Neonatal antiphospholipid syndrome (APS) is an exceptionally rare but clinically significant thrombotic disorder associated with antiphospholipid antibodies (aPL) in the neonatal period. Two principal pathogenic mechanisms have been proposed: passive transplacental transfer of maternal antiphospholipid antibodies and de novo neonatal production of aPL. Although approximately 30% of neonates born to aPL-positive mothers exhibit detectable antibodies at birth, thrombotic complications remain exceedingly uncommon. A “second-hit” model involving additional prothrombotic triggers such as infection, perinatal stress, inherited thrombophilia, or vascular catheters likely contributes to thrombogenesis. Available evidence from case reports and small series indicates that arterial thrombosis predominates, particularly neonatal arterial ischemic stroke, while venous thrombosis is less frequent. Diagnosis remains challenging because no validated neonatal-specific classification criteria exist, and interpretation of laboratory findings is confounded by transient maternal antibody transfer. Current diagnostic approaches rely on clinical suspicion, thrombosis confirmation, maternal antibody testing, serial neonatal aPL measurements, and exclusion of other prothrombotic conditions. Management strategies are extrapolated from pediatric and adult APS guidelines, with low-molecular-weight heparin representing the mainstay of anticoagulant therapy in affected neonates. Neonatal APS remains a diagnostic challenge due to its rarity and atypical presentations. Establishing age-specific criteria and long-term neurodevelopmental follow-up is critical for improving clinical outcomes and understanding the prognosis of this early-onset autoimmune condition. This narrative review aims to summarize current evidence regarding the pathophysiology, clinical manifestations, diagnostic challenges, and management of APS-associated thrombosis regarding the distinct neonatal population.
The introduction and refinement of tyrosine kinase inhibitors (TKIs) over the past 25 years have resulted in dramatic improvements in life expectancy in individuals with chronic myeloid leukemia (CML). There are now multiple effective and well-tolerated TKIs available, and because most patients will be receiving TKIs for their lifetime, quality-of-life (QoL) considerations are an increasing concern. Patients with CML receiving TKIs have worse QoL than the general population, but TKIs have a generally less negative impact on QoL factors than previously available treatments for CML. Commonly used TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib, asciminib, and olverembatinib) all have positive and negative impacts on QoL, each of which can be impacted by patient preference and priorities, as well as line of therapy. The inclusion of patient-reported QoL outcomes in clinical trials will be vital to helping physicians understand the patient experience of CML and thereby improve disease management.
Non-transfusion-dependent β-thalassemia (NTDT) was historically regarded as a relatively mild form of thalassemia because patients survive without regular transfusion therapy. However, growing evidence has challenged this perception and uncovered substantial morbidity and premature mortality driven by chronic anemia, iron overload, and hypercoagulability. This review examines three major clinical paradoxes that have reshaped the understanding of NTDT: the anemia paradox, whereby transfusion-independent patients may actually benefit from anemia correction; the iron overload paradox, characterized by clinically significant iron accumulation despite minimal or no transfusion exposure; and the hypercoagulability paradox, whereby chronic anemia coexists with a prothrombotic state. These evolving concepts have transformed NTDT from a condition traditionally managed through observation into a disease requiring proactive, risk-based intervention.
Differentiation syndrome (DS) is a life-threatening complication of all-trans retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia (APL). This review synthesizes the current understanding of DS pathogenesis, from PML::RARA degradation to cytokine storm, endothelial injury, and multi-organ damage, alongside diagnostic criteria, severity grading, and risk stratification. We describe a graded treatment framework encompassing prophylactic, therapeutic, and refractory-phase strategies, with particular emphasis on special populations, predictive models, and emerging therapies. Integrating mechanistic insights with risk-adapted, stepwise therapeutic strategies is essential to reduce DS-associated morbidity and mortality, thereby further improving outcomes in this highly curable disease.
Polycythemia vera (PV) is a clonal myeloproliferative neoplasm in which erythrocytosis, although driven by constitutive JAK2 signaling, remains dependent on iron availability. This dependency provides a rationale for therapeutic targeting of the hepcidin-ferroportin axis, whose modulation induces functional iron restriction and constrains erythropoiesis. The hepcidin mimetic rusfertide has shown durable hematocrit control and marked reduction of phlebotomy requirements across phase 2 and phase 3 studies, with predictable changes in systemic iron markers. However, current evidence is largely based on surrogate hematologic endpoints, and whether iron-directed strategies reduce thrombotic risk or modify disease trajectory remains undefined. Within this framework, iron metabolism can be viewed as a downstream, regulatable determinant of erythropoietic output, distinct from but integrated with clonal and inflammatory signaling. This review summarizes biological and clinical evidence on iron homeostasis in PV, focusing on the hepcidin-ferroportin axis and its integration with clone-directed therapies.
