In vitro studies show synergistic effects of a procoagulant bispecific antibody and bypassing agents.

CONCLUSIONS: SIA (600 nM) or aPCC (0.5 U/mL) alone resulted in peak thrombin concentrations (Cmax ) of 21.4 and 38.6 nM, respectively, both lower than normal (83.7 ± 29.8 nM). SIA plus aPCC (0.5 U/mL) increased Cmax 17-fold over SIA alone, exceeding reference plasma by 4.2-fold. This hypercoagulable effect occurred with 600 nM SIA combined with as little as 0.25 U/mL aPCC, confirmed by ROTEM. FIX was the main driver for enhanced TG. SIA plus rFVIIa (1.75 μg/mL) induced a 1.8-fold increase in thrombin Cmax in platelet-rich plasma, but did not reach normal range. These in vitro experiments demonstrate excessive TG after combining aPCC and SIA at clinically relevant doses. Careful judgment may be required when treating breakthrough bleeding in patients receiving emicizumab. This article is protected by copyright. All rights reserved.
PMID: 29888855 [PubMed - as supplied by publisher]

Source: Thrombosis and Haemostasis - June 11, 2018 Category: Hematology Authors: Hartmann R, Feenstra T, Valentino L, Dockal M, Scheiflinger F Tags: J Thromb Haemost Source Type: research