Fibrinogen and the Risk of Thrombosis

Fibrinogen contributes to thrombosis risk in different ways. Indeed, various mutations in the fibrinogen genes predispose to thrombosis. At the same time, high levels of fibrinogen are also associated with thrombotic complications. Although the underlying causative mechanisms are not clear, this most likely involves the associated inflammatory and hypercoagulable states. In the last few years, particular attention has focused on the polymorphisms of fibrinogen genes involved in increased fibrinogen levels or fibrinogen qualitative changes. The association between dysfibrinogenemia and risk of thrombosis is well known, and some mechanisms have been clearly identified. Paradoxically, some patients with either hypofibrinogenemia or afibrinogenemia may also suffer from severe thromboembolic complications. The management of these patients is particularly challenging because they are not only at risk of thrombosis but also of bleeding. This review discusses the various quantitative and qualitative defects of fibrinogen associated with thrombosis, the tests that may predict the thrombotic risk, as well as some preventive or therapeutic approaches.

[1]  L. Rallidis,et al.  G-455A polymorphism of beta-fibrinogen gene and the risk of premature myocardial infarction in Greece. , 2010, Thrombosis research.

[2]  Virgil L. Woods,et al.  High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension. , 2009, Blood.

[3]  D. Kurnik,et al.  Genetic variants and risk for venous thromboembolic events: Summing up the evidence , 2009, Thrombosis and Haemostasis.

[4]  P. Reitsma,et al.  Genetics of venous thrombosis , 2009, Journal of thrombosis and haemostasis : JTH.

[5]  G. Peck,et al.  The genetics of venous thromboembolism , 2009, Thrombosis and Haemostasis.

[6]  P. de Moerloose,et al.  Congenital Fibrinogen Disorders , 2009, Seminars in thrombosis and hemostasis.

[7]  N. Dowling,et al.  Fibrinogen gamma gene 3’-end polymorphisms and risk of venous thromboembolism in the African-American and Caucasian population , 2009, Thrombosis and Haemostasis.

[8]  E. Boerwinkle,et al.  Antihypertensive pharmacogenetic effect of fibrinogen-beta variant −455G>A on cardiovascular disease, end-stage renal disease, and mortality: the GenHAT study , 2009, Pharmacogenetics and genomics.

[9]  C. Bai,et al.  Fibrinogen independently predicts the development of ischemic stroke in a Taiwanese population: CVDFACTS study. , 2009, Stroke.

[10]  A. Demchuk,et al.  Hyperfibrinogenemia and functional outcome from acute ischemic stroke. , 2009, Stroke.

[11]  C. Gieger,et al.  Association of Novel Genetic Loci With Circulating Fibrinogen Levels: A Genome-Wide Association Study in 6 Population-Based Cohorts , 2009, Circulation. Cardiovascular genetics.

[12]  A. Peters,et al.  Fibrinogen genes modify the fibrinogen response to ambient particulate matter. , 2009, American journal of respiratory and critical care medicine.

[13]  A. Algra,et al.  Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke , 2009, Journal of thrombosis and haemostasis : JTH.

[14]  A. Peters,et al.  Common genetic polymorphisms and haplotypes of fibrinogen alpha, beta, and gamma chains affect fibrinogen levels and the response to proinflammatory stimulation in myocardial infarction survivors: the AIRGENE study. , 2008, Journal of the American College of Cardiology.

[15]  A. Hofman,et al.  Variation in fibrinogen FGG and FGA genes and risk of stroke , 2008, Thrombosis and Haemostasis.

[16]  G. Castaman,et al.  New approaches in the measurement of coagulation , 2008, Haemophilia : the official journal of the World Federation of Hemophilia.

[17]  P. de Moerloose,et al.  Treatment of congenital fibrinogen disorders , 2008 .

[18]  M. Woodward,et al.  Associations of plasma pro‐inflammatory cytokines, fibrinogen, viscosity and C‐reactive protein with cardiovascular risk factors and social deprivation: the fourth Glasgow MONICA study , 2008, British journal of haematology.

[19]  C. Ladenvall,et al.  Fibrinogen gene variation and ischemic stroke , 2008, Journal of thrombosis and haemostasis : JTH.

[20]  F. Rosendaal,et al.  Polymorphisms in coagulation factors and the risk of recurrent cardiovascular events in men after a first myocardial infarction , 2008, Journal of thrombosis and haemostasis : JTH.

[21]  C. Carlson,et al.  Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults , 2008, Thrombosis and Haemostasis.

[22]  N. Cook,et al.  Rationale, design, and methodology of the Women's Genome Health Study: a genome-wide association study of more than 25,000 initially healthy american women. , 2008, Clinical chemistry.

[23]  A. Hofman,et al.  Haplotypes of the fibrinogen gene and cerebral small vessel disease: the Rotterdam scan study , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[24]  J. Danesh,et al.  Associations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies: the fibrinogen studies collaboration. , 2007, American journal of epidemiology.

[25]  M. Woodward,et al.  A comparison of the associations between seven hemostatic or inflammatory variables and coronary heart disease , 2007, Journal of thrombosis and haemostasis : JTH.

[26]  M. Hennerici,et al.  Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial , 2006, The Lancet.

[27]  C. Négrier,et al.  Use of calibrated automated thrombinography ± thrombomodulin to recognise the prothrombotic phenotype , 2006, Thrombosis and Haemostasis.

[28]  A. Girolami,et al.  Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review , 2006, Haemophilia : the official journal of the World Federation of Hemophilia.

[29]  M. Rieder,et al.  Association between patterns of nucleotide variation across the three fibrinogen genes and plasma fibrinogen levels: the Coronary Artery Risk Development in Young Adults (CARDIA) study , 2006, Journal of thrombosis and haemostasis : JTH.

[30]  J. Houwing-Duistermaat,et al.  Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. , 2005, Blood.

[31]  Shah Ebrahim,et al.  Does Elevated Plasma Fibrinogen Increase the Risk of Coronary Heart Disease?: Evidence from a Meta-Analysis of Genetic Association Studies , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[32]  A. Hamsten,et al.  Quest for genes regulating plasma fibrinogen concentration: still a long way to go. , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[33]  L. Almasy,et al.  A Genome Search for Genetic Determinants That Influence Plasma Fibrinogen Levels , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[34]  S. Daskalopoulou,et al.  Peripheral arterial disease: a missed opportunity to administer statins so as to reduce cardiac morbidity and mortality. , 2005, Current medicinal chemistry.

[35]  D. Perry,et al.  The rare coagulation disorders – review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation , 2004, Haemophilia : the official journal of the World Federation of Hemophilia.

[36]  R. Schuepbach,et al.  Lepirudin therapy for thrombotic complications in congenital afibrinogenaemia , 2004, Thrombosis and Haemostasis.

[37]  W. Korte,et al.  Increased prothrombin activation in a patient with congenital afibrinogenemia is reversible by fibrinogen substitution , 1994, The clinical investigator.

[38]  F. Rosendaal,et al.  High levels of fibrinogen are associated with the risk of deep venous thrombosis mainly in the elderly , 2003, Journal of thrombosis and haemostasis : JTH.

[39]  J. Weisel,et al.  Functional Analysis of the Fibrinogen A&agr; Thr312Ala Polymorphism: Effects on Fibrin Structure and Function , 2003, Circulation.

[40]  D. Levy,et al.  A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study. , 2003, Thrombosis research.

[41]  W. Koenig Fibrin(ogen) in cardiovascular disease: an update , 2003, Thrombosis and Haemostasis.

[42]  M. Mosesson Antithrombin I. Inhibition of thrombin generation in plasma by fibrin formation , 2003, Thrombosis and Haemostasis.

[43]  T. Hayes Dysfibrinogenemia and thrombosis. , 2009, Archives of pathology & laboratory medicine.

[44]  A. Ruiz-Sáez,et al.  Inhibition of Thrombin Generation in Plasma by Fibrin Formation (Antithrombin I) , 2002, Thrombosis and Haemostasis.

[45]  H. Ni,et al.  Association of (cid:2) A/ (cid:2) ’ Fibrinogen Levels and Coronary Artery Disease , 2022 .

[46]  C. Soria,et al.  Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin. , 2001, Thrombosis research.

[47]  J. Sixma,et al.  Absence of Fibrinogen in Afibrinogenemia Results in Large but Loosely Packed Thrombi under Flow Conditions , 2001, Thrombosis and Haemostasis.

[48]  A. Carter,et al.  α-Fibrinogen Thr312Ala polymorphism and venous thromboembolism , 2000 .

[49]  Thomas N. Sato,et al.  Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. , 2000, The Journal of clinical investigation.

[50]  D. Levy,et al.  Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial. , 2000, JAMA.

[51]  P. Mannucci,et al.  Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia , 1999, British journal of haematology.

[52]  F. Rosendaal,et al.  Increased Levels of Factor VIII and Fibrinogen in Patients with Venous Thrombosis Are not Caused by Acute Phase Reactions , 1999, Thrombosis and Haemostasis.

[53]  B. Sobel,et al.  Increased reactivity of platelets induced by fibrinogen independent of its binding to the IIb-IIIa surface glycoprotein: a potential contributor to cardiovascular risk. , 1999, Journal of the American College of Cardiology.

[54]  G. Retzinger,et al.  Adsorption of fibrinogen to droplets of liquid hydrophobic phases. Functionality of the bound protein and biological implications. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[55]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[56]  J. Powell,et al.  Vasoactive effects of fibrinogen on saphenous vein , 1996, Nature.

[57]  A. Evans,et al.  β Fibrinogen Gene Polymorphisms Are Associated With Plasma Fibrinogen and Coronary Artery Disease in Patients With Myocardial Infarction , 1996 .

[58]  M. Samama,et al.  Familial Dysfibrinogenemia and Thrombophilia , 1995, Thrombosis and Haemostasis.

[59]  P. Reitsma,et al.  Factor VII and Fibrinogen Levels as Risk Factors for Venous Thrombosis , 1994, Thrombosis and Haemostasis.

[60]  J. Loscalzo,et al.  Recent observations on the role of hemostatic determinants in the development of the atherothrombotic plaque. , 1994, Atherosclerosis.

[61]  T. Vischer,et al.  Absence of correlation between interleukin 6 and C-reactive protein blood levels in systemic lupus erythematosus compared with rheumatoid arthritis. , 1993, The Journal of rheumatology.

[62]  W. Nieuwenhuizen,et al.  A Monoclonal Antibody-Based Qunatitative Enzyme Immunoassay for the Determination of Plasma Fibrinogen Concentartions , 1988, Thrombosis and Haemostasis.

[63]  A. Girolami,et al.  von Willebrand factor interaction with the glycoprotein IIb/IIa complex. Its role in platelet function as demonstrated in patients with congenital afibrinogenemia. , 1986, The Journal of clinical investigation.

[64]  G. Crabtree,et al.  Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion. , 1985, Proceedings of the National Academy of Sciences of the United States of America.