Clinical and laboratory investigation of the effects of ϵ-aminocaproic acid on hemostasis

David Green*, Chung Hsin Ts'ao, Leonard Cerullo, Isaac Cohen, Tsuen I. Ruo, Arthur J. Atkinson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

We previously reported that ε{lunate}-aminocaproic acid (EACA) prolonged the bleeding time in patients with intracranial aneurysms when given in doses of 36 to 48 gm/day. We now show that doses of 24 gm/day also prolong the bleeding time, but only after 72 hours of continuous infusion. The effect on the bleeding time correlates with the duration of EACA therapy but not with the plasma level of the drug. Bleeding times return toward normal within 72 hours of discontinuing EACA infusions. The factors responsible for the bleeding time prolongation were investigated. In vitro, EACA inhibited adenosine diphosphate- and collagen-induced platelet aggregation and the release of platelet adenosine triphosphate and serotonin. It also prevented the adenosine diphosphate-stimulated binding of fibrinogen to intact as well as to chymotrypsin-treated platelets. However, platelets obtained from patients who had received EACA showed little functional impairment. This observation indicates that the focus of EACA activity in vivo is probably not the platelet per se, but the platelet-vessel wall interaction or a vascular component alone. EACA did not enhance prostacyclin production or release from cultured bovine endothelial cells. The fact that the effects of the drug on the bleeding time were related to the duration of EACA therapy suggests that an accumulation of the drug on the vessel wall may be required before alterations in hemostasis are observed. EACA in a daily dose of 24 gm significantly impaired fibrinolysis, but supranormal levels of fibrinolytic activity were observed within 72 hours of stopping the drug. The use of EACA in patients with intracranial aneurysms requires the judicious balancing of effects on the bleeding time with changes in fibrinolytic activity to provide optimal hemostatic management.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalThe Journal of laboratory and clinical medicine
Volume105
Issue number3
StatePublished - Mar 1985

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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