Extrinsic pathway of blood coagulation and thrombin in the cerebrospinal fluid after subarachnoid hemorrhage

OBJECTIVE: The involvement of thrombin in the pathophysiology of subarachno id hemorrhage (SAH) was investigated by comparing thrombin expression and e xtrinsic pathway activation in the cerebrospinal fluid (CSF) and blood of p atients with SAH with the neurological grades, outcome, and presence of del ayed cerebral vasospasm. METHODS: Blood and CSF samples were obtained from 38 patients with SAH on D ays 3 through 5, 7 through 9, and 12 through 14 after the onset of SAH. CSF samples were also obtained from control patients. Thrombin-antithrombin II I complex, prothrombin fragment F1+2, tissue factor, and tissue factor path way inhibitor were analyzed using enzyme-linked immunosorbent assay. RESULTS: No markers in the blood or CSF were correlated with neurological g rades and outcome. Thrombin-antithrombin III complex and prothrombin fragme nt F1+2 levels were significantly higher in the CSF of patients with SAH th an in the blood or the CSF of control patients and were significantly highe r in patients with vasospasm than in patients without vasospasm on Days 7 t hrough 9. Tissue factor levels were significantly higher in the CSF of pati ents with SAH than in the blood, but the levels were close to those in the CSF of control patients. Tissue factor pathway inhibitor levels in the CSF of patients with SAH and control patients were under the detection limit. CONCLUSION: Thrombin in the blood may not reflect the pathophysiology of SA H. Imbalance between tissue factor and tissue factor pathway inhibitor in t he CSF may tend to thrombin generation under normal physiological condition s and also after SAH. Thrombin in the CSF may be involved in the pathophysi ology of vasospasm.