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Journal of Thrombosis and Thrombolysis

Erschienen in:

04.07.2020

The genetics of venous thromboembolism: a systematic review of thrombophilia families

verfasst von: Yu Zhang, Zhu Zhang, Shi Shu, Wenquan Niu, Wanmu Xie, Jun Wan, Zhenguo Zhai, Chen Wang

Erschienen in: Journal of Thrombosis and Thrombolysis | Ausgabe 2/2021

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Abstract

Genetic risk factors are important for the occurrence and prognosis of venous thromboembolism (VTE). The studies of thrombophilia families are important for dissecting the genetic background of the thrombotic disease. We conducted the systematic review of all published family-based studies on VTE genetics across all racial groups through PubMed and Embase prior to 13th April 2020. This systematic review of 287 families (including 225 Caucasian families, 52 East Asian families, and families of other ethnicities) revealed a total of 21 different genes; the five most reported mutated genes were F5 (88/287, 30.7%), SERPINC1 (67/287, 23.3%), PROC (65/287, 22.6%), F2 (40/287, 13.9%) and PROS1 (48/287, 16.7%). For Caucasian families, F5 mutations were most frequently reported at 37.8% (85/225), while PROS1 mutations were most frequently reported, at 40.4% (21/52), for East Asian families (Chinese, Japanese and Korean). Factor V Leiden was reported more frequently in Caucasians than in East Asians. Missense mutations were reported frequently in the SERPINC1, PROC and PROS1 genes. In conclusion, our study found the most likely mutated genes associated with VTE among different ethnic groups and provided indications for VTE genetic testing and research in the future.

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Shahi A, Chen AF, Tan TL, Maltenfort MG, Kucukdurmaz F, Parvizi J (2017) The incidence and economic burden of in-hospital venous thromboembolism in the United States. J Arthroplast 32(4):1063–1066. https://doi.org/10.1016/j.arth.2016.10.020CrossRef

Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ, Hylek EM, Kakkar A, Konstantinides SV, McCumber M, Ozaki Y, Wendelboe A, Weitz JI, Day ISCfWT (2014) Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol 34(11):2363–2371. https://doi.org/10.1161/ATVBAHA.114.304488CrossRefPubMed

Zhang Z, Lei J, Shao X, Dong F, Wang J, Wang D, Wu S, Xie W, Wan J, Chen H, Ji Y, Yi Q, Xu X, Yang Y, Zhai Z, Wang C, China Venous Thromboembolism Study G (2019) Trends in hospitalization and in-hospital mortality from VTE, 2007 to 2016, in China. Chest 155(2):342–353. https://doi.org/10.1016/j.chest.2018.10.040CrossRefPubMed

Morange PE, Suchon P, Tregouet DA (2015) Genetics of venous thrombosis: update in 2015. Thromb Haemost 114(5):910–919. https://doi.org/10.1160/TH15-05-0410CrossRefPubMed

Tregouet DA, Morange PE (2018) What is currently known about the genetics of venous thromboembolism at the dawn of next generation sequencing technologies. Br J Haematol 180(3):335–345. https://doi.org/10.1111/bjh.15004CrossRefPubMed

Dandine-Roulland C, Perdry H (2015) Where is the causal variant? On the advantage of the family design over the case–control design in genetic association studies. Eur J Hum Genet 23(10):1357–1363. https://doi.org/10.1038/ejhg.2014.284CrossRefPubMedPubMedCentral

Cai H, Hua B, Fan L, Wang Q, Wang S, Zhao Y (2010) A novel mutation (g2172-->c) in the factor V gene in a Chinese family with hereditary activated protein C resistance. Thromb Res 125(6):545–548. https://doi.org/10.1016/j.thromres.2010.02.009CrossRefPubMed

Roman-Gonzalez A, Cardona H, Cardona-Maya W, Alvarez L, Castaneda S, Martinez J, Torres JD, Tobón L, Bedoya G, Cadavid A (2009) The first homozygous family for prothrombin G20210A polymorphism reported in Latin America. Clin Appl Thromb Hemost 15(1):113–116. https://doi.org/10.1177/1076029608325049CrossRefPubMed

Morales-Borges RH (2012) Autosomal-dominant inheritance of the prothrombin gene mutation in a Puerto Rican family: a case study. P R Health Sci J 31(4):232–234PubMed

10.

Miljic P, Gvozdenov M, Takagi Y, Takagi A, Pruner I, Dragojevic M, Tomic B, Bodrozic J, Kojima T, Radojkovic D, Djordjevic V (2017) Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism. J Thromb Haemost 15(4):670–677. https://doi.org/10.1111/jth.13618CrossRefPubMed

11.

Djordjevic V, Kovac M, Miljic P, Murata M, Takagi A, Pruner I, Francuski D, Kojima T, Radojkovic D (2013) A novel prothrombin mutation in two families with prominent thrombophilia—the first cases of antithrombin resistance in a Caucasian population. J Thromb Haemost 11(10):1936–1939. https://doi.org/10.1111/jth.12367CrossRefPubMed

12.

Valentina D, Kovac M, Pruner I, Francuski D, Radojkovic D (2013) A novel prothrombin c.1787G>A mutation in Serbian family with recurrent thromboembolism-another case of antithrombin resistance. J Thromb Haemost 11:374

13.

Bulato C, Radu CM, Campello E, Gavasso S, Spiezia L, Tormene D, Simioni P (2016) New prothrombin mutation (Arg596Trp, prothrombin Padua 2) associated with venous thromboembolism. Arterioscler Thromb Vasc Biol 36(5):1022–1029. https://doi.org/10.1161/ATVBAHA.115.306914CrossRefPubMed

14.

Mulder R, Lisman T, Meijers JCM, Huntington JA, Mulder AB, Meijer K (2019) Linkage analysis combined with whole exome sequencing identifies a novel prothrombin (F2) gene mutation in a Dutch Caucasian family with unexplained thrombosis. Haematologica. https://doi.org/10.3324/haematol.2019.232504CrossRefPubMedPubMedCentral

15.

Miyawaki Y, Suzuki A, Fujita J, Maki A, Okuyama E, Murata M, Takagi A, Murate T, Kunishima S, Sakai M, Okamoto K, Matsushita T, Naoe T, Saito H, Kojima T (2012) Thrombosis from a prothrombin mutation conveying antithrombin resistance. N Engl J Med 366(25):2390–2396. https://doi.org/10.1056/NEJMoa1201994CrossRefPubMed

16.

Yoshida R, Seki S, Hasegawa J, Koyama T, Yamazaki K, Takagi A, Kojima T, Yoshimura M (2018) Familial pulmonary thromboembolism with a prothrombin mutation and antithrombin resistance. J Cardiol Cases 17(6):197–199. https://doi.org/10.1016/j.jccase.2018.02.001CrossRefPubMedPubMedCentral

17.

Kishimoto M, Suzuki N, Murata M, Ogawa M, Kanematsu T, Takagi A, Kiyoi H, Kojima T, Matsushita T (2016) The first case of antithrombin-resistant prothrombin Belgrade mutation in Japanese. Ann Hematol 95(3):541–542. https://doi.org/10.1007/s00277-015-2533-6CrossRefPubMed

18.

Miyawaki Y, Suzuki A, Fujimori Y, Fujita J, Maki A, Takagi A, Murate T, Sakai M, Okamoto K, Matsushita T, Kojima T (2011) A novel prothrombin gene mutation leads to an atresistant thrombin in a family with inherited thrombophilia. J Thromb Haemost 9:162. https://doi.org/10.1111/j.1538-7836.2011.04380_1.xCrossRef

19.

Sun G, Jia Y, Meng J, Ou M, Zhu P, Cong S, Luo Y, Sui W, Dai Y (2017) A genetic risk factor for thrombophilia in a Han Chinese family. Mol Med Rep 15(4):1668–1672. https://doi.org/10.3892/mmr.2017.6217CrossRefPubMedPubMedCentral

20.

Wang L, Liu JM, Rong J, Han R, Zhao Q, Gong S, He J (2017) Thrombosis associated with congenital prothrombin deficiency: a severe procoagulant defect contrasting with thrombosis in a congenital prothrombin deficient family. Am J Respir Crit Care Med. https://doi.org/10.1164/ajrccmconference.2017.C57

21.

Wu X, Dai J, Xu X, Li F, Li L, Lu Y, Xu Q, Ding Q, Wu W, Wang X (2020) Prothrombin Arg541Trp mutation leads to defective PC (protein C) pathway activation and constitutes a novel genetic risk factor for venous thrombosis. Arterioscler Thromb Vasc Biol 40(2):483–494. https://doi.org/10.1161/ATVBAHA.119.313373CrossRefPubMed

22.

Voorberg J, Roelse J, Koopman R, Buller H, Berends F, ten Cate JW, Mertens K, van Mourik JA (1994) Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V. Lancet (London, England) 343(8912):1535–1536CrossRef

23.

Brenner B, Zivelin A, Lanir N, Greengard JS, Griffin JH, Seligsohn U (1996) Venous thromboembolism associated with double heterozygosity for R506Q mutation of factor V and for T298M mutation of protein C in a large family of a previously described homozygous protein C-deficient newborn with massive thrombosis. Blood 88(3):877–880CrossRef

24.

Xin-Guang C, Yong-Qiang Z, Shu-Jie W, Lian-Kai F, Hua-Cong C (2015) Prevalence of the factor V E666D mutation and its correlation with activated protein C resistance in the Chinese population. Clin Appl Thromb Hemost 21(5):480–483. https://doi.org/10.1177/1076029613514130CrossRefPubMed

25.

Santamaría A, Soria JM, Tirado I, Mateo J, Coll I, Souto JC, Fontcuberta J (2005) Double heterozygosity for factor V Leiden and factor V Cambridge mutations associated with low levels of activated protein C resistance in a Spanish thrombophilic family. Thromb Haemost 93(6):1193–1195CrossRef

26.

Norstrom E, Thorelli E, Dahlback B (2002) Functional characterization of recombinant FV Hong Kong and FV Cambridge. Blood 100(2):524–530. https://doi.org/10.1182/blood-2002-02-0343CrossRefPubMed

27.

Castoldi E, Simioni P, Kalafatis M, Lunghi B, Tormene D, Girelli D, Girolami A, Bernardi F (2000) Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family. Blood 96(4):1443–1448CrossRef

28.

Castoldi E, Rosing J, Girelli D, Hoekema L, Lunghi B, Mingozzi F, Ferraresi P, Friso S, Corrocher R, Tans G, Bernardi F (2000) Mutations in the R2 FV gene affect the ratio between the two FV isoforms in plasma. Thromb Haemost 83(3):362–365CrossRef

29.

Faioni EM, Franchi F, Bucciarelli P, Margaglione M, De Stefano V, Castaman G, Finazzi G, Mannucci PM (1999) Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). Blood 94(9):3062–3066CrossRef

30.

Peng Y, Wang T, Zheng Y, Lian A, Zhang D, Xiong Z, Hu Z, Xia K, Shu C (2019) A novel variation of SERPINC1 caused deep venous thrombosis in a Chinese family: a case report. Medicine 98(1):e13999. https://doi.org/10.1097/MD.0000000000013999CrossRefPubMedPubMedCentral

31.

Li L, Wu X, Wu W, Ding Q, Cai X, Wang X (2019) Clinical manifestation and mutation spectrum of 53 unrelated pedigrees with protein S deficiency in China. Thromb Haemost 119(3):449–460. https://doi.org/10.1055/s-0038-1677031CrossRefPubMed

32.

Zhu R, Cao Z, Wu W (2019) Inherited antithrombin III deficiency: a case report of familial pedigree and gene mutation screening. Eur J Vasc Endovasc Surg 58(6):e379. https://doi.org/10.1016/j.ejvs.2019.06.1011CrossRef

33.

Maruyama K, Morishita E, Karato M, Kadono T, Sekiya A, Goto Y, Sato T, Nomoto H, Omi W, Tsuzura S, Imai H, Asakura H, Ohtake S, Nakao S (2013) Antithrombin deficiency in three Japanese families: one novel and two reported point mutations in the antithrombin gene. Thromb Res 132(2):e118–e123. https://doi.org/10.1016/j.thromres.2013.06.001CrossRefPubMed

34.

Niiya K, Kiguchi T, Dansako H, Fujimura K, Fujimoto T, Iijima K, Tanimoto M, Harada M (2001) Two novel gene mutations in type I antithrombin deficiency. Int J Hematol 74(4):469–472. https://doi.org/10.1007/bf02982095CrossRefPubMed

35.

Okajima K, Abe H, Wagatsuma M, Okabe H, Takatsuki K (1995) Antithrombin III kumamoto II; a single mutation at Arg393-His increased the affinity of antithrombin III for heparin. Am J Hematol 48(1):12–18. https://doi.org/10.1002/ajh.2830480104CrossRefPubMed

36.

Jang MJ, Lee JG, Chong SY, Huh JY, Jang MA, Kim HJ, Oh D (2011) A novel splice-site mutation c.42-2A>T (IVS1-2A>T) of SERPINC1 in a Korean family with inherited antithrombin deficiency. Blood Coagul Fibrinolysis 22(8):742–745. https://doi.org/10.1097/MBC.0b013e32834a7e17CrossRefPubMed

37.

Carrasco Exposito M, Tirado Garcia I, Romero RL, Vilalta Seto N, Mateo Arranz J, Millon Caño JA, Fontcuberta Boj J (2017) Extensive molecular characterization of a family with thrombophilia: implication of multiple genetic alterations of low thrombotic risk profile. Res Pract Thromb Haemost 1:1141. https://doi.org/10.1002/rth2.12012CrossRef

38.

Orlando C, Jochmans K, Lissens W, Liebaers I, De Waele M (2009) Hereditary antithrombin deficiency caused by heterozygous Cambridge II mutation in combination with a large gene deletion. J Thromb Haemost 7(S2):376. https://doi.org/10.1111/j.1538-7836.2009.03473-2.xCrossRef

39.

Perry DJ, Daly ME, Tait RC, Walker ID, Brown K, Beauchamp NJ, Preston FE, Gyde H, Harper PL, Carrell RW (1998) Antithrombin Cambridge II (Ala384Ser): clinical, functional and haplotype analysis of 18 families. Thromb Haemost 79(2):249–253CrossRef

40.

Lane DA, Erdjument H, Flynn A, Di Marzo V, Panico M, Morris HR, Greaves M, Dolan G, Preston FE (1989) Antithrombin Sheffield: amino acid substitution at the reactive site (Arg393 to His) causing thrombosis. Br J Haematol 71(1):91–96. https://doi.org/10.1111/j.1365-2141.1989.tb06280.xCrossRefPubMed

41.

David D, Ribeiro S, Ferrao L, Gago T, Crespo F (2004) Molecular basis of inherited antithrombin deficiency in Portuguese families: identification of genetic alterations and screening for additional thrombotic risk factors. Am J Hematol 76(2):163–171. https://doi.org/10.1002/ajh.20067CrossRefPubMed

42.

Lane DA, Erdjument H, Thompson E, Panico M, Di Marzo V, Morris HR, Leone G, De Stefano V, Thein SL (1989) A novel amino acid substitution in the reactive site of a congenital variant antithrombin. Antithrombin pescara, Arg393 to Pro, caused by CGT to CCT mutation. J Biol Chem 264(17):10200–10204CrossRef

43.

Fidalgo T, Martinho P, Salvado R, Manco L, Oliveira AC, Pinto CS, Goncalves E, Marques D, Sevivas T, Martins N, Ribeiro ML (2015) Familial thrombotic risk based on the genetic background of protein C deficiency in a Portuguese study. Eur J Haematol 95(4):294–307. https://doi.org/10.1111/ejh.12488CrossRefPubMed

44.

Dávid M, Losonczy H, Sas G, Nagy A, Kutscher G, Meyer M (2000) Identification of mutations in 15 Hungarian families with hereditary protein C deficiency. Br J Haematol 111(1):129–135. https://doi.org/10.1046/j.1365-2141.2000.02324.xCrossRefPubMed

45.

Koenderman JS, Bertina RM, Reitsma PH, De Visser MCH (2011) Over 50% of Dutch VTE families with protein C deficiency share a founder R272C mutation. J Thromb Haemost 9:164. https://doi.org/10.1111/j.1538-7836.2011.04380_1.xCrossRef

46.

Liu H, Wang HF, Tang L, Yang Y, Wang QY, Zeng W, Wu YY, Cheng ZP, Hu B, Guo T, Hu Y (2015) Compound heterozygous protein C deficiency in a family with venous thrombosis: identification and in vitro study of p.Asp297His and p.Val420Leu mutations. Gene 563(1):35–40. https://doi.org/10.1016/j.gene.2015.03.002CrossRefPubMed

47.

Wu Y, Xu G, Ding Q, Xi X, Wang X, Wang H (2009) Combined occurrence of hereditary protein C and protein S deficiency in two Chinese families with venous thrombosis. J Thromb Haemost 7(S2):1043. https://doi.org/10.1111/j.1538-7836.2009.03473-2.xCrossRef

48.

Zhou RF, Cai XH, Xie S, Wang XF, Wang HL (2006) Molecular mechanism for hereditary protein C deficiency in two Chinese families with thrombosis. J Thromb Haemost 4(5):1154–1156. https://doi.org/10.1111/j.1538-7836.2006.01913.xCrossRefPubMed

49.

Yue Y, Liu S, Han X, Xiao L, Huang Q, Li S, Zhuang K, Yang M, Zou C, Fu Y (2019) Pathogenic variants of PROC gene caused type I activity deficiency in a familial Chinese venous thrombosis. J Cell Mol Med 23(10):7099–7104. https://doi.org/10.1111/jcmm.14563CrossRefPubMedPubMedCentral

50.

Wu D, Zhong Z, Chen Y, Ding H, Yang M, Lian N, Huang Z, Zhang Q, Zhao J, Deng C (2019) Analysis of PROC and PROS1 single nucleotide polymorphisms in a thrombophilia family. Clin Respir J 13(8):530–537. https://doi.org/10.1111/crj.13055CrossRefPubMed

51.

Su K, Zhang H, Fang W, Zhang F, Yang L, Jin Y, Wang M (2018) Protein C deficiency (a novel mutation: ala291Thr) with systemic lupus erythematosus leads to the deep vein thrombosis. Blood Coagul Fibrinolysis 29(8):714–719. https://doi.org/10.1097/mbc.0000000000000778CrossRefPubMed

52.

Chen C, Yang L, Villoutreix BO, Wang X, Ding Q, Rezaie AR (2017) Gly74Ser mutation in protein C causes thrombosis due to a defect in protein S-dependent anticoagulant function. Thromb Haemost 117(7):1358–1369. https://doi.org/10.1160/th17-01-0043CrossRefPubMedPubMedCentral

53.

Hoshi S, Hijikata M, Togashi Y, Aoyagi T, Kono C, Yamada Y, Amano H, Keicho N, Yamaguchi T (2007) Protein C deficiency in a family with thromboembolism and identified gene mutations. Intern Med 46(13):997–1003. https://doi.org/10.2169/internalmedicine.46.6277CrossRefPubMed

54.

Hayashida M, Yamada H, Yamazaki S, Nomura H, Yoshimura K, Kitahara O, Momose K, Kubo K, Kurihara M, Hamasaki N (2003) Combined protein C and protein S deficiency in a family with repetitive thromboembolism and segregated gene mutations. Intern Med 42(3):268–272CrossRef

55.

Park HJ, Chong SY, Oh D, Huh JY, Kim HJ, Yun-Choi HS, Park S (2011) A novel insertion mutation 718dupG in the PROC gene in a Korean thrombophilic family. Thromb Res 127(2):176–178. https://doi.org/10.1016/j.thromres.2010.07.019CrossRefPubMed

56.

Ireland HA, Boisclair MD, Taylor J, Thompson E, Swee Lay T, Girolami A, De Caterina M, Scopacasa F, De Stefano V, Leone G, Finazzi G, Cohen H, Lane DA (1996) Two novel (R(-11)C; T394D) and two repeat missense mutations in the protein C gene associated with venous thrombosis in six kindreds. Hum Mutat 7(2):176–179. https://doi.org/10.1002/(SICI)1098-1004(1996)7:2<176::AID-HUMU16>3.0.CO;2-#CrossRefPubMed

57.

Tomczak JA, Ando RA, Sobel HG, Bovill EG, Long GL (1994) Genetic analysis of a large kindred exhibiting type I protein C deficiency and associated thrombosis. Thromb Res 74(3):243–254. https://doi.org/10.1016/0049-3848(94)90112-0CrossRefPubMed

58.

Formstone CJ, Hallam PJ, Tuddenham EGD, Voke J, Layton M, Nicolaides K, Hann IM, Cooper DN (1996) Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation. Blood 87(9):3731–3737CrossRef

59.

Esmon CT (1983) Protein-C: biochemistry, physiology, and clinical implications. Blood 62(6):1155–1158CrossRef

60.

Espinosa-Parrilla Y, Morell M, Souto JC, Tirado I, Fontcuberta J, Estivill X, Sala N (1999) Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency. Hum Mutat 14(1):30–39. https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<30::AID-HUMU4>3.0.CO;2-XCrossRefPubMed

61.

Beauchamp NJ, Daly ME, Cooper PC, Makris M, Preston FE, Peake IR (1996) Molecular basis of protein S deficiency in three families also showing independent inheritance of factor V Leiden. Blood 88(5):1700–1707CrossRef

62.

Formstone CJ, Wacey AI, Berg LP, Rahman S, Bevan D, Rowley M, Voke J, Bernardi F, Legnani C, Simioni P, Girolami A, Tuddenham EG, Kakkar VV, Cooper DN (1995) Detection and characterization of seven novel protein S (PROS) gene lesions: evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy. Blood 86(7):2632–2641CrossRef

63.

Falk G, Sartori MT, Patrassi GM, Vettore S, Girolami A, Wiman B (1997) Identification of an 18 basepair deletion in the PAI-1 gene promoter region in a family with thrombotic disease. Fibrinolysis Proteolysis 11(5–6):239–244CrossRef

64.

Öhlin AK, Marlar RA (1999) Thrombomodulin gene defects in families with thromboembolic disease: a report on four families. Thromb Haemost 81(3):338–344CrossRef

65.

Shlebak AA, Katsarou AD, Adams G, Fernando F (2017) A novel mutation in exon 2 of FGB caused by c.221G>T† substitution, predicting the replacement of the native arginine at position 74 with a leucine (p.Arg74Leu†) in a proband from a Kurdish family with dysfibrinogenaemia and familial venous and arterial thrombosis. J Thromb Thrombolysis 43(2):263–270. https://doi.org/10.1007/s11239-016-1439-zCrossRefPubMed

66.

Fernández-Cadenas I, Penalba A, Boada C, Msc CC, Bueno SR, Quiroga A, Monasterio J, Delgado P, Anglés-Cano E, Montaner J (2016) Exome sequencing and clot lysis experiments demonstrate the R458C mutation of the alpha chain of fibrinogen to be associated with impaired fibrinolysis in a family with thrombophilia. J Atheroscler Thromb 23(4):431–440. https://doi.org/10.5551/jat.30676CrossRefPubMed

67.

Hanss MM, Ffrench PO, Mornex JF, Chabuet M, Biot F, De Mazancourt P, Dechavanne M (2003) Two novel fibrinogen variants found in patients with pulmonary embolism and their families. J Thromb Hemost 1(6):1251–1257CrossRef

68.

Brennan SO, Hammonds B, Spearing R, George PM (1997) Electrospray ionisation mass spectrometry facilitates detection of fibrinogen (Bβ14 Arg→Cys) mutation in a family with thrombosis. Thromb Haemost 78(6):1484–1487CrossRef

69.

Salomon O, Barel O, Eyal E, Ganor RS, Kleinbaum Y, Shohat M (2019) C.259A>c in the fibrinogen gene of alpha chain (FGA) is a fibrinogen with thrombotic phenotype. Appl Clin Genet 12:27–33. https://doi.org/10.2147/TACG.S190599CrossRefPubMedPubMedCentral

70.

Siebenlist KR, Mosesson MW, Meh DA, DiOrio JP, Albrecht RM, Olson JD (2000) Coexisting dysfibrinogenemia (gammaR275C) and factor V Leiden deficiency associated with thromboembolic disease (fibrinogen Cedar Rapids). Blood Coagul Fibrinolysis 11(3):293–304PubMed

71.

Cheah CY, Brennan SO, Kennedy H, Januszewicz EH, Maxwell E, Burbury K (2012) Fibrinogen Melbourne: a novel congenital hypodysfibrinogenemia caused by γ326Cys-Phe in the fibrinogen γ chain, presenting as massive splanchnic venous thrombosis. Blood Coagul Fibrinolysis 23(6):563–565. https://doi.org/10.1097/MBC.0b013e328354a23bCrossRefPubMed

72.

Koopman J, Haverkate F, Grimbergen J, Lord ST, Mosesson MW, DiOrio JP, Siebenlist KS, Legrand C, Soria J, Soria C et al (1993) Molecular basis for fibrinogen Dusart (A alpha 554 Arg-->Cys) and its association with abnormal fibrin polymerization and thrombophilia. J Clin Invest 91(4):1637–1643. https://doi.org/10.1172/jci116371CrossRefPubMedPubMedCentral

73.

Ortiz AS (2005) Complexity of the genetic contribution of different thrombotic risk factors in a Spanish thrombophilic family. Thromb Haemost 93(5):997–998CrossRef

74.

Chang WA, Sheu CC, Liu KT, Shen JH, Yen MC, Kuo PL (2018) Identification of mutations in SLC4A1, GP1BA and HFE in a family with venous thrombosis of unknown cause by next-generation sequencing. Exp Ther Med 16(5):4172–4180. https://doi.org/10.3892/etm.2018.6693CrossRefPubMedPubMedCentral

75.

Fu Y, Sun S, Liang J, Liu S, Jiang Y, Xu L, Mei J (2016) PEAR1 gene polymorphism in a Chinese pedigree with pulmonary thromboembolism. Medicine (United States) 95(51):e5687. https://doi.org/10.1097/MD.0000000000005687CrossRef

76.

Zakai NA, McClure LA (2011) Racial differences in venous thromboembolism. J Thromb Haemost 9(10):1877–1882. https://doi.org/10.1111/j.1538-7836.2011.04443.xCrossRefPubMed

77.

Rees DC, Cox M, Clegg JB (1995) World distribution of factor V Leiden. Lancet 346(8983):1133–1134. https://doi.org/10.1016/s0140-6736(95)91803-5CrossRefPubMed

78.

Rosendaal FR, Doggen CJ, Zivelin A, Arruda VR, Aiach M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston FE, Reitsma PH (1998) Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 79(4):706–708CrossRef

79.

Rosendaal FR, Reitsma PH (2009) Genetics of venous thrombosis. J Thromb Haemost 7(Suppl 1):301–304. https://doi.org/10.1111/j.1538-7836.2009.03394.xCrossRefPubMed

80.

Wolberg AS, Rosendaal FR, Weitz JI, Jaffer IH, Agnelli G, Baglin T, Mackman N (2015) Venous thrombosis. Nat Rev Dis Primers 1:15006. https://doi.org/10.1038/nrdp.2015.6CrossRefPubMed

81.

Lindstrom S, Wang L, Smith EN, Gordon W, van Hylckama VA, de Andrade M, Brody JA, Pattee JW, Haessler J, Brumpton BM, Chasman DI, Suchon P, Chen MH, Turman C, Germain M, Wiggins KL, MacDonald J, Braekkan SK, Armasu SM, Pankratz N, Jackson RD, Nielsen JB, Giulianini F, Puurunen MK, Ibrahim M, Heckbert SR, Damrauer SM, Natarajan P, Klarin D, Million Veteran P, de Vries PS, Sabater-Lleal M, Huffman JE, Group CHW, Bammler TK, Frazer KA, McCauley BM, Taylor K, Pankow JS, Reiner AP, Gabrielsen ME, Deleuze JF, O'Donnell CJ, Kim J, McKnight B, Kraft P, Hansen JB, Rosendaal FR, Heit JA, Psaty BM, Tang W, Kooperberg C, Hveem K, Ridker PM, Morange PE, Johnson AD, Kabrhel C, Tregouet DA, Smith NL (2019) Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. Blood 134(19):1645–1657. https://doi.org/10.1182/blood.2019000435CrossRefPubMedPubMedCentral

82.

Connors JM (2017) Thrombophilia testing and venous thrombosis. N Engl J Med 377(12):1177–1187. https://doi.org/10.1056/NEJMra1700365CrossRefPubMed

83.

Moran J, Bauer KA (2020) Managing thromboembolic risk in patients with hereditary and acquired thrombophilias. Blood 135(5):344–350. https://doi.org/10.1182/blood.2019000917CrossRefPubMed

Titel: The genetics of venous thromboembolism: a systematic review of thrombophilia families
verfasst von: Yu Zhang
Zhu Zhang
Shi Shu
Wenquan Niu
Wanmu Xie
Jun Wan
Zhenguo Zhai
Chen Wang
Publikationsdatum: 04.07.2020
Verlag: Springer US
Erschienen in: Journal of Thrombosis and Thrombolysis / Ausgabe 2/2021
Print ISSN: 0929-5305
Elektronische ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-020-02203-7

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