Pathogenetic mechanisms of hypofibrinogenemia in COVID-19

Rabotinskiy, S. E.; Bulanova, E. L.

Background. Coagulopathy in patients with new coronavirus infection COVID-19 is important for the course and prognosis of the disease. Hypercoagulation, hyperfibrinogenemia and thrombosis are typical manifestations of coagulopathy in the acute phase of the disease. Hypofibrinogenemia in COVID-19 is not widely reported in the literature, and the frequency and reasons of its development are unknown. The use of genetically engineered biological drugs (GEBD) may be one of the possible causes of hypofibrinogenemia but the mechanisms of its development are not clear. Objectives: To determine the role of therapy with interleukin-6 receptor antagonists in the development of hypofibrinogenemia in patients with COVID-19-pneumonia, the clinical significance of hypofibrinogenemia and the mechanism of its occurrence. Patients/Methods. A randomized retrospective study included 239 patients aged 18 to 96 years with confirmed by polymerase chain reaction SARS-CoV-2 infection, computed tomography signs (upon admission to the hospital) of viral pneumonia (grade 2–4) and a duration of hospitalization of more than 2 days. All patients underwent laboratory monitoring, including the determination of hemoglobin, platelets, C-reactive protein (CRP), liver enzymes and fibrinogen according to Claus. All patients received initial therapy with hydroxychloroquine and azithromycin. At the time of the study, tocilizumab was the only GEBD drug used in the hospital. Therapy with tocilizumab was performed in 164 (68.6%) patients. The study took into account the maximum and minimum values of hemoglobin, platelet, fibrinogen and CRP levels during the hospitalization. Results. Hypofibrinogenemia of varying severity was observed in 39 patients treated with tocilizumab, that was significantly higher than hypofibrinogenemia frequency in 2 patients who did not receive tocilizumab (RR = 8.9;95% CI = 2.2–25.9). Conclusions. Tocilizumab usage in patients with COVID-19 significantly increases the risk of hypofibrinogenemia. © Gemostaz i Reologia LLC, 2021.