Coagulation profile of human COVID-19 convalescent plasma

Allan M Klompas,Noud Van Helmond,Jeffrey L Winters,Matthew A Sexton,Juan C Diaz Soto,Camille M Van Buskirk,Stephen A Klassen,James R Stubbs,Katherine A Senese,Scott A Hammel,Justin E Juskewitch,Rajiv K Pruthi,Michael J Joyner,Jonathon W Senefeld

doi:10.1038/s41598-021-04670-1

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.

Highlights

Passive immunotherapy has been used since the late nineteenth century, and in 1901, the first Nobel Prize in Physiology or Medicine was awarded for serum therapy for patients with diphtheria[1]
COVID-19 convalescent plasma contained more protein C antigen than standard fresh frozen plasma but was otherwise not different for any coagulation measures including 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, and alpha-2 plasmin inhibitor (Table 2; Fig. 1). These data suggest that the coagulation profile is not different between fresh frozen plasma and COVID-19 convalescent plasma
When comparing pathogen reduction treated convalescent plasma to fresh frozen plasma and regular convalescent plasma, we found prolonged activated partial thromboplastin time, thrombin time, while pathogen reduction treatment reduced fibrinogen, factors II, V, VIII, IX,X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor

Summary

Introduction

Passive immunotherapy has been used since the late nineteenth century, and in 1901, the first Nobel Prize in Physiology or Medicine was awarded for serum therapy for patients with diphtheria[1]. The coronavirus disease 2019 (COVID-19) pandemic renewed interest in passive immunotherapy and involved the widespread use of convalescent plasma to treat patients with COVID-19. Despite the reports of safety, there are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade among patients with severe COVID-19 receiving convalescent plasma transfusions[4]. Fresh frozen plasma contains physiological ratios of both pro- and anti-coagulant proteins[5]. Plasma from a convalesced COVID-19 patient could contain more procoagulant or less anticoagulant proteins than regular fresh frozen plasma, and when transfused to a current COVID-19 patient contribute to risk of thrombosis. Our primary purpose was to evaluate the coagulation profile of COVID-19 convalescent plasma in comparison to standard fresh frozen plasma. We hypothesized that the coagulation profile of COVID-19 convalescent plasma would not be different from fresh frozen plasma. Variable No of males No of females Total no Age (years) Time spent frozen (days) Time since prior COVID + test (days) Time since COVID symptom resolution (days)

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