| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Activation of platelets and a hypercoagulable state generally occur in acute and chronic ischemic stroke. Protein C is activated to activated protein C (APC) by thrombin, which combines with thrombomodulin in endothelial cells. APC functions as an anticoagulant by inhibiting the activity of coagulation cofactors Va and VIIIa. The concentration of APC has been expressed as the % change or antigen values, not absolute values. The purpose of the present study was to determine the absolute values of the APC concentration and to assess their importance in acute ischemic stroke.
We examined APC in 47 acute ischemic stroke patients, which included 21 with atherothrombotic infarction (ATI) (mean age 73), 15 with lacunar infarction (LI) (mean age 70) and 11 with cardiogenic embolism (CE) (mean age 80). The APC concentration was estimated by enzyme capture assay (ECA) (Teijin). Anti-Protein C monoclomal antibodies were immobilized in microplates, and the surface was blocked. Samples containing AP
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C and benzamidine, a reversible inhibitor of APC, were incubated in the wells for capture of APC antigen. Unbound sample constituents and the benzamidine were removed by extensive washing. The amidolytic activity of the captured APC was measured using a chromogenic substrate. The measurements were performed at the hyperacute (within 24 hours after onset), acute (4-7 days), subacute (8-14 days) and chronic (30 days) stages in each patient. Coagulant and fibrinolytic markers were determined simultaneously at each stage.
The absolute APC concentration within 24 hours after onset was 3.3±0.9 in ATI, 2.5±0.8 in LI and 3,1±1.1 in CE. A significant difference was observed between ATI and LI (p<0.01), When the cases were divided into perforating artery infarction and cortical infarction, no significant difference in APC concentration was evident between them. As regards chronological changes of APC concentration, it tended to decline gradually with time in CE and ATI, but not in LI. We examined the relationship between coagulant and fibrinolytic markers and the APC concentration, and found a significant correlation between prothrombin fragment 1+2 and the APC concentration in CE (p<0.05). Concerning the severity of disease, no correlation existed between the APC concentration and NIH Stroke Scale scores.
We determined the absolute concentration of APC in acute ischemic stroke patients for the first time. Elevation of the APC concentration was found in CE and ATI at the acute stage. The correlation between APC and prothrombin fragment 1+2 indicated that APC could represent one of the hypercoagulable markers in acute stroke. However, further research is needed to enhance the accuracy of measurement and to evaluate the most appropriate measuring time, especially at the acute stage. Supplementary administration of APC might provide a new therapy for acute ischemic stoke in the future. Less
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