Jenny Ross1, Rustam Al-Shahi Salman. 1. Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Abstract
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.
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.
Authors: Sara Juliana de A de Vasconcellos; Edmundo M do Nascimento-Júnior; Marcel Vinícius de Aguiar Menezes; Mário Luis Tavares Mendes; Rafael de Souza Dantas; Paulo Ricardo Saquete Martins-Filho Journal: JAMA Otolaryngol Head Neck Surg Date: 2018-09-01 Impact factor: 6.223
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Authors: Rob A Dineen; Stefan Pszczolkowski; Katie Flaherty; Zhe K Law; Paul S Morgan; Ian Roberts; David J Werring; Rustam Al-Shahi Salman; Tim England; Philip M Bath; Nikola Sprigg Journal: BMJ Open Date: 2018-02-03 Impact factor: 2.692