Stroke Risk of Inherited Thrombophilia is Low
Abstracts & Commentary
Sources: Jerrard-Dunne P, et al. Ethnic differences in markers of thrombophilia. Stroke. 2003;34:1821-1826; Hankey GJ, Eikelboom JW [editorial]. Routine thrombophilia testing in stroke patients is unjustified. Stroke. 2003;34:1826-1827.
The term "thrombophilia" is commonly used to describe disorders of the hemostatic mechanisms that are likely to predispose to thrombosis. Examples of inherited factors are deficiency of protein C, protein S, or antithrombin; activated protein C resistance resulting from the Factor V Leiden mutation; and the prothrombin gene (20210G/A) mutation and dysfibrinogenemia. The acquired thrombophilias include the lupus anticoagulant and the anticardiolipin antibodies. Of mixed or unknown origin are high levels of coagulation factors VIII, IX, or XII, among others. The prevalence of inherited thrombophilic states shows a marked interethnic variation. For example, at least one thrombophilic disorder is present in 10-15% of the white population of Western Europe. Data on the normal reference ranges for inherited thrombophilias in the black community are lacking, however. Individuals of African and African-Caribbean descent have a higher incidence of ischemic stroke compared with whites and present with stroke at a younger age. Therefore, Jerrard-Dunne and associates estimated the ethnic-specific reference ranges in a community population to determine the prevalence of thrombophilic states in a multiethnic stroke population. They determined the levels of inherited and acquired markers of thrombophilia in 130 consecutive ischemic stroke patients 65 years of age or younger. The populations included 15 black Caribbeans, 30 black Africans, 50 whites, and 130 community controls. Black African controls had significantly lower protein S and protein C levels and a trend to lower antithrombin III levels compared with white controls. Black Caribbean and African controls had his/her diluted Russell’s viper venom time ratios compared with whites. In ethnic-specific reference ranges, 8 controls and 11 stroke patients had thrombophilic abnormalities. The study demonstrated significant ethnic differences in normal ranges for markers of thrombophilia. Using the normal reference ranges determined from a white population, a significant proportion of healthy black community controls would be classified as having abnormal thrombophilia screening. When appropriate reference ranges were used, thrombophilia was not a significant risk factor for stroke either overall or in any of the 3 ethnic groups studied.
Commentary
As pointed out in Hankey and Eikelboom’s accompanying editorial, thrombophilias are an established independent causal risk factor for venous thromboembolism (VTE) and may account for a substantial proportion of cases of recurrent VTE. For example, in contrast to community controls, a thrombophilic disorder is present in as many as 30% of unselected individuals with VTE and 50-70% of those with recurrent VTE.1 Clinical management of patients with thrombophilia and VTE differs slightly from that of individuals with VTE without thrombophilia. Both groups usually are treated with anticoagulation for a period of time, but patients who have a thrombophilia that predisposes to further episodes of VTE may be treated with anticoagulation indefinitely. In contrast to these cases of VTE, the prevalence of inherited thrombophilia in patients with ischemic stroke is not different from that among the general community. Therefore, the role, if any, of inherited thrombophilia in the causation of ischemic stroke is uncertain. In the present paper, Jerrard-Dunne et al found that 6% of community controls and 8.5% of ischemic stroke cases had a thrombophilia. Similar results have been obtained by others and indicate that inherited thrombophilias account for < 10% of cases of ischemic stroke. An exception to this statement is that prevalence of the acquired thrombophilias, the lupus anticoagulant, and anticardiolipin antibodies is significantly higher in arterial thromboses compared with controls and appears to be an independent predictor of stroke.2 The data suggest that the risk conferred by an inherited thrombophilia for ischemic stroke is likely to be low overall and almost nonexistent in some ethnic groups such as individuals of African or African-Caribbean descent. The risk may be higher in some particular subtypes of stroke, like thromboembolism from venous stasis via a right-to-left shunt such as a patent foramen ovale or pulmonary AV fistula. Nevertheless, in such patients with stroke caused by thromboembolism from venous or cardiac source, long-term anticoagulation is likely to be instituted regardless of the presence or absence of a thrombophilia. Certainly, there appears to be no justification for the routine screening for thrombophilia in most patients, especially older patients with ischemic stroke, in the absence of any reliable data linking the inherited thrombophilias to a particular subtype of ischemic stroke or to a favorable response to a particular intervention. — John J. Caronna, MD, Vice-Chairman, Department of Neurology, Cornell University Medical Center; Professor of Clinical Neurology, New York Hospital; Associate Editor, Neurology Alert.
References
1. Seligsohn U, Lubetsky A. N Engl J Med. 2001;344: 1222-1231.
2. Galli M, et al. Blood. 2003;101:1827-1832.
This study suggests that the risk conferred by an inherited thrombophilia for ischemic stroke is likely to be low overall and almost nonexistent in some ethnic groups such as individuals of African or African-Caribbean descent.
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