INTRACRANIAL BLEEDING AND HEMOSTASIS - IM PROVED MANAGEMENT OF PATIENTS WITH INTRACRANIAL BLEEDING BY MEASUREMENTS OF ACTIVATION PRODUCTS OF COAGULATION AND ITS CONTROL

Objective: The aim of the study was to improve the detection of small hemorrhages with minimal symptoms and of unruptured aneurysmas after a subdural and subarachnoid bleeding by the control of the intravascula r hemostatic system. Design: Prospective, open study. Setting: Neurosu rgical intensive care unit of a university hospital. Patients: 44 pati ents undergoing a cranial trepanation. Patients of group 1 (control n= 11) had an intrasellar hypophysoma, patients of group 2 (n=12) a chron ic subdural hematoma without a previous traumatic incident and patient s of group 3 (n=15) a subarachnoid hemorrhage caused by an intracrania l aneurysm. Interventions: After cranial trepanation changes of plasma tic hemostasis have been assessed by means of immunologically determin ed parameters of coagulation. The investigation included blood paramet ers (hemoglobin, hematocrit, thrombocytes), clotting status (prothromb in time, partial thromboplastin time, thrombin time, fibrinogen, plasm inogen, antithrombin III [AT III] activity and proteinase inhibitors), as well as immunological methods such as fibrinopeptide A (FPA), thro mbin-antithrombin III (TAT), protein C and factor XIII: activity (F XI II activity). Results: In comparison to group 1 (control) a significan t difference (p<0.001) was seen in groups 2 and 3 for thrombin-antithr ombin III (TAT), fibrinopeptide A (FPA), protein C, and the antithromb in III activity. Intra- and postoperatively increased TAT levels in gr oups 2 (16.9 ng/ml) and 3 (21.1 ng/ml) and decreased protein C levels (group 2: 61% and group 3: 58%) demonstrated an intravascular thrombin generation. On account of the elevated FPA levels in groups 2 (6.5 ng /ml) and 3 (5.7 ng/ml) and decreased AT III activity in groups 2 (58%) and 3 (62%.), this thrombin. generation was only incompletely compens ated. Caused by proteolytic thrombin effects, another sign for a throm bin-induced turnover of clotting factors is the significant reduction (p<0.001) of F XIII activity in groups 2 (40%) and 3 (44%). In compari son to group 1 this significantly reduced F XIII activity in groups 2 and 3 was correlated (r=0.99) to changes in FPA and TAT plasma levels, an indication of latent chronic clotting activity. No significant dif ference was found concerning total amount of infusion, intra- and post operative blood loss and blood parameters. Eight patients (group 2: 5 patients, group 3: 3 patients) showed a rebleeding episode without ope rative interventions. In these patients increased clotting activity (T AT, FPA, protein C) caused by proteolytic thrombin effects was combine d with a factor XIII activity smaller than 40%. Conclusion: The result s of the recent study indicated that immunologically determined TAT, F PA, protein C, factor XIII and AT III activities might serve to improv e management in patients with intracranial bleeding events. In view of these parameters the evaluation of risks for a rebleeding is improved . A decrease of the plasma factor XIII activity under 40% associated w ith a latent clotting activity induced by a thrombin generation caused a higher risk of rebleeding after an initial intracranial bleeding ev ent. The necessity of substituting factor XIII in such cases should be elucidated to minimize risks of rebleeding.