Aims: The antifibrinolytic drug tranexamic acid (TXA) improves survival after trauma. Antifibrinolytic drugs
may also improve outcome after spontaneous bleeding, so we conducted a systematic review of the frequency of
thrombotic events associated with their use after spontaneous bleeding, to help design future randomized controlled trials.
Methods: We sought trials or observational studies of ≥20 adults involving any antifibrinolytic drug (TXA, epsilonaminocaproic
acid (EACA) or aprotinin) for spontaneous (non-traumatic, non-surgical/iatrogenic), non-heamophiliac
bleeding. We searched the Cochrane Central Register of Controlled Trials, OVID Medline from 1966, EMBASE from
1980, and the bibliographies of relevant articles in October 2009. We meta-analysed proportions of patients with
thrombotic events, using a random effects model.
Results: We found 57 studies involving 5,049 patients, 3,616 (72%) of whom had spontaneous subarachnoid
haemorrhage. 3,414 (68%) patients received TXA-based treatment and 1,635 (32%) received EACA. The frequencies of
limb ischaemia and myocardial infarction were <1% for TXA and EACA. The frequency of deep vein thrombosis or
pulmonary embolism was 1.9% (95% confidence interval (CI) 1.1 to 2.9) for TXA and 3.0% (95% CI 1.8 to 4.6) for
EACA. The occurrence of cerebral infarction was restricted to studies of subarachnoid haemorrhage when compared to
other indications, both for TXA (9.7% [95% CI 5.5 to 14.8] versus 0% [95% CI 0 to 0.5]) and for EACA (7.7% [95% CI
1.8 to 17.4] versus 0% [95% CI 0 to 2.1]).
Conclusions: Thrombotic events have occurred infrequently with antifibrinolytic drugs after spontaneous bleeding apart
from subarachnoid haemorrhage, so further exploration of their safety and efficacy after spontaneous bleeding is justified
in randomized trials.