Hamostaseologie最新文献

Introduction:  Treatment options for patients with hemophilia (PWH) have changed substantially in the last years. This study aimed to compare hemophilia treatment in the eastern part of Germany in 2021 with data from 2015.

Methods:  Substitution diaries and patient records of PWH from 2021 were collected in 13 hemophilia centers from the "Kompetenznetz Hämorrhagische Diathese Ost" (KHDO) and compared with 2015.

Results:  A total of 130 children and 357 adults, 411 hemophilia A (HA) and 76 hemophilia B (HB), were included in 2021, and 359 were already analyzed in 2015. In 2021, 97.8% of children and 95.7% of adults with severe hemophilia had prophylaxis compared with 98.8 and 80.2% in 2015. Plasma-derived concentrates were used in 25.6%, recombinant in 30.2%, extended half-life (EHL) factor concentrates in 24.4%, and emicizumab in 19.8% of the children with severe HA (sHA). In adults with sHA, plasma-derived, recombinant concentrates, EHL, and emicizumab were used in 21.0, 33.2, 31.2, and 14.2%, respectively. All children and 93.3% of the adults with severe HB (sHB) were on EHL. Median annual factor consumption per body weight increased in adults with sHA, remained stable in children with sHA and adults with sHB, and decreased in children with sHB between 2015 and 2021. Annualized bleeding rate (ABR) decreased in children with sHB and sHA.

Conclusion:  The use of EHL and emicizumab has changed hemophilia treatment. About 50% of the sHA patients switched to EHL or emicizumab and almost all sHB patients to EHL. More adults with sHA received prophylaxis and ABR decreased in children.

Thrombocytopenia at admission predicts mortality in multiple myeloma (MM) and might link to disease progression. Although thrombocytopenia is known to be associated with MM, a possible thrombopathy is clinically less known. We conducted a case-control study comparing platelet responses of MM patients to controls via flow cytometry, integrin αIIbβ3 activation and P-selectin exposure, and a bioluminescent assay, ATP release. No difference was found at baseline, but upon platelet stimulation, MM patients had decreased αIIbβ3 activation, partly impaired P-selectin exposure, and reduced δ-granule (ATP) secretion. Aspirin treatment in patients did not account for these diminished platelet responses. In total, 29% of patients had thrombocytopenia, while 60% had decreased αIIbβ3 activation and 67% had reduced platelet secretion capacity. Importantly, as secretion capacity was corrected for platelet count, granule release per platelet was reduced in patients versus controls. Of 6 patients with thrombocytopenia 4 displayed a thrombopathy, while for 15 patients with normal count, 64% had reduced αIIbβ3 activation and 73% had reduced platelet secretion capacity. Of all patients, 10% had thrombocytopenia combined with reduced αIIbβ3 activation plus low secretion capacity (one patient showed no qualitative or quantitative platelet defect). Our data suggest that beyond the known thrombocytopenia, MM patients also have reduced platelet function, which could reflect impaired platelet vitality. Combined measurement of platelet count and function, especially secretion capacity, gives a more comprehensive view of platelet phenotype than count alone. Large prospective follow-up studies are needed to confirm the importance of the acquired platelet secretion defect on the prognosis of MM patients.

Patients with thrombosis at an unusual site will need to be explored for rare causes of thrombosis. Two of these rare causes include myeloproliferative neoplasms (MPNs) and paroxysmal nocturnal hemoglobinuria (PNH). It is important not to overlook these causes, since they require specific management, in addition to antithrombotic treatment (anticoagulants, antiplatelet agents). Unusual sites of venous thrombosis include upper extremity veins, splanchnic veins, cerebral veins, and retinal veins, and unusual sites of arterial thrombosis include renal, adrenal, splenic and mesenteric arteries, and intracardiac and aortal locations. Suspicion for MPN and PNH should be raised if there are concomitant abnormalities, such as elevated or decreased blood cell counts or splenomegaly. Diagnosis of MPN and PNH should include JAK2V617F mutational screening as well as flow cytometric assessment of GPI-anchored proteins in the peripheral blood, respectively. Specific treatments for MPN may include phlebotomy or cytoreductive drugs such as hydroxyurea, anagrelide, pegylated interferon-alpha, or Janus kinase inhibitors. Drugs used for PNH treatment include terminal complement inhibitors, such as eculizumab and ravulizumab, as well as proximally acting inhibitors such as pegcetacoplan or iptacopan. Patients with MPN and PNH are at high risk for thrombosis during their entire lifetime and should thus be followed by specialists experienced in the care of these diseases.

The 2025 Annual Congress of the Society of Thrombosis and Haemostasis Research (GTH) takes its inspiration from ARTE-Advances, Research, Technology, and Education in the field of thrombosis and hemostasis. The numerous scientific contributions of the congress highlight the most recent progresses in this field, and reveal the profound connection between the rigor of science and the beauty of human creativity. ARTE, the Italian word for "art," refers to the deep synergy existing between analytical precision and imaginative expression, which is vividly reflected in this year's contributions to our themed congress issue.

Combining diagnostics and research in academic laboratories faces challenges and bears great opportunities. In this short review, we describe the objectives of diagnostic and research laboratories dealing with thrombosis and hemostasis questions. We give an overview of specific goals for diagnostic and research laboratories and explain the synergies and tasks which need to be managed in an interdisciplinary team.

Hereditary bleeding disorders encompass a range of hemostasis defects that impair the blood coagulation process. Although these disorders affect both men and women, research and clinical management have historically been predominantly focused on male patients, particularly those with hemophilia. Consequently, the impact of these disorders on women has been undervalued and frequently overlooked. The intricate relationship between a woman's tendency to bleed and the various gynecological and obstetric processes gives rise to distinctive health challenges for women with hereditary bleeding disorders. Heavy menstrual bleeding (HMB), excessive bleeding during miscarriages, postpartum hemorrhage, and hemorrhagic ovarian cysts represent some of the most common complications. Despite the high prevalence and significant impact of these symptoms, many women experience delays in diagnosis and treatment, which in turn may result in iron-deficiency anemia, anxiety, influence on reproductive decisions, and a decreased quality of life. This review aims to summarize the distinctive characteristics of hereditary bleeding disorders in women, emphasizing the clinical challenges and hormonal management strategies for HMB.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer immunotherapy, particularly for hematological malignancies. This personalized approach is based on genetically engineering T cells derived from the patient to target antigens expressed-among others-on malignant cells. Nowadays they offer new hope where conventional therapies, such as chemotherapy and radiation, have often failed. Since the first FDA approval in 2017, CAR T cell therapy has rapidly expanded, proving highly effective against previously refractory diseases with otherwise a dismal outcome. Despite its promise, CAR T cell therapy continues to face significant challenges, including complex manufacturing, the management of toxicities, resistance mechanisms that impact long-term efficacy, and limited access as well as high costs, which continue to shape ongoing research and clinical applications. This review aims to provide an overview of CAR T cell therapy, including its fundamental concepts, clinical applications, current challenges, and future directions in hematological malignancies.

In this review, we aim to highlight the extent of inappropriate hemostasis testing and provide practical guidance on how to prevent it. We will focus on the acute setting, including but not limited to the emergency department and intensive care unit. To this end, we will first discuss the significance of inappropriateness, in the general context of laboratory medicine. This includes acknowledging the importance of the phenomenon and attempting to define it. Next, we describe the harmful consequences of inappropriate testing. Finally, we focus on the inappropriate use of hemostasis testing in the acute setting. The second section describes how interventions-in particular, the implementation of guidance for testing-can efficiently reduce inappropriateness. In the third section, we summarize the available recommendations for rational use of hemostasis testing (platelet count, activated partial thromboplastin time, prothrombin time/international normalized ratio, fibrinogen, thrombin time, D-dimer, anti-Xa assay, antithrombin, ADAMTS13 activity, antiheparin-PF4 antibodies, viscoelastometric tests, coagulation factors, and platelet function testing), as supported by guidelines, recommendations, and/or expert opinions. Overall, this review is intended to be a toolkit in the effort to promote the appropriate use of hemostasis testing. Hopefully, the new In Vitro Diagnostic Medical Device Regulation (EU) 2017/746 (IVDR) should help in improving the availability of evidence regarding clinical performance of hemostasis assays.

Binding of platelet activators to their receptors initiates a signal transduction network, where intracellular signal is filtered, amplified, and transformed. Computational systems biology methods could be a powerful tool to address and analyze dynamics and regulation of the crucial steps in this cascade. Here we review these approaches and show the logic of their use for a relatively simple case of SFLLRN-induced procoagulant activity. Use of a typical model is employed to track signaling events along the main axis, from the binding of the peptide to PAR1 receptor down to the mPTP opening. Temporal dynamics, concentration dependence, formation of calcium oscillations and their deciphering, and role of stochasticity are quantified for all essential signaling molecules and their complexes. The initial step-wise activation stimulus is transformed to a peak at the early stages, then to oscillation calcium spikes, and then back to a peak shape. The model can show how both amplitude and width of the peak encode the information about the activation level, and show the principle of decoding calcium oscillations via integration of the calcium signal by the mitochondria. Use of stochastic algorithms can reveal that the complexes of Gq, in particular the complex of phospholipase C with Gq, which are the limiting steps in the cascade with their numbers not exceeding several molecules per platelet at any given time; it is them that cause stochastic appearance of the signals downstream. Application of reduction techniques to simplify the system is demonstrated.