Seminars in thrombosis and hemostasis最新文献

The antiphospholipid syndrome (APS) is a complex autoimmune disease that causes a state of hypercoagulability that can result in recurrent venous and arterial thromboses. APS may lead to cardiac manifestations requiring cardiac surgery with cardiopulmonary bypass. Perioperative anticoagulation management in APS patients is complex. This complexity arises from both the prothrombotic nature of APS and interference of antiphospholipid antibodies (aPLs) with phospholipid-dependent coagulation assays like activated clotting time (ACT). Given that current literature on cardiopulmonary bypass (CPB) management in APS patients is largely limited to isolated case reports and lacks a comprehensive synthesis, this review summarizes the cardiac manifestations of APS, challenges posed by CPB, and current strategies for intraoperative anticoagulation management, including heaprin dosing, anticoagulation monitoring methods and protamine reversal practices. We further highlight gaps in evidence and propose a practical three-category framework for managing aPL-positive patients undergoing CPB.

Clot waveform analysis (CWA) extends routine coagulation assays (activated partial thromboplastin time [aPTT] and prothrombin time [PT]) by incorporating continuous optical monitoring to generate kinetic profiles of clot formation. This method provides both qualitative and quantitative information on hemostasis, with increasing evidence for its clinical utility in detecting factor deficiencies and characterizing thrombotic and bleeding disorders. Despite the growing body of evidence, translation of CWA into routine clinical practice remains limited.This review identifies three principal barriers: (1) variability arising from differences in optical detection methods (absorbance vs. transmittance), (2) interreagent variation even within the same analyzer platform, and (3) lack of a clear distinction between standard CWA, performed with commercially available reagents, and modified CWA, incorporating in-house adjustments. To address these challenges, we encourage adopting distinct nomenclature for detection modalities (CWA-A; A for absorbance and CWA-T; T for transmittance), establishing standardized reporting requirements including reagent and platform details, and establishing quality assurance frameworks for CWA.Standardization of terminology and reporting will enhance reproducibility, enable cross-study comparisons, and accelerate the clinical translation of CWA from the laboratory bench to the bedside.

People with hemophilia (PwH) face persistent joint damage risk despite prophylactic factor replacement therapies. While muscles are recognized as biomechanical stabilizers, their broader protective mechanisms remain poorly understood. This review provides an integrative theoretical framework that examines how muscles protect joints in PwH through three interconnected dimensions: (1) mechanical-via joint stabilization and force absorption; (2) neuromuscular control; and (3) biochemical regulation through exercise-induced myokines (exerkines). Muscle contractions provide joint stabilization and attenuate mechanical impacts via eccentric actions and muscle-tendon buffering, thereby reducing joint loading during daily activities. Neuromuscular control maintains joint stability through coordinated muscle activation, though excessive co-contraction in arthropathy can paradoxically increase joint stress. Critically, the endocrine function of skeletal muscle, producing anti-inflammatory and cartilage-protective exerkines including interleukin-6, irisin, and lubricin (among others), represents an underexplored yet crucial protective mechanism. Physical inactivity and intramuscular fat accumulation impair these protective functions, accelerating joint degeneration. This integrative theoretical perspective offers a comprehensive framework for understanding how muscles protect joints in hemophilia. Understanding these integrated mechanisms is essential for developing targeted rehabilitation strategies and guiding future research to optimize joint health in PwH.

Background: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by factor VIII inhibitors. Standard therapies are limited by thrombotic risk and prolonged hospitalization. Emicizumab, approved for congenital hemophilia A, has emerged as a potential alternative in AHA based on case reports and early clinical trial data.

Objectives: To evaluate the efficacy and safety of emicizumab in AHA through a retrospective real-world case series and a systematic literature review with patient-level data analysis.

Methods: We retrospectively analysed five AHA cases treated with Emicizumab at two Italian centres and performed a PRISMA-compliant systematic review of published reports, extracting and analysing patient-level data using JBI tools.

Results: In the real-world cohort, early emicizumab use in five patients with high-titer inhibitors and severe bleeding led to rapid hemorrhagic control, early withdrawal of bypassing agents, and no thrombotic or adverse events. All the five patients received immunosuppression and inhibitor eradication was achieved in 60% of patients but for 40% follow up is still ongoin. The literature review identified 24 patients from 18 publications. Early emicizumab administration (at admission) was associated with reduced bleeding recurrence (0% vs. 56.3%), shorter in-hospital stay (median 23.5 vs. 39 days), and lower bleeding-related mortality (0% vs. 12.5%) compared to delayed administration.

Conclusions: Early emicizumab initiation appears to be a safe and effective strategy for AHA management, particularly in fragile or high-risk populations. Its subcutaneous route, favourable safety profile, and ability to reduce hospitalization support its integration into first-line therapeutic algorithms. Further prospective studies are warranted to define.

Available products for the treatment of von Willebrand disease (VWD) now include a new recombinant von Willebrand factor (rVWF) in addition to plasma-derived concentrates (pdVWF). However, these two therapies have never been compared directly in either preclinical studies or real-world inpatient settings.The Hopscotch Will II study examined the treatment of VWD in hospitals and compared the use of pdVWF and rVWF.Five Rare Bleeding Diseases Centers in Western France retrospectively included patients with VWD over a 48-month period. The data was collected from the BERHLINGO Research Database as well as the French Hospital database, which contains medical information from patient records.Of the 866 patients evaluated in the study, 285 underwent 648 hospitalizations; 126 adult patients (VWD type 3 excluded) were given VWF concentrates during 249 of those hospital stays. rVWF was used in 61% of the cases. The majority of the hospitalizations were motivated by cutaneous-mucosal symptoms in gastroenterology, stomatology, gynecology, and obstetrics. Consumption of rVWF was lower, though the difference in total VWF consumption per stay or per patient per year was not significant: 51 (57)/34 (30) IU/kg/patient/year for pdVWF versus 40 (47)/27 (26) for rVWF (mean [SD]/median [IQR], Wilcoxon rank sum test, p = 0.2025).rVWF was used in similar patient profiles and for identical procedures, but the cost of treatment with rVWF was significantly lower, regardless of whether or not FVIII was added.

Congenital factor VII (FVII) deficiency is the most common rare hemorrhagic disorder. Acquired FVII deficiency can be isolated or associated with other low coagulation factor levels. FVII levels do not accurately predict a patient's bleeding risk. In the case of surgery, the perioperative management needs to be evaluated on a case-by-case basis, considering the patient's bleeding history and the type of surgery. We present 12 patients with congenital or acquired FVII deficiency and describe the perioperative management with plasma-derived nonactivated FVII (pd-FVII) concentrate. Patients with factor VII deficiency treated with pd-FVII for perioperative hemostasis, between April 2022 and May 2025. We report thirteen procedures in 12 patients (11 males and 1 female; age range: 15-78 years). Two patients were affected by acquired deficiency, and 10 patients presented congenital deficiency. Perioperative prophylaxis with pd-FVII was performed at doses ranging from 20 to 40 IU/kg/dose. Total pd-FVII consumption ranged between 20 and 320 IU/kg. During and after surgery, there were no major bleeding or thrombotic events. In the postoperative period, only one patient presented with hematuria.

Worldwide, one in four adults and three in four children fail to meet the physical activity targets recommended by the World Health Organization (WHO). Patients with chronic diseases and disabilities represent some of the least active populations. WHO guidelines encourage regular physical activity for individuals with disabilities, considering functional capacity and clinical status. Recommended interventions include moderate-to-vigorous activity, muscle-strengthening exercises at least twice weekly, and functional balance training at least three times per week, with specialist consultation as needed. Data on physical activity and sports participation in patients with chronic conditions such as inherited bleeding disorders are very limited. This narrative review updates the literature, focusing on von Willebrand disease and rare coagulation defects and highlighting the need for individualized, multidisciplinary recommendations to promote safe physical activity and optimize health outcomes.

Dysfunctional or quantitatively deficient von Willebrand factor (VWF) underlies von Willebrand disease (VWD), the most common inherited bleeding disorder. Type 2A VWD is a qualitative defect marked by impaired VWF-dependent platelet adhesion, typically reflected in disproportionately reduced ratios of platelet-dependent VWF activity to antigen (VWF activity/VWF:Ag) and collagen binding to antigen (VWF:CB/VWF:Ag). This phenotype results from a selective reduction or lack of high- and intermediate-molecular-weight multimers, which are essential for effective hemostasis under high shear stress. The lack of multimer arises from impaired multimer assembly and/or increased proteolytic cleavage of VWF by ADAMTS13. Clinically, type 2A tends to present with greater severity than other type 2 variants, manifesting as mucocutaneous bleeding, often including heavy menstrual bleeding, epistaxis, post-surgical bleeding and gastrointestinal hemorrhage from angiodysplasia. Diagnosis relies on functional assays and VWF multimer analysis, supported by genetic testing that identifies subtype-specific mutations affecting VWF multimeric structure and therefore its function. Type 2A is typically inherited in an autosomal dominant manner, with rare exceptions of autosomal recessive inheritance. Structural and molecular studies are continuing to elucidate how domain-specific variants disrupt multimeric structure and thus interactions with its ligands. Management is guided by bleeding severity and includes desmopressin (following responsiveness testing) and VWF replacement therapy. This review provides an in-depth update on type 2A VWD, covering its epidemiology, pathophysiology across distinct subtypes, clinical manifestations, diagnostic approach, molecular and structural insights, and current therapeutic strategies.

Unfractionated heparin (UFH) remains a major anticoagulant therapy applied within the acute hospital system. Due to intra- and interpatient variability, UFH monitoring needs to be applied to ensure patients remain free of thrombotic and bleeding complications at too low and too high an UFH level, respectively. Monitoring of UFH therapy is usually achieved using either an activated partial thromboplastin time (aPTT) or an anti-factor Xa (anti-Xa) method. The former is a clotting assay that evaluates both the anti-factor IIa (anti-IIa or anti-thrombin) and anti-Xa anticoagulant activity of UFH and the latter is a chromogenic assay that evaluates just the anti-Xa anticoagulant activity of UFH. The aPTT method is perhaps more widely utilized since aPTT testing is performed by all hemostasis laboratories performing routine coagulation tests. However, the aPTT method requires establishment of an aPTT UFH therapeutic range. The anti-Xa method is favored in larger hospital sites and by most experts and uses a standard UFH therapeutic range. We report findings for aPTT and anti-Xa testing for UFH monitoring in our geographic region using recent data (testing for the past 5 years; 2020-2024 inclusive) from the Royal College of Pathologists of Australasia Quality Assurance Program, an international external quality assessment (EQA) program, with over 110 enrolments for this EQA module. Four samples are assessed each year, with these comprising various levels of UFH. Good reproducibility was observed for duplicate samples sent in different surveys. Coefficient of variation (%) data revealed moderate variation for samples containing UFH (10-40% for anti-Xa; 10-25% for aPTT). Anti-Xa reagents containing dextran sulphate tended to yield higher anti-Xa values than those without. Interpretations regarding UFH levels being below, within, or above therapeutic levels were generally reported as expected, according to the level of UFH present in the sample, especially for anti-Xa testing.