[Methodological recommendations for surgical care in patients with hemophilia A receiving prophylactic therapy with emicizumab]. / Metodicheskie rekomendatsii po okazaniyu khirurgicheskoi pomoshchi u patsientov s gemofiliei A, poluchayushchikh profilakticheskuyu terapiyu emitsizumabom.

Methodological recommendations for surgical care in patients with hemophilia A receiving prophylactic therapy with emicizumab. Recommendations of the expert group. Moscow, 2024.

[Hemostasis disorders in patients with systemic AL-amyloidosis].

AIM: To analyze the frequency and nature of hemorrhagic and thrombotic complications in patients with systemic AL-amyloidosis and compare with laboratory changes in the hemostasis system. MATERIALS AND METHODS: The prospective study included 40 patients with newly diagnosed AL-amyloidosis. To detect amyloid, all patients underwent bone marrow trephine biopsy and duodenal biopsy, and 28 (70%) patients underwent biopsy of the affected organ. Before the start of therapy, all patients were determined the platelet count, activated partial thromboplastin time, thrombin time, fibrinogen concentration, time of XIIa-dependent fibrinolysis, antithrombin III, D-dimer, activity of blood coagulation factors VIII, X and vWF. The statistical part of the study was carried out using the IBM SPSS Statistics 2017 system software (SPSS, Chicago, IL, USA). RESULTS: In 20 (50%) patients, hemorrhages on the skin and mucous membranes were diagnosed as vascular purpura. Before the start of therapy, 7 (17.5%) patients had thrombosis, including leg vein thrombosis (5 patients), ischemic stroke (2 patients). There was a direct correlation between thrombotic complications and cutaneous hemorrhagic syndrome (p=0.007). In 15 (75%) cases, cutaneous hemorrhagic syndrome was accompanied by hypercoagulable shifts in the hemostasis system. Of the 20 patients with cutaneous hemorrhagic syndrome, 19 (95%) patients had kidney damage, including 15 patients with nephrotic syndrome. Hematoma type of bleeding, as well as heavy bleeding was not observed, including after a biopsy of the internal organs. According to the totality of hemostasis indicators, hypercoagulation syndrome was more often observed (in 23; 56% of patients). Hypocoagulation was diagnosed only in 2 (5%) patients with liver damage, 16 (39%) patients had normocoagulation. CONCLUSION: Cutaneous hemorrhagic syndrome is the most common clinical manifestation of disorders in the hemostasis system in patients with AL-amyloidosis. The relationship of hemorrhages on the skin with nephrotic syndrome has been established, which may indicate a single pathogenetic mechanism. Cutaneous hemorrhagic syndrome is associated with hypercoagulable shifts in hemostasis and a high risk of thrombotic complications.

[Surgery in patients with severe or inhibitory hemophilia A under prevention injection of emicizumab]. / Khirurgicheskie vmeshatel'stva u bol'nykh tyazheloi ili ingibitornoi formoi gemofilii A na fone profilakticheskogo vvedeniya emitsizumaba.

OBJECTIVE: To determine the features of preoperative hemostatic therapy and laboratory control in patients with severe and inhibitory forms of hemophilia A under preventive treatment by FVIII. MATERIAL AND METHODS: Four patients with severe and inhibitory forms of hemophilia A underwent surgery between 2021 and 2022. All patients received Emicizumab (the first monoclonal drug for «non-factor¼ therapy of hemophilia) for prevention of specific hemorrhagic signs of hemophilia. RESULTS: Surgical intervention under preventive Emicizumab therapy was essential. Additional hemostatic therapy was not carried out or performed in reduced mode. There were no hemorrhagic, thrombotic or other complications. Thus, the so-called «non-factor¼ therapy is one of the variants for uncontrollable hemostasis in patients with severe and inhibitory forms of hemophilia. CONCLUSION: Preventive injection of Emicizumab ensures certain buffer of hemostasis system and stable lower limit of coagulation potential. This is the result of stable concentration of Emicizumab when used in any of the registered forms regardless of age and other individual characteristics. The risk of acute severe hemorrhage is excluded, while the probability of thrombosis is not increased. Indeed, FVIII has higher affinity than Emicizumab and displaces Emicizumab from coagulation cascade that does not result summation of total coagulation potential.

[Unsolved issues of treatment of adult patients with hemophilia A].

BACKGROUND: Sufficient supply of coagulation factors products has significantly improved life quality and expectancy in patients with hemophilia. Certain difficulties, however, persist when it comes to the treatment of the disease. AIM: To analyze current therapeutic approaches and identify major unsolved issues in the treatment of patients with hemophilia A. MATERIALS AND METHODS: An online survey of 100 adult patients with hemophilia A was held. RESULTS: More than a half of the surveyed sample (59%) are patients aged 19 to 40 with the severe form of the disease, 73% of respondents receive a replacement therapy with plasmatic factors, 42% of patients inject drugs 3 times a week or more. More than a half of all age groups with hemophilia have persistent pain and limited joint mobility, in 70% of the patients, bleeding into the joints occurred 4 or more times within the past year, 47% of the patients with hemophilia A are partially satisfied or dissatisfied with their state of health, 92% of the patients would like to improve their quality of life. At the same time, about 1/3 of the patients would like to reduce the frequency of drug administration. More than 40% of the respondents did not visit a hematologist during the year, 85% do not conduct regular laboratory monitoring. CONCLUSION: The survey results demonstrate numerous areas of potential change pertaining to the approaches towards therapy and to the innovative drugs for the treatment of patients with hemophilia.

Kinetics of Platelet Adhesion to Protein-Coated Surface in Whole Blood Samples at High Flow Rates.

We studied platelet adhesion to fibrinogen-coated surface in whole blood samples under conditions of high flow rates. The degree of platelet adhesion was evaluated by the intensity of laser light scattered from protein-coated optical surface with adhered platelets. The intensity of adhesion in whole blood samples at high flow rates was by 2.7 (2.4; 4.1) times higher than in platelet-rich plasma samples. Among the factors intensifying platelet adhesion in the whole blood at high flow rates, von Willebrand factor is of utmost importance. At low flow rates, platelet adhesion almost totally depends on platelet-fibrinogen interaction. At high flow rates, the interactions of platelets with both fibrinogen and von Willebrand factor become equally important.

Constrictive pericarditis in a patient with inherited factor VII deficiency.

Constrictive pericarditis (CP) is the final stage of a chronic inflammatory process characterized by fibrous thickening and calcification of the pericardium that impairs diastolic filling, reduces cardiac output, and ultimately leads to heart failure. We present a clinical case of CP in a patient with rare inherited bleeding disorder - factor VII deficiency. Heart failure due to CP was suspected based on clinical symptoms, results of ultrasonic and radiological investigations. The diagnosis was verified by the results of cardiac magnetic resonance imaging. Pericardectomy was performed resulting in significant improvement in the patient's condition.

Literature review and clinical observation of acquired idiopathic hemophilia with a new missense mutation in the factor VIII gene (His2026Arg).

The article provides review of possible mechanisms of inhibitor coagulopathies, in particular of acquired hemophilia A. This pathology is an extremely rare disease occurring in 1-2 cases in 1 million per year. In the present study we provide data for two clinical cases of hemophilia A in women. These cases had different development mechanisms, although both women have a newly discovered missense mutation His2026Arg in the VIII factor gene. The matter of main interest is the description of the disease development in the patient with an acquired idiopathic hemophilia A with a possible disease occurrence due to an asymmetric X-chromosome inactivation (lyonization). In this particular case lyonization led to the late manifestation of the hemophilia A carrier's state and development of severe form of the inhibitor-associated acquired hemophilia A. We also discuss therapeutic approaches to these forms of the disease, considering there are no concise protocols for case management due to an extreme rarity of the pathology. Acquainting the clinical personnel working it the different areas of medicine with suchlike inhibitor coagulopathies has a major practical importance.

[Hereditary afibrinogenemia: A literature review and clinical observations]. / Nasledstvennaia afibrinogenemiia: obzor literatury i klinicheskie nabliudeniia.

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.