Background. Internationally published data about the course of COVID-19 in patients with congenital bleeding disorders (CBDs) are limited. There are questions about how COVID-19 affects the course of CBDs and, conversely, how CBDs affect the course of coronavirus infection.Aim — to analyze the course of COVID-19 in patients with CBDs in Russia.Materials and methods. A cross-sectional survey was conducted at the National Medical Research Center for Hematology (Moscow) for the period from June 25 to July 31, 2022. A cluster of 187 patients from different regions and cities of Russia were interviewed with a questionnaire based on survey administration software (Google forms) containing 27 questions.Results. COVID-19 affected 115 (62 %) of 187 surveyed patients and 22 (19 %) patients suffered from coronavirus infection twice. Hospitalization was required for 14 (12 %) patients with an average age of 42 years (10 patients with severe hemophilia A, 1 patient with moderate hemophilia B, 2 patients with von Willebrand disease and 1 patient with hypoproconvertinemia). During COVID-19 bleeding was observed in 9 (8 %) patients and was represented by hemarthrosis, ecchymosis, hematomas, nosebleeds, menorrhagia, hemorrhoidal bleeding, hemorrhage in the eyeball. There were no cases of thrombosis among 115 COVID-19 patients. Among patients with CBDs who had COVID-19, compared with patients who had not COVID-19, von Willebrand disease was statistically significantly more common (p = 0.04). Changes in the course of CBD after COVID-19 were noted by 21 (18 %) of 115 patients: 11 (10 %) of those who were ill noted increased joint pain, 9 (8 %) complained of joint pain that had not been previously experienced; 10 % of patients described changes of hemorrhagic syndrome.Conclusion. The probability of hospitalization of patients with CBDs and COVID-19 older than 40 is statistically significantly higher. Von Willebrand disease can be considered as a potential risk factor for COVID-19. Given the absence of cases of thrombosis in the interviewed group of patients, the results of the study suggest that the presence of hypocoagulation in patients with CBDs may be a protective pathophysiological mechanism that prevents the development of COVID-19-associated thrombotic complications.

Introduction. The most widely accepted notion of the function of blood clotting factor XII (FXII, Hageman factor) is its involvement in the internal blood clotting pathway. However, the biological role of FXII is diverse.Aim – to review the diverse biological functions of FXII.Main findings. FXII is a serine protease. The structure of FXII has a high degree of homology with plasminogen, tissue plasminogen activator and urokinase plasminogen activator. Activated FXII (FXIIa) has five substrates: high-molecular kininogen, precallikrein, FXI, plasminogen, complement proteins (C1s, C1r). FXII provides hemostatic balance by participating in the processes of blood clotting and fibrinolysis. FXII regulates inflammatory and allergic reactions by interacting with the kallikreinkinin system and the complement system. FXII has biological activity in various cells in vivo: endotheliocytes, platelets, monocytes, neutrophils, fi broblasts, dendritic cells, which determines its diverse role in physiological and pathological processes.

Hemophilia A (HA) is one of the most widespread, X-linked, inherited bleeding disorders, which results from defects in the F8 gene. Nowadays, more than 3500 different pathogenic variants leading to HA have been described. Mutation analysis in HA is essential for accurate genetic counseling of patients and their relatives. We analyzed patients from 273 unrelated families with different forms of HA. The analysis consisted of testing for intron inversion (inv22 and inv1), and then sequencing all functionally important F8 gene fragments. We identified 101 different pathogenic variants in 267 patients, among which 35 variants had never been previously reported in international databases. We found inv22 in 136 cases and inv1 in 12 patients. Large deletions (1–8 exons) were found in 5 patients, and we identified a large insertion in 1 patient. The remaining 113 patients carried point variants involving either single nucleotide or several consecutive nucleotides. We report herein the largest genetic analysis of HA patients issued in Russia.

Afibrinogenemia is a rare congenital coagulopathy that leads to life-threatening bleeding. In afibrinogenemia, plasma fibrinogen levels are less than 0.1 g/L. The clinical manifestations of the disease can be both bleeding and thromboses of different localizations, which is determined by the multifunctional role of fibrinogen in hemostasis. The described cases demonstrate different clinical phenotypes of the disease. In both cases the diagnosis was confirmed by genetic examinations that revealed homozygous mutations in the fibrinogen A genes. The nature of the mutations assumes consanguineous marriages, as confirmed by the results of a genealogical analysis. Fibrinogen preparations are promising in treating afibrinogenemia in Russia.

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