key: cord-0890236-mdlmypgq
authors: Gazzaruso, Carmine; Valenti, Cinzia; Coppola, Adriana; Gallotti, Pietro
title: Impact of convalescent and nonimmune plasma on mortality of patients with COVID-19. A potential role for antithrombin
date: 2020-09-09
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.09.007
sha: e1655a776508248b609ebb1c1f196e7f7b4d3862
doc_id: 890236
cord_uid: mdlmypgq

nan

We have read with attention the review about the treatment of COVID-19 with convalescent plasma [1] and the commentary on the thromboprophylaxis in patients hospitalized for COVID-19 [2] . We found both articles of great interest and we believe that some considerations may link them each other. Convalescent plasma is considered a potential effective treatment for severe COVID-19 [1] . To date, there are still small studies that provided quite positive results on survival, especially if convalescent plasma was given early in the course of the disease [1] . Therefore, clinical trials to assess its real effectiveness are ongoing, even if they are at high risk of bias, as correctly outlined [1] .

Severe COVID-19 is characterized by a procoagulant state that can lead to fatal venous and arterial thromboembolic events, such as pulmonary embolism, disseminated intravascular coagulopathy, venous thromboembolism, stroke, myocardial ischemia [2, 3] . In other words, mortality in patients with COVID-19 is mainly attributed to thromboembolic complications [2, 3] . So, prophylactic or therapeutic anticoagulation is recommended in all the patients hospitalized for COVID-19 [2, 3] . However, despite the anticoagulation, usually with heparin, mortality due to thromboembolic events is high [2, 3] . This suggests that heparin is ineffective in a significant proportion of patients with COVID-19, but most of the reasons remain unknown [2, 3] .

Several recent studies have shown that acute antithrombin deficiency is common in patients with COVID-19 [3, 4, 5] . Antithrombin deficiency may be present in at least 25% of the patients with severe COVID-19 [3, 4, 5] . The clinical efficacy of heparin is mainly due to its interaction with antithrombin and therefore anticoagulation may be ineffective in COVID-19 patients with low antithrombin levels [3, 5, 6] . In addition, heparin treatment itself may further reduce antithrombin levels [3, 6] . Low antithrombin levels seem to be strongly associated with mortality and need for mechanical ventilation in patients with COVID-19 [3] .

However, in patients with antithrombin deficiency anticoagulation with heparin may become effective if antithrombin concentrate or fresh frozen plasma are administered [6, 7] .

These new findings suggest some considerations about the results obtained by the studies on the treatment of COVID-19 with convalescent plasma. Indeed, we cannot exclude that some of the positive effects of convalescent plasma on survival of the patients may be due to the antithrombin present in the plasma, when this plasma was used in patients with unknown antithrombin deficiency. Therefore, ongoing and future trials on convalescent plasma should take into account antithrombin levels of the patients to correctly measure the impact of the treatment on the outcomes. These analyses may even suggest that convalescent plasma may become the elective treatment for COVID-19 patients with antithrombin deficiency, as it could act not only on the viral infection but also on the antithrombin deficiency. 

Treatment of COVID-19 with convalescent plasma: lessons from past coronavirus outbreaks

Thromboprophylaxis for medical inpatients with coronavirus disease

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

Prominent changes in blood coagulation of patients with SARS-CoV-2 infection

Anticoagulation With Argatroban in Patients With Acute Antithrombin Deficiency in Severe COVID-19

Antithrombin: Anti-Inflammatory Properties and Clinical Applications

Treating Heparin Resistance with Antithrombin or Fresh Frozen Plasma