Clot waveform analysis for perioperative hemostatic monitoring in a hemophilia A patient on emicizumab undergoing liver transplantation

Abstract While the prognosis and the quality of life of hemophilia A patients have been improved greatly, liver diseases due to hepatitis virus infection from blood products previously administered, which require liver transplantation, are increasing. How to optimize perioperative factor VIII (FVIII) replacement through hemostatic monitoring is critically important in hemophilia A patients undergoing liver transplantation. Clot waveform analysis (CWA) extends the interpretation of measurement curves for activated partial thromboplastin time (APTT) or prothrombin time to provide global information about coagulation abnormalities and disorders such as coagulation factor deficiencies. We performed CWA to monitor perioperative hemostasis in a hemophilia A patient on emicizumab undergoing liver transplantation using a brain-dead donor for liver cirrhosis due to hepatitis virus C infection. To gain accurate results of APTT-CWA as well as of APTT and FVIII activity measurement, plasma samples were treated with anti-idiotype monoclonal antibodies against emicizumab to cancel its interference with the coagulation assays due to binding human activated FIX (FIXa) and FX to functionally mimic FVIIIa. Kinetics of the maximum coagulation velocity and acceleration roughly mimicked that of the FVIII activity. These CWA parameters better correlated with FVIII activity than APTT. The plateaus of them were observed at FVIII activity of 100% or more, likely supporting the protocol for perioperative FVIII replacement. Thus, CWA may measure coagulation potential in hemophilia A patients undergoing liver transplantation, aiding in optimizing perioperative FVIII replacement for proper hemostatic management.