Russian recombinant coagulation factors: the technological background and the results of clinical studies

The prolongation of survival and the improvement of quality of life in patients with hemophilia A and B are only possible if hemostatic disorders caused by coagulation factor VIII and IX deficiency are managed effectively. Recombinant coagulation factors are playing an ever-increasing role in the preventive care of affected patients. The development, production and use of domestic recombinant coagulation factors opened up new treatment opportunities and improved access to preventive care for hemophilia patients. The results of clinical studies on the efficacy and safety of the Russian recombinant factors showed that they had similar efficacy and safety compared to the plasma derived clotting factors.

Familial cases of Mexican patients with Legg-Calvé-Perthes disease

BackgroundLegg-Calvé-Perthes Disease (LCPD) is described as an avascular necrosis of the femoral head. Although its etiology is still not fully understood, evidences suggest heritable thrombotic disorders and other factors may be implicated in its onset and progress. Our objective is to describe, in three enrolled families, the genetic, biochemical and environmental factors that may be associated with the etiology and development of LCPD. MethodsTherefore, we set out to evaluate the following alterations of collagen genes: MTHFR rs1801133, CBS rs115742905, and PT rs1799963 and their relationship with LCPD. Thrombophilia associated markers (FI, FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FvW, PC, PS, AT, and homocysteine) were evaluated using coagulometry methods. Results: Seven LCPD patients and 14 healthy volunteers were enrolled. Concentrations in hemoglobin (p ≤ 0.0001), fibrinogen (P ≤ 0.0001), homocysteine (p = 0.0414), factor IX activity percentage (p ≤ 0.0001), and protein S (p = 0.0478) showed statistically significant differences. None of the evaluated polymorphisms showed statistically significant differences. However, all patients presented the mutated MTHFR C677T polymorphism in a homozygous (T/T) or heterozygous manner (C/T).ConclusionsOur results show environmental elements from every family and hemostatic disorders may be involved in suffering and developing LCPD. Also, heritable factors could contribute to the onset of the disease. Clearly, environmental, genetic, and prothrombotic factors are involved in this pathology.

Altered platelet and coagulation function in moderate-to-severe COVID-19

To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about ¼ of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.

Exfoliative dermatitis as a complication of drug eruption associated with COVID-19

We report a clinical case of exfoliative dermatitis associated with a novel coronavirus disease. A patient with moderate COVID-19 and decompensation of insulin-dependent diabetes mellitus, hypertension and obesity developed a generalized drug eruption. Treatment of coronavirus infection included drugs associated with the frequent development of skin allergic reactions: third-generation cephalosporin and hydroxychloroquine. In this clinical case, the patient had a generalized form of exfoliative dermatitis with moderate COVID-19. Thus, the generalization of drug eruption occurred with a decrease in the viral pneumonia foci area and was accompanied by repeated deterioration of general condition of the patient. Skin rashes resolved in the correction of concomitant pathology. Erythroderma has a benign course in hemostatic disorders and the use of systemic glucocorticosteroids, hyperglycemia therapy. For managing such patients, it is important to use an integrated approach, providing both the treatment of the underlying disease and the correction of comorbidity and complications. This is relevant for both dermatologist-venereologist and specialists involved in the treatment of COVID-19.

Pathogenesis, Diagnosis, and Treatment of Hemostatic Disorders in COVID-19 Patients

The novel coronavirus infection named COVID-19 was first detected in Wuhan, China, in December 2019, and it has been responsible for significant morbidity and mortality in scores of countries. At the time this article was being written, the number of infected and deceased patients continued to grow worldwide. Most patients with severe forms of the disease suffer from pneumonia and pulmonary insufficiency; in many cases, the disease is generalized and causes multiple organ failures and a dysfunction of physiological systems. One of the most serious and prognostically ominous complications from COVID-19 is coagulopathy, in particular, decompensated hypercoagulability with the risk of developing disseminated intravascular coagulation. In most cases, local and diffuse macro- and microthromboses are present, a condition which causes multiple-organ failure and thromboembolic complications. The causes and pathogenic mechanisms of coagulopathy in COVID-19 remain largely unclear, but they are associated with systemic inflammation, including the so-called cytokine storm. Despite the relatively short period of the ongoing pandemic, laboratory signs of serious hemostatic disorders have been identified and measures for specific prevention and correction of thrombosis have been developed. This review discusses the causes of COVID-19 coagulopathies and the associated complications, as well as possible approaches to their early diagnosis, prevention, and treatment.