Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis

2011 ◽  
Vol 105 (02) ◽  
pp. 269-273 ◽  
Author(s):  
Ophira Salomon ◽  
David Steinberg ◽  
Michal Zucker ◽  
David Varon ◽  
Ariella Zivelin ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Large Population ◽  
Population Based ◽  
Expected Number ◽  
Factor Xi ◽  
Population Based Study ◽  
Factor Xi Deficiency ◽  
Vein Thrombosis ◽  
Low Incidence ◽  
Deep Vein

SummaryFactor XI (FXI) plays a dual role in haemostasis and thrombosis. It contributes to thrombin generation and promotes inhibition of fibrinolysis. Severe FXI deficiency was shown to confer protection against arterial and venous thrombosis in animal models without compromising haemostasis. We have previously shown that patients with severe FXI deficiency have a low incidence of ischaemic stroke, but display the usual incidence of myocardial infarction. In the present study, we compared the incidence of deep-vein thrombosis (DVT) in 219 unrelated patients with severe FXI deficiency aged 20–94 to the incidence in a large population-based study. No cases of DVT were observed in the FXI-deficient cohort, a result that is significantly lower than the expected number (4.68) computed from the population-based study. The low incidence remains statistically significant when compared to three other population-based studies. These data suggest that severe FXI deficiency provides protection against DVT.

scholarly journals The risk and trend of pulmonary embolism and deep vein thrombosis in rheumatoid arthritis: a general population-based study

Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 188-195
Author(s):  
Lingyi Li ◽  
Na Lu ◽  
Ana Michelle Avina-Galindo ◽  
Yufei Zheng ◽  
Diane Lacaille ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
General Population ◽  
Population Based ◽  
Case Definition ◽  
Population Based Study ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Deep Vein

Abstract Objectives To estimate the overall risk of venous thromboembolism (VTE), pulmonary embolism (PE) and deep vein thrombosis (DVT) among patients newly diagnosed with RA compared with the general population without RA; and to estimate the risk trends of VTE, PE and DVT after RA diagnosis up to 5 years compared with the general population. Methods Using previously validated RA case definition, we conducted a matched cohort study using the population-based administrative health database from the province of British Columbia, Canada. We calculated incidence rates (IRs) and fully adjusted hazard ratios (HRs) for the risk of VTE, DVT and PE after RA index date. Results Among 39 142 incident RA patients (66% female, mean age 60), 1432, 543 and 1068 developed VTE, PE and DVT, respectively. IRs for the RA cohort were 3.79, 1.43 and 2.82 per 1000 person-years vs 2.70, 1.03 and 1.94 per 1000 person-years for the non-RA cohort. After adjusting for VTE risk factors, the HRs (95% CI) were 1.28 (1.20, 1.36), 1.25 (1.13, 1.39) and 1.30 (1.21, 1.40) for VTE, PE and DVT, respectively. The fully adjusted HRs for VTE during the first five years after RA diagnosis were 1.60, 1.47, 1.40, 1.30 and 1.28, respectively. A similar trend was shown in PE. Conclusion This population-based study demonstrates that RA patients have an increased risk of VTE, PE and DVT after diagnosis compared with the general population. This risk is independent of traditional VTE risk factors and is highest during the first year after RA diagnosis, then progressively declined.

A Replication Study of Gene Variants Associated with Venous Thrombosis. Results From a Population-Based Nested Case-Cohort Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3985-3985 ◽  
Author(s):  
Willem M Lijfering ◽  
Irene D Bezemer ◽  
Sverre C Christiansen ◽  
Inger-Anne Naess ◽  
Frits Rosendaal ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thrombosis ◽  
Population Based ◽  
Gene Variants ◽  
Odds Ratios ◽  
Population Based Study ◽  
Vein Thrombosis ◽  
Risk Alleles ◽  
Increased Risk ◽  
Deep Vein

Abstract Abstract 3985 Poster Board III-921 Background Venous thrombosis has genetic and acquired risk factors, and it has been proposed that several risk factors are needed for the occurrence of the disease. The identification of common gene variants associated with venous thrombosis may improve the ability to predict the risk and understanding of this disease. In a recent study, we aimed to identify genetic variants that are associated with deep vein thrombosis in individuals aged younger than 70 years (JAMA 2008; 299:1306-14). Of nearly 20000 single nucleotide polymorphisms (SNPs) that were genotyped, 7 SNPs were associated with deep vein thrombosis (range odds ratios, 1.1-1.3). However, studies of thousands of SNPs can lead to false-positive associations. Replication studies are therefore pivotal to account for false-positive associations. Objective To assess the risk of venous thrombosis of aforementioned SNPs in a large population based study. Methods From the residents of Nord-Trøndelag county in Norway aged 20 years and older (n = 94194), we identified all patients with an objectively verified diagnosis of venous thrombosis that occurred between 1995 and 2001. By this date we had registered 515 patients with a first venous thrombosis; an age- and sex-stratified random sample of 1476 controls without previous venous thrombosis was drawn from the original cohort. Patients and diagnosis characteristics were retrieved from medical records. Of the 7 SNPs that were associated with deep vein thrombosis in our previous study, 6 were analyzed in the present study, i.e. rs13146272 in CYP4V2; rs2227589 in SERPINC1; rs1613662 in GP6; rs670659 in RGS7; rs1523127 in NR1I2; and rs6048 in F9. DNA concentrations were standardized to 10 ng/μL using PicoGreen (Molecular Probes, Invitrogen Corp, Carlsbad, CA, USA) fluorescent dye. Genotyping of individual DNA samples were demonstrated by polymerase chain reactions using the TaqMan assay. The technicians were blinded to whether the samples came from patients or control subjects. Results The median age of both cases and controls at baseline was 70 years (range, 20-98). Almost half of patients and controls were men. Two thirds of the patients had deep vein thrombosis and one third had pulmonary embolism. Among the 515 events, 246 were idiopathic (48%). The prevalences of the 6 analyzed risk alleles were 17-96% in the patients and 16-96% in the control group. Only the F9 (rs6048) risk allele in men was consistently associated with an increased risk of venous thrombosis with odds ratios of 1.27 (95% CI, 0.83-1.93) for deep vein thrombosis, 1.62 (95% CI, 0.91-2.89) for pulmonary embolism, and 1.38 (95% CI, 0.97-1.97) for total venous thrombosis. For all other risk alleles we found odds ratios for venous thrombosis close to 1.0 compared to their reference allele. Odds ratios for provoked or idiopathic venous thrombosis again showed that only the F9 risk allele in men was consistently associated with an increased risk with an odds ratio of 1.30 (95% CI, 0.82-2.08) for provoked venous thrombosis and 1.47 (95% CI, 0.90-2.38) for idiopathic venous thrombosis, respectively, compared to men with the G allele. To make the current analysis more similar with our previous study, we restricted the analysis to those who were younger than 70 years. This resulted in slightly higher odds ratios for venous thrombosis in CYP4V2, SERPINC1 and GP6 variants (Table). Conclusion This population based study confirmed the previous finding that men with the A allele of rs6048 in F9 have an increased risk of venous thrombosis, while we could not replicate the association of gene variants in CYP4V2, SERPINC1, GP6, RGS7 and NR1I2 with venous thrombosis, possibly excepted for CYP4V2, SERPINC1 and GP6 gene variants in individuals aged younger than 70 years. Disclosures: No relevant conflicts of interest to declare.

Factor XI in Clinical Bleeding and Thrombotic Disorders

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-21-SCI-21
Author(s):  
Uri Seligsohn ◽  
Ophira Salomon
Keyword(s):  
Myocardial Infarction ◽  
Deep Vein Thrombosis ◽  
Ischemic Stroke ◽  
Allele Frequencies ◽  
Bleeding Disorders ◽  
Expected Number ◽  
Factor Xi ◽  
Similar Frequency ◽  
Vein Thrombosis ◽  
Deep Vein

Abstract Abstract SCI-21 Severe inherited bleeding disorders have served as models for unraveling the role of specific coagulation factors in hemostasis and thrombosis and for design of antithrombotic agents. Factor XI (FXI) deficiency, was described in 1953 as a mild to moderate autosomal dominant bleeding disorder. Later studies indicated that inheritance is autosomal recessive with homozygotes or compound heterozygotes having a major deficiency of FXI and heterozygotes exhibiting a minor deficiency. FXI deficiency is the most frequent entity among rare inherited bleeding disorders; in worldwide surveys and registries, its relative frequency ranged between 24–60%. The prevalence of heterozygous FXI deficiency is very high in Ashkenazi Jews (1:11) in whom two predominant mutations, Glu117X and Phe283Leu, of similar frequency were described, with allele frequencies of 0.0217 and 0.0254, respectively. The Glu117X is also found in Iraqi Jews, Arabs and Italians at decreasing prevalences. A Cys38Arg mutation is prevalent in French Basques, and a Cys128X is prevalent in Britons with allele frequencies of 0.005 and 0.009, respectively. More than 185 additional mutations have been described usually in individual patients (www.factorXI.org). The common presentation of severe FXI deficiency is injury related bleeding, e.g. tooth extractions. Alternatively, a pronged aPTT in a routine examination leads to the diagnosis. Surgery or trauma at sites with increased fibrinolytic activity can be associated with excessive bleeding in 53–67% of untreated patients (Salomon et al. Haemophilia 2006, 12:490). The frequency of bleeding in heterozygotes with partial FXI deficiency is substantially lower than in patients with a severe deficiency. An additional hemostatic abnormality in such instances is likely. The procoagulant and antifibrinolytic effects of FXI mediated by augmented thrombin generation and activation of thrombin activatable fibrinolysis inhibitor could imply that elevated FXI levels confer an increased risk of thrombosis. This was indeed found in patients with deep vein thrombosis and ischemic stroke but is controversial in acute myocardial infarction suggesting that low levels of FXI might be protective at least against ischemic stroke and deep vein thrombosis. This assumption is also supported by animal models of venous and arterial thrombosis in which severe FXI deficiency confers protection against thrombosis yet without causing bleeding. In a cohort of 115 patients older than 45 years with severe FXI deficiency, we recently showed that 19 have had a myocardial infarction, implying a frequency that was expected in the Israeli population. In contrast, only 1 patient had an ischemic stroke, whereas the expected number of ischemic strokes in an Israeli health survey of 9509 subjects was 8.56 (p=0.0037) after adjustment for ischemic stroke risk factors (Salomon et al. Blood 2008, 111:4113). In another cohort of 219 patients with severe FXI deficiency, the expected number of subjects with deep vein thrombosis derived from a population based study was 4.65, whereas the observed number was 0 (p=0.019). These data suggest that severe FXI deficiency provides protection against deep vein thrombosis and ischemic stroke but not against myocardial infarction. These variable manifestations probably stem from differences in the aforementioned vascular beds. Collectively, these observations warrant development of means to induce FXI deficiency for potential use as new antithrombotic treatment modalities. Disclosures: Seligsohn: ISIS Pharmaceuticals, U.S.A.: Membership on an entity's Board of Directors or advisory committees.

scholarly journals PB2438 DEEP-VEIN THROMBOSIS IN PATIENTS WITH FACTOR XI DEFICIENCY FROM THE SOUTH OF TUNISIA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 1080
Author(s):  
F. Kotti ◽  
F. Megdiche ◽  
L. Mbarek ◽  
M. Ghorbel ◽  
O. Kassar ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
The South ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Vein Thrombosis ◽  
Deep Vein

Die vollständige Kompressionssonographie zur Diagnose der proximalen und distalen Venenthrombose – eine retrospektive Untersuchung

VASA ◽  
2001 ◽  
Vol 30 (4) ◽  
pp. 253-257 ◽  
Author(s):  
Sebastian M. Schellong ◽  
T. Schwarz ◽  
T. Pudollek ◽  
B. Schmidt ◽  
H. E. Schroeder
Keyword(s):  
Deep Vein Thrombosis ◽  
Outcome Study ◽  
Repeated Testing ◽  
Clinical Safety ◽  
Vein Thrombosis ◽  
Clinical Probability ◽  
Compression Ultrasound ◽  
Low Incidence ◽  
Deep Vein

Background: Compression ultrasound is considered the preferred test for the diagnosis of deep vein thrombosis of the leg (DVT). Since sensitivity for distal thrombosis is low additional tests are required. We developed a protocol of complete compression ultrasound of all venous segments of the leg (CCUS). A retrospective outcome study was performed to get an estimate of the rate of indeterminate results necessitating repeated testing as well as for the clinical safety of CCUS in a cohort of consecutive, unselected patients. Patients and methods: Case records of all patients referred for clinical suspicion of deep vein thrombosis within a three months period were reviewed. Patients with negative CCUS were followed directly or via the general practitioner in order to know whether an episode of venous thromboembolism had been documented since the initial CCUS. Results: 132 inpatients and 154 outpatients were identified. Clinical probability was high in 50 patients, medium in 142, and low in 94. The first CCUS was negative in 209 cases. Five patients (1,8%) had repeated CCUS within the next 7 days because of incomplete visualisation of the distal veins and turned out to be negative as well. Of all 214 patients with negative CCUS a clinical follow-up information was obtained after 168 ± 25 days. Five patients had died, none due to pulmonary embolism. In two patients deep vein thrombosis had been documented (0,9% [95% CI: 0,1–3,3%]) 148 and 172 days after CCUS, respectively. Conclusion: CCUS for diagnosis of DVT needs to be repeated in very few cases only. Clinical safety seems to fall into the same range as with combined algorithms and should be tested in a prospective design. Patients with medium and high probability showed a very low incidence of DVT within three months following CCUS; therefore, they may be included in a prospective outcome study.

scholarly journals Thromboprophylaxis for Deep Vein Thrombosis and Pulmonary Embolism after Total Joint Arthroplasty in a Low Incidence Population

2013 ◽  
Vol 25 (2) ◽  
pp. 43-53 ◽  
Author(s):  
Kang-Il Kim ◽  
Dong-Geun Kang ◽  
Sumit S. Khurana ◽  
Sang-Hak Lee ◽  
Young-Joo Cho ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Total Joint Arthroplasty ◽  
Joint Arthroplasty ◽  
Vein Thrombosis ◽  
Low Incidence ◽  
Deep Vein

scholarly journals Metabolic syndrome increases risk of venous thromboembolism recurrence after acute deep vein thrombosis

2020 ◽  
Vol 4 (1) ◽  
pp. 127-135 ◽  
Author(s):  
Lauren K. Stewart ◽  
Jeffrey A. Kline
Keyword(s):  
Metabolic Syndrome ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Large Population ◽  
Rank Statistic ◽  
Explanatory Variables ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Recurrent Venous Thromboembolism ◽  
Deep Vein

Abstract An improved understanding of which patients are at higher risk of recurrent venous thromboembolism (VTE) is important to designing interventions to reduce degraded quality of life after VTE. Although metabolic syndrome (MetS), the clustering of hypertension, hyperlipidemia, diabetes mellitus, and obesity has been associated with a hypofibrinolytic state, data linking VTE recurrence with MetS remain limited. The purpose of this study was to measure the prevalence of MetS in patients with deep vein thrombosis (DVT) across a large population and determine its effect on VTE recurrence. This was a retrospective analysis of a large statewide database from 2004 to 2017. We measured the frequency with which patients with DVT carried a comorbid International Coding of Diseases diagnosis of MetS components. Association of MetS with VTE recurrence was tested with a multiple logistic regression model and VTE recurrence as the dependent variable. Risk of VTE recurrence conferred by each MetS component was assessed by Kaplan-Meier curves with the log-rank statistic. A total of 151 054 patients with DVT were included in this analysis. Recurrence of VTE occurred in 17% overall and increased stepwise with each criterion for MetS. All 4 components of MetS had significant adjusted odds ratios (OR) for VTE recurrence, with hyperlipidemia having the largest (OR, 1.8), representing the 4 largest ORs of all possible explanatory variables. All 4 MetS variables were significant on Kaplan-Meier analysis for recurrence of VTE. These data imply a role for appropriate therapies to reduce the effects of MetS as a way to reduce risk of VTE recurrence.

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