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Factor V Leiden (factor + v_leiden)
Terms modified by Factor V Leiden Selected AbstractsPrevalence of Factor V Leiden in three ethnic groups of patients with deep vein thrombosis in the Western Cape province of South AfricaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2000Riva Rubinstein 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] Inherited defects of coagulation Factor V: the thrombotic sideJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2006H. L. VOS Summary., DNA variations in the Factor V gene have played a major role in thrombosis research ever since the discovery of Factor V Leiden. Here, all relatively common DNA variations in the coding regions of the Factor V gene are discussed. Many of them have been associated with venous thrombosis or related diseases. However, most variations have been studied separately, without taking the presence of other variations in the same gene into account. This means that their association with disease should be interpreted with caution, as it may reflect linkage with another variation. An approach in which a haplotype-based analysis of the Factor V gene is combined with in vitro assays of recombinant proteins is advocated. Finally, a possible reason for the relatively polymorphic nature of the Factor V protein is discussed. [source] Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Ashkan Emadi The objective of this study is to systematically review methods for detecting Factor V Leiden or prothrombin G20210A. English-language literature from MEDLINE®, EMBASE®, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo©, 2000-December 2008. Studies assessed methods for detection of these mutations in at least 10 human blood samples and reported concordance, discordance, or reproducibility. Two investigators abstracted data on the sample selection criteria, test operators, DNA extraction, experimental test, reference standard, commercial instruments, concordance rates, explanation of any discordance, and whether discordance resolved after repetition. We assessed strength of the evidence using the GRADE criteria. We reviewed 7,777 titles and included 66 articles. The majority of the reviewed studies used PCR-RFLP or AS-PCR as the reference standard. The studies demonstrated that commercially available and precommercial tests have high analytic validity with all having greater than 99% concordance with the reference standard. With a few exceptions, discordance resolved with repetition of the test, suggesting operator or administrative errors were responsible for the discordant results. In the quality assurance studies, greater than 98% of laboratories demonstrated high, even perfect, accuracy when asked to diagnose a sample with a known mutation. The majority of errors came from a limited number of laboratories. Although not all methods may be accurate, there is high-grade evidence that genetic tests for the detection of FVL and prothrombin G20210A have excellent analytic validity. There is high-grade evidence that most, but not all, clinical laboratories test for FVL and prothrombin G20210A accurately. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Polymorphisms in various coagulation genes in black South African women with placental abruptionBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 5 2002B. Hira This pilot study examined Factor V Leiden (R506Q), prothrombin (20210G , A), thrombomodulin (A455V) and MTHFR (677C ,T) in 100 Zulu-speaking black South African women with placental abruption and 217 controls. The Factor V Leiden and prothrombin variant gene alleles were not detected in either patient or control groups. The thrombomodulin polymorphic variant was not seen in the patient group but three heterozygotes (1%) were found in the controls. No homozygotes for the MTHFR T677 variant were detected in the patients but two (1%) were noted in the controls; the normal and heterozygote genotype and allele frequencies for this polymorphism were similar in the two groups. [source] Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriageBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2001M.F. Reznikoff-Etiévant Objective To determine whether there is an association between early recurrent miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A prothrombin mutations. Design A prospective study. Setting Department of Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France. Population Two groups of women: those with early unexplained recurrent miscarriage before 10 weeks of pregnancy (n=260) and control healthy women without a previous history of thromboembolism (n=240). Methods Screening for defects in the protein C anticoagulant pathway was performed using the anticoagulant response to agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation testing was performed for each low ACV level. Each sample was tested for the G20210A prothrombin mutation. Results Factor V Leiden and G20210A mutations were found to be associated with early recurrent spontaneous miscarriage before 10 weeks of pregnancy, the odds ratios being 2.4 (95% CI 1,5) and 2.7 (95% CI 1,7), respectively. Similar results were found whether or not women had had a previous live birth. Conclusions Early recurrent miscarriage before 10 weeks of pregnancy is significantly associated with Factor V or G20210A prothrombin mutations. These results indicate a possible role for anticoagulant prevention in these early miscarriages. [source] Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot studyACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010C. Termine Termine C, Trotti R, Ondei P, Gamba G, Montani N, Gamba A, De Simone M, Marni E, Balottin U. Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot study. Acta Neurol Scand: 2010: 122: 91,96. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To investigate the prevalence of mitral valve prolapse (MVP) and abnormalities of haemostasis in children and adolescents with migraine with aura (MA) compared with peers affected by other idiopathic headaches. Materials and methods,,, We recruited 20 MA patients (10 men and 10 women; age range 8,17 years) and 20 sex- and age-matched subjects with other idiopathic headaches. Both groups underwent colour Doppler transthoracic echocardiography to detect MVP and the following laboratory work-up: plasma prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, protein C, protein S, homocysteine, lupus anticoagulant, von Willebrand factor (vWF) ristocetin cofactor activity, immunoglobulins (Ig) G and M anticardiolipin antibodies (aCL). Factor V Leiden, factor II and methylenetetrahydrofolate reductase were investigated (we did not test the entire genes, but screened for specific point mutations). Results,,, The prevalence of MVP was significantly higher in the MA subjects than in the patients affected by other idiopathic headaches (40% vs 10%; P < 0.05). Moreover, the MA patients showed a higher rate of above-normal IgM aCL titres (45% vs 10%; P < 0.05). Finally, in the group of patients with MVP we found a higher prevalence of aCL in those with MA compared with those affected by other idiopathic headaches. Conclusions,,, A proportion, at least, of the MA patients showed a more complex phenotype characterized by MVP and/or positive aCL titres. The pathogenetic role of these associations is obscure and larger studies are needed to confirm the usefulness of echocardiographic and laboratory investigations in this area and to identify possible new treatment approaches that might be explored in this group of MA patients. [source] Factor V Leiden and prothrombin 21210G>A mutation and paediatric ischaemic stroke: a case,control study and two meta-analysesACTA PAEDIATRICA, Issue 8 2010R Laugesaar Abstract Aim:, To determine whether factor V Leiden (FVL) and prothrombin (PT) 20210G>A mutation are associated with paediatric ischaemic stroke. Methods:, The study consisted of two parts. Case,control study included neuroradiologically confirmed paediatric ischaemic stroke patients from two tertiary children's hospitals in Estonia. For control group, DNA was obtained from 400 anonymous screening test cards of newborns born consecutively in all delivery departments of Estonia in January 2005. Meta-analyses was performed to assess the association between paediatric sinovenous thrombosis and FVL and PT 20210G>A. Results:, A total of 75 children (45 boys, 30 girls) were included into the case,control study: 19 with childhood arterial ischaemic stroke, 49 with perinatal arterial ischaemic stroke and seven with cerebral venous thrombosis. Both FVL and PT 20210G>A occurred significantly more frequently among patients with sinovenous thrombosis compared with controls (OR = 12.9; 95% CI: 2.3,73.0 and OR = 11.9; 95% CI: 2.1,67.2, respectively). The difference was not significant between childhood/perinatal arterial ischaemic stroke and controls. Meta-analyses (including our study) revealed that both FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis (OR = 3.1; 95% CI: 1.8,5.5 and OR = 3.1; 95% CI: 1.4,6.8, respectively). Conclusion:, FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis. [source] Neonatal renal vein thrombosis and prothrombotic riskACTA PAEDIATRICA, Issue 7 2010SL Harris Abstract A case of extensive deep venous thrombosis in a four a day old infant was presented. Unusually this patient was shown to be heterozygous for three thrombophilia genes; Factor V Leiden, prothrombin and antithrombin gene mutations, the latter being novel. Conclusion: There are no randomized controlled trials to guide management in deep venous thrombosis in the newborn but knowledge of the prothrombotic risk factors may help direct treatment. [source] Stroke in children: inherited and acquired factors and age-related variations in the presentation of 48 paediatric patientsACTA PAEDIATRICA, Issue 7 2009Francesca Del Balzo Abstract Aim:, Stroke is relatively rare in children and the clinical presentation of paediatric stroke is often subtle. Numerous predisposing risk factors are known, and these can be both inherited and acquired. They include cardiac disease, vascular abnormalities, endothelial damage, infectious diseases, collagen tissue diseases, certain inborn errors of metabolism and anticardiolipin antibody, lupus anticoagulant and deficiencies of protein C, protein S, antithrombin or plasminogen. In addition, abnormal activated protein C resistance (or Factor V Leiden), Factor II G20219A variant, and the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR C677T) need to be considered. Methods:, To explore the prevalence of different predisposing conditions in paediatric stroke patients, we evaluated 48 patients, including subjects with ischaemic and haemorrhagic stroke subtypes. Results:, Only 7 out of 48 (14.5%) had no recognizable risk factors: the majority of paediatric stroke patients had pre-existing risk factors that predisposed to the condition. The major genetic risk factor in our series of patients was homozygosity for the MTHFR C677T mutation (7 out of 48 patients); three more patients were found to be heterozygous for the Factor V Leiden mutation. Acquired predisposing conditions were present in 23 out of 48 patients and included pulmunar stenosis, head trauma, hyperlipidaemia and varicella infection. A total of 17 patients had both genetic and acquired predisposing factors. Conclusion:, Our results emphasize that multiple predisposing risk factors commonly predispose to paediatric stroke. In addition, the primary clinical presentation appeared to differ between the older and younger children: hemiparesis was the typical presentation in children <1 year of age while seizure predominated in older children. [source] Factor V Leiden and hepatic artery thrombosis after liver transplantationCLINICAL TRANSPLANTATION, Issue 1 2006Ty B Dunn Abstract:, Factor V Leiden (FVL) and other thrombophilias can be acquired during liver transplantation and can have a significant impact on clinical outcomes as well as cost. Standard practice does not include screening deceased donors for heritable thrombophilias, even if they have a personal history of thrombosis. Here we report a case of hepatic artery thrombosis in a liver recipient whose native and donor livers were heterozygous for FVL. The patient subsequently underwent a successful retransplant. FVL and its variants are expressed phenotypically as activated protein C (APC) resistance. We believe that testing liver donors (deceased or living) for APC resistance , a surrogate marker for the most common liver-based thrombophilia , will reduce the incidence of thrombotic events by identifying a need for posttransplant prophylactic anticoagulation in patients at risk. The estimated cost of testing all liver donors in the US for APC resistance is less than the cost of two complications secondary to thrombosis. Testing for APC resistance may further improve outcome and reduce cost after liver transplantation. [source] Milder clinical presentation of haemophilia A with severe deficiency of factor VIII as measured by one-stage assayHAEMOPHILIA, Issue 1 2001K. Ghosh During the course of investigations we encountered 11 patients with haemophilia A who had severe factor VIII deficiency as measured by one-stage assay but had surprisingly mild clinical presentation. Four of these patients had either a brother, nephew or maternal uncle with severe clinical manifestations. Two patients had low protein S levels, and one was heterozygous for the factor V Leiden mutation. One patient had a combined deficiency of protein C and antithrombin III. Four patients had a two-stage factor VIII assay value that was much higher than the one-stage assay value. Five patients were heterozygous for the MTHFR gene C677T polymorphism, of whom two patients were also deficient for protein S and one had two-stage factor assay values higher than the one-stage assay values. The patient who was both factor VIII deficient and heterozygous for factor V Leiden had mild clinical presentation as compared to his maternal uncle who was only factor-VIII deficient. The maternal cousin of the same patient was heterozygous for factor V Leiden and had suffered two thrombotic episodes. Thus, the present study advocates that the physiological inhibitors of blood coagulation also play an important role in cases of haemophilia A in the final outcome of haemostasis in vivo. [source] Comparison between two functional assays to detect factor V LeidenINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1p1 2010G. Gessoni No abstract is available for this article. [source] Multiple thrombophilic factors in a patient with Budd,Chiari syndromeINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2002V. BRANCACCIO Myeloproliferative disorders are the main cause of Budd,Chiari syndrome in western countries. Inherited or acquired thrombophilic factors have also been implicated. A novel mutation of the prothrombin gene (G,A20210) has only been described in a few cases of Budd,Chiari syndrome so far. Venous thrombosis is often the result of multiple concomitant thrombophilic factors. We report the case of a patient with essential thrombocythemia and Budd,Chiari syndrome in which heterozygosity for both factor V Leiden and the mutation G20210A of the prothrombin gene were identified. [source] Double inherited thrombophilias and adverse pregnancy outcomes: Fashion or science?JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2010Giovanni Larciprete Abstract Aim:, To determine to what extent double inherited thrombophilias are associated with adverse obstetric complications correlated with fetoplacental insufficiency, such as preeclampsia, hemolytic anemia elevated liver enzymes and low platelet count (HELLP) syndrome, gestational hypertension, fetal growth restriction (FGR), intrauterine death (ID), abruptio placentae and disseminated intravascular coagulopathy. Methods:, Pregnant women coming to delivery were retrospectively divided into two groups: group A (controls) and group B (cases). Patients belonging to group B had one of the following: severe preeclampsia, HELLP syndrome, gestational hypertension, FGR, intrauterine death, abruptio placentae of disseminated intravascular coagulopathy. We detected methylenetetrahydrofolate reductase (MTHFR) A1298C, MTHFR C677T, factor V Leiden, PAI-1, mutant prothrombin G20210A, plasma homocysteine, antithrombin III, protein S and activated protein C resistance. Normal pregnant women or pregnant women with double defects were enrolled in this study. Results:, The combination of MTHFR C677T mutation with PAI-1 (5G/5G) mutation was significantly linked with the occurrence of ID. HELLP syndrome was significantly related to the simultaneous presence of factor VIII and X mutations. The combination of MTHFR C677T with factor VIII mutation and the combination of factor II and V mutations were significantly related to the occurrence of abruptio placentae. We found an association between double isoforms MTHFR mutation and FGR. Conclusion:, It seems that some thrombophilias and a combination of thrombophilic factors carry a greater risk than others for a given adverse outcome. Further studies are needed to check the link between thrombophilic gene mutations and adverse pregnancy outcomes, such as recurrent miscarriages and deep venous thrombosis. [source] Duration of anticoagulation and risk of recurrent thromboembolism in carriers of factor V Leiden or prothrombin mutationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2008P. PRANDONI No abstract is available for this article. [source] Type and location of venous thromboembolism in patients with factor V Leiden or prothrombin G20210A and in those with no thrombophiliaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2007I. MARTINELLI Summary.,Background: Patients with factor (F) V Leiden or the prothrombin G20210A polymorphism are at increased risk of developing deep vein thrombosis (DVT). On the other hand, the risk of developing pulmonary embolism (PE) appears to be low in carriers of FV Leiden, perhaps because of a lower tendency to develop iliofemoral DVT than non-carriers. For prothrombin G20210A, data are scanty and controversial. Methods: The clinical manifestations (isolated DVT, DVT and PE, and isolated PE), the extension of DVT, and the presence of transient risk factors were retrospectively investigated in 115 patients with heterozygous FV Leiden, 87 with prothrombin G20210A and 200 with no thrombophilia marker. Results: Isolated symptomatic PE was less prevalent in patients with FV Leiden (6%) than in those with prothrombin G20210A (21%) and no thrombophilia (23%) (P > 0.0001). The rate of distal DVT was higher in patients with no thrombophilia (16% vs. 7% for FV Leiden and 6% for prothrombin G20210A) (P = 0.02). No difference in the incidence of PE from distal and proximal DVT, the extension of proximal DVT and the type of transient risk factors for venous thromboembolism (VTE) was found in the three groups. Patients with prothrombin G20210A had a younger age at their first VTE (24 years, P < 0.0001) and a higher rate of DVT accompanying PE (P = 0.04) than those with FV Leiden or no thrombophilia. Conclusions: Carriers of prothrombin G20210A, unlike those of FV Leiden, have an increased risk of developing isolated PE. This difference was not explained by a different rate of distal DVT, extension of proximal DVT, or distribution of transient risk factors in the two groups. Patients with prothrombin G20210A have more severe clinical manifestations than those with FV Leiden or no thrombophilia. [source] More on: factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control ,NOHA First' studyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2006G. LISSALDE-LAVIGNE No abstract is available for this article. [source] Old and new risk factors for upper extremity deep venous thrombosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2005J. W. BLOM Summary.,Background: Well known risk factors for upper extremity deep venous thrombosis are the presence of a central venous catheter (CVC) and malignancy, but other potential risk factors, such as surgery, injury and hormone replacement therapy (HRT), have not yet been explored. Methods: We performed a population-based case-control study including 179 consecutive patients, aged 18,70 years with upper extremity deep venous thrombosis and 2399 control subjects. Participants reported on acquired risk factors in a questionnaire and factor V Leiden and prothrombin 20210A mutation were ascertained. Information on CVC was obtained from discharge letters. Results: Forty-two patients (23%) and one control subject (0.04%) had a CVC (ORadj: 1136, 95% CI: 153,8448, adjusted for age and sex). Cancer patients without a CVC had an eightfold increased risk of venous thrombosis of the arm (ORcrude: 7.7, 95% CI: 4.6,13.0). Other evident risk factors were prothrombotic mutations, surgery, immobilization of the arm (plaster cast), oral contraceptive use and family history, with odds ratios varying from 2.0 up to 13.1. The risk in the presence of injury and during puerperium was twofold or more increased, although not significantly. In contrast HRT, unusual exercise, travel and obesity did not increase the risk. Hormone users had an increased risk in the presence of prothrombotic mutations or surgery. Obese persons (BMI > 30 kg m,2) undergoing surgery had a 23-fold increased risk of arm thrombosis compared with non-obese persons not undergoing surgery. Conclusion: A CVC is a very strong risk factor for arm thrombosis. Most risk factors for thrombosis in the leg are also risk factors for arm thrombosis. [source] The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsiaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2005A. GERHARDT Summary., Hereditary risk determinants of venous thrombosis have been reported to be associated with severe preeclampsia. So far there are no data to support whether these risk determinants are related to the time of onset of severe preeclampsia. We used a case,control design, studying 97 women with severe preeclampsia in previous pregnancies and 277 normal women, to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. A case-only design comprising solely the 97 women with a history of preeclampsia was used to evaluate these risk factors as risk determinants for early onset of severe preeclampsia. Using the case,control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia [factor V Leiden, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.4, 2.2; prothrombin mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT genotype, OR 0.8, 95% CI 0.4, 1.8; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.2, 95% CI 0.7, 2.1; PAI-1 5G/5G genotype, OR 1.0, 95% CI 0.5, 1.8]. However, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.1 weeks, P = 0.046) and in women with the PAI-1 5G/5G genotype (25.7 weeks vs. 30.8 weeks, P = 0.024). Hereditary risk factors for venous thrombosis do not predispose for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI-1 5G/5G genotype are at risk for early onset of severe preeclampsia. It appears that these risk factors do not induce the pathomechanism but accelerate the course of preeclampsia. [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] The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE Study,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2003N. F. Dowling Summary., The aim of this study was to assess, comprehensively, medical and genetic attributes of venous thromboembolism (VTE) in a multiracial American population. The Genetic Attributes and Thrombosis Epidemiology (GATE) study is an ongoing case,control study in Atlanta, Georgia, designed to examine racial differences in VTE etiology and pathogenesis. Between 1998 and 2001, 370 inpatients with confirmed VTE, and 250 control subjects were enrolled. Data collected included blood specimens for DNA and plasma analysis and a medical lifestyle history questionnaire. Comparing VTE cases, cancer, recent surgery, and immobilization were more common in caucasian cases, while hypertension, diabetes, and kidney disease were more prevalent in African-American cases. Family history of VTE was reported with equal frequency by cases of both races (28,29%). Race-adjusted odds ratios for the associations of factor V Leiden and prothrombin G20210A mutations were 3.1 (1.5, 6.7) and 1.9 (0.8, 4.4), respectively. Using a larger external comparison group, the odds ratio for the prothrombin mutation among Caucasians was a statistically significant 2.5 (1.4, 4.3). A case-only analysis revealed a near significant interaction between the two mutations among Caucasians. We found that clinical characteristics of VTE patients differed across race groups. Family history of VTE was common in white and black patients, yet known genetic risk factors for VTE are rare in African-American populations. Our findings underscore the need to determine gene polymorphisms associated with VTE in African-Americans. [source] Comparison of characteristics from White- and Black-Americans with venous thromboembolism: A cross-sectional study,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010John A. Heit When compared with Whites, Black-Americans may have a 40% higher incidence venous thromboembolism (VTE) incidence. However, whether other VTE characteristics and risk factors vary by race is uncertain. To compare demographic and baseline characteristics among White- and Black-Americans with VTE, we used data prospectively collected from consecutive consenting adults enrolled in seven Centers for Disease Control (CDC) Thrombosis and Hemostasis Centers from August 2003 to March 2009. These characteristics were compared among Whites (n = 2002) and Blacks (n = 395) with objectively diagnosed VTE, both overall, and by age and gender. When compared with Whites, Blacks had a significantly higher proportion with pulmonary embolism (PE), including idiopathic PE among Black women, and a significantly higher proportion of Blacks were women. Blacks had a significantly higher mean BMI and a significantly lower proportion with recent surgery, trauma or infection, family history of VTE, and documented thrombophilia (solely from reduced factor V Leiden and prothrombin G20210A prevalence). Conversely, Blacks had a significantly higher proportion with hypertension, diabetes mellitus, chronic renal disease and dialysis, HIV, and sickle cell disease. When compared with White women, Black women had a significantly lower proportion with recent oral contraceptive use or hormone therapy. We conclude that Whites and Blacks differ significantly regarding demographic and baseline characteristics that may be risk factors for VTE. The prevalence of transient VTE risk factors and idiopathic VTE among Blacks appears to be lower and higher, respectively, suggesting that heritability may be important in the etiology of VTE among Black-Americans. Am. J. Hematol. 85:467,471, 2010 © 2010 Wiley-Liss, Inc. [source] Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Ashkan Emadi The objective of this study is to systematically review methods for detecting Factor V Leiden or prothrombin G20210A. English-language literature from MEDLINE®, EMBASE®, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo©, 2000-December 2008. Studies assessed methods for detection of these mutations in at least 10 human blood samples and reported concordance, discordance, or reproducibility. Two investigators abstracted data on the sample selection criteria, test operators, DNA extraction, experimental test, reference standard, commercial instruments, concordance rates, explanation of any discordance, and whether discordance resolved after repetition. We assessed strength of the evidence using the GRADE criteria. We reviewed 7,777 titles and included 66 articles. The majority of the reviewed studies used PCR-RFLP or AS-PCR as the reference standard. The studies demonstrated that commercially available and precommercial tests have high analytic validity with all having greater than 99% concordance with the reference standard. With a few exceptions, discordance resolved with repetition of the test, suggesting operator or administrative errors were responsible for the discordant results. In the quality assurance studies, greater than 98% of laboratories demonstrated high, even perfect, accuracy when asked to diagnose a sample with a known mutation. The majority of errors came from a limited number of laboratories. Although not all methods may be accurate, there is high-grade evidence that genetic tests for the detection of FVL and prothrombin G20210A have excellent analytic validity. There is high-grade evidence that most, but not all, clinical laboratories test for FVL and prothrombin G20210A accurately. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Maternal carriership of factor V Leiden associated with pathological uterine artery Doppler measurements during pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2001Pelle G. Lindqvist To determine whether increased vascular resistance in the uterine artery is associated with carriership of factor V Leiden, a retrospective study was undertaken of 231 pregnant women who were monitored with Doppler velocimetry of the uterine arteries. These women had been part of a prospective study of 2480 pregnant women in whom factor V Leiden had been analysed. When compared with non-carriers of factor V Leiden, carriers had a tendency towards an increased proportion of pathological Doppler measurements, including a significant increase in bilateral uterine artery notches (7/33 vs 16/198, relative risk 3.1; 95% CI 1.2,8.1). This suggests an increased vascular resistance in the uteroplacental circulation among carriers of factor V Leiden. [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] Hormonal contraceptives as a risk factor for cerebral venous and sinus thrombosisACTA NEUROLOGICA SCANDINAVICA, Issue 5 2007M. Saadatnia This review will focus on recent developments in our understanding of cerebral venous and sinus thrombosis (CVST), as a side effect of combined oral contraceptives (COCs) use. Case,control studies have shown an increased risk of CVST in women who use COCs, especially third-generation contraceptives that contain gestodene or desogestrel. Several studies have indicated that the combination of COCs and thrombophilia greatly increased the risk of CVST, particularly in women with hyperhomocysteinaemia, factor V Leiden and the prothrombin-gene mutation. Women with thrombophilia who developed CVST while taking oral contraceptives should be definitively advised to stop using COCs. These patients should be considered for preventive therapy with low doses of heparin in prothrombotic situations such as bed rest or pregnancy, and the duration of anticoagulation should be considered on a case-by-case basis. Patients may be considered candidates for chronic treatment with antiplatelet agents. The best and most cost-effective screening method for thrombophilia in women who are planning to conceive is selective screening based on the presence of previous personal or family history of either prior extracerebral or cerebral venous thromboembolism events. [source] 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,CANCER, Issue 2 2003Results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study Abstract BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. Cancer 2003;97:508,16. © 2003 American Cancer Society. DOI 10.1002/cncr.11042 [source] Factor V Leiden and prothrombin 21210G>A mutation and paediatric ischaemic stroke: a case,control study and two meta-analysesACTA PAEDIATRICA, Issue 8 2010R Laugesaar Abstract Aim:, To determine whether factor V Leiden (FVL) and prothrombin (PT) 20210G>A mutation are associated with paediatric ischaemic stroke. Methods:, The study consisted of two parts. Case,control study included neuroradiologically confirmed paediatric ischaemic stroke patients from two tertiary children's hospitals in Estonia. For control group, DNA was obtained from 400 anonymous screening test cards of newborns born consecutively in all delivery departments of Estonia in January 2005. Meta-analyses was performed to assess the association between paediatric sinovenous thrombosis and FVL and PT 20210G>A. Results:, A total of 75 children (45 boys, 30 girls) were included into the case,control study: 19 with childhood arterial ischaemic stroke, 49 with perinatal arterial ischaemic stroke and seven with cerebral venous thrombosis. Both FVL and PT 20210G>A occurred significantly more frequently among patients with sinovenous thrombosis compared with controls (OR = 12.9; 95% CI: 2.3,73.0 and OR = 11.9; 95% CI: 2.1,67.2, respectively). The difference was not significant between childhood/perinatal arterial ischaemic stroke and controls. Meta-analyses (including our study) revealed that both FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis (OR = 3.1; 95% CI: 1.8,5.5 and OR = 3.1; 95% CI: 1.4,6.8, respectively). Conclusion:, FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis. [source] | ||||||||||||||||||||||