Clinical hematology international最新文献

Factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by unstable hemostatic clots due to defective fibrin cross‑linking. Congenital FXIII deficiency arises from variants in the F13A1 (FXIII-A subunit) or F13B (FXIII-B subunit) genes, and classically presents with delayed umbilical stump hemorrhage, soft‑tissue and intracranial bleeding, impaired wound healing, and recurrent pregnancy loss. Acquired deficiency stems from inhibitory autoantibodies or from reduced synthesis or consumption in critical illness and surgery. Routine coagulation screening tests are normal and diagnosis relies on quantitative FXIII activity assays with or without antigenic phenotyping and, when indicated, inhibitor testing and molecular confirmation. Plasma‑derived FXIII concentrate reduces spontaneous and intracranial bleeding; recombinant FXIII‑A2 is appropriate for F13A1 defects but not patients with F13B variants. Perioperative and obstetric care target activity thresholds suited to procedural risk and individual pharmacokinetics. This review synthesizes the molecular biology, epidemiology, clinical features, diagnostic methods, and evidence‑based management of FXIII deficiency, with practical guidance for assay selection, validation, and result interpretation.

Spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK) inhibitors have emerged as promising targeted therapies for adult immune thrombocytopenia (ITP). However, a comprehensive synthesis of their benefits compared to placebo has not been previously conducted. This study aims to analyze the efficacy and safety of SYK and BTK inhibitors in comparison to placebo for the treatment of adult patients with ITP. A systematic search was performed across four major databases (Medline, Europe PMC, Scopus, and ClinicalTrials.gov) for randomized controlled trials (RCTs) evaluating SYK and/or BTK inhibitors versus placebo in adults with ITP. We utilized random-effects models to evaluate the risk ratio (RR) and mean difference (MD) for the occurrence of outcomes. Five RCTs across four publications were included. Both SYK and BTK inhibitors significantly improved overall platelet response (RR 3.95; 95%CI: 2.68 - 5.81, p<0.00001) and durable response rates (RR 12.50; 95%CI: 3.99 - 39.18, p<0.0001) compared to placebo. Treatment also resulted in shorter time to response and reduced need for rescue interventions. Although total AEs and rash were more common in the intervention group, these were predominantly grade 1-2 and did not lead to increased discontinuation or serious AE rates. No significant differences were observed in the specific events such as gastrointestinal symptoms, cytopenias, liver enzyme elevations, infections, or hypertension. SYK and BTK inhibitors demonstrate superior efficacy over placebo in improving platelet outcomes in adult ITP without compromising safety. These findings support their role as effective treatment options, especially for patients unresponsive to other therapies.

Clonal Hematopoiesis of indeterminate potential (CHIP) has been increasingly recognised as a risk factor for cardiovascular disease (CVD). Recent epidemiological and experimental studies have linked CHIP as an independent risk factor for myocardial infarction, stroke, and coronary artery disease, with specific mutations carrying a higher CVD risk. During the aging process, somatic mutations in genes, including DNMT3A and TET2, accumulate in the hematopoietic stem cells (HSCs), conferring both epigenetic and metabolic advantages that not only drive hematopoiesis towards a pro-inflammatory myeloid lineage but also reprogram innate immune cells, promoting a persistent inflammatory state. These myeloid derivatives, via increased IL-1β and IL-6 production, establish a pro-atherogenic environment and contribute to plaque instability, leading to an increased thrombotic risk and accelerated vascular aging. Although routine screening is not recommended for asymptomatic adults, targeted detection in high-risk individuals could benefit from preventive strategies. Incorporating CHIP into risk models may enable precision prevention, but prospective trials are needed to determine whether CHIP-guided interventions improve cardiovascular outcomes.

The use of proteasome inhibitors (PI) and immunomodulatory drugs (IMiD) such as lenalidomide (Len) in early lines of therapy in multiple myeloma (MM) has resulted in a high proportion of patients with relapsed or refractory multiple myeloma (RRMM) being Len-refractory. Len refractoriness is associated with inferior outcomes, constituting an unmet need in clinical practice. This retrospective single-center study aimed to provide real-world characteristics and outcomes in RRMM previously exposed to PI and Len during 1-3 prior lines of therapy (LOT), stratified by Len refractoriness. RRMM patients between Jan 2017 and May 2023 were included. We studied clinical characteristics, treatments and survival outcomes. A total of 218 patients were included (n=85 Len refractory). The median progression-free survival was 13.6 months in Len-refractory versus 14.9 months in Len non-refractory patients. The median overall survival was 20.3 months in Len refractory, and not reached in Len non-refractory patients. The overall response rates to the subsequent LOT were 58.8% and 61.7% in Len refractory and non-refractory cohorts, respectively. IMiD-based and anti-CD38 monoclonal antibody-containing regimens were the most frequent subsequent LOT, 44% and 41%, respectively. This study shows suboptimal outcomes in Len refractory RRMM patients, highlighting the need to develop effective treatment options.

Ramadan fasting induces significant physiological adaptations that can affect patients with hematological disorders. While fasting is generally safe for healthy individuals, reduced hydration and nutritional intake during the 13-18 hour fasting period can pose risks for those with anemia, coagulopathies, or malignancies. High-risk patients - such as those on intensive chemotherapy, post stem-cell transplantation, or with severe anemia (hemoglobin <8 g/dL) - are advised not to fast to avoid complications (e.g. vaso-occlusive crises, thrombotic events, or worsening anemia). Patients with stable hematologic conditions, however, may fast safely with careful pre-Ramadan evaluation, medication timing adjustments, and strict hydration and nutrition plans. Given the limited clinical data, an individualized risk stratification approach is essential. Shared decision-making, balancing religious aspirations with medical safety, is encouraged. Future studies are needed to establish evidence-based guidelines, but until then, thorough risk assessment, proactive monitoring, and patient education form the cornerstone of safe Ramadan fasting for individuals with hematological disorders.

Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm with highly variable, multisystem manifestations that present significant diagnostic and therapeutic challenges. This retrospective multicenter case series included 11 adult patients diagnosed with biopsy-proven ECD across Canada between January 2015 and June 2024. The cohort comprised six females and five males with a median age of 55 years (range 41-74). PET-CT was used for disease staging and treatment monitoring in nine cases. The most commonly involved sites were bone (n=8), kidney (n=6), and lungs (n=5). BRAF V600E mutations were detected in seven patients. Treatments included vemurafenib, interferon, tocilizumab, cladribine, cobimetinib, and cytarabine. Treatment responses varied, with several patients achieving remission or stable disease, while others had progressive or end-stage disease. This study highlights the clinical heterogeneity of ECD and the value of integrating histopathology, molecular profiling, and imaging to guide management and improve outcomes.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by uncontrolled immune activation and hemophagocytosis. In adults, Epstein-Barr virus (EBV) infection is a known trigger. This report describes a novel approach to treating EBV-induced HLH in a 29-year-old female, avoiding the potential toxicities of chemotherapy-based regimens, such as infertility. The patient presented febrile, tachycardic, and hypotensive following a week of high fever, bilious emesis, and diarrhea. Laboratory results showed elevated AST and ALT, hyperbilirubinemia, leukopenia, thrombocytopenia, and hyperferritinemia. Imaging revealed splenomegaly, and a positive mononucleosis rapid test confirmed EBV infection. Based on her clinical presentation, laboratory findings, and a bone marrow biopsy showing phagocytic histiocytes, she was diagnosed with EBV-induced HLH, fulfilling 7 of the 8 diagnostic criteria (5 required). The patient was started on the DAIR regimen two days after transfer. DAIR combines dexamethasone for its potent anti-inflammatory properties (used in HLH-94/HLH-2004), anakinra to control the cytokine storm, IVIG for passive immune support and antiviral action, and rituximab to target EBV-infected B cells. The patient responded well to treatment. EBV became undetectable within three weeks, and by seven weeks, blood counts, liver function, ferritin, triglycerides, and fibrinogen levels had normalized. Ten weeks after symptom onset, she returned to work and is now pregnant, with no signs of relapse. This case demonstrates the effectiveness of DAIR as a chemotherapy-free alternative for EBV-induced HLH, offering a targeted approach to the syndrome's complex pathogenesis while achieving sustained remission.