Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms

Abstract

One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind, placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid (TXA) in the management of ruptured intracranial aneurysms. The incidence of recurrent haemorrhage between active and placebo groups was identical (12%) and the mortality from recurrent haemorrhage was 7% and 5%, respectively. The overall incidence of cerebral infarction before surgery, at discharge and at 6 months follow-up was greater in the TXA group (27%) than in the control group (11%). Post-operative cerebral ischaemia was significantly more frequent in the active, 18 of 29 as compared to 6 of 32 patients, in the placebo group. In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow (CBF) on the side of the ruptured aneurysm in the TXA treated group. It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group. There was no significant difference in the incidence of cerebral vasospasm, hydrocephalus, visual disturbances and gastrointestinal disturbances. More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5% level. Given that disability was due to either vasospasm or recurrent haemorrhage than a patient under TXA treatment was significantly more likely to have disability due to vasospasm (p less than 0.04); the reverse was true for the placebo patient (p less than 0.05).

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage

“…144 Similar findings were reported by Kassell et al 240 in a nonrandomized, controlled study; a 40% reduction in rebleeding in patients receiving antifibrinolytic therapy was offset by a 43% increase in focal ischemic deficits. In a double-blind, placebo-controlled trial of tranexamic acid, 249 there was no difference in rebleeding between groups, and an increase in cerebral ischemia was seen for treated patients, although the sample size was not sufficient to demonstrate significance. Retrospective studies 250,251 have shown similar results regardless of the duration of antifibrinolytic therapy with either epsilon aminocaproic acid (36 g/d) or tranexamic acid (6 to 12 g/d).…”

Ultra-Early Hemostatic Therapy for Intracerebral Hemorrhage

“…Clinical trials and large observational studies indicate that these agents reduce the frequency of rebleeding after aneurysmal subarachnoid hemorrhage but increase the frequency of delayed cerebral ischemia and other thrombotic complications, resulting in no overall benefit on outcome. [72][73][74] Aprotinin is a polypeptide that inhibits the action of several serine proteases (including plasmin and kallikrein) by forming reversible enzyme-inhibitor complexes. 57 By inhibiting kallikrein, aprotinin indirectly inhibits the formation of activated factor XII, which disrupts coagulation.…”

Microthrombosis after Aneurysmal Subarachnoid Hemorrhage: An Additional Explanation for Delayed Cerebral Ischemia

“…However, there was no effect on the overall outcome as a result of an increased incidence of DCI, and impeded recovery from DCI, if this occurred (Vermeulen et al, 1984;Roos, 2000;Roos et al, 2003). As tranexamic acid does not influence the rate of cerebral vasospasm, direct hemostatic effects are a more plausible explanation for the increased incidence of DCI (Tsementzis et al, 1990). Therefore, it seems that the incidence and recovery from DCI can be influenced by drugs without a clear effect on vasospasm.…”