Search Results (108)

Immune checkpoint inhibitor-induced immune thrombocytopenia (ICI-ITP) is a rare but severe adverse event that may lead to bleeding complications and may require therapeutic changes or interventions. The clinical condition and interventions are highly complex; there are certainly tumour-type and combination-therapy differences, as well as individual ICI-agent factors that modify the risk of thrombocytopenia. ICI-ITP shares some common features, even though its pathogenesis differs markedly from that of traditional ITP. However, ICI-ITP is a clinically important complication; a deeper analysis of factors related to ICI–platelet interactions is also necessary. White blood cell–lymphocyte and platelet count ratios may have prognostic value in predicting the development of a low platelet count. Platelet counts themselves might influence the effectiveness of ICI-type anticancer interventions by facilitating T-cell-induced neoexpression of PD-1 on platelet surfaces. Baseline platelet counts and immunoglobulin levels may also modify treatment outcomes. Platelet activation can also promote immune-related adverse events. ICI-induced ITP-like syndrome’s prognostic factors are not only experimental facts but also clinically important. The connections among platelet counts, activation, immunoglobulins, and cell ratios are likely important factors influencing ICI-induced ITP risk reduction and the improvement of tumour-directed immune response by tailoring ICI selection to tumour type and specific baseline cellular characteristics. Full article

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced melanoma treatment but introduced unique immune-related adverse events (irAEs). Hematological irAEs (Hem-irAEs) are rare but carry disproportionately high morbidity and mortality. This review systematically synthesizes current literature to comprehensively understand the incidence, pathophysiology, clinical presentation, and management of Hem-irAEs in modern melanoma therapy. Methods: A comprehensive Web of Science literature search (January 2015 to January 2026) identified studies reporting hematological adverse events associated with melanoma immunotherapy and targeted therapies. After screening 2274 records, 130 relevant studies were included for quantitative data extraction, focusing on incidence rates and toxicity grading. Results: Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess staggering mortality rates between 12% and 15.5%. The most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia. Combination regimens significantly amplify toxicity frequency and severity. Diagnosis requires meticulous baseline monitoring and bone marrow biopsies to differentiate peripheral destruction from central marrow failure. First-line management mandates ICI discontinuation and high-dose corticosteroids, utilizing targeted second-line immunosuppressants for refractory syndromes. Conclusions: Hem-irAEs embody a profound clinical paradox: while mild toxicities often herald a robust anti-tumor response, severe hematological events drastically increase non-cancer mortality, negating these oncological benefits. Navigating this “double-edged sword” demands a paradigm shift toward proactive risk stratification. Integrating predictive biomarkers including baseline autoantibodies, Human Leukocyte Antigens (HLA) profiling, and systemic inflammatory indices is crucial to identify vulnerable populations before treatment. Optimizing outcomes requires highly personalized vigilance to balance the life-saving efficacy of immunotherapy against the catastrophic threat of hematopoietic failure. Full article

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory indices and their association with complications, mortality, treatment response, and relapse in patients with ITP. In this single-center retrospective study, 166 adult patients diagnosed with primary ITP between January 2015 and December 2024 were analyzed. Demographic, clinical, and laboratory data at diagnosis were collected. Inflammatory indices derived from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were evaluated. Their associations with clinical outcomes were assessed using appropriate statistical methods. During the observation period based on retrospective medical records, complications occurred in 12% of patients, and mortality was observed in 6.6%. Patients with complications had significantly higher D-dimer levels and reduced bone marrow megakaryocyte production. In group comparisons, mortality was significantly associated with advanced age, male sex, and comorbidities. Laboratory findings revealed that lower hemoglobin, lymphocyte count, mean platelet volume, and albumin levels, along with higher PLR, erythrocyte sedimentation rate, bilirubin, and D-dimer levels, were significantly associated with mortality. Inflammatory indices such as NLR and PLR were not associated with complication development, but PLR was significantly associated with mortality. Response to intravenous immunoglobulin (IVIG) therapy was significantly associated with higher total protein, albumin, and fibrinogen levels, and lower erythrocyte sedimentation rate. Relapse was significantly associated in group comparisons with increased inflammatory activity, higher reticulocyte count, and positivity for antinuclear antibodies and Helicobacter pylori antigen. Systemic inflammation and impaired megakaryopoiesis play critical roles in the prognosis of ITP. While conventional inflammatory indices showed limited predictive value for complications, markers such as PLR, D-dimer, and albumin were associated with mortality and clinical outcomes. These findings suggest that readily available laboratory parameters may provide valuable insights for risk stratification and personalized management in patients with ITP. Full article

Thrombopoietin receptor agonists (TPO-RAs) have become central second-line treatments for children with persistent or chronic immune thrombocytopenia (ITP). Their efficacy has encouraged broad use, but difficult-to-treat patients who respond suboptimally may be exposed to repeated agent switching, prolonged treatment, or doses exceeding approved limits. This commentary uses a focused narrative approach to address whether the risk of treatment-associated marrow fibrosis should be interpreted primarily as a consequence of treatment duration or as a risk marker linked to supraphysiological treatment intensity in non-responders. A recent Haematologica report by Ma and colleagues identified clinically significant bone marrow myelofibrosis in a highly selected cohort of children with chronic ITP undergoing marrow re-evaluation after suboptimal response or loss of efficacy during TPO-RA therapy. The most relevant message is not simply that fibrosis can occur, but that it was independently associated with treatment intensification, particularly overdose and frequent switching. The biological plausibility of this association is supported by the known capacity of sustained megakaryocytic stimulation to promote local pro-fibrotic signaling and reticulin deposition. This commentary places this safety concern in the context of pediatric ITP epidemiology, current regulatory indications, expert approaches to refractory disease, and practical surveillance considerations. TPO-RAs should not be viewed as routine treatment for newly diagnosed pediatric ITP; their principal role remains in selected children with persistent or chronic disease who require second-line therapy. Failure to respond at the maximum approved dose should prompt diagnostic and therapeutic reassessment rather than automatic treatment escalation. The emerging lesson is that response-adapted therapy must also be risk-adapted therapy. Full article

Thrombopoietin receptor agonists (TPO-RAs) have become an important component of pediatric immune thrombocytopenia (ITP) management, with growing evidence supporting their use in other hematologic disorders. We conducted a retrospective single-center study evaluating TPO-RA use at a pediatric oncohematology center in Poland between 1 January 2016, and 31 March 2026. Clinical indications, treatment patterns, efficacy, and safety outcomes were analyzed. Treatment response was defined as initial response (IR, platelet count [PLT] > 50 × 10⁹/L), complete response (CR, PLT > 100 × 10⁹/L), and sustained response (SR, PLT > 50 × 10⁹/L maintained in ≥75% of visits over 6 months). Thirty-five patients were included in the analysis. The most common indication was ITP (27/35, 77%), followed by severe aplastic anemia (5/35, 14%), poor graft function (2/35, 6%), and inherited platelet disorders (1/35, 3%). TPO-RA use increased over time, with more than half of patients (20/35, 57%) initiating therapy between 2024 and 2026. Overall IR, CR, and SR rates were 77%, 63%, and 61%, respectively, with a median time to response of 7 days (interquartile range [IQR], 7–12.5). TPO-RAs were increasingly used earlier in the disease course, including in rescue and off-label settings. Treatment was well tolerated, with only grade 1–2 adverse events reported. Our real-world data confirm the high efficacy and favorable safety profile of TPO-RAs in pediatric patients and support their expanding role in pediatric hematology beyond disease-specific indications. Full article

Background: The etiological diagnosis of chronic thrombocytopenia in children remains challenging and is often established by exclusion. In this article, we present the case of a patient in whom we used whole-exome sequencing (WES) to help identify the underlying cause and determine the appropriate treatment. Methods: Whole-exome sequencing was performed to clarify the genetic background of the disease. Based on the results, transmission electron microscopy (TEM) was also carried out to confirm or exclude the pathogenic role of the identified NBEAL2 gene variant and to assess the presence of gray platelet syndrome. Results: In this patient, despite the presence of the NBEAL2 gene variant, neither gray platelet syndrome nor a pathogenic role of the variant could be confirmed. However, the genetic findings identified by WES led to numerous additional investigations, causing a considerable burden on both the patient and the family. Conclusions: Our case highlights that WES testing, which is emerging in pediatric hematology practice, offers not only diagnostic advantages but also pitfalls. Whole-exome sequencing has recently emerged as a new diagnostic tool and has been available nationwide in pediatric hematology-oncology care in Hungary for just over two years. While personalized treatment strategies for benign hematologic diseases increasingly rely on high-throughput genetic testing, the clinical application of WES requires a cautious, critical evaluation of results. Despite the method’s promise, the heterogeneity of the findings underscores the need to interpret WES results carefully and to place them in a clinical context in every case. Full article

Background and Objectives: Thrombocytopenia complicates 6.6–11.6% of pregnancies. While gestational thrombocytopenia (GT) is usually benign, etiologies such as immune thrombocytopenia (ITP), preeclampsia, and HELLP syndrome require individualized management. This study aimed to characterize the etiological spectrum, maternal peripartum hematologic outcomes, blood product utilization, and mode of delivery in a tertiary-center cohort of thrombocytopenic pregnancies and to assess whether platelet count should influence delivery mode decisions. Materials and Methods: This retrospective cohort study included 137 thrombocytopenic pregnant women at a tertiary center (2010–2019), categorized by etiology and severity. Peripartum hemoglobin, hematocrit, and platelet counts were compared between delivery groups. Blood product utilization was recorded and analyzed using t-test, ANOVA, chi-square, Fisher’s exact, and Fisher–Freeman–Halton tests; binary logistic regression was used for multivariable analysis. Results: GT (43.1%) and ITP (32.1%) were the most prevalent diagnoses; cesarean delivery rate was 52.6%. Postpartum Hb was higher in the vaginal delivery group (10.24 ± 1.28 vs. 9.80 ± 1.26 g/dL; p = 0.003), while platelet counts were paradoxically lower (p = 0.039). Platelet transfusion rates did not differ significantly between delivery modes (23.1% vs. 27.8%; p = 0.621). Severe thrombocytopenia required platelet transfusion in 92.6% of cases versus 11.6% (moderate) and 0% (mild) (p < 0.001). RBC transfusion was highest in gestational hypertensive disease (41.2%) versus GT (5.1%) and ITP (2.3%) (p < 0.001). General anesthesia was used in 75% of cesarean cases. Conclusions: Delivery mode in thrombocytopenic pregnancies should be guided by obstetric indications, not platelet count alone. Although postpartum platelet counts declined more steeply after vaginal delivery, this did not increase transfusion requirements. Gestational hypertensive disorders carried the greatest hemorrhagic burden, highlighting the need for etiology-specific multidisciplinary planning. The high general anesthesia rate warrants prospective institutional audit of anesthetic decision-making protocols to determine adherence to current neuraxial anesthesia thresholds. This study is limited to maternal peripartum hematologic outcomes; neonatal outcomes were not captured and should be addressed in future prospective research. Full article

Immune thrombocytopenia (ITP) is an autoimmune disease. Megakaryocyte dysfunction caused by autoimmune response can lead to thrombocytopenia, and the underlying mechanism is still unclear. Single-cell sequencing analysis revealed the heterogeneity of CD34 + HSPCs in bone marrow between ITP patients and healthy groups. Pre-B cell population 1 (pre-B1) showed a significantly lower percentage contribution in ITP groups, and the underlying mechanism involves cell cycle-, cell apoptosis- and cell death-related pathways. The number of eosinophil–basophil mast cell progenitors (EBMPs) is significantly increased in ITP patients and the DEGs of the EBMPs in ITP patients were significantly enriched in immune-related pathways. Further, immunofluorescent staining and Western blot assay highlight C-X-C Motif Chemokine Ligand 8 (CXCL8) and Interferon Regulatory Factor 1 (IRF1) expression were significantly increased in the EBMPs of ITP patients. Furthermore, cell–cell communication analysis identified an impaired LGALS9-CD44 axis between EBMP cells and MkP1 cells in ITP patients, suggesting that targeting the LGALS9-CD44 interaction might hold promise as a therapeutic approach for ITP. Our observations indicate that ITP patients exhibit an elevated proportion of EBMP cells alongside a reduced proportion of pre-B1 cells. CXCL8 and IRF1 are potentially associated with EBMP cell dysfunction and the ITP disease process. Furthermore, the diminished LGALS9-CD44 axis between EBMP and MkP1 cells may contribute to ITP progression, suggesting a direction for future therapeutic investigation. Full article

Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article

Immune thrombocytopenia (ITP) is a hematological disorder commonly found in individuals of any gender, race, or age. Patients with ITP will present with thrombocytopenia either in a primary form or because of an infection or a dysfunction in the immune system. The severity of ITP is linked to diminished production of platelets due to the blockage of production in the bone marrow niche and increased destruction of platelets, which confirms the diagnosis of the disorder. The investigation of the pathogenesis of ITP is of critical importance as it can give an important indication of the state of the patient, guiding us through risk assessment and treatment. Proteomics can provide tools to explore the protein profile of ITP. In this review, we aimed to uncover different biomarkers, both diagnostic and prognostic, that have been investigated with proteomic methodologies and that might help in understanding the pathogenesis of ITP and providing personalized treatment to patients. Several differentially abundant proteins were identified, including haptoglobin isoforms, heat shock proteins (HSPA6, HSPA8), integrin β3 (ITGB3), 14-3-3 protein eta (YWHAH), vitamin D-binding protein, fibrinogen chains, MYH9, and FETUB, which are involved in key signaling pathways, such as PI3K/akt, TNF-a, and mTOR, and they demonstrate potential as diagnostic and prognostic biomarkers. Collectively, current data support the value of proteomics for uncovering the molecular landscape of ITP and guiding the development of precision diagnostics and personalized therapeutic strategies. Full article

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated platelet destruction, resulting in a platelet count below 100 × 10⁹/L and an increased risk of bleeding complications that significantly impair quality of life. Despite advances in ITP management, the unpredictable and heterogeneous nature of the disease continues to challenge treatment selection. This review compares the efficacy, safety, and mechanisms of action of Fostamatinib, Flebogamma DIF, and Romiplostim in adult and pediatric ITP patients. Peer-reviewed studies published over the past 20 years, including randomized and non-randomized clinical trials, observational studies, and real-world evidence, were screened for relevance, with data extracted on dosage, response rates, safety outcomes, and patient characteristics. The sample sizes varied across studies and were reported when available. Study quality and risk of bias were assessed using the ROBINS-I tools. Flebogamma DIF produced rapid increases in platelet count, although its effects were transient. Fostamatinib, the only oral spleen tyrosine kinase inhibitor approved for ITP, was reported to have demonstrated clinical benefit in adults with refractory disease but was contraindicated in pediatric populations. Romiplostim was reported to show sustained platelet responses and facilitate treatment-free remission, particularly in chronic ITP, with an elevated risk of thrombosis. Overall, these therapies offer distinct advantages depending on disease chronicity, patient age, comorbidities, and treatment history. This review underscores the importance of personalized treatment strategies and highlights the need for further long-term, comparative studies to guide evidence-based ITP management. Full article

Background: Pediatric-onset Evans syndrome (pES) is a rare autoimmune disorder defined by the coexistence or sequential development of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), frequently accompanied by autoimmune neutropenia (AIN) and characterized by a relapsing, multilineage course. Increasing evidence suggests that pES may represent a broader immune dysregulation phenotype rather than an isolated hematologic disorder. Methods: We conducted a retrospective, single-center study of children diagnosed with pES and followed for up to 13 years at a tertiary referral center. Clinical data regarding hematologic evolution, extra-hematological immunopathological manifestations, treatment requirements, infectious complications, and genetic findings were analyzed descriptively. Results: Six children (4 males) were included, with a median age at first cytopenia of 7 years (range 3–15) and a median follow-up of 8 years (range 1–13). ITP preceded AIHA in 3/6 patients (50%), one patient (16.7%) developed AIHA first, and two (33.3%) showed partial or evolving multilineage disease with DAT positivity prior to overt hemolysis. AIN occurred in 3/6 patients (50%). Extra-hematological immunopathological manifestations occurred in 5/6 patients (83.3%), with two (33.3%) developing more than one. Second-line therapy was required in 3/6 patients (50%). Infectious episodes occurred in 83.3% of patients, predominantly viral or mild bacterial infections, with no life-threatening events. Whole-exome sequencing performed in three patients identified a heterozygous TNFAIP3 variant of uncertain significance in one case; no pathogenic variants were detected. Conclusions: pES demonstrates clinical heterogeneity, frequent multilineage cytopenia, and substantial extra-hematological immune involvement. Multisystem manifestations may be associated with increased treatment burden. Long-term multidisciplinary monitoring and cautious interpretation of genetic findings are essential for individualized pediatric care. Full article

Key mechanisms underlying immune thrombocytopenia (ITP) pathophysiology include impaired platelet production and macrophage-mediated platelet destruction, the latter of which is the disease driver in more than half of patients. Traditional sequential treatment approaches achieve suboptimal responses in many patients. This review summarizes ITP pathogenesis and the treatment landscape and proposes a personalized treatment approach for ITP after first-line treatment (corticosteroids, intravenous immunoglobulin, anti-D therapy) based on targeting underlying disease mechanisms with immunomodulatory and bone marrow-supportive therapies (fostamatinib, rituximab, and thrombopoietin receptor agonists [TPO-RAs]) prior to proceeding to later-line therapies. Clinical evidence of monotherapy and real-world studies of combination therapy are reviewed to support mechanism-based treatment selection, focusing on the complementary actions of fostamatinib (to target platelet destruction) and TPO-RAs (to stimulate platelet production). In prior studies, fostamatinib with or without TPO-RAs demonstrated durable platelet responses and manageable safety as second-line or later ITP treatment. The proposed treatment framework augments guidelines by recommending fostamatinib, rituximab, or TPO-RAs as second-line therapy options based on patient-specific disease characteristics and risks. Patients with inadequate response to fostamatinib or TPO-RA monotherapy may combine these therapies to address both platelet destruction and platelet production deficits. This novel framework tailors therapy to patient-specific pathophysiology by preferentially targeting both impaired platelet production and increased platelet destruction to support individualized care. Full article

Background: Fas/FasL-mediated apoptosis is central to immune homeostasis and is implicated in autoimmune lymphoproliferative syndrome (ALPS) and immune thrombocytopenia (ITP). We aimed to compare whole-blood transcriptional levels of CASP8 and CASP3 across ALPS, chronic ITP, and healthy controls. Methods: CASP8 and CASP3 mRNA expression was quantified by real-time PCR in whole blood from clinically diagnosed ALPS patients, chronic ITP patients, and healthy controls. Results: CASP8 mRNA expression was significantly increased in ALPS and ITP versus controls (p = 0.0009 and p < 0.0001, respectively) and was lower in ALPS than in ITP (p = 0.0265). CASP3 mRNA was also increased in both patient groups versus controls (ALPS: p = 0.0045; ITP: p < 0.0001), with no significant difference between ALPS and ITP (p = 0.1692). Conclusions: ALPS and chronic ITP show distinct CASP8 transcriptional patterns and a shared upregulation of CASP3 at the whole-blood mRNA level. These findings are descriptive and do not directly assess caspase activation or apoptotic pathway activity; further protein- and cell subset-based studies are needed to clarify functional implications. Full article

Background/Objectives: Eltrombopag, a thrombopoietin receptor agonist, is widely used in the treatment of relapsed or refractory (R/R) immune thrombocytopenia (ITP). This study aimed to compare the efficacy, safety, and tolerability of generic eltrombopag (Rompag^®) with original eltrombopag (Revolade^®) in adult patients with R/R ITP. Methods: In this prospective, multicenter study conducted at 10 centers, 104 adult ITP patients were followed for at least 3 months. A total of 35 (33.7%) patients received Rompag^® and 69 (66.3%) received Revolade^®. The primary endpoint was platelet (PLT) response, defined as achieving a PLT count ≥50 × 10⁹/L and at least a twofold increase from baseline, without the need for rescue therapy or transfusion. Secondary endpoints included bleeding rates, fatigue-related quality of life, adverse events (AEs), and rescue therapy requirements. Results: PLT response was achieved in 94.2% of patients in the Revolade^® group and 85.7% in the Rompag^® group (p = 0.16). Bleeding rates decreased significantly in both groups (Revolade^®: 56.5% to 2.9%, p < 0.001; Rompag^®: 62.9% to 2.9%, p < 0.001). Although overall AE rates were similar (30.4% in the Revolade^® group and 42.9% in the Rompag^® group; p = 0.22), arthralgia (28.6% vs. 7.2%, p = 0.01) and vomiting (11.4% vs. 0%, p = 0.008) were more frequent with Rompag^®. Conclusions: Both generic and original eltrombopag demonstrated no statistically significant difference in efficacy in achieving PLT response, reducing bleeding, and improving fatigue-related quality of life in adult patients with R/R ITP. Although minor differences in AE profiles were observed, particularly arthralgia and vomiting, both formulations showed acceptable safety and tolerability. Full article