COVID-19: A case for plasma derived natural anticoagulants?

Convalescent plasma was proposed for passive immunization against COVID-19; but so far there are conflicting results and still open questions. However, besides antibodies, other plasma proteins may be good candidates for further research and application. Thromboinflammation frequently complicates severe COVID-19, and classical anticoagulants like heparins seem to have limited effect. The natural protease inhibitors antithrombin III (ATIII), α ₁ -antitrypsin (α ₁ -AT) and α ₂ -macroglobulin (α ₂ -M), which are found decreased in severe COVD-19, play a crucial role in prothrombotic and inflammatory pathways. While ATIII and α ₁ -AT are licensed as commercially prepared therapeutic concentrates, there is no preparation of α ₂ -M available. The diagnostic, prognostic, and even therapeutic potential of plasma protease inhibitors should be further explored.
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