Hamostaseologie最新文献

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.

Based on clinical trials that have been conducted and published in the past decade, direct oral anticoagulants (DOACs) are increasingly being used as an antithrombotic treatment in children with venous thrombotic events and to prevent thrombotic events in children at risk. In this review, current indications and standards for the initiation of DOACs in children are summarized for the treatment of venous thrombotic events and for the primary and secondary prevention in children at risk of developing thromboses based on the published randomized controlled trials (RCT). Similarly, indications for DOACs in children with underlying cardiac disease are portrayed based on RCT findings. Lastly, available real-world data are reviewed for the use of DOACs in pediatric patients with a focus on patients at higher risk of both thrombosis and bleeding who were primarily excluded from the RCTs. DOACs contribute largely to the evolving individualization of care of thrombotic events in children, but at-risk patient populations remain underrepresented regarding DOAC experience, such as preterm infants, and children with severe renal or hepatic disease. Real-world data from observational studies and registries will continue to be necessary to establish DOACs' effectiveness and safety in children in everyday clinical use.

As the prevalence of heart failure is increasing globally, left ventricular assist devices (LVADs) have become essential therapeutic options in managing advanced heart failure. This review explores the development of LVAD technology, with a focus on the shift from pulsatile to continuous-flow devices, particularly the HeartMate 3, the most advanced generation of LVADs. The evolution in design has significantly enhanced patient survival and quality of life. However, hemocompatibility-related adverse events (HRAEs)-such as pump thrombosis, ischemic and hemorrhagic strokes, and gastrointestinal bleeding-remain major clinical challenges. Striking the delicate balance between preventing thromboembolic events and minimizing hemorrhagic risks remains critical in LVAD patient management. Current therapeutic strategies typically involve long-term anticoagulation with vitamin K antagonists and antiplatelet therapy, though optimal management must be individualized based on patient-specific factors and device characteristics. Emerging alternatives, including low-dose anticoagulation, direct oral anticoagulants such as apixaban, and aspirin-free regimens, offer promising potential to reduce adverse outcomes. This review also highlights the role of innovative mechanical designs in minimizing shear stress and alternative treatments in preventing complications like gastrointestinal bleeding. Despite these advancements, personalized treatment strategies are critical, as no single therapeutic regimen fits all LVAD recipients. Ongoing research into both device technology and pharmacological therapies is essential to further reduce HRAEs and improve long-term outcomes for LVAD patients.

Objectives:  Trauma-induced coagulopathy (TIC) is common in severely injured patients and is associated with significant morbidity and mortality.

Method:  The association of two parameters of blood gas analysis (hemoglobin [Hb], base excess [BE]) with standard coagulation tests (SCTs) and rotational thrombelastometry (ROTEM) using the database of the TraumaRegister DGU between 2015 and 2022 was studied. In a stepwise approach, the occurrence of a TIC, the correlations between Hb/BE levels and SCT, as well as ROTEM were calculated respectively. Then we aimed to detect relations between different Hb/BE levels and the occurrence of TIC, using standard clotting studies and/or ROTEM respectively.

Results:  TIC occurred in 17.2% of the 68,996 primarily admitted adult patients with Injury Severity Score ≥9. A high correlation was found between Hb/BE and SCT. With a decrease in Hb and BE, the frequency of TIC increased and at an admission Hb <8 g/dL and BE < -6 mmol/L, >60% of patients presented with TIC. Clinical conditions associated with TIC were Glasgow Coma Scale ≤8, blood pressure ≤90 mmHg on the scene or at hospital admission, prehospital volume >1,000 mL, serious injuries to the head and/or the thorax and/or the abdomen and/or the extremities.

Conclusion:  Almost one-sixth of patients present with a TIC at hospital admission. Blood gas analysis samples showed relevant correlations between Hb/BE levels and SCT. The combined closer inspection of Hb/BE and the clinical presentation of the patient is able to predict TIC in the majority of patients.

Background:  The risk of thrombosis and bleeding in myelofibrosis (MF) has been historically underappreciated. We sought to investigate potential molecular and clinical risk factors for venous (VTE) and arterial (ATE) thrombotic events as well as bleeding episodes.

Methods:  Data from 246 consecutive MF patients were analyzed. Driver mutations were tested in 191 patients.

Results:  In total, 181 mutations were found in 177 MF patients: 118 (61.8%) patients showed JAK2-V617F, 50 patients (26.2%) showed CALR, and 6 patients (3.1%) showed MPL mutations. Two patients were JAK2-V617F and MPL positive and one patient was positive for all three genes. Fourteen (7.3%) patients were triple negative. The JAK2-V617F allele burden was assessed in 63 JAK2-V617F-mutated patients, revealing a median of 35.6% (range: 5.0-96.0). At the time of MF diagnosis and during follow-up, 84 thrombotic events (52 VTEs and 32 ATEs) were observed, corresponding to 6.6% of patients per year. A significant association was found between JAK2-V617F mutation (OR: 2.5, 95% CI: 1.1-5.6) and prior VTE (OR: 7.6, 95% CI: 2.1-27.1) with an increased risk of VTE. Patients with prefibrotic MF had a higher rate of ATE than patients with overt MF. Hemorrhagic events occurred in 34 (13.8%) patients, corresponding to 3.8% of patients per year. Fibrosis grade 3 was associated with bleeding risk (OR: 3.4, 95% CI: 1.2-9.2, p = 0.02).

Conclusions:  The presence of the JAK2-V617F mutation, regardless of allele burden, and prior thrombosis were strongly associated with an increased risk of VTE. Patients with prefibrotic MF might be considered at high risk for developing ATE.

Thrombophilia management is based on the personal and family history of thrombosis. Current guidelines recommend performing thrombophilia testing only when the results will change clinical management. To investigate to what extent treatment recommendations changed following thrombophilia testing, clinical and laboratory data of 255 patients with and without venous thromboembolism who underwent thrombophilia screening were assessed retrospectively. A local score based on clinical indicators for thrombophilia was used to assess the pretest probability of thrombophilia. A total of 144 patients (57.6%) were found to have a clear thrombophilic phenotype, of which 78 were predicted to have definite thrombophilia and considered for indefinite anticoagulation; 66 were likely to have thrombophilia and were considered for indefinite or prolonged anticoagulation. Eighty-three (32.5%) could not be clearly classified and 28 (11%) were asymptomatic. A thrombophilic risk factor was diagnosed in 98 (38.4%) patients; this included 64 of 144 (44.5%) patients with a clear thrombophilic phenotype and 26 of 83 (31.3%) patients who could not be easily classified. Treatment recommendations changed in 57 of 255 (22%) patients following thrombophilia testing. Eight patients were switched from direct oral anticoagulants to vitamin K antagonists due to confirmed triple-positive antiphospholipid syndrome. In 49 patients, the anticoagulant dose was either increased (n = 3) or treatment was prolonged (n = 46) following diagnosis of high-risk thrombophilia. Clinically, assessing thrombophilia probability score before thrombophilia testing improves thrombophilia management recommendations.