Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection
The SARS-CoV-2 pandemic has focused attention on prevention, restriction and treatment methods that are acceptable worldwide. This means that they should be simple and inexpensive. This review examines the possible role of glycosaminoglycan (GAG) antithrombotics in the treatment of COVID-19. The pathophysiology of this disease reveals a complex interplay between the hemostatic and immune systems that can be readily disrupted by SARS-CoV-2. Some of the GAG antithrombotics also possess immune-modulatory actions and since they are relatively inexpensive they could play an important role in the management of COVID-19 and its complications.
It is clear that both disruption of immune reactions to inflammatory responses and hemostatic changes play a great role in the development of severe morbidity in COVID-19. While many drugs may prevent one or other of the responses those that combine both actions, such as many of the currently available GAG antithrombotics, may offer more effective and safer prophylaxis and/or treatment. Given the extreme complexity of the immune and hemostasis interactions to infection by the COVID-19 virus it is probably unlikely that a single GAG antithrombotic with immune-modulatory activity could fit into the management plan for all patients. Two possible GAG candidates, taking-into-account their safety in comparison with the heparins, are sulodexide and danaparoid with (possibly) different effects on hemostasis and the immune/inflammatory systems. Animal and ex-vivo/in-vitro experiments offer useful information but direct extrapolation to infected patients is confounded by uncertainties concerning whether either of these purified antithrombotics compares chemically and physiologically with their natural unextracted counterparts, tissue specificity of structure/function relationships and species differences in responses to the various stimuli used to mimic the pathophysiological changes seen in patients. While both drugs on paper offer interesting insights danaparoid has been used in more of the acute critical clinical situations that arise in COVID-19 infection than sulodexide. The other advantage is their relatively low cost. Whether sulodexide would be more useful in the early stages as preventative therapy and danaparoid more useful once complications are threatening or emerging, or indeed neither or both eventualities, requires a well-designed clinical trial that includes the whole clinical spectrum of COVID-19 patients otherwise treated according to accepted recommendations for the extent and severity of their disease.
