The in vitro effect of anticoagulant agents on coagulation and fibrinolysis in the presence of emicizumab in the plasmas from patients with haemophilia A.

Autor: Onishi T; Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan., Harada S; Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan., Shimo H; Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan., Tashiro Y; Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan., Soeda T; Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan., Nogami K; Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
Jazyk: angličtina
Zdroj: Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2023 Nov; Vol. 29 (6), pp. 1529-1538. Date of Electronic Publication: 2023 Sep 27.
DOI: 10.1111/hae.14877
Abstrakt: Introduction: Emicizumab is used as hemostatic prophylaxis for patients with hemophilia A (PwHA), irrespective of the presence of inhibitors. Although bacterial infection can lead to a procoagulant state, there is limited information on coagulation and fibrinolysis potentials in emicizumab-treated PwHA and on the use of anticoagulants in such cases.
Aim: We examined whether anticoagulants affect the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab.
Methods: Plasma from PwHA was in vitro supplemented with emicizumab (50 μg/mL; emi-plasma) and anticoagulants (recombinant thrombomodulin (rTM), nafamostat mesylate (NM), unfractionated heparin (UFH), or low-molecular-weight heparin (LMH)). PwHA plasma spiked with rFVIII (1 IU/mL) was used as a reference (ref-plasma). The coagulation and fibrinolysis potentials in plasma was measured by thrombin and plasmin generation assay (T/P-GA) and clot-fibrinolysis waveform analysis (CFWA).
Results: In T/P-GA and CFWA, coagulation potentials (maximum coagulation velocity; |min1|, and peak thrombin; Th-Peak) in plasma rose with increasing concentrations of emicizumab and rFVIII, but fibrinolytic potentials (peak plasmin; Plm-Peak, and maximum fibrinolytic velocity; |FL-min1|) remained unchanged. Adding rTM, NM, and UFH to emi-plasma suppressed coagulation and fibrinolysis potentials, similar to ref-plasma. Regarding the heparin, UFH and LMH inhibited the improved coagulation in emi-plasma. UFH inhibited fibrinolysis as well, but LMH did not.
Conclusions: Anticoagulants could exhibit the inhibitory effects on the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab, similar to those in normal plasma.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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