribution in our series was similar to that expected in the Caucasian population. Among the traditional cardiovascular risk factors, very poor metabolizer patients (*2/*2, *3/*3 or *2/*3) had a greater tendency to present diabetes mellitus needing insuline (P=.067). Conversely, when we compared very poor, poor and normal metabolizers vs. rapid and ultrarapid metabolizers we found significant differences in those diabetic patients under insulin treatment (64 patients [18%] vs. 17 patients [11%]; P=.032). On the contrary, analytical parameters, systemic arterial hypertension, dyslipidemia, smoking or the personal/family history of coronary artery disease did not reach statistical significance regardless of CYP2C19 activity. Similarly, the number and the type of coronary disease (thrombotic, fibrotic or both) did not differ between patients with different CYP2C19 enzyme activity. Patients with an acute coronary event and a very poor, poor and normal CYP2C19 metabolizer genotype have a higher prevalence of diabetes mellitus needing insuline than patients with the rapid and ultrarapid metabolizers CPY2C19 genotype. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Sex differences in case fatality before and after admission to hospital after acute cardiac events: analysis of community based coronary heart disease register.

PubMed Central

Sonke, G. S.; Beaglehole, R.; Stewart, A. W.; Jackson, R.; Stewart, F. M.

1996-01-01

OBJECTIVE: To determine whether the reported higher case fatality in hospital after an acute cardiac event in women can be explained by sex differences in mortality before admission and in baseline risk factors. DESIGN: Analyses of data from a community based coronary heart disease register. SETTING: Auckland region, New Zealand. SUBJECTS: 5106 patients aged 25-64 years with an acute cardiac event leading to coronary death or definite myocardial infarction within 28 days of onset, occurring between 1986 and 1992. MAIN OUTCOME MEASURES: Case fatality before admission, 28 day case fatality for patients in hospital, and total case fatality after an acute cardiac event. RESULTS: Despite a more unfavourable risk profile women tended to have lower case fatality before admission than men (crude odds ratio 0.88; 95% confidence interval 0.77 to 1.02). Adjustment for age, living arrangements, smoking, medical history, and treatment increased the effect of sex (0.72; 0.60 to 0.86). After admission to hospital, women had a higher case fatality than men (1.76; 1.43 to 2.17), but after adjustment for confounders this was reduced to 1.18 (0.89 to 1.58). Total case fatality 28 days after an acute cardiac event showed no significant difference between men and women (0.85; 0.70 to 1.02) CONCLUSIONS: The higher case fatality after an acute cardiac event in women admitted to hospital is largely explained by differences in living status, history, and medical treatment and is balanced by a lower case fatality before admission. PMID:8870571

Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer.

PubMed

Revel-Vilk, S; Yacobovich, J; Tamary, H; Goldstein, G; Nemet, S; Weintraub, M; Paltiel, O; Kenet, G

2010-09-01

The use of central venous catheters (CVCs) has greatly improved the quality of care in children with cancer, yet these catheters may cause serious infectious and thrombotic complications. The aim of this prospective registry study was to assess the host and CVC-related risk factors for CVC-created thrombotic complications. Patients undergoing CVC insertion for chemotherapy were followed prospectively for CVC complications. At the time of enrollment, demographic, clinical, and CVC-related data, and family history of thrombosis were collected. Survival and Cox regression analyses were performed. A total of 423 CVCs were inserted into 262 patients for a total of 76,540 catheter days. The incidence of CVC-related deep-vein thrombosis (DVT) was 0.13 per 1000 catheter-days (95% confidence interval [CI], 0.06-0.24). Insertion of peripherally inserted central catheters (PICCs) and insertion in an angiography suite significantly increased the risk of symptomatic CVC-related DVT. The incidence of CVC occlusion was 1.35 per 1000 catheter-days (95% CI, 1.1-1.63). Positive family history of thrombosis significantly increased the risk of CVC occlusion (hazard ratio [HR], 2.16; 95% CI, 1.2-3.8). The CVC-related risk factors were insertion of Hickman catheters, insertion in angiography suite, and proximal-tip location. Patients developing at least 1 episode of both CVC occlusion and infection had an increased risk for developing symptomatic CVC-related DVT (HR, 4.15; 95% CI, 1.2-14.4). Both patient-related and CVC-related factors are associated with higher risk of symptomatic thrombotic complications. These risk factors could be used in the clinical setting and in developing future studies for CVC thromboprophylaxis.

Analyzing discharge strategies during acute care: a discrete-event simulation study.

PubMed

Crawford, Elizabeth A; Parikh, Pratik J; Kong, Nan; Thakar, Charuhas V

2014-02-01

We developed a discrete-event simulation model of patient pathway through an acute care hospital that comprises an ED and several inpatient units. The effects of discharge timing on ED waiting and boarding times, ambulance diversions, leave without treatment, and readmissions were explicitly modeled. We then analyzed the impact of 1 static and 2 proactive discharge strategies on these system outcomes. Our analysis indicated that although the 2 proactive discharge strategies significantly reduced ED waiting and boarding times, and several other measures, compared with the static strategy (P < 0.01), the number of readmissions increased substantially. Further analysis indicated that these findings are sensitive to changes in patient arrival rate and conditions for ambulance diversion. Determining the appropriate time to discharge patients not only can affect individual patients' health outcomes, but also can affect various aspects of the hospital. The study improves our understanding of how individual inpatient discharge decisions can be objectively viewed in terms of their impact on other operations, such as ED crowding and readmission, in an acute care hospital.

Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction

PubMed Central

Eicher, John D.; Wakabayashi, Yoshiyuki; Vitseva, Olga; Esa, Nada; Yang, Yanqin; Zhu, Jun; Freedman, Jane E.; McManus, David D.; Johnson, Andrew D.

2016-01-01

Transcripts in platelets are largely produced in precursor megakaryocytes but remain physiologically-active as platelets translate RNAs and regulate protein/RNA levels. Recent studies using transcriptome sequencing (RNA-seq) characterized the platelet transcriptome in limited numbers of non-diseased individuals. Here, we expand upon these RNA-seq studies by completing RNA-seq in platelets from 32 patients with acute myocardial infarction (MI). Our goals were to characterize the platelet transcriptome using a population of patients with acute MI and relate gene expression to platelet aggregation measures and ST-segment elevation MI (STEMI) (n=16) versus non-STEMI (NSTEMI) (n=16) subtypes. Similar to other studies, we detected 9,565 expressed transcripts, including several known platelet-enriched markers (e.g., PPBP, OST4). Our RNA-seq data strongly correlated with independently ascertained platelet expression data and showed enrichment for platelet-related pathways (e.g., wound response, hemostasis, and platelet activation), as well as actin-related and post-transcriptional processes. Several transcripts displayed suggestively higher (FBXL4, ECHDC3, KCNE1, TAOK2, AURKB, ERG, and FKBP5) and lower (MIAT, PVRL3and PZP) expression in STEMI platelets compared to NSTEMI. We also identified transcripts correlated with platelet aggregation to TRAP (ATP6V1G2, SLC2A3), collagen (CEACAM1, ITGA2), and ADP (PDGFB, PDGFC, ST3GAL6). Our study adds to current platelet gene expression resources by providing transcriptome-wide analyses in platelets isolated from patients with acute MI. In concert with prior studies, we identify various genes for further study in regards to platelet function and acute MI. Future platelet RNA-seq studies examining more diverse sets of healthy and diseased samples will add to our understanding of platelet thrombotic and non-thrombotic functions. PMID:26367242

Paraoxonase 1 (Q192R) gene polymorphism, coronary heart disease and the risk of a new acute coronary event.

PubMed

Martínez-Quintana, Efrén; Rodríguez-González, Fayna; Medina-Gil, José María; Garay-Sánchez, Paloma; Tugores, Antonio

Paraoxonase 1 (PON1) plays a major role in the oxidation of low density lipoprotein and in the prevention of coronary atherogenesis. In this context, coding region polymorphisms of PON1 gene, responsible for the enzyme activity, has become of interest as a marker for atherogenesis. A study and follow-up was conducted on 529 patients with an acute coronary event in order to assess the association between the PON1 Q192R (rs662;A/G) polymorphism, the type of acute coronary syndrome, cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidaemia, and smoking), the extent and severity of coronary atherosclerosis, and the medium-term clinical follow-up. The QQ genotype was found in 245 (46.3%) patients, with 218 (41.2%) patients showing the QR genotype, and 66 (14.5%) patients had the RR genotype. No significant differences were found between the QQ and QR/RR genotypes as regards the clinical characteristics, the analytical data, and the angiographic variables. Similarly, Kaplan-Meier survival analysis showed no significant differences in presenting with a new acute coronary event (p=0.598), cardiac mortality (p=0.701), stent thrombosis (p=0.508), or stent re-stenosis (p=0.598) between QQ and QR/RR genotypes during the follow-up period (3.3±2.2 years). In patients with an acute coronary syndrome, the PON1 Q192R genotypes did not influence the risk of suffering a new acute coronary event during the medium-term follow-up. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

PubMed Central

Armstrong, Paul C.; Kirkby, Nicholas S.; Zain, Zetty N.; Emerson, Michael; Mitchell, Jane A.; Warner, Timothy D.

2011-01-01

Background Clinical use of selective inhibitors of cyclooxygenase (COX)-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice. Methodology/Principal Findings A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control) diclofenac (1 mg.kg−1, i.v.) and parecoxib (0.5 mg.kg−1, i.v.) on thrombus formation induced by collagen or the thromboxane (TX) A2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist. Conclusions/Significance Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA2, but not that induced by U46619, which is independent of platelet TXA2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis. PMID:21629780

Hospital admissions for asthma and acute bronchitis in El Paso, Texas: do age, sex, and insurance status modify the effects of dust and low wind events?

PubMed

Grineski, Sara E; Staniswalis, Joan G; Bulathsinhala, Priyangi; Peng, Yanlei; Gill, Thomas E

2011-11-01

El Paso County (Texas) is prone to still air inversions and is one of the dust "hot spots" in North America. In this context, we examined the sub-lethal effects of airborne dust and low wind events on human respiratory health (i.e., asthma and acute bronchitis) between 2000 and 2003, when 110 dust and 157 low wind events occurred. Because environmental conditions may not affect everyone the same, we explored the effects of dust and low wind within three age groups (children, adults, and the elderly), testing for effect modifications by sex and insurance status, while controlling for weather and air pollutants. We used a case-crossover design using events matched with referent days on the same day-of-the-week, month, and year with conditional logistic regression to estimate the probability of hospital admission, while controlling for apparent temperature (lag 1), nitrogen dioxide, and particulate matter of 2.5μm or less. Children (aged 1-17) were 1.19 (95% confidence interval: 1.00-1.41) times more likely to be hospitalized for asthma three days after a low wind event, and 1.33 (95% CI: 1.01-1.75) times more likely to be hospitalized for acute bronchitis one day after a dust event than on a clear day. Girls were more sensitive to acute bronchitis hospitalizations after dust events (1.83, 95% CI: 1.09-3.08) than boys, but less sensitive than boys to acute bronchitis hospitalizations after low wind events (0.68, 95% CI: 0.46-1.00). We found general trends with regard to dust and low wind events being associated with increased odds of hospitalization for asthma and bronchitis amongst all ages and adults (aged 18-64). Adults covered by Medicaid and adults without health insurance had higher risks of hospitalization for asthma and acute bronchitis after both low wind and dust events. Results suggest that there were respiratory health effects associated with dust and low wind events in El Paso, with stronger impacts among children and poor adults. Girls and boys with

Hospital admissions for asthma and acute bronchitis in El Paso, Texas: Do age, sex, and insurance status modify the effects of dust and low wind events?

PubMed Central

Staniswalis, Joan G.; Bulathsinhala, Priyangi; Peng, Yanlei; Gill, Thomas E.

2013-01-01

Background El Paso County (Texas) is prone to still air inversions and is one of the dust “hot spots” in North America. In this context, we examined the sub-lethal effects of airborne dust and low wind events on human respiratory health (i.e., asthma and acute bronchitis) between 2000 and 2003, when 110 dust and 157 low wind events occurred. Because environmental conditions may not affect everyone the same, we explored the effects of dust and low wind within three age groups (children, adults, and the elderly), testing for effect modifications by sex and insurance status, while controlling for weather and air pollutants. Methods We used a case-crossover design using events matched with referent days on the same day-of-the-week, month, and year with conditional logistic regression to estimate the probability of hospital admission, while controlling for apparent temperature (lag 1), nitrogen dioxide, and particulate matter of 2.5 micrometers or less. Results Children (aged 1–17) were 1.19 (95% confidence interval: 1.00–1.41) times more likely to be hospitalized for asthma three days after a low wind event, and 1.33 (95% CI: 1.01–1.75) times more likely to be hospitalized for acute bronchitis one day after a dust event than on a clear day. Girls were more sensitive to acute bronchitis hospitalizations after dust events (1.83, 95% CI: 1.09–3.08) than boys, but less sensitive than boys to acute bronchitis hospitalizations after low wind events (0.68, 95% CI: 0.46–1.00). We found general trends with regard to dust and low wind events being associated with increased odds of hospitalization for asthma and bronchitis amongst all ages and adults (aged 18–64). Adults covered by Medicaid and adults without health insurance had higher risks of hospitalization for asthma and acute bronchitis after both low wind and dust event Conclusions Results suggest that there were respiratory health effects associated with dust and low wind events in El Paso, with stronger

von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review.

PubMed

Morici, Nuccia; Cantoni, Silvia; Panzeri, Francesco; Sacco, Alice; Rusconi, Chiara; Stucchi, Miriam; Oliva, Fabrizio; Cattaneo, Marco

2017-07-01

Deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is central to the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a microangiopathic syndrome that presents as an acute medical emergency. In this review we will explore the evidence of a two-way relationship between TTP and ACS. Moreover, we will review the evidence emerged from epidemiological studies of an inverse relationship between the plasma levels of ADAMTS13 and the risk of ACS. Pubmed, MEDLINE and EMBASE, CINHAL, COCHRANE and Google Scholar databases were searched from inception to January 2017. The search yielded 43 studies representing 23 unique patient cases, 5 case series, 5 cohort studies and 10 case-control studies. Most ACS cases developing in the setting of TTP resolved with standard treatment of the underlying microangiopathy, with only a few requiring coronary invasive management. Antiplatelet therapy was not usually prescribed and all of the currently used P2Y 12 were felt to be a potential trigger for a TTP-like syndrome, although our review revealed that the occurrence of TTP in patients treated with new P2Y 12 antagonists is rare. Most studies confirmed the inverse association among ADAMTS13 levels and ACS. The heart is a definite target organ in TTP. The clinical spectrum of its involvement is probably influenced by local factors that add on to the systemic deficiency characteristic of TTP. It follows that patients with TTP should be carefully monitored for ACS events, especially when multiple risk factors for coronary disease exist. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rutosides for treatment of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2013-04-30

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. To determine the effectiveness and safety of rutosides for treatment of PTS in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. Two authors (JM and DNK) independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two authors (JM and SEY) extracted information from the trials. Disagreements were resolved by discussion. Data were extracted using designated data extraction forms. The Cochrane risk of bias tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post-thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of deep venous thrombosis or pulmonary embolism, compliance with therapy, and adverse effects. All of the outcome measures were analysed using Mantel-Haenzel fixed-effect model odds ratios. The unit of analysis was the number of patients. Ten reports of nine studies were identified

Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reduced-intensity conditioning: The incidence is not reduced.

PubMed

Shimoni, Avichai; Yeshurun, Moshe; Hardan, Izhar; Avigdor, Abraham; Ben-Bassat, Isaac; Nagler, Arnon

2004-07-01

Thrombotic microangiopathy (TMA) is one of the most severe complications of stem cell transplantation (SCT). Endothelial cell injury caused by the toxic effects of high-dose chemoradiotherapy is likely the primary event in pathogenesis. The incidence, clinical settings, and risk factors for TMA in the era of nonmyeloablative conditioning have not been well defined. The data on 147 consecutive SCTs in a single center were collected, and patients with TMA were identified. Patient characteristics, response to therapy, and outcome were recorded, and risk factors were determined. TMA occurred in 22 of 147 transplantations, with a projected incidence of 20% +/- 4%. TMA occurred in 3 clinical settings: classic multifactorial TMA, TMA associated with severe hepatic graft-versus-host disease (GVHD), and TMA associated with second SCT, with a projected incidence of 8% +/- 3%, 73% +/- 14%, and 70% +/- 16% of patients at risk, respectively. TMA occurred after 23% +/- 6% of nonmyeloablative and 16% +/- 5% of myeloablative conditioning regimens (not significant). Univariate analysis determined SCT from unrelated donors, SCT during advanced or active disease, second SCT within 6 months of a prior SCT, and acute GVHD as risk factors for TMA. The last 2 factors remained significant in a multivariate model. Thirty-two percent of patients responded to therapy. The peri-TMA mortality rate was 68% +/- 10%. Six patients had diffuse alveolar hemorrhage complicating TMA. SCT-associated TMA is a relatively common complication with unsatisfactory therapy and grim prognosis. Fludarabine-based nonmyeloablative conditioning does not confer a lesser risk for TMA. This observation may relate to the selective use of these regimens in elderly and heavily pretreated patients or to the lack of reduction of GVHD with these regimens, and fludarabine itself may be involved in causing endothelial damage. Further exploration of novel preventive and therapeutic measurements is required in high

[Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura: classification based on molecular etiology and review of recent developments in diagnostics].

PubMed

Prohászka, Zoltán

2008-07-06

Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are overlapping clinical entities based on historical classification. Recent developments in the unfolding of the pathomechanisms of these diseases resulted in the creation of a molecular etiology-based classification. Understanding of some causative relationships yielded detailed diagnostic approaches, novel therapeutic options and thorough prognostic assortment of the patients. Although haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are rare diseases with poor prognosis, the precise molecular etiology-based diagnosis might properly direct the therapy of the affected patients. The current review focuses on the theoretical background and detailed description of the available diagnostic possibilities, and some practical information necessary for the interpretation of their results.

Nonurgent commercial air travel after acute coronary syndrome: a review of 288 patient events.

PubMed

Pearce, Emily; Haffner, Faith; Brady, Lauren B; Sochor, Mark; Duchateau, Francois X; O'Connor, Robert E; Verner, Laurent; Brady, William J

2014-01-01

We studied a population of individuals who experienced an acute coronary syndrome (ACS) event while traveling abroad and required nonurgent commercial air travel to the home region. This retrospective study gathered data from 288 patients enrolled in a travel-based medical assistance program. Interventions, complications, and travel home were assessed for trends. Descriptive and comparison statistical analyses were performed. Two hundred eighty-eight patients were identified and entered into the review. Of the patients in this study, 77.1% were male with an average age of 67.7 years. One hundred sixteen (40.3%) patients were diagnosed with unstable angina pectoris (USAP), whereas the remaining 172 (59.7%) patients experienced acute myocardial infarction (AMI). Regarding inpatient complications during the initial admission, 121 (42.0%) patients experienced 1 or more adverse event. The average number of days after an ACS event that a patient began to travel home was 10.5 days for the entire patient population (USAP patients = 8.8 days, AMI patients = 11.8 days). Two hundred twenty (76.4%) patients traveled with a medical escort, and 48 (16.7%) patients received supplemental oxygen during air travel. Four (1.4%) in-flight adverse events occurred in the following ACS diagnostic groups: 2 in the complicated AMI group, 1 in the uncomplicated USAP group, and 1 in the uncomplicated AMI group. No in-flight deaths occurred. Nine (3.1%) deaths were noted within 2 weeks after returning to the home region. The deaths after returning to the home region occurred in the following ACS diagnostic groups: 2 in the complicated USAP group, 1 in the uncomplicated USAP group, and 6 in the complicated AMI group. None of the patients who experienced in-flight events died after returning to their home region. Upon discharge, the vast majority of ACS patients who travel to their home region via commercial air do not experience adverse events in-flight; when such adverse events occur in

Access to primary health care for acute vascular events in rural low income settings: a mixed methods study.

PubMed

Ahmed, Shyfuddin; Chowdhury, Muhammad Ashique Haider; Khan, Md Alfazal; Huq, Nafisa Lira; Naheed, Aliya

2017-01-18

Cardiovascular diseases (CVDs) are the leading cause of global mortality. Among the CVDs, acute vascular events (AVE) mainly ischemic heart diseases and stroke are the largest contributors. To achieve 25% reduction in preventable deaths from CVDs by 2025, health systems need to be equipped with extended service coverage in order to provide person-centered care. The overall goal of this proposed study is to assess access to health care in-terms of service availability, care seeking patterns and barriers to access care after AVE in rural Bangladesh. We will consider myocardial infarction (MI) and stroke as acute vascular events. We will conduct a mixed methods study in rural Matlab, Bangladesh. This study will comprise of a) health facility survey, b) structured questionnaire interview and c) qualitative study. We will assess service availabilities by creating an inventory of public and private health facilities. Readiness of the facilities to deliver services for AVE will be assessed through a health facility survey using 'service availability and readiness assessment' (SARA) tools of the World Health Organization (WHO). We will interview survivors of AVE and caregivers (present and accompanied the person during the event) of person who died from AVE for exploring patterns of care seeking during an AVE. For exploring barriers to access care for AVE, we will conduct in-depth interview with survivors of AVE and caregivers of the person who died from AVE. We will also conduct key informant interviews with the service providers at primary health care (PHC) facilities and government high level officials at central health administration of Bangladesh. This study will provide a comprehensive picture of access to primary health care services during acute cardiovascular events as stroke & MI in rural context of Bangladesh. It will explore available service facilities in rural area for management, utilization of services and barriers to access care during an acute emergency

Acute and recent air pollution exposure and cardiovascular events at labour and delivery

PubMed Central

Männistö, Tuija; Mendola, Pauline; Grantz, Katherine Laughon; Leishear, Kira; Sundaram, Rajeshwari; Sherman, Seth; Ying, Qi; Liu, Danping

2017-01-01

Objective To study the relationship between acute air pollution exposure and cardiovascular events during labour/delivery. Methods The Consortium on Safe Labor (2002–2008), an observational US cohort with 223 502 singleton deliveries provided electronic medical records. Air pollution exposure was estimated by modified Community Multiscale Air Quality models. Cardiovascular events (cardiac failure/arrest, stroke, myocardial infarcts and other events) were recorded in the hospital discharge records for 687 pregnancies (0.3%). Logistic regression with generalised estimating equations estimated the relationship between cardiovascular events and daily air pollutant levels for delivery day and the 7 days preceding delivery. Results Increased odds of cardiovascular events were observed for each IQR increase in exposure to nitric oxides at 5 and 6 days prior to delivery (OR=1.17, 99% CI 1.04 to 1.30 and OR=1.15, 1.03 to 1.28, respectively). High exposure to toxic air pollution species such as ethylbenzene (OR=1.50, 1.08 to 2.09), m-xylene (OR=1.54, 1.11 to 2.13), o-xylene (OR=1.51, 1.09 to 2.09), p-xylene (OR=1.43, 1.03 to 1.99) and toluene (OR=1.42, 1.02 to 1.97) at 5 days prior to delivery were also associated with cardiovascular events. Decreased odds of events were observed with exposure to ozone. Conclusions Air pollution in the days prior to delivery, especially nitrogen oxides and some toxic air pollution species, was associated with increased risk of cardiovascular events during the labour/delivery admission. PMID:26105036

Ticagrelor (Brilinta)--better than clopidogrel (Plavix)?

PubMed

2011-09-05

The FDA has approved ticagrelor (Brilinta-AstraZeneca), an oral antiplatelet drug, for use with low-dose aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). It will compete with clopidogrel (Plavix) and prasugrel (Effient) for such use. Clopidogrel is expected to become available generically in the US within the next few months. © 2011 The Medical Letter, Inc.

The Positive Emotions after Acute Coronary Events behavioral health intervention: Design, rationale, and preliminary feasibility of a factorial design study.

PubMed

Huffman, Jeffery C; Albanese, Ariana M; Campbell, Kirsti A; Celano, Christopher M; Millstein, Rachel A; Mastromauro, Carol A; Healy, Brian C; Chung, Wei-Jean; Januzzi, James L; Collins, Linda M; Park, Elyse R

2017-04-01

Positive psychological constructs, such as optimism, are associated with greater participation in cardiac health behaviors and improved cardiac outcomes. Positive psychology interventions, which target psychological well-being, may represent a promising approach to improving health behaviors in high-risk cardiac patients. However, no study has assessed whether a positive psychology intervention can promote physical activity following an acute coronary syndrome. In this article we will describe the methods of a novel factorial design study to aid the development of a positive psychology-based intervention for acute coronary syndrome patients and aim to provide preliminary feasibility data on study implementation. The Positive Emotions after Acute Coronary Events III study is an optimization study (planned N = 128), subsumed within a larger multiphase optimization strategy iterative treatment development project. The goal of Positive Emotions after Acute Coronary Events III is to identify the ideal components of a positive psychology-based intervention to improve post-acute coronary syndrome physical activity. Using a 2 × 2 × 2 factorial design, Positive Emotions after Acute Coronary Events III aims to: (1) evaluate the relative merits of using positive psychology exercises alone or combined with motivational interviewing, (2) assess whether weekly or daily positive psychology exercise completion is optimal, and (3) determine the utility of booster sessions. The study's primary outcome measure is moderate-to-vigorous physical activity at 16 weeks, measured via accelerometer. Secondary outcome measures include psychological, functional, and adherence-related behavioral outcomes, along with metrics of feasibility and acceptability. For the primary study outcome, we will use a mixed-effects model with a random intercept (to account for repeated measures) to assess the main effects of each component (inclusion of motivational interviewing in the exercises

A Case of Systemic Lupus Erythematosus developing Two years after Remission of Thrombotic Thrombocytopenic Purpura

PubMed Central

Myung, Seung-Jae; Yoo, Bin; Lee, Kyoo-Hyung; Yoo, Mi-Ran; Choi, Seung-Won; Yoo, Eun-Sil; Chi, Hyun-Sook; Moon, Hee-Bom

1996-01-01

We describe a 17-year-old male who presented with thrombotic thrombocytopenic purpura (TTP) and 2 years thereafter developed central nervous system lupus and nephritis. The association of TTP and systemic lupus erythematosus has been described, but the unusual sequence and chronological separation is very rare. PMID:8854658

Platelets miRNA as a Prediction Marker of Thrombotic Episodes

PubMed Central

Dzieciol, Malgorzata

2016-01-01

The blood platelets are crucial for the coagulation physiology to maintain haemostatic balance and are involved in various pathologies such as atherosclerosis and thrombosis. The studies of recent years have shown that anucleated platelets are able to succeed protein synthesis. Additionally, mRNA translation in blood platelets is regulated by miRNA molecules. Recent works postulate the possibility of using miRNAs as biomarkers of atherosclerosis and ischemic episodes. This review article describes clinical studies that presented blood platelets miRNAs expression profile changes in different thrombotic states, which suggest use of these molecules as predictive biomarkers. PMID:28042196

Catastrophic health expenditure on acute coronary events in Asia: a prospective study.

PubMed

Jan, Stephen; Lee, Stephen W-L; Sawhney, Jitendra P S; Ong, Tiong K; Chin, Chee Tang; Kim, Hyo-Soo; Krittayaphong, Rungroj; Nhan, Vo T; Itoh, Yohji; Huo, Yong

2016-03-01

To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia. Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models. Of 12,922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia. Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe.

The influence of the platelet count on the incidence of thrombotic and haemorrhagic complications in polycythaemia vera

PubMed Central

Dawson, Audrey A.; Ogston, D.

1970-01-01

In polycythaemia vera, those patients who have an elevated platelet count develop more thrombotic and more haemorrhagic complications than those with a normal count, even when the haematocrit is maintained by therapy within the normal range. PMID:5416508

Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis.

PubMed

Sakthirajan, R; Dhanapriya, J; Dineshkumar, T; Gopalakrishnan, N; Murugan, S; Balasubramaniyan, T

2017-01-01

Rheumatoid arthritis (RA) is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and edema. Renal biopsy showed TMA with patchy cortical necrosis. She improved with hemodialysis and plasmapheresis.

Upper-Extremity Deep-Vein Thrombosis: A Retrospective Cohort Evaluation of Thrombotic Risk Factors at a University Teaching Hospital Antithrombosis Clinic.

PubMed

Stone, Rebecca H; Bress, Adam P; Nutescu, Edith A; Shapiro, Nancy L

2016-08-01

Upper-extremity deep-vein thrombosis (UEDVT) causes significant morbidity and mortality and is not well characterized in the existing literature, particularly in underrepresented minorities such as African Americans. To describe the characteristics of a cohort of patients with UEDVT seen at an urban academic medical center. This was a retrospective cohort study among patients with a confirmed UEDVT at the University of Illinois Hospital and Health Sciences System between 1996 and 2011. Patients were identified by ICD-9 code for UEDVT. Variables collected include thrombotic risk factors and outcomes, including recurrent thrombosis and bleeding. We identified 229 patients with UEDVT; 71% were African American, and 11% were diagnosed with sickle cell disease. The average number of UEDVT risk factors was 4.40 ± 1.5, the most common being central venous catheter (CVC) use (178, 78%). In the year following UEDVT, 13% experienced recurrent thrombosis, and 6% experienced major bleeding. Of 181 patients receiving warfarin after an UEDVT, 36% of international normalized ratio (INR) values were therapeutic. Patients with sickle cell disease had a lower proportion of INRs within the target range (25% vs 38%, P < 0.01), and were more likely to be lost to follow-up (67% vs 46%, P = 0.05) and experience a recurrent thrombotic event (29% vs 11%, P = 0.02). A CVC is the most common risk factor for UEDVT; however, patients with sickle cell disease demonstrate additional unique demographics and risk factors. Patients included in this underrepresented demographic cohort had a low quality of anticoagulation control, particularly those with sickle cell disease. © The Author(s) 2016.

Measuring Cognitive and Affective Constructs in the Context of an Acute Health Event

PubMed Central

Boudreaux, Edwin D.; Moon, Simon; Tappe, Karyn A.; Bock, Beth; Baumann, Brigitte; Chapman, Gretchen B.

2013-01-01

The latest recommendations for building dynamic health behavior theories emphasize that cognitions, emotions, and behaviors – and the nature of their inter-relationships -- can change over time. This paper describes the development and psychometric validation of four scales created to measure smoking-related causal attributions, perceived illness severity, event-related emotions, and intention to quit smoking among patients experiencing acute cardiac symptoms. After completing qualitative work with a sample of 50 cardiac patients, we administered the scales to 300 patients presenting to the emergency department for cardiac-related symptoms. Factor analyses, alpha coefficients, ANOVAS, and Pearson correlation coefficients were used to establish the scales' reliability and validity. Factor analyses revealed a stable factor structures for each of the four constructs. The scales were internally consistent, with the majority having an alpha of >0.80 (range: 0.57 to 0.89). Mean differences in ratings of the perceived illness severity and event-related emotions were noted across the three time anchors. Significant increases in intention to quit at the time of enrollment, compared to retrospective ratings of intention to quit before the event, provide preliminary support for the sensitivity of this measure to the motivating impact of the event. Finally, smoking-related causal attributions, perceived illness severity, and event-related emotions correlated in the expected directions with intention to quit smoking, providing preliminary support for construct validity. PMID:22970703

Role of central obesity in risk stratification after an acute coronary event: does central obesity add prognostic value to the Global Registry of Acute Coronary Events (GRACE) risk score in patients with acute coronary syndrome?

PubMed

Martins, Albino; Ribeiro, Sílvia; Gonçalves, Pierre; Correia, Adelino

2013-10-01

Accurate risk stratification is an important step in the initial management of acute coronary syndrome (ACS), and current guidelines recommend the use of risk scores, such as the Global Registry of Acute Coronary Events risk score (GRACE RS). Recent studies have suggested that abdominal obesity is associated with cardiovascular events in patients with ACS. However, little is known about the additional value of abdominal obesity beyond risk scores. The aim of our study was thus to assess whether waist circumference, a surrogate of abdominal adiposity, adds prognostic information to the GRACE RS. This was a retrospective cohort study of ACS patients admitted consecutively to a cardiac care unit between June 2009 and July 2010. The composite of all-cause mortality or myocardial reinfarction within six months of index hospitalization was used as the endpoint for the analysis. A total of 285 patients were studied, 96.1% admitted for myocardial infarction (with or without ST elevation) and 3.9% for unstable angina. At the end of the follow-up period, 10 patients had died and the composite endpoint had been reached in 27 patients (9.5%). More than 70% of the study population were obese or overweight, and abdominal obesity was present in 44.6%. The GRACE RS showed poor predictive accuracy (area under the curve 0.60), and most of the GRACE variables did not reach statistical significance in multivariate analysis. The addition of waist circumference to the GRACE RS did not improve its discriminatory performance. Abdominal obesity does not add prognostic information to the GRACE RS to predict six-month mortality or myocardial reinfarction.

Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.

PubMed

Go, Alan S; Hsu, Chi-Yuan; Yang, Jingrong; Tan, Thida C; Zheng, Sijie; Ordonez, Juan D; Liu, Kathleen D

2018-06-07

AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge. Copyright © 2018 by the American Society of Nephrology.

Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study.

PubMed

Dekkers, Olaf M; Horváth-Puhó, Erzsébet; Cannegieter, Suzanne C; Vandenbroucke, Jan P; Sørensen, Henrik Toft; Jørgensen, Jens Otto L

2017-01-01

Several studies have shown an increased risk for cardiovascular disease (CVD) in hyperthyroidism, but most studies have been too small to address the effect of hyperthyroidism on individual cardiovascular endpoints. Our main aim was to assess the association among hyperthyroidism, acute cardiovascular events and mortality. It is a nationwide population-based cohort study. Data were obtained from the Danish Civil Registration System and the Danish National Patient Registry, which covers all Danish hospitals. We compared the rate of all-cause mortality as well as venous thromboembolism (VTE), acute myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism, atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated. The study included 85 856 hyperthyroid patients and 847 057 matched population-based controls. Mean follow-up time was 9.2 years. The HR for mortality was highest in the first 3 months after diagnosis of hyperthyroidism: 4.62, 95% CI: 4.40-4.85, and remained elevated during long-term follow-up (>3 years) (HR: 1.35, 95% CI: 1.33-1.37). The risk for all examined cardiovascular events was increased, with the highest risk in the first 3 months after hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial fibrillation (HR: 7.32, 95% CI: 6.58-8.14) and arterial embolism (HR: 6.08, 95% CI: 4.30-8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and PCI were increased also 2- to 3-fold. We found an increased risk for all-cause mortality and acute cardiovascular events in patients with hyperthyroidism. © 2017 European Society of Endocrinology.

Vascular Nitric Oxide-Superoxide Balance and Thrombus Formation after Acute Exercise.

PubMed

Przyborowski, Kamil; Proniewski, Bartosz; Czarny, Joanna; Smeda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Zoladz, Jerzy A; Chlopicki, Stefan

2018-02-21

An acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity. At different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (O2) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α. An acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of O2 in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations. An acute bout of strenuous exercise in mice reduced NO and in parallel increased O2 production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased O2 production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice.

Evidence Linking Hypoglycemic Events to an Increased Risk of Acute Cardiovascular Events in Patients With Type 2 Diabetes

PubMed Central

Johnston, Stephen S.; Conner, Christopher; Aagren, Mark; Smith, David M.; Bouchard, Jonathan; Brett, Jason

2011-01-01

OBJECTIVE This retrospective study examined the association between ICD-9-CM–coded outpatient hypoglycemic events (HEs) and acute cardiovascular events (ACVEs), i.e., acute myocardial infarction, coronary artery bypass grafting, revascularization, percutaneous coronary intervention, and incident unstable angina, in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Data were derived from healthcare claims for individuals with employer-sponsored primary or Medicare supplemental insurance. A baseline period (30 September 2006 to 30 September 2007) was used to identify eligible patients and collect information on their clinical and demographic characteristics. An evaluation period (1 October 2007 to 30 September 2008) was used to identify HEs and ACVEs. Patients aged ≥18 years with type 2 diabetes were selected for analysis by a modified Healthcare Effectiveness Data and Information Set algorithm. Data were analyzed with multiple logistic regression and backward stepwise selection (maximum P = 0.01) with adjustment for important confounding variables, including age, sex, geography, insurance type, comorbidity scores, cardiovascular risk factors, diabetes complications, total baseline medical expenditures, and prior ACVEs. RESULTS Of the 860,845 patients in the analysis set, 27,065 (3.1%) had ICD-9-CM–coded HEs during the evaluation period. The main model retained 17 significant independent variables. Patients with HEs had 79% higher regression-adjusted odds (HE odds ratio [OR] 1.79; 95% CI 1.69–1.89) of ACVEs than patients without HEs; results in patients aged ≥65 years were similar to those for the entire population (HE OR 1.78, 95% CI 1.65–1.92). CONCLUSIONS ICD-9-CM–coded HEs were independently associated with an increased risk of ACVEs. Further studies of the relationship between hypoglycemia and the risk of ACVEs are warranted. PMID:21421802

Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes.

PubMed

Chow, Clara K; Jolly, Sanjit; Rao-Melacini, Purnima; Fox, Keith A A; Anand, Sonia S; Yusuf, Salim

2010-02-16

Although preventive drug therapy is a priority after acute coronary syndrome, less is known about adherence to behavioral recommendations. The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events. The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio, 0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise. Adherence to behavioral advice (diet, exercise, and smoking cessation) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events. These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary

Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio

PubMed Central

Amory, Colum F.; Levine, Steve R.; Brey, Robin L.; Gebregziabher, Mulugeta; Tuhrim, Stanley; Tilley, Barbara C.; Simpson, Ann-Catherin N.; Sacco, Ralph L.; Mohr, J.P.

2015-01-01

Background There are very limited prospective data on the significance of persistent of antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) two newer aPL assays, (2) an aPL portfolio, and (3) persistent aPL positivity following stroke. Methods 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and β2-glycoprotein-I (anti-β2GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, MI, TIA, DVT, PE, or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. Results Persistent anti-β2GPI decreased the time to TOE/death after adjustment for potential confounders (HR=2.86, CI 1.21-6.76, p=0.017). When persistent anti-β2GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR=3.79, CI 1.18-12.14, p=0.025). Neither persistent aCL, persistent aPS alone, nor a single positive anti-β2GPI or aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL, or any persistent aPL increased the rate of TOE/death. Conclusions Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-β2GPI alone and with persistent second aPL were independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio, and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs. PMID:26513489

Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event.

PubMed

Fazekas, Franz; Enzinger, Christian; Schmidt, Reinhold; Grittner, Ulrike; Giese, Anne-Katrin; Hennerici, Michael G; Huber, Roman; Jungehulsing, Gerhard J; Kaps, Manfred; Kessler, Christof; Martus, Peter; Putaala, Jukka; Ropele, Stefan; Tanislav, Christian; Tatlisumak, Turgut; Thijs, Vincent; von Sarnowski, Bettina; Norrving, Bo; Rolfs, Arndt

2015-06-01

Fabry disease (FD) may cause stroke and is reportedly associated with typical brain findings on magnetic resonance imaging (MRI). In a large group of young patients with an acute cerebrovascular event, we wanted to test whether brain MRI findings can serve to suggest the presence of FD. The Stroke in Young Fabry Patients (SIFAP 1) study prospectively collected clinical, laboratory, and radiological data of 5023 patients (18-55 years) with an acute cerebrovascular event. Their MRI was interpreted centrally and blinded to all other information. Biochemical findings and genetic testing served to diagnose FD in 45 (0.9%) patients. We compared the imaging findings between FD and non-FD patients in patients with at least a T2-weighted MRI of good quality. A total of 3203 (63.8%) patients had the required MRI data set. Among those were 34 patients with a diagnosis of FD (1.1%), which was definite in 21 and probable in 13 cases. The median age of patients with FD was slightly lower (45 versus 46 years) and women prevailed (70.6% versus 40.7%; P<0.001). Presence or extent of white matter hyperintensities, infarct localization, vertebrobasilar artery dilatation, T1-signal hyperintensity of the pulvinar thalami, or any other MRI finding did not distinguish patients with FD from non-FD cerebrovascular event patients. Pulvinar hyperintensity was not present in a single patient with FD but seen in 6 non-FD patients. Brain MRI findings cannot serve to suspect FD in young patients presenting with an acute cerebrovascular event. This deserves consideration in the search for possible causes of young patients with stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2015 American Heart Association, Inc.

Differentiation of pernicious anemia from thrombotic thrombocytopenic purpura: The clinical value of subtle pathologic findings.

PubMed

Abbott, Daniel W; Friedman, Kenneth D; Karafin, Matthew S

2016-12-01

Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia that requires emergent treatment with plasma exchange and is one of the most important conditions for which apheresis service professionals are consulted. Careful interpretation of initial laboratory values and the peripheral blood smear is a critical first step to determining the need for plasma exchange because other conditions can show deceptively similar red cell morphology, and ADAMTS13 levels are often not rapidly available. We report a case of a patient who was initially diagnosed with TTP and treated with plasma exchange based on preliminary laboratory data and a peripheral blood smear that contained bizarre microcytic red blood cells presumed to be schistocytes. The peripheral blood smear was later interpreted by the hematopathologist to be inconsistent with TTP, and further workup led to a diagnosis of severe vitamin B12 deficiency secondary to pernicious anemia. This case highlights the diagnostic complexity of thrombotic microangiopathies and the importance of a critical evaluation of the blood smear and presenting laboratory data when there is a concern for TTP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Catastrophic health expenditure on acute coronary events in Asia: a prospective study

PubMed Central

Lee, Stephen W-L; Sawhney, Jitendra PS; Ong, Tiong K; Chin, Chee Tang; Kim, Hyo-Soo; Krittayaphong, Rungroj; Nhan, Vo T; Itoh, Yohji; Huo, Yong

2016-01-01

Abstract Objective To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia. Methods Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models. Findings Of 12 922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia. Conclusion Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe. PMID:26966330

Impact of Hormone-Associated Resistance to Activated Protein C on the Thrombotic Potential of Oral Contraceptives: A Prospective Observational Study

PubMed Central

Müller, Jens; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther C.; Oldenburg, Johannes; Rudlowski, Christian; Pötzsch, Bernd

2014-01-01

Introduction The increased thrombotic risk of oral contraceptives (OC) has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC). To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use. Patients and Methods Blood samples were collected prospectively from healthy women (n = 21) before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA) technology. Thrombin generation markers and other hemostasis parameters were measured additionally. Results All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur. Conclusions In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as

The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis

PubMed Central

Carter, Corey A.; Browning, Robert; Oronsky, Bryan T.; Scicinski, Jan J.; Brzezniak, Christina

2016-01-01

A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome. PMID:26933422

The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis.

PubMed

Carter, Corey A; Browning, Robert; Oronsky, Bryan T; Scicinski, Jan J; Brzezniak, Christina

2016-01-01

A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome.

Adverse events associated with single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

PubMed

Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J

2015-10-13

This is an update of a Cochrane overview published in Issue 9, 2011; that overview considered both efficacy and adverse events. This overview considers adverse events, with efficacy dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the adverse events associated with individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews. To provide an overview of adverse event rates associated with single-dose oral analgesics, compared with placebo, for acute postoperative pain in adults. We identified systematic reviews in The Cochrane Database of Systematic Reviews on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group. We extracted information related to participants experiencing any adverse event, and reports of serious adverse events, and deaths from the individual reviews. Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 participants. Most studies involved younger participants with pain following removal of molar teeth.For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo. For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo. Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events.Serious adverse events were rare, occurring a rate of about 1 in 3200 participants.Most reviews did not report specific adverse events. Despite

Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio.

PubMed

Amory, Colum F; Levine, Steven R; Brey, Robin L; Gebregziabher, Mulugeta; Tuhrim, Stanley; Tilley, Barbara C; Simpson, Ann-Catherin C; Sacco, Ralph L; Mohr, Jay P

2015-01-01

There are very limited prospective data on the significance of persistent antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) 2 newer aPL assays, (2) an aPL portfolio and (3) persistent aPL positivity following stroke. A total of 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and anti-β2-glycoprotein-I (anti-β2GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis, pulmonary embolism or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. Persistent anti-β2GPI decreased the time to TOE/death after adjustment for potential confounders (hazards ratio (HR) 2.86, 95% CI 1.21-6.76, p = 0.017). When persistent anti-β2GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR 3.79, 95% CI 1.18-12.14, p = 0.025). Neither persistent anticardiolipin antibodies nor persistent aPS alone nor a single positive anti-β2GPI nor aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL or any persistent aPL increased the rate of TOE/death. Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-β2GPI alone, and with persistent second aPL, was independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs. © 2015 S. Karger AG, Basel.

Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study.

PubMed

Mendichovszky, I A; Priest, A N; Bowden, D J; Hunter, S; Joubert, I; Hilborne, S; Graves, M J; Baglin, T; Lomas, D J

2017-06-01

Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. • MRI can distinguish between acute and evolving or chronic lower limb DVT • Two advanced MRI techniques can follow the evolution of lower limb DVT • MRI could be used to avoid an incorrect diagnosis of recurrent DVT • MRI could help avoid the risks and complications of lifelong anticoagulation therapy.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

PubMed

Vedantham, Suresh; Goldhaber, Samuel Z; Julian, Jim A; Kahn, Susan R; Jaff, Michael R; Cohen, David J; Magnuson, Elizabeth; Razavi, Mahmood K; Comerota, Anthony J; Gornik, Heather L; Murphy, Timothy P; Lewis, Lawrence; Duncan, James R; Nieters, Patricia; Derfler, Mary C; Filion, Marc; Gu, Chu-Shu; Kee, Stephen; Schneider, Joseph; Saad, Nael; Blinder, Morey; Moll, Stephan; Sacks, David; Lin, Judith; Rundback, John; Garcia, Mark; Razdan, Rahul; VanderWoude, Eric; Marques, Vasco; Kearon, Clive

2017-12-07

The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. Among patients

Calcium Channel Blockers in Secondary Cardiovascular Prevention and Risk of Acute Events: Real-World Evidence from Nested Case-Control Studies on Italian Hypertensive Elderly.

PubMed

Bettiol, Alessandra; Lucenteforte, Ersilia; Vannacci, Alfredo; Lombardi, Niccolò; Onder, Graziano; Agabiti, Nera; Vitale, Cristiana; Trifirò, Gianluca; Corrao, Giovanni; Roberto, Giuseppe; Mugelli, Alessandro; Chinellato, Alessandro

2017-12-01

Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention. Three case-control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n = 25,204), all-cause hospitalizations (n = 19,237), or all-cause mortality (n = 17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Compared to past users, current CCB users had significant reductions in risks of CV events [OR 0.88 (95% CI: 0.84-0.91)], hospitalization [0.90 (0.88-0.93)] and mortality [0.48 (0.47-0.49)]. Current users of long-acting dihydropyridines (DHPs) had the lowest risk [OR 0.87 (0.84-0.90), 0.86 (0.83-0.90), 0.55 (0.54-0.56) for acute CV events, hospitalizations and mortality], whereas current users of short-acting CCBs had an increased risk of acute CV events [OR 1.77 (1.13-2.78) for short-acting DHPs; 1.19 (1.07-1.31) for short-acting non-DHPs] and hospitalizations [OR 1.84 (0.96-3.51) and 1.23 (1.08-1.42)]. The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.

Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention.

PubMed

Boersma, E; Akkerhuis, K M; Théroux, P; Califf, R M; Topol, E J; Simoons, M L

1999-11-16

Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.

RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia.

PubMed

Boucher, Maria O; Smitherman, Andrew B; Pahl, Kristy S; Rao, Kathleen W; Deal, Allison M; Blatt, Julie

2016-04-01

RUNX1 (AML1) amplification in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poor survival for unclear reasons. Our anecdotal experience suggests that children with B-ALL and RUNX1 amplification might be predisposed to thrombosis. We performed a retrospective cohort study of children with B-ALL treated from 2008 to 2014 at the North Carolina Children's Hospital. Patient demographics, cytogenetics, and diagnosis of thrombosis were extracted by blinded chart review. Analysis was performed examining the relationship between RUNX1 amplification and thrombosis. We identified 119 patients with B-ALL and a median age of 4.9 years (interquartile range, 2.9 to 8.6 y) at diagnosis. Four patients (3%) had RUNX1 amplification. The average number of RUNX1 copies among those with amplification was 5 (SD 0.81 [range, 4 to 6]). Eighteen thromboses were diagnosed within 6 months of starting treatment. These events were more likely among patients with RUNX1 amplification than in patients without amplification (75% vs. 13%; RR 5.75, 95% confidence interval, 2.75-12.01). RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings.

Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

PubMed Central

Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

2015-01-01

Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

PubMed

Benhamou, Y; Boelle, P-Y; Baudin, B; Ederhy, S; Gras, J; Galicier, L; Azoulay, E; Provôt, F; Maury, E; Pène, F; Mira, J-P; Wynckel, A; Presne, C; Poullin, P; Halimi, J-M; Delmas, Y; Kanouni, T; Seguin, A; Mousson, C; Servais, A; Bordessoule, D; Perez, P; Hamidou, M; Cohen, A; Veyradier, A; Coppo, P

2015-02-01

Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. To assess the predictive value of cTnI in patients with TTP for death or refractoriness. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP. © 2014 International Society on Thrombosis and Haemostasis.

Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group.

PubMed

Go, Ronald S; Winters, Jeffrey L; Leung, Nelson; Murray, David L; Willrich, Maria A; Abraham, Roshini S; Amer, Hatem; Hogan, William J; Marshall, Ariela L; Sethi, Sanjeev; Tran, Cheryl L; Chen, Dong; Pruthi, Rajiv K; Ashrani, Aneel A; Fervenza, Fernando C; Cramer, Carl H; Rodriguez, Vilmarie; Wolanskyj, Alexandra P; Thomé, Stephan D; Hook, C Christopher

2016-09-01

Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Factors associated with emergency medical services scope of practice for acute cardiovascular events.

PubMed

Williams, Ishmael; Valderrama, Amy L; Bolton, Patricia; Greek, April; Greer, Sophia; Patterson, Davis G; Zhang, Zefeng

2012-01-01

To examine prehospital emergency medical services (EMS) scope of practice for acute cardiovascular events and characteristics that may affect scope of practice; and to describe variations in EMS scope of practice for these events and the characteristics associated with that variability. In 2008, we conducted a telephone survey of 1,939 eligible EMS providers in nine states to measure EMS agency characteristics, medical director involvement, and 18 interventions authorized for prehospital care of acute cardiovascular events by three levels of emergency medical technician (EMT) personnel. A total of 1,292 providers responded to the survey, for a response rate of 67%. EMS scope of practice interventions varied by EMT personnel level, with the proportion of authorized interventions increasing as expected from EMT-Basic to EMT-Paramedic. Seven of eight statistically significant associations indicated that EMS agencies in urban settings were less likely to authorize interventions (odds ratios <0.7) for any level of EMS personnel. Based on the subset of six statistically significant associations, fire department-based EMS agencies were two to three times more likely to authorize interventions for EMT-Intermediate personnel. Volunteer EMS agencies were more than twice as likely as nonvolunteer agencies to authorize interventions for EMT-Basic and EMT-Intermediate personnel but were less likely to authorize any one of the 11 interventions for EMT-Paramedics. Greater medical director involvement was associated with greater likelihood of authorization of seven of the 18 interventions for EMT-Basic and EMT-Paramedic personnel but had no association with EMT-Intermediate personnel. We noted statistically significant variations in scope of practice by rural vs. urban setting, medical director involvement, and type of EMS service (fire department-based/non-fire department-based; volunteer/paid). These variations highlight local differences in the composition and capacity of EMS

Prasugrel versus clopidogrel in patients with acute coronary syndromes.

PubMed

Wiviott, Stephen D; Braunwald, Eugene; McCabe, Carolyn H; Montalescot, Gilles; Ruzyllo, Witold; Gottlieb, Shmuel; Neumann, Franz-Joseph; Ardissino, Diego; De Servi, Stefano; Murphy, Sabina A; Riesmeyer, Jeffrey; Weerakkody, Govinda; Gibson, C Michael; Antman, Elliott M

2007-11-15

Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention. To compare prasugrel, a new thienopyridine, with clopidogrel, we randomly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel (a 60-mg loading dose and a 10-mg daily maintenance dose) or clopidogrel (a 300-mg loading dose and a 75-mg daily maintenance dose), for 6 to 15 months. The primary efficacy end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The key safety end point was major bleeding. The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel (hazard ratio for prasugrel vs. clopidogrel, 0.81; 95% confidence interval [CI], 0.73 to 0.90; P<0.001). We also found significant reductions in the prasugrel group in the rates of myocardial infarction (9.7% for clopidogrel vs. 7.4% for prasugrel; P<0.001), urgent target-vessel revascularization (3.7% vs. 2.5%; P<0.001), and stent thrombosis (2.4% vs. 1.1%; P<0.001). Major bleeding was observed in 2.4% of patients receiving prasugrel and in 1.8% of patients receiving clopidogrel (hazard ratio, 1.32; 95% CI, 1.03 to 1.68; P=0.03). Also greater in the prasugrel group was the rate of life-threatening bleeding (1.4% vs. 0.9%; P=0.01), including nonfatal bleeding (1.1% vs. 0.9%; hazard ratio, 1.25; P=0.23) and fatal bleeding (0.4% vs. 0.1%; P=0.002). In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups. (ClinicalTrials.gov number, NCT

How I treat children and adolescents with acute promyelocytic leukaemia.

PubMed

Abla, Oussama; Ribeiro, Raul C

2014-01-01

Acute promyelocytic leukaemia (APL) is a rare subtype of acute myeloid leukaemia. The outcome of paediatric APL has improved substantially over the past 20 years; cure rates above 80% are expected when all-trans retinoic acid (ATRA) is given with anthracycline-based regimens. The presenting features of paediatric APL may include severe bleeding and thrombotic complications, which contribute to the high early death rate. The incidence of leucocytosis and the microgranular subtype is greater in paediatric than adult APL, and children experience greater ATRA-related toxicity. It is crucial to begin ATRA therapy and intensive platelet and fibrinogen replacement on first suspicion of APL. Recent risk-adapted therapeutic trials have shown that patients at greater risk of relapse benefit from the introduction of high-dose cytarabine during consolidation. Combination therapy with ATRA and arsenic trioxide provides very effective frontline treatment and may reduce the need for subsequent anthracycline therapy. © 2013 John Wiley & Sons Ltd.

How I Treat Children and Adolescents with Acute Promyelocytic Leukaemia

PubMed Central

Abla, Oussama; Ribeiro, Raul C.

2016-01-01

Summary Acute promyelocytic leukaemia (APL) is a rare subtype of acute myeloid leukaemia. The outcome of paediatric APL has improved substantially over the past 20 years; cure rates above 80% are expected when all-trans retinoic acid (ATRA) is given with anthracycline-based regimens. The presenting features of paediatric APL may include severe bleeding and thrombotic complications, which contribute to the high early death rate. The incidence of leucocytosis and the microgranular subtype is greater in paediatric than adult APL, and children experience greater ATRA-related toxicity. It is crucial to begin ATRA therapy and intensive platelet and fibrinogen replacement on first suspicion of APL. Recent risk-adapted therapeutic trials have shown that patients at greater risk of relapse benefit from the introduction of high-dose cytarabine during consolidation. Combination therapy with ATRA and arsenic trioxide provides very effective frontline treatment and may reduce the need for subsequent anthracycline therapy. PMID:24117210

Low incidence of ADAMTS13 missense mutation R1060W in adult Egyptian patients with thrombotic thrombocytopenic purpura.

PubMed

El Sissy, Maha H; El Hafez, A Abd; El Sissy, A H

2014-01-01

Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening disorder, characterized by thrombocytopenia, microangiopathic hemolytic anemia, widespread microvascular thrombi and consequent clinical sequelae due to ischemic organ damage. TTP is most commonly associated with deficiency or inhibition of von Willebrand factor-cleaving protease (ADAMTS13) activity. ADAMTS13 mutations and polymorphisms have been reported in childhood congenital TTP, but their significance in adult-onset TTP is still under investigation. Two mutations stand out: the single base insertion 4143insA in exon 29 and the missense mutation R1060W in exon 24 have both been observed in several unrelated families, mainly in adult-onset TTP, and over a wide geographic area. Our objective in this study is to identify the prevalence of R1060W missense mutation in exon 24 ADAMTS13 in a sample of adult Egyptian TTP patients. Thirty-one adult-onset TTP patients were included in this study, with a male/female ratio of 1:4. Twenty-six cases (84%) presented with acute idiopathic TTP, 2 cases were drug abusers and 3 cases were pregnant. None of the study cases provided a history of suspicious TTP symptoms during childhood (2 cases gave a history of episodes of thrombocytopenia during childhood). All cases showed statistically significant decreased ADAMTS13 activity compared to normal controls (p < 0.001). The study revealed a high statistical difference regarding the ADAMTS13 inhibitor level in primary versus secondary cases (p = 0.003). None of our Egyptian cases or of the healthy normal controls are positive for exon 24 missense mutation. Larger studies and regional and national TTP registries are recommended. © 2013 S. Karger AG, Basel.

In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra) viscera hydrolysate.

PubMed

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Addepalli, Rama; Chen, Wei; Gobe, Glenda C; Osborne, Simone A

2017-07-01

Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients. Graphical abstract Schematic showing preparation of bioactive extracts and fractions from blacklip abalone.

Acute cardiac events and deployment of emergency medical teams and automated external defibrillators in large football stadiums in the Netherlands.

PubMed

van de Sandt, Femke; Umans, Victor

2009-10-01

The incidence of acute cardiac events - including out-of-hospital cardiac arrest - may be increased in visitors of large sports stadiums when compared with the general population. This study sought to investigate the incidence of acute cardiac events inside large Dutch football stadiums, as well as the emergency response systems deployed in these stadiums and the success rate for in-stadium resuscitation. Retrospective cohort study using a questionnaire sent to the 20 Dutch stadiums that hosted professional matches during the 2006-2007 and 2007-2008 football seasons. Stadium capacity ranged from 3600 to 51 600 spectators. Nearly 13 million spectators attended 686 'Eredivisie' (Honorary Division) and European football matches. All stadiums distribute multiple emergency medical teams among the spectators. Eighty-five percent of the stadiums have an ambulance standby during matches, 95% of the stadiums were equipped with automated external defibrillators (AEDs) during the study period. On an average, one AED was available for every 7576 spectators (range 1800-29 600). Ninety-three cardiac events were reported (7.3 per 1 million spectators). An AED was used 22 times (1.7 per 1 million spectators). Resuscitation was successful in 18 cases (82%, 95% confidence interval: 61-93). The incidence of out-of-hospital cardiac arrest inside large football stadiums in the Netherlands, albeit increased when compared with the general population, is low. The success rate for in-stadium resuscitation by medical teams equipped with AEDs is high. Dutch stadiums appear vigilant in regard to acute cardiac events. This report highlights the importance of adequate emergency medical response systems (including AEDs) in large sports venues.

Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

PubMed

Mancini, I; Ricaño-Ponce, I; Pappalardo, E; Cairo, A; Gorski, M M; Casoli, G; Ferrari, B; Alberti, M; Mikovic, D; Noris, M; Wijmenga, C; Peyvandi, F

2016-12-01

Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10 -14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10 -5 to 7.60 × 10 -5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10 -19 ). Imputation of classic

Computed Tomography Imaging Features in Acute Uncomplicated Stanford Type-B Aortic Dissection Predict Late Adverse Events.

PubMed

Sailer, Anna M; van Kuijk, Sander M J; Nelemans, Patricia J; Chin, Anne S; Kino, Aya; Huininga, Mark; Schmidt, Johanna; Mistelbauer, Gabriel; Bäumler, Kathrin; Chiu, Peter; Fischbein, Michael P; Dake, Michael D; Miller, D Craig; Schurink, Geert Willem H; Fleischmann, Dominik

2017-04-01

Medical treatment of initially uncomplicated acute Stanford type-B aortic dissection is associated with a high rate of late adverse events. Identification of individuals who potentially benefit from preventive endografting is highly desirable. The association of computed tomography imaging features with late adverse events was retrospectively assessed in 83 patients with acute uncomplicated Stanford type-B aortic dissection, followed over a median of 850 (interquartile range 247-1824) days. Adverse events were defined as fatal or nonfatal aortic rupture, rapid aortic growth (>10 mm/y), aneurysm formation (≥6 cm), organ or limb ischemia, or new uncontrollable hypertension or pain. Five significant predictors were identified using multivariable Cox regression analysis: connective tissue disease (hazard ratio [HR] 2.94, 95% confidence interval [CI]: 1.29-6.72; P =0.01), circumferential extent of false lumen in angular degrees (HR 1.03 per degree, 95% CI: 1.01-1.04, P =0.003), maximum aortic diameter (HR 1.10 per mm, 95% CI: 1.02-1.18, P =0.015), false lumen outflow (HR 0.999 per mL/min, 95% CI: 0.998-1.000; P =0.055), and number of intercostal arteries (HR 0.89 per n, 95% CI: 0.80-0.98; P =0.024). A prediction model was constructed to calculate patient specific risk at 1, 2, and 5 years and to stratify patients into high-, intermediate-, and low-risk groups. The model was internally validated by bootstrapping and showed good discriminatory ability with an optimism-corrected C statistic of 70.1%. Computed tomography imaging-based morphological features combined into a prediction model may be able to identify patients at high risk for late adverse events after an initially uncomplicated type-B aortic dissection. © 2017 American Heart Association, Inc.

Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi

2017-03-01

This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome events and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome events. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

Role of xanthine oxidoreductase in the anti-thrombotic effects of nitrite in rats in vivo.

PubMed

Kramkowski, K; Leszczynska, A; Przyborowski, K; Kaminski, T; Rykaczewska, U; Sitek, B; Zakrzewska, A; Proniewski, B; Smolenski, R T; Chabielska, E; Buczko, W; Chlopicki, S

2016-01-01

The mechanisms underlying nitrite-induced effects on thrombosis and hemostasis in vivo are not clear. The goal of the work described here was to investigate the role of xanthine oxidoreductase (XOR) in the anti-platelet and anti-thrombotic activities of nitrite in rats in vivo. Arterial thrombosis was induced electrically in rats with renovascular hypertension by partial ligation of the left renal artery. Sodium nitrite (NaNO2, 0.17 mmol/kg twice daily for 3 days, p.o) was administered with or without one of the XOR-inhibitors: allopurinol (ALLO) and febuxostat (FEB) (100 and 5 mg/kg, p.o., for 3 days). Nitrite treatment (0.17 mmol/kg), which was associated with a significant increase in NOHb, nitrite/nitrate plasma concentration, resulted in a substantial decrease in thrombus weight (TW) (0.48 ± 0.03 mg vs. vehicle [VEH] 0.88 ± 0.08 mg, p < 0.001) without a significant hypotensive effect. The anti-thrombotic effect of nitrite was partially reversed by FEB (TW = 0.63 ± 0.06 mg, p < 0.05 vs. nitrites), but not by ALLO (TW = 0.43 ± 0.02 mg). In turn, profound anti-platelet effect of nitrite measured ex vivo using collagen-induced whole-blood platelet aggregation (70.5 ± 7.1% vs. VEH 100 ± 4.5%, p < 0.05) and dynamic thromboxaneB2 generation was fully reversed by both XOR-inhibitors. In addition, nitrite decreased plasminogen activator inhibitor-1 concentration (0.47 ± 0.13 ng/ml vs. VEH 0.62 ± 0.04 ng/ml, p < 0.05) and FEB/ALLO reversed this effect. In vitro the anti-platelet effect of nitrite (1 mM) was reversed by FEB (0.1 mM) under hypoxia (0.5%O2) and normoxia (20%O2). Nitrite treatment had no effect on coagulation parameters. In conclusion, the nitrite-induced anti-platelet effect in rats in vivo is mediated by XOR, but XOR does not fully account for the anti-thrombotic effects of nitrite.

Endogenous pro-thrombotic biomarkers from the arm and leg may not have the same value.

PubMed

Lattimer, Christopher R; Kalodiki, Evi; Geroulakos, George; Hoppensteadt, Debra; Fareed, Jawed

2016-05-01

Assessments of endogenous pro-thrombotic biomarkers are performed invariably on arm blood. However, the commonest site for thrombosis is in the leg. A leg blood sample may reflect local pro-thrombotic processes more accurately than systemic arm blood. The aim was to determine whether pro-thrombotic biomarkers from standard venous arm samples differed significantly from leg samples. Concurrent blood samples were taken from an ankle/lower calf varicose vein and an ante-cubital vein in 24 patients awaiting laser treatment as well as age approximated and sex matched healthy controls without venous disease. The following assays were performed: thrombin-antithrombin (ng/ml), antithrombin (%) activity, microparticles (nM), fibrinogen (mg/dl), prothrombin fragment 1.2 (F1.2) (pM) and P-selectin (ng/ml). Expressed as median (inter-quartile range). Significant arm/leg differences were observed in thrombin-antithrombin, antithrombin, prothrombin fragment 1.2 and P-selectin. The legs of patients had significantly reduced antithrombin activity and P-selectin concentrations compared to their arms (leg: 101 (90-108) versus arm: 112 (99-126), P = 0.001 and leg: 42 (26-52) versus 45 (27-52), P = 0.044, respectively). Control leg samples had significantly increased thrombin-antithrombin and P-selectin compared to control arm samples (leg: 2.1 (0.9-3.2) versus arm: 0.8 (0.5-1.7), P = 0.015 and leg: 36 (24-50) versus arm: 30 (23-41), P = 0.007, respectively). However, the control legs had significantly reduced F1.2 (leg: 265 (230-333) versus arm: 299 (236-361), P = 0.028). No significant arm/leg differences were detected in the microparticle or fibrinogen levels. These findings indicate that venous arm blood is significantly different from venous leg blood in four out of six biomarkers studied. Recognition of local venous leg sampling as a site for investigation may unravel why the leg has a greater predisposition to thrombosis and lead the way towards an arm

Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Kim, Myung-Hee Y.; Cucinotta, Francis A.

2011-01-01

In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients.

PubMed

Alvarez-Larrán, A; Cervantes, F; Bellosillo, B; Giralt, M; Juliá, A; Hernández-Boluda, J C; Bosch, A; Hernández-Nieto, L; Clapés, V; Burgaleta, C; Salvador, C; Arellano-Rodrigo, E; Colomer, D; Besses, C

2007-06-01

The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.

Acute hazardous substance releases resulting in adverse health consequences in children: Hazardous Substances Emergency Events Surveillance system, 1996-2003.

PubMed

Wattigney, Wendy A; Kaye, Wendy E; Orr, Maureen F

2007-11-01

Because of their small size and ongoing organ development, children may be more susceptible than adults to the harmful effects of toxic chemicals. The objective of the study reported here was to identify frequent locations, released substances, and factors contributing to short-term chemical exposures associated with adverse health consequences experienced by children. The study examined the Hazardous Substances Emergency Events Surveillance (HSEES) system data from 1996-2003. Eligible events involved the acute release of a hazardous substance associated with at least one child being injured. The study found that injured children were predominantly at school, home, or a recreational center when events took place. School-related events were associated with the accidental release of acids and the release of pepper spray by pranksters. Carbon monoxide poisonings occurring in the home, retail stores, entertainment facilities, and hotels were responsible for about 10 percent of events involving child victims. Chlorine was one of the top chemicals harmful to children, particularly at public swimming pools. Although human error contributed to the majority of releases involving child victims, equipment failure was responsible for most chlorine and ammonia releases. The authors conclude that chemical releases resulting in injury to children occur mostly in schools, homes, and recreational areas. Surveillance of acute hazardous chemical releases helped identify contributing causes and can guide the development of prevention outreach activities. Chemical accidents cannot be entirely prevented, but efforts can be taken to provide safer environments in which children can live, learn, and play. Wide dissemination of safety recommendations and education programs is required to protect children from needless environmental dangers.

Plasminogen activator inhibitor links obesity and thrombotic cerebrovascular diseases: The roles of PAI-1 and obesity on stroke.

PubMed

Chen, Rui; Yan, Jinchuan; Liu, Peijing; Wang, Zhongqun; Wang, Cuiping

2017-06-01

One of the global socioeconomic phenomena occurred during the last decades is the increased prevalence of obesity, with direct consequence on the risk of developing thrombotic disorders. As the physiological inhibitor of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) is well known for its role in fibrinolysis. More and more evidences have shown that PAI-1 involves in physiopathologic mechanisms of many diseases and metabolic disorder. Increased serum level of PAI-1 has been observed in obesity and it also contributes to the development of adipose tissue and then has effects on obesity. Meantime, obesity affects also the PAI-1 levels. These evidences indicate the complicated interaction between PAI-1 and obesity. Many clinic studies have confirmed that obesity relates to the stroke outcome although there are many contradictory results. Simultaneously, correlation is found between plasma PAI-1 and thrombotic cerebrovascular diseases. This article reviews contemporary knowledge regarding the complex interplay of obesity, PAI-1 and stroke.

Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

PubMed

Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

2015-02-01

De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

Objective evaluation of acute adverse events and image quality of gadolinium-based contrast agents (gadobutrol and gadobenate dimeglumine) by blinded evaluation. Pilot study.

PubMed

Semelka, Richard C; Hernandes, Mateus de A; Stallings, Clifton G; Castillo, Mauricio

2013-01-01

The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation. Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5-85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated. No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients. Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events. Copyright © 2013 Elsevier Inc. All rights reserved.

Shape optimization of pulsatile ventricular assist devices using FSI to minimize thrombotic risk

NASA Astrophysics Data System (ADS)

Long, C. C.; Marsden, A. L.; Bazilevs, Y.

2014-10-01

In this paper we perform shape optimization of a pediatric pulsatile ventricular assist device (PVAD). The device simulation is carried out using fluid-structure interaction (FSI) modeling techniques within a computational framework that combines FEM for fluid mechanics and isogeometric analysis for structural mechanics modeling. The PVAD FSI simulations are performed under realistic conditions (i.e., flow speeds, pressure levels, boundary conditions, etc.), and account for the interaction of air, blood, and a thin structural membrane separating the two fluid subdomains. The shape optimization study is designed to reduce thrombotic risk, a major clinical problem in PVADs. Thrombotic risk is quantified in terms of particle residence time in the device blood chamber. Methods to compute particle residence time in the context of moving spatial domains are presented in a companion paper published in the same issue (Comput Mech, doi: 10.1007/s00466-013-0931-y, 2013). The surrogate management framework, a derivative-free pattern search optimization method that relies on surrogates for increased efficiency, is employed in this work. For the optimization study shown here, particle residence time is used to define a suitable cost or objective function, while four adjustable design optimization parameters are used to define the device geometry. The FSI-based optimization framework is implemented in a parallel computing environment, and deployed with minimal user intervention. Using five SEARCH/ POLL steps the optimization scheme identifies a PVAD design with significantly better throughput efficiency than the original device.

Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

PubMed

Gerber, Jeffrey S; Ross, Rachael K; Bryan, Matthew; Localio, A Russell; Szymczak, Julia E; Wasserman, Richard; Barkman, Darlene; Odeniyi, Folasade; Conaboy, Kathryn; Bell, Louis; Zaoutis, Theoklis E; Fiks, Alexander G

2017-12-19

Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Broad-spectrum antibiotics vs narrow-spectrum antibiotics. In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868

Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States.

PubMed

Minassian, Caroline; Thomas, Sara L; Smeeth, Liam; Douglas, Ian; Brauer, Ruth; Langan, Sinéad M

2015-12-01

Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥ 65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75-1.74) and unvaccinated (IR 1.78, 95% CI 1.68-1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study's power to assess the role of vaccination. Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a

Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States

PubMed Central

Minassian, Caroline; Thomas, Sara L.; Smeeth, Liam; Douglas, Ian; Brauer, Ruth; Langan, Sinéad M.

2015-01-01

Background Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. Methods and Findings The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17–2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47–1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75–1.74) and unvaccinated (IR 1.78, 95% CI 1.68–1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study’s power to assess the role of vaccination. Conclusions Stroke and MI rates are transiently increased after

Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

PubMed

Uva, Laura; Breschi, Gian Luca; Gnatkovsky, Vadym; Taverna, Stefano; de Curtis, Marco

2015-02-18

Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure. Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.

Relationship Between Acute Benzodiazepine Poisoning and Acute Pancreatitis Risk

PubMed Central

Liaw, Geng-Wang; Hung, Dong-Zong; Chen, Wei-Kung; Lin, Cheng-Li; Lin, I-Ching; Kao, Chia-Hung

2015-01-01

Abstract We designed a population-based retrospective cohort study to investigate the association between the event of benzodiazepine (BZD) poisoning and the risk of acute pancreatitis. In the present study, 12,893 patients with BZD poisoning during 2000 to 2011 were enrolled and matched with 4 comparison patients according to mean age and sex. We determined the cumulative incidences and adjusted hazard ratios of acute pancreatitis. A significant association was observed between BZD poisoning and acute pancreatitis. After adjustment for potential risk factors, the patients with BZD poisoning had a 5.33-fold increased risk of acute pancreatitis compared with the controls without BZD poisoning (HR = 5.33, 95% CI = 2.26–12.60). The results revealed that acute pancreatitis in patients with BZD poisoning occurred in a follow-up time of ≤1 month (HR = 50.0, P < .001), and the risk of acute pancreatitis was no different between the patients with and without BZD poisoning when the follow-up time was >1 month (HR = 1.07, P > .05). This population-based study revealed the positive correlation between the event of BZD poisoning and an increased risk of acute pancreatitis. The findings warrant further large-scale and in-depth investigation. PMID:26717383

Contemporary management of acute coronary syndromes: does the practice match the evidence? The global registry of acute coronary events (GRACE).

PubMed

Carruthers, K F; Dabbous, O H; Flather, M D; Starkey, I; Jacob, A; Macleod, D; Fox, K A A

2005-03-01

To determine to what extent evidence based guidelines are followed in the management of acute coronary syndromes (ACS) in the UK, elsewhere in Europe, and multinationally, and what the outcomes are. Multinational, prospective, observational registry (GRACE, global registry of acute coronary events) with six months' follow up. Patients presenting to a cluster of hospitals. The study was designed to collect data representative of the full spectrum of ACS in specific geographic populations. Patients admitted with a working diagnosis of unstable angina or suspected myocardial infarction (MI). Death during hospitalisation and at six months' follow up (adjusted for baseline risks). In ST elevation MI, reperfusion was applied more often in the UK (71%) than in Europe (65%) and multinationally (59%) (p < 0.01). However, this was almost entirely by lytic treatment, in contrast with elsewhere (primary percutaneous coronary intervention 1%, 29%, 16%, respectively). Statins were applied more frequently in the UK for all classes of patients with ACS (p < 0.0001). In contrast there was lower use of revascularisation procedures in non-ST MI (20% v 37% v 28%, respectively) and glycoprotein IIb/IIIa antagonists (6% v 25% v 26%, respectively). In-hospital death rates, adjusted for baseline risk, were not significantly different but six month death rates were higher in the UK for ST elevation MI (7.2% UK, 4.3% Europe, 5.3% multinationally; p < 0.0001) and non-ST elevation MI (7.5%, 6.2%, and 6.7%, respectively; p = 0.012, UK v Europe). Current management of ACS in the UK more closely follows the recommendations of the National Service Framework than British or European guidelines. Differences in practice may account for the observed higher event rates in the UK after hospital discharge.

Proteasome inhibitor associated thrombotic microangiopathy.

PubMed

Yui, Jennifer C; Van Keer, Jan; Weiss, Brendan M; Waxman, Adam J; Palmer, Matthew B; D'Agati, Vivette D; Kastritis, Efstathios; Dimopoulos, Meletios A; Vij, Ravi; Bansal, Dhruv; Dingli, David; Nasr, Samih H; Leung, Nelson

2016-09-01

A variety of medications have been implicated in the causation of thrombotic microangiopathy (TMA). Recently, a few case reports have emerged of TMA attributed to the proteasome inhibitors (PI) bortezomib and carfilzomib in patients with multiple myeloma. The aim of this case series was to better characterize the role of PI in the etiology of drug-induced TMA. We describe eleven patients from six medical centers from around the world who developed TMA while being treated with PI. The median time between medication initiation and diagnosis of TMA was 21 days (range 5 days to 17 months). Median laboratory values at diagnosis included hemoglobin-7.5 g dL(-1) , platelet count-20 × 10(9) /L, LDH-698 U L(-1) , creatinine-3.12 mg dL(-1) . No patient had any other cause of TMA, including ADAMTS13 inhibition, other malignancy or use of any other medication previously associated with TMA. Nine patients had resolution of TMA without evidence of hemolysis after withdrawal of PI. Two patients had stabilization of laboratory values but persistent evidence of hemolysis despite medication withdrawal. One patient had recurrence of TMA with rechallenge of PI. There is a strong level of evidence that PI can cause DITMA. In evaluating patients with suspected TMA, PI use should be recognized as a potential etiology, and these medications should be discontinued promptly if thought to be the cause of TMA. Am. J. Hematol. 91:E348-E352, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Residual vein thrombosis and onset of post-thrombotic syndrome: influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene.

PubMed

Incalcaterra, Egle; Meli, Francesco; Muratori, Ida; Corrado, Egle; Amato, Corrado; Canino, Baldassare; Ferrara, Filippo

2014-03-01

Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n=85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n=83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment. These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis. Copyright © 2013. Published by Elsevier Ltd.

Impact of aspirin on presentation and hospital outcomes in patients with acute coronary syndromes (The Global Registry of Acute Coronary Events [GRACE]).

PubMed

Spencer, Frederick A; Santopinto, Jose J; Gore, Joel M; Goldberg, Robert J; Fox, Keith A A; Moscucci, Mauro; White, Kami; Gurfinkel, Enrique P

2002-11-15

The long-term use of aspirin (ASA) reduces the risk of subsequent acute coronary syndromes in patients with coronary artery disease (CAD). It is less clear whether ASA therapy benefits patients who develop an acute coronary syndrome despite its use. Baseline characteristics, type of acute coronary syndrome, and in-hospital events were compared on the basis of previous use of ASA in 11,388 patients with and without a history of CAD presenting to 94 multinational hospitals. A total of 73.0% of patients with a history of CAD (n = 4,974) were previously on long-term ASA therapy compared with 19.4% of patients without a history of CAD (n = 6,414). After multivariate regression analysis controlling for various potentially confounding factors, patients with a history of CAD who were previously taking ASA were significantly less likely to present with ST-segment elevation myocardial infarction (MI) (adjusted odds ratio [OR] 0.52, 95% confidence intervals [CI] 0.44 to 0.61) or die during hospitalization (OR 0.69, 95% CI 0.50 to 0.95) in comparison to patients who were not taking ASA. Patients without a history of CAD and who were previously taking ASA also had a lower risk of developing ST-segment elevation MI (OR 0.35, 95% CI 0.30 to 0.40) and a trend toward a decreased hospital death rate (OR 0.77, 95% CI 0.55 to 1.07). These results demonstrate that patients with a history of CAD who present with an acute coronary syndrome despite prior ASA use have less severe clinical presentation, fewer hospital complications, and lower in-hospital death rates than patients not previously taking ASA.

Socio-Economic and Clinical Factors as Predictors of Disease Evolution and Acute Events in COPD Patients

PubMed Central

Pandolfi, Paolo; Zanasi, Alessandro; Musti, Muriel Assunta; Stivanello, Elisa; Pisani, Lara; Angelini, Sabrina; Maffei, Francesca; Hrelia, Silvana; Angeloni, Cristina; Zenesini, Corrado; Hrelia, Patrizia

2015-01-01

Background Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Methods Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant’Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. Results 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01–16.54), having two or more comorbidities (HR = 4.71; 95% CI 2.52–8.83), belonging to moderate (HR = 3.50; 95% CI 1.01–12.18) or very severe COPD stage (HR = 8.23; 95% CI 2.35–28.85). Conclusions Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients. PMID:26252571

Management and outcomes following an acute coronary event in patients with chronic heart failure 1999-2007.

PubMed

Ranasinghe, Isuru; Naoum, Chris; Aliprandi-Costa, Bernadette; Sindone, Andrew P; Steg, P Gabriel; Elliott, John; McGarity, Bruce; Lefkovits, Jeffrey; Brieger, David

2012-05-01

The outcome of patients with chronic heart failure (CHF) following an ischaemic event is poorly understood. We evaluated the management and outcomes of CHF patients presenting with an acute coronary syndrome (ACS) and explored changes in outcomes over time. A total of 5556 patients enrolled in the Australia-New Zealand population of the Global Registry of Acute Coronary Events (GRACE) between 1999 and 2007 were included. Patients with CHF (n = 609) were compared with those without CHF (n = 4947). Patients with CHF were on average 10 years older, were more likely to be female, had more co-morbidities and cardiac risk factors, and were more likely to have a prior history of angina, myocardial infarction, and revascularization by coronary artery bypass graft (CABG) when compared with those without CHF. CHF was associated with a substantial increase in in-hospital renal failure [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.15-2.71], readmission post-discharge (OR 1.47, 95% CI 1.17-1.90), and 6-month mortality (OR 2.25, 95% CI 1.55-3.27). Over the 9 year study period, in-hospital and 6 month mortality in those with CHF declined by absolute rates of 7.5% and 14%, respectively. This was temporally associated with an increase in prescription of thienopyridines, beta-blockers, statins, and angiotensin II receptor blockers, increased rates of coronary angiography, and 31.8% absolute increase in referral rates for cardiac rehabilitation. Acute coronary syndrome patients with pre-existing CHF are a very high risk group and carry a disproportionate mortality burden. Encouragingly, there was a marked temporal improvement in outcomes over a 9 year period with an increase in evidence-based treatments and secondary preventative measures.

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

Sithu, Srinivas D.; Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202; Srivastava, Sanjay

Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not causemore » pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.« less

Acute deep vein thrombosis and endovascular techniques: It is time for a new aggiornamento!

PubMed

Pernès, J-M; Auguste, M; Kovarski, S; Borie, H; Renaudin, J-M; Coppe, G

2012-10-01

The stated aims of treating acute deep vein thrombosis (DVT) are to prevent a pulmonary embolism, stop the clot from spreading, reduce the risk of a recurrence; they are less concerned with the late morbidity associated with post-thrombotic syndrome (PTS). In accordance with the French (Afssaps, 2009) and North American (ACCP, 2008) recommendations, anticoagulants (LMWH, heparin, AVK) form the cornerstone for treating DVT. These treatments appear to be far less effective in preventing post-thrombotic syndrome (PTS), associated with venous hypertension, residual occlusion, and with reflux caused by valve incompetence. Given that, the new aim is to optimise the prevention of PTS, the ACCP guidelines, unlike those of Afssaps, "suggest" for selected patients suffering from acute iliofemoral DVT, the use of both classic anticoagulants, and in situ percutaneous administration of thrombolytic drugs (recommendation grade 2B) and simultaneous correction of any underlying anatomical anomalies using angioplasty and stenting (recommendation 2C). Contemporary endovascular methods, referred to collectively as "facilitated" thrombolysis, combine low doses of rtPa or Urokinase administered locally, and the removal of the clot using various mechanical, rotating, rheolytic systems, or using ultrasound. The results of non-randomised, heterogeneous studies objectivised a lysis rate of 80%, a 50% lower risk of haemorrhage complications compared with systemic thrombolysis (<4%), and a clear reduction in treatment time (one-shot methods possible for procedures lasting less than 2 hours). This data ties in with the modern "open vein" concept which underpins the hope of an improvement in the late prognosis of acute DVT, through the removal of a clot, thereby improving permeability and valve integrity; this hypothesis is supported by the results at 24 months of a randomised CaVent objectifying absolute risk reduction of 15% in the thrombolysis in situ. The current randomised study (ATTRACT

BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient.

PubMed

Lopes da Silva, R; Ferreira, I; Teixeira, G; Cordeiro, D; Mafra, M; Costa, I; Bravo Marques, J M; Abecasis, M

2011-04-01

BK virus (BKV) infection occurs most often in immunocompromised hosts, in the setting of renal or bone marrow transplantation. Hemorrhagic cystitis is the commonest manifestation but in recent years infections in other organ systems have been reported. We report an unusual case of biopsy-proven BKV encephalitis in a hematopoietic stem cell transplant patient who subsequently developed thrombotic microangiopathy. As far as we know, this is the first report of such an association in a transplant patient. © 2010 John Wiley & Sons A/S.

Adverse cardiovascular events in acute coronary syndrome with indications for anticoagulation.

PubMed

Knight, Stacey; McCubrey, Raymond O; Yuan, Zhong; Woller, Scott C; Horne, Benjamin D; Bunch, T Jared; Le, Viet T; Mills, Roger M; Muhlestein, Joseph B

2016-08-01

Randomized acute coronary syndrome (ACS) trials testing various antithrombotic (AT) regimens have largely excluded patients with coexisting conditions and indications for anticoagulation (AC). The purpose of this study is to examine the 2-year clinical outcomes of patients with ACS with indication for AC due to venous thromboembolism (VTE) during hospitalization for the ACS event or a prior or new diagnosis of atrial fibrillation (AF) with a CHADS2 (Congestive heart failure; Hypertension; Age; Diabetes; previous ischemic Stroke) score ⩾2. ACS patients with AC indication from 2004 to 2009 were identified (n = 619). A Cox proportional hazards model was used to examine the primary efficacy outcome of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) or stroke. The primary explanatory variable was at-discharge antithrombotic strategy [single antiplatelet ± AC, dual antiplatelet (DAP) ± AC or AC only; referent DAP + AC]. A total of 261 (42.2%) patients had a MACE event. AT strategy was not a significant factor for MACE (all p > 0.09). The factors associated with MACE were high mortality risk score [hazard ratio (HR)=1.87, 95% confidence interval (CI): 1.39- 2.52; p < 0.001), prior MI (HR = 1.44, 95% CI: 1.03-2.01; p= 0.033) and presentation of ST elevation MI (HR = 2.70, 95% CI: 1.61-4.51; p < 0.001) or non-ST elevation MI (HR = 1.70, 95% CI: 1.15-2.49; p < 0.001) compared with angina. In this real world observational study, the at-discharge AT strategy was not significantly associated with the 2-year risk of MACE. These findings do not negate the need for randomized trials to generate evidence-based approaches to management of this important population. © The Author(s), 2016.

Adverse cardiovascular events in acute coronary syndrome with indications for anticoagulation

PubMed Central

Knight, Stacey; McCubrey, Raymond O.; Yuan, Zhong; Woller, Scott C.; Horne, Benjamin D.; Bunch, T. Jared; Le, Viet T.; Mills, Roger M.; Muhlestein, Joseph B.

2016-01-01

Objectives: Randomized acute coronary syndrome (ACS) trials testing various antithrombotic (AT) regimens have largely excluded patients with coexisting conditions and indications for anticoagulation (AC). The purpose of this study is to examine the 2-year clinical outcomes of patients with ACS with indication for AC due to venous thromboembolism (VTE) during hospitalization for the ACS event or a prior or new diagnosis of atrial fibrillation (AF) with a CHADS2 (Congestive heart failure; Hypertension; Age; Diabetes; previous ischemic Stroke) score ⩾2. Methods: ACS patients with AC indication from 2004 to 2009 were identified (n = 619). A Cox proportional hazards model was used to examine the primary efficacy outcome of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) or stroke. The primary explanatory variable was at-discharge antithrombotic strategy [single antiplatelet ± AC, dual antiplatelet (DAP) ± AC or AC only; referent DAP + AC]. Results: A total of 261 (42.2%) patients had a MACE event. AT strategy was not a significant factor for MACE (all p > 0.09). The factors associated with MACE were high mortality risk score [hazard ratio (HR)=1.87, 95% confidence interval (CI): 1.39– 2.52; p < 0.001), prior MI (HR = 1.44, 95% CI: 1.03–2.01; p= 0.033) and presentation of ST elevation MI (HR = 2.70, 95% CI: 1.61–4.51; p < 0.001) or non-ST elevation MI (HR = 1.70, 95% CI: 1.15–2.49; p < 0.001) compared with angina. Conclusions: In this real world observational study, the at-discharge AT strategy was not significantly associated with the 2-year risk of MACE. These findings do not negate the need for randomized trials to generate evidence-based approaches to management of this important population. PMID:26920371

El Salvador earthquakes: relationships among acute stress disorder symptoms, depression, traumatic event exposure, and resource loss.

PubMed

Sattler, David N; de Alvarado, Ana Maria Glower; de Castro, Norma Blandon; Male, Robert Van; Zetino, A M; Vega, Raphael

2006-12-01

Four and seven weeks after powerful earthquakes in El Salvador, the authors examined the relationships among demographics, traumatic event exposure, social support, resource loss, acute stress disorder (ASD) symptoms, depression, and posttraumatic growth. Participants were 253 college students (Study 1) and 83 people in the community (Study 2). In Study 1, female gender, traumatic event exposure, low social support, and loss of personal characteristic, condition, and energy resources contributed to ASD symptoms and depression. In Study 2, damage to home and loss of personal characteristic and object resources contributed to ASD symptoms and depression. Posttraumatic growth was not associated with ASD symptoms or depression. Findings support the conservation of resources stress theory (Hobfoll, 1998). Resource loss spirals, excessive demands on coping, and exposure to multiple disasters are discussed.

[An health education program for patients admitted to CCU for an acute coronary event].

PubMed

Amodeo, Raffaello; De Ponti, Anna; Sorbara, Loredana; Imperatore, Patrizia Fusar; Berizzi, Margherita; Di Rocco, Egidia; Saltarel, Ivan; Marigliani, Catia; Avanzini, Fausto

2006-01-01

In spite of the broad recognition of the importance of health education, time for structured one-to -one initiatives of health education during the hospital stay is limited. The organization of an health education meeting for patients admitted to CCU for an acute coronary event is described. The planning and implementation of the initiative lasted two years and involved 7 nurses and one doctor. The organization required efforts related to the event itself (preparation of training aids, identification or contents and methods for delivery) but also organizative changes. Dietitians in fact had to be involved because the healthy diet recommended was different from the hospital diet. The assessment of the effectiveness of the health education was also planned: administration of a questionnaire to explore lifestyles and knowledge of the illness before and after the meeting; phone interviews after 3, 6 and 12 months from the meeting. Since may 2003, in the first 3 years 74 meetings have been organised, involving 507 patients and 329 relatives. Each meeting lasts 2 hours and contents delivered encompass the coronary event, risk factors and their modification, healthy lifestyles. Initial preliminary results on the impact of the meeting on lifestyle changes are promising. Initiatives are ongoing to include this activity among officially recognised nursing activities.

A missed penalty kick triggered coronary death in the husband and broken heart syndrome in the wife.

PubMed

Y-Hassan, Shams; Feldt, Kari; Stålberg, Marcus

2015-11-15

Events that induce emotional stress and frustration in a large number of subjects under specific circumstances, such as earthquakes, war conditions, and sporting occasions, may increase the incidence of cardiovascular events, such as acute myocardial infarction, arrhythmias, and sudden cardiac death. This report describes a married couple who expressed an apparently passionate interest in football with hazardous consequences after a tense football match during the FIFA 2014 World Championships. A series of emotional stressors initiated by defeat in this football game lead to cardiac arrest in a 58-year-old man caused by a thrombotic occlusion of the left anterior descending artery and ending in the death of the patient. An hour and 15 minutes after the onset of cardiac arrest of the patient, his 64-year-old wife also had chest pain caused by an acute midventricular takotsubo syndrome. She survived the acute stage of the disease, and there was complete resolution of the left ventricular dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Thrombotic manifestations in SAPHO syndrome. Review of the literature.

PubMed

Carranco-Medina, Tatiana Elizabeth; Hidalgo-Calleja, Cristina; Calero-Paniagua, Ismael; Sánchez-González, María Dolores; Quesada-Moreno, Alba; Usategui-Martín, Ricardo; Pérez-Garrido, Laura; Gómez-Castro, Susana; Montilla-Morales, Carlos Alberto; Martínez-González, Olga; Del Pino-Montes, Javier

2015-01-01

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a cluster of osteo-cutaneous manifestations that can lead to serious complications such as thrombosis of the subclavian vein or superior vena cava, mainly in patients with significant inflammatory involvement of the anterior-chest-wall. The objective of this study was to review the cases published in the medical literature related with the presence of thrombotic complications in patients diagnosed with SAPHO syndrome and to try to determine their possible pathogenic mechanism and risk factors. We analyzed 11 published reports of isolated clinical cases or case series, a total of 144 patients, which described a total of 15 cases of venous thrombosis. The clinical characteristics of these patients, evaluated to determine whether they meet the ASAS criteria for axial and peripheral spondyloarthritis, is analyzed the need for early diagnosis and treatment is highlighted. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Acute physical exercise is safe in patients with primary antiphospholipid syndrome with exclusive venous thrombosis and under oral anticoagulation with warfarin.

PubMed

Garcia, Carolina Borges; Seguro, Luciana Parente Costa; Perandini, Luiz Augusto; de Sá Pinto, Ana Lúcia; Lima, Fernanda Rodrigues; Negrão, Carlos Eduardo; Bonfa, Eloisa; Borba, Eduardo Ferreira

2014-12-01

The purpose of present study was to evaluate the effects of maximal acute physical exercise on prothrombin time/international normalized ratio (PT/INR) in patients with primary antiphospholipid syndrome (PAPS) under oral anticoagulation with warfarin and the safety of acute exercise in regard to thrombosis and bleeding risk. Eighteen physically inactive women with PAPS (Sydney criteria) with exclusive venous events and without thrombocytopenia were included. All patients were under stable warfarin therapy (PT/INR target: 2.0-3.0). Eighteen age-matched healthy sedentary women without thrombosis/bleeding disorders were selected as controls. All subjects performed a maximal exercise test, and capillary blood samples were obtained pre-, post- and at 1-h post-exercise (recovery time) for PT/INR analysis using a portable CoaguCheck. PAPS patients and controls had similar mean age (31.50 ± 8.06 vs. 29.61 ± 7.05 years, p = 0.46) and body mass index (24.16 ± 3.67 vs. 24.66 ± 2.71 kg/m(2), p = 0.65). PAPS had a mild but significant increase in PT/INR value at 1-h post-exercise (recovery) compared with pre- (2.33 ± 0.34 vs. 2.26 ± 0.29, p = 0.001) and post-exercise (2.33 ± 0.34 vs. 2.26 ± 0.32, p = 0.001) that was observed in 61.11 % of these patients. None of the subjects had thrombotic or bleeding complications related to the acute exercise. Acute exercise in patients with PAPS with exclusive venous thrombosis was safe with a minor increase in PT/INR. This is an important step to introduce regular exercise training as a therapeutic tool in the management of these patients.

Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: a refractory case without lupus activity.

PubMed

Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel

2013-01-01

The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab. Copyright © 2012 Elsevier España, S.L. All rights reserved.

The course of posttraumatic stress symptoms and functional impairment following a disaster: what is the lasting influence of acute vs. ongoing traumatic events and stressors?

PubMed Central

Cerdá, M.; Bordelois, P.M.; Galea, S.; Norris, F.; Tracy, M.; Koenen, K.C.

2012-01-01

Purpose Ongoing traumatic events and stressors, rather than acute sources of trauma, may shape long-term post-disaster mental health. The purpose of this study was to compare the influence of acute hurricane-related exposures and ongoing post-hurricane exposures on the short- and long-term course of posttraumatic stress symptoms (PTSS) and functional impairment (FI). Methods A random sample of adults (n=658) in Galveston and Chambers Counties, Texas, was selected 2–6 months after Hurricane Ike and interviewed 3 times over eighteen months. Hurricane-related exposures included traumatic events such as death of a family member due to the hurricane and stressors such as loss/damage to personal property due to the hurricane. Post-hurricane exposures included traumatic events such as sexual assault and stressors such as divorce or serious financial problems. Results Experiencing an acute hurricane-related traumatic event or stressor was associated with initial post-hurricane PTSS [RR=1.92(95% CI=1.13–3.26) and RR=1.62(1.36–1.94), respectively] and FI [RR=1.76; (1.05–2.97) and RR=1.74(1.46–2.08)], respectively, and acute hurricane-related stressors were associated with a higher rate of increase in FI over time [RR=1.09; (1.01–1.19)]. In contrast, ongoing post-hurricane daily stressors were not associated within initial PTSS and FI, but were associated with PTSS and FI at the second and third interviews. Conclusions While immediate postdisaster interventions may influence short-term mental health, investment in the prevention of ongoing stressors may be instrumental to manage long-term mental health status. PMID:22878832

Antiplatelet therapy in elderly patients with acute coronary syndrome: Between scientific evidence and future perspectives.

PubMed

Barillà, Francesco; Torromeo, Concetta; Iorio, Riccardo; Porco, Luigina; Paravati, Vincenzo; Gaudio, Carlo

2018-06-07

Dual antiplatelet therapy (DAPT) is an important strategy for reducing cardiovascular events (CV) after an acute coronary syndrome (ACS). Elderly patients undergoing DAPT have a higher risk of bleeding than younger patients for a variety of reasons. Stratification of thrombotic/hemorrhagic risk is mandatory in order to decide on the type and duration of DAPT. The percentage of patients ≥ 75 years represented in clinical trials is not large, so very often elderly people are prescribed treatment protocols only experimented on younger patients with a lower hemorrhagic risk. However, even in patients aged ≥ 75 treated with invasive or conservative therapy, after an ACS, a DAPT with aspirin 80-100 mg/day plus a P2Y12 receptor inhibitor for 12 months is recommended. In elderly patients, DAPT should be considered a dynamic process that can be modified over time based on the patient's clinical conditions, or any other necessities (non-procrastinating surgical interventions, comorbid-like effects that can increase hemorrhagic risk). In patients with moderate-high or very high hemorrhagic risk, DAPT treatment should last less than 12 months. A prolongation of DAPT beyond 12 months in this setting is limited to a very low percentage of patients, after careful assessment of ischemic/hemorrhagic profile.

Emotional stressors trigger cardiovascular events.

PubMed

Schwartz, B G; French, W J; Mayeda, G S; Burstein, S; Economides, C; Bhandari, A K; Cannom, D S; Kloner, R A

2012-07-01

To describe the relation between emotional stress and cardiovascular events, and review the literature on the cardiovascular effects of emotional stress, in order to describe the relation, the underlying pathophysiology, and potential therapeutic implications. Targeted PUBMED searches were conducted to supplement the authors' existing database on this topic. Cardiovascular events are a major cause of morbidity and mortality in the developed world. Cardiovascular events can be triggered by acute mental stress caused by events such as an earthquake, a televised high-drama soccer game, job strain or the death of a loved one. Acute mental stress increases sympathetic output, impairs endothelial function and creates a hypercoagulable state. These changes have the potential to rupture vulnerable plaque and precipitate intraluminal thrombosis, resulting in myocardial infarction or sudden death. Therapies targeting this pathway can potentially prevent acute mental stressors from initiating plaque rupture. Limited evidence suggests that appropriately timed administration of beta-blockers, statins and aspirin might reduce the incidence of triggered myocardial infarctions. Stress management and transcendental meditation warrant further study. © 2012 Blackwell Publishing Ltd.

Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial.

PubMed

Murphy, Sabina A; Cannon, Christopher P; Blazing, Michael A; Giugliano, Robert P; White, Jennifer A; Lokhnygina, Yuliya; Reist, Craig; Im, KyungAh; Bohula, Erin A; Isaza, Daniel; Lopez-Sendon, Jose; Dellborg, Mikael; Kher, Uma; Tershakovec, Andrew M; Braunwald, Eugene

2016-02-02

Intensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin. This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy. All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Lipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878). Copyright © 2016 American College of

The spectrum of renal thrombotic microangiopathy in lupus nephritis

PubMed Central

2013-01-01

Introduction Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Methods Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. Results In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group

Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

NASA Technical Reports Server (NTRS)

Carnell, Lisa; Blattnig, Steve; Hu, Shaowen; Huff, Janice; Kim, Myung-Hee; Norman, Ryan; Patel, Zarana; Simonsen, Lisa; Wu, Honglu

2016-01-01

Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation.

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat

PubMed Central

Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-01-01

Background & objectives: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation & conclusions: High

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat.

PubMed

Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-06-01

Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. High fructose feeding to rats and hamsters led to the development of insulin

Previous Use of Antithrombotic Agents Reduces Mortality and Length of Hospital Stay in Patients With High-risk Upper Gastrointestinal Bleeding.

PubMed

Dunne, Philip D J; Laursen, Stig B; Laine, Loren; Dalton, Harry R; Ngu, Jing H; Schultz, Michael; Rahman, Adam; Anderloni, Andrea; Murray, Iain A; Stanley, Adrian J

2018-04-26

Anti-thrombotic agents are risk factors for upper gastrointestinal bleeding (UGIB). However, few studies have evaluated their effects on patient outcomes. We assessed the effects of anti-thrombotic agents on outcomes of patients with high-risk UGIB. We performed a prospective study of 619 patients with acute UGIB (defined by hematemesis, coffee-ground vomit or melena) who required intervention and underwent endoscopy at 8 centers in North America, Asia, and Europe, from March 2014 through March 2015. We collected data recorded on use of anti-thrombotic agents, clinical features, and laboratory test results to calculate AIMS65, Glasgow-Blatchford Score, and full Rockall scores. We also collected and analyzed data on co-morbidities, endoscopic findings, blood transfusion, interventional radiology results, surgeries, length of hospital stay, rebleeding, and mortality. Of the 619 patients who required endoscopic therapy, data on use of anti-thrombotic agents was available for 568; 253 of these patients (44%) used anti-thrombotic agents. Compared to patients not taking anti-thrombotic agents, patients treated with anti-thrombotics were older (P < .001), had a higher mean American Society of Anesthesiologists classification score (P < .0001), had a higher mean Rockall score (P < .0001), a higher mean AIMS65 score (P < .0001), and more frequently bled from ulcers (P < .001). There were no differences between groups in sex, systolic blood pressure, level of hemoglobin at hospital admission, frequency of malignancies, Glasgow-Blatchford Score, need for surgery or interventional radiology, number of rebleeding events, or requirement for transfusion. All-cause mortality was lower in patients who took anti-thrombotic drugs (11 deaths, 4%) than in patients who did not (37 deaths, 12%) (P = .002); this was due to lower bleeding-related mortality in patients taking anti-thrombotic drugs (3 deaths, 1%) than in patients who were not (19 deaths, 6%) (P = .003). Patients

Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major Vascular Events.

PubMed

Lee, Keon-Joo; Kim, Beom Joon; Han, Moon-Ku; Kim, Joon-Tae; Cho, Ki-Hyun; Shin, Dong-Ick; Yeo, Min-Ju; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Kim, Dong-Eog; Ryu, Wi-Sun; Park, Jong-Moo; Kang, Kyusik; Lee, Soo Joo; Oh, Mi-Sun; Yu, Kyung-Ho; Lee, Byung-Chul; Hong, Keun-Sik; Cho, Yong-Jin; Choi, Jay Chol; Sohn, Sung Il; Hong, Jeong-Ho; Park, Tai Hwan; Park, Sang-Soon; Kwon, Jee-Hyun; Kim, Wook-Joo; Lee, Jun; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B; Bae, Hee-Joon

2018-01-01

This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events. Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively. Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P =0.004) and secondary ( P <0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant ( P <0.05). When predictive power of BP parameters was compared using a statistic of -2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively. Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters. © 2017 American Heart Association, Inc.

Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.

PubMed

Zhu, Qiuyu Martin; Ko, Kyung Ae; Ture, Sara; Mastrangelo, Michael A; Chen, Ming-Huei; Johnson, Andrew D; O'Donnell, Christopher J; Morrell, Craig N; Miano, Joseph M; Lowenstein, Charles J

2017-02-01

To identify and characterize the effect of a SNP (single-nucleotide polymorphism) in the STXBP5 locus that is associated with altered thrombosis in humans. GWAS (genome-wide association studies) have identified numerous SNPs associated with human thrombotic phenotypes, but determining the functional significance of an individual candidate SNP can be challenging, particularly when in vivo modeling is required. Recent GWAS led to the discovery of STXBP5 as a regulator of platelet secretion in humans. Further clinical studies have identified genetic variants of STXBP5 that are linked to altered plasma von Willebrand factor levels and thrombosis in humans, but the functional significance of these variants in STXBP5 is not understood. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) techniques to produce a precise mouse model carrying a human coding SNP rs1039084 (encoding human p. N436S) in the STXBP5 locus associated with decreased thrombosis. Mice carrying the orthologous human mutation (encoding p. N437S in mouse STXBP5) have lower plasma von Willebrand factor levels, decreased thrombosis, and decreased platelet secretion compared with wild-type mice. This thrombosis phenotype recapitulates the phenotype of humans carrying the minor allele of rs1039084. Decreased plasma von Willebrand factor and platelet activation may partially explain the decreased thrombotic phenotype in mutant mice. Using precise mammalian genome editing, we have identified a human nonsynonymous SNP rs1039084 in the STXBP5 locus as a causal variant for a decreased thrombotic phenotype. CRISPR/Cas9 genetic editing facilitates the rapid and efficient generation of animals to study the function of human genetic variation in vascular diseases. © 2016 American Heart Association, Inc.

Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk.

PubMed

Seeger, Julia; Bothner, Carlo; Dahme, Tillman; Gonska, Birgid; Scharnbeck, Dominik; Markovic, Sinisa; Rottbauer, Wolfgang; Wöhrle, Jochen

2016-03-01

The randomized PROTECT AF trial demonstrated non-inferiority of left atrial appendage (LAA) closure to oral anticoagulation with warfarin. Current guidelines give a class IIb recommendation for LAA closure. We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk. 101 consecutive non-valvular atrial fibrillation patients (age 74.7 ± 7.5 years) at high risk for stroke (CHA2DS2-VASc Score 4.4 ± 1.6) and high bleeding risk (HAS-BLED Score 4.2 ± 1.3) received LAA closure with either the Watchman closure device (n = 38) or the Amplatzer cardiac plug (n = 63). Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3-6 months after device implantation, followed by long-term antiplatelet therapy with aspirin. No anticoagulation was given after device implantation. Mean follow-up was 400 days. One patient (1 %) experienced a transient ischemic attack, and two patients (2 %) suffered from ischemic stroke. While on recommended antiplatelet therapy, bleeding occurred in 12/101 patients (12 %). Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy (3.0 vs. 16.2 %, p < 0.05) while ischemic or thrombotic events were similar. Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score. Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events.

Geospatial relationships of air pollution and acute asthma events across the Detroit-Windsor international border: study design and preliminary results.

PubMed

Lemke, Lawrence D; Lamerato, Lois E; Xu, Xiaohong; Booza, Jason C; Reiners, John J; Raymond Iii, Delbert M; Villeneuve, Paul J; Lavigne, Eric; Larkin, Dana; Krouse, Helene J

2014-07-01

The Geospatial Determinants of Health Outcomes Consortium (GeoDHOC) study investigated ambient air quality across the international border between Detroit, Michigan, USA and Windsor, Ontario, Canada and its association with acute asthma events in 5- to 89-year-old residents of these cities. NO2, SO2, and volatile organic compounds (VOCs) were measured at 100 sites, and particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) at 50 sites during two 2-week sampling periods in 2008 and 2009. Acute asthma event rates across neighborhoods in each city were calculated using emergency room visits and hospitalizations and standardized to the overall age and gender distribution of the population in the two cities combined. Results demonstrate that intra-urban air quality variations are related to adverse respiratory events in both cities. Annual 2008 asthma rates exhibited statistically significant positive correlations with total VOCs and total benzene, toluene, ethylbenzene and xylene (BTEX) at 5-digit zip code scale spatial resolution in Detroit. In Windsor, NO2, VOCs, and PM10 concentrations correlated positively with 2008 asthma rates at a similar 3-digit postal forward sortation area scale. The study is limited by its coarse temporal resolution (comparing relatively short term air quality measurements to annual asthma health data) and interpretation of findings is complicated by contrasts in population demographics and health-care delivery systems in Detroit and Windsor.

[Value of DC and DRs in prediction of cardiovascular events in acute myocardial infarction patients].

PubMed

Gao, L; Chen, Y D; Shi, Y J; Xue, H; Wang, J L

2016-05-24

To investigate the value of deceleration capacity of rate (DC) and heart rate deceleration runs(DRs) in predicting cardiovascular events in patient with acute myocardial infarction (AMI). This study included 166 patients with AMI, who underwent ECG with sinus rhythm.These patients were followed-up for major adverse cardiac events (MACE). The receiver operating characteristic curve (ROC) was drawn to determine the best values for estimating the MACE. The mean follow-up time was (20.5±2.8) months, with 13 cases of cardiac death.There was statistically significant difference of DC, DRs and standard diviation of NN intervals(SDNN-24) between the death group and survival group.The area under the curve (AUC) of DC, DR4 and DR8 were larger than SDNN-24 (0.874, 0.804 vs 0.727). The values of DC, DR2, DR4 and root mean square of the successive differences(RMSSD) in the group of patients who underwent cardiac adverse events were smaller than the group of patients who didn't, and the AUC of DC was slightly higher than that of RMSSD. DC and DRs have important predictive value for cardiac death and MACE and can screen high-risk patients in patients with AMI.

Health Economic Analysis of Antiplatelet Therapy for Acute Coronary Syndromes in the Context of Five Eastern Asian Countries.

PubMed

Wu, Bin; Tobe, Ruoyan Gai; Liu, Yuchen; He, Ben

2018-04-30

The economic outcomes of dual antiplatelet therapy in East Asian patients are still unclear. We aimed to evaluate the economic outcomes of ticagrelor versus clopidogrel for patients with acute coronary syndrome (ACS) in China, Japan, Korea, Taiwan and Hong Kong. A two-phase model consisting of a 1-year decision tree and a lifetime Markov model was used to estimate the economic outcomes. The data from the East Asian subgroup of Platelet Inhibition and Patient Outcomes (PLATO) and PHILO studies were used for the calculation of the events rate for ticagrelor and clopidogrel in the first 12 months, whereas the costs were obtained from East Asian sources and utility from the published literature. Sensitivity analyses were conducted to test model robustness. Ticagrelor showed the marginal lifetime quality-adjusted life-year (QALY) of 0.0050, 0.0091, 0.0107, 0.0050, and 0.0050 in China, Japan, Korea, Taiwan, and Hong Kong compared with clopidogrel, with marginal healthcare costs of (all values in US dollars) $562, $595, $975, $611, and $672, respectively. The marginal cost per QALY gained with ticagrelor was $112,051, $65,692, $91,207, $121,838, and $133,953 from a public healthcare system perspective of China, Japan, Korea, Taiwan, and Hong Kong, respectively. The sensitivity analysis showed consistent results. Treatment of ACS for 12 months with ticagrelor is not a cost-effective option for the prevention of thrombotic events in East Asia.

Thrombus Extraction Catheters vs. Angiojet Rheolytic Thrombectomy in Thrombotic Lesions/SV Grafts

PubMed Central

Alexopoulos, Dimitrios; Davlouros, Periklis A

2012-01-01

Primary percutaneous coronary intervention, (pPCI), of native coronaries and saphenous vein grafts (SVGs), is the recommended reperfusion strategy for STEMI, and an early invasive approach is recommended for high risk patients with UA/NSTEMI. Although PCI effectively restores flow in the infarct related artery/culprit vessel in both situations, myocardial perfusion often remains suboptimal due to microvascular obstruction, partly attributed to distal embolization of thrombus. Hence, thrombectomy (manual or mechanical), prior to stenting may further reduce hard clinical end points in patients with ACS. This article discusses accumulated evidence regarding the safety and effectiveness of thrombectomy in culprit native coronaries and SVGs in such patients, as well as possible strategies for maximizing its benefits relative to the size of the thrombotic burden. PMID:22920486

Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

PubMed

Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Aquino, Melissa; Kini, Annapoorna S; Rao, Sunil; Weintraub, William; Henry, Timothy D; Farhan, Serdar; Vogel, Birgit; Sorrentino, Sabato; Ge, Zhen; Kapadia, Samir; Muhlestein, Joseph B; Weiss, Sandra; Strauss, Craig; Toma, Catalin; DeFranco, Anthony; Effron, Mark B; Keller, Stuart; Baker, Brian A; Pocock, Stuart; Dangas, George; Mehran, Roxana

2018-03-01

Potent P2Y 12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction. Copyright © 2018. Published by Elsevier Inc.

Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.

PubMed

Glueck, Charles J; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

2016-01-01

When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

A taurine-supplemented vegan diet may blunt the contribution of neutrophil activation to acute coronary events.

PubMed

McCarty, Mark F

2004-01-01

Neutrophils are activated in the coronary circulation during acute coronary events (unstable angina and myocardial infarction), often prior to the onset of ischemic damage. Moreover, neutrophils infiltrate coronary plaque in these circumstances, and may contribute to the rupture or erosion of this plaque, triggering thrombosis. Activated neutrophils secrete proteolytic enzymes in latent forms which are activated by the hypochlorous acid (HOCl) generated by myeloperoxidase. These phenomena may help to explain why an elevated white cell count has been found to be an independent coronary risk factor. Low-fat vegan diets can decrease circulating leukocytes--neutrophils and monocytes--possibly owing to down-regulation of systemic IGF-I activity. Thus, a relative neutropenia may contribute to the coronary protection afforded by such diets. However, vegetarian diets are devoid of taurine - the physiological antagonist of HOCl--and tissue levels of this nutrient are relatively low in vegetarians. Taurine has anti-atherosclerotic activity in animal models, possibly reflecting a role for macrophage-derived myeloperoxidase in the atherogenic process. Taurine also has platelet-stabilizing and anti-hypertensive effects that presumably could reduce coronary risk. Thus, it is proposed that a taurine-supplemented low-fat vegan diet represents a rational strategy for diminishing the contribution of activated neutrophils to acute coronary events; moreover, such a regimen would work in a number of other complementary ways to promote cardiovascular health. Moderate alcohol consumption, the well-tolerated drug pentoxifylline, and 5-lipoxygenase inhibitors--zileuton, boswellic acids, fish oil--may also have potential in this regard. Copyright 2004 Elsevier Ltd.

Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure.

PubMed

Pitts, Reynaria; Gunzburger, Elise; Ballantyne, Christie M; Barter, Philip J; Kallend, David; Leiter, Lawrence A; Leitersdorf, Eran; Nicholls, Stephen J; Shah, Prediman K; Tardif, Jean-Claude; Olsson, Anders G; McMurray, John J V; Kittelson, John; Schwartz, Gregory G

2017-01-10

Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF <40%), III, or IV HF were excluded. Aldosterone was measured at randomization in 4073 patients. The primary outcome was a composite of coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00658515. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Thromboembolic events in patients with severe pandemic influenza A/H1N1.

PubMed

Avnon, Lone Sølling; Munteanu, Daniela; Smoliakov, Alexander; Jotkowitz, Alan; Barski, Leonid

2015-10-01

The 2009 pandemic influenza A/H1N1 developed as a novel swine influenza which caused more diseases among younger age groups than in the elderly. Severe hypoxemic respiratory failure from A/H1N1 pneumonia resulted in an increased need for ICU beds. Several risk groups were identified that were at a higher risk for adverse outcomes. Pregnant women were a particularly vulnerable group of patients The CDC reported on the first ten patients with severe illness and acute hypoxemic respiratory failure associated with A/H1N1 infection, none of whom were pregnant, but they noticed that half of the patients had a pulmonary embolism. During a four-month period from September to December 2009, 252 patients were admitted to our hospital with confirmed pandemic influenza H1N1 by real-time reverse transcriptase-polymerase chain reaction test (rRT-PCR). We cared for twenty patients (7.9%) admitted to MICU with severe A/H1N1. Results on Thrombotic events were identified in five (25%) of our critically ill patients. We recommend that patients with severe influenza A/H1N1 pneumonitis and respiratory failure be administered DVT prophylaxis in particular if there are additional risk factors for TVE. Further prospective studies on the relationship of influenza A/H1N1 and VTE are needed. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

A Prospective Open-label Pilot Study of Fluvastatin on Pro-inflammatory and Pro-thrombotic Biomarkers in Antiphospholipid Antibody Positive Patients

PubMed Central

Erkan, Doruk; Willis, Rohan; Murthy, Vijaya L.; Basra, Gurjot; Vega, JoAnn; Ruiz Limón, Patricia; Carrera, Ana Laura; Papalardo, Elizabeth; Martínez-Martínez, Laura Aline; González, Emilio B.; Pierangeli, Silvia S.

2014-01-01

Objective: To determine if pro-inflammatory and pro-thrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: a) Primary Antiphospholipid Syndrome (PAPS); b) Systemic Lupus Erythematosus (SLE) with APS (SLE/APS); c) Persistent aPL positivity without SLE or APS (Primary aPL); and d) Persistent aPL positivity with SLE but no APS (SLE/aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for three months. At three months, patients stopped the study medication and they were followed for another three months. Blood samples for 12 pro-inflammatory and pro-thrombotic biomarkers were collected monthly for six months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin [IL]-6, IL1β, vascular endothelial growth factor [VEGF], tumor necrosis factor [TNF]-□α, interferon [IFN]-α, inducible protein-10 [IP10], soluble CD40 ligand [sCD40L], soluble tissue factor [sTF], and intracellular cellular adhesion molecule [ICAM]-1) were significantly elevated. Twenty-four patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L, and sTF). Conclusion: Our prospective mechanistic study demonstrates that pro-inflammatory and pro-thrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients. PMID:23933625

Approach to chest pain and acute myocardial infarction.

PubMed

Pandie, S; Hellenberg, D; Hellig, F; Ntsekhe, M

2016-03-01

Patient history, physical examination, 12-lead electrocardiogram (ECG) and cardiac biomarkers are key components of an effective chest pain assessment. The first priority is excluding serious chest pain syndromes, namely acute coronary syndromes (ACSs), aortic dissection, pulmonary embolism, cardiac tamponade and tension pneumothorax. On history, the mnemonic SOCRATES (Site Onset Character Radiation Association Time Exacerbating/relieving factor and Severity) helps differentiate cardiac from non-cardiac pain. On examination, evaluation of vital signs, evidence of murmurs, rubs, heart failure, tension pneumothoraces and chest infections are important. A 12-lead ECG should be interpreted within 10 minutes of first medical contact, specifically to identify ST elevation myocardial infarction (STEMI). High-sensitivity troponins improve the rapid rule-out of myocardial infarction (MI) and confirmation of non-ST elevation MI (NSTEMI). ACS (STEMI and NSTEMI/unstable anginapectoris (UAP)) result from acute destabilisation of coronary atheroma with resultant complete (STEMI) or subtotal (NSTEMI/UAP) thrombotic coronary occlusion. The management of STEMI patients includes providing urgent reperfusion: primary percutaneous coronary intervention(PPCI) if available, deliverable within 60 - 120 minutes, and fibrinolysis if PPCI is not available. Essential adjunctive therapies include antiplatelet therapy (aspirin, P2Y12 inhibitors), anticoagulation (heparin or low-molecular-weight heparin) and cardiac monitoring.

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

PubMed Central

Mahe, Julien; Meurette, Aurélie; Moreau, Anne; Vercel, Caroline; Jolliet, Pascale

2013-01-01

Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. PMID:23950639

Genetic testing in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cost-effectiveness analysis.

PubMed

Lala, A; Berger, J S; Sharma, G; Hochman, J S; Scott Braithwaite, R; Ladapo, J A

2013-01-01

The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. We aimed to evaluate the cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with two 'no testing' strategies (empiric clopidogrel or prasugrel). We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet-related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis-related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45 per day. A generic estimate for clopidogrel of $1.00 per day was used and genetic testing was assumed to cost $500. Base case analyses demonstrated little difference between treatment strategies. The genetic testing-guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype-guided strategy compared with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with wild-type individuals treated with clopidogrel. Above a 47% increased risk, a genotype-guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost-effective. Among ACS patients undergoing PCI, a genotype-guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective. © 2012 International Society on Thrombosis and Haemostasis.

Acute Central Retinal Vein Occlusion Secondary to Reactive Thrombocytosis after Splenectomy

PubMed Central

Oncel Acir, Nursen; Borazan, Mehmet

2014-01-01

The diagnosis and treatment of central retinal vein occlusion was reported in a young patient. Central retinal vein occlusion was probably related to secondary to reactive thrombocytosis after splenectomy. The patient was treated with steroids for papilledema and administered coumadin and aspirin. The symptoms resolved, and the findings returned to normal within three weeks. Current paper emphasizes that, besides other well-known thrombotic events, reactive thrombocytosis after splenectomy may cause central retinal vein occlusion, which may be the principal symptom of this risky complication. Thus, it can be concluded that followup for thrombocytosis and antithrombotic treatment, when necessary, are essential for these cases. PMID:25276452

Diabetes mellitus: a prothrombotic state Implications for outcomes after coronary revascularization

PubMed Central

Cola, Clarissa; Brugaletta, Salvatore; Yuste, Victoria Martín; Campos, Bieito; Angiolillo, Dominick J; Sabaté, Manel

2009-01-01

Coronary stent thrombosis is a serious problem in the drug-eluting stent era. Despite aggressive antiplatelet therapy during and after percutaneous coronary intervention (PCI), the incidence of sub-acute stent thrombosis remains approximately 0.5%–2%, which may represent a catastrophic clinical situation. Both procedural factors and discontinuation of antiplatelet therapy are normally associated with this event. We report on simultaneous stent thromboses of two drug-eluting stents implanted in two different vessels, which resulted in a life-threatening clinical condition. Possible contributing factors that led to synergistic thrombotic effects are discussed. PMID:19436654

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.

PubMed

Fox, Lucy C; Cohney, Solomon J; Kausman, Joshua Y; Shortt, Jake; Hughes, Peter D; Wood, Erica M; Isbel, Nicole M; de Malmanche, Theo; Durkan, Anne; Hissaria, Pravin; Blombery, Piers; Barbour, Thomas D

2018-06-01

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA. © 2018 Asian Pacific Society of Nephrology.

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.

PubMed

Fox, Lucy C; Cohney, Solomon J; Kausman, Joshua Y; Shortt, Jake; Hughes, Peter D; Wood, Erica M; Isbel, Nicole M; de Malmanche, Theo; Durkan, Anne; Hissaria, Pravin; Blombery, Piers; Barbour, Thomas D

2018-06-01

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA. © 2018 Royal Australasian College of Physicians.

Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

PubMed

Tan, Xing-Lin; Xue, Yue-Qiang; Ma, Tao; Wang, Xiaofang; Li, Jing Jing; Lan, Lubin; Malik, Kafait U; McDonald, Michael P; Dopico, Alejandro M; Liao, Francesca-Fang

2015-06-24

Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.

Acute adverse events associated with the administration of Crotalidae polyvalent immune Fab antivenom within the North American Snakebite Registry.

PubMed

Kleinschmidt, Kurt; Ruha, Anne-Michelle; Campleman, Sharan; Brent, Jeffrey; Wax, Paul

2018-04-24

Crotalidae Polyvalent Immune Fab (Fab Antivenom) is the primary Viperid antivenom used in the United States since 2000. Adverse event data associated with its use are limited. The purpose of this study is to describe the prevalence of acute adverse events associated with the use of Fab antivenom. The American College of Medical Toxicology's Toxicology Investigators Consortium maintains a prospective case registry of poisoned and envenomated patients managed by medical toxicologists at the bedside. This registry includes the North American Snakebite sub-registry. We performed a review of 438 cases entered into the Snakebite sub-registry. A total of 373 (85.2%) received at least one vial of Fab Antivenom. Forty percent were children. Adverse events occurred in 10 patients (2.7%) of whom six were adults. Rash was the most common adverse event. More severe adverse events (hypotension, bronchospasm, and/or angioedema) occurred in four (1.1%) patients. Prophylaxis was administered prior to Fab antivenom in 4.0%. Eight patients received various treatments for their adverse events. Neither the initial number of Fab antivenom vials, atopic history, nor prior envenomation correlated with the prevalence of adverse events. This prevalence of adverse events was lower than in previous studies and in a meta-analysis of 11 studies. The types of adverse events and treatments used are consistent with those in previous reports. There were no prior reports of prophylaxis use with which to compare. The prevalence of Fab antivenom adverse events in the North American Snakebite Registry was 2.7%.

Thrombotic microangiopathy in marginal kidneys after sirolimus use.

PubMed

Pellé, Gaëlle; Xu, Ychen; Khoury, Noujoud; Mougenot, Béatrice; Rondeau, Eric

2005-12-01

The increasing shortage of cadaver donor kidneys has prompted the use of expanded or marginal donor kidneys, ie, from older donors or those with a history of hypertension or diabetes. These marginal kidneys may be especially susceptible to calcineurin inhibitor (CNI)-mediated vasoconstriction and nephrotoxicity. Recipients of renal transplants from marginal donors therefore require non-nephrotoxic immunosuppression. Some investigators have proposed using sirolimus, a novel and potent immunosuppressant, instead of CNIs. Moreover, another complication of solid-organ transplantation is thrombotic microangiopathy (TMA), which affects 3% to 14% of patients on immunosuppression therapy treated with CNIs. Therefore, it was suggested that CNIs may be substituted by sirolimus in patients with posttransplantation CNI-induced TMA. We report 3 patients who received marginal cadaveric kidneys and were administered maintenance immunosuppression with sirolimus, prednisone, and mycophenolate mofetil. They each developed de novo TMA despite never having been previously administered a CNI. In these cases, TMA occurred in marginal kidneys with possible endothelial injury before transplantation. Sirolimus may have prevented recovery from these injuries and thus may have promoted TMA in these marginal kidneys. The risk for such a vascular complication should be kept in mind in patients who receive marginal kidneys and are administered sirolimus, even when sirolimus is used without CNIs.

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2011-01-01

Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

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

Myocardial Bridge and Acute Plaque Rupture

PubMed Central

Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A.; Schnittger, Ingela

2016-01-01

A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered. PMID:28251167

Myocardial Bridge and Acute Plaque Rupture.

PubMed

Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A; Schnittger, Ingela

2016-01-01

A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered.

Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura.

PubMed

Kopić, A; Benamara, K; Piskernik, C; Plaimauer, B; Horling, F; Höbarth, G; Ruthsatz, T; Dietrich, B; Muchitsch, E-M; Scheiflinger, F; Turecek, M; Höllriegl, W

2016-07-01

Essentials ADAMTS-13-deficiency is a cause of thrombotic thrombocytopenic purpura (TTP). Preclinical safety of recombinant human ADAMTS-13 (BAX930) was shown in animal models. Preclinical efficacy of BAX930 was shown in a mouse model of TTP. BAX930 showed advantageous efficacy over fresh frozen plasma, the current standard of care. Click to hear Dr Cataland and Prof. Lämmle present a seminar on Thrombotic Thrombocytopenic Purpura (TTP): new Insights in Pathogenesis and Treatment Modalities. Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by microthrombosis in small blood vessels of the body, resulting in a low platelet count. Baxalta has developed a new recombinant ADAMTS-13 (rADAMTS-13) product (BAX930) for on-demand and prophylactic treatment of patients with hereditary TTP (hTTP). Objectives To evaluate the pharmacokinetics, efficacy and safety of BAX930 in different species, by use of an extensive preclinical program. Methods The prophylactic and therapeutic efficacies of BAX930 were tested in a previously established TTP mouse model. Pharmacokinetics were evaluated after single intravenous bolus injection in mice and rats, and after repeated dosing in cynomolgus monkeys. Toxicity was assessed in rats and monkeys, safety pharmacology in monkeys, and local tolerance in rabbits. Results BAX930 was shown to be efficacious, as demonstrated by a stabilized platelet count in ADAMTS-13 knockout mice that were thrombocytopenic when treated. Prophylactic efficacy was dose-dependent and comparable with that achieved by treatment with fresh frozen plasma, the mainstay of hTTP treatment. Therapeutic efficacy was treatment interval-dependent. Safety pharmacology evaluation did not show any deleterious effects of BAX930 on cardiovascular and respiratory functions in monkeys. The compound's pharmacokinetics were similar and dose-proportional in mice, rats, and monkeys. BAX930 was well tolerated in rats, monkeys, and rabbits, even

Familial acquired thrombotic thrombocytopenic purpura in siblings - no immunogenetic link with associated human leucocyte antigens.

PubMed

Gödel, Philipp; Fischer, Julia; Scheid, Christoph; Gathof, Birgit S; Wolf, Jürgen; Rybniker, Jan

2017-03-01

Acquired immunoglobulin G (IgG)-mediated thrombotic thrombocytopenic purpura (TTP) has not yet been described in non-twin siblings. We report two cases of acquired TTP in Caucasian sisters with inactive ADAMTS13 metalloprotease due to ADAMTS13 autoantibodies suggesting a role of genetic determinants in this life-threatening disease. However, human leucocyte antigen (HLA) class II types presumably associated with acquired TTP were not identified in the patients, indicating that HLA class II typing may not be useful in acquired TTP risk assessment of family members. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transient ventricular dysfunction after an asphyxiation event: stress or hypoxia?

PubMed

Valletta, Mary E; Haque, Ikram; Al-Mousily, Faris; Udassi, Jai; Saidi, Arwa

2008-11-01

This report of a pediatric patient with acute upper airway obstruction causing asphyxiation emphasizes the need to maintain clinical suspicion for acquired myocardial dysfunction, despite the presumed role of noncardiogenic causes for pulmonary edema after an acute upper airway obstruction. Case report. A tertiary pediatric intensive care unit. A 10-year-old girl with no significant medical history who developed flash pulmonary edema and acute myocardial dysfunction after an acute upper airway obstruction. Serial echocardiograms, exercise stress test, and coronary angiography were performed. Serial pro-brain natriuretic peptide, troponins, and CK-MB levels were also followed. Troponin level normalized approximately 7 days after the acute event. CK-MB and pro-brain natriuretic peptide levels decreased but had not completely normalized by time of discharge. The patient was discharged home 10 days after the event on an anticipated 6-month course of metoprolol without any signs or symptoms of cardiac dysfunction. Myocardial dysfunction is rarely documented in children after an acute upper airway obstruction or an asphyxiation event. Pediatric intensivists and hospitalists should maintain a high degree of clinical suspicion and screen for possible myocardial dysfunction in the pediatric patient with an acute severe hypoxic event especially when accompanied by pulmonary edema. Prompt evaluation ensures appropriate support. Additionally, some role may exist for early adrenergic receptor blockade.

Identification of the "minimal triangle" and other common event-to-event transitions in conflict and containment incidents.

PubMed

Bowers, Len; James, Karen; Quirk, Alan; Wright, Steve; Williams, Hilary; Stewart, Duncan

2013-07-01

Although individual conflict and containment events among acute psychiatric inpatients have been studied in some detail, the relationship of these events to each other has not. In particular, little is known about the temporal order of events for individual patients. This study aimed to identify the most common pathways from event to event. A sample of 522 patients was recruited from 84 acute psychiatric wards in 31 hospital locations in London and the surrounding areas during 2009-2010. Data on the order of conflict and containment events were collected for the first two weeks of admission from patients' case notes. Event-to-event transitions were tabulated and depicted diagrammatically. Event types were tested for their most common temporal placing in sequences of events. Most conflict and containment occurs within and between events of the minimal triangle (verbal aggression, de-escalation, and PRN medication), and the majority of these event sequences conclude in no further events; a minority transition to other, more severe, events. Verbal abuse and medication refusal were more likely to start sequences of disturbed behaviour. Training in the prevention and management of violence needs to acknowledge that a gradual escalation of patient behaviour does not always occur. Verbal aggression is a critical initiator of conflict events, and requires more detailed and sustained research on optimal management and prevention strategies. Similar research is required into medication refusal by inpatients.

Modeling the acute health effects of astronauts from exposure to large solar particle events.

PubMed

Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

2009-04-01

Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial.

PubMed

Wiviott, Stephen D; Braunwald, Eugene; McCabe, Carolyn H; Horvath, Ivan; Keltai, Matyas; Herrman, Jean-Paul R; Van de Werf, Frans; Downey, William E; Scirica, Benjamin M; Murphy, Sabina A; Antman, Elliott M

2008-04-19

Intracoronary stenting can improve procedural success and reduce restenosis compared with balloon angioplasty in patients with acute coronary syndromes, but can also increase the rate of thrombotic complications including stent thrombosis. The TRITON-TIMI 38 trial has shown that prasugrel-a novel, potent thienopyridine-can reduce ischaemic events compared with standard clopidogrel therapy. We assessed the rate, outcomes, and prevention of ischaemic events in patients treated with prasugrel or clopidogrel with stents in the TRITON-TIMI 38 study. Patients with moderate-risk to high-risk acute coronary syndromes were included in our analysis if they had received at least one coronary stent at the time of the index procedure following randomisation in TRITON-TIMI 38, and were further subdivided by type of stent received. Patients were randomly assigned in a 1 to 1 fashion to receive a loading dose of study drug (prasugrel 60 mg or clopidogrel 300 mg) as soon as possible after randomisation, followed by daily maintenance therapy (prasugrel 10 mg or clopidogrel 75 mg). All patients were to receive aspirin therapy. Treatment was to be continued for a minimum of 6 months and a maximum of 15 months. Randomisation was not stratified by stents used or stent type. The primary endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Stent thrombosis was assessed using Academic Research Consortium definitions, and analysis was by intention to treat. TRITON-TIMI 38 is registered with ClinicalTrials.gov, number NCT00097591. 12,844 patients received at least one coronary stent; 5743 received only drug-eluting stents, and 6461 received only bare-metal stents. Prasugrel compared with clopidogrel reduced the primary endpoint (9.7 vs 11.9%, HR 0.81, p=0.0001) in the stented cohort, in patients with only drug-eluting stents (9.0 vs 11.1%, HR 0.82, p=0.019), and in patients with only bare-metal stents (10.0 vs 12.2%, HR 0.80, p=0

Management of venous thromboembolism in patients with acute leukemia at high bleeding risk: a multi-center study.

PubMed

Napolitano, Mariasanta; Valore, Luca; Malato, Alessandra; Saccullo, Giorgia; Vetro, Calogero; Mitra, Maria Enza; Fabbiano, Francesco; Mannina, Donato; Casuccio, Alessandra; Lucchesi, Alessandro; Del Principe, Maria Ilaria; Candoni, Anna; Di Raimondo, Francesco; Siragusa, Sergio

2016-01-01

In the last decades, evaluation of clinically relevant thrombotic complications in patients with acute leukemia (AL) has been poorly investigated. The authors performed a multi-center study to evaluate the management of symptomatic venous thromboembolism (VTE) in adult patients with AL. The intention was to find as clinically relevant the following: symptomatic Venous Thrombosis (VT) occurred in typical (lower limbs) and atypical (cerebral, upper limbs, abdominal, etc) sites with or without pulmonary embolism (PE). Over a population of 1461 patients with AL, 22 cases of symptomatic VTE were recorded in hospitalized patients with a mean age of 54.6 years. The absolute incidence of VTE was 1.5%. VTE occurred during chemotherapy in 17/22 (77.2%) cases, mainly (14/17, 82.3%) during the induction phase. Treatment of acute VTE was based on Low Molecular Weight Heparin (LMWH) at full dosage for the first month from diagnosis and reduced dosage (75%) for the following months.

Association of adiponectin with future cardiovascular events in patients after acute myocardial infarction.

PubMed

Huang, Shao-Sung; Huang, Po-Hsun; Chen, Ying-Hwa; Chiang, Kuang-Hsing; Chen, Jaw-Wen; Lin, Shing-Jong

2010-03-31

There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease risk, particularly in patients after acute myocardial infarction (AMI). The goal of this study was to determine whether plasma adiponectin levels could predict future cardiovascular events in patients after AMI, and to elucidate the role of adiponectin in cardioprotection. A total of 102 patients with AMI were enrolled. Plasma adiponectin levels were examined from blood samples collected 18 months after AMI. All subjects were followed-up for 43+/-12 months. The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, nonfatal MI, revascularization with percutaneous coronary intervention or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. A total of 30 MACE occurred, including one case of cardiovascular death, five cases of nonfatal MI, and nine cases of ischemic stroke. Patients with MACE had lower plasma adiponectin levels (p=0.013). In addition, adiponectin was positively associated with changes in left ventricular ejection fraction (p=0.005). All patients were divided into a high-adiponectin group (>or=6.46 microg/mL) and a low-adiponectin group (<6.46 microg/mL). The incidence of MACE was significantly reduced in the high-adiponectin group (p=0.021). In multivariate Cox regression analysis that included adiponectin, classical risk factors, and medications, adiponectin was an independent predictor of MACE in patients after AMI (HR, 0.821; 95% CI, 0.691 to 0.974; p=0.024). The results indicate a potential association between plasma adiponectin levels and future cardiovascular events in patients after AMI. Moreover, plasma adiponectin concentrations appear to play a pivotal role in atherothrombosis and cardioprotection.

Antenatal magnesium sulfate exposure and acute cardiorespiratory events in preterm infants.

PubMed

De Jesus, Lilia C; Sood, Beena G; Shankaran, Seetha; Kendrick, Douglas; Das, Abhik; Bell, Edward F; Stoll, Barbara J; Laptook, Abbot R; Walsh, Michele C; Carlo, Waldemar A; Sanchez, Pablo J; Van Meurs, Krisa P; Bara, Rebecca; Hale, Ellen C; Newman, Nancy S; Ball, M Bethany; Higgins, Rosemary D

2015-01-01

Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg. This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates. We evaluated 1544 infants <29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed group). Mothers in the anteMg group were more likely to have higher education, pregnancy-induced hypertension, and antenatal corticosteroids, while their infants were younger in gestation and weighed less (P < .05). The primary outcome (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in the anteMg group. Among preterm infants age <29 weeks' gestation, anteMg exposure was not associated with an increase in cardiorespiratory events in the early newborn period. The safety of anteMg as measured by the need for DR intubation or respiratory support on day 1 of life was comparable between groups. Copyright © 2015 Elsevier Inc. All rights reserved.

[Sequence of venous blood flow alterations in patients after recently endured acute thrombosis of lower-limb deep veins based on the findings of ultrasonographic duplex scanning].

PubMed

Tarkovskiĭ, A A; Zudin, A M; Aleksandrova, E S

2009-01-01

This study was undertaken to investigate the sequence of alterations in the venous blood flow to have occurred within the time frame of one year after sustained acute thrombosis of the lower-limb deep veins, which was carried out using the standard technique of ultrasonographic duplex scanning. A total of thirty-two 24-to-62-year-old patients presenting with newly onset acute phlebothrombosis were followed up. All the patients were sequentially examined at 2 days, 3 weeks, 3 months, 6 months and 12 months after the manifestation of the initial clinical signs of the disease. Amongst the parameters to determine were the patency of the deep veins and the condition of the valvular apparatus of the deep, superficial and communicant veins. According to the obtained findings, it was as early as at the first stage of the phlebohaemodynamic alterations after the endured thrombosis, i. e., during the acute period of the disease, that seven (21.9%) patients were found to have developed valvular insufficiency of the communicant veins of the cms, manifesting itself in the formation of a horizontal veno-venous reflux, and 6 months later, these events were observed to have occurred in all the patients examined (100%). Afterwards, the second stage of the phlebohaemodynamic alterations was, simultaneously with the process of recanalization of the thrombotic masses in the deep veins, specifically characterized by the formation of valvular insufficiency of the latter, manifesting itself in the form of the development of a deep vertical veno-venous reflux, which was revealed at month six after the onset of the disease in 56.3% of the examined subjects, to be then observed after 12 months in 93.8% of the patients involved. Recanalization of thrombotic masses was noted to commence 3 months after the onset of thrombosis in twelve (37.5%) patients, and after 12 months it was seen to ensue in all the patients (100%), eventually ending in complete restoration of the patency of the affected

Pancreatic Cancer in Pregnancy Presenting with Thromboembolic Events: Case Report and Review of the Literature.

PubMed

Wakefield, Brian W; Masterson, Crystal M C; Borges, Manuel T; Hurt, K Joseph

2018-06-08

Stroke and hepatic vein thrombosis are highly associated with neoplasia but are extremely rare events in young, pregnant women. Rare and recurrent thrombotic events in pregnancy increase the suspicion for occult malignancy. We describe the case of a healthy 31-year-old G2P1 who presented with visual changes and dysarthria during pregnancy. Imaging showed cerebral infarcts. Her thrombophilia evaluation was negative. During delivery, she was diagnosed with fulminant Budd-Chiari Syndrome. Hepatic ultrasound suggested malignancy or metastasis, and postpartum CT scan and biopsy confirmed the diagnosis of Stage IV pancreatic cancer. Although rare in pregnancy, a new diagnosis of malignancy should be considered in patients with recurrent unexplained hypercoagulable complications. We propose an evidence-based algorithm for evaluation of occult malignancy in pregnancy based upon this case and review of the literature. © 2018 S. Karger AG, Basel.

Clinical usefulness of a functional assay for the von Willebrand factor cleaving protease (ADAMTS 13) and its inhibitor in a patient with thrombotic thrombocytopenic purpura.

PubMed

Rick, M E; Austin, H; Leitman, S F; Krizek, D M; Aronson, D L

2004-02-01

Decreased von Willebrand factor cleaving protease activity (VWFCP, ADAMTS 13) leads to persistence of unusually large multimers of von Willebrand factor that bind to platelets, causing platelet aggregates, microangiopathic hemolysis, and thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP). The clinical value of measuring ADAMTS 13 and its inhibitor is not fully defined; the case reported here illustrates the usefulness of the assay to help confirm the clinical diagnosis in a patient with other potential causes for thrombotic microangiopathy; the assay also helped in making treatment decisions. A patient with systemic lupus erythematosis (SLE) presented with fever and abdominal pain, thrombocytopenia, and anemia. Thrombotic microangiopathy was diagnosed by the appearance of schistocytes, decreasing platelet count, and evidence of hemolysis. ADAMTS 13 was decreased and an inhibitor was demonstrated in the patient's initial blood sample within 24 hr of admission. Plasma exchange was initiated, and serial assays showed increased ADAMTS 13 activity and decreased inhibitor after each plasma exchange; there was a rebound in inhibitor and a decrease in ADAMTS 13 activity prior to the next exchange that lessened over time. Increasing levels of protease activity correlated with clinical and laboratory improvement. Measurement of ADAMTS 13 activity and its inhibitor aided in the diagnosis of this complicated case of a patient with other potential causes for microangiopathic hemolysis. Subsequent levels correlated with the clinical course, and disappearance of the inhibitor indicated that long-term plasma exchange or other immunosuppressive treatment was not needed.

Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

PubMed

Cataland, S R; Wu, H M

2015-06-01

Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

PubMed Central

Bleeker, Jonathan S.; Hogan, William J.

2011-01-01

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665

Engaged patients, engaged partnerships: singles and partners dealing with an acute cardiac event.

PubMed

Bertoni, Anna; Donato, Silvia; Graffigna, Guendalina; Barello, Serena; Parise, Miriam

2015-01-01

A few studies examine patients' (and partners') individual and relational functioning after an acute cardiac event and no research focuses on the individual and relational factors associated with the patient's engagement in his/her disease management. The present study aimed at exploring these variables in male and female patients as well as their partners. We pursued our objectives by taking advantage of a dyadic research design that involved both partners in the data collection, when present, and by including women patients in the sample. Findings showed that patients in a couple, compared to single patients, perceive that their illness had less serious consequences for their life and they were more engaged in their health care; that patients and partners showed comparable levels of distress; and that less depressed, more confident, and better informed patients were more likely to actively engage in their treatment. Findings are discussed in light of their implications for clinical practice.

Clinical outcomes associated with per-operative discontinuation of aspirin in patients with coronary artery disease: A systematic review and meta-analysis.

PubMed

Luni, Faraz Khan; Riaz, Haris; Khan, Abdur Rahman; Riaz, Talha; Husnain, Muhammad; Riaz, Irbaz Bin; Khan, Muhammad Shahzeb; Taleb, Mohammed; Kanjwal, Yusuf; Cooper, Christopher J; Khuder, Sadik A

2017-06-01

Postoperative state is characterized by increased thrombotic risk by virtue of platelet activation. Whether aspirin ameliorates this risk in patients with established coronary artery disease undergoing cardiac or noncardiac surgery is unknown. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiac events (MACE) and the risk of bleeding in patients with early (3-5 or more days before surgery) vs. late discontinuation(<3-5 days)/no discontinuation of aspirin. Multiple databases were searched from inception of these databases until March 2015 to identify studies that reported discontinuation of aspirin in patients undergoing surgery. The outcomes measured were all cause mortality, nonfatal myocardial infarction and other relevant thrombotic events (MACE) which also may include, fatal and nonfatal MI, stent thrombosis and restenosis, stroke, perioperative cardiovascular complications (heart failure, MI, VTE, acute stroke) and perioperative bleeding during the perioperative period to up to 30 days after surgery. A total of 1,018 titles were screened, after which six observational studies met the inclusion criteria. Our analysis suggests that there is no difference in MACE with planned discontinuation of aspirin (OR = 1.17, 95% CI = 0.76-1.81; P = 0.05; I 2  = 55%). Early discontinuation of aspirin showed a decreased risk of peri-operative bleeding (OR 0.82, 95% CI = 0.67-0.99; P = 0.04; I 2  = 42%). Our analysis suggests that planned short-term discontinuation in the appropriate clinical setting appears to be safe in the correct clinical setting with no increased risk of thrombotic events and with a decreased risk of bleeding. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation: an Update

PubMed Central

Stavrou, Evi; Lazarus, Hillard M.

2010-01-01

Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents. Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended. PMID:21776339

Short Sleep Duration, Obstructive Sleep Apnea, Shiftwork, and the Risk of Adverse Cardiovascular Events in Patients After an Acute Coronary Syndrome.

PubMed

Barger, Laura K; Rajaratnam, Shantha M W; Cannon, Christopher P; Lukas, Mary Ann; Im, KyungAh; Goodrich, Erica L; Czeisler, Charles A; O'Donoghue, Michelle L

2017-10-10

It is unknown whether short sleep duration, obstructive sleep apnea, and overnight shift work are associated with the risk of recurrent cardiovascular events in patients after an acute coronary syndrome. SOLID-TIMI 52 (The Stabilization of PLaques UsIng Darapladib-Thrombolysis in Myocardial Infarction 52 Trial) was a multinational, double-blind, placebo-controlled trial that enrolled 13 026 patients ≤30 days of acute coronary syndrome. At baseline, all patients were to complete the Berlin questionnaire to assess risk of obstructive sleep apnea and a sleep and shift work survey. Median follow-up was 2.5 years. The primary outcome was major coronary events (MCE; coronary heart disease death, myocardial infarction, or urgent revascularization). Cox models were adjusted for clinical predictors. Patients who reported <6 hours sleep per night had a 29% higher risk of MCE (adjusted hazard ratio, 1.29; 95% confidence interval, 1.12-1.49; P <0.001) compared with those with longer sleep. Patients who screened positive for obstructive sleep apnea had a 12% higher risk of MCE (1.12; 1.00-1.24; P =0.04) than those who did not screen positive. Overnight shift work (≥3 night shifts/week for ≥1 year) was associated with a 15% higher risk of MCE (1.15; 1.03-1.29; P =0.01). A step-wise increase in cardiovascular risk was observed for individuals with more than 1 sleep-related risk factor. Individuals with all 3 sleep-related risk factors had a 2-fold higher risk of MCE (2.01; 1.49-2.71; P <0.0001). Short sleep duration, obstructive sleep apnea, and overnight shift work are under-recognized as predictors of adverse outcomes after acute coronary syndrome. Increased efforts should be made to identify, treat, and educate patients about the importance of sleep for the potential prevention of cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01000727. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design.

PubMed

Li, Jing; Dreyer, Rachel P; Li, Xi; Du, Xue; Downing, Nicholas S; Li, Li; Zhang, Hai-Bo; Feng, Fang; Guan, Wen-Chi; Xu, Xiao; Li, Shu-Xia; Lin, Zhen-Qiu; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Jiang, Li-Xin

2016-01-05

Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients' experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs). The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients' medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities.

Design and baseline data from the Gratitude Research in Acute Coronary Events (GRACE) study

PubMed Central

Huffman, Jeff C.; Beale, Eleanor E.; Beach, Scott R.; Celano, Christopher M.; Belcher, Arianna M.; Moore, Shannon V.; Suarez, Laura; Gandhi, Parul U.; Motiwala, Shweta R.; Gaggin, Hanna; Januzzi, James L.

2015-01-01

Background Positive psychological constructs, especially optimism, have been linked with superior cardiovascular health. However, there has been minimal study of positive constructs in patients with acute coronary syndrome (ACS), despite the prevalence and importance of this condition. Furthermore, few studies have examined multiple positive psychological constructs and multiple cardiac-related outcomes within the same cohort to determine specifically which positive construct may affect a particular cardiac outcome. Materials and methods The Gratitude Research in Acute Coronary Events (GRACE) study examines the association between optimism/gratitude 2 weeks post-ACS and subsequent clinical outcomes. The primary outcome measure is physical activity at 6 months, measured via accelerometer, and key secondary outcome measures include levels of prognostic biomarkers and rates of nonelective cardiac rehospitalization at 6 months. These relationships will be analyzed using multivariate linear regression, controlling for sociodemographic, medical, and negative psychological factors; associations between baseline positive constructs and subsequent rehospitalizations will be assessed via Cox regression. Results Overall, 164 participants enrolled and completed the baseline 2-week assessment; the cohort had a mean age of 61.5 +/− 10.5 years and was 84% men; this was the first ACS for 58% of participants. Conclusion The GRACE study will determine whether optimism and gratitude are prospectively and independently associated with physical activity and other critical outcomes in the 6 months following an ACS. If these constructs are associated with superior outcomes, this may highlight the importance of these constructs as independent prognostic factors post-ACS. PMID:26166171

Design and baseline data from the Gratitude Research in Acute Coronary Events (GRACE) study.

PubMed

Huffman, Jeff C; Beale, Eleanor E; Beach, Scott R; Celano, Christopher M; Belcher, Arianna M; Moore, Shannon V; Suarez, Laura; Gandhi, Parul U; Motiwala, Shweta R; Gaggin, Hanna; Januzzi, James L

2015-09-01

Positive psychological constructs, especially optimism, have been linked with superior cardiovascular health. However, there has been minimal study of positive constructs in patients with acute coronary syndrome (ACS), despite the prevalence and importance of this condition. Furthermore, few studies have examined multiple positive psychological constructs and multiple cardiac-related outcomes within the same cohort to determine specifically which positive construct may affect a particular cardiac outcome. The Gratitude Research in Acute Coronary Events (GRACE) study examines the association between optimism/gratitude 2weeks post-ACS and subsequent clinical outcomes. The primary outcome measure is physical activity at 6months, measured via accelerometer, and key secondary outcome measures include levels of prognostic biomarkers and rates of nonelective cardiac rehospitalization at 6months. These relationships will be analyzed using multivariable linear regression, controlling for sociodemographic, medical, and negative psychological factors; associations between baseline positive constructs and subsequent rehospitalizations will be assessed via Cox regression. Overall, 164 participants enrolled and completed the baseline 2-week assessment; the cohort had a mean age of 61.5+/?10.5years and was 84% men; this was the first ACS for 58% of participants. The GRACE study will determine whether optimism and gratitude are prospectively and independently associated with physical activity and other critical outcomes in the 6months following an ACS. If these constructs are associated with superior outcomes, this may highlight the importance of these constructs as independent prognostic factors post-ACS. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of a male or female thrombotic family history on contraceptive counseling: a cohort study.

PubMed

van Vlijmen, E F W; Veeger, N J G M; Middeldorp, S; Hamulyák, K; Prins, M H; Kluin-Nelemans, H C; Meijer, K

2016-09-01

Essentials It is unknown if a male or female thrombotic family history influences risk in female relatives. We assessed thrombotic risk in female relatives of male and female patients with thrombosis. A hormonally related female thrombotic family history further increases risk in female relatives. This information could be important in counseling women on contraceptive options. Click to hear Prof. Rosendaal's perspective on venous thrombosis: etiology, pathogenesis, and prognosis Background Women from thrombophilic families have increased risk of venous thromboembolism (VTE), which increases further during oral contraceptive (COC) use and pregnancy-postpartum. Whether this additional risk differs between relatives of male and female patients, or is different when that female patient had a hormonally related VTE (during COC use/pregnancy), is unknown. Methods One thousand five female relatives of consecutive patients with VTE from a family-based cohort were retrospectively followed for incident VTE from ages 15 to 50, first VTE, or study inclusion. Absolute and relative VTE risks adjusted for factors of patients (sex, age) and relatives (thrombophilia, COC use, pregnancy) were estimated in relatives of female and male patients and in relatives of female patients with and without hormonally related VTE. Results Absolute risk in relatives of female (0.32 [95% confidence interval [CI] 0.23-0.43]) vs. male patients (0.39 [95% CI 0.28-0.53]) was comparable. However, the heterogeneity analysis of risk estimates suggested that in relatives of female vs. male patients, the contribution of pregnancy-postpartum (hazard ratio [HR] 11.6 [95% CI 6.3-21.3] vs. HR6.6 [95% CI 2.8-15.2]) and, to a lesser extent, COC use (HR3.6 [95% CI 1.8-7.1] vs. HR2.7 [95% CI 1.5-5.0]) to the VTE risk differs. Absolute risk was significantly higher in relatives of female patients with hormonally related VTE (0.43 [95% CI 0.3-0.6]) vs. relatives of female patients without hormonally related VTE (0

Ambient air pollutants and acute case-fatality of cerebro-cardiovascular events: Takashima Stroke and AMI Registry, Japan (1988-2004).

PubMed

Turin, Tanvir Chowdhury; Kita, Yoshikuni; Rumana, Nahid; Nakamura, Yasuyuki; Ueda, Kayo; Takashima, Naoyuki; Sugihara, Hideki; Morita, Yutaka; Ichikawa, Masaharu; Hirose, Kunihiko; Nitta, Hiroshi; Okayama, Akira; Miura, Katsuyuki; Ueshima, Hirotsugu

2012-01-01

Apart from the conventional risk factors, cerebro-cardiovascular disease (CVD) are also reported to be associated with air pollution, thus lowering the level of exposure might contribute in prevention activities to reduce the associated adverse outcomes. Though few studies conducted in Japan have reported on the CVD mortality but none have explored the effect of air pollutant exposure on the acute case-fatality of CVD. We investigated the effects of air pollution exposure on acute case-fatality of stroke and acute myocardial infarction (AMI) in a setting where pollutant levels are rather low. We leveraged the data from the Takashima Stroke and AMI Registry, which covers a population of approximately 55,000 in Takashima County located in central Japan. The study period of 6,210 days (16 years, leap years also taken into account) were divided into quartiles of daily average pollutant concentration; suspended particulate matter (SPM), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and photochemical oxidants (Ox). The stroke and AMI events were categorized to corresponding quartiles based on the pollution levels of the onset day. To study the effects of air pollutants, we estimated the fatality rate ratio across quartiles of the pollutants where the lowest quartile served as the reference. There were 307 (men: 153 and women: 154) fatal stroke cases within 28 days of onset among the 2,038 first ever stroke during 1988-2004. In the same period, there were 142 (men: 94 and women: 54) fatal AMI cases within 28 days of onset among the 429 first ever AMI events. The mean of the measured pollutant levels were as follows: SPM 26.9 µg/m(3), SO(2) 3.9 ppb, NO(2) 16.0 ppb, and Ox 28.4 ppb. Among the pollutants, higher levels of NO(2) showed increased fatality risk. In multi-pollutant model, the highest quartile of NO(2) was associated with 60% higher stroke case-fatality risk in comparison to lowest quartile of NO(2). In the fully adjusted model the fatality-rate ratio was 1

Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study.

PubMed

Jabbour, Elias; Kantarjian, Hagop; Ravandi, Farhad; Thomas, Deborah; Huang, Xuelin; Faderl, Stefan; Pemmaraju, Naveen; Daver, Naval; Garcia-Manero, Guillermo; Sasaki, Koji; Cortes, Jorge; Garris, Rebecca; Yin, C Cameron; Khoury, Joseph D; Jorgensen, Jeffrey; Estrov, Zeev; Bohannan, Zachary; Konopleva, Marina; Kadia, Tapan; Jain, Nitin; DiNardo, Courtney; Wierda, William; Jeanis, Vicky; O'Brien, Susan

2015-11-01

aspartate aminotransferase and alanine aminotransferase concentration (14 [38%] patients), thrombotic events (three [8%]), myocardial infarction (three [8%]), hypertension (six [16%]), skin rash (eight [22%]), and pancreatitis (six [16%] patients). Two patients died from from myocardial infarction potentially related to treatment; another patient also died from myocardial infarction related to sepsis. Two further patients died, one from bleeding and another from infection, both deemed unrelated to treatment. The first results of this ongoing trial indicate that the combination of chemotherapy with ponatinib is effective in achieving early sustained remissions in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia. New strategies, including dosing titration of ponatinib and optimised control of vascular risk factors, might further improve outcomes. ARIAD Pharmaceuticals Inc. Copyright © 2015 Elsevier Ltd. All rights reserved.

Change in Growth Differentiation Factor 15, but Not C-Reactive Protein, Independently Predicts Major Cardiac Events in Patients with Non-ST Elevation Acute Coronary Syndrome

PubMed Central

Hernandez-Baldomero, Idaira F.; Bosa-Ojeda, Francisco

2014-01-01

Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase. PMID:24839357

[Two cases of acute coronary syndrome after intake of Clavis Panax].

PubMed

Atar, Aslı İnci; Er, Okan; Güven, Abdullah; Eryonucu, Beyhan

2012-04-01

Atherosclerotic cardiovascular disease is an epidemic in today's world. It is one of the most common causes of hospitalization and death. Therefore, remedies to control or heal the disease are continuously sought. In addition to scientifically researched therapies, patients frequently utilize alternative medicine. However, effective and toxic doses, metabolisms, and drug interactions of the herbs and herbal nutrition supplements are largely unknown. Herein, we present two cases with acute coronary syndrome. The first case was admitted with a diagnosis of acute inferior myocardial infaction (MI) and a stent was implanted to the occluded right coronary artery (RCA). There was a 50% stenosis in his left anterior descending artery (LAD). He was admitted with a diagnosis of non-ST elevation MI (NSTEMI) 6 months later. In the coronary angiogram, there was stent restenosis in RCA, the lesion in LAD had become thrombotic and progressed to a stenosis of 90%. He was referred to surgical revascularization. The second case was admitted for acute inferior MI and a stent was implanted to the occluded circumflex artery. Two months later, he was hospitalized for NSTEMI. Progression of coronary plaques to stenosis and stent restenosis was detected and he was referred to surgical revascularization. Both patients used the product sold as Clavis Panax, which contains panax ginseng, tribulus terrestris, and oat, after their first coronary intervention. Intake of a mixture of plant extracts may have serious consequences in humans as drug interactions and side effects are unknown.

Nonbacterial Thrombotic Endocarditis in a Patient with Bowel Infarction due to Mesenteric Vein Thrombosis.

PubMed

Kim, Hyue Mee; Kim, Hack-Lyoung; Lee, Hak Seung; Jung, Ji-Hyun; Kim, Chee Hae; Oh, Sooyeon; Kim, Jung Ho; Zo, Joo-Hee

2014-05-01

Ante mortem cases of venous thrombosis in patients with nonbacterial thrombotic endocarditis (NBTE) have not yet been reported. We describe a rare case of NBTE in a patient with mesenteric vein thrombosis. A healthy 37-year-old man with abdominal pain and fever underwent emergency small bowel resection due to bowel ischemia resulting from mesenteric vein thrombosis. Transthoracic echocardiography revealed multiple mobile masses attached to the anterior leaflet of the mitral valves and their chordae tendineae. On suspicion of infective endocarditis, the cardiac masses were excised through open-heart surgery. However, pathologic reviews were compatible with NBTE. The patient was stable after the cardiac surgery and was treated with warfarin. Laboratory and imaging findings regarding his hypercoagulable condition were all negative.

Polycythemia vera: the natural history of 1213 patients followed for 20 years. Gruppo Italiano Studio Policitemia.

PubMed

1995-11-01

To reassess the natural history of polycythemia vera and to obtain reliable estimates of both incidence of thrombosis and survival for use in defining the sample size for therapeutic clinical trials. Retrospective cohort study of patients with polycythemia who had been followed for 20 years. 11 Italian hematology institutions. 1213 patients with polycythemia vera, which was diagnosed according to criteria established by the Polycythemia Vera Study Group and commonly used in clinical practice. All-cause mortality, venous and arterial thrombosis, and hematologic and nonhematologic neoplastic disease. Myocardial infarction and stroke were classified as major thrombotic events, and venous and peripheral arterial thrombosis were considered minor thrombotic events. The number of patients who died and the number of those who had major thrombotic events (combined end point) were used as a comprehensive measure of the benefit-risk ratio associated with the use of myelosuppressive agents. 634 fatal and nonfatal arterial and venous thromboses were recorded in 485 patients (41%); 36% of these episodes occurred during follow-up in 230 patients (19%), and 64% occurred either at presentation or before diagnosis. Thrombotic events occurred more frequently in the 2 years preceding diagnosis, suggesting a causal relation between the latent myeloproliferative disorder and the vascular event. The incidence of thrombosis during follow-up was 3.4%/y; older patients or those with a history of thrombosis had a higher risk for thrombosis. Overall mortality was 2.9/100 patients per year; thrombotic events and hematologic or nonhematologic cancers had similar effects on mortality. Patients receiving chemotherapy died three to four times more frequently than those not receiving chemotherapy. The increased risk for cancer in patients receiving myelosuppressive agents was seen approximately 6 years after diagnosis. In addition, the combined end point, computed as the sum of the hardest

Risks from Solar Particle Events for Long Duration Space Missions Outside Low Earth Orbit

NASA Technical Reports Server (NTRS)

Over, S.; Myers, J.; Ford, J.

2016-01-01

The Integrated Medical Model (IMM) simulates the medical occurrences and mission outcomes for various mission profiles using probabilistic risk assessment techniques. As part of the work with the Integrated Medical Model (IMM), this project focuses on radiation risks from acute events during extended human missions outside low Earth orbit (LEO). Of primary importance in acute risk assessment are solar particle events (SPEs), which are low probability, high consequence events that could adversely affect mission outcomes through acute radiation damage to astronauts. SPEs can be further classified into coronal mass ejections (CMEs) and solar flares/impulsive events (Fig. 1). CMEs are an eruption of solar material and have shock enhancements that contribute to make these types of events higher in total fluence than impulsive events.

Asparaginase-associated pancreatitis in children.

PubMed

Raja, Raheel Altaf; Schmiegelow, Kjeld; Frandsen, Thomas Leth

2012-10-01

l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis. © 2012 Blackwell Publishing Ltd.

Rituximab maintenance for relapsed refractory thrombotic thrombocytopenic purpura.

PubMed

Bhagirath, Vinai C; Kelton, John G; Moore, Jane; Arnold, Donald M

2012-12-01

Rituximab, an anti-CD20 chimeric monoclonal antibody, has been used successfully to treat patients with relapsed or refractory thrombotic thrombocytopenic purpura (TTP); however, the optimal dose and frequency and the role of rituximab maintenance remain uncertain. We describe a 45-year-old woman with chronic relapsing immune thrombocytopenia who responded to rituximab retreatment administered in four doses over the course of 12 months. Previously, she had received four doses of rituximab and sustained a remission for 19 months. During her latest TTP relapse, multiple treatments were administered including rituximab retreatment. After the first dose (375 mg/m2), she developed serum sickness requiring further doses to be deferred. Three subsequent doses were administered at 4-month intervals over the course of 12 months. ADAMTS13 activity was measured by von Willebrand factor (VWF) digestion. ADAMTS13 inhibition was measured by a modification of the VWF digestion assay and anti-ADAMTS13 antibodies were measured by enzyme-linked immunoassay (enzyme-linked immunosorbent assay, American Diagnostica). Clinical and laboratory remission were achieved after one dose of rituximab, with normalization of ADAMTS13 activity and disappearance of ADAMTS13 inhibitor. Three subsequent doses of rituximab were given without incident and the patient remained in remission after 3.5 years of follow-up (2.5 years since her last dose of rituximab). Maintenance dosing of rituximab should be considered in some patients with relapsing TTP. © 2012 American Association of Blood Banks.

A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial.

PubMed

Niikura, Ryota; Nagata, Naoyoshi; Yamada, Atsuo; Doyama, Hisashi; Shiratori, Yasutoshi; Nishida, Tsutomu; Kiyotoki, Shu; Yada, Tomoyuki; Fujita, Tomoki; Sumiyoshi, Tetsuya; Hasatani, Kenkei; Mikami, Tatsuya; Honda, Tetsuro; Mabe, Katsuhiro; Hara, Kazuo; Yamamoto, Katsumi; Takeda, Mariko; Takata, Munenori; Tanaka, Mototsugu; Shinozaki, Tomohiro; Fujishiro, Mitsuhiro; Koike, Kazuhiko

2018-04-03

The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. UMIN-CTR Identifier, UMIN000021129 . Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173 . Registered on 24 March 2017.

China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design

PubMed Central

Li, Jing; Dreyer, Rachel P; Li, Xi; Du, Xue; Downing, Nicholas S; Li, Li; Zhang, Hai-Bo; Feng, Fang; Guan, Wen-Chi; Xu, Xiao; Li, Shu-Xia; Lin, Zhen-Qiu; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Jiang, Li-Xin

2016-01-01

Background: Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients’ experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs). Methods: The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients’ medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. Conclusion: The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities. PMID:26712436

Economic burden of cardiovascular events and fractures among patients with end-stage renal disease.

PubMed

Doan, Quan V; Gleeson, Michelle; Kim, John; Borker, Rohit; Griffiths, Robert; Dubois, Robert W

2007-07-01

To quantify direct medical costs of fractures and cardiovascular diseases among end-stage renal disease (ESRD) patients. Medicare claims data from year 2001 of the United States Renal Data System were used to quantify direct medical costs of acute episodic events (acute myocardial infarction (MI), stroke, heart valve repair, heart valve replacement, fractures) and chronic conditions (arrhythmia, peripheral vascular disease (PVD), heart valve disease (HVD), congestive heart failure (CHF), coronary heart disease, and non-acute stroke). Costs of hospitalized episodes of arrhythmia, PVD, CHF, and angina were also quantified. For acute events, costs were quantified using an episode-of-care approach. For chronic conditions, annualized costs were reported. Only costs specific to the events or conditions of interest were included and reported, in 2006 US dollars. Drug and dialysis-related costs were excluded. Diagnosis and procedure codes were used to identify these events and conditions. Among acute events analyzed as clinical episodes, PVD ($358 million) was associated with the greatest economic burden, followed by CHF, arrhythmia, angina, acute MI, heart valve replacement, hip fracture, acute stroke, heart valve repair, vertebral fracture, and pelvic fracture ($8.6 million). The cost per episode ranged from approximately $12,000 to 104,000. Among chronic conditions, CHF ($681 million) contributed the greatest economic burden; HVD ($100 million) contributed the least. The costs per patient-year ranged from $23,000 to 45,000 among chronic conditions. The costing methodology utilized could contribute to an underestimate of the economic impact of each condition; therefore these results are considered conservative. The economic burden of these selected conditions was substantial to health services payers who finance ESRD patient care. Episodic costs were high for most acute events.

[Antiphospholipid syndrome with autoimmune hemolytic anemia which mimics thrombotic thrombocytopenic purpura].

PubMed

Karasawa, Naoki; Taniguchi, Yasuhiro; Hidaka, Tomonori; Katayose, Keiko; Kameda, Takuro; Side, Kotaro; Shimoda, Haruko; Nagata, Kenji; Kubuki, Yoko; Matsunaga, Takuya; Shimoda, Kazuya

2010-04-01

A 67-year-old woman was admitted to the hospital for lethargy, fever, hemolytic anemia, thrombocytopenia, and consciousness disturbance. Direct Coombs test was positive, and anti-cardiolipin beta2-glycoprotein I antibody was detected. She was diagnosed with antiphospholipid syndrome complicated with autoimmune hemolytic anemia (AIHA). She demonstrated variable consciousness disturbance, inability to distinguish right from left, dysgraphia and dyscalculia. Multiple cerebral infarctions, especially dominant cerebral hemisphere infarctions, were observed on magnetic resonance imaging. A ventilation-perfusion scan demonstrated the presence of a ventilation-perfusion mismatch in both lung fields, and multiple veinous embolisms in the right femoral, bilateral the great saphenous and popliteal veins. Therefore, pulmonary embolism and thrombophlebitis were diagnosed. Based on these findings, it was necessary to distinguish this diagnosis from thrombotic thrombocytopenic purpura (TTP). As ADAMTS-13 activity was within the normal range, TTP was denied. Thereafter, the patient was treated with 1 mg/kg of prednisolone for AIHA, 3 mg of warfarin, and 3500 units of low-molecular-weight heparin for thrombosis, and her condition improved.

Catheter-Directed Thrombolysis via Small Saphenous Veins for Treating Acute Deep Venous Thrombosis.

PubMed

Yang, Bin; Xu, Xiao-Dong; Gao, Peng; Yu, Ji-Xiang; Li, Yu; Zhu, Ai-Dong; Meng, Ran-Ran

2016-08-23

BACKGROUND There is little data comparing catheter-directed thrombolysis (CDT) via small saphenous veins vs. systematic thrombolysis on complications and efficacy in acute deep venous thrombosis patients. The aim of our study was to compare the efficacy and safety of CDT via the small saphenous veins with systematic thrombolysis for patients with acute deep venous thrombosis (DVT). MATERIAL AND METHODS Sixty-six patients with acute DVT admitted from June 2012 to December 2013 were divided into 2 groups: 27 patients received systemic thrombolysis (ST group) and 39 patients received CDT via the small saphenous veins (CDT group). The thrombolysis efficiency, limb circumference differences, and complications such as post-thrombotic syndrome (PTS) in the 2 groups were recorded. RESULTS The angiograms demonstrated that all or part of the fresh thrombus was dissolved. There was a significant difference regarding thrombolysis efficiency between the CDT group and ST group (71.26% vs. 48.26%, P=0.001). In both groups the postoperative limb circumference changes were higher compared to the preoperative values. The differences between postoperative limb circumferences on postoperative days 7 and 14 were significantly higher in the CDT group than in the ST group (all P<0.05). The incidence of postoperative PTS in the CDT group (17.9%) was significantly lower in comparison to the ST group (51.85%) during the follow-up (P=0.007). CONCLUSIONS Catheter-directed thrombolysis via the small saphenous veins is an effective, safe, and feasible approach for treating acute deep venous thrombosis.

Association of acquired thrombotic thrombocytopaenic purpura in a patient with pernicious anaemia

PubMed Central

Podder, Sidhertha; Cervates, Jose; Dey, Bimalangshu R

2015-01-01

Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation. PMID:26464409

Association of acquired thrombotic thrombocytopaenic purpura in a patient with pernicious anaemia.

PubMed

Podder, Sidhertha; Cervates, Jose; Dey, Bimalangshu R

2015-10-13

Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation. 2015 BMJ Publishing Group Ltd.

Cardiovascular Events Following Smoke-Free Legislations: An Updated Systematic Review and Meta-Analysis

PubMed Central

Jones, Miranda R.; Barnoya, Joaquin; Stranges, Saverio; Losonczy, Lia; Navas-Acien, Ana

2014-01-01

Background Legislations banning smoking in indoor public places and workplaces are being implemented worldwide to protect the population from secondhand smoke exposure. Several studies have reported reductions in hospitalizations for acute coronary events following the enactment of smoke-free laws. Objective We set out to conduct a systematic review and meta-analysis of epidemiologic studies examining how legislations that ban smoking in indoor public places impact the risk of acute coronary events. Methods We searched MEDLINE, EMBASE, and relevant bibliographies including previous systematic reviews for studies that evaluated changes in acute coronary events, following implementation of smoke-free legislations. Studies were identified through December 2013. We pooled relative risk (RR) estimates for acute coronary events comparing post- vs. pre-legislation using inverse-variance weighted random-effects models. Results Thirty-one studies providing estimates for 47 locations were included. The legislations were implemented between 1991 and 2010. Following the enactment of smoke-free legislations, there was a 12 % reduction in hospitalizations for acute coronary events (pooled RR: 0.88, 95 % CI: 0.85–0.90). Reductions were 14 % in locations that implemented comprehensive legislations compared to an 8 % reduction in locations that only had partial restrictions. In locations with reductions in smoking prevalence post-legislation above the mean (2.1 % reduction) there was a 14 % reduction in events compared to 10 % in locations below the mean. The RRs for acute coronary events associated with enacting smoke-free legislation were 0.87 vs. 0.89 in locations with smoking prevalence pre-legislation above and below the mean (23.1 %), and 0.87 vs. 0.89 in studies from the Americas vs. other regions. Conclusion The implementation of smoke-free legislations was related to reductions in acute coronary event hospitalizations in most populations evaluated. Benefits are greater

The coagulopathy in acute promyelocytic leukaemia--what have we learned in the past twenty years.

PubMed

Kwaan, Hau C; Cull, Elizabeth H

2014-03-01

Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the coagulopathy are far from being realised. Thrombotic and bleeding complications remain the major causes of early deaths. In this chapter, the known causes of abnormalities in haemostatic function, namely the coagulopathy and changes in the fibrinolytic system, will be reviewed. Major risk factors for these complications are identified. Current available measures for correction of the coagulopathy and their effectiveness are critically examined. Unless the coagulopathy can be effectively controlled, bleeding complications will remain an obstacle to achieving a cure for this disease. The issues that need to be addressed in next phase of investigations are also discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

PubMed

Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

2016-02-03

Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases

The expanded Global Registry of Acute Coronary Events: baseline characteristics, management practices, and hospital outcomes of patients with acute coronary syndromes.

PubMed

Goodman, Shaun G; Huang, Wei; Yan, Andrew T; Budaj, Andrzej; Kennelly, Brian M; Gore, Joel M; Fox, Keith A A; Goldberg, Robert J; Anderson, Frederick A

2009-08-01

The Global Registry of Acute Coronary Events (GRACE)-a prospective, multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was designed to improve the quality of care for patients with an ACS. Expanded GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practices to an international reference cohort. We describe the objectives; study design; study and data management; and the characteristics, management, and hospital outcomes of patients > or =18 years old enrolled with a presumptive diagnosis of ACS. From 2001 to 2007, 31,982 patients were enrolled at 184 hospitals in 25 countries; 30% were diagnosed with ST-segment elevation myocardial infarction, 31% with non-ST-segment myocardial infarction, 26% with unstable angina, and 12% with another cardiac/noncardiac final diagnosis. The median age was 65 (interquartile range 55-75) years; 24% were >75 years old, and 33% were women. In general, increases were observed over time across the spectrum of ACS (1) in the use in the first 24 hours and at discharge of aspirin, clopidogrel, beta-blockers, and angiotensin-converting enzyme inhibitors/receptor blockers; (2) in the use at discharge of statins; (3) in the early use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin; and (4) in the use of cardiac catheterization and percutaneous coronary intervention. An increase in the use of primary percutaneous coronary intervention and a similar decrease in the use of fibrinolysis in ST-segment elevation myocardial infarction were also seen. Over the course of 7 years, general increases in the use of evidence-based therapies for ACS patients were observed in the expanded GRACE.

A 14-Year Experience in the Management of Patients with Acquired Immune Thrombotic Thrombocytopenic Purpura in Northern Israel.

PubMed

Rinott, Nadav; Mashiach, Tatiana; Horowitz, Netanel A; Schliamser, Liliana; Sarig, Galit; Keren-Politansky, Anat; Dann, Eldad J

2015-01-01

Acquired idiopathic thrombotic thrombocytopenic purpura (I-TTP) is a life-threatening microangiopathic disorder usually treated with therapeutic plasma exchange (TPE). The current study assessed the role of rituximab in the treatment of complicated I-TTP. The sequence of TTP events was compared in a group of I-TTP patients treated with TPE and a cohort of refractory or relapsed patients who also received rituximab. This retrospective evaluation included 45 I-TTP patients, treated between January 2000 and October 2013, who underwent at least 3 TPE procedures and were followed up until December 2013 or death. Thirty-one patients with an uncomplicated course received TPE only. Fourteen patients had a complicated course due to either a primary refractory/exacerbated disease (n = 5) or relapse (n = 9) and received rituximab together with TPE. The median number of TPE procedures performed in the first TTP episode in the uncomplicated cohort and groups with primary refractory or relapsed TTP was 11, 27 and 45, respectively. The relapse rates per follow-up year in the uncomplicated I-TTP, primary refractory and relapsed I-TTP groups were 0.18, 0.2 and 0.6 episodes, respectively. After rituximab therapy this rate dropped to 0.2 per year in the relapsed subgroup. In conclusion, about a quarter of patients with I-TTP had a complicated course and experienced a major benefit from rituximab in terms of effectiveness and safety. © 2015 S. Karger AG, Basel.

Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

NASA Astrophysics Data System (ADS)

Kennedy, Ann; Cengel, Keith

2012-07-01

A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute

A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients.

PubMed

Straub, Niels; Beivers, Andreas; Lenk, Ekaterina; Aradi, Daniel; Sibbing, Dirk

2014-02-01

Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incremental-cost-effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.

Acute coronary disease Athero-Inflammation: Therapeutic approach

PubMed Central

Altman, Raul

2003-01-01

Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events. Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease. PMID:12904261

It is just a game: lack of association between watching football matches and the risk of acute cardiovascular events.

PubMed

Barone-Adesi, Francesco; Vizzini, Loredana; Merletti, Franco; Richiardi, Lorenzo

2010-08-01

The role of trigger factors in acute cardiovascular events has been much studied in the past few years. A recent study analysed changes in the rates of cardiac emergencies in Bavaria (Germany) during the last Football World Cup. The authors reported a 2.7-fold increase in the incidence of cardiac emergencies in the 12 h before and after football matches involving the German team, which sparked the debate on the necessity of the introduction of ad hoc cardiovascular preventive measures. We studied 25,159 hospital admissions for acute myocardial infarction (AMI) among the Italian population during three international football competitions: the World Cup 2002, the European Championship 2004 and the World Cup 2006. Poisson regression was used to estimate the relative risk of hospital admission for AMI on the days when football matches involving the Italian team were disputed, compared with the other days of the three competitions. Furthermore, we reviewed the available published studies regarding the association between football matches and the risk of cardiovascular events. We did not find an increase in the rates of admission for AMI on the days of football matches involving Italy in either the single competitions or the three competitions combined (relative risk 1.01; 95% confidence interval 0.98-1.05). We identified 10 studies published on this topic. With the exception of the recently published German study and two small Swiss studies, all relative risk estimates were between 0.7 and 1.3. The cardiovascular effects of watching football matches are likely to be, if anything, very small.

Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia

PubMed Central

De Stefano, Valerio; Za, Tommaso; Rossi, Elena; Fiorini, Alessia; Ciminello, Angela; Luzzi, Claudia; Chiusolo, Patrizia; Sica, Simona; Leone, Giuseppe

2009-01-01

It is uncertain whether the JAK2 V617F mutation increases the thrombotic risk in patients with essential thrombocythemia, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects. We studied 132 patients with essential thrombocythemia, 38 of them (29%) with a history of thrombosis. The JAK2 mutation was present in 83 (63%), and inherited thrombophilia in 7. The mutated patients <60 years had a relative risk (RR) for thrombosis at any time of 3.83 (95%CI 1.27–11.49) in comparison with wild-type patients; in those with both the mutation and thrombophilia the RR was 2.23 (95%CI 1.57–3.18) and 7.66 (95%CI 2.66–22.03) in comparison with mutated or wild-type patients without thrombophilia, respectively. During the follow-up, only the homozygotes for JAK2 V617F were more prone to thrombosis (RR 17.25, 95%CI 2.33–127.4). Among the patients >60 years, no increase in RR was associated with the JAK2 mutation. In conclusion, in the younger patients with ET the thrombotic risk is higher in the JAK2 V617F-mutated and is further increased by the presence of inherited thrombophilia. PMID:19336736

[The Health Department of Sicily "Regional recommendations for hospital discharge and communication with patients after admission due to a cardiologic event" decree].

PubMed

Abrignani, Maurizio Giuseppe; De Luca, Giovanni; Gabriele, Michele; Tourkmani, Nidal

2014-06-01

Mortality and rehospitalizations still remain high after discharge for an acute cardiologic event. In this context, hospital discharge represents a potential pitfall for heart disease patients. In the setting of care transitions, the discharge letter is the main instrument of communication between hospital and primary care. Communication, besides, is an integral part of high-quality, patient-centered interventions aimed at improving the discharge process. Inadequate information at discharge significantly affects the quality of treatment compliance and the adoption of lifestyle modifications for an effective secondary prevention. The Health Department of Sicily, in 2013, established a task force with the aim to elaborate "Regional recommendations for hospital discharge and communication with patients after admission due to a cardiologic event", inviting to participate GICR-IACPR and many other scientific societies of cardiology and primary care, as discharge letter and communication are fundamental junctions of care transitions in cardiology. These recommendations have been published as a specific decree and contain: a structured model of discharge letter, which includes all of the parameters characterizing patients at high clinical risk, high thrombotic risk and low risk according to the Consensus document ANMCO/GICR-IACPR/GISE; is thus possible to identify these patients, choosing consequently the most appropriate follow-up pathways. A particular attention has been given to the "Medication Reconciliation" and to the identification of therapeutic targets; an educational Kit, with different forms on cardiac diseases, risk factors, drugs and lifestyle; a check-list about information given to the patient and caregivers. The "Recommendations" represent, in conclusion, the practical realization of the fruitful cooperation between scientific societies and political-administrative institutions that has been realized in Sicily in the last years.

Medical costs in patients with heart failure after acute heart failure events: one-year follow-up study.

PubMed

Kim, Eugene; Kwon, Hye-Young; Baek, Sang Hong; Lee, Haeyoung; Yoo, Byung-Su; Kang, Seok-Min; Ahn, Youngkeun; Yang, Bong-Min

2018-03-01

This study investigated annual medical costs using real-world data focusing on acute heart failure. The data were retrospectively collected from six tertiary hospitals in South Korea. Overall, 330 patients who were hospitalized for acute heart failure between January 2011 and July 2012 were selected. Data were collected on their follow-up medical visits for 1 year, including medical costs incurred toward treatment. Those who died within the observational period or who had no records of follow-up visits were excluded. Annual per patient medical costs were estimated according to the type of medical services, and factors contributing to the costs using Gamma Generalized Linear Models (GLM) with log link were analyzed. On average, total annual medical costs for each patient were USD 6,199 (±9,675), with hospitalization accounting for 95% of the total expenses. Hospitalization cost USD 5,904 (±9,666) per patient. Those who are re-admitted have 88.5% higher medical expenditure than those who have not been re-admitted in 1 year, and patients using intensive care units have 19.6% higher expenditure than those who do not. When the number of hospital days increased by 1 day, medical expenses increased by 6.7%. Outpatient drug costs were not included. There is a possibility that medical expenses for AHF may have been under-estimated. It was found that hospitalization resulted in substantial costs for treatment of heart failure in South Korea, especially in patients with an acute heart failure event. Prevention strategies and appropriate management programs that would reduce both frequency of hospitalization and length of stay for patients with the underlying risk of heart failure are needed.

Coming safely to a stop: a review of platelet activity after cessation of antiplatelet drugs.

PubMed

Ford, Isobel

2015-08-01

The platelet P2Y12 antagonists are widely used, usually in combination with aspirin, to prevent atherothrombotic events in patients with acute coronary syndromes during percutaneous coronary intervention and after placement of arterial stents. Inhibition by clopidogrel or prasugrel lasts for the lifetime of the affected platelets and platelet haemostatic function gradually recovers after stopping the drug, as new unaffected platelets are formed. The optimal durations for dual antiplatelet therapy are prescribed by clinical guidelines. Continuation beyond the recommended duration is associated with an increased mortality, mainly associated with major bleeding. Fear of a 'rebound' of prothrombotic platelet activity on stopping the drug has provoked much discussion and many studies. However, review of the available literature reveals no evidence for production of hyper-reactive platelets after cessation of clopidogrel in patients who are stable. Any increase in acute coronary and other vascular events after stopping seems most likely therefore to be due to premature discontinuation or disruption of treatment while thrombotic risk is still high. No difference in rebound was found with the newer P2Y12 inhibitors, although ticagrelor and prasugrel are more potent platelet inhibitors than clopidogrel. Recent randomized controlled trials confirm it is safe to stop the thienopyridine and continue with aspirin alone in most patients after the duration of treatment recommended by the guidelines. Decisions on when to stop therapy in individuals, however, remain challenging and there is a growing rationale for platelet testing to assist clinical judgement in certain situations such as patients stopping dual antiplatelet therapy before surgery or in individuals at highest bleeding or thrombotic risk.

Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial

PubMed Central

Murphy, Sabina A.; Antman, Elliott M.; Wiviott, Stephen D.; Weerakkody, Govinda; Morocutti, Giorgio; Huber, Kurt; Lopez-Sendon, Jose; McCabe, Carolyn H.; Braunwald, Eugene

2008-01-01

Aims In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary endpoint (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel. Methods and results Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event. Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46–0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25–0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71–0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug). Conclusion While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with ACS. PMID:18682445

Acquired Thrombotic Thrombocytopenic Purpura in a Patient with Pernicious Anemia.

PubMed

Pandey, Ramesh Kumar; Dahal, Sumit; Fadlalla, Kamal Fadlalla El Jack; Bhagat, Shambhu; Bhattarai, Bikash

2017-01-01

Introduction . Acquired thrombotic thrombocytopenic purpura (TTP) has been associated with different autoimmune disorders. However, its association with pernicious anemia is rarely reported. Case Report . A 46-year-old male presented with blood in sputum and urine for one day. The vitals were stable. The physical examination was significant for icterus. Lab tests' results revealed leukocytosis, macrocytic anemia, severe thrombocytopenia, renal dysfunction, and unconjugated hyperbilirubinemia. He had an elevated LDH, low haptoglobin levels with many schistocytes, nucleated RBCs, and reticulocytes on peripheral smear. Low ADAMTS13 activity (<10%) with elevated ADAMTS13 antibody clinched the diagnosis of severe acquired TTP, and plasmapheresis was started. There was an initial improvement in his hematological markers, which were however not sustained on discontinuation of plasmapheresis. For his refractory TTP, he was resumed on daily plasmapheresis and Rituximab was started. Furthermore, the initial serum Vitamin B12 and reticulocyte index were low in the presence of anti-intrinsic factor antibody. So with the concomitant diagnosis of pernicious anemia, Vitamin B12 was supplemented. The rest of the immunological workups were negative. Subsequently, his symptoms resolved and his hematological parameters improved. Discussion . While pernicious anemia can masquerade as TTP, an actual association between the two can also occur and needs further evaluation and characterization.

Acquired Thrombotic Thrombocytopenic Purpura in a Patient with Pernicious Anemia

PubMed Central

Bhagat, Shambhu

2017-01-01

Introduction. Acquired thrombotic thrombocytopenic purpura (TTP) has been associated with different autoimmune disorders. However, its association with pernicious anemia is rarely reported. Case Report. A 46-year-old male presented with blood in sputum and urine for one day. The vitals were stable. The physical examination was significant for icterus. Lab tests' results revealed leukocytosis, macrocytic anemia, severe thrombocytopenia, renal dysfunction, and unconjugated hyperbilirubinemia. He had an elevated LDH, low haptoglobin levels with many schistocytes, nucleated RBCs, and reticulocytes on peripheral smear. Low ADAMTS13 activity (<10%) with elevated ADAMTS13 antibody clinched the diagnosis of severe acquired TTP, and plasmapheresis was started. There was an initial improvement in his hematological markers, which were however not sustained on discontinuation of plasmapheresis. For his refractory TTP, he was resumed on daily plasmapheresis and Rituximab was started. Furthermore, the initial serum Vitamin B12 and reticulocyte index were low in the presence of anti-intrinsic factor antibody. So with the concomitant diagnosis of pernicious anemia, Vitamin B12 was supplemented. The rest of the immunological workups were negative. Subsequently, his symptoms resolved and his hematological parameters improved. Discussion. While pernicious anemia can masquerade as TTP, an actual association between the two can also occur and needs further evaluation and characterization. PMID:28473932

Acute stress affects prospective memory functions via associative memory processes.

PubMed

Szőllősi, Ágnes; Pajkossy, Péter; Demeter, Gyula; Kéri, Szabolcs; Racsmány, Mihály

2018-01-01

Recent findings suggest that acute stress can improve the execution of delayed intentions (prospective memory, PM). However, it is unclear whether this improvement can be explained by altered executive control processes or by altered associative memory functioning. To investigate this issue, we used physical-psychosocial stressors to induce acute stress in laboratory settings. Then participants completed event- and time-based PM tasks requiring the different contribution of control processes and a control task (letter fluency) frequently used to measure executive functions. According to our results, acute stress had no impact on ongoing task performance, time-based PM, and verbal fluency, whereas it enhanced event-based PM as measured by response speed for the prospective cues. Our findings indicate that, here, acute stress did not affect executive control processes. We suggest that stress affected event-based PM via associative memory processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of acute coronary syndromes in Maghreb countries: The ACCESS (ACute Coronary Events - a multinational Survey of current management Strategies) registry.

PubMed

Moustaghfir, Abdelhamid; Haddak, Mohand; Mechmeche, Rachid

2012-11-01

The burden of cardiovascular diseases is anticipated to rise in developing countries. We sought to describe the epidemiology, management, and clinical outcomes of patients hospitalized with acute coronary syndromes (ACS) in three countries in western North Africa. Adult patients hospitalized with a diagnosis of ACS were enrolled in the prospective ACute Coronary Events - a multinational Survey of current management Strategies (ACCESS) registry over a 13-month period (January 2007 to January 2008). We report on patients enrolled at sites in Algeria, Morocco and Tunisia. A standardized form was used to collect data on patient characteristics, treatments and outcomes. A total of 1687 patients with confirmed ACS were enrolled (median age 59 [interquartile range 52, 68] years; 76% men), 59% with ST-elevation myocardial infarction (STEMI) and 41% with non-ST-elevation ACS (NSTE-ACS). During hospitalization, most patients received aspirin (96%) and a statin (90%), 83% received a beta-blocker and 74% an angiotensin-converting enzyme inhibitor. Among eligible STEMI patients, 42% (419/989) did not receive fibrinolysis or undergo percutaneous coronary intervention. All-cause death at 12 months was 8.1% and did not differ significantly between patients with STEMI or NSTE-ACS (8.3% vs 7.7%, respectively; Log-rank test P=0.82). Clinical factors associated with higher risk of death at 12 months included cardiac arrest, cardiogenic shock, bleeding episodes and diabetes, while percutaneous coronary intervention and male sex were associated with lower risk. In this observational study of ACS patients from three Maghreb countries, the use of evidence-based pharmacological therapies for ACS was quite high; however, 42% of the patients with STEMI were not given any form of reperfusion therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Event-Related Potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats

PubMed Central

Ehlers, Cindy L.; Desikan, Anita; Wills, Derek N.

2014-01-01

Background The present study explored the hypothesis that adolescent ethanol exposure may cause long lasting changes in ethanol sensitivity by exploring the age-related effects of acute alcohol on intoxication and on event-related potential (ERP) responses to acoustic stimuli in ethanol naïve adolescent and adult male Wistar rats and in adult rats that were exposed to chronic ethanol/control conditions during adolescence. Methods Ethanol naïve adolescent (postnatal day 32 (PD32)) and adult male rats (PD99) were included in the first study. In a second study, rats were exposed to 5 weeks of ethanol vapor (Blood ethanol concentrations @ 175 mg%) or air from PD24 to PD59 and allowed to mature until PD90. In both studies rats were implanted with cortical recording electrodes, and the effects of acute ethanol (0.0, 1.5, and 3.0 g/kg) on behavioral and ERP responses were assessed. Results Adolescents were found to have higher amplitude and longer latency P3a and P3b components at baseline as compared to adult rats, and ethanol was found to produce a robust dose-dependent increase in the latency of the P3a and P3b components of the auditory ERP recorded in cortical sites in both adolescents and adults. However, ethanol produced significantly larger delays in P3a and P3b latencies in adults as compared to adolescents. Acute ethanol administration was also found to produce a robust dose dependent increase in the latency of the P3a and P3b components in adult animals exposed to ethanol vapor as adolescents and air exposed controls; however, larger acute ethanol-induced increases in P3a and P3b latencies were seen in controls as compared to adolescent vapor exposed rats. Conclusions Adolescent rats have a less intense P3 latency response to acute ethanol administration when compared to adult rats. Exposure to chronic ethanol during adolescence can cause “retention” of the adolescent phenotype of reduced P3 latency sensitivity to ethanol. PMID:24483322

Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin on the First Day of Admission for Adverse Events in Patients With Acute Decompensated Heart Failure.

PubMed

Nakada, Yasuki; Kawakami, Rika; Matsui, Masaru; Ueda, Tomoya; Nakano, Tomoya; Takitsume, Akihiro; Nakagawa, Hitoshi; Nishida, Taku; Onoue, Kenji; Soeda, Tsunenari; Okayama, Satoshi; Watanabe, Makoto; Kawata, Hiroyuki; Okura, Hiroyuki; Saito, Yoshihiko

2017-05-18

Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in acute decompensated heart failure patients, its significance remains poorly understood. This study aimed to investigate the prognostic value of U-NGAL on the first day of admission for the occurrence of acute kidney injury and long-term outcomes in acute decompensated heart failure patients. We studied 260 acute decompensated heart failure patients admitted to our department between 2011 and 2014 by measuring U-NGAL in 24-hour urine samples collected on the first day of admission. Primary end points were all-cause death, cardiovascular death, and heart failure admission. Patients were divided into 2 groups according to their median U-NGAL levels (32.5 μg/gCr). The high-U-NGAL group had a significantly higher occurrence of acute kidney injury during hospitalization than the low-U-NGAL group ( P =0.0012). Kaplan-Meier analysis revealed that the high-U-NGAL group exhibited a worse prognosis than the low-U-NGAL group in all-cause death (hazard ratio 2.07; 95%CI 1.38-3.12, P =0.0004), cardiovascular death (hazard ratio 2.29; 95%CI 1.28-4.24, P =0.0052), and heart failure admission (hazard ratio 1.77; 95%CI 1.13-2.77, P =0.0119). The addition of U-NGAL to the estimated glomerular filtration rate significantly improved the predictive accuracy of all-cause mortality ( P =0.0083). In acute decompensated heart failure patients, an elevated U-NGAL level on the first day of admission was related to the development of clinical acute kidney injury and independently associated with poor prognosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Surface modification of a biodegradable magnesium alloy with phosphorylcholine (PC) and sulfobetaine (SB) functional macromolecules for reduced thrombogenicity and acute corrosion resistance.

PubMed

Ye, Sang-Ho; Jang, Yong-Seok; Yun, Yeo-Heung; Shankarraman, Venkat; Woolley, Joshua R; Hong, Yi; Gamble, Lara J; Ishihara, Kazuhiko; Wagner, William R

2013-07-02

Siloxane functionalized phosphorylcholine (PC) or sulfobetaine (SB) macromolecules (PCSSi or SBSSi) were synthesized to act as surface modifying agents for degradable metallic surfaces to improve acute blood compatibility and slow initial corrosion rates. The macromolecules were synthesized using a thiol-ene radical photopolymerization technique and then utilized to modify magnesium (Mg) alloy (AZ31) surfaces via an anhydrous phase deposition of the silane functional groups. X-ray photoelectron spectroscopy surface analysis results indicated successful surface modification based on increased nitrogen and phosphorus or sulfur composition on the modified surfaces relative to unmodified AZ31. In vitro acute thrombogenicity assessment after ovine blood contact with the PCSSi and SBSSi modified surfaces showed a significant decrease in platelet deposition and bulk phase platelet activation compared with the control alloy surfaces. Potentiodynamic polarization and electrochemical impedance spectroscopy data obtained from electrochemical corrosion testing demonstrated increased corrosion resistance for PCSSi- and SBSSi-modified AZ31 versus unmodified surfaces. The developed coating technique using PCSSi or SBSSi showed promise in acutely reducing both the corrosion and thrombotic processes, which would be attractive for application to blood contacting devices, such as vascular stents, made from degradable Mg alloys.

Surface modification of a biodegradable magnesium alloy with phosphorylcholine (PC) and sulfobetaine (SB) functional macromolecules for reduced thrombogenicity and acute corrosion resistance

PubMed Central

Ye, Sang-Ho; Jang, Yong-Seok; Yun, Yeo-Heung; Shankarraman, Venkat; Woolley, Joshua R.; Hong, Yi; Gamble, Lara J.; Ishihara, Kazuhiko; Wagner, William R.

2013-01-01

Siloxane functionalized phosphorylcholine (PC) or sulfobetaine (SB) macromolecules (PCSSi or SBSSi) were synthesized to act as surface modifying agents for degradable metallic surfaces to improve acute blood compatibility and slow initial corrosion rates. The macromolecules were synthesized using a thiol-ene radical photopolymerization technique and then utilized to modify magnesium (Mg) alloy (AZ31) surfaces via an anhydrous phase deposition of the silane functional groups. X-ray photoelectron spectroscopy surface analysis results indicated successful surface modification based on increased nitrogen and phosphorus or sulfur composition on the modified surfaces relative to unmodified AZ31. In vitro acute thrombogenicity assessment after ovine blood contact with the PCSSi and SBSSi modified surfaces showed a significant decrease in platelet deposition and bulk phase platelet activation compared with the control alloy surfaces. Potentiodynamic polarization and electrochemical impedance spectroscopy data obtained from electrochemical corrosion testing demonstrated increased corrosion resistance for PCSSi and SBSSi modified AZ31 versus unmodified surfaces. The developed coating technique using PCSSi or SBSSi showed promise in acutely reducing both the corrosion and thrombotic processes, which would be attractive for application to blood contacting devices, such as vascular stents, made from degradable Mg alloys. PMID:23705967

Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

PubMed

Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

2017-12-31

To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058). In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.

Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome

PubMed Central

Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

2017-01-01

Aim To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). Methods This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). Results The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC = 0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC = 0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC = 0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC = 0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC = 0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC = 0.88; 95% CI 1.018-1.072) and on discharge (AUC = 0.78; 95% CI 1.000-1.058). Conclusions In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR. PMID:29308832

Climatic Events and Historical Disturbances Control Acute and Chronic Water-Quality Impairment After Wildfire

NASA Astrophysics Data System (ADS)

Murphy, S. F.; Martin, D. A.; McCleskey, R. B.; Writer, J. H.

2016-12-01

Many studies have shown that surface water quality can be impaired after wildfire. The majority of these studies are typically conducted for short periods (1-2 years), and until recently, usually employed routine (fixed-interval) sampling. We monitored stream water quality for five years after a wildfire in the Colorado Front Range using a combination of routine sampling, storm sampling, and continuous sensors. This five-year study facilitated the measurement of post-wildfire water-quality response to a number of climatic events, including low- to moderate-intensity rain storms, drought, extreme rainfall (based on amount of rain that fell in a 7-day period), and the highest spring runoff recorded from the watershed during 23 years of record. Post-wildfire water quality was controlled by the hydrologic response to these climatic events, and by a legacy of historical disturbance from mining and related activities. Increased surface runoff during rain storms led to mobilization of sediment from hillslopes to stream channels. The sediment remained in stream channels during a drought that led to reduced (25% of mean) spring runoff, but this sediment, and associated constituents such as dissolved organic carbon and manganese, were remobilized into the water column and transported downstream during sustained high-flow spring runoff in the third year. We infer that the relative proportions of surface and subsurface runoff were altered by the wildfire and during the extreme rainfall, possibly leading to greater flow through abandoned mine adits and tunnels, and thus causing increased instream metal concentrations (such as arsenic and manganese). Post-wildfire water-quality issues were both acute, with significant water-quality impairment during storm events, and chronic, with elevated concentrations of sediment, nitrate, dissolved organic carbon, manganese, and arsenic for months to years after the wildfire. Such variable source water quality, in both contaminant type and

Association Between Hyperuricemia and Major Adverse Cardiac Events in Patients with Acute Myocardial Infarction.

PubMed

Ranjith, Naresh; Myeni, Nomcebo N; Sartorius, Ben; Mayise, Chamsanqua

2017-02-01

To investigate the association between hyperuricemia and major adverse cardiac events (MACE) in patients with acute myocardial infarction (AMI). Consecutive patients admitted with AMI to the Coronary Care Unit at R. K. Khan Hospital (Durban, South Africa) between the years 2006 and 2014 were included. Demographic data, including clinical and biochemical information stored in an electronic database, were obtained from all patients. A total of 2683 patients were studied, of whom 65% were males. The mean age of the participants was 57.1 ± 11.5 years, with 79% presenting with ST elevation myocardial infarction. Sixty-one percent were smokers, 59% had diabetes mellitus, 52% had hypertension, and 58% presented with a family history of premature coronary artery disease. Twenty-six percent (n = 690) had hyperuricemia, were older (59 ± 12.1 vs. 56.5 ± 11.2 years) and more likely to present with hypertension (P < 0.001), lower ejection fraction (P < 0.001), and higher median creatinine levels (P < 0.001). A significantly greater proportion of patients with hyperuricemia experienced MACE (45% vs. 30%, P < 0.001). In both sexes, considerable heterogeneity for risk factors and clinical events was noted in individuals with hyperuricemia. Multivariable analyses for risk factors associated with mortality suggest that hyperuricemia conferred a significantly increased risk of mortality after adjustment [odds ratio (OR) 1.7 (95% confidence interval 1.0-2.8); P = 0.042]. A significant increasing risk trend for MACE was observed for increasing tertiles of serum uric acid concentrations above normal (P < 0.001), particularly for cardiac failure (P < 0.001) and death (P = 0.006). Hyperuricemia is significantly associated with hypertension, renal dysfunction, MACE, and independently confers a higher risk of mortality in patients with AMI. Significant heterogeneity was found by gender for risk factors and clinical events in individuals

Intracranial and visceral arterial embolization of a cardiac myxoma that was treated with endovascular stent-retriever therapy

PubMed Central

Thibodeau, Cheryl; McGowan, Amelia

2016-01-01

We report a case of a ruptured left atrial myxoma with multiple synchronous sites of embolization, including the intracranial cerebral (left middle cerebral artery (MCA) and basilar), visceral (renal, superior mesenteric artery (SMA)) and peripheral circulatory beds (aorta and lower extremities). This synchronous embolization resulted in a catastrophic neurologic and systemic event. An intracranial stent retriever was used to restore cerebral circulation in the symptomatic left MCA distribution, which resulted in resolution of the acute neurologic deficits. Endovascular and open surgical interventions were later performed to address the residual cardiac mass and other embolic sites. The patient survived the event with the loss of her right leg below the knee and a transient dialysis requirement. The purpose of this case report is to document the successful utilization of a stent-retriever device in removing an embolized myxoma from the cerebral circulation, to review the unique pathology of this source of embolic stroke and to reiterate the importance of considering embolic and non-thrombotic etiologies of acute ischemic stroke, especially in atypical patient populations and patient presentations. PMID:27306523

Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles

PubMed Central

2013-01-01

Background Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear. Methods To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin–induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter. Results DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice. Conclusion This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in

Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles.

PubMed

Nemmar, Abderrahim; Subramaniyan, Deepa; Yasin, Javed; Ali, Badreldin H

2013-04-15

Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear. To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter. DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice. This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.

The Thrombolytic Effect of Diagnostic Ultrasound-Induced Microbubble Cavitation in Acute Carotid Thromboembolism.

PubMed

Porter, Thomas R; Xie, Feng; Lof, John; Powers, Jeffry; Vignon, Francois; Shi, William; White, Matthew

2017-08-01

Acute ischemic stroke is often due to thromboembolism forming over ruptured atherosclerotic plaque in the carotid artery (CA). The presence of intraluminal CA thrombus is associated with a high risk of thromboembolic cerebral ischemic events. The cavitation induced by diagnostic ultrasound high mechanical index (MI) impulses applied locally during a commercially available intravenous microbubble infusion has dissolved intravascular thrombi, especially when using longer pulse durations. The beneficial effects of this in acute carotid thromboembolism is not known. An oversized balloon injury was created in the distal extracranial common CA of 38 porcine carotid arteries. After this, a 70% to 80% stenosis was created in the mid common CA proximal to the injury site using partial balloon inflation. Acute thrombotic CA occlusions were created just distal to the balloon catheter by injecting fresh autologous arterial thrombi. After angiographic documentation of occlusion, the common carotid thrombosis was treated with either diagnostic low MI imaging alone (0.2 MI; Philips S5-1) applied through a tissue mimicking phantom (TMP) or intermittent diagnostic high MI stable cavitation (SC)-inducing impulses with a longer pulse duration (0.8 MI; 20 microseconds' pulse duration) or inertial cavitation (IC) impulses (1.2 MI; 20 microseconds' pulse duration). All treatment times were for 30 minutes. Intravenous ultrasound contrast (2% Definity; Lantheus Medical) was infused during the treatment period. Angiographic recanalization in 4 intracranial and extracranial vessels downstream from the CA occlusion (auricular, ascending pharyngeal, buccinator, and maxillary) was assessed with both magnetic resonance 3-dimensional time-of-flight and phase contrast angiography. All magnetic resonance images were interpreted by an independent neuroradiologist using the thrombolysis in cerebral infarction (TICI) scoring system. By phase contrast angiography, at least mild recanalization (TICI 2a

An increase in epicardial fat in women is associated with thrombotic risk.

PubMed

Basurto Acevedo, Lourdes; Barrera Hernández, Susana; Fernández Muñoz, María de Jesús; Saucedo García, Renata Patricia; Rodríguez Luna, Ana Karen; Martínez Murillo, Carlos

2018-01-29

A decrease in fibrinolytic activity and an increase in the thickness of the epicardial adipose tissue have been observed in patients with coronary artery disease. The aim of this study was to determine the association between epicardial adipose tissue and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). A cross-sectional study was conducted on 56 apparently healthy women aged 45 to 60 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Epicardial thickness was assessed by transthoracic echocardiography. The concentration of PAI-1 was directly associated with the thickness of the epicardial adipose tissue (r=0.475, P=.001), body mass index (BMI), visceral adipose tissue, insulin resistance, glucose, and HDL-cholesterol. The multivariate regression analysis indicated that epicardial fat independently predicts the concentrations of PAI-1. Women with thicker epicardial adipose tissue have reduced fibrinolytic activity, and consequently greater thrombotic risk. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Late endovascular removal of Günther-Tulip inferior vena cava filter and stent reconstruction of chronic post-thrombotic iliocaval obstruction after 4753 days of filter dwell time: a case report with review of literature.

PubMed

Doshi, Mehul Harshad; Narayanan, Govindarajan

2016-12-01

Chronic post-thrombotic obstruction of the inferior vena cava (IVC) or iliocaval junction is an uncommon complication of long indwelling IVC filter. When such an obstruction is symptomatic, endovascular treatment options include stent placement with or without filter retrieval. Filter retrieval becomes increasingly difficult with longer dwell times. We present a case of symptomatic post-thrombotic obstruction of the iliocaval junction related to Günther-Tulip IVC filter (Cook Medical Inc, Bloomington, IN) with dwell time of 4753 days, treated successfully with endovascular filter removal and stent reconstruction. Filter retrieval and stent reconstruction may be a treatment option in symptomatic patients with filter-related chronic IVC or iliocaval junction obstruction, even after prolonged dwell time.

Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3: protocol for a longitudinal study.

PubMed

Alabas, O A; West, R M; Gillott, R G; Khatib, R; Hall, A S; Gale, C P

2015-06-23

Patients with cardiovascular disease are living longer and are more frequently accessing healthcare resources. The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3 national study is designed to improve understanding of the effect of quality of care on health-related outcomes for patients hospitalised with acute coronary syndrome (ACS). EMMACE-3 is a longitudinal study of 5556 patients hospitalised with an ACS in England. The study collects repeated measures of health-related quality of life, information about medications and patient adherence profiles, a survey of hospital facilities, and morbidity and mortality data from linkages to multiple electronic health records. Together with EMMACE-3X and EMMACE-4, EMMACE-3 will assimilate detailed information for about 13 000 patients across more than 60 hospitals in England. EMMACE-3 was given a favourable ethical opinion by Leeds (West) Research Ethics committee (REC reference: 10/H131374). On successful application, study data will be shared with academic collaborators. The findings from EMMACE-3 will be disseminated through peer-reviewed publications, at scientific conferences, the media, and through patient and public involvement. ClinicalTrials.gov Identifier: NCT01808027. Information about the study is also available at EMMACE.org. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of Ocean Acidification on the Brown Alga Padina pavonica: Decalcification Due to Acute and Chronic Events

PubMed Central

Gil-Díaz, Teba; Haroun, Ricardo; Tuya, Fernando; Betancor, Séfora; Viera-Rodríguez, María A.

2014-01-01

Since the industrial revolution, anthropogenic CO2 emissions have caused ocean acidification, which particularly affects calcified organisms. Given the fan-like calcified fronds of the brown alga Padina pavonica, we evaluated the acute (short-term) effects of a sudden pH drop due to a submarine volcanic eruption (October 2011–early March 2012) affecting offshore waters around El Hierro Island (Canary Islands, Spain). We further studied the chronic (long-term) effects of the continuous decrease in pH in the last decades around the Canarian waters. In both the observational and retrospective studies (using herbarium collections of P. pavonica thalli from the overall Canarian Archipelago), the percent of surface calcium carbonate coverage of P. pavonica thalli were contrasted with oceanographic data collected either in situ (volcanic eruption event) or from the ESTOC marine observatory data series (herbarium study). Results showed that this calcified alga is sensitive to acute and chronic environmental pH changes. In both cases, pH changes predicted surface thallus calcification, including a progressive decalcification over the last three decades. This result concurs with previous studies where calcareous organisms decalcify under more acidic conditions. Hence, Padina pavonica can be implemented as a bio-indicator of ocean acidification (at short and long time scales) for monitoring purposes over wide geographic ranges, as this macroalga is affected and thrives (unlike strict calcifiers) under more acidic conditions. PMID:25268231

Safety of preoperative erythropoietin in surgical calvarial remodeling: an 8-year retrospective review and analysis.

PubMed

Naran, Sanjay; Cladis, Franklyn; Fearon, Jeffrey; Bradley, James; Michelotti, Brett; Cooper, Gregory; Cray, James; Katchikian, Hurig; Grunwaldt, Lorelei; Pollack, Ian F; Losee, Joseph

2012-08-01

Calvarial remodeling is typically associated with significant blood loss. Although preoperative erythropoiesis-stimulating agents have proven to significantly decrease the need for blood transfusions, recent data in adults have raised concerns that elevating hemoglobin levels greater than 12.5 g/dl may increase the risk of thrombotic events. This study was designed to assess the risks of erythropoietin in the pediatric population. Records were retrospectively reviewed from 2000 to 2008 at three major metropolitan children's hospitals of all children undergoing calvarial remodeling after receiving preoperative erythropoietin. Demographic and perioperative outcome data were reviewed, including transfusion reactions, pressure ulcer secondary to prolonged positioning, pneumonia, infection, deep vein thrombosis, cerebrovascular accident, pulmonary embolism, sagittal sinus thrombosis, pure red cell aplasia, and myocardial infarction. A total of 369 patients met the inclusion criteria (mean age, 0.86±1.1 years). On average, three preoperative doses of erythropoietin were administered (600 U/kg). Iron was also supplemented. No complications associated with dosing were noted, there were no thrombotic events identified, and no other major complications were seen (i.e., death or blindness). Thirty-one patients (8.40 percent) experienced one or more postoperative complications. There was no significant correlation between hemoglobin levels greater than 12.5 g/dl and the occurrence of any noted complication. With zero thrombotic postoperative complications, the authors estimate the risk of a thrombotic event in the pediatric population to be less than 0.81 percent (95 percent confidence). These data suggest that preoperative administration of erythropoietin in children undergoing calvarial remodeling does not appear to increase the incidence of thrombotic events or other significant complications. Therapeutic, IV.

Twice-daily therapeutical plasma exchange-based salvage therapy in severe autoimmune thrombotic thrombocytopenic purpura: the French TMA Reference Center experience.

PubMed

Soucemarianadin, Myriam; Benhamou, Ygal; Delmas, Yahsou; Pichereau, Claire; Maury, Eric; Pène, Frédéric; Halimi, Jean-Michel; Presne, Claire; Thouret, Jean-Marc; Veyradier, Agnès; Coppo, Paul

2016-08-01

Daily therapeutic plasma exchange (TPE) and rituximab improved thrombotic thrombocytopenic purpura (TTP) prognosis. In the more severe cases, salvage therapies including twice-daily TPE and/or cyclophosphamide may be proposed and require evaluation. TTP was defined as a thrombotic microangiopathy (TMA) with severe (<10%) acquired ADAMTS13 deficiency. Among patients included in the French Reference Center for TMA registry, we considered those with a severe disease (i.e., unresponsive to daily TPE and rituximab) who received twice-daily TPE. Nineteen of 289 (6.6%) patients with TTP were treated by twice-daily TPE between 2008 and 2014. Twice-daily TPE was associated with rituximab in 16 cases. The median duration of twice-daily TPE treatment was 3 d (2-22 d). In 6 patients (31.6%), additional treatments (mainly pulses of cyclophosphamide) were performed because of a persistently refractory disease (4 cases) or an exacerbation (2 cases), despite twice-daily TPE. Only one patient (5.3%) died. The other 18 achieved a durable complete remission 25.5 d (13-68 d) after the first TPE. The median follow-up was 14.4 months (7 d-45 months). Twice-daily TPE may be an efficient strategy in the more severe TTP patients with a short-term life-threatening disease that could overcome their poor prognosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease

A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

PubMed

Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

2012-09-01

Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to

Post-thrombotic syndrome after central venous catheter removal in childhood cancer survivors: A prospective cohort study.

PubMed

Polen, E; Weintraub, M; Stoffer, C; Jaffe, D H; Burger, A; Revel-Vilk, S

2015-02-01

Although the use of central venous catheters (CVCs) has greatly improved the quality of care of children with cancer, these catheters increase the risk of deep vein thrombosis (DVT) and the potential long-term complication of post-thrombotic syndrome (PTS). We aimed to study PTS post-CVC removal using physical, functional and health related quality of life (HRQoL) domains in childhood cancer and bone marrow transplantation (BMT) survivors. We conducted a prospective study in a cohort of childhood cancer and BMT survivors post-CVC use. Participants were evaluated for PTS with the Modified Villalta Score (MVS) and the Manco-Johnson Instrument (MJI). HRQoL was assessed using the PedsQL™ questionnaire. A total of 158 children were enrolled at a median of 41 (4-149) months from CVC removal. Signs and symptoms of PTS were present in 34% (95% confidence interval [CI] 27-43%) (MVS criteria) and 30.5% (95% CI 23.1-37.8%) (MJI criteria). Diagnosis of PTS was associated with history of CVC occlusion, history of CVC-related DVT and the use of ≥2 CVCs. The presence of signs and symptoms of PTS was a predictor for low HRQoL tested by the PedsQL™ Total Scale scores and Physical Health Summary scores. PTS post-CVC removal in pediatric cancer survivors is not a rare event. The association between PTS and the history of CVC occlusion confirms earlier findings, and suggests that CVC occlusion may indicate asymptomatic DVT. PTS is also associated with lower HRQoL scores highlighting the need to study preventive measures, especially for high risk groups. Pediatr Blood Cancer 2015;62:285-290. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

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

PubMed Central

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

2013-01-01

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

Evaluation of neutrophil/leukocyte ratio and organ failure score as predictors of reversibility and survival following an acute-on-chronic liver failure event.

PubMed

Agiasotelli, Danai; Alexopoulou, Alexandra; Vasilieva, Larisa; Kalpakou, Georgia; Papadaki, Sotiria; Dourakis, Spyros P

2016-05-01

Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of liver disease with high mortality in patients with cirrhosis. The early mortality in ACLF is associated with organ failure and high leukocyte count. The time needed to reverse this condition and the factors affecting mortality after the early 30-day-period were evaluated. One hundred and ninety-seven consecutive patients with cirrhosis were included. Patients were prospectively followed up for 180 days. ACLF was diagnosed in 54.8% of the patients. Infection was the most common precipitating event in patients with ACLF. On multivariate analysis, only the neutrophil/leukocyte ratio and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score were associated with mortality. Hazard ratios for mortality of patients with ACLF compared with those without at different time end-points post-enrollment revealed that the relative risk of death in the ACLF group was 8.54 during the first 30-day period and declined to 1.94 during the second period of observation. The time varying effect of neutrophil/leukocyte ratio and CLIF-C score was negative (1% and 18% decline in the hazard ratio per month) while that of Model for End-Stage Liver Disease (MELD) was positive (3% increase in the hazard ratio per month). The condition of ACLF was reversible in patients who survived. During the 30-180-day period following the acute event, the probability of death in ACLF became gradually similar to the non-ACLF group. The impact of inflammatory response and organ failure on survival is powerful during the first 30-day period and weakens thereafter while that of MELD increases. © 2015 The Japan Society of Hepatology.

Galectin 3 complements BNP in risk stratification in acute heart failure.

PubMed

Fermann, Gregory J; Lindsell, Christopher J; Storrow, Alan B; Hart, Kimberly; Sperling, Matthew; Roll, Susan; Weintraub, Neal L; Miller, Karen F; Maron, David J; Naftilan, Allen J; McPherson, John A; Sawyer, Douglas B; Christenson, Robert; Collins, Sean P

2012-12-01

Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events.

Galectin 3 complements BNP in risk stratification in acute heart failure

PubMed Central

Fermann, Gregory J.; Lindsell, Christopher J.; Storrow, Alan B.; Hart, Kimberly; Sperling, Matthew; Roll, Susan; Weintraub, Neal L.; Miller, Karen F.; Maron, David J.; Naftilan, Allen J.; Mcpherson, John A.; Sawyer, Douglas B.; Christenson, Robert; Collins, Sean P.

2013-01-01

Background Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Methods Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Results Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. Conclusion In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events. PMID:22998064

Acute ischemic cerebrovascular events on antiplatelet therapy: what is the optimal prevention strategy?

PubMed

Milionis, Haralampos; Michel, Patrik

2013-01-01

Even though patients who develop ischemic stroke despite taking antiplatelet drugs represent a considerable proportion of stroke hospital admissions, there is a paucity of data from investigational studies regarding the most suitable therapeutic intervention. There have been no clinical trials to test whether increasing the dose or switching antiplatelet agents reduces the risk for subsequent events. Certain issues have to be considered in patients managed for a first or recurrent stroke while receiving antiplatelet agents. Therapeutic failure may be due to either poor adherence to treatment, associated co-morbid conditions and diminished antiplatelet effects (resistance to treatment). A diagnostic work up is warranted to identify the etiology and underlying mechanism of stroke, thereby guiding further management. Risk factors (including hypertension, dyslipidemia and diabetes) should be treated according to current guidelines. Aspirin or aspirin plus clopidogrel may be used in the acute and early phase of ischemic stroke, whereas in the long-term, antiplatelet treatment should be continued with aspirin, aspirin/extended release dipyridamole or clopidogrel monotherapy taking into account tolerance, safety, adherence and cost issues. Secondary measures to educate patients about stroke, the importance of adherence to medication, behavioral modification relating to tobacco use, physical activity, alcohol consumption and diet to control excess weight should also be implemented.

Clinical indicators for recurrent cardiovascular events in acute coronary syndrome patients treated with statins under routine practice in Thailand: an observational study.

PubMed

Chinwong, Dujrudee; Patumanond, Jayanton; Chinwong, Surarong; Siriwattana, Khanchai; Gunaparn, Siriluck; Hall, John Joseph; Phrommintikul, Arintaya

2015-06-16

Acute coronary syndrome (ACS) patients are at very high cardiovascular risk and tend to have recurrent cardiovascular events. The clinical indicators for subsequent cardiovascular events are limited and need further investigation. This study aimed to explore clinical indicators that were associated with recurrent cardiovascular events following index hospitalization. The data of patients hospitalized with ACS at a tertiary care hospital in northern Thailand between January 2009 and December 2012 were retrospectively reviewed from medical charts and the electronic hospital database. The patients were classified into three groups based on the frequency of recurrent cardiovascular events (nonfatal ACS, nonfatal stroke, or all-cause death) they suffered: no recurrent events (0), single recurrent event (1), and multiple recurrent events (≥2). Ordinal logistic regression was performed to explore the clinical indicators for recurrent cardiovascular events. A total of 405 patients were included; 60 % were male; the average age was 64.9 ± 11.5 years; 40 % underwent coronary revascularization during admission. Overall, 359 (88.6 %) had no recurrent events, 36 (8.9 %) had a single recurrent event, and 10 (2.5 %) had multiple recurrent events. The significant clinical indicators associated with recurrent cardiovascular events were achieving an LDL-C goal of < 70 mg/dL (Adjusted OR = 0.43; 95 % CI = 0.27-0.69, p-value < 0.001), undergoing revascularization during admission (Adjusted OR = 0.44; 95 % CI = 0.24-0.81, p-value = 0.009), being male (Adjusted OR = 1.85; 95 % CI = 1.29-2.66, p-value = 0.001), and decrease estimated glomerular filtration rate (Adjusted OR = 2.46; 95 % CI = 2.21-2.75, p-value < 0.001). The routine clinical practice indicators assessed in ACS patients that were associated with recurrent cardiovascular events were that achieving the LDL-C goal and revascularization are protective factors

Anithrombotic prevention in vascular disease: bases for a new strategy in antithrombotic therapy

PubMed Central

Altman, Raul

2007-01-01

A tendency toward bleeding often undercuts the beneficial preventive effect of higher doses of a single antithrombotic drug or combined antithrombotic therapy. Although high doses of antithrombotic drugs may be necessary for optimal prevention, such therapy can also elicit more frequent bleeding. Although major bleeding could be a reversible event is likely to lead clinicians to discontinue antithrombotic therapy which in turn could increase the risk of myocardial infarction, stroke, and cardiovascular death. Thus, to prevent thrombotic events without frequent bleeding complications, the preferred approach might be to use anti-inflammatory drugs in addition to the first-line antithrombotic drugs to reduce inflammation and thrombin formation in atheroma. Although some preliminary data have been already published, to confirm the potential benefit of anti-inflammatory drugs in acute coronary syndromes large prospective double-bind randomized trials are necessary. PMID:17727726

Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

PubMed Central

Saif, Muhammad W.; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N.

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered. PMID:21687621

Cerebrovascular accidents associated with sorafenib in hepatocellular carcinoma.

PubMed

Saif, Muhammad W; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered.

The pathophysiology of cigarette smoking and cardiovascular disease: an update.

PubMed

Ambrose, John A; Barua, Rajat S

2004-05-19

Cigarette smoking (CS) continues to be a major health hazard, and it contributes significantly to cardiovascular morbidity and mortality. Cigarette smoking impacts all phases of atherosclerosis from endothelial dysfunction to acute clinical events, the latter being largely thrombotic. Both active and passive (environmental) cigarette smoke exposure predispose to cardiovascular events. Whether there is a distinct direct dose-dependent correlation between cigarette smoke exposure and risk is debatable, as some recent experimental clinical studies have shown a non-linear relation to cigarette smoke exposure. The exact toxic components of cigarette smoke and the mechanisms involved in CS-related cardiovascular dysfunction are largely unknown, but CS increases inflammation, thrombosis, and oxidation of low-density lipoprotein cholesterol. Recent experimental and clinical data support the hypothesis that cigarette smoke exposure increases oxidative stress as a potential mechanism for initiating cardiovascular dysfunction.

A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone.

PubMed

Schleinitz, Mark D; Heidenreich, Paul A

2005-02-15

Although clopidogrel plus aspirin is more effective than aspirin alone in preventing subsequent vascular events in patients with unstable angina, the cost-effectiveness of this combination has yet to be examined in this high-risk population. To determine the cost-effectiveness of clopidogrel plus aspirin compared with aspirin alone. Cost-utility analysis. Published literature. Patients with unstable angina and electrocardiographic changes or non-Q-wave myocardial infarction. time horizon: Lifetime. Societal. Combination therapy with clopidogrel, 75 mg/d, plus aspirin, 325 mg/d, for 1 year, followed by aspirin monotherapy, was compared with lifelong aspirin therapy, 325 mg/d. Lifetime costs, life expectancy in quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. Patients treated with aspirin alone lived 9.51 QALYs after their initial event and incurred expenses of 127,700 dollars; the addition of clopidogrel increased life expectancy to 9.61 QALYs and costs to 129,300 dollars. The incremental cost-effectiveness ratio for clopidogrel plus aspirin compared with aspirin alone was 15,400 dollars per QALY. The analysis of 1 year of therapy was robust to all sensitivity analyses. In the probabilistic sensitivity analysis, fewer than 3% of simulations resulted in cost-effectiveness ratios over 50,000 dollars per QALY. The cost-effectiveness of longer combination therapy depends critically on the balance of thrombotic event rates, durable efficacy, and the increased bleeding rate in patients taking clopidogrel. This analysis may not apply to patients with severe heart failure, those undergoing long-term anticoagulant therapy, those recently managed with revascularization, or those undergoing short-term treatment with glycoprotein IIb/IIIa inhibitors. In patients with high-risk acute coronary syndromes, 1 year of therapy with clopidogrel plus aspirin results in greater life expectancy than aspirin alone, at a cost within the traditional limits

A Retrospective Propensity Score-Matched Early Thromboembolic Event Analysis of Prothrombin Complex Concentrate vs Fresh Frozen Plasma for Warfarin Reversal Prior to Emergency Neurosurgical Procedures.

PubMed

Agarwal, Prateek; Abdullah, Kalil G; Ramayya, Ashwin G; Nayak, Nikhil R; Lucas, Timothy H

2017-06-29

Reversal of therapeutic anticoagulation prior to emergency neurosurgical procedures is required in the setting of intracranial hemorrhage. Multifactor prothrombin complex concentrate (PCC) promises rapid efficacy but may increase the probability of thrombotic complications compared to fresh frozen plasma (FFP). To compare the rate of thrombotic complications in patients treated with PCC or FFP to reverse therapeutic anticoagulation prior to emergency neurosurgical procedures in the setting of intracranial hemorrhage at a level I trauma center. Sixty-three consecutive patients on warfarin therapy presenting with intracranial hemorrhage who received anticoagulation reversal prior to emergency neurosurgical procedures were retrospectively identified between 2007 and 2016. They were divided into 2 cohorts based on reversal agent, either PCC (n = 28) or FFP (n = 35). The thrombotic complications rates within 72 h of reversal were compared using the χ 2 test. A multivariate propensity score matching analysis was used to limit the threat to interval validity from selection bias arising from differences in demographics, laboratory values, history, and clinical status. Thrombotic complications were uncommon in this neurosurgical population, occurring in 1.59% (1/63) of treated patients. There was no significant difference in the thrombotic complication rate between groups, 3.57% (1/28; PCC group) vs 0% (0/35; FFP group). Propensity score matching analysis validated this finding after controlling for any selection bias. In this limited sample, thrombotic complication rates were similar between use of PCC and FFP for anticoagulation reversal in the management of intracranial hemorrhage prior to emergency neurosurgical procedures. Copyright © 2017 by the Congress of Neurological Surgeons

Role of high shear rate in thrombosis.

PubMed

Casa, Lauren D C; Deaton, David H; Ku, David N

2015-04-01

Acute arterial occlusions occur in high shear rate hemodynamic conditions. Arterial thrombi are platelet-rich when examined histologically compared with red blood cells in venous thrombi. Prior studies of platelet biology were not capable of accounting for the rapid kinetics and bond strengths necessary to produce occlusive thrombus under these conditions where the stasis condition of the Virchow triad is so noticeably absent. Recent experiments elucidate the unique pathway and kinetics of platelet aggregation that produce arterial occlusion. Large thrombi form from local release and conformational changes in von Willebrand factor under very high shear rates. The effect of high shear hemodynamics on thrombus growth has profound implications for the understanding of all acute thrombotic cardiovascular events as well as for vascular reconstructive techniques and vascular device design, testing, and clinical performance. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.

PubMed

Grall, Maximilien; Azoulay, Elie; Galicier, Lionel; Provôt, François; Wynckel, Alain; Poullin, Pascale; Grange, Steven; Halimi, Jean-Michel; Lautrette, Alexandre; Delmas, Yahsou; Presne, Claire; Hamidou, Mohamed; Girault, Stéphane; Pène, Frédéric; Perez, Pierre; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Chauveau, Dominique; Ojeda-Uribe, Mario; Barbay, Virginie; Veyradier, Agnès; Coppo, Paul; Benhamou, Ygal

2017-04-01

Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure. © 2017 Wiley Periodicals, Inc.

Deep vein thrombosis associated with dengue fever.

PubMed

Roy, Amrita; Chaudhuri, Jasodhara; Chakraborty, Swapna

2013-11-08

Hemorrhagic manifestations are common with Dengue but thrombotic events are uncommonly reported. 11-year-old boy who presented with ileo-femoral deep vein thrombosis associated with serologically confirmed infection with DEN1 dengue virus. There was no other history or investigation suggestive of a procoagulant state. Successfully treated with enoxaparin and warfarin. Thrombotic complications are possible with dengue infection.

[Telemedicine in thrombotic microangiopathies: A way forward in rare diseases requiring emergency care].

PubMed

Coppo, P; Corre, E; Rondeau, E; Benhamou, Y; Bachet, A; Stépanian, A; Veyradier, A

2016-08-01

Thrombotic microangiopathies (TMA) represent rare diseases requiring a high skill for their management that deserved in France the identification of a dedicated National reference center. TMA are short-term life-threatening diseases; however, with an adapted management, their prognosis can be excellent. It is therefore mandatory to recognize and treat them rapidly according to standard guidelines. Telemedicine is a specialized hub consisting of highly skilled staff trained in a specific domain of medicine. The telemedicine activity of a reference center is an important representative indicator of its expertise and recourse ability. It requires to be accurately evaluated and promoted. In this work, we report the French reference center for TMA telemedicine activity since its setting-up. TMA represent an interesting model of diseases that required a specific organization of telemedicine activity to adapt to clinicians demand, which includes particularly the need to answer resorts in real time 24/7. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Apixaban with antiplatelet therapy after acute coronary syndrome.

PubMed

Alexander, John H; Lopes, Renato D; James, Stefan; Kilaru, Rakhi; He, Yaohua; Mohan, Puneet; Bhatt, Deepak L; Goodman, Shaun; Verheugt, Freek W; Flather, Marcus; Huber, Kurt; Liaw, Danny; Husted, Steen E; Lopez-Sendon, Jose; De Caterina, Raffaele; Jansky, Petr; Darius, Harald; Vinereanu, Dragos; Cornel, Jan H; Cools, Frank; Atar, Dan; Leiva-Pons, Jose Luis; Keltai, Matyas; Ogawa, Hisao; Pais, Prem; Parkhomenko, Alexander; Ruzyllo, Witold; Diaz, Rafael; White, Harvey; Ruda, Mikhail; Geraldes, Margarida; Lawrence, Jack; Harrington, Robert A; Wallentin, Lars

2011-08-25

Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P=0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P=0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.).

Anticoagulants for secondary prevention after acute myocardial infarction: lessons from the past decade

PubMed Central

Atar, Dan; Bode, Christoph; Stuerzenbecher, André; Verheugt, Freek W A

2014-01-01

The impact of an acute coronary syndrome (ACS) event, such as an acute myocardial infarction (MI), is not limited to the acute management phase; patients face an elevated risk of residual atherothrombotic events that commonly requires chronic management for months or even years. Significant advances have been made in both the acute and chronic management of patients with acute MI over the past decade, resulting in improved prognoses. One of the hallmarks of modern treatment strategies is more aggressive antiplatelet treatment regimens. However, the risks of further ACS events, stroke and premature death remain elevated in these patients, and addressing this residual risk is challenging owing to interpatient variability, differences in management strategies between centres and countries, incomplete understanding of the specific pathophysiology of post-ACS thrombosis and limitations of current therapeutic approaches. The recent approval in Europe of the direct oral anticoagulant rivaroxaban for use in this setting in combination with clopidogrel and acetylsalicylic acid offers another strategy to consider in the management of these patients, and clinical strategies in this area continue to evolve. In this review, we chart the progress made over the past decade in reducing the burden of secondary thromboembolic events after acute MI and discuss the current position of and future perspectives on the inclusion of oral anticoagulants into care pathways in this setting. PMID:24494730

Decision making processes in people with symptoms of acute myocardial infarction: qualitative study

PubMed Central

Pattenden, Jill; Watt, Ian; Lewin, Robert J P; Stanford, Neil

2002-01-01

Objective To identify the themes that influence decision making processes used by patients with symptoms of acute myocardial infarction. Design Qualitative study using semistructured interviews. Setting Two district hospitals in North Yorkshire. Participants 22 patients admitted to hospital with confirmed second, third, or fourth acute myocardial infarction. Main outcome measure Patients' perceptions of their experience between the onset of symptoms and the decision to seek medical help. Results Six main themes that influence the decision making process were identified: appraisal of symptoms, perceived risk, previous experience, psychological and emotional factors, use of the NHS, and context of the event. Conclusions Knowledge of symptoms may not be enough to promote prompt action in the event of an acute myocardial infarction. Cognitive and emotional processes, individual beliefs and values, and the influence of the context of the event should also be considered in individual interventions designed to reduce delay in the event of symptoms of acute myocardial infarction. What is already known on this topicIndividual sociodemographic and clinical characteristics affect the time to seeking medical care in patients with symptoms of acute myocardial infarctionAppraisal of symptoms is difficult; people with classic and severe symptoms are more likely to take prompt actionWhat this study addsThe decision to seek medical help in patients who have had one or more previous myocardial infarctions is a complex processSimply providing patients with information on symptoms of acute myocardial infarction, and what to do in the event of these symptoms, may not be sufficient to promote prompt action PMID:11976241

[Survey of nurses about compression therapy of acute deep venous thrombosis. Field study in Saxony-Anhalt].

PubMed

Thieme, Dorothea; Langer, Gero; Behrens, Johann

2010-03-01

In clinical practice, the compression therapy is an established method for the treatment of acute deep vein thrombosis (DVT). The aim of this study was to clarify the extent to which current guidelines and results of studies done in the field for the treatment of acute DVT--particularly compression therapy--are implemented in clinical practice. All hospitals in Saxony-Anhalt using primary diagnosis and therapy for DVT (n = 34) were informed about a survey in 2007 and the nursing staff of angiology and internistical wards in these hospitals was asked to take part. The collection of data was done with the help of a questionnaire that had been designed and tested for its validity in a specialised hospital. 510 questionnaires were distributed. The response rate of questionnaires was 69 percent. 79 percent of the nursing staff of internistical wards in Saxony-Anhalt and 94 percent of the nursing staff of angiology wards said that patients with acute DVT have initially received a compression bandage. Significant deficits were visible in transferring the knowledge of evidence-based medicine and nursing regarding techniques of compression bandage. The recommended Fischer-Bandage was only put on in exceptional cases in internistical wards (3 percent) and Angiology (2 percent). Compression stockings were not a suitable method into the treatment of acute deep vein thrombosis of Angiology. 21 percent of the nursing staff of internistical wards said that they have initially applied compression stockings. The treatment of acute DVT is important in clinical practice. The compression bandage should be effectively put on the leg. The quality of care and long-term compliance of the patients could be increased this way, leading to prevention of post thrombotic syndrome (PTS) and reduction the duration of patients stay in the clinics.

Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature.

PubMed

Abu-Hishmeh, Mohammad; Sattar, Alamgir; Zarlasht, Fnu; Ramadan, Mohamed; Abdel-Rahman, Aisha; Hinson, Shante; Hwang, Caroline

2016-10-25

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathic (TMA) syndromes, caused by severely reduced activity of the vWF-cleaving protease ADAMTS13. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune disease that affects various organs in the body, including the hematopoietic system. SLE can present with TMA, and differentiating between SLE and TTP in those cases can be very challenging, particularly in patients with no prior history of SLE. Furthermore, an association between these 2 diseases has been described in the literature, with most of the TTP cases occurring after the diagnosis of SLE. In rare cases, TTP may precede the diagnosis of SLE or occur concurrently. CASE REPORT We present a case of a previously healthy 34-year-old female who presented with dizziness and flu-like symptoms and was found to have thrombocytopenia, hemolytic anemia, and schistocytes in the peripheral smear. She was subsequently diagnosed with TTP and started on plasmapheresis and high-dose steroids, but without a sustained response. A diagnosis of refractory TTP was made, and she was transferred to our facility for further management. Initially, the patient was started on rituximab, but her condition continued to deteriorate, with worsening thrombocytopenia. Later, she also fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of SLE. Treatment of TTP in SLE patients is generally similar to that in the general population, but in refractory cases there are few reports in the literature that show the efficacy of cyclophosphamide. We started our patient on cyclophosphamide and noticed a sustained improvement in the platelet count in the following weeks. CONCLUSIONS Thrombotic thrombocytopenic purpura is a life-threatening hematological emergency which must be diagnosed and treated in a timely manner. Refractory cases of TTP have been described in the literature, but without clear evidence

Spatial Hotspot Analysis of Acute Myocardial Infarction Events in an Urban Population: A Correlation Study of Health Problems and Industrial Installation

PubMed Central

NAMAYANDE, Motahareh Sadat; NEJADKOORKI, Farhad; NAMAYANDE, Seyedeh Mahdieh; DEHGHAN, Hamidreza

2016-01-01

Background: The current study’s objectives were to find any possible spatial patterns and hotspot of cardiovascular events and to perform a correlation study to find any possible relevance between cardiovascular disease (CVE) and location of industrial installation said above. Methods: We used the Acute Myocardial Infarction (AMI) hospital admission record in three main hospitals in Yazd, Yazd Province, Iran during 2013, because of CVDs and searched for possible correlation between industries as point-source pollutants and non-random distribution of AMI events. Results: MI incidence rate in Yazd was obtained 531 per 100,000 person-year among men, 458 per 100,000 person-year among women and 783/100,000 person-yr totally. We applied a GIS Hotspot analysis to determine feasible clusters and two sets of clusters were observed. Mean age of 56 AMI events occurred in the cluster cells was calculated as 62.21±14.75 yr. Age and sex as main confounders of AMI were evaluated in the cluster areas in comparison to other areas. We observed no significant difference regarding sex (59% in cluster cells versus 55% in total for men) and age (62.21±14.7 in cluster cells versus 63.28±13.98 in total for men). Conclusion: We found proximity of AMI events cluster to industries installations, and a steel industry, specifically. There could be an association between road-related pollutants and the observed sets of cluster due to the proximity exist between rather crowded highways nearby the events cluster. PMID:27057527

A case report of uncompensated alkalosis induced by daily plasmapheresis in a patient with thrombotic thrombocytopenic purpura.

PubMed

Nagai, Yoshiko; Itabashi, Mitsuyo; Mizutani, Mayuko; Ogawa, Tetsuya; Yumura, Wako; Tsuchiya, Ken; Nitta, Kosaku

2008-02-01

Plasmapheresis (PP) is widely known as the standard therapy for thrombotic thrombocytopenic purpura (TTP). Citrate is used as an anticoagulant in fresh frozen plasma, and the large amount of citrate infused during PP induces metabolic alkalosis. A 29-year-old woman was diagnosed with TTP associated with systemic lupus erythematosus, and was treated by daily PP in addition to a steroid, an immunosuppressant, vincristine, and cyclophosphamide. Uncompensated alkalosis caused by a combination of metabolic and respiratory alkalosis developed after artificial ventilation was discontinued. Her metabolic status improved after controlling her respiratory status and the activity of the TTP. Metabolic alkalosis is a common complication in TTP patients treated by frequent PP, but several factors that affect metabolic status may aggravate the alkalosis and induce uncompensated alkalosis.

Management of acute coronary syndromes in developing countries: acute coronary events-a multinational survey of current management strategies.

PubMed

2011-11-01

The burden of cardiovascular diseases is predicted to escalate in developing countries. We investigated the descriptive epidemiology, practice patterns, and outcomes of patients hospitalized with acute coronary syndromes (ACS) in African, Latin American, and Middle Eastern countries. In this prospective observational registry, 12,068 adults hospitalized with a diagnosis of ACS were enrolled between January 2007 and January 2008 at 134 sites in 19 countries in Africa, Latin America, and the Middle East. Data on patient characteristics, treatment, and outcomes were collected. A total of 11,731 patients with confirmed ACS were enrolled (46% with ST-elevation myocardial infarction [STEMI], 54% with non-ST elevation-ACS). During hospitalization, most patients received aspirin (93%) and a lipid-lowering medication (94%), 78% received a β-blocker, and 68% received an angiotensin-converting enzyme inhibitor. Among patients with STEMI, 39% did not receive fibrinolysis or undergo percutaneous coronary intervention. All-cause death at 12 months was 7.3% and was higher in patients with STEMI versus non-ST elevation-ACS (8.4% vs 6.3%, P < .0001). Clinical factors associated with higher risk of death at 12 months included cardiac arrest, antithrombin treatment, cardiogenic shock, and age >70 years. In this observational study of patients with ACS, the use of evidence-based pharmacologic therapies for ACS was quite high, yet 39% of eligible patients with STEMI received no reperfusion therapy. These findings suggest opportunities to further reduce the risk of long-term ischemic events in patients with ACS in developing countries. Copyright © 2011 Mosby, Inc. All rights reserved.

In vivo aerobic metabolism of the rainbow trout gut and the effects of an acute temperature increase and stress event.

PubMed

Brijs, Jeroen; Gräns, Albin; Hjelmstedt, Per; Sandblom, Erik; van Nuland, Nicole; Berg, Charlotte; Axelsson, Michael

2018-05-24

The fish gut is responsible for numerous potentially energetically costly processes, yet, little is known about its metabolism. Here, we provide the first in vivo measurements for aerobic metabolism of the gut in a teleost fish by measuring gut blood flow, as well as arterial and portal venous oxygen content. At 10°C, gut oxygen uptake rates were 4.3±0.5 ml O 2 h -1 kg -1 (∼11% of whole animal oxygen uptake). Following acute warming to 15°C, gut blood flow increased ∼3.4-fold and gut oxygen uptake rate increased ∼3.7-fold (16.0±3.3 ml O 2 h -1 kg -1 ), now representing ∼25% of whole animal oxygen uptake. Although gut blood flow decreased following an acute stress event at 15°C, gut oxygen uptake remained unchanged due to a ∼2-fold increase in oxygen extraction. The high metabolic thermal sensitivity of the gut discovered here could have important implications on the overall aerobic capacity and performance of fish and warrants further investigations. © 2018. Published by The Company of Biologists Ltd.

Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

PubMed

Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

2015-10-01

The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

[The strategy and process of out-hospital emergency care of acute cardiovascular events].

PubMed

Sun, Gang; Wu, Li-e; Li, Qian-ying; Yang, Ye; Wang, Zi-chao; Zhang, Jing-yin; Li, Shu-jun; Yan, Xu-long; Wang, Ming; Zhang, Wen-xiang; Huang, Guan-hua

2009-06-01

To study the strategy and process of out-hospital emergency care of acute cardiovascular events. One hundred and eighty-three patients in the Second Affiliated Hospital of Baotou Medical College were prospectively studied. The patients were divided into two groups according to the different ways of out-hospital care, one group consisted of patients who received first-aid care after calling "120" (94 cases), another was self-aid group consisting of patients sent to hospital by relatives (89 cases). The proportion of persons with higher than high school education and better knowledge for emergency care of patients with heart disease in first-aid group was higher than self-aid group (50.0% vs. 29.2%, 83.0% vs. 60.7%, both P<0.05). When the patients were brought to the emergency room, they were all treated according to our standard procedure and then registered. All patients were followed up at the end of first and third month after illness. Cardiovascular events were mainly myocardial infarction (61.7%) among 183 patients. There were statistically significant differences between two groups in self-aid response time, first disposal time and out-hospital rescuing time [(32.3+/-5.6) minutes vs. (89.6+/- 8.4) minutes, (47.3+/-7.3) minutes vs. (149.8+/-13.5) minutes, (61.7+/-8.3) minutes vs. [(149.8+/- 13.5) minutes, all P<0.01], but no difference was found in in-hospital rescuing time [(29.9+/-5.3) minutes vs. (31.1+/-4.5) minutes, P>0.05]. Morbidity rate was lower in first-aid group than self-aid group in 1st and 3rd month, respectively (2.1% vs. 9.0%, 4.2% vs. 12.4%, both P<0.05). Excellent emergency system and procedure can shorten initial disposal time and out-hospital rescuing time, thus improve patients' prognosis. The education level and health knowledge of patients and their relatives directly affect their mode of arriving hospital and prognosis.

Aortic valve replacement for Libman-Sacks endocarditis

PubMed Central

Keenan, Jack B; Janardhanan, Rajesh; Larsen, Brandon T; Khalpey, Zain

2016-01-01

A 24-year-old man with systemic lupus erythematosus and antiphospholipid syndrome complicated by lupus nephritis presented with acute limb ischaemia secondary to an embolus. Following embolectomy, the patient underwent a transthoracic echocardiogram which revealed a large vegetation on all three cusps of the aortic valve. The patient was taken for an urgent aortic valve replacement with a mechanical valve. Cultures of one cusp remained sterile. Histopathological examination of the remaining two cusps revealed sterile fibrin-rich thrombotic vegetations characteristic of non-bacterial thrombotic endocarditis. PMID:27702929

A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection

PubMed Central

Rossi, Fernanda C.; Angerami, Rodrigo N.; de Paula, Erich V.; Orsi, Fernanda L.; Shang, Dezhi; del Guercio, Vânia M.; Resende, Mariângela R.; Annichino-Bizzacchi, Joyce M.; da Silva, Luiz J.; Zheng, X. Long; Castro, Vagner

2011-01-01

BACKGROUND Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue. PMID:19788513

A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection.

PubMed

Rossi, Fernanda C; Angerami, Rodrigo N; de Paula, Erich V; Orsi, Fernanda L; Shang, Dezhi; del Guercio, Vânia M; Resende, Mariângela R; Annichino-Bizzacchi, Joyce M; da Silva, Luiz J; Zheng, X Long; Castro, Vagner

2010-01-01

Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue.

Purpura fulminans associated with acute West Nile virus encephalitis.

PubMed

Shah, Sheevam; Fite, Laura Paul; Lane, Natalie; Parekh, Palak

2016-02-01

Purpura fulminans is a progressive thrombotic disorder that presents with widespread purpura due to deficiency or dysfunction of protein C or protein S. Lesions present as well-demarcated erythematous macules that progress to irregular areas of hemorrhagic necrosis.West Nile virus is a member of the Flaviviridae family transmitted to humans through the bite of various mosquito species. It manifests as West Nile fever in 25% of those infected and less commonly as neuroinvasive disease. An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data. He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities. Infectious work up revealed positive testing for IgM and IgG antibodies in serum and cerebrospinal fluid leading to the diagnosis of acute West Nile Virus encephalitis. We present this case to describe the rarely reported association of purpura fulminans with West Nile Virus infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.

PubMed

Valgimigli, Marco; Frigoli, Enrico; Leonardi, Sergio; Rothenbühler, Martina; Gagnor, Andrea; Calabrò, Paolo; Garducci, Stefano; Rubartelli, Paolo; Briguori, Carlo; Andò, Giuseppe; Repetto, Alessandra; Limbruno, Ugo; Garbo, Roberto; Sganzerla, Paolo; Russo, Filippo; Lupi, Alessandro; Cortese, Bernardo; Ausiello, Arturo; Ierna, Salvatore; Esposito, Giovanni; Presbitero, Patrizia; Santarelli, Andrea; Sardella, Gennaro; Varbella, Ferdinando; Tresoldi, Simone; de Cesare, Nicoletta; Rigattieri, Stefano; Zingarelli, Antonio; Tosi, Paolo; van 't Hof, Arnoud; Boccuzzi, Giacomo; Omerovic, Elmir; Sabaté, Manel; Heg, Dik; Jüni, Peter; Vranckx, Pascal

2015-09-10

Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin

Pathogenetic role of Factor VII deficiency and thrombosis in cross-reactive material positive patients.

PubMed

Girolami, A; Sambado, L; Bonamigo, E; Ferrari, S; Lombardi, A M

2013-12-01

Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.

Short-term effects of air pollution, markers of endothelial activation, and coagulation to predict major adverse cardiovascular events in patients with acute coronary syndrome: insights from AIRACOS study.

PubMed

Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Rodríguez, Sergio; Avanzas, Pablo; Juarez-Prera, Ruben A

2017-07-01

The aim of this study was to determine whether markers of inflammation and coagulation are associated with short-term particulate matter exposure and predict major adverse cardiovascular events at 360 d in patients with acute coronary syndrome (ACS). We included 307 consecutive patients, and assessed the average concentrations of data on atmospheric pollution in ambient air and meteorological variables from 1 d up to 7 d prior to admission. In patients with ACS, the markers of endothelial activation and coagulation, but not black carbon exposure, are associated with major adverse cardiovascular events at one-year follow-up.

Acute hypoxia stress induced abundant differential expression genes and alternative splicing events in heart of tilapia.

PubMed

Xia, Jun Hong; Li, Hong Lian; Li, Bi Jun; Gu, Xiao Hui; Lin, Hao Ran

2018-01-10

Hypoxia is one of the critical environmental stressors for fish in aquatic environments. Although accumulating evidences indicate that gene expression is regulated by hypoxia stress in fish, how genes undergoing differential gene expression and/or alternative splicing (AS) in response to hypoxia stress in heart are not well understood. Using RNA-seq, we surveyed and detected 289 differential expressed genes (DEG) and 103 genes that undergo differential usage of exons and splice junctions events (DUES) in heart of a hypoxia tolerant fish, Nile tilapia, Oreochromis niloticus following 12h hypoxic treatment. The spatio-temporal expression analysis validated the significant association of differential exon usages in two randomly selected DUES genes (fam162a and ndrg2) in 5 tissues (heart, liver, brain, gill and spleen) sampled at three time points (6h, 12h, and 24h) under acute hypoxia treatment. Functional analysis significantly associated the differential expressed genes with the categories related to energy conservation, protein synthesis and immune response. Different enrichment categories were found between the DEG and DUES dataset. The Isomerase activity, Oxidoreductase activity, Glycolysis and Oxidative stress process were significantly enriched for the DEG gene dataset, but the Structural constituent of ribosome and Structural molecule activity, Ribosomal protein and RNA binding protein were significantly enriched only for the DUES genes. Our comparative transcriptomic analysis reveals abundant stress responsive genes and their differential regulation function in the heart tissues of Nile tilapia under acute hypoxia stress. Our findings will facilitate future investigation on transcriptome complexity and AS regulation during hypoxia stress in fish. Copyright © 2017 Elsevier B.V. All rights reserved.

Experience with Event Timing Does not Alter Emergent Timing: Further Evidence for Robustness of Event and Emergent Timing.

PubMed

Pope, Megan A; Studenka, Breanna E

2018-02-15

Although, event and emergent timings are thought of as mutually exclusive, significant correlations between tapping and circle drawing (Baer, Thibodeau, Gralnick, Li, & Penhune, 2013 ; Studenka, Zelaznik, & Balasubramaniam, 2012 ; Zelaznik & Rosenbaum, 2010 ) suggest that emergent timing may not be as robust as once thought. We aimed to test this hypothesis in both a younger (18-25) and older (55-100) population. Participants performed one block of circle drawing as a baseline, then six blocks of tapping, followed by circle drawing. We examined the use of event timing. Our hypothesis that acute experience with event timing would bias an individual to use event timing during an emergent task was not supported. We, instead, support the robustness of event and emergent timing as independent timing modes.

Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA).

PubMed

Stone, Adam F M; Mendall, Michael A; Kaski, Juan-Carlos; Edger, Tracey M; Risley, Paul; Poloniecki, Jan; Camm, A John; Northfield, Timothy C

2002-09-03

Infection with Helicobacter pylori and Chlamydia pneumoniae is associated with coronary heart disease. We conducted an intervention study using antibiotics against these bacteria in patients with acute coronary syndromes to determine whether antibiotics reduce inflammatory markers and adverse cardiac events. Patients (n=325) admitted with acute myocardial infarction or unstable angina (acute coronary syndromes) were randomized to receive a 1-week course of 1 of 3 treatment regimens: (1) placebo; (2) amoxicillin (500 mg twice daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily); or (3) azithromycin (500 mg once daily), metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily). Serum fibrinogen, white cell count, and high-sensitivity C-reactive protein were measured at study entry and at 1, 3, and 12 months during follow-up. Cardiac death and readmission with acute coronary syndrome were considered clinical end points. Patients were followed for 1 year. C-reactive protein levels were reduced (P=0.03) in unstable angina patients receiving amoxicillin, and fibrinogen was reduced in both patient groups receiving antibiotics (P=0.06). There were 17 cardiac deaths and 71 readmissions with acute coronary syndrome. No difference in frequency or timing of end points was observed between the 2 antibiotic groups. At 12 weeks, there was a 36% reduction in all end points in patients receiving antibiotics compared with placebo (P=0.02). This reduction persisted during the 1-year follow-up. Neither C pneumoniae nor H pylori antibody status was significantly related to response to treatment. Antibiotic treatment significantly reduced adverse cardiac events in patients with acute coronary syndromes, but the effect was independent of H pylori or C pneumoniae seropositivity.

Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies.

PubMed

von Baeyer, Hans

2002-08-01

Current reimbursement policy of health insurance for therapeutic plasmapheresis requires proof of efficacy using the concept of evidence-based medicine. The aim of this paper is to review the outcome of plasmapheresis used to treat thrombotic microangiopathy (TMA)-associated syndromes in the last decade to provide scientific evidence to back up reimbursement applications. The strength of evidence of each reviewed study was assessed using the five levels of evidence criteria as defined by the American Society of Hematology in 1996 for assessment of the treatment of immune thrombocytopenia. The level Experimental indication was added for situations where only case reports or small series supported by pathophysiological reasoning are available. The definitions of evidence used in this paper are as follows: Level I, randomized clinical trial with low rates of error (p < 0.01); Level II, randomized clinical trial with high rates of error (p < 0.05); Level III, nonrandomized studies with concurrent control group; Level IV, nonrandomized studies with historical control group; Level V, case series without a control group or expert opinion; and Experimental, case reports and pathophysiological reasoning. The results of this analysis based on the published data is summarized as follows: The indication of plasmapheresis is assigned to Level IV evidence for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); cancer/chemotherapy-associated TTP/HUS is assigned to Level V evidence; and TTP/HUS refractory to standard plasma exchange and post-bone marrow transplantation TTP/HUS are assigned to Experimental indication. For both subsets, protein A immunoadsorption is reportedly successful. The other TMA-associated syndromes, hemolysis elevated liver enzymes low platelets and HUS in early childhood, are no indication of plasmapheresis. Two randomized clinical trials were performed in order to demonstrate the superiority of plasma exchange/fresh frozen plasma (PEX

The Bangladesh Risk of Acute Vascular Events (BRAVE) Study: objectives and design.

PubMed

Chowdhury, Rajiv; Alam, Dewan S; Fakir, Ismail Ibrahim; Adnan, Sheikh Daud; Naheed, Aliya; Tasmin, Ishrat; Monower, Md Mostafa; Hossain, Farzana; Hossain, Fatema Mahjabin; Rahman, Md Mostafizur; Afrin, Sadia; Roy, Anjan Kumar; Akter, Minara; Sume, Sima Akter; Biswas, Ajoy Kumer; Pennells, Lisa; Surendran, Praveen; Young, Robin D; Spackman, Sarah A; Hasan, Khaled; Harshfield, Eric; Sheikh, Nasir; Houghton, Richard; Saleheen, Danish; Howson, Joanna M M; Butterworth, Adam S; Raqib, Rubhana; Majumder, Abdulla Al Shafi; Danesh, John; Di Angelantonio, Emanuele

2015-07-01

During recent decades, Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases. Coronary heart disease (CHD), with myocardial infarction (MI) as its main manifestation, is a major cause of death in the country. However, there is limited reliable evidence about its determinants in this population. The Bangladesh Risk of Acute Vascular Events (BRAVE) study is an epidemiological bioresource established to examine environmental, genetic, lifestyle and biochemical determinants of CHD among the Bangladeshi population. By early 2015, the ongoing BRAVE study had recruited over 5000 confirmed first-ever MI cases, and over 5000 controls "frequency-matched" by age and sex. For each participant, information has been recorded on demographic factors, lifestyle, socioeconomic, clinical, and anthropometric characteristics. A 12-lead electrocardiogram has been recorded. Biological samples have been collected and stored, including extracted DNA, plasma, serum and whole blood. Additionally, for the 3000 cases and 3000 controls initially recruited, genotyping has been done using the CardioMetabochip+ and the Exome+ arrays. The mean age (standard deviation) of MI cases is 53 (10) years, with 88 % of cases being male and 46 % aged 50 years or younger. The median interval between reported onset of symptoms and hospital admission is 5 h. Initial analyses indicate that Bangladeshis are genetically distinct from major non-South Asian ethnicities, as well as distinct from other South Asian ethnicities. The BRAVE study is well-placed to serve as a powerful resource to investigate current and future hypotheses relating to environmental, biochemical and genetic causes of CHD in an important but under-studied South Asian population.

Maternal organ donation and acute injuries in surviving children.

PubMed

Redelmeier, Donald A; Woodfine, Jason D; Thiruchelvam, Deva; Scales, Damon C

2014-12-01

The purpose of this study is to test whether maternal deceased organ donation is associated with rates of subsequent acute injuries among surviving children after their mother's death. This is a longitudinal cohort analysis of children linked to mothers who died of a catastrophic brain event in Ontario, Canada, between April 1988 and March 2012. Surviving children were distinguished by whether their mother was an organ donor after death. The primary outcome was an acute injury event in surviving children during the year after their mother's death. Surviving children (n=454) had a total of 293 injury events during the year after their mother's death, equivalent to an average of 65 events per 100 children per year and a significant difference comparing children of mothers who were organ donors to children of mothers who were not organ donors (21 vs 82, P<.001). This difference in subsequent injury rates between groups was equal to a 76% relative reduction in risk (95% confidence interval, 62%-85%). Deceased organ donation was associated with a reduction in excess acute injuries among surviving children after their mother's death. An awareness of this positive association provides some reassurance about deceased organ donation programs. Copyright © 2014 Elsevier Inc. All rights reserved.

Aortic valve replacement for Libman-Sacks endocarditis.

PubMed

Keenan, Jack B; Janardhanan, Rajesh; Larsen, Brandon T; Khalpey, Zain

2016-10-04

A 24-year-old man with systemic lupus erythematosus and antiphospholipid syndrome complicated by lupus nephritis presented with acute limb ischaemia secondary to an embolus. Following embolectomy, the patient underwent a transthoracic echocardiogram which revealed a large vegetation on all three cusps of the aortic valve. The patient was taken for an urgent aortic valve replacement with a mechanical valve. Cultures of one cusp remained sterile. Histopathological examination of the remaining two cusps revealed sterile fibrin-rich thrombotic vegetations characteristic of non-bacterial thrombotic endocarditis. 2016 BMJ Publishing Group Ltd.

Accounting for Selection Bias in Studies of Acute Cardiac Events.

PubMed

Banack, Hailey R; Harper, Sam; Kaufman, Jay S

2018-06-01

In cardiovascular research, pre-hospital mortality represents an important potential source of selection bias. Inverse probability of censoring weights are a method to account for this source of bias. The objective of this article is to examine and correct for the influence of selection bias due to pre-hospital mortality on the relationship between cardiovascular risk factors and all-cause mortality after an acute cardiac event. The relationship between the number of cardiovascular disease (CVD) risk factors (0-5; smoking status, diabetes, hypertension, dyslipidemia, and obesity) and all-cause mortality was examined using data from the Atherosclerosis Risk in Communities (ARIC) study. To illustrate the magnitude of selection bias, estimates from an unweighted generalized linear model with a log link and binomial distribution were compared with estimates from an inverse probability of censoring weighted model. In unweighted multivariable analyses the estimated risk ratio for mortality ranged from 1.09 (95% confidence interval [CI], 0.98-1.21) for 1 CVD risk factor to 1.95 (95% CI, 1.41-2.68) for 5 CVD risk factors. In the inverse probability of censoring weights weighted analyses, the risk ratios ranged from 1.14 (95% CI, 0.94-1.39) to 4.23 (95% CI, 2.69-6.66). Estimates from the inverse probability of censoring weighted model were substantially greater than unweighted, adjusted estimates across all risk factor categories. This shows the magnitude of selection bias due to pre-hospital mortality and effect on estimates of the effect of CVD risk factors on mortality. Moreover, the results highlight the utility of using this method to address a common form of bias in cardiovascular research. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study

PubMed Central

Gronich, Naomi; Lavi, Idit; Rennert, Gad

2011-01-01

Background: Combined oral contraceptives are a common method of contraception, but they carry a risk of venous and arterial thrombosis. We assessed whether use of drospirenone was associated with an increase in thrombotic risk relative to third-generation combined oral contraceptives. Methods: Using computerized records of the largest health care provider in Israel, we identified all women aged 12 to 50 years for whom combined oral contraceptives had been dispensed between Jan. 1, 2002, and Dec. 31, 2008. We followed the cohort until 2009. We used Poisson regression models to estimate the crude and adjusted rate ratios for risk factors for venous thrombotic events (specifically deep vein thrombosis and pulmonary embolism) and arterial thromboic events (specifically transient ischemic attack and cerebrovascular accident). We performed multivariable analyses to compare types of contraceptives, with adjustment for the various risk factors. Results: We identified a total of 1017 (0.24%) venous and arterial thrombotic events among 431 223 use episodes during 819 749 woman-years of follow-up (6.33 venous events and 6.10 arterial events per 10 000 woman-years). In a multivariable model, use of drospirenone carried an increased risk of venous thrombotic events, relative to both third-generation combined oral contraceptives (rate ratio [RR] 1.43, 95% confidence interval [CI] 1.15–1.78) and second-generation combined oral contraceptives (RR 1.65, 95% CI 1.02–2.65). There was no increase in the risk of arterial thrombosis with drospirenone. Interpretation: Use of drospirenone-containing oral contraceptives was associated with an increased risk of deep vein thrombosis and pulmonary embolism, but not transient ischemic attack or cerebrovascular attack, relative to second- and third-generation combined oral contraceptives. PMID:22065352