In vitro effects of emicizumab on activated clotting time in blood samples from cardiac surgical patients.

Autor: Tanaka KA; Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, USA., Henderson R; Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA., Thangaraju K; Departments of Pathology and Pediatrics, Center for Blood Oxygen Transport, University of Maryland, Baltimore, Maryland, USA., Morita Y; Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, USA., Mazzeffi MA; Department of Anesthesiology & Critical Care Medicine, George Washington University School of Medicine, Washington, District of Columbia, USA., Strauss E; Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA., Katneni U; Departments of Pathology and Pediatrics, Center for Blood Oxygen Transport, University of Maryland, Baltimore, Maryland, USA., Buehler PW; Departments of Pathology and Pediatrics, Center for Blood Oxygen Transport, University of Maryland, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2022 Jan; Vol. 28 (1), pp. 183-190. Date of Electronic Publication: 2021 Nov 04.
DOI: 10.1111/hae.14452
Abstrakt: Background: Heparin management in hemophilia A (HA) patients with a factor VIII (FVIII) inhibitor can be challenging due to severe activated clotting time (ACT) prolongations. It is important to better understand the impact of emicizumab, a FVIII mimetic on ACT, and tissue factor (TF)-based coagulation assays.
Methods: Whole blood from 18 patients undergoing cardiopulmonary bypass (CPB) were mixed in vitro with pooled normal plasma, FVIII-deficient or FVIII-inhibitor plasma to affect functional FVIII levels. ACTs and heparin concentration by protamine titration were measured in whole blood mixture with/without emicizumab (50-100 μg/ml). Thrombin generation and plasmin generation were measured in the patient's plasma mixed with normal plasma or FVIII-inhibitor plasma to assess the impact of emicizumab under low TF activation.
Results: FVIII inhibitors prolonged ACTs by 2.2-fold compared to those in normal plasma mixture at baseline. During CPB, ACTs in normal plasma mixture, and FVIII-deficient mixture were in 400s, but ACTs reached 900s in FVIII-inhibitor mixture. Emicizumab shortened ACTs by up to 100s in normal plasma mixture, and FVIII-deficient mixtures. ACTs remained over 600s in FVIII-inhibitor mixture, despite adding emicizumab at 100 μg/ml. Heparin concentration measured by TF-based protamine titration was unaffected. Emicizumab enhanced thrombin peak in the presence of FVIII inhibitors, whereas plasmin generation was mainly affected by thrombin generation, and systemic use of ɛ-aminocaproic acid.
Conclusions: FVIII inhibitors extensively prolong ACTs in heparinized whole blood, and clinical levels of emicizumab partially reverse ACT values. Protamine titration should be considered for optimal heparin monitoring in emicizumab-treated patients with FVIII inhibitors.
(© 2021 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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