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Thrombotic Risk (thrombotic + risk)
Selected AbstractsAGEING, OESTROGEN, PLATELETS AND THROMBOTIC RISKCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007Virginia M Miller SUMMARY 1Adverse thrombotic cardiovascular events increase in women coincident with the onset of menopause. 2Age past menopause may be an important variable in defining the benefit/risk of hormone treatments. 3Few studies have examined hormonal status as a variable of ageing using a polygenomic approach of both humoral and cellular components of the coagulation system. 4Longitudinal studies of a global set of platelet functions that define procoagulant activity (i.e. adhesion, aggregation, secretion and thrombin production) in individuals with documented hormonal status are needed to better understand how hormonal changes associated with ageing impact thrombotic risk. [source] Diagnosis, clinical features and molecular assessment of the dysfibrinogenaemiasHAEMOPHILIA, Issue 5 2008M. HILL Summary., Hereditary dysfibrinogenaemia is characterized by the presence of functionally abnormal plasma fibrinogen. Dysfibrinogenaemia is a heterogeneous disorder associated with different mutations throughout the three genes that code for the fibrinogen sub-units, affecting many different aspects of fibrinogen/fibrin activity. Dysfibrinogenaemia may be discovered during the investigation of individuals who present with bleeding or thombosis, or may be found in individuals during routine coagulation screening. More specialized coagulation tests may confirm the diagnosis of dysfibrinogenaemia but do not reliably distinguish between the different fibrinogen variants and are not usually useful in predicting bleeding or thrombotic risk. Advances in molecular diagnostics have facilitated the investigation of the molecular causes of fibrinogen disorders. Several ,hot spot' areas have been identified where mutations causing a high proportion of cases of dysfibrinogenaemia are found (A,Arg16 and ,Arg275). Molecular diagnostics have also shown that many fibrinogen variants share the same causative mutation. There is a discrepancy between the quality of the molecular and functional data available for each mutation and the clinical information on individuals and their family members. However, there are accumulating data that the ,hot spot' mutations accounting for 60,80% of cases of dysfibringenaemia are not associated with a significant bleeding or thrombosis in the absence of other risk factors. Rapid screening for these mutations may provide reassurance for patients in the presurgical setting. [source] Antiphospholipid antibodies and hepatitis C virus infection in Iranian thalassemia major patientsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2008S. KASHEF Summary Although the precise nature of Antiphospholipid antibodies is still not clearly defined, they are known to have association with thromboembolic events and have been found in hepatitis C virus (HCV) infection. Moreover, high prevalence of HCV infection and thrombotic risk is described in thalassemia. We aimed at investigating the prevalence of anticardiolipin antibodies (aCLAbs), lupus anticoagulant (LA), and their relation with HCV infection in Iranian thalassemic patients. Presence of anti-HCV antibody, serum HCV-RNA, aCLAbs, and LA activity was determined in 131 patients with thalassemia major (male/female: 63/68 aged 3,29 years) registered at thalassemia unit, Dastgheib Hospital, Shiraz, Iran. Sixty-one healthy controls were also included. Anti-HCV antibody was positive in 24 (18.3%), IgG aCLAbs in 56 (42.7%), and LA activity in 9 (6.9%) patients. 87.5% of patients positive for aCLAbs had a low titer of aCLAbs. Although none of the participants had a previous history of thrombosis, higher prevalence of aCLAbs was detected in thalassemic patients compared with controls. No significant difference in the prevalence of aCLAbs was found between HCV-infected and noninfected patients. A high prevalence of aCLAbs, the majority in low titers, was detected in Iranian thalassemic patients irrespective of previous history of thrombosis and presence of HCV infection. [source] Anticoagulation After Coronary Artery Surgery in Patients With Polycythemia Vera: Report of Two CasesJOURNAL OF CARDIAC SURGERY, Issue 5 2007Bilgehan Sava, Oz M.D. Normalization of the hematocrit and elevated platelet counts is obligatory to reduce the thrombotic risk of patients with PV. Therapeutic strategies include phlebotomy, myelosuppressive agents, and, more recently, interferon-,. In addition, appropriate antiplatelet therapy should be administered to prevent life-threatening complications and reducing the viscosity of the blood. Although aspirin is widely preferred in such patients, this monodrug therapy or combined with clopidogrel as an alternative approach might not be enough, especially after coronary artery surgery. Therefore, warfarin should be added to anticoagulant therapy. This short report describes the use of warfarin, associated with aspirin and clopidogrel as an anticoagulant regimen after coronary artery bypass surgery in two cases with polycythemia vera. We believe that a combination of warfarin with other oral antiplatelet agents may be more effective in preventing the coronary artery bypass graft thrombosis. [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] Variation in 24 hemostatic genes and associations with non-fatal myocardial infarction and ischemic strokeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2008N. L. SMITH Summary., Background:, Arterial thrombosis involves platelet aggregation and clot formation, yet little is known about the contribution of genetic variation in fibrin-based hemostatic factors to arterial clotting risk. We hypothesized that common variation in 24 coagulation,fibrinolysis genes would contribute to risk of incident myocardial infarction (MI) or ischemic stroke (IS). Methods:, We conducted a population-based, case,control study. Subjects were hypertensive adults and postmenopausal women 30,79 years of age, who sustained a first MI (n = 856) or IS (n = 368) between 1995 and 2002, and controls matched on age, hypertension status, and calendar year (n = 2689). We investigated the risk of MI and IS associated with (i) global variation within each gene as measured by common haplotypes and (ii) individual haplotypes and single nucleotide polymorphisms (SNPs). Significance was assessed using a 0.2 threshold of the false discovery rate q -value, which accounts for multiple testing. Results:, After accounting for multiple testing, global genetic variation in factor (F) VIII was associated with IS risk. Two haplotypes in FVIII and one in FXIIIa1 were significantly associated with increased IS risk (all q -values < 0.2). A plasminogen gene SNP was associated with MI risk. All are new discoveries not previously reported. Another 24 tests had P -values < 0.05 and q -values > 0.2 in MI and IS analyses, 23 of which are new and hypothesis generating. Conclusions:, Apart from the association of FVIII variation with IS, we found little evidence that common variation in the 24 candidate fibrin-based hemostasis genes strongly influences arterial thrombotic risk, but our results cannot rule out small effects. [source] Impact of progestagens on activated protein C (APC) resistance among users of oral contraceptivesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2004M. Alhenc-Gelas Summary., Oral contraceptive (OC) use is associated with an increased risk of venous thromboembolism. Previous data reported higher thrombotic risk in women using third-generation combined OC than in those using second generation OC. The difference could be explained by differential effects of progestagens on plasma sensitivity to activated protein C (APC). The main purpose of this cross-sectional study was to assess the influence of a progestagen-only OC (chlormadinone acetate) as well as the effect of several combined OC with different progestagen components on APC resistance. The effect of APC on endogenous thrombin potential (ETP) was investigated in the plasma of healthy women using either combined OC (n = 82) or progestagen-only OC (n = 28), and in non-users (n = 64). Carriers of factor V Leiden were excluded. Compared with non-users, there was no significant change in APC resistance in women using progestagen-only OC. Women who used combined OC were less sensitive to APC than non-users (P < 0.001) and the difference was significantly more pronounced in women using third-generation OC (n = 41) than in those who used second-generation OC containing levonorgestrel (n = 22) (P < 0.05). Compared with OC containing levonorgestrel, use of norethisterone-containing OC (n = 9) was associated with an increased resistance to APC (P < 0.05). Women who used cyproterone-containing OC (n = 10) were less sensitive to APC than those using third-generation OC (P < 0.05) or second-generation OC containing levonorgestrel (P < 0.05). Protein S, factor II and FVIII levels explained in part the OC-related changes in APC sensitivity variations. ETP-based APC resistance may contribute to explain why different brands of OC can be associated with different levels of thrombogenicity. [source] Linkage analysis of factor VIII and von Willebrand factor loci as quantitative trait lociJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2003M. C. H. De Visser Summary., Elevated factor (F)VIII levels contribute to venous thrombotic risk. FVIII levels are determined to a large extent by levels of von Willebrand factor (VWF), its carrier protein which protects FVIII against proteolysis. VWF levels are largely dependent on ABO blood group. Subjects with blood group non-O have higher VWF and FVIII levels than individuals with blood group O. Apart from ABO blood group no genetic determinants of high FVIII levels have been identified, whereas clustering of FVIII levels has been reported within families even after adjustment for ABO blood group and VWF levels. We investigated the FVIII and VWF loci as possible quantitative trait loci (QTL) influencing FVIII and VWF levels. Two sequence repeats in the FVIII gene and three repeats in the VWF gene were typed in 52 FV Leiden families. Multipoint sib-pair linkage analysis was performed with the MAPMAKER/SIBS program. FVIII levels adjusted for VWF levels and age, and VWF levels adjusted for ABO blood group and age, were used for this linkage analysis. No linkage of FVIII levels to the FVIII locus was found, whereas we found evidence that the VWF locus contains a QTL for VWF levels [maximum likelihood no dominance variance lod score = 0.70 (P = 0.04) and non-parametric Z-score = 1.92 (P = 0.03)]. About 20% of the total variation in VWF levels may be attributed to this VWF locus. [source] Ornithine transcarbamylase deficiency: A possible risk factor for thrombosis,,PEDIATRIC BLOOD & CANCER, Issue 1 2009Lakshmi Venkateswaran MD Abstract Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. Thromboembolic complications have not heretofore been linked with this diagnosis. We describe four patients with neonatal-onset OTC deficiency who developed vascular thromboses. One patient had arterial thrombosis; the rest developed venous thromboses. Multiple pro-thrombotic risk factors were identified. Low plasma arginine levels were observed in all patients at the time of thrombosis. Arginine deficiency and the resultant nitric oxide insufficiency may contribute to thrombotic risk. Careful normalization of plasma arginine and citrulline levels and increased surveillance for thrombotic complications should be considered in patients with OTC deficiency. Pediatr Blood Cancer 2009;53:100,102. © 2009 Wiley-Liss, Inc. [source] Fatal case of bilateral internal jugular vein thrombosis following IVIg infusion in an adolescent girl treated for ITPAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2008Pui-Ying Iroh Tam Intravenous immunoglobulin (IVIg) is often used as therapy in immune-mediated diseases and is generally considered a safe therapeutic agent. However, thrombotic complications such as myocardial infarction and deep vein thrombosis have been reported, although primarily in older adults. We describe a 13-year-old girl who received one dose of IVIg for immune thrombocytopenic purpura and developed fatal bilateral jugular venous thromboses. This is the first known case of IVIg-associated thrombosis in an adolescent and alsothe first report describing internal jugular vein thrombosis associated with IVIg infusion. We identify additional risks that may potentiate the agent's thrombotic risk. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc. [source] PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2004Alessandro M. Vannucchi Summary Females with the monoclonal type of essential thrombocythaemia (ET), based on the X-chromosome inactivation pattern (XCIP), have previously been shown to present a higher incidence of thrombosis than polyclonal ones. We aimed to assess correlations between XCIP, thrombosis, and three epigenetic markers of ET, namely PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P = 0·009). The frequency of abnormalities of PRV-1, EEC, or Mpl was similar in monoclonal and polyclonal subjects (respectively, 28%, 48%, 75%, and 37%, 27%, 63%), and none of them correlated with thrombosis. We conclude that the exploited epigenetic markers constitute independent phenotypic variations and are not clustered according to monoclonality of myelopoiesis in ET; none of them could serve as a surrogate marker of thrombotic risk in male subjects with ET. [source] Factor XIII Val34Leu and the risk of venous thromboembolism in factor V Leiden carriersBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2000Rendrik F. Franco A mutation in factor XIII (Val34Leu) was reported to protect against venous thromboembolism. We evaluated the effect of Val34Leu on thrombotic risk in 352 factor V Leiden carriers who were first-degree relatives of 132 thrombotic propositi carrying factor V Leiden. The total observation period was 2594 years in 92 Val34Leu carriers and 7444 years in 260 non-carriers. The annual incidence of a first episode of venous thromboembolism was 0·31% in Val34Leu carriers and 0·44% in non-carriers [relative risk (RR) for venous thromboembolism: 0·7, 95% CI 0·3,1·5]. Age-specific RR for venous thromboembolism were (for Val34Leu carriers and non-carriers respectively): 1·0 (95% CI 0·3,3·2) in the age group of 15,30 years, 0·4 (95% CI 0·05,3·0) in the age group of 30,45 years, 0·6 (95% CI 0·1,2·9) in the group aged 45,60 years and 0·5 (95% CI 0·06,4·5) in relatives older than 60 years. In conclusion, the impact of FXIII Val34Leu on the venous thromboembolic risk is modest, suggesting that screening for this mutation in factor V Leiden carriers is not justified. [source] AGEING, OESTROGEN, PLATELETS AND THROMBOTIC RISKCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007Virginia M Miller SUMMARY 1Adverse thrombotic cardiovascular events increase in women coincident with the onset of menopause. 2Age past menopause may be an important variable in defining the benefit/risk of hormone treatments. 3Few studies have examined hormonal status as a variable of ageing using a polygenomic approach of both humoral and cellular components of the coagulation system. 4Longitudinal studies of a global set of platelet functions that define procoagulant activity (i.e. adhesion, aggregation, secretion and thrombin production) in individuals with documented hormonal status are needed to better understand how hormonal changes associated with ageing impact thrombotic risk. [source] Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction,CLINICAL TRANSPLANTATION, Issue 1 2005Kadriye Reis Abstract:, Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. [source] | ||||||||||