Coagulopathies and Ischemic Stroke

Introduction

In ischemic stroke coagulopathies are characterized by a condition in which blood is too quick to clot. Such coagulation abnormalities may be genetic or acquired. Coagulation abnormalities are identified as the cause of ischemic stroke in less than 1% of unselected series. Accordingly, in the vast majority of patients with ischemic stroke an extensive evaluation to identify a coagulopathy is not warranted. In few specific setting testing for a coagulopathy may provide diagnostic evidence for an otherwise unexplained stroke.

The common coagulopathies and estimates of their prevalence in a general population are listed in Table 115.1 . These coagulopathies sometimes referred to as thrombophilias are mostly associated with venous thrombotic episodes (VTE) . They can be associated with arterial occlusive events including stroke under circumstances of paradoxical embolization and in association with cerebral sinus and vein occlusions.

Antithrombin

Antithrombin inactivates thrombin as well as coagulation factors X, IX, XI, and XII. More than 250 loss-of-function mutations are described causing either decreased circulating levels of protein or decreased activity. Antithrombin deficiencies are a leading contributor to thrombophilia associated VTE but are not associated with stroke as a sole contributor.

Protein C and Protein S

Protein C, which is activated by thrombin, complexes with endothelial protein C receptor and thrombomodulin and together with protein S forms the activated protein C complex that inactivates activated coagulation factors V and VIII. This is a pivotal step in regulation of the coagulation cascade. Protein C and protein S deficiencies are less common than antithrombin deficiency and either low levels or activity can give rise to VTE. Low protein C levels have been associated with silent strokes in adult population studies and apparent arterial strokes in children . Venous thrombosis that include cerebral vein and intracranial sinus thrombosis is most associated with these deficiencies, but arterial thrombosis and stroke have been reported .