Sulodexide may be a real alternative to low molecular weight heparins in the prevention of COVID‐19 induced vascular complications

Dear Editor,

In their work Demirbaş et al presented a patient with COVID‐19‐associated superficial thrombophlebitis successfully treated with enoxaparine, ¹ a low molecular weight heparin (LMWH) medication and also gave a brief, but detailed overview on SARS‐Cov‐2 induced coagulopathy and the intensive cross‐talk between immune system and hemostasis. ¹ Besides the frequently quoted acute respiratory distress syndrome and dysregulation of coagulation and fibrinolytic systems, COVID‐19 infection is often associated with complement activation, ¹ hypoxaemia, ¹ higher blood viscosity, ² inflammatory endothelial damage (endotheliitis), ³ and arterial hypertension ⁴ predisposing patients to venous as well as arterial vasculopathy. Demirbaş et al found enoxaparin a putatively beneficial therapeutical agent implicating anticoagulatory and antiinflammatory effects ¹ ; however, LMWH and unfractionated heparin (UHF) that demands regular monitoring of activated partial thromboplastin time (aPTT) often generate heparin‐induced thrombocytopenia (HIT) and occasionally major bleeding. ⁵ By contrast, theraputic dosages may induce resistance to UHF or LMWH in a certain subset of SARS‐CoV‐2 infected patients. ⁵ Danaparoid is a blend of heparan sulfate, dermatan sulfate and chondroitin sulfate and would seem theoretically a candidate against COVID‐19‐associated vasculo‐ and coagulopathies but has never been tested extensively for this purpose. ⁶ According to in vitro studies direct oral anticoagulant medications (DOACs) would represent a predictable effect in COVID‐19 however clinical studies have only partially confirmed this theory. ⁶ The expensive parenteral anticoagulant fondaparinux does not cause HIT however its utility in COVID‐19 infection is still under investigation. ⁶ The application of vitamin‐K antagonists is associated with numerous limitations such as the need of routine coagulation monitoring and interactions with food and medications. ⁶

Sulodexide (SDX) is a natural glycosaminoglycane composed of 80% fast moving heparin (FMH) plus 20% dermatan sulfate and its in vitro antihemostatic effects are at least comparable with those of enoxaparine. ⁷ Biological activity comprises arterial and venous antithrombotic and profibrinolytic (increased tissue plasminogen activator level, inhibition of platelet aggregation), antiinflammatory (eg, suppressed interleukin‐6 production) and beneficial hemorheologic (lipid profile modification) effects. ⁷ SDX protects and repairs endothelial layer by glycocalyx restoration and vascular tone regulation, ⁷ , ⁸ displays senolytic activity, ⁹ and attenuates ischemia‐reperfusion injury. ⁷ Compared with LMWHs it is less likely associated with bleeding risk, much weaker in HIT and renal insufficiency does not demand dose reduction. ⁷

In COVID‐19 infection the pleiotropic SDX may represent an alternative to LMWH as a prophylactic agent. Unlike other heparins, SDX can be administered orally with sufficient intestinal absorption providing a median bioavailability of appoximately 40% which also eliminates the fear of needles of LMWH injections. It is safe to use in renal insufficiency and less likely related to HIT, major bleeding and drug‐induced hypersensitivity compared with LMWHs. ⁷

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

DATA AVAILABILITY STATEMENT

Data openly available in a public repository that issues datasets with DOIs