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We would like to thank our colleagues for their letter in response to our manuscript. The letter raises important theoretical concerns about the impact of procoagulant factors in plasma on the coagulation cascade in the context of patients with severe COVID-19.
Generally, we agree with the word of caution regarding the use of convalescent plasma in the context of patients with severe COVID-19 and evidence of dysregulated hemostasis, as observed among patients who required extracorporeal membrane oxygenation (ECMO) support.
Theoretically, if transfused to a patient that is prothrombotic, plasma can contribute to ongoing dysregulated hemostasis. Despite the theoretical concerns enumerated by our colleagues, some evidence suggests that transfusion of fresh frozen plasma in nonbleeding critically ill patients does not aggravate their inflammatory response, and it might stabilize endothelial condition.
the low rate (∼0.5%) of thrombotic and thromboembolic events—113 events in 20,000 patients with COVID-19—is encouraging, particularly given the high prevalence of both COVID-19 associated–respiratory failure and hypoxemia in the observed patients. Herein, the rate of thrombotic and thromboembolic events was stratified using a 6-level ordinal scale to assess the clinical course of COVID-19,6 with higher scores indicating worse condition at time of enrollment (Figure). The rate of thrombotic and thromboembolic events appears to increase with more advanced clinical course of COVID-19; however, the rate of events is objectively low among patients in the most severe category of COVID-19 (∼0.8%).
In summary, we agree with the word of caution provided by our colleagues, particularly among patients with COVID-19 who have a dysregulated coagulation system promoting hypercoagulation. The coagulation profile of plasma and its likely effect on hemostatic balance should be a factor in clinical decisions about the therapeutic use of convalescent plasma. However, the low rate of thrombotic and thromboembolic events provides strong support of the safety profile of convalescent plasma, even among hospitalized patients with severe COVID-19.
Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past.
Joyner et al1 recently provided a safety update on the use of convalescent plasma (CP) in a population of 20,000 patients with coronavirus disease-19 (COVID-19). The results on the safety aspects, elegantly presented by the authors, may seem encouraging from many perspectives. However, we would like to comment on an extremely important aspect when considering the use of CP.
To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized coronavirus 2019 (COVID-19) patients, having previously demonstrated safety in 5000 hospitalized patients.