Thrombin

Not so long ago, events altering neurologic function were classified as “spells,” underscoring their cryptic nature. In time, many of these events were found to be ischemic strokes. That cerebral ischemia can be accompanied by alterations in the plasma is the basis for the hunt for convenient markers of brain injury that may suggest the cause. First among these is the evidence of platelet activation, changes in the hemostatic system, and changes in the plasminogen activator-inhibitor axis in the days following ischemia onset.1–7⇓⇓⇓⇓⇓⇓ There is a substantial rise in β-thromboglobulin from platelet α-granules and fibrin(ogen) degradation products 1 to 2 weeks after ischemic stroke.4 Often groups of stroke patients have been compared with “control” populations, generating the impression that ischemia can cause alterations in hemostasis (e.g., platelet activation).1,3,4⇓⇓ Longitudinal studies have further supported the notion that ischemia can activate the coagulation system when elevated levels of a marker (e.g., fibrinopeptide A) descend to plateaus over time following the ischemic event.4,7⇓ However, nearly all such studies suffer from the absence of pre-ictal levels of the markers of interest. As an alternative to these approaches, Furie et al.8 prospectively compared evidence of coagulation system activation, through evidence of thrombin generation, between two stroke subgroups (cryptogenic versus non-cryptogenic) who received aspirin in the Warfarin Aspirin Recurrent Stroke Study (WARSS).9 Central to the Furie et al.8 report is the relationship between thrombin and ischemia. Thrombin is the active serine …