key: cord-0050805-9x667lqu
authors: Wooding, Denise J.; Bach, Horacio
title: Treatment of COVID-19 with convalescent plasma' – Author’s reply
date: 2020-09-29
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.09.039
sha: c8d0c9fc6757be8186a0b8c3fbbbb2247c6ba213
doc_id: 50805
cord_uid: 9x667lqu

nan

To the Editor, 10 11

We would like to thank Gazzaruso and colleagues for their interest in our review of 12 convalescent plasma (CP) for treating COVID-19. The authors describe an intriguing potential 13 link between CP and thromboembolic therapy, suggesting that CP may exert its therapeutic 14 effects through anticoagulant properties, specifically via antithrombin replacement. This new 15 theory provides an interesting angle to the mechanism of CP as a therapeutic agent and may 16 lend insight into future research. However, the gaps in the literature are too broad to make 17 clinical recommendations. 18

The authors state that "mortality in patients with COVID-19 is mainly attributed to 19 thromboembolic complications" and that "despite the anticoagulation, usually with heparin, 20 mortality due to thromboembolic events is high." While such complications have indeed been 21 described in COVID-19 patients, the cited articles are not so definitive as to say that they are a 22 primary cause of death. The first cited article describes that only a few studies have 23 investigated the burden of thromboembolic complications in COVID-19 patients, with an 24 care patients (1). In addition, most of these studies had small sample sizes, and the clinical 26 significance of such thromboembolic events, such as whether they increase mortality, remains 27 uncertain. The second article demonstrates a relationship between low antithrombin and 28 mortality, but this cannot be assumed to be a result of fewer thromboembolic events (2). 29

In addition, the authors describe that antithrombin deficiency may explain why some 30 patients do not respond to heparin therapy. The authors cite that approximately 25% of 31 patients with severe COVID-19 have antithrombin deficiency (3). This, in addition to the fact 32 that even the highest estimates of VTE incidence in COVID-19 are only 35%, leaves us with a 33 small proportion of patients who could theoretically benefit from antithrombin replacement, 34 and all this is in the absence of clinical data to demonstrate that VTE causes a significant 35 mortality burden. 36

There is little data to either support or refute this hypothesis at present. The lack of 37 certainty in clinical data is to no fault of the authors and simply reflects the nature of this ever-38 evolving pandemic. Similar to the studies cited in our review, most of the data available to us is 39 derived from observational studies with small sample sizes. The suggestion that CP could 40 provide antithrombotic effects for those patients who are antithrombin deficient and thus 41 potentially refractory to heparin is indeed intriguing. As suggested, it does seem theoretically 42 reasonable for future studies to assess antithrombin status in CP recipients. However, given 43 that CP therapy is already fraught with practical challenges, prioritizing improved knowledge of 44 the chain of assumptions underlying this theory may prove more beneficial, including the 45 assumptions that 1) thromboembolic events contribute significantly to COVID-19 mortality; 2) 46 those patients for whom heparin is ineffective. 48 

Thromboprophylaxis for medical inpatients with 60 coronavirus disease 2019

Association 62 between antithrombin and mortality in patients with COVID-19. A possible link with obesity

The 65 procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome