Hamostaseologie最新文献

In the case of familial thrombocytopenia, a congenital defect should be considered; however, in particular older patients who have had thrombocytopenia for a long time have often not yet been genetically analyzed using modern sequencing methods. Remarkably, sometimes they are still suspected of suffering from chronic immune thrombocytopenia until genetic testing reveals a congenital defect. We report on elderly Finnish siblings (both older than 60 years) with lifelong thrombocytopenia. The lifelong bleeding tendency in both the siblings was usually treated with tranexamic acid and platelet transfusions when necessary. In 2022, the older brother presented at the University Hospital in Helsinki because he had recently been suffering from gastrointestinal bleeding and also had mild pancytopenia. Because his sister lived abroad, the Finnish colleagues recommended that the sister should present to the University Hospital in Freiburg. Independent genetic testing of both the siblings using NGS identified the diagnosis of NBEAL2-associated gray platelet syndrome. The disease comprises macrothrombocytopenia and a reduction of α-granules in platelets, resulting in a grayish appearance of platelets on the blood smear. Patients usually suffer from a mild to moderate bleeding diathesis. Interestingly, during the last years a more syndromic character of the disease has been described: besides the platelet phenotype, the immune system can also be affected. In the course of the disease patients may develop pancytopenia, splenomegaly, and bone marrow fibrosis. Comprehensive diagnostics including molecular genetic analyses are particularly important to provide these patients with adequate care and treatment.

Hereditary combined vitamin K-dependent coagulation factor deficiency (VKCFD) is an extremely rare autosomal recessive genetic disorder characterized by deficiencies in vitamin K-dependent coagulation factors and natural anticoagulants. The condition presents with a spectrum of bleeding symptoms ranging from mild to severe, often beginning in the neonatal period. These bleeding episodes can be particularly severe and even life-threatening, occurring spontaneously or during surgery. In addition to bleeding problems, individuals with VKCFD may experience a variety of non-hemostatic problems, including skeletal deformities, cardiovascular abnormalities, and skin conditions.VKCFD is caused by variants in the genes encoding either γ-glutamyl carboxylase or the vitamin K 2,3-epoxide reductase complex. Both proteins play a critical role in γ-carboxylation, a posttranslational modification that is essential for the proper function of vitamin K-dependent proteins. Timely and accurate diagnosis is essential to differentiate VKCFD from other genetic and acquired disorders, and genetic testing is required to identify the specific variant.The primary treatment for VKCFD is the administration of vitamin K, with transfusions of fresh frozen plasma often required during surgery or in cases of severe bleeding. In certain situations, alternative therapies such as prothrombin complex concentrates (PCCs) or a combination of recombinant activated factor VII and vitamin K may be considered. With appropriate treatment, individuals with VKCFD generally have a good clinical outcome, and the condition has a limited impact on their quality of life. This article presents a comprehensive review of all 57 VKCFD cases documented in the literature, as well as 4 new, unpublished cases from France.

Congenital afibrinogenemia and hypofibrinogenemia are rare hereditary coagulation disorders characterized by the absence or deficiency of fibrinogen. These conditions pose unique challenges for women across their lifespan, including heavy menstrual bleeding (HMB), hemorrhagic ovarian cysts, complications during pregnancy and the postpartum period, as well as bleeding occurring later in life. HMB is frequent and adversely impacts quality of life, often necessitating hormonal therapy, antifibrinolytics, or fibrinogen replacement. Hemorrhagic ovarian cysts can result in life-threatening hemoperitoneum, requiring prompt intervention to manage bleeding and preserve ovarian function. Pregnancy in women with severe fibrinogen deficiencies carries a high risk of miscarriage, placental abruption, and postpartum hemorrhage. Multidisciplinary care, fibrinogen replacement, and vigilant monitoring are crucial to optimize maternal and fetal outcomes. Although understudied in this population, bleeding can occur later in their life, especially due to the increased incidence of gynecological pathologies. Tailored management strategies, including hormonal and surgical interventions, are essential. Despite recent advances in our understanding of these conditions, significant knowledge gaps persist regarding the prevalence, risk factors, and optimal management of specific complications. This review synthesizes current findings and provides practical recommendations to guide the care of young and ageing women with afibrinogenemia and hypofibrinogenemia. Further research is needed to refine treatment protocols and improve outcomes for this vulnerable population.

Rare bleeding disorders (RBDs), defined as hereditary coagulation factor deficits other than haemophilia, are characterized by a heterogenous clinical phenotype ranging from life-threatening bleeding to thrombosis. There are uncertainties concerning treatment intensity and levels needed to achieve haemostasis, and epidemiological data from Germany, Austria, and Switzerland (GTH region) are scarce.We performed a narrative literature review, focusing on bleeding phenotype and thrombotic risk. Epidemiologic data, including adults and children, and general treatment approaches have been collected via an online survey among GTH haemophilia centres (all categories) and the general information service of the German national registry (Deutsches Hämophilieregister, DHR).We provided an overview on RBDs, revealing that especially in FV, FVII, and FXI deficiencies, the correlation between factor levels and bleeding phenotype is poor. A thrombotic risk needs to be considered in FVII deficiency and afibrinogenaemia or dysfibrinogenaemia. The survey was completed by 34 centres from Germany, Austria, and Switzerland, and compared with 137 centres reporting data to the DHR. FVII deficiency was confirmed to be the most frequent, and FII deficiency was the rarest RBD in this region. For treatment, single factor concentrates were preferred over multifactor concentrates or plasma, and tranexamic acid was often part of the treatment. Approximately 30, 40, and <10% of patients with severe FV, FVII, and FXI deficiency (defined as factor level <10%), respectively, were receiving prophylactic treatment, suggesting an overall milder bleeding phenotype.More detailed registry data could give insights into the treatment landscape of RBDs, considering the challenge of clinical trials in rare diseases.

Nonacog beta pegol (N9-GP) is a glycoPEGylated FIX replacement product with extended half-life for treatment of haemophilia B patients. Monitoring of N9-GP with clotting-based one-stage FIX assays is complicated by high variations, mainly due to reagent-specific interference with polyethylene glycol.In 11 distinct specialized coagulation laboratories in Austria, N9-GP spiked samples were measured in replicates in two distinct surveys, 3 years apart, using five different one-stage assay reagents and one chromogenic FIX assay. Regression analysis was used to investigate if back-calculation of N9-GP levels is feasible.We could demonstrate a linear relationship between the spiked N9-GP concentration and measured FIX activity levels for all examined assays, suggesting that N9-GP activity may be back-calculated using reagent-/platform-specific conversion factors. Within-laboratory variation after 3 years was acceptable in most, but not all, laboratories.We demonstrate that back-calculation of N9-GP activity levels may be possible when using one-stage FIX assays. However, we recommend that every laboratory ascertain its own conversion factor. When measuring real patient samples, we encourage simultaneous measurement of N9-GP spiked control material with known concentrations to ensure the validity of the current back-calculation.

Venous thromboembolism (VTE) is an increasingly frequent complication of solid tumors and hematological malignancies, significantly contributing to morbidity and mortality. In patients with acute cancer-associated VTE, therapeutic anticoagulation with direct oral factor Xa inhibitors (DXIs) or low-molecular-weight heparin (LMWH) for 3 to 6 months is recommended by clinical practice guidelines based on randomized controlled trials. Although extended secondary VTE prophylaxis should be considered in patients with persisting active cancer, the type, intensity, and duration of continued anticoagulation have not been rigorously studied until recently. In non-cancer patients, low-dose DXIs (apixaban 2.5 mg BID or rivaroxaban 10 mg OD) are the preferred options to prevent recurrent VTE beyond the first 6 months of treatment. The recently published API-CAT trial compared low-dose with full-dose apixaban for extended secondary VTE prophylaxis in 1,766 patients with active cancer. Over a 12-month period, low-dose apixaban was associated with similar efficacy, but significantly improved safety compared with full-dose apixaban, with cumulative incidence rates of recurrent VTE and major or clinically relevant non-major bleeding of 2.1% versus 2.8% (adjusted subhazard ratio [sHR]: 0.76; 95% confidence interval [CI]: 0.41-1.41; p < 0.001 for noninferiority) and 12.1% versus 15.6% (adjusted sHR: 0.75; 95% CI: 0.58-0.97; p = 0.03 for superiority), respectively. Based on these findings, extended secondary VTE prophylaxis with low-dose DXIs, preferably apixaban 2.5 mg BID, is proposed for most patients with persisting active cancer. To facilitate informed decision-making in clinical practice, we provide an expert consensus on criteria that either justify cessation of anticoagulation or require continued full-dose anticoagulation.