Heparin sodium

Heparin sodium, as as anti-coagulants, belongs to a class of glucans, which can interact with a variety of proteins to produce a variety of biological activities.^[1][2] Heparin sodium is routinely use for preventing the deep venous thrombosis in medical and surgical patients^[5].

In vitro experiment it demonstrated that SARS-CoV-2 spike protein binds with a much higher affinity to heparin with K D of 55 nM compared to the RBD with K D of 1 μM alone. And heparin has no effect on angiotensin-converting enzyme 2 binding or proteolytic processing of the spike.^[6] Moreover, heparin can inhibit the proteolytic activity of Mpro with an inhibition constant Ki of 6.9 nM and a half maximal inhibitory concentrations (IC₅₀) of 7.8 ± 2.6 nM. ^[7].

In vivo clinical study it shown that treatment with continuous heparin sodium 12 500 U throughout 24 hours with intravenous pump for 5 days in heparin sodium group patients, and with low molecular weight heparin sodium (LMWHS) patients were given LMWHS 2 500 U subcutaneously, twice a day for 5 days, incidence of bleeding during treatment in LMWHS group was remarkably lower than that in heparin sodium group. Moreover, the platelet count in both LMWHS group and heparin sodium group was markedly increased compared with that before treatment; activated partial thromboplastin time also in heparin sodium group was significantly prolonged compared with that before treatment.^[3] In the clinical test, there is no obvious difference in the duration of catheter patency or incidence of phlebitis was observed between the adult patients received 1 mL of a heparin sodium 100 units/mL flush solution and adult patients received a 0.9% sodium chloride flush solution by intermittent intravenous devices were randomly assigned.^[4] In the clinical trail, treatment with low-dose heparin, patients with diabetes mellitus or chronic renal insufficiency are especially predisposed to hyperkalemia.^[5].

References:
[1]Capila I, et al. Heparin-protein interactions. Angew Chem Int Ed Engl. 2002 Feb 1;41(3):391-412.
[2]Hashii N, et al. Heparin identification test and purity test for OSCS in heparin sodium and heparin calcium by weak anion-exchange high-performance liquid chromatography. Biologicals. 2010 Sep;38(5):539-43.
[3]Li Y, et al. [Comparison of the effect of low molecular weight heparin sodium and that of heparin sodium on pre-disseminated intravascular coagulation stage in patients suffering from exertional heat stroke]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015 Aug;27(8):649-52. Chinese.
[4]Hamilton RA, et al. Heparin sodium versus 0.9% sodium chloride injection for maintaining patency of indwelling intermittent infusion devices. Clin Pharm. 1988 Jun;7(6):439-43.
[5]Edes TE, et al. Heparin-induced hyperkalemia. Arch Intern Med. 1985 Jun;145(6):1070-2.
[6]Liu L, et al. Heparan Sulfate Proteoglycans as Attachment Factor for SARS-CoV-2. ACS Cent Sci. 2021 Jun 23;7(6):1009-1018.
[7]Li J, et al. Heparin interacts with the main protease of SARS-CoV-2 and inhibits its activity. Spectrochim Acta A Mol Biomol Spectrosc. 2022 Feb 15;267(Pt 2):120595.