Coagulation profile of human COVID-19 convalescent plasma

Abstract

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.

Figure 1

Coagulation profile of COVID-19 convalescent plasma (purple), pathogen reduced COVID-19 convalescent plasma (green), and standard fresh frozen plasma (yellow). The following measurements were made: prothrombin time (PT, s), activated partial thromboplastin time (aPTT, s), thrombin time (TT, s), fibrinogen (FGN, mg/dL), D-Dimer (D-D, ng/dL fibrinogen equivalent units [FEU]), von Willebrand factor (vWF) activity (%), von Willebrand factor antigen (%), various coagulation factors II, V, VII–XII (FII, FV, FVII–FXII, %), protein S (PS) activity (%), protein C (PC) antigen (%), and alpha-2 plasmin inhibitor (a2-PI, %). Individual data are represented as symbols and summary statistics (mean ± standard deviation [SD]) are represented as bar charts. Grouped data are compared using one-way analysis of variance with Tukey’s honestly significant difference (HSD) post hoc test to determine p values; *p < 0.05; **p < 0.01; and ***p < 0.001). Horizontal bars above given columns indicate the comparisons being made. Whole blood reference ranges are denoted by grey filled areas bound by dotted black lines. Reference ranges are not available for FGN, FV:C, FVIII:C, and PC antigen.