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Thromboembolism
Kinds of Thromboembolism Terms modified by Thromboembolism Selected AbstractsEFFECT OF PARAPROSTHETIC MODERETE TO SEVERE MITRAL REGURGITATION ON EMBOLIC EVENTS IN PATIENTS WITH PROSTHETIC MITRAL VALVESECHOCARDIOGRAPHY, Issue 5 2004C. Cevik Thromboembolism is the major chronic risk for patients with mechanical prosthetic heart valves. Although optimal oral anticoagulantion is the key determinant for embolic events (EE) in these patients; other factors also contribute to this complication. We studied the prevalence and determinants of embolic events in patients with mitral prosthetic heart valves undergoing transesophageal echocardiography (TEE). 210 patients (86 male and 124 female, mean age 45.1 +/, 9.6 years) underwent a TEE study for evaluation of prosthetic valve functions. Clinical and TEE findings of the patients were as follows: Atrial fibrillation in 132 (%62) patients, prosthetic valve thrombus in 55 (%26) suboptimal INR (INR < 1.8) in 61 (%29) pts, left atrial spontenous echocardiographic contrast (SEC) in 31 (%14) patients, paraprosthetic moderete-severe mitral regurgitation (MR) in 28 (%13), left atrial (LA) and/or left atrial appendix (LAA) thrombus in 41 (%19), LA and/or LAA outflow velocities <0.25 m/sn in 21 patiens (%10), left atrial diameter >6 cm in 47 (%22). 72 patients had a history of EE in the previous 6 months (%34). In no patients were there any EE in the presence of paraprosthetic moderate to severe MR. Both with univariate and multivariate analysis presence of prosthetic valve and LA and/or LAA thrombus, absence of paraprosthetic moderete-severe MR, suboptimal INR, atrial fibrillation were found to be independent predictors for embolic events. Conclusions: Although the presence of prosthetic valve and LA and/or LAA thrombus, suboptimal INR, and AF predict EE, clinical and echocardiographic data support the protective effect of paraprosthetic moderate to severe MR against EE in pts with mitral prosthetic valves. [source] Thromboembolism in a patient with transient eosinophilia and thrombocytopeniaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2000Y. Sherer Summary A 24-year-old woman with an unremarkable medical history who developed bilateral deep venous thrombosis and pulmonary emboli is presented. Associated findings were severe eosinophilia and moderate thrombocytopenia. Since the major acquired and hereditary thrombogenic disorders were ruled out in this case (including antiphospholipid syndrome and heparin-induced thrombocytopenia), we believe that the severe eosinophilia per se could be the pro-coagulant factor leading to thrombosis and embolism in our patient. The role of eosinophilia in thrombosis is discussed. [source] Increased Levels of Tissue Plasminogen Activator Antigen and Factor VIII Activity in Nonvalvular Atrial Fibrillation: Relation to Predictors of ThromboembolismJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2001TZUNG-DAU WANG M.D. Atrial Fibrillation and Hypercoagulability.Introduction: Given that nonvalvular atrial fibrillation (AF)-associated stroke can be either cardioembolic or atherothrombotic, we investigated the relationships between nonvalvular AF and hemostatic factors reflecting intrinsic thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA] antigen, plasminogen activator inhibitor-1, and factor VIII activity). We also evaluated the clinical applicability of these hemostatic factors by examining whether AF subjects with established clinical or echocardiographic predictors of thromboembolism had higher levels of these factors. Methods and Results: Of the 3,212 participants of a Chinese population-based study, 53 subjects (1.7%) with AF were identified. Among the hemostatic factors measured, t-PA antigen (median 12.8 vs 8.1 ng/mL; P < 0.01) and factor VIII activity (median 155% vs 133%; P < 0.05) were significantly higher in AF subjects after adjustment for age and sex. In multivariate analysis, features independently associated with t-PA antigen levels were AF, age, sex, body mass index, systolic blood pressure, total cholesterol, triglycerides, and left ventricular systolic dysfunction. Features independently associated with factor VIII activity levels included AF, age, and total cholesterol. Levels of both t-PA antigen and factor VIII activity were primarily elevated in AF subjects with predictors of thromboembolism (age > 75 years, hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF subjects with no thromboembolic predictors, plasma levels of hemostatic factors examined were similar to those without AF. Conclusion: We demonstrated that nonvalvular AF was independently associated with increased peripheral levels of t-PA antigen and factor VIII activity. Levels of both hemostatic factors were primarily elevated in AF subjects with predictors of thromboembolism. Whether these hemostatic factors are independently predictive of future thromboembolic events in AF patients requires further investigation. [source] Thromboembolism and Rebleeding Paradox in Stent-Assisted Embolization for Intracranial AneurysmsJOURNAL OF NEUROIMAGING, Issue 2 2010Ramachandra P. Tummula MD No abstract is available for this article. [source] Factor V Leiden as a Common Genetic Risk Factor for Venous ThromboembolismJOURNAL OF NURSING SCHOLARSHIP, Issue 1 2006McDonald K. Horne III Purpose: To increase nurses' knowledge of the Factor V Leiden (FVL) genetic trait for venous thromboembolism. Organizing Framework: An overview of the history, prevalence, and predisposition of the FVL genetic mutation, including who should be tested and how and in what circumstances people with FVL should be treated. Findings: FVL is the most commonly recognized genetic trait associated with venous thrombosis. It is found predominantly in Caucasian populations. Biochemically it causes "activated protein C resistance (APCR)." The decision to test for FVL depends on whether the information gained will potentially improve the health care of the person or family. For people who have had deep venous thrombosis, testing for FVL will likely not alter treatment approaches. Currently the advantage for testing is primarily limited to asymptomatic family members who carry FVL and who have had deep vein thrombosis. Close relatives who also carry the mutated gene might benefit from prophylactic anticoagulation when their risk of thrombosis is increased by temporary factors such as surgery. Conclusions: Nurses are in a unique position to provide accurate information and counseling when patients and their family members are presented with the results of thrombophilia testing. [source] Thromboxane and prostacyclin biosynthesis in heart failure of ischemic origin: effects of disease severity and aspirin treatmentJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2010F. SANTILLI Summary.,Background: Thromboembolism is a relatively common complication of chronic heart failure (HF) and the place of antiplatelet therapy is uncertain. Objectives: We characterized the rate of thromboxane and prostacyclin biosynthesis in chronic HF of ischemic origin, with the aim of separating the influence of HF on platelet activation from that of the underlying ischemic heart disease (IHD). Patients and Methods: We compared urinary 11-dehydro-thromboxane (TX)B2, 2,3 dinor 6-keto-PGF1,, 8-iso-prostaglandin (PG)F2,, and plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), asymmetric dimethylarginine (ADMA), and soluble CD40 ligand (sCD40L), in 84 patients with HF secondary to IHD, 61 patients with IHD without HF and 42 healthy subjects. Results: HF patients not on aspirin had significantly higher urinary 11-dehydro-TXB2 as compared with healthy subjects (P < 0.0001) and IHD patients not on aspirin (P = 0.028). They also showed significantly higher 8-iso-PGF2, (P =,0.018), NT-pro-BNP (P = 0.021) and ADMA (P < 0.0001) than IHD patients not on aspirin. HF patients on low-dose aspirin had significantly lower 11-dehydro-TXB2 (P < 0.0001), sCD40L (P = 0.007) and 2,3-dinor-6-keto-PGF1, (P = 0.005) than HF patients not treated with aspirin. HF patients in NYHA classes III and IV had significantly higher urinary 11-dehydro-TXB2 than patients in classes I and II, independently of aspirin treatment (P < 0.05). On multiple linear regression analysis, higher NT-pro-BNP levels, lack of aspirin therapy and sCD40L, predicted 11-dehydro-TXB2 excretion rate in HF patients (R2 = 0.771). Conclusions: Persistent platelet activation characterizes HF patients. This phenomenon is related to disease severity and is largely suppressable by low-dose aspirin. The homeostatic increase in prostacyclin biosynthesis is impaired, possibly contributing to enhanced thrombotic risk in this setting. [source] Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2007A. A. KHORANA [source] The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatmentJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2005V. DE STEFANO Summary.,Background:,Thromboembolism can occur during acute leukemia, especially acute lymphoid leukemia (ALL) treated with l -asparaginase. Yet, most reports are anecdotical and scarce data are available on the risk of thrombosis in acute myeloid leukemia (AML). Objectives:,To evaluate the risk of thrombosis in patients with acute leukemia. Patients and methods:,Three-hundred and seventy-nine consecutive adult patients with newly diagnosed acute leukemia were recruited in an observational cohort study conducted from January 1994 to December 2003. Diagnosis was ALL in 69 patients, acute promyelocytic leukemia (APL; FAB subtype M3) in 31, and non-M3 AML in 279. All first or recurrent symptomatic thromboembolic events objectively diagnosed were recorded. Results:,Twenty-four patients of the overall 379 (6.3%; 95% CI 4.1%,9.2%) had a first thrombosis, venous in 80% of the cases and arterial in 20%. At diagnosis, thrombosis was a presenting manifestation in 13 cases (3.4% of the whole cohort): 1.4% in ALL, 9.6% in APL, and 3.2% in non-M3 AML patients. Follow-up was carried out on 343 patients without thrombosis at diagnosis and further 11 thrombotic events (3.2%) were recorded. At 6 months from diagnosis, the cumulative incidence of thrombosis was 10.6% in ALL, 8.4% in APL, and 1.7% in non-M3 AML patients. The patients who received l -asparaginase had a 4.9-fold increased risk of thrombosis in comparison with those who did not (95% CI 1.5,16.0). The fatality rate due to thrombosis was 0.8%. Conclusions:,In patients with acute leukemia, the risk of thrombosis is not negligible. Thombosis can be a presenting symptom at diagnosis in a significant portion of cases with APL (9.6%) and non-M3 AML (3.2%); a similar rate of thrombosis can occur during the subsequent course of the disease. The incidence of symptomatic thrombosis at diagnosis is relatively low in ALL patients (1.4%), but is significantly increased by further treatment up to 10.6%. Strategies of antithrombotic prophylaxis should be investigated in this setting. [source] Could Prolonged Air Travel Be Causally Associated with Subclavian Vein Thromboembolism?JOURNAL OF TRAVEL MEDICINE, Issue 1 2002Theodore Teruya Background: Air travel associated with venous thromboembolism has recently achieved public awareness due to intense media coverage. The interest has focused on deep vein thrombosis (DVT) of the lower limbs with pulmonary embolism. The World Health Organization (WHO) is planning several international multicenter trials to study the problem and, if it exists, try to find a means for prevention. Methods: This is a case presentation of acute venous thromboembolism of the upper limbs associated with long-haul flights. Five patients were admitted to Straub Hospital in Honolulu after 5 to 10 hours' flight. Results: Patient 1 had a previous shoulder injury with DVT; patient 2 had chronic atrial fibrillation; patients 3 and 5 had clavicular fractures; and patient 4 had a subclavian vein compression. Conclusion: It is not possible to draw any conclusions about the association between air flights and subclavian vein thrombosis from this small retrospective case study. Our objective was to indicate the possibility of such a relationship. [source] Retrospective Study of Streptokinase Administration in 46 Cats with Arterial ThromboembolismJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2000Kari E. Moore DVM Summary A retrospective evaluation was performed on 46 cats with arterial thromboembolism (ATE) that were treated with streptokinase (SK). Significant heart disease was diagnosed in 45/46 cats, and 21/46 cats had congestive heart failure. Variable dosing schemes of streptokinase were administered within 1,20 hours following the onset of clinical signs (median = 5.5 hours). There was no difference between survivors (S) and non-survivors (NS), based on time of administration of SK after onset of clinical signs. Twenty-five (54%) of the cats had return of pulses within 2,24 hours of treatment. Fourteen (30%) of the cats had return of motor function between 9 hours and 6 days. Fifteen of the cats (33%) were discharged from the hospital, 18 (39%) died in the hospital, and 13 (28%) cats were euthanized due to complications or poor response to treatment. Four of 5 cats (80%) with single limb dysfunction survived to hospital discharge. Life threatening hyperkalemia was diagnosed in 16 cats (35%) after SK administration. Hyperkalemia was more likely to occur with the longer duration of SK infusion. Eleven cats (24%) developed clinical signs of bleeding following SK administration and 3 of these cats required a blood transfusion. Laboratory testing documented coagulopathy following SK administration in 11 out of 17 cats tested. Hypothermia and azotemia prior to SK administration and the development of hyperkalemia were negatively associated with survival. [source] Use of Rheolytic Thrombectomy in the Treatment of Feline Distal Aortic ThromboembolismJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2006S. Brent Reimer The purpose of this prospective clinical trial was to evaluate the safety and efficacy of a commercially available rheolytic thrombectomy system in the treatment of naturally occurring feline aortic thromboembolic disease. All 6 cats enrolled in the investigation were affected at the level of the distal aorta and had signs of the disease affecting both pelvic limbs. Cats were anesthetized and an arteriotomy was performed on 1 carotid artery to gain access to the arterial system. Selective arterial angiography was used to confirm the presence of thromboembolic disease. The thrombectomy system was advanced to the level of the thrombus using fluoroscopic guidance. Repeat angiography was used intermittently to assess progress of thromboembolus dissolution throughout the procedure. The use of the rheolytic thrombectomy system resulted in successful thrombus dissolution in 5 of 6 cats. Three of 6 cats survived to discharge. Both of these results compare favorably with conventional therapies used in the treatment of this disease. Feline distal aortic thromboembolism is a frustrating disease that warrants a guarded to poor prognosis. Rheolytic thrombectomy may provide veterinarians with an alternative therapy in the treatment of thromboembolic diseases, including feline distal aortic thromboembolism. [source] Prognostic Factors for Mortality and Thromboembolism in Canine Immune-Mediated Hemolytic Anemia: A Retrospective Study of 72 DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2002Anthony P. Carr Medical records of 72 dogs diagnosed with immune-mediated hemolytic anemia (IMHA) were reviewed to find risk factors for the disease, for mortality, and for thromboembolism. Coagulation data of 32 patients were evaluated for mortality or thromboembolism risk factors. Cocker Spaniels were at increased risk for IMHA (P= .012). Timing of vaccination was not associated with development of IMHA. PCV ranged from 5 to 33%, with a mean of 16 ± 5%. Autoagglutination was present in 42% of the dogs. Platelet counts (n = 60) varied from 3,000 to 793,000/,L (mean, 160,117 ± 133,571; median, 144,000). Thrombocytopenia (platelet count, <200,000/,L) was present in 70% of the dogs, with severe thrombocytopenia (platelet count, <50,000/,L) being present in 22%. One-step prothrombin time (OSPT) was prolonged in 28% of the dogs tested, and activated partial thromboplastin time (APTT) was prolonged in 47% of the dogs tested. Fibrin(ogen) degradation products (FDPs) were detected in 16 of 28 dogs tested (57%). Disseminated intravascular coagulation (DIC) was diagnosed in 10 of 31 (32%) dogs and was suspected in 8 dogs. Thromboemboli were found in 20 of 25 dogs given postmortem examinations. Mortality rate was 58%. Thrombocytopenia (P= .008) and serum bilirubin concentration of >5 mg/dL (P= .015) were risk factors for mortality, and hypoalbuminemia approached significance (P= .053). Severe thrombocytopenia (P= .046), serum bilirubin concentration of >5 mg/dL (P= .038), and hypoalbuminemia (P= .016) were risk factors for thromboembolism. On evaluation of continuous data, decreased platelet count (P= .057), increased bilirubin (P= .062), and decreased albumin (P= .054) approached significance for decreased survival. A higher risk for thrombosis was found with increased alkaline phosphatase (ALKP) (P= .042), increased bilirubin (P= .047), and decreased albumin (P= .012). [source] Plasma Homocysteine, B Vitamins, and Amino Acid Concentrations in Cats with Cardiomyopathy and Arterial ThromboembolismJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2000M.A. McMichael Arterial thromboembolism (ATE) is a common complication of cats with cardiomyopathy (CM), but little is known about the pathophysiology of ATE. In people, high plasma concentrations of homocysteine and low B vitamin concentrations are risk factors for peripheral vascular disease. In addition, low plasma arginine concentrations have been linked to endothelial dysfunction. The purpose of this study was to compare concentrations of homocysteine, B vitamins, and amino acids in plasma of normal cats to those of cats with CM and ATE. Plasma concentrations of homocysteine, vitamin B6, vitamin B12, folate, and amino acids were measured in 29 healthy cats, 27 cats with CM alone, and 28 cats with both CM and ATE. No differences were found between groups in homocysteine or folate. Mean vitamin B12 concentration (mean ± standard deviation) was lower in cats with ATE (866 ± 367 pg/mL) and cats with CM (939 ± 389 pg/mL) compared with healthy controls (1,650 ± 700 pg/mL; P < .001). Mean vitamin B6 concentration was lower in cats with ATE (3,247 ± 1,215 pmol/mL) and cats with CM (3,200 ± 906 pmol/mL) compared with healthy control animals (4,380 ± 1,302 pmol/mL; P= .005). Plasma arginine concentrations were lower in cats with ATE (75 ± 33 nmol/mL) compared with cats with CM (106 ± 25 nmol/mL) and healthy control animals (96 ± 25 nmol/ mL; P < .001). Vitamin B12 concentration was significantly correlated with left atrial size. We interpret the results of this study to suggest that vitamin B12 and arginine may play a role in CM and ATE of cats. [source] Thromboembolism in children with sarcomaPEDIATRIC BLOOD & CANCER, Issue 2 2007Uma Athale MD Abstract Background Thromboembolism (TE) is a common complication and cause of death in adults with cancer. Cancer has been identified as a major risk factor in children with TE. However, the information regarding the epidemiology of TE in children with cancer, especially in association with childhood solid tumors, is scant. Objective To define the prevalence and epidemiology of TE in children with sarcoma. Procedure Hospital records of children ,18 years of age with sarcoma diagnosed and treated at McMaster Children's Hospital during January 1990 to December 2005 were reviewed for demographic details, details of diagnosis and therapy for sarcoma, and details of diagnosis and management of TE. Statistical analysis was performed using Fisher's exact t -test. Results Ten of 70 (14.3%; 95% CI; 7.1, 24.7) patients with sarcoma developed symptomatic TE. Patients with CVL-dysfunction (n,=,9) were at significantly higher risk for symptomatic TE compared to those without CVL dysfunction (n,=,61) (55.5 vs. 8.2%; P,=,0.002, 95% CI; 14.2, 80.5). Patients with pulmonary disease (n,=,23) had higher prevalence of TE compared to those without pulmonary disease (n,=,47) (26 vs.8.5%; P,=,0.07, 95% CI; ,2.06, 37.2). Older patients, patients with metastatic disease and those with Ewing sarcoma had higher prevalence of TE. Conclusions TE is a significant complication in children with sarcoma. Over 50% of patients with CVL dysfunction had symptomatic TE; such patients may warrant careful evaluation for associated TE. Large prospective studies are needed to define the epidemiology and identify risk factors predisposing to TE in children with sarcoma. Pediatr Blood Cancer 2007;49:171,176. © 2006 Wiley-Liss, Inc. [source] Thromboembolism of the leg following prophylactic balloon occlusion of the uterine arteriesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 9 2009S Chouliaras No abstract is available for this article. [source] Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute protocols: effect of age and risk stratification of diseaseBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2005Uma H. Athale Summary Children with acute lymphoblastic leukaemia (ALL) are at increased risk for thromboembolism (TE). Identification of a susceptible population is crucial for effective thromboprophylaxis. However, the risk factors for ALL-associated TE are unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to increase the incidence of TE. Dana-Farber Cancer Institute (DFCI)-ALL protocols use a combination of ASP and steroids during the postinduction intensification phase when high-risk (HR) patients receive thrice the steroid-dose given to standard-risk (SR) patients. We studied prospectively assembled cohorts of children treated on two consecutive DFCI-ALL protocols to define the risk factors for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight (seven HR) during intensification. Seven (44%) of 16 older patients (,10 years) compared with three of 75 (4%) younger patients developed TE (P < 0·0001). Nine of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0·0006). Gender, ALL-immunophenotype, steroid-type or ASP dosing schedule did not alter the risk but older age and HR-disease were factors predisposing to TE associated with DFCI-ALL protocols. Age-related risk may partly reflect the effect of ALL-risk stratification. Higher dose steroids combined with ASP may lead to an increased risk of TE in HR patients. [source] Role of Transthoracic Echocardiography in Atrial FibrillationECHOCARDIOGRAPHY, Issue 4 2000RICHARD W. ASINGER M.D. Atrial fibrillation is a major clinical problem that is predicted to be encountered more frequently as the population ages. The clinical management of atrial fibrillation has become increasingly complex as new therapies and strategies have become available for ventricular rate control, conversion to sinus rhythm, maintenance of sinus rhythm, and prevention of thromboembolism. Clinical and transthoracic echocardiographic features are important in determining etiology and directing therapy for atrial fibrillation. Left atrial size, left ventricular wall thickness, and left ventricular function have independent predictive value for determining the risk of developing atrial fibrillation. Left atrial size may have predictive value in determining the success of cardioversion and maintaining sinus rhythm in selected clinical settings but has less value in the most frequently encountered group, patients with nonvalvular atrial fibrillation, in whom the duration of atrial fibrillation is the most important feature. When selecting pharmacological agents to control ventricular rate, convert to sinus rhythm, and maintain normal sinus rhythm, transthoracic echocardiography (TTE) allows noninvasive evaluation of left ventricular function and hence guides management. The combination of clinical and transthoracic echocardiographic features also allows risk stratification for thromboembolism and hemorrhagic complications in atrial fibrillation. High-risk clinical features for thromboembolism supported by epidemiological observations, results of randomized clinical trials, and meta-analyses include rheumatic valvular heart disease, prior thromboembolism, congestive heart failure, hypertension, older (> 75 years old) women, and diabetes. Small series of cases also suggest those with hyperthyroidism and hypertrophic cardiomyopathy are at high risk. TTE plays a unique role in confirming or discovering high-risk features such as rheumatic valvular disease, hypertrophic cardiomyopathy, and decreased left ventricular function. Validation of the risk stratification scheme used in the Stroke Prevention in Atrial Fibrillation-III trial is welcomed by clinicians who are faced daily with balancing the benefit and risks of anticoagulation to prevent thromboembolism inpatients with atrial fibrillation. [source] Transesophageal Echocardiography Risk Factors for Stroke in Nonvalvular Atrial FibrillationECHOCARDIOGRAPHY, Issue 4 2000F.R.C.P.C., SUSAN M. FAGAN M.D. Atrial fibrillation is a common arrhythmia, particularly in the older age groups. It confers an increased risk of thromboembolism to these patients, and multiple clinical risk factors have been identified to be useful in predicting the risks of thromboembolic events. Recent studies have evaluated the role of transesophageal echocardiography (TEE) in the evaluation of patients with atrial fibrillation. The purpose of this review is to evaluate the significance of transesophageal echocardiography findings in the prediction of thromboembolic events, particularly stroke, in patients with nonvalvular atrial fibrillation, with an emphasis on recently reported prospective studies. Aortic plaque and left atrial appendage abnormalities are identified as independent predictors of thromboembolic events. Although they are associated with clinical events, they also have independent incremental prognostic values. Other transesophageal echocardiographic findings, such as patent foramen ovale and atrial septal aneurysm, have not been found to be predictors of thromboembolic events in this patient group. Thus, TEE is a useful tool in stratifying patients with nonvalvular atrial fibrillation into different risk groups in terms of thromboembolic events, and it will likely play an important role in future studies to assess new treatment strategies in high-risk patients with atrial fibrillation. [source] Current concepts for the prevention of venous thromboembolismEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005P. Bramlage Abstract Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide and the annual incidence of VTE is 1 per 1000. The individual risk for venous thromboembolism may be substantially higher and is determined by expositional and dispositional factors. Unfractionated heparin and warfarin have been the mainstays for the prevention of VTE until the early 1980s. Bleeding complications and side effects limited the use of these agents and subsequently low molecular weight heparins (LMWH) were introduced into clinical practice. These are most commonly used for the prophylaxis and treatment of VTE today. In the last decade, the pace of development of further anticoagulants has accelerated with the introduction of new treatment regimens and new substances. In this context, novel drugs directed against clotting factor Xa (such as fondaparinux) and direct thrombin inhibitors (such as melagatran/ximelagatran) have been developed. Fondaparinux shows a favourable efficacy/safety profile and has been documented to be cost-effective compared to enoxaparin in the US and the UK. [source] Rivaroxaban , an oral, direct Factor Xa inhibitor , lessons from a broad clinical study programmeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Sylvia Haas Abstract Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside. [source] A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2008Marie Von Lilienfeld-Toal Abstract Thalidomide monotherapy in relapsed/refractory multiple myeloma (MM) has a response rate of 30%. The combination of thalidomide with dexamethasone (Thal/Dex) is expected to improve responses, but it is unknown if the combination increases the rate of adverse events. Here, we conducted a systematic review of studies evaluating Thal/Dex in relapsed/refractory MM. Twelve studies were included, comprising 451 patients. The response rate (CR and PR) was 46% (95% CI 42,51%). Therapy-related toxicity was comparable to thalidomide monotherapy and included somnolence (26%, 95% CI 22,31%), constipation (37%, 95% CI 32,42%) and peripheral neuropathy (27%, 95% CI 23,32%). Only venous thromboembolism appeared to occur more often with Thal/Dex (5%, 95% CI 3,8%). Thus, using Thal/Dex results in an improved response rate in relapsed/refractory MM, with a toxicity rate comparable to thalidomide monotherapy. [source] Appraisal of current vitamin K dosing algorithms for the reversal of over-anticoagulation with warfarin: the need for a more tailored dosing regimenEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Elizabeth A. Sconce Abstract:, Warfarin is the most commonly prescribed oral anticoagulant in the UK for the treatment and prevention of thromboembolic disorders. Vitamin K administration is an effective way of reversing excessive anticoagulation. Over-anticoagulated patients present with a wide range of international normalized ratio (INR) values and may respond differently to a fixed dose of vitamin K. Current dosing algorithms for vitamin K administration in the non-urgent treatment of over-anticoagulation do not take this variability in response into account. Consequently, over a third of over-anticoagulated patients still remain outside their target INR 24 h after treatment. Such patients are therefore prone to either haemorrhage (if the patient is still over-anticoagulated) or thromboembolism (if the INR reversal is over-corrected). A number of factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose and CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the rate and extent of INR reversal. There is a need for a more individualized approach to the reversal of over-anticoagulation in asymptomatic or mildly haemorrhagic patients in order to improve the safety of warfarin therapy. [source] Etiology of thrombocytopenia in all patients treated with heparin productsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2005Damian A. Laber Abstract:,Purpose:,To characterize the cause of thrombocytopenia in all patients treated with heparin products, to determine the incidence of heparin-induced thrombocytopenia (HIT) in unselected hospitalized patients, and to have modern data of the magnitude of this problem. Methods:,Retrospective hospital-based cohort study. During a random 2-month period, we reviewed the medical records of all patients treated with heparin agents, screened them for thrombocytopenia, and determined the cause of it. Results:,Out of 674 patients who received heparin products, 110 (16%) had thrombocytopenia. The most common causes included cancer chemotherapy, surgery, sepsis, and medications. Three patients met the clinical criteria for HIT. One had antibodies for heparin-platelet factor-4, and received a direct thrombin inhibitor. The other two individuals had a clinical syndrome that resembled immune HIT, but were not tested for HIT antibodies. One suffered a thrombotic episode that led to the death of her fetus. The other died of a possible thromboembolism. Conclusions:,This study provides evidence-based data for the differential diagnosis of thrombocytopenia after treatment with heparin products. Our findings suggest that increased awareness of the HIT syndrome might reduce morbidity and mortality. Patients exposed to heparin products, who develop thrombocytopenia, should not be overlooked. [source] Neurologic manifestations of ulcerative colitisEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2007R. Scheid Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS-manifestations, similarities between UC-associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome. [source] Thrombin-mediated impairment of fibroblast growth factor-2 activityFEBS JOURNAL, Issue 12 2009Pierangela Totta Thrombin generation increases in several pathological conditions, including cancer, thromboembolism, diabetes and myeloproliferative syndromes. During tumor development, thrombin levels increase along with several other molecules, including cytokines and angiogenic factors. Under such conditions, it is reasonable to predict that thrombin may recognize new low-affinity substrates that usually are not recognized under low-expression levels conditions. In the present study, we hypothesized that fibroblast growth factor (FGF)-2 may be cleaved by thrombin and that such action may lead to an impairment of its biological activity. The evidence collected in the present study indicates that FGF-2-induced proliferation and chemotaxis/invasion of SK-MEL-110 human melanoma cells were significantly reduced when FGF-2 was pre-incubated with active thrombin. The inhibition of proliferation was not influenced by heparin. Phe-Pro-Arg-chloromethyl ketone, a specific inhibitor of the enzymatic activity of thrombin, abolished the thrombin-induced observed effects. Accordingly, both FGF-2-binding to cell membranes as well as FGF-2-induced extracellular signal-regulated kinase phosphorylation were decreased in the presence of thrombin. Finally, HPLC analyses demonstrated that FGF-2 is cleaved by thrombin at the peptide bond between residues Arg42 and Ile43 of the mature human FGF-2 sequence. The apparent kcat/Km of FGF-2 hydrolysis was 1.1 × 104 m,1·s,1, which is comparable to other known low-affinity thrombin substrates. Taken together, these results demonstrate that thrombin digests FGF-2 at the site Arg42-Ile43 and impairs FGF-2 activity in vitro, indicating that FGF-2 is a novel thrombin substrate. [source] Metalloproteinase-9 in circulating monocytes in pulmonary hypertensionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2006Caroline Cantini-Salignac Abstract The role of matrix metalloproteinases (MMPs) in pulmonary hypertension (PH) is complex as MMPs are involved in both the vascular and cardiac remodelling associated with PH. To gain insight into this problem, monocytes were isolated from pulmonary arterial blood in patients suffering from PH, related to chronic obstructive pulmonary disease (n = 6), chronic pulmonary thromboembolism (n = 3) or pulmonary arterial hypertension (n = 8). The severity of PH was associated with decreases in cardiac index (CI) and mixed venous blood oxygen saturation (SO2), and an increase in right atrial pressure (). Monocyte pro-MMP-9 content (zymography) was positively correlated with SO2 (r = 0.73, P < 0.05) and CI (r = 0.66, P < 0.05), and negatively with (r = 0.54, P < 0.05); there was no significant correlation with pulmonary vascular resistance. In conclusion, the pro-MMP-9 content of circulating monocytes was lower in the more severe forms of PH which showed heart failure suggesting that such MMP enzymatic activity reflects heart failure following pulmonary vascular and myocardial remodelling in PH. [source] An overview of the data presented at the International Society on Thrombosis and Haemostasis Congress, where results were reported of three major clinical trials on prevention, management and prophylaxis in patients at risk of venous thromboembolism in the hospital care setting.FUTURE PRESCRIBER, Issue 3 2007Rhonda Siddall [source] Fatal postoperative pulmonary embolism in mild haemophiliaHAEMOPHILIA, Issue 2 2006J. H. BUTCHER Summary., The use of thromboprophylaxis in patients with haemophilia receiving factor replacement is often not considered necessary, but remains an area of debate. In this report we describe a patient with mild haemophilia A, who underwent major pelvic surgery. He had several underlying risk factors associated with the development of thromboembolism, and ultimately died as a direct consequence of multiple pulmonary emboli. The need for thromboprophylaxis and the risk balance ratio should always be considered in patients with bleeding disorders if they fall into what would otherwise be high-risk category for hospital acquired venous thromboembolism. [source] Estradiol enhances long term potentiation in hippocampal slices from aged apoE4-TR miceHIPPOCAMPUS, Issue 12 2007Sung Hwan Yun Abstract Hormone replacement therapy to treat or prevent Alzheimer Disease (AD) in postmenopausal women is controversial because it may pose other health risks such as cancer and thromboembolism. ApoE status is thought to influence the nootropic efficacy of hormone therapy, but findings are neither consistent nor well understood. We used a known in vitro memory model (long-term potentiation, LTP) in aged (24,27 month) female targeted replacement mice expressing human apoE3 or E4 to compare the effects of exogenous estradiol. Recording medial perforant path evoked field potentials in dentate gyrus of hippocampal slices, we found that both strains exhibited comparable basal synaptic transmission as assessed by input/output functions and paired pulse depression, and that these measures were not affected by estradiol. Vehicle-treated groups from both strains showed comparable LTP. Estradiol had no effect on LTP in apoE3-TR, but selectively increased LTP magnitude in apoE4-TR. The estradiol induced enhancement of LTP in aged female apoE4-TR is consistent with recent clinical observations that estrogen replacement decreases AD risk in some women with apoE4. Elucidating the mechanism of this selective enhancement may lead to more informed treatment decisions as well as to the development of safer alternatives to hormone therapy. © 2007 Wiley-Liss, Inc. [source] An investigation of the association of the prothrombin G20210A gene mutation and inflammatory bowel disease: Factor II and IBDINFLAMMATORY BOWEL DISEASES, Issue 2 2001Neil Haslam Abstract Background A thrombotic etiology for inflammatory bowel disease (IBD) has been proposed as a result of its association with thromboembolic complications, smoking, the oral contraceptive pill, and the response of ulcerative colitis (UC) patients to heparin. We have previously demonstrated an increased prevalence of the Factor V Leiden mutation in UC and wished to investigate the frequency of the recently discovered prothrombin G20210A gene mutation in IBD. The aim of the study was to investigate the hypothesis that the prothrombic state associated with the prothrombin G20210A gene mutation is involved in the etiology of IBD. Patients and Methods A prospective cohort study of patients attending the Bristol Royal Infirmary and Gloucestershire Royal Hospital's IBD clinics was performed. Thirty-nine patients with IBD (24 with Crohn's disease and 15 with UC) and 100 historical controls were screened for the presence of the prothrombin gene mutation using a heteroduplex-based polymerase chain reaction technique. None of the patients with IBD had a personal history of thromboembolism, while three of them had a family history. Results No IBD patients had the prothrombin gene mutation compared with four (4%) controls (allelic frequency 2%). Conclusion There does not appear to be an association of the prothrombin gene mutation with IBD and therefore it is unlikely to be involved in the etiology of IBD. 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