Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in patients with von Willebrand disease (VWD) who have a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, noncontrolled, international phase 3 trial, investigated the efficacy and safety of Wilate prophylaxis in severe patients with VWD. Male and female patients 6 years or older with VWD types 1, 2 (except 2N), or 3 who had completed a prospective, 6-month, on-demand, run-in study (WIL-29) were eligible to receive Wilate prophylaxis for 12 months. At baseline, patients (n = 33) had a median age of 18 years. Six (18%) patients had severe type 1, 5 (15%) had type 2, and 22 (67%) had type 3 VWD. The primary end point of a >50% reduction in mean total annualized bleeding rate (TABR) with Wilate prophylaxis vs prior on-demand treatment was met; mean TABR during prophylaxis was 5.2, representing an 84.4% reduction. The bleeding reduction was consistent across age, sex, and VWD types. The mean spontaneous ABR was 3.2, representing an 86.9% reduction vs on-demand treatment. During prophylaxis, 10 (30.3%) patients had 0 bleeding events and 15 (45.5%) patients had 0 spontaneous bleeding events. Of 173 BEs, 84.4% were minor and 69.9% treated. No serious adverse events related to study treatment and no thrombotic events were recorded. Overall, WIL-31 showed that Wilate prophylaxis was efficacious and well-tolerated in pediatric and adult patients with VWD of all types. The WIL-29 and WIL-31 trials were registered at www.ClinicalTrials.gov as #NCT04053699 and #NCT04052698,
respectivelyvon Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of 0.6% to 1.3%.1 In VWD, hemostasis is impaired due to deficiency or dysfunction of von Willebrand factor (VWF).2 The severity of the bleeding phenotypes differs widely between patients with VWD, ranging from mild to severe, with type 3 VWD characterized by a severe bleeding phenotype.3 Long-term prophylaxis is recommended and well established in hemophilia. The goal of prophylaxis is to reduce bleeding rates to a minimum, reduce the risk of joint damage, and improve quality of
life.4 The positive experience with prophylaxis in hemophilia provides a rationale for prophylaxis in VWD.5,6 Indeed, in a post-hoc analysis of 331 patients with VWD, patients on VWF prophylaxis had fewer bleeds, fewer hospitalizations due to bleeds, and a lower likelihood for joint damage and moderate chronic pain, compared with patients who were eligible for but not receiving prophylaxis.7 Current guidelines recommend that patients with VWD who have a history of severe and frequent bleeds should use long-term prophylaxis with a VWF product.8 However, long-term prophylaxis is not the current standard of care for patients with VWD. In a survey of 6208 patients with VWD, only 1.6% received prophylaxis, most of them type 3 patients who had experienced joint bleeding.9 Wilate is a plasma-derived factor concentrate containing VWF and factor VIII (FVIII) in a physiological 1:1 activity ratio, which is indicated in patients with VWD for treatment of bleeds and perioperative management of bleeding and for prophylaxis.10,11 Across 4 clinical trials of patients with VWD, 19 patients received Wilate for prophylaxis, and their bleeding rates were reduced during prophylaxis compared with previous treatment.12 Here, we present the efficacy and safety results of the phase 3 WIL-31 study, which collected data specifically in patients with VWD undergoing regular prophylaxis with Wilate after a prospective 6-month run-in phase of on-demand treatment (WIL-29).

The presence of coagulopathy as part of the systemic inflammatory response syndrome is a characteristicfeature of severe coronavirus disease 2019 (COVID-19). Hematological changes (increased D-dimer [DD],prolonged activated partial thromboplastin clotting time [APTT] and prothrombin time [PT], highfibrinogen levels) have been observed in hospitalized patients with COVID-19, which characterizethe risk of thrombotic events. Against the background of COVID-19 there is endothelial dysfunction,hypoxia and pulmonary congestion, mediated by thrombosis and microvascular occlusion. Up to71.4% of patients who died from COVID-19 had disseminated intravascular coagulation syndrome,compared with only 0.6% of survivors. The main manifestation of COVID-19-associated coagulopathyis a significant increase in DD without a decrease in platelet count or prolongation of APTT and PT,indicating increased thrombin formation and the development of local fibrinolysis. An increase in DDlevels of more than 3–4 times was associated with higher in-hospital mortality. Therefore, COVID-19requires assessment of the severity of the disease for further tactics of thromboprophylaxis. The need forcontinued thromboprophylaxis, or therapeutic anticoagulation, in patients after inpatient treatment fortwo weeks using imaging techniques to assess of thrombosis assessment.

УДК 616.13-002-036-053.2-07:616.155.02

Kawasaki disease (KD) is an acute systemic vasculitis that is the most common cause of acquired heart disease in children under 5 years of age with hyperthermia. Diagnosis of KD is a clinical challenge, given the wide range of clinical manifestations and similarities with many viral and bacterial diseases. Purpose - to describe a clinical case of refractory КD in a three-month-old girl with an emphasis on the importance of echocardiography and coronary angiography for the final verification of the disease, urgent initiation of treatment with minimal suspicion of КD. Clinical case. The article reports on a three-month-old patient with a difficult diagnosis of refractory form of КD. The disease debuted with hyperthermia, enterocolitis, obstructive bronchitis, and hepatoliver syndrome. The manifestations of skin exanthema were initially considered as an allergic dermatitis to the use of a cephalosporin antibiotic. Multisystemic inflammatory syndrome associated with SARS-CoV-2 infection was suspected. After the use of immunosuppressive therapy with mega-doses of dexamethasone and intravenous human immunoglobulin 2 g/kg/day for 3 days, clinical improvement was achieved. Subsequently, the haemogram showed an increase in neutrophilic hyperleukocytosis to the appearance of blast cells, hyperthrombocytosis and severe anaemia. A differentiation was made between a leukemic reaction, the debut of myeloproliferative disease, juvenile myelomonocytic leukaemia. Against the background of a rapid decrease in the number of leukocytes, the girl developed hyperthermia, migratory intermittent maculopapular rash, and foots edema. Laboratory findings included thrombocytosis and an increase in acute-phase parameters. Echocardiography revealed left ventricular dilation, a small amount of excess fluid in the pericardium, dilatation of the left coronary artery evenly to the bifurcation. Computed tomography revealed giant coronary artery aneurysms, which gave grounds to diagnose KD