The (Patho)physiology of Fibrinogen γ′

Fraser L. Macrae; Marco M. Domingues; Alessandro Casini; Robert A. S. Ariëns

doi:10.1055/s-0036-1572353

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2016; 42(04): 344-355
DOI: 10.1055/s-0036-1572353

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The (Patho)physiology of Fibrinogen γ′

Autor*innen

Fraser L. Macrae

¹Thrombosis and Tissue Repair Group, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
Marco M. Domingues

¹Thrombosis and Tissue Repair Group, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
Alessandro Casini

¹Thrombosis and Tissue Repair Group, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
Robert A. S. Ariëns

¹Thrombosis and Tissue Repair Group, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom

Abstract

Fibrinogen γ′ is a splice variant of the fibrinogen γ-chain, which leads to a negatively charged extension at the C-terminus of the γ-chain. In fibrinogen, the splice variant appears mainly as a heterodimer with the common γA chain, as γA/γ′ fibrinogen. This variant has been shown to modulate thrombin and factor XIII (FXIII) activity, influence clot architecture, and lack a platelet-binding site. Clinically γA/γ′ fibrinogen levels have been associated with arterial and venous thromboses, indicating that the functional effects of γA/γ′ fibrinogen may contribute to the pathology of thrombosis. In view of the fact that the splice variant has several functional effects and is found so far in all individuals, this review provides an up-to-date summary of the key biologic aspects of this fibrinogen variant and discusses any inconsistencies in current reports.

Keywords

fibrinogen - venous - arterial - thrombosis - FXIII - thrombin - clot structure

Volltext

Referenzen

References
1 Kant JA, Fornace Jr AJ, Saxe D, Simon MI, McBride OW, Crabtree GR. Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion. Proc Natl Acad Sci U S A 1985; 82 (8) 2344-2348
2 Mosesson MW, Finlayson JS, Umfleet RA. Human fibrinogen heterogeneities. 3. Identification of chain variants. J Biol Chem 1972; 247 (16) 5223-5227
3 Francis CW, Marder VJ, Martin SE. Demonstration of a large molecular weight variant of the gamma chain of normal human plasma fibrinogen. J Biol Chem 1980; 255 (12) 5599-5604
4 Fornace Jr AJ, Cummings DE, Comeau CM, Kant JA, Crabtree GR. Structure of the human gamma-fibrinogen gene. Alternate mRNA splicing near the 3′ end of the gene produces gamma A and gamma B forms of gamma-fibrinogen. J Biol Chem 1984; 259 (20) 12826-12830
5 Peerschke EI, Francis CW, Marder VJ. Fibrinogen binding to human blood platelets: effect of gamma chain carboxyterminal structure and length. Blood 1986; 67 (2) 385-390
6 Chung DW, Chan WY, Davie EW. Characterization of a complementary deoxyribonucleic acid coding for the gamma chain of human fibrinogen. Biochemistry 1983; 22 (13) 3250-3256
7 Chung DW, Davie EW. gamma and gamma' chains of human fibrinogen are produced by alternative mRNA processing. Biochemistry 1984; 23 (18) 4232-4236
8 Wolfenstein-Todel C, Mosesson MW. Human plasma fibrinogen heterogeneity: evidence for an extended carboxyl-terminal sequence in a normal gamma chain variant (gamma'). Proc Natl Acad Sci U S A 1980; 77 (9) 5069-5073
9 Wolfenstein-Todel C, Mosesson MW. Carboxy-terminal amino acid sequence of a human fibrinogen gamma-chain variant (gamma'). Biochemistry 1981; 20 (21) 6146-6149
10 Uitte de Willige S, de Visser MC, Houwing-Duistermaat JJ, Rosendaal FR, Vos HL, Bertina RM. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Blood 2005; 106 (13) 4176-4183
11 Nowak-Göttl U, Weiler H, Hernandez I , et al. Fibrinogen alpha and gamma genes and factor V Leiden in children with thromboembolism: results from 2 family-based association studies. Blood 2009; 114 (9) 1947-1953
12 Cheung EY, Uitte de Willige S, Vos HL , et al. Fibrinogen gamma' in ischemic stroke: a case-control study. Stroke 2008; 39 (3) 1033-1035
13 Mosesson MW, Hernandez I, Raife TJ , et al. Plasma fibrinogen gamma' chain content in the thrombotic microangiopathy syndrome. J Thromb Haemost 2007; 5 (1) 62-69
14 Uitte de Willige S, Rietveld IM, De Visser MC, Vos HL, Bertina RM. Polymorphism 10034C>T is located in a region regulating polyadenylation of FGG transcripts and influences the fibrinogen gamma'/gammaA mRNA ratio. J Thromb Haemost 2007; 5 (6) 1243-1249
15 Beyer K, Dandekar T, Keller W. RNA ligands selected by cleavage stimulation factor contain distinct sequence motifs that function as downstream elements in 3′-end processing of pre-mRNA. J Biol Chem 1997; 272 (42) 26769-26779
16 Mannila MN, Lovely RS, Kazmierczak SC , et al. Elevated plasma fibrinogen gamma' concentration is associated with myocardial infarction: effects of variation in fibrinogen genes and environmental factors. J Thromb Haemost 2007; 5 (4) 766-773
17 Lovely RS, Moaddel M, Farrell DH. Fibrinogen gamma' chain binds thrombin exosite II. J Thromb Haemost 2003; 1 (1) 124-131
18 Sabo TM, Farrell DH, Maurer MC. Conformational analysis of gamma' peptide (410-427) interactions with thrombin anion binding exosite II. Biochemistry 2006; 45 (24) 7434-7445
19 Pineda AO, Chen ZW, Marino F, Mathews FS, Mosesson MW, Di Cera E. Crystal structure of thrombin in complex with fibrinogen gamma' peptide. Biophys Chem 2007; 125 (2–3) 556-559
20 Pospisil CH, Stafford AR, Fredenburgh JC, Weitz JI. Evidence that both exosites on thrombin participate in its high affinity interaction with fibrin. J Biol Chem 2003; 278 (24) 21584-21591
21 de Bosch NB, Mosesson MW, Ruiz-Sáez A, Echenagucia M, Rodriguez-Lemoin A. Inhibition of thrombin generation in plasma by fibrin formation (Antithrombin I). Thromb Haemost 2002; 88 (2) 253-258
22 Fredenburgh JC, Stafford AR, Leslie BA, Weitz JI. Bivalent binding to gammaA/gamma'-fibrin engages both exosites of thrombin and protects it from inhibition by the antithrombin-heparin complex. J Biol Chem 2008; 283 (5) 2470-2477
23 Cooper AV, Standeven KF, Ariëns RA. Fibrinogen gamma-chain splice variant gamma' alters fibrin formation and structure. Blood 2003; 102 (2) 535-540
24 Moaddel M, Falls LA, Farrell DH. The role of gamma A/gamma ' fibrinogen in plasma factor XIII activation. J Biol Chem 2000; 275 (45) 35656
25 Kremers RM, Wagenvoord RJ, Hemker HC. The effect of fibrin(ogen) on thrombin generation and decay. Thromb Haemost 2014; 112 (3) 486-494
26 Lorand L. Factor XIII: structure, activation, and interactions with fibrinogen and fibrin. Ann N Y Acad Sci 2001; 936: 291-311
27 Lorand L, Maldonado N, Fradera J, Atencio AC, Robertson B, Urayama T. Haemorrhagic syndrome of autoimmune origin with a specific inhibitor against fibrin stabilizing factor (factor XIII). Br J Haematol 1972; 23 (1) 17-27
28 Allan P, Uitte de Willige S, Abou-Saleh RH, Connell SD, Ariëns RA. Evidence that fibrinogen γ' directly interferes with protofibril growth: implications for fibrin structure and clot stiffness. J Thromb Haemost 2012; 10 (6) 1072-1080
29 Gaffney PJ, Whitaker AN. Fibrin crosslinks and lysis rates. Thromb Res 1979; 14 (1) 85-94
30 Siebenlist KR, Mosesson MW. Progressive cross-linking of fibrin gamma chains increases resistance to fibrinolysis. J Biol Chem 1994; 269 (45) 28414-28419
31 Greenberg CS, Shuman MA. The zymogen forms of blood coagulation factor XIII bind specifically to fibrinogen. J Biol Chem 1982; 257 (11) 6096-6101
32 Mosesson MW, Finlayson JS. Biochemical and chromatographic studies of certain activities associated with human fibrinogen preparations. J Clin Invest 1963; 42: 747-755
33 Siebenlist KR, Meh DA, Mosesson MW. Plasma factor XIII binds specifically to fibrinogen molecules containing gamma chains. Biochemistry 1996; 35 (32) 10448-10453
34 Moaddel M, Farrell DH, Daugherty MA, Fried MG. Interactions of human fibrinogens with factor XIII: roles of calcium and the gamma' peptide. Biochemistry 2000; 39 (22) 6698-6705
35 Siebenlist KR, Meh DA, Mosesson MW. Protransglutaminase (factor XIII) mediated crosslinking of fibrinogen and fibrin. Thromb Haemost 2001; 86 (5) 1221-1228
36 Siebenlist KR, Mosesson MW, Hernandez I , et al. Studies on the basis for the properties of fibrin produced from fibrinogen-containing gamma' chains. Blood 2005; 106 (8) 2730-2736
37 Gersh KC, Lord ST. An investigation of factor XIII binding to recombinant gamma'/gamma' and gamma/gamma' fibrinogen [abstract]. Blood 2006; 108 (11) 485a
38 Smith KA, Adamson PJ, Pease RJ , et al. Interactions between factor XIII and the alphaC region of fibrinogen. Blood 2011; 117 (12) 3460-3468
39 Lovely RS, Boshkov LK, Marzec UM, Hanson SR, Farrell DH. Fibrinogen gamma' chain carboxy terminal peptide selectively inhibits the intrinsic coagulation pathway. Br J Haematol 2007; 139 (3) 494-503
40 Omarova F, Uitte De Willige S, Ariëns RA, Rosing J, Bertina RM, Castoldi E. Inhibition of thrombin-mediated factor V activation contributes to the anticoagulant activity of fibrinogen γ'. J Thromb Haemost 2013; 11 (9) 1669-1678
41 Segers K, Dahlbäck B, Bock PE, Tans G, Rosing J, Nicolaes GA. The role of thrombin exosites I and II in the activation of human coagulation factor V. J Biol Chem 2007; 282 (47) 33915-33924
42 Omarova F, Uitte de Willige S, Simioni P , et al. Fibrinogen γ' increases the sensitivity to activated protein C in normal and factor V Leiden plasma. Blood 2014; 124 (9) 1531-1538
43 Vu TT, Stafford AR, Leslie BA, Kim PY, Fredenburgh JC, Weitz JI. Histidine-rich glycoprotein binds fibrin(ogen) with high affinity and competes with thrombin for binding to the gamma'-chain. J Biol Chem 2011; 286 (35) 30314-30323
44 Poon IK, Patel KK, Davis DS, Parish CR, Hulett MD. Histidine-rich glycoprotein: the Swiss Army knife of mammalian plasma. Blood 2011; 117 (7) 2093-2101
45 Leung LL. Interaction of histidine-rich glycoprotein with fibrinogen and fibrin. J Clin Invest 1986; 77 (4) 1305-1311
46 Laurens N, Koolwijk P, de Maat MPM. Fibrin structure and wound healing. J Thromb Haemost 2006; 4 (5) 932-939
47 Cheung EYL, Weijers EM, Tuk B , et al. Specific effects of fibrinogen and the γA and γ'-chain fibrinogen variants on angiogenesis and wound healing. Tissue Eng Part A 2015; 21 (1–2) 106-114
48 Hawiger J, Timmons S, Kloczewiak M, Strong DD, Doolittle RF. gamma and alpha chains of human fibrinogen possess sites reactive with human platelet receptors. Proc Natl Acad Sci U S A 1982; 79 (6) 2068-2071
49 Kloczewiak M, Timmons S, Hawiger J. Localization of a site interacting with human platelet receptor on carboxy-terminal segment of human fibrinogen gamma chain. Biochem Biophys Res Commun 1982; 107 (1) 181-187
50 Kloczewiak M, Timmons S, Hawiger J. Recognition site for the platelet receptor is present on the 15-residue carboxy-terminal fragment of the gamma chain of human fibrinogen and is not involved in the fibrin polymerization reaction. Thromb Res 1983; 29 (2) 249-255
51 Kloczewiak M, Timmons S, Lukas TJ, Hawiger J. Platelet receptor recognition site on human fibrinogen. Synthesis and structure-function relationship of peptides corresponding to the carboxy-terminal segment of the gamma chain. Biochemistry 1984; 23 (8) 1767-1774
52 Harfenist EJ, Packham MA, Mustard JF. Effects of variant gamma chains and sialic acid content of fibrinogen upon its interactions with ADP-stimulated human and rabbit platelets. Blood 1984; 64 (6) 1163-1168
53 Hettasch JM, Bolyard MG, Lord ST. The residues AGDV of recombinant gamma chains of human fibrinogen must be carboxy-terminal to support human platelet aggregation. Thromb Haemost 1992; 68 (6) 701-706
54 Farrell DH, Thiagarajan P. Binding of recombinant fibrinogen mutants to platelets. J Biol Chem 1994; 269 (1) 226-231
55 Lancellotti S, Rutella S, De Filippis V, Pozzi N, Rocca B, De Cristofaro R. Fibrinogen-elongated gamma chain inhibits thrombin-induced platelet response, hindering the interaction with different receptors. J Biol Chem 2008; 283 (44) 30193-30204
56 Lovely RS, Rein CM, White TC , et al. gammaA/gamma' fibrinogen inhibits thrombin-induced platelet aggregation. Thromb Haemost 2008; 100 (5) 837-846
57 Nagy Jr B, Simon Z, Bagoly Z, Muszbek L, Kappelmayer J. Binding of plasma factor XIII to thrombin-receptor activated human platelets. Thromb Haemost 2009; 102 (1) 83-89
58 Cox AD, Devine DV. Factor XIIIa binding to activated platelets is mediated through activation of glycoprotein IIb-IIIa. Blood 1994; 83 (4) 1006-1016
59 Kieffer N, Guichard J, Farcet JP, Vainchenker W, Breton-Gorius J. Biosynthesis of major platelet proteins in human blood platelets. Eur J Biochem 1987; 164 (1) 189-195
60 Francis CW, Nachman RL, Marder VJ. Plasma and platelet fibrinogen differ in gamma chain content. Thromb Haemost 1984; 51 (1) 84-88
61 Mosesson MW, Homandberg GA, Amrani DL. Human platelet fibrinogen gamma chain structure. Blood 1984; 63 (5) 990-995
62 Uitte de Willige S, Standeven KF, Philippou H, Ariëns RA. The pleiotropic role of the fibrinogen gamma' chain in hemostasis. Blood 2009; 114 (19) 3994-4001
63 Undas A, Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31 (12) e88-e99
64 Riedelová-Reicheltová Z, Kotlín R, Suttnar J , et al. A novel natural mutation AαPhe98Ile in the fibrinogen coiled-coil affects fibrinogen function. Thromb Haemost 2014; 111 (1) 79-87
65 Park R, Doh HJ, An SS, Choi JR, Chung KH, Song KS. A novel fibrinogen variant (fibrinogen Seoul II; AalphaGln328Pro) characterized by impaired fibrin alpha-chain cross-linking. Blood 2006; 108 (6) 1919-1924
66 Collet JP, Soria J, Mirshahi M , et al. Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure. Blood 1993; 82 (8) 2462-2469
67 Fatah K, Hamsten A, Blombäck B, Blombäck M. Fibrin gel network characteristics and coronary heart disease: relations to plasma fibrinogen concentration, acute phase protein, serum lipoproteins and coronary atherosclerosis. Thromb Haemost 1992; 68 (2) 130-135
68 Fatah K, Silveira A, Tornvall P, Karpe F, Blombäck M, Hamsten A. Proneness to formation of tight and rigid fibrin gel structures in men with myocardial infarction at a young age. Thromb Haemost 1996; 76 (4) 535-540
69 Undas A, Podolec P, Zawilska K , et al. Altered fibrin clot structure/function in patients with cryptogenic ischemic stroke. Stroke 2009; 40 (4) 1499-1501
70 Undas A, Zawilska K, Ciesla-Dul M , et al. Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives. Blood 2009; 114 (19) 4272-4278
71 Lovely RS, Falls LA, Al-Mondhiry HA , et al. Association of gammaA/gamma' fibrinogen levels and coronary artery disease. Thromb Haemost 2002; 88 (1) 26-31
72 Kim PY, Vu TT, Leslie BA, Stafford AR, Fredenburgh JC, Weitz JI. Reduced plasminogen binding and delayed activation render γ'-fibrin more resistant to lysis than γA-fibrin. J Biol Chem 2014; 289 (40) 27494-27503
73 Falls LA, Farrell DH. Resistance of gammaA/gamma' fibrin clots to fibrinolysis. J Biol Chem 1997; 272 (22) 14251-14256
74 Pieters M, Kotze RC, Jerling JC, Kruger A, Ariëns RA. Evidence that fibrinogen γ' regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans. Blood 2013; 121 (16) 3254-3260
75 Collet JP, Nagaswami C, Farrell DH, Montalescot G, Weisel JW. Influence of gamma' fibrinogen splice variant on fibrin physical properties and fibrinolysis rate. Arterioscler Thromb Vasc Biol 2004; 24 (2) 382-386
76 Gersh KC, Nagaswami C, Weisel JW, Lord ST. The presence of gamma' chain impairs fibrin polymerization. Thromb Res 2009; 124 (3) 356-363
77 Domingues MM, Macrae FL, Duval C , et al. Thrombin and fibrinogen γ' impact clot structure by marked effects on intrafibrillar structure and protofibril packing. Blood 2015;
78 Drouet L, Paolucci F, Pasqualini N , et al. Plasma gamma'/gamma fibrinogen ratio, a marker of arterial thrombotic activity: a new potential cardiovascular risk factor?. Blood Coagul Fibrinolysis 1999; 10 (Suppl. 01) S35-S39
79 Farrell DH. γ' Fibrinogen as a novel marker of thrombotic disease. Clin Chem Lab Med 2012; 50 (11) 1903-1909
80 van den Herik EG, Cheung EY, de Lau LM , et al. Fibrinogen γ' levels in patients with intracerebral hemorrhage. Thromb Res 2012; 129 (6) 807-809
81 Lovely RS, Kazmierczak SC, Massaro JM, D'Agostino Sr RB, O'Donnell CJ, Farrell DH. Gamma' fibrinogen: evaluation of a new assay for study of associations with cardiovascular disease. Clin Chem 2010; 56 (5) 781-788
82 Pieters M, Boshuizen H, de Lange Z , et al. Relationship of coagulation and fibrinolytic variables with arterial structure and function in Africans. Thromb Res 2014; 134 (1) 78-83
83 Lovely R, Hossain J, Ramsey JP , et al. Obesity-related increased γ' fibrinogen concentration in children and its reduction by a physical activity-based lifestyle intervention: a randomized controlled study. J Pediatr 2013; 163 (2) 333-338
84 Appiah D, Schreiner PJ, MacLehose RF, Folsom AR. Association of Plasma γ' Fibrinogen With Incident Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol 2015; 35 (12) 2700-2706
85 Cheung EY, Vos HL, Kruip MJ, den Hertog HM, Jukema JW, de Maat MP. Elevated fibrinogen gamma' ratio is associated with cardiovascular diseases and acute phase reaction but not with clinical outcome. Blood 2009; 114 (20) 4603-4604 , author reply 4604–4605
86 van den Herik EG, Cheung EY, de Lau LM , et al. γ'/total fibrinogen ratio is associated with short-term outcome in ischaemic stroke. Thromb Haemost 2011; 105 (3) 430-434
87 Farrell DH. Primetime for γ'. Blood 2014; 124 (9) 1389-1390
88 Mosesson MW, Cooley BC, Hernandez I, Diorio JP, Weiler H. Thrombosis risk modification in transgenic mice containing the human fibrinogen thrombin-binding gamma' chain sequence. J Thromb Haemost 2009; 7 (1) 102-110
89 Walton BL, Getz TM, Bergmeier W, Lin FC, Uitte de Willige S, Wolberg AS. The fibrinogen γA/γ' isoform does not promote acute arterial thrombosis in mice. J Thromb Haemost 2014; 12 (5) 680-689
90 Smalberg JH, Koehler E, Darwish Murad S , et al; European Network for Vascular Disorders of the Liver (EN-Vie). Fibrinogen γ' and variation in fibrinogen gamma genes in the etiology of portal vein thrombosis. Thromb Haemost 2013; 109 (3) 558-560
91 Jobse A, Pieters M, Nienaber-Rousseau C, Boshuizen H, Hoekstra T, de Maat MP. The contribution of genetic and environmental factors to changes in total and γ' fibrinogen over 5 years. Thromb Res 2015; 135 (4) 703-709
92 Kotzé RC, Nienaber-Rousseau C, De Lange Z, De Maat MP, Hoekstra T, Pieters M. Genetic polymorphisms influencing total and γ' fibrinogen levels and fibrin clot properties in Africans. Br J Haematol 2015; 168 (1) 102-112
93 Grünbacher G, Weger W, Marx-Neuhold E , et al. The fibrinogen gamma (FGG) 10034C>T polymorphism is associated with venous thrombosis. Thromb Res 2007; 121 (1) 33-36
94 Uitte de Willige S, Pyle ME, Vos HL , et al. Fibrinogen gamma gene 3′-end polymorphisms and risk of venous thromboembolism in the African-American and Caucasian population. Thromb Haemost 2009; 101 (6) 1078-1084
95 Bahadori B, Uitz E, Dehchamani D, Pilger E, Renner W. The fibrinogen gamma 10034C>T polymorphism is not associated with Peripheral Arterial Disease. Thromb Res 2010; 126 (4) 350-352
96 Mannila MN, Eriksson P, Lundman P , et al. Contribution of haplotypes across the fibrinogen gene cluster to variation in risk of myocardial infarction. Thromb Haemost 2005; 93 (3) 570-577
97 Uitte DE Willige S, Doggen CJ, DE Visser MC, Bertina RM, Rosendaal FR. Haplotypes of the fibrinogen gamma gene do not affect the risk of myocardial infarction. J Thromb Haemost 2006; 4 (2) 474-476
98 Lovely RS, Yang Q, Massaro JM , et al. Assessment of genetic determinants of the association of γ' fibrinogen in relation to cardiovascular disease. Arterioscler Thromb Vasc Biol 2011; 31 (10) 2345-2352
99 Kotzé RC, Ariëns RA, de Lange Z, Pieters M. CVD risk factors are related to plasma fibrin clot properties independent of total and or γ' fibrinogen concentration. Thromb Res 2014; 134 (5) 963-969
100 Nienaber-Rousseau C, de Lange Z, Pieters M. Homocysteine influences blood clot properties alone and in combination with total fibrinogen but not with fibrinogen γ' in Africans. Blood Coagul Fibrinolysis 2015; 26 (4) 389-395
101 Hill M, Dolan G. Diagnosis, clinical features and molecular assessment of the dysfibrinogenaemias. Haemophilia 2008; 14 (5) 889-897
102 de Moerloose P, Boehlen F, Neerman-Arbez M. Fibrinogen and the risk of thrombosis. Semin Thromb Hemost 2010; 36 (1) 7-17
103 Bornikova L, Peyvandi F, Allen G, Bernstein J, Manco-Johnson MJ. Fibrinogen replacement therapy for congenital fibrinogen deficiency. J Thromb Haemost 2011; 9 (9) 1687-1704
104 Doolittle RF, Hong S, Wilcox D. Evolution of the fibrinogen γ' chain: implications for the binding of factor XIII, thrombin and platelets. J Thromb Haemost 2009; 7 (8) 1431-1433
105 Kollman JM, Pandi L, Sawaya MR, Riley M, Doolittle RF. Crystal structure of human fibrinogen. Biochemistry 2009; 12 ;48(18): 3877-3886