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Editorial
. 2020;45(3):357-362.
doi: 10.1159/000508460. Epub 2020 May 25.

COVID-19, Low-Molecular-Weight Heparin, and Hemodialysis

Alessandra F Perna  1 , Giovanna Capolongo  2 , Francesco Trepiccione  2 , Mariadelina Simeoni  2 , Miriam Zacchia  2 , Diego Ingrosso  3
Affiliations
Editorial

COVID-19, Low-Molecular-Weight Heparin, and Hemodialysis

Alessandra F Perna et al. Kidney Blood Press Res. 2020.
No abstract available

Keywords: COVID-19; Hemodialysis; Low-molecular-weight heparin.

PubMed Disclaimer

Conflict of interest statement

A.F.P. and D.I. received funding from Gnosis, SpA, and EUTox.

Figures

Fig. 1
Fig. 1
Mechanism of action of UFH and LMWH with the major ligand-binding interactions involved. One of the key proteins for the activity of heparin is antithrombin, a serine protease inhibitor (SERPINSC1) that inactivates several clotting factors. Mechanistically, heparin binds to antithrombin, thus exposing the antithrombin protease inhibitor binding site and forming equimolecular complexes with its ligands. Antithrombin uses unique and extensive conformational change mechanisms to inhibit its protease ligands [8]. Heparin increases by orders of magnitude the tendency of antithrombin to interact with a number of plasma proteins. The resulting complex, in particular with thrombin (factor IIa) and factors IXa, Xia, and Xa, inhibits the protease activities of these clotting factors. Heparin indeed works as an antithrombin-protease-inhibiting cofactor without being consumed, and, once the antithrombin-protease complex is formed, heparin is released in its intact conformation, thus repeatedly activating new antithrombin molecules. Heparin biological activity crucially depends indeed on the endogenous antithrombin anticoagulant activity. The role of antithrombin is pivotal in coagulation regulation by shifting thrombin from procoagulant to anticoagulant activity. The presence of heparin dramatically increases the complex stability of antithrombin with the above-mentioned coagulation factors [8, 9]. One important difference between UFH and LMWH is that the interaction of antithrombin with UHF almost equally induces inhibition and degradation of both Xa and thrombin, while LMWH preferentially determines degradation of factor Xa. Various other potential benefits of heparin in COVID-19 have been put forward recently [28].
Fig. 2
Fig. 2
Scheme of the anticoagulant activity of the protein C anticoagulant pathway. Protein C is activated by thrombin (not shown), forming APC [29]. Protein S in turn is a cofactor of APC for the inactivation of activated coagulation factors VIIIa and Va. Only free protein S, i.e., the fraction which is not bound to C4b-binding protein (not shown) in circulation, retains its anticoagulant activity. Activated factor V (factor Va) procoagulant activity is inactivated by APC-catalyzed cleavage at the Arg506 level, yielding factor Vi. Beyond its intrinsic procoagulant activity, Factor Va also exerts an anticoagulant activity as a cofactor for APC and protein S, in inactivation of the procoagulant factor VIIIa yielding factor VIIIi [30]. This function is also compromised in the presence of factor V resistance to cleavage by APC (APC-R; hatched box), mainly due to the Arg506Gln mutation (factor VLeiden), which indeed represents the most common cause of APC resistance in the population.
See this image and copyright information in PMC

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