Background: Despite the global burden of disseminated intravascular coagulation (DIC) and decades of scoring system development, no international assessment has evaluated current global practices among clinicians. Objectives: To describe international diagnostic and treatment practices for DIC, identify barriers, and examine differences across country income levels. Methods: The International Society on Thrombosis and Haemostasis (ISTH) Scientific Standardization Subcommittee on DIC conducted an international survey (March 2024 to February 2025) to assess global diagnostic and treatment practices. Analysis was stratified by country income level based on World Bank classifications. Results: A total of 153 clinicians from 27 countries completed the survey, with most respondents from high-income countries (64%). The most suggestive clinical features of DIC were bleeding (89%), petechiae (77%), and shock (63%). Standard laboratory tests, such as platelet count (93%), prothrombin time/international normalized ratio (85%), fibrinogen (78%), and D-dimer (76%), were commonly used; however, respondents from middle-income countries had reduced access to fibrinogen testing, serial monitoring, and advanced diagnostics. Only 28% of clinicians used a formal DIC scoring system (ISTH 21%; sepsis-induced coagulopathy 14%), despite 76% reporting familiarity with the ISTH definition. First-line management relied primarily on fresh-frozen plasma (65%), platelets (38%), and cryoprecipitate (32%), whereas middle-income clinicians more frequently used whole blood and less frequently specialized factor concentrates. Major challenges in the diagnosis and management of DIC included diagnostic uncertainty due to variable underlying disorders (59%) and a heterogeneous clinical presentation (47%). Resource limitations, including restricted laboratory testing (57%), inadequate transfusion supplies (54%), and insufficient critical care support (38%), were more frequent challenges in middle-income countries (P < .001 for all comparisons). Conclusion: Despite strong global awareness, major gaps persist between recommended and real-world DIC practice, particularly in resource-limited settings. Efforts to expand access to diagnostics, strengthen transfusion and critical care networks, and support guideline-based management are needed.

Type 2B von Willebrand disease (VWD) is a rare qualitative variant, accounting for ∼5% of all VWD cases. It is characterized by increased affinity of abnormal von Willebrand factor (VWF) for the platelet glycoprotein Ibα receptor, resulting in enhanced clearance of both high-molecular-weight VWF multimers and platelets from circulation. The management of women with type 2B VWD during pregnancy and the postpartum period poses unique challenges due to complex hemostatic abnormalities, a high risk of bleeding complications, and a lack of evidence-based guidelines. A recent systematic review, international registry analysis, and global physician survey highlighted several unmet clinical needs in this population, including gaps in early diagnosis, prenatal counseling, pregnancy monitoring, and peripartum management. In response, the International Society on Thrombosis and Haemostasis Scientific Subcommittees on VWF and on Women’s Health Issues in Thrombosis and Haemostasis collaborated to develop consensus-based guidance for the management of type 2B VWD in pregnancy and postpartum. Using the real-time Delphi methodology, 14 international experts reviewed 26 initial statements on diagnosis, monitoring, and treatment. After 2 rounds of anonymous voting and revisions based on participants’ feedback, consensus was achieved on 25 statements. These consensus statements, grounded in the best available evidence and expert opinion, aim to standardize care, guide management, and improve clinical outcomes for women with type 2B VWD during pregnancy and postpartum.

Abstract:Thrombi are not uniform structures, and neither are the red blood cells (RBCs) that populate them. Most models of thrombosis, however, implicitly treat erythrocytes as mechanically and biologically uniform, obscuring a key determinant of clot architecture: RBC heterogeneity. Circulating RBCs vary widely in size, shape, deformability, membrane composition, and biochemical state, generating subpopulations that behave differently under flow and within forming thrombi. These differences actively govern how RBCs marginate, where they localize during thrombus growth, how they interact with fibrin and platelets, and how they resist or accommodate platelet-driven contraction. The outcome is not merely variable RBC content but spatially organized thrombi with region-specific mechanics, permeability, and fibrinolytic susceptibility. Experimental models and analyses of patient-derived thrombi demonstrate that RBCs are unevenly distributed within clots. This spatial variability shapes local fibrin architecture, platelet activity, and clot mechanics in ways that cannot be inferred from total RBC content or average erythrocyte properties, highlighting RBC heterogeneity as a critical, yet underrecognized, determinant of thrombus formation. In this review, we present a conceptual framework of thrombus heterogeneity along three coupled axes, namely, mechanical, structural, and biochemical, illustrating how erythrocyte subpopulations influence clot formation and function. We synthesize emerging evidence, discuss approaches for identifying RBC subpopulations, and explore implications for thrombosis modeling, thrombolysis, thrombectomy, and clinical outcomes.

Disseminated intravascular coagulopathy (DIC) in pregnancy is a severe maternal morbidity that is associated with short- and long-term complications. However, information regarding the causes of DIC treatments and outcomes in pregnancy is based on local reports. To address this gap, 2 Scientific and Standardization Committees, the Women's Health Issues in Thrombosis and Hemostasis and Disseminated Intravascular Coagulation of the International Society on Thrombosis and Hemostasis, joined to establish an international global registry. This registry was developed to examine the current definitions, clinical presentations, and current practices around laboratory diagnosis and management of DIC worldwide. We collected data between 2018 and 2024; there were 148 data entries to the registry (13 countries); 104 of them included patients' clinical and laboratory information. Placental abruption is the leading cause for ante- and intrapartum DIC, especially when associated with stillbirth. The leading etiology for postpartum DIC was uterine atony, especially following/during caesarean sections. The contribution of abnormally implanted placenta (ie, placenta accreta and/or previa) to the development of DIC is increasing. The leading pregnancy complications associated with DIC were placental abruption in HIC and preeclampsia in LMIC. Hemostatic parameters differed between women who had a positive pregnancy-specific DIC score and those who did not meet that criterion. Women with placental-mediated pregnancy complications had a lower median pregnancy-specific DIC score than those without such complications at the time of diagnosis of DIC and following recovery, suggesting a different mechanism of disease in the 2 groups.

Coagulopathies, infection, and CNS infiltration are common complications during induction therapy of acute myeloid leukemia (AML). Early identification of adverse-risk patients may improve outcomes. This study evaluated the predictive value of coagulation markers, von Willebrand Factor antigen (vWF-ag), von Willebrand Factor–ristocetin cofactor (vWF-RCof), antihemophilic factor (FVIII), and D-dimer on risk stratification, severity and outcomes of AML patients. Fifty AML patients treated at Oncology Center Mansoura University hospital, from February 2023 to February 2024 were recruited and stratified into three risk groups favourable, intermediate, and adverse risk groups respectively according to the 2022 European leukemianet (ELN) risk stratification for AML. vWF-ag, vWF: RCof, FVIII, and D-dimer were measured at diagnosis and at remission. Adverse-risk group had the highest median levels of vWF-ag, vWF-RCof, FVIII and D-dimer at, both diagnosis and remission (p < 0.05). All markers significantly declined after remission (p < 0.05). vWF-ag, vWF-RCof, and D-dimer differed significantly among risk groups at both diagnosis and remission. ROC analysis showed that in the adverse-risk group, D-dimer had an AUC of 0.813 (cutoff > 1.6), vWF: Ag 0.780 (> 295), and vWF: RCo 0.761 (> 223). FVIII showed lower predictive value (AUC 0.625). Infection was the most frequent complication, followed by bleeding and thrombosis. Infection correlated with higher vWF: Ag after remission; thrombosis correlated with elevated vWF: Ag at diagnosis and remission and bleeding with lower vWF-ag. CNS infiltration showed no association. vWF-ag, vWF–RCof, and D-dimers may be associated with risk and complications in AML, but these findings require external validation in larger cohorts.

The International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool (BAT) is widely used to screen for inherited bleeding disorders. Adult reference ranges are age- and sex-specific. However, a single reference range (0-2) is currently applied to all individuals under 18 years. Adolescent developmental changes and global differences in healthcare access may influence bleeding scores, necessitating validation in a large international pediatric cohort. We aimed to evaluate age- and sex-specific ranges for ISTH-BAT scores in individuals <18 years using an international dataset. Under the auspices of 2 ISTH Scientific Subcommittees, healthy participants <18 years were recruited from 7 countries across 5 continents. ISTH-BAT assessments were completed by trained investigators using a standard protocol. Participants were stratified by age quartile, sex, country, and World Bank income. Reference ranges were defined using the 2.5th to 97.5th percentile and assessed with 95% CIs. A total of 1168 participants were included (mean age ± SD, 7.7 ± 5.2 years; 50.5% female). The overall ISTH-BAT score reference range was 0 to 2. The overall distribution of scores across age quartiles was not statistically significantly different (P = .065). A significant positive trend in the proportion of participants with scores >0 was observed across increasing age quartiles (linear-by-linear association χ² = 47.3; P < .001). Females -more often than males- had a bleeding score > 0 (P = .02), with significant sex differences observed only in quartile 4 (P = .003). The 2.5th to 97.5th percentile for quartile 4 females was 0 to 3. Scores varied by country and income classification (P ≤ .001), but reference ranges remained stable. We conclude that the ISTH-BAT reference range of 0 to 2 is appropriate for individuals <18 years. For females (12-17 years), 0 to 3 may be considered and interpreted in conjunction with clinical context when guiding referral decisions.

Abstract Platelets, the smallest blood cells, weave through health and disease, their history profound, some of their functions yet to be revealed. Terminology often drifts, but by naming with precision, we illuminate understanding, guide newcomers and set a clear path for research and collaboration.

ABSTRACT:Platelet-type von Willebrand disease (PT-VWD) refers to a rare bleeding disorder caused by gain-of-function mutations in platelet glycoprotein Ibα (GPIbα). These mutations lead to a hyperactive protein-protein interaction (PPI) with von Willebrand factor (VWF) and pathological platelet aggregation. Counterintuitively, patients with PT-VWD present with a bleeding diathesis as opposed to thrombosis. Despite well-defined genetic etiology, no targeted therapy exists for PT-VWD. Here, we sought to develop a peptide inhibitor that selectively targets the aberrant interaction in PT-VWD. Using the In Silico Protein Synthesizer, we designed and screened 10 000 peptides for predicted affinity and specificity toward GPIbαMet239Val. Functional validation of top-ranked peptides included a combination of in vitro functional assays using GPIbαGly233Val, Met239Val and ex vivo platelet assays from patients with PT-VWD. One peptide, G14, emerged as a potent and selective inhibitor of the GPIbαGly233Val, Met239Val-VWF PPI. Functional assays demonstrated that G14 disrupts this interaction without binding GPIbαWT or VWF alone. The peptide also displays picomolar affinity (6.6 pM) for GPIbαGly233Val, Met239Val. Structural modeling predicted G14 binds the β-switch region of GPIbαGly233Val, Met239Val involving the disease-associated Val239 residue. In platelet-rich plasma from a patient with PT-VWD, G14 selectively inhibited platelet-VWF binding and ristocetin-induced agglutination, with no measurable effect on healthy samples. The G14 peptide appears to be a highly specific inhibitor of the GPIbαGly233Val, Met239Val-VWF interaction, providing proof-of-concept data for therapeutic development in PT-VWD. Furthermore, the protein and platelet specificity of these data suggest that G14 may be a potential diagnostic tool for PT-VWD. The approach highlights the utility of artificial intelligence in targeting disease-specific PPIs with high precision.

INTRODUCTION:Red blood cells (RBCs) possess distinct biomechanical properties that enable their survival and efficient oxygen delivery. Cancer-associated anemia, frequently compounded by chemotherapy, is a major clinical challenge, yet little is known about how RBC biomechanics contribute to its pathophysiology. This study evaluates the biomechanical properties of RBCs in patients with cancer compared to controls and within patients before and after chemotherapy. METHODS:Biomechanical properties of RBCs were assessed in 110 women with breast, ovarian, or endometrial cancer, measured before and after chemotherapy, and compared findings with 35 healthy female controls. Thirteen biomechanical parameters were assessed using the MIZAR automated rheometer. RESULTS:Relative to controls, pre-chemotherapy cancer patients exhibited significantly higher RBC aggregation and elasticity. Within the cancer cohort, anemic patients demonstrated more deformable and elastic RBCs, with increased aggregation compared to non-anemic patients. Following chemotherapy, patients displayed reduced RBC deformability but further increased elasticity, consistent with chemotherapy-induced alterations to membrane structure and function; these effects were most pronounced in anemic patients. CONCLUSION:We report novel rheological observations indicating that both cancer and chemotherapy are associated with alterations in RBC biomechanics, and that anemia further amplifies these changes. Importantly, cancer-associated anemia appears to involve impaired RBC quality. Recognition of biomechanical dysfunction may provide new insights into the mechanisms of cancer-related anemia and support the development of more comprehensive diagnostic and management strategies.