Ethnic differences in markers of thrombophilia - Implications for the investigation of ischemic stroke in multiethnic populations: The South London Ethnicity and Stroke Study

Background and Purpose-The role of hypercoagulable states in the pathogenesis of ischemic stroke in black subjects is not known, and data on normal reference ranges in black populations are lacking. This study estimated ethnic-specific reference ranges in a community population to determine the prevalence of thrombophilic states in a multiethnic stroke population. Methods-Free protein S, protein C, antithrombin III, activated protein C resistance, IgG anticardiolipin antibodies, and lupus anticoagulant were determined in 130 consecutive ischemic stroke cases less than or equal to65 years of age (50 black Caribbeans, 30 black Africans, 50 whites) and 130 community controls. Results-Black African controls had significantly lower protein S (P<0.001) and protein C (P=0.049) and a trend toward lower antithrombin III (P=0.056) levels compared with white controls. Black Caribbean and African controls had higher diluted Russell's viper venom time ratios compared with whites (P=0.001, P<0.001). Using ethnic-specific reference ranges, 8 controls (6.3%) and 11 cases (8.5%) had thrombophilia abnormalities (odds ratio [OR], 1.39; 95% confidence interval [CI], 0.54 to 3.57; P=0.50). ORs were 0.96 (95% CI, 0.18 to 4.99; P=0.96) for whites, 1.57 ( 95% CI, 0.41 to 5.94; P=0.51) for black Caribbeans, and 2.07 (95% CI, 0.18 to 24.2; P=0.95) for black Africans. Conclusions-Failure to account for ethnic differences in the normal reference ranges for thrombophilia markers may lead to inappropriate diagnosis and investigation of hypercoagulable states in black individuals. Protein S and protein C deficiencies and lupus anticoagulant may contribute to stroke risk in a minority of black cases, but they are unlikely to be major contributors to the excess stroke risk seen in young individuals of African and African-Caribbean descent.