Adam Cuker

Most reference intervals (RI) for absolute neutrophil count (ANC) and white blood cell count (WBC) in the United States (US) are not representative of people with the Duffy null phenotype (10% of the US population), which leads to misdiagnoses and inequity in care. We aimed to verify the adult Duffy null ANC RI and develop WBC and ANC RIs for pediatrics. 1,412 healthy Duffy null participants from 23 sites were included. All sites agreed on eligibility criteria. Otherwise, this was a pragmatic design with site-specific variation in collection approach. ANC and WBC were stratified into 5 age categories: 6 months-2 years, 3-6 years, 7-12 years, 13-17 years, and 18+ years. RI were calculated by Clinical and Laboratory Standards Institute guidelines. Duffy null-specific ANC RI were 0.53-4.50×109/L (6 months-2 years, n=184), 0.78-4.67×109/L (3-6 years, n=160), 0.87-5.34×109/L (7-12 years, n=190), 0.90-4.89×109/L (13-17 years, n=216), and 1.03-7.30×109/L (18+ years, n=662). 25% of adults had ANC <2.00×109/L and 24-53% of children had ANC <1.50×109/L. Sensitivity analyses did not show any significant differences in ANC RI when accounting for blood draw type, setting, collection site, hematology analyzer, or hemoglobin and platelet counts. This study provides the first report of Duffy null-specific pediatric ANC and WBC RI, as well as a large-scale verification of adult Duffy null-specific ANC and WBC RI. Adoption of Duffy null-specific RIs is necessary for the accurate interpretation of laboratory values that will support appropriate and equitable medical decision-making.

Background: Since publication of the American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia (ITP), new clinical trials have been completed, and new treatments have become available. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are a focused update of the 2019 ASH ITP guidelines, centering on treatment of adults with primary ITP. Methods: ASH formed a multidisciplinary guideline panel that included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The University of Oklahoma supported the guideline development process, including updating or performing systematic evidence reviews (up to 19 July 2025). The panel prioritized clinical questions and outcomes according to their importance to clinicians and patients and identified areas with new data or in which application of new methods would be of benefit. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks and the GRADE framework for multiple comparisons, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on recommendations for adults with primary ITP regarding initial therapy and second-line therapy for patients who failed first-line corticosteroids. The panel also issued good practice statements on thrombopoietic agent switching and splenectomy. Conclusions: Novel recommendations of these guidelines include (1) initial therapy with a combination of rituximab plus corticosteroids or a thrombopoietic agent plus corticosteroids rather than corticosteroids alone (conditional recommendation) and (2) a thrombopoietic agent (strong recommendation) or rituximab (conditional recommendation) for patients who failed first-line corticosteroids.

The rapid development of novel cancer therapies has considerably improved the care of cancer patients and cancer-related survival; however, these therapies are associated with a broad range of adverse events that have become a major burden in this population. Alongside other cancer-related factors, vascular toxicity from anticancer therapies contributes to an increased risk of venous thromboembolism. Among anticancer drugs, chemotherapeutic agents (eg, anthracyclines, platinum-based drugs, antimetabolites), hormonal therapies (eg, selective estrogen receptor modulators), agents used for multiple myeloma (including immunomodulatory drugs and proteasome inhibitors), asparaginase, as well as targeted inhibitors to immune checkpoints, vascular endothelial growth factor, epidermal growth factor receptor, tyrosine kinases, cyclin-dependent kinases, and poly(ADP-ribose) polymerase are primarily associated with increased risk of venous thromboembolism. Vascular adverse events associated with anticancer drugs are frequently underestimated, and significant gaps remain in the risk stratification, prevention, and management of thromboembolic events in patients receiving systemic anticancer therapies. This review examines the evidence linking anticancer drug exposure to the incidence of venous thromboembolism, summarizes the key underlying pathobiological mechanisms, and highlights current guideline recommendations for the prevention and treatment of cancer-associated thrombosis. Arterial thrombotic events are also discussed where clinically or mechanistically relevant. This review also offers advanced cardio-oncology perspectives on the identification, risk stratification, and therapeutic targeting of drug-induced vascular toxicity.

Background: Antithrombotic-associated intracranial hemorrhage (ICH) is a life-threatening condition, and rapid treatment in the setting of antithrombotic agents may limit hematoma expansion and improve outcomes. This focused update evaluated the available evidence after publication of the 2016 guidelines. Methods: The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, generated five questions to guide a systematic review and meta-analysis. Three of these questions update prior recommendations, while two are newly introduced. Each question followed a Population, Intervention, Comparator, Outcome (PICO) framework and focused on the management of acute ICH including spontaneous intraparenchymal hemorrhage (IPH) and traumatic ICH. The topics addressed were: (1) andexanet alfa versus 4-factor prothrombin complex concentrate (4F-PCC) for treatment of oral factor Xa inhibitor effects; (2) platelet transfusion versus no transfusion for treatment in the setting of antiplatelet agent use; (3) desmopressin versus no desmopressin for treatment in the setting of antiplatelet agent use; (4) treatment of anticoagulant effects versus no treatment in the setting of small IPH; and (5) use of viscoelastic hemostatic assays (VHAs) to treat coagulopathy in traumatic ICH. Recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: The panel generated eight recommendations. For patients with acute ICH, the panel issued the following conditional recommendations: use 4F-PCC rather than andexanet alfa for the treatment of the anticoagulant effects of factor Xa inhibitors, avoid platelet transfusion in non-neurosurgical patients with spontaneous IPH on antiplatelet agents, administer platelet transfusion in patients with spontaneous IPH on aspirin who are undergoing surgery, and use VHAs to guide treatment of coagulopathy in traumatic ICH. The panel was unable to issue recommendations regarding platelet transfusion for treatment of antiplatelet effects in traumatic ICH, use of desmopressin for treatment of antiplatelet effects, or treatment of anticoagulant effects in small IPH. Conclusions: The guideline writing panel provided new conditional recommendations for the treatment of antithrombotic-associated acute ICH. These recommendations are intended for consideration along with the patient’s clinical status and patient-specific factors.