One of the major clinical concerns of the antiphospholipid syndrome (APS) is the propensity of antiphospholipid(aPL) antibodiesto cause thrombosis in both the large and small vessels of the brain. In this article, we review the current understandingof haemostasis in cerebral circulation and discuss this in the context of antiphospholipidantibodies. The systemic-defect-local-phenotypeparadox is of particular importance in this discussion. In this paradigm, a systemic defect in thrombosis and haemostasis leads to a localized pattern of thrombotic disease because the regional physiological variations in the several prothromboticand anticoagulantfactors and the defect interact so as to favour thrombosis at a particular site. One possible mechanism of initiation of thrombosis in APS is the activation of endothelialcells by aPL that could occur in the cerebral vessels and provoke thrombosis. We review the evidence from gene knockout mice, other animal models and human postmortem examination studies as to which pro- and antithrombotic mechanisms are effecting haemostasis in the cerebral circulation. We conclude that there are large deficits in the understanding of the regulation of haemostasis in the human brain. As a consequencethere is a lack of knowledgeabout the effect of aPL on cerebral endothelium and thrombosis. Recent developments in gene expression profiling may have an impact on our understandingof endothelialfunctionin the brain. More research is required.
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