Search Results (563)

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors exhibit increased rates of psychological comorbidities, cognitive impairment (CI), and reduced health-related quality of life (HRQoL). This cross-sectional study investigated the prevalence of CI and its association with reduced HRQoL and depression among iTTP survivors. Methods: iTTP survivors completed the Beck Depression Inventory (BDI-II), the SF-36 for evaluation of HRQoL, and the NIH Toolbox Cognition Battery. SF-36 scores and fluid cognition and crystallized cognition composite scores from the cognition battery were compared to the reference population. We examined associations of cognitive impairment with depression and HRQoL. Results: We enrolled 47 patients with iTTP; 76.6% were female, the median age was 51 (IQR 39, 60), and the median number of episodes was 2 (1, 3.5). Compared to the reference, iTTP survivors had significantly lower mean scores in seven SF-36 domains (physical function, physical limitation, general, mental health, vitality, social functioning, and emotional limitation) as well as the mental component score (MCS) (p < 0.0001) and physical component scores (PCS) (p < 0.0001). A lower physical HRQoL score was observed in those with mild (49.3 vs. 37.7, p = 0.005) and major (49.3 vs. 38.4, p = 0.007) CI compared to no CI. The fluid cognition composite score correlated strongly with the SF-36 Physical Component Summary (r = 0.548, p = 0.0002) but not the Mental Component Summary (r = 0.113, p = 0.489). Conclusions: Cognitive impairment in iTTP survivors is associated with reduced physical HRQoL. Identifying and addressing cognitive deficits in iTTP may improve HRQoL. Given that 40% of participants had depressive symptoms, which were associated with reduced mental HRQoL, iTTP survivors may also benefit from routine mental health screening t. Full article

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled macrophage activation. Secondary HLH is more common in adults and may be triggered by infection, malignancy, or autoimmune disease. Dyslipidemia, particularly hypolipoproteinemia, has been described but remains underexplored. Methods: We retrospectively reviewed 18 adult HLH cases diagnosed between 2012 and 2020 at two institutions where complete lipid profiles were obtained at or near diagnosis. HLH was defined according to HLH-2004 criteria. Results: Among 18 patients, 17 (94%) had secondary HLH, most commonly idiopathic (n = 5, 28%) or Epstein–Barr virus-associated (n = 3, 17%). Hypolipidemia was nearly universal: all (18/18) had HDL-C < 30 mg/dL, 15/18 (83%) had HDL-C < 20 mg/dL, and 12/18 (67%) had HDL-C < 10 mg/dL. LDL-C was <100 mg/dL in 12/18 (67%), with 6/18 (33%) undetectable. Triglycerides were variably elevated (median 279 mg/dL, range 96–1658 mg/dL). Three representative cases with profound hypolipoproteinemia demonstrated lipid normalization after HLH-directed therapy. Conclusions: Severe reductions in HDL-C and LDL-C appear to accompany HLH and may contribute to its pathophysiology by impairing antioxidant defenses, destabilizing membranes, and potentiating macrophage activation. This case series highlights a consistent association between hypolipoproteinemia and HLH, suggesting potential diagnostic value. However, the observational design and small cohort limit generalizability. Larger prospective studies are needed to clarify mechanisms and evaluate whether full lipid profiling should be incorporated into diagnostic algorithms. Full article

Background and Clinical Significance: Common Variable Immunodeficiency (CVID) is a prevalent manifestation of primary immunodeficiency disorder. The current mainstay of treatment is immunoglobulin replacement therapy; however, in patients with severe complications or refractory disease, hematopoietic stem cell transplant (HSCT) is indicated. Despite this, there has been little research regarding HSCT as a treatment for CVID, with few case reports demonstrating clinical benefit. Case presentation: We present a unique case of common variable immunodeficiency Type XII (CVID12) with rare NFKB mutation and its management. A 20-year-old female with autoimmune alopecia, eczema, and a congenital atrophic right kidney presented to the emergency department with a three-month history of intermittent fever, malaise, lymphadenopathy, mouth sores, diarrhea, and odynophagia, accompanied by a 5 lb. unintentional weight loss and night sweats. Previously, she received multiple steroid prescriptions for these symptoms, providing only temporary relief with each course. Lab findings revealed severe neutropenia and imaging demonstrated hepatosplenomegaly and lymphadenopathy. Flow cytometry revealed a slightly atypical CD8-positive T-cell population and bone marrow biopsy revealed variable cellular marrow with trilineage hematopoiesis. Genetic testing confirmed the diagnosis of Autosomal Dominant Common Variable Immunodeficiency Type XII with an NFKB1 mutation. Pre-transplant treatments included monthly IVIG, weekly rituximab, and daily filgrastim, all of which failed to improve her autoimmune neutropenia and hypogammaglobulinemia and failed to reduce her symptomatic burden. Given the patient’s young age and refractory autoimmune neutropenia, it was decided to manage them definitively with hematopoietic stem cell transplantation (HSCT). She ultimately underwent allogenic stem cell transplantation (haploidentical, donor was the mother) with 3.96 × 10⁸/kg TNC without immediate post-transplant complications. Conclusions: This article demonstrates a rare case of NFKB1-positive CVID that was successfully treated with HSCT and highlights the importance of considering transplant therapy in younger patients with clinically significant, refractory autoimmune cytopenia. Full article

Background/Objectives: In haematology, a wide range of blood disorders are hereditary. The thalassaemias are hereditary anaemias characterised by a high burden of disease at the public health level, challenging the resources of many health systems. This review focuses on thalassaemias for which many countries have developed screening and prevention programmes. To manage this heavy burden, two approaches were introduced over the years. The first one focused on reducing the annual affected births consequent to appropriate non-directive genetic counselling, offering to the parents the chance to make an informed choice concerning their reproductive lives. The second approach was related to the development of curative treatments such as haematopoietic stem cell transplantation (HSCT) in the early years, with continued ongoing efforts for improvements, followed by successful advances in gene-based holistic cures in more recent years. Genetic counselling is a vital component in successful prevention, aiming at informing individuals who are found to be carriers and couples who are both carriers with a 25% risk at every pregnancy of having an affected child in the case of recessive, Mendelian inheritance. The issues are many, and that may have to be discussed, highlighting the level of skills which a genetic counsellor is expected to possess and utilise appropriately in every counselling session. The concern is that such trained and skilled professionals are few in number and not well integrated into the multidisciplinary groups addressing the control of these complex disorders. It is our experience that for blood disorders, counselling is rarely in the hands of qualified scientists. It is our firm belief that it is necessary to incorporate genetic counselling as an integral part of haematology services. Methods: To investigate current practices we have drawn on the experience of existing programmes, as well as published literature. Results: Currently, in almost all haemoglobinopathy prevention programmes, counselling is offered by the clinicians in charge of clinical care or, in some settings, by the nurse of the clinic or the screening laboratory scientist. Conclusions: The Thalassaemia International Federation suggests and is in the process of developing special training in counselling as part of haematology training, as well as professional development modules for those already in practice. Considering the complexity of the issues that must be discussed, a multidisciplinary approach to counselling should be considered where possible. Full article

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, poses a substantial risk for venous thromboembolism (VTE). Managing CML in patients with such prothrombotic predispositions presents complex therapeutic challenges, particularly in selecting an appropriate TKI and managing anticoagulation. Case Presentation: A 33-year-old woman with congenital thrombophilia (type I protein S deficiency and heterozygous Factor V Leiden mutation) and a history of VTE on long-term anticoagulation with acenocoumarol presented with CML. She exhibited primary resistance to first-line imatinib and poor tolerance with suboptimal response to second-line bosutinib. Third-line treatment with asciminib led to a rapid and sustained major molecular response (MR4.5) without bleeding or thrombotic complications. Conclusions: This case highlights the importance of individualized, multidisciplinary management in CML patients with coexisting thrombophilia. Asciminib, with its favorable cardiovascular safety profile, represents a promising therapeutic option in high-risk patients where other TKIs may be contraindicated due to resistance, intolerance, or thrombotic risk. Full article

Background/Objectives: Hematogones, B cell precursors, are considered a clock of bone marrow reconstitution after chemotherapy and hematopoietic stem cell transplantation (HSCT). Methods: In this retrospective observational monocentric study, we investigated the prognostic role of hematogone expansion after allogeneic HSCT and its association with clinical and molecular features. Results: Using a cut-off value of 0.1%, hematogones were detected in 60% of patients at the first re-evaluation after HSCT (median, 2.4%; range, 0.2–9.0%) and in 63% of subjects at the most recent evaluation (MRR) (median, 1.4%; range, 0.1–5.1%). In particular, prolonged hematogone expansion was associated with longer overall survival (p = 0.0043) and relapse-free survival (p = 0.0002). No associations were described between hematogone frequency and stem cell sources or acute or chronic graft versus host disease incidence. Conclusions: In conclusion, our results confirmed that hematogones mirrored bone marrow fitness and reconstitution ability; thus, they could be used as a prognostic marker of HSCT outcomes. Full article

Background: Sickle cell disease (SCD) is among the most prevalent inherited hemoglobinopathies and is strongly associated with numerous coagulation abnormalities, hence constituting a severe hypercoagulable state. Methods: We conducted a single-center retrospective observational study of patients with SCD who were monitored at Hippokration Hospital of Thessaloniki between 1999 and 2024. Demographic characteristics, hemoglobin (Hb) genotype, medical history, anticoagulant and antiplatelet therapy, dosage of anticoagulant treatment, recurrence of the first episode of venous thromboembolism (VTE) and relevant laboratory values were examined as possible risk factors. Results: Among 46 patients, 12 (26.1%) developed thrombosis with the majority (75%) carrying the HbS/β-thal genotype. The prevalence of VTE in this study was 17.4%. Variables significantly associated with an increased risk of thrombosis included age at the time of thrombosis, patient age, use of anticoagulant treatment, anticoagulant dosage, antiplatelet therapy and type of transfusion (p < 0.05). On multivariate analysis, anticoagulant treatment and its dosage retained statistical significance (p < 0.05). Conclusions: These findings reinforce the strong association between SCD and thrombotic events. Despite the availability of a broad therapeutic armamentarium and increasing knowledge of the underlying disease mechanisms, the prevention and management of thrombosis in these patients remains a challenge. Full article

Spontaneous intramuscular hematomas (SMHs) are rare but potentially serious complications of oral anticoagulation therapy. Although often attributed solely to anticoagulant use, such lesions may mask underlying soft tissue sarcomas or paraneoplastic conditions. We report the case of an 80-year-old man on warfarin who presented with a painful thigh mass initially interpreted as a hematoma but ultimately diagnosed as a malignant fibrous histiocytoma (MFH). In addition, we provide a narrative review of published cases, focusing on clinical presentation, diagnostic challenges, imaging strategies, and outcomes. Key pitfalls leading to delayed diagnosis include attribution bias, inadequate imaging, and premature management decisions. Epidemiological data show that while the incidence of SMHs is estimated at 0.5–1.5% among patients on vitamin K antagonists, clinically significant cases are increasingly reported with direct oral anticoagulants (DOACs). Suggested measures include clinical algorithms to prompt imaging and biopsy in persistent masses, validation of magnetic resonance imaging (MRI) criteria, and the establishment of prospective registries, aimed at facilitating earlier recognition of malignant lesions and improving patient outcomes. These strategies may improve early detection of malignancy and optimize care in anticoagulated patients presenting with soft tissue lesions. Full article

Background: Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of mature T-cell lymphoma, accounting for fewer than 5% of peripheral T-cell lymphomas, with an aggressive course and poor prognosis. There are two types of this disease based on morphology and immunophenotype: type I, which is often, but not always, associated with celiac disease (classic EATL), and type 2, monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Risk factors for classic EATL are poor adherence to a gluten-free diet, advanced age, male sex, and HLA-DQ2 homozygosity. The treatment options include surgery and various chemotherapy regimens with autologous stem cell transplantation, but the outcomes are discouraging, and clinical trials with targeted and biologic therapies are needed. Case Presentation: We report three cases of type 1 EATL, all with lethal outcomes, with one patient dying during initial treatment, one dying following several surgical interventions and without waiting to start chemotherapy, and one dying following a good treatment response but with severe infection. Full article

Background/Objectives: Platelet counts can be affected by storage conditions, potentially leading to pseudothrombocytopenia. The present study aimed to investigate temperature-dependent changes in platelet counts and morphology in whole blood samples anticoagulated with heparin or EDTA. We also examined the molecular mechanism of cold-induced aggregation via integrin GPIIb/IIIa–fibrinogen interaction using established bioinformatics technologies (docking simulation). Methods: Peripheral blood was collected from healthy volunteers (n = 6) and treated with either heparin or EDTA. The samples were stored at 4 °C, room temperature, or incubated at 37 °C. Platelet counts were measured using an automated hematology analyzer. The morphology of various blood cells in smears was assessed using the May-Grünwald Giemsa staining method. Docking simulations using an available software (HADDOCK 2.4) were performed to evaluate integrin–fibrinogen binding at different temperatures. Results: In automated blood cell counting, platelet counts in heparinized blood were significantly decreased under low-temperature conditions (4 °C), but this decrease was restored to levels comparable to those at room temperature upon warming to 37 °C (p < 0.05). No significant changes were observed in EDTA-treated samples. Microscopical findings showed platelet aggregation only in heparinized samples at 4 °C, with normal morphology restored upon warming (37 °C). Docking simulations estimated stronger integrin GPIIb/IIIa–fibrinogen binding at 4 °C than at 37 °C (p = 0.0286), suggesting temperature-dependent enhancement of molecular interactions. Conclusions: These findings indicate that heparin can induce reversible platelet aggregation at low temperatures in whole blood samples, leading to pseudothrombocytopenia. This phenomenon may be mediated by increased integrin GPIIb/IIIa–fibrinogen binding. Full article

Background and Clinical Significance: Hemophilia A presents a considerable challenge in cardiac surgery due to the elevated risk of perioperative bleeding, particularly during procedures involving cardiopulmonary bypass. Standard management typically involves standard half-life (SHL) factor VIII (FVIII) concentrates, which require frequent dosing. Extended half-life (EHL) FVIII products offer theoretical advantages, including prolonged action and reduced infusion frequency, but their use in cardiac surgery remains largely undocumented. Case Presentation: We report the case of a 73-year-old male with mild Hemophilia A who underwent successful aortic valve replacement using a 25 mm Carpentier-Edwards Magna Ease biological prosthesis. The patient was managed perioperatively with an anti-hemorrhagic protocol based on EHL recombinant FVIII. The surgery and postoperative course were uneventful, with no bleeding complications or need for transfusion. Conclusions: This case illustrates the potential role of EHL FVIII in safely managing hemophilic patients undergoing major cardiac surgery. Given the lack of existing reports in the literature, further studies are warranted to evaluate the efficacy and safety of EHL FVIII in this setting and to potentially optimize perioperative care protocols for this patient population. Full article

Background and Significances: In patients with Epstein–Barr virus-driven hemophagocytic lymphohistiocytosis (EBV-HLH), identifying the underlying cause poses a significant diagnostic challenge. HLH may precede overt disease, and early directed treatment for HLH can obscure histopathological findings. A liquid biopsy enables the detection of tumor-derived DNA from various sources, including cell-free DNA, circulating tumor cells, extracellular vesicles, and tumor-educated platelets, and might aid in this setting. Case Presentation: This case presents a young patient with EBV-HLH, in which genomic analysis of tumor-derived DNA from circulating tumor cells led to the diagnosis of an EBV-positive NK/T-cell lymphoma—where conventional tissue biopsies had failed. Conclusions: This report underscores the potential of the liquid biopsy as a valuable diagnostic tool in complex cases of EBV-HLH. Full article

Background/Objectives: The advent of tyrosine kinase inhibitors (TKIs) revolutionized the management of chronic myeloid leukemia (CML), achieving survival rates near those of the general population. Despite this success, prolonged therapy presents challenges, including physical, emotional, and financial burdens. Treatment-free remission (TFR), defined as sustained deep molecular response (DMR) after discontinuing TKIs, has emerged as a viable clinical goal. This study evaluates real-world data from the Canary Islands Registry of CML (RCLMC) to explore outcomes, predictors, and the feasibility of TFR. Methods: This retrospective observational study included 393 patients diagnosed with CML-CP between 2007 and 2023. Molecular response was monitored according to international guidelines. Survival probabilities were estimated using the Kaplan–Meier method. Logistic regression analysis was performed to identify predictors of molecular relapses after TKI discontinuation. Results: Of the 383 patients who received TKI treatment, 58.3% achieved molecular response grade 2 (MR2) (BCR-ABL1 ≤ 1%), 95.05% achieved MR2, and 50.5% reached MR4 within the first year. Of the 107 patients attempting TFR, 73.2% maintained remission at 36 months. Relapses occurred in 24 patients, all regaining molecular response upon reintroduction of TKIs. No cases of disease progression were observed. Conclusions: Our findings support the feasibility and safety of TFR in a real-world clinical setting for well-selected patients, with outcomes consistent with international studies. The study underscores the importance of molecular monitoring and patient-specific strategies to optimize outcomes. Full article

Background/Objective: Candidemia is a serious complication following intensive chemotherapy and is associated with high mortality in pediatric patients. This study aimed to identify the factors associated with 28-day mortality in pediatric patients with candidemia. Methods: We retrospectively analyzed 63 pediatric patients diagnosed with acute leukemia and candidemia following intensive chemotherapy. Clinical characteristics, laboratory findings, and epidemiological data were collected. Antifungal susceptibility data were available for 60 patients. Kaplan–Meier survival analysis was used to estimate the 28-day mortality rate, and Cox regression was performed to identify prognostic factors. Results: The 28-day mortality rate among the 63 patients (57.1% male, median age 9.74 years) was 36.5%. Candida tropicalis was the predominant species (96.8%). Antifungal susceptibility rates were 100% for amphotericin B and caspofungin and 22.2% for fluconazole. The factors independently associated with reduced 28-day mortality were an absolute lymphocyte count (ALC) ≥ 0.2 G/L at the time of candidemia diagnosis (5.3% vs. 50% mortality; hazard ratio [HR] = 0.08; 95% confidence interval [CI], 0.01–0.61), the use of antifungal prophylaxis (AFP) (26.3% vs. 52%; HR 0.31; 95% CI, 0.13–0.74), and granulocyte transfusion (GTX) combined with granulocyte colony-stimulating factor (G-CSF) (20% vs. 47.4%; HR = 0.31; 95% CI, 0.11–0.85). Conclusions: Our findings suggest that an ALC ≥ 0.2 G/L, AFP, and the administration of a GTX combined with G-CSF may be considered favorable prognostic factors. Full article

Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid malignancies. However, the extent of this oncogenic risk appears to vary between specific gene variants. Understanding the genotype–phenotype relationship is essential for patient counseling and management. This report presents a multigenerational family carrying the rare c.−118C > G variant in the 5′ untranslated region of ANKRD26, contributing to the discussion on variant-specific cancer predisposition. Case Presentation: Two sisters aged 57 and 60 presented with lifelong bleeding diathesis and moderate thrombocytopenia. Their symptoms included easy bruising, menorrhagia, and excessive postoperative bleeding. Genetic testing confirmed heterozygosity for the ANKRD26 c.−118C > G variant. Bone marrow analysis revealed abnormal megakaryopoiesis without evidence of dysplasia or somatic mutations. One sister underwent major surgery without complications when managed with prophylactic hemostatic therapy. Their family history included multiple female relatives with similar symptoms, although formal testing was limited. Notably, none of the affected individuals developed hematologic malignancy, and only one developed esophageal cancer, with no current evidence linking this variant to solid tumors. Conclusions: This case underscores the importance of distinguishing between ANKRD26 variants when assessing malignancy risk. While ANKRD26-RT is associated with myeloid neoplasms, the c.−118C > G variant may confer a lower oncogenic potential. Variant-specific risk stratification and genetic counseling are crucial for optimizing surveillance and avoiding unnecessary interventions in low-risk individuals. Full article