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• W2073144480 abstract "HomeStrokeVol. 34, No. 12Tests for Hereditary Thrombophilia Are of Limited Value in the Black Population Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBTests for Hereditary Thrombophilia Are of Limited Value in the Black Population Raj K. Patel, MRCPath and Roopen Arya, PhD Raj K. PatelRaj K. Patel Department of Haematological Medicine, King’s College Hospital, London, UK Search for more papers by this author and Roopen AryaRoopen Arya Department of Haematological Medicine, King’s College Hospital, London, UK Search for more papers by this author Originally published1 Dec 2003https://doi.org/10.1161/01.STR.0000104160.96489.18Stroke. 2003;34:e236Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 1, 2003: Previous Version 1 To the Editor:We read with interest the recent article by Jerrard-Dunne et al in which they established race-specific ranges for thrombophilia markers in blacks.1 Testing for hereditary thrombophilia has been advocated for a myriad of both arterial and venous disorders and the association with venous thromboembolism (VTE) but not arterial disease has been established in well-conducted studies.2 A common feature in thrombophilia research is the tendency to ignore the potential for ethnicity to influence disease. The conventional hereditary thrombophilia tests performed in the United Kingdom include a range of investigations: genotyping for factor V Leiden (FVL) and prothrombin mutations, and measurement of protein C (PC), protein S (PS), and antithrombin (AT) phenotype. These prothrombotic markers are informative in 30% to 70% of Europeans presenting with VTE and recurrent VTE3 but are rare in black populations.4,5 This is supported by data from our own institution in which only 13 of 142 black subjects (9.1%) with a history of VTE had a thrombophilic marker, compared with 30% of white subjects.6 Of the positive thrombophilia tests in blacks (30% African and 70% Caribbean), 4 had PS deficiency, 6 had PC deficiency, 1 had AT deficiency, and 2 were heterozygous for FVL. In their study, Jerrard-Dunne et al have found that a significant proportion of healthy black controls would be misdiagnosed as having PC, PS, and possibly AT deficiency using reference ranges derived from white populations. This will be of concern to those of us involved in the treatment of VTE in multi-ethnic populations who are aware of both the psychosocial and medical consequences that may associated with the diagnosis of a “genetic disorder.” Negative results in black patients undergoing thrombophilia testing may lead to a false reassurance of normality, and positive results using inappropriate reference ranges should now be viewed as unreliable.As the genetic basis for hereditary thrombophilia in blacks is poorly characterized but a family history of VTE is as common in blacks subjects as white subjects with VTE,4 it is likely that black populations possess prothrombotic genetic risk factors that are yet to be determined. The Camberwell Thrombophilia Study is a population-based study investigating thrombophilia in the black population. We have recently shown that elevated factor VIII:C (FVIII) level is a major risk factor for VTE in the black population with odds ratio for DVT of 11.1 (95% CI 4.29 to 29.43) for FVIII:C >228 IU/dL (the 90th centile value in controls).6 Elevated FVIII is also associated with a moderately increased risk of stroke in whites7,8 and has been associated with coronary heart disease and stroke in African-Americans with diabetes.9 Elevated fibrinogen level is an established risk factor for arterial disease2 and has recently been linked to VTE in blacks.10 Thus FVIII and fibrinogen are thrombophilic markers in blacks that should be considered when assessing risk factors for both venous or arterial thrombosis.We support the view that an awareness of ethnic differences in reference ranges is vital in order to avoid misdiagnosis of hereditary thrombophilia. More importantly, conventional thrombophilia tests are not generally useful in the black population and may provide false reassurance when negative results are obtained. There is thus an urgent need for further race-specific research into the genetic basis of arterial and venous thrombosis.1 Jerrard-Dunne P, Evans A, McGovern R, Hajat C, Kalra L, Rudd A, Wolfe C, Markus HS. Ethnic differences in markers of thrombophilia: implications for the investigation of ischaemic stroke in multiethnic populations: the South London Ethnicity and Stroke Study. Stroke. 2003; 34: 1821–1827.LinkGoogle Scholar2 Lane DA, Grant PJ. Role of haemostatic gene polymorphisms in venous and arterial disease. Blood. 2000; 95: 1517–1532.CrossrefMedlineGoogle Scholar3 Hankey G, Eikelboom JW. Routine thrombophilia testing in stroke patients is unjustified. Stroke. 2003; 34: 1826–1827.LinkGoogle Scholar4 Dowling NF, Austin H, Dilley A, Whitsett C, Evatt BL, Hooper WC. The epidemiology of venous thromboembolism in Caucasians and Afro-Americans: the GATE study. J Thromb Haemost. 2002; 1: 80–87.Google Scholar5 Rees DC, Chapman NH, Webster MT, Guerreiro JF, Rochette J, Clegg JB. Born to clot: the European burden. Br J Haematol. 1999; 105: 564–566.CrossrefMedlineGoogle Scholar6 Patel RK, Ford E, Thumpston J, Arya R. Risk factors for venous thrombosis in the black population. Thromb Haemost. 2003; 90: 835–839.MedlineGoogle Scholar7 Folsom AR, Rosamond WD, Shahar E, Cooper LS, Aleksic N, Nieto FJ, Rasmussen ML, Wu KK. Prospective study of markers of hemostatic function with risk of ischaemic stroke. Circulation. 1999; 100: 736–742.CrossrefMedlineGoogle Scholar8 Tracy RP, Arnold AM, Ettinger W, Fried L, Meilahn E, Savage P. The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease in the elderly: results from the Cardiovascular Health Study. Arterioscler Thromb and Vasc Biol. 1999; 19: 1776–1783.CrossrefMedlineGoogle Scholar9 Adeniyi A, Folsom AR, Brancati FL, Desvorieux M, Pankow JS, Taylor H. Incidence and risk factors for cardiovascular disease in African Americans with diabetes: the Atherosclerosis Risk in Communities (ARIC) study. J Natl Med Assoc. 2002; 94: 1025–1035.MedlineGoogle Scholar10 Austin H, Hooper WC, Lally C, Dilley A, Ellingsen D, Wideman C, Wenger NK, Rawlins P, Silva V, Evatt B. Venous thrombosis in relation to fibrinogen and factor VII genes among African-Americans. J Clin Epidemiol. 2000; 53: 997–1001.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Gillard P, Sucharew H, Kleindorfer D, Belagaje S, Varon S, Alwell K, Moomaw C, Woo D, Khatri P, Flaherty M, Adeoye O, Ferioli S and Kissela B (2015) The negative impact of spasticity on the health-related quality of life of stroke survivors: a longitudinal cohort study, Health and Quality of Life Outcomes, 10.1186/s12955-015-0340-3, 13:1, Online publication date: 1-Dec-2015. Patel J, Patel R, Roberts L, Marsh M, Green B, Davies J and Arya R (2014) Changes in thrombin generation and D-dimer concentrations in women injecting enoxaparin during pregnancy and the puerperium, BMC Pregnancy and Childbirth, 10.1186/s12884-014-0384-0, 14:1, Online publication date: 1-Dec-2014. Pakbaz Z and Wun T (2014) Role of the Hemostatic System on Sickle Cell Disease Pathophysiology and Potential Therapeutics, Hematology/Oncology Clinics of North America, 10.1016/j.hoc.2013.11.011, 28:2, (355-374), Online publication date: 1-Apr-2014. Lubinsky M (2012) Hypothesis: Estrogen related thrombosis explains the pathogenesis and epidemiology of gastroschisis, American Journal of Medical Genetics Part A, 10.1002/ajmg.a.35203, 158A:4, (808-811), Online publication date: 1-Apr-2012. Patel R and Arya R (2008) Venous thromboembolism: racial and ethnic influences, Therapy, 10.2217/14750708.5.2.169, 5:2, (169-175), Online publication date: 1-Mar-2008. December 2003Vol 34, Issue 12 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000104160.96489.18PMID: 14657554 Originally publishedDecember 1, 2003 PDF download Advertisement" @default.
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