Factor XI as a target for preventing venous thromboembolism

2022 ◽  
Author(s):  
David Gailani
Keyword(s):  
Venous Thromboembolism ◽  
Factor Xi

Association of common genetic variations and idiopathic venous thromboembolism

2010 ◽  
Vol 103 (06) ◽  
pp. 1161-1169 ◽  
Author(s):  
Aurélien Delluc ◽  
Lénaïck Gourhant ◽  
Karine Lacut ◽  
Bernard Mercier ◽  
Marie-Pierre Audrezet ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Coagulation Cascade ◽  
Factor V ◽  
Cascade Process ◽  
Nucleotide Polymorphisms ◽  
Factor Xi ◽  
Bonferroni Adjustment ◽  
Adrenergic Systems

SummaryVenous thromboembolism (VTE) is a multifactorial disease, caused by interacting environmental and genetic risk factors. Gene-centric geno-typing strategy is one of the approaches to explore unexplained associations between risk factors and VTE. It was the objective of this study to evaluate, using a gene-centric genotyping strategy, polymorphisms in genes involved in the following pathways: coagulation cascade process, renin-angiotensin or adrenergic systems, lipid metabolism, platelet aggregation. Allele frequency was compared between 677 cases with idiopathic VTE and their matched controls. After Bonferroni adjustment, four single nucleotide polymorphisms (SNPs) were significantly associated with VTE: Factor XI rs925451 polymorphism, factor XI rs2289252 polymorphism, factor II rs1799963 (G20210A) polymorphism and factor V Leiden rs6025. An additive mode of inheritance fitted best both factor XI polymorphisms. In this hospital-based case-control study, two polymorphisms located on the factor XI gene were significantly associated with VTE. Other newly investigated polymorphisms with potentially false negatives may warrant further analyses.

Inherited Factor XI Deficiency Is Associated with Decrease Risk for Cardiovascular Adverse Event and Venous Thromboembolism - Israeli Population Based Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1387-1387
Author(s):  
Meir Preis ◽  
Julianna Hirsch ◽  
Antonio Kotler ◽  
Nili Stein ◽  
Ahmad Zoabi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cardiovascular Event ◽  
Coagulation Factors ◽  
Activity Level ◽  
Activity Levels ◽  
Proportional Hazard ◽  
Factor Xi ◽  
Adverse Cardiovascular Event ◽  
Factor Xi Deficiency ◽  
Severe Deficiency

Abstract Introduction Israel contains within it a unique variety of groups predisposed to autosomal recessive diseases secondary to the history of segregated religious communities. Indicated groups include Ashkenazi Jews and Israeli Arabs. Factor XI deficiency is one of the conditions that can be included in this group of diseases. It is reported to have a prevalence of 8-13.4% within the Ashkenazi Jewish community as compared to a 1 in a million in the general population. Due to the risk for bleeding and delayed coagulation as a result of a deficient Factor XI, it has been postulated that an underlying cardiovascular benefit may protect the Factor XI deficient subjects from developing an adverse cardiovascular event or venous thromboembolism. Methods This is an observational, historical cohort study performed using the electronic data base of Clalit Health organization, largest HMO in Israel. The objective of this study is to determine the effects of possessing a Factor XI deficiency on adverse cardiovascular event the venous thromboembolism. The study was approved by a centralized IRB committee. All subjects tested for Factor XI activity were included in the study and divided in 3 groups based on factor XI activity level: Group A - Moderate to Severe deficiency (less than 30% activity), Group B - Mild deficiency (30-50% activity), Group C - Normal (more than 50% activity). Proportional hazard regression analysis was used to assess the association between the time to event and factors XI activity, adjusting for potential confounders. Distribution of time to the tested event will be presented by Kaplan-Meier curves and compared with the log rank test. Proportional hazard regression analysis will be used to assess the association between time to event and coagulation factors activity, adjusting for potential confounders. The P value for trend will be calculated by including the predefined categories of the coagulation factors as continuous variable in the model. The association will estimated with hazard ratio (HR) with 95% confidence interval (CI), comparing each factor category with the highest category as reference. Results Total of 10,193 subjects were tested for Factor XI activity levels between 2002-2015. Moderate to Severe factor XI deficiency (<=30%) was identified in 542 (5.3%) of tested individuals. Mild factor XI deficiency (30-50%) was identified in 693 (6.8%) of tested individuals. Compare to Individuals with factor XI activity >50%, factor XI deficiency was associated with decreased risk of the composite end point of major cardiovascular event (MI, stroke or TIA): For factor XI activity <=30% HR was 0.56 (95% CI, 0.34-0.9); For factor XI activity 30-50% HR was 0.54 (95% CI, 0.33-0.89). Factor XI activity levels of less than 50% were associated with decrease risk for venous thromboembolism (PE or DVT), HR-0.25 (95% CI, 0.08-0.81, p<0.021) Conclusions Factor XI deficiency is associated with decrease risk for adverse cardiovascular event and decreased risk for thromboembolic events. Mild factor XI deficiency (activity level of 30-50%) is associated with a similar decrease in risk as moderate to severe deficiency. Disclosures No relevant conflicts of interest to declare.

scholarly journals Novel antithrombotic strategies for treatment of venous thromboembolism

Blood ◽  
2020 ◽  
Vol 135 (5) ◽  
pp. 351-359 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Noel C. Chan
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Postthrombotic Syndrome ◽  
Factor Xii ◽  
Factor Xi ◽  
Vein Thrombosis ◽  
New Anticoagulants

Abstract Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cause of vascular death after heart attack and stroke. Anticoagulation therapy is the cornerstone of VTE treatment. Despite such therapy, up to 50% of patients with DVT develop postthrombotic syndrome, and up to 4% of patients with PE develop chronic thromboembolic pulmonary hypertension. Therefore, better therapies are needed. Although direct oral anticoagulants are more convenient and safer than warfarin for VTE treatment, bleeding remains the major side effect, particularly in cancer patients. Factor XII and factor XI have emerged as targets for new anticoagulants that may be safer. To reduce the complications of VTE, attenuation of thrombin activatable fibrinolysis inhibitor activity is under investigation in PE patients to enhance endogenous fibrinolysis, whereas blockade of leukocyte interaction with the vessel wall is being studied to reduce the inflammation that contributes to postthrombotic syndrome in DVT patients. Focusing on these novel antithrombotic strategies, this article explains why safer anticoagulants are needed, provides the rationale for factor XII and XI as targets for such agents, reviews the data on the factor XII– and factor XI–directed anticoagulants under development, describes novel therapies to enhance fibrinolysis and decrease inflammation in PE and DVT patients, respectively, and offers insights into the opportunities for these novel VTE therapies.

scholarly journals Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events

Blood ◽  
2017 ◽  
Vol 129 (9) ◽  
pp. 1210-1215 ◽  
Author(s):  
Meir Preis ◽  
Julianna Hirsch ◽  
Antonio Kotler ◽  
Ahmad Zoabi ◽  
Nili Stein ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Lower Risk ◽  
Cardiovascular Events ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Key Points ◽  
Thromboembolism Events ◽  
Reduced Risk

Key Points Factor XI deficiency is associated with reduced risk of cardiovascular events. Factor XI deficiency is associated with reduced risk of VTE.

Patients with Severe Factor XI Deficiency Have a Reduced Incidence of Venous Thromboembolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3491-3491 ◽  
Author(s):  
Ophira Salomon ◽  
Ariella Zivelin ◽  
Ilia Tamarin ◽  
David M. Steinberg ◽  
David Varon ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Incidence Rate ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
G20210a Mutation ◽  
Increased Risk ◽  
The Common

Abstract Abstract 3491 Poster Board III-428 Patients with severe factor XI deficiency (level ≤15U/dL) were recently found to be protected against ischemic stroke but not against myocardial infarction (Blood 2008, 111:4113). Regarding venous thrombosis, several clinical and experimental observations suggest that factor XI deficiency might confer protection. Thus, only 2 patients with severe factor XI deficiency have been reported with unprovoked venous thromboembolism, and protection against FeCl3 Cinduced thrombosis in the vena cava was observed in factor XI deficient mice (J Thromb Haemost 2006, 4:1982). Other studies established that an increased level of factor XI is associated with an increased risk of venous thromboembolism. In the present study, we investigated whether patients with severe factor XI deficiency are protected against venous thromboembolism. We interviewed 222 unrelated patients with severe FXI deficiency and reviewed their medical charts. In the cohort, there were 126 females and 96 males aged 20-94 years of whom 137 were 50 years or older. The expected incidence rates of venous thromboembolism in the general population for males and females at different age groups were extracted from a population-based study of venous thromboembolism (J Thromb Haemost 2007,5:692). The expected incidence rate of venous thromboembolism in the factor XI deficiency cohort was 4.67 (2.37 in females and 2.30 in males), while the observed incidence rate was 0/222. This difference was statistically significant taking into account age and sex by the Poisson test (p=0.036). The prevalence of the common inherited thrombophilias was examined in 194 of the 222 patients. Seven (3.6%) patients harbored factor V Leiden, and 17 (8.8%) harbored the prothrombin G20210A mutation; the corresponding proportions in the general Israeli population are 3.9% for factor V Leiden, and 5.4% for prothrombin G20210A mutation. Thus, there was no decreased prevalence of the common thrombophilias in the factor XI deficient cohort. Collectively, the data suggest that patients with severe factor XI deficiency are protected against venous thromboembolism. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prospective study of circulating factor XI and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE)

2015 ◽  
Vol 90 (11) ◽  
pp. 1047-1051 ◽  
Author(s):  
Aaron R. Folsom ◽  
Weihong Tang ◽  
Nicholas S. Roetker ◽  
Susan R. Heckbert ◽  
Mary Cushman ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Prospective Study ◽  
Factor Xi ◽  
Longitudinal Investigation

scholarly journals Epidemiologic and clinical data linking factors XI and XII to thrombosis

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 66-70 ◽  
Author(s):  
Nigel S. Key
Keyword(s):  
Myocardial Infarction ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
Venous Thromboembolism ◽  
Plasma Levels ◽  
Fibrinolytic Activity ◽  
Bleeding Risk ◽  
Factor Xi ◽  
Mucosal Surfaces ◽  
Design Type

Abstract Currently available evidence supports the contention that elevated levels of factor XI (fXI) are associated with a greater risk of venous thromboembolism and ischemic stroke, but, less convincingly, with myocardial infarction. Conversely, reduced plasma levels of fXI seem to offer some protection from venous thromboembolism and stroke, but not myocardial infarction. Factor XI-deficient patients are at risk for certain types of bleeding, particularly posttraumatic hemorrhage on mucosal surfaces where there is a high endogenous fibrinolytic activity. In contrast, the situation with fXII in human thrombosis remains enigmatic. Deficiency of fXII is clearly not associated with any bleeding risk, but neither does it seem to be protective against thrombosis. The longstanding debate as to whether partial fXII deficiency represents a risk factor for thrombosis remains unresolved, with seemingly conflicting results depending on study design, type of assay used, and analyte evaluated. The possibility that elevated fXII levels represent a risk factor for thrombosis is not borne out in the literature.

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