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Introduction: Hematopoietic stem cell transplantation (HCST) is a widely used therapy in the management of hematological malignancies, leading to cytopenias that require transient transfusions. Platelet recovery (PR) following HSCT is assessed by monitoring platelet count (PC). Immature platelet fraction (IPF) is a research parameter offered by Sysmex® on XN series analyzers, enabling rapid diagnostic orientation in the event of thrombocytopenia. It has also been described as a predictive factor for PR after chemotherapy or HSCT, and thresholds have been proposed., Methods: The objective of this study was to assess the predictive capability of IPF for PR in a prospective cohort of patients undergoing HSCT and to evaluate its utility in guiding platelet transfusion decision., Results: An optimized A-IPF (absolute number of IPF) threshold of 2.5 × 10 9 /L was predictive of a PC greater than 50 × 10 9 /L at day 30 with a sensitivity of 78.9%, specificity of 78.6%, positive predictive value (PPV) of 83.3% and negative predictive value (NPV) of 73.3%. We were able to distinguish patients recovering PC before day 15 with an earlier %IPF peak, greater IPF recovery kinetics and faster neutrophil recovery., Conclusion: A-IPF shows promise as a predictor of PR following HSCT. A multicenter study could help confirm both A-IPF and %IPF (IPF) clinical utility before it is made available to clinicians., (© 2024 The Author(s). International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

Background: The causes of acute febrile illness (AFI) in South India have been challenging to identify. As health care facilities in many endemic areas lack good laboratory support for the diagnosis of AFI, there is difficulty in ascertaining the causes of AFI, resulting in a delay in the initiation of treatment. This study aimed to evaluate the sensitivity and specificity of surveillance criteria and rapid diagnostic tests in the diagnosis of patients presenting with AFI and thrombocytopenia., Materials and Methods: Our study enrolled 225 participants presenting with AFI who fulfilled the predetermined inclusion and exclusion criteria. The study was conducted in the medical wards of YMCH from January 2018 to January 2019, after obtaining institutional ethics clearance. The patients were selected according to the inclusion criteria after obtaining informed consent. The collected data were analyzed using SPSS v23.0 operating on Windows 10 to determine the diagnostic characteristics, such as sensitivity and specificity of surveillance criteria and rapid diagnostic tests., Results: Our study enrolled 225 participants, with a majority (71.3%) falling within the 20-40 age range, and a significant male predominance. Around 68% of patients had a fever lasting <5 days. The clinical diagnosis was made using surveillance criteria in all 225 participants, of which 44% of cases were dengue, 35% were malaria, 12% were leptospirosis, and 7% were scrub typhus. However, when a definitive diagnosis was made using more specific tests (ELISA for dengue, leptospirosis, and scrub typhus; MP smear for malaria), it was found that 32% had dengue, 26% had malaria, 7% had leptospirosis, 5% had scrub typhus, 27% had undifferentiated fever, and 1.8% had coinfection. The overall accuracy of the surveillance criteria in diagnosing dengue is 66.37%, malaria is 76.91%, leptospirosis is 84.07%, and scrub typhus is 89.46%., Conclusion: This study validates the effectiveness of the surveillance case definition in identifying AFI with thrombocytopenia, demonstrating high sensitivity and moderate specificity. It should be followed by routine rapid diagnostic tests and more specific investigations to arrive at a definitive diagnosis of AFI., (© Journal of The Association of Physicians of India 2025.)

Background: Following the current guidelines, immunoassays for the diagnosis of heparin-induced thrombocytopenia (HIT) are interpreted dichotomously, with test results categorized as either positive or negative. However, the extent to which test results hold diagnostic significance across the entire dynamic range remains unclear., Objectives: We utilized data from the prospective towards precise and rapid diagnosis of heparin-induced thrombocytopenia study, comprising 1393 consecutive patients with suspected HIT, to assess the diagnostic significance of 2 heparin/platelet factor 4 immunoassay test results across their respective dynamic ranges: HemoSil Acustar HIT IgG (chemiluminescence immunoassay [CLIA]) and Lifecodes PF4 immunoglobulin G (enzyme-linked immunosorbent assay [ELISA])., Methods: HIT diagnosis was determined by a washed platelet heparin-induced platelet activation assay. For each measurement point in the dataset, we computed likelihood ratios (LRs), sensitivities, and specificities. To provide posttest probabilities for individual test results, we calculated interval-specific LRs and integrated them into a web-based calculator., Results: The prevalence of HIT was 8.5% (n = 119). An LR of ≥10 was first achieved at 0.3% of the dynamic range (0.4 U/mL; CLIA) and then at 16% (0.64 optical density; ELISA). An LR of ≥100 was present at 9.4% (12 U/mL; CLIA) and 75.0% (3.0 optical density; ELISA). The slope of the linear regression line (LR ∼ dynamic range) was 9.5 (CLIA) and 0.9 (ELISA)., Conclusion: Despite both immunoassays showing an association between results and diagnostic significance, the strength of the association varies by assay. CLIA has a larger increase per measurement unit. Posttest probabilities for individual patients can be estimated using a web-based calculator: https://pcd-research.shinyapps.io/BayesianCalculator/., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Heparin-induced thrombocytopenia (HIT) is an adverse reaction characterized by anti-PF4-heparin antibody generation and hypercoagulability. Imaging flow cytometry (IFC) provides a detailed morphological analysis of platelets, which change upon activation. We evaluated IFC-derived morphometric features to detect platelet activation and developed a functional assay for HIT diagnosis. We analysed blood samples from 42 patients with suspected HIT and extracted platelet size, shape and texture features using IFC. The morphological features were compared with CD62P expression, light transmission aggregometry (LTA) and a serotonin release assay (SRA) in terms of their ability to predict a HIT diagnosis. Five IFC-derived morphological features (area, circularity, contrast, diameter and major axis) significantly distinguished resting from activated platelets. The major axis feature performed best for HIT diagnosis, with a sensitivity of 89.3% and a specificity of 92.9% versus functional assays (LTA/SRA); this diagnostic performance was similar to that of CD62P expression on the same platelet donors. The area and diameter had similar specificity (92.9%) and a slightly lower sensitivity (85.7%). The morphological features associated with platelet activation might be effective markers for the diagnosis of HIT, matching platelet CD62P expression assay performance. The high-throughput IFC exploration of platelet activation offers new perspectives in label-free analysis and time-saving., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

MYH9-related disorders are a group of autosomal dominant disorders caused by mutations in MYH9, and are characterized by thrombocytopenia, sensorineural hearing loss, cataracts, and renal failure. Here, we report a case of chronic renal failure due to MYH9-related disorder with renal symptoms in a patient who underwent living-donor renal transplantation. The patient was diagnosed with proteinuria during a health checkup at the age of 12 years. Her renal function gradually deteriorated, and hemodialysis was initiated at 34 years of age. No definitive diagnosis of renal disease was made through renal biopsy. At the age of 35, she underwent living-donor renal transplantation from her mother as the donor. Six years after transplantation, her renal function remained stable, and no evidence of recurrent nephritis was found during renal biopsies. The family history revealed that her father, uncle, and younger brother had end-stage kidney disease. Genetic testing revealed a mutation (p.E1653D) related to the MYH9 gene. As her father had a history of renal biopsy and was diagnosed with focal segmental glomerulosclerosis (FSGS), we diagnosed chronic renal failure due to FSGS associated with MYH9 disorder. There were no findings suggestive of hearing loss, cataracts, or thrombocytopenia in the recipient or their family members with renal failure, and no symptoms other than renal failure were noted., Competing Interests: Declaration. Conflict of interest: The authors have declared that there are no conflicts of interest to declare. Informed consent: The study participants provided informed consent., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 10 9 /L. Whether this association occurs in patients with thrombocytopenia is unclear. Pacritinib, a JAK2/IRAK1/ACVR1 inhibitor, demonstrated improved SVR versus best available therapy (BAT [best available therapy]; including ruxolitinib) in patients with myelofibrosis and platelet counts ≤ 100 × 10 9 /L in the PERSIST-2 study. Patients on study at the start of the 12-week SVR window on pacritinib 200 mg twice daily or BAT were included. OS was evaluated among SVR responders versus non-responders using different SVR thresholds (≥ 35%, ≥ 20%, ≥ 10%, and > 0%). Among patients on pacritinib (n = 89), SVR ≥ 10% demonstrated the greatest separation in OS curves between responders and non-responders (HR, 0.00; 95% CI, 0.00-0.14; p < 0.01), though SVR ≥ 0% and SVR ≥ 20% were also associated with improved OS. No SVR threshold conferred OS benefit on BAT (n = 84), including ruxolitinib (n = 39). In patients with myelofibrosis and platelets ≤ 100 × 10 9 /L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: When haemolytic anaemia, thrombocytopenia and renal failure are present, a thrombotic microangiopathic (TMA) condition should be suspected. We describe the various differential diagnoses of primary TMA syndromes, their clinical findings, clinical workup and treatment., Case Presentation: A previously healthy man in his fifties was hospitalised with anaemia, thrombocytopenia, bilirubinaemia and acute renal failure. He was in good general condition without neurological symptoms. Due to suspicion of thrombotic microangiopathy (mainly thrombotic thrombocytopenic purpura (TTP)), he was referred to a university clinic for immediate plasma exchange. His renal failure deteriorated and haemodialysis was initiated. However, ADAMTS13 level was normal. Thus, complement-mediated thrombotic microangiopathy was suspected and eculizumab was administered. Due to previous abdominal discomfort a faecal sampling was performed, detecting enterohaemorrhagic E. coli (EHEC) DNA (Shigatoxin 2f). Hence, the diagnosis was Shigatoxin-induced haemolytic uraemic syndrome (ST-HUS). Supportive care was continued and renal function normalised., Interpretation: When thrombotic microangiopathy is suspected, an assessment is made whether to initiate plasmapheresis and immunomodulatory treatment. A thorough workup is needed to differentiate between the various primary TMA syndromes. Thus, treatment with expensive and possibly harmful drugs can be avoided. The various primary TMA syndromes have overlapping clinical features, and the diagnosis can be difficult.

Background: Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse drug reaction with numerous diagnostic challenges. Diagnosis of HIT begins with 4T score clinical assessment, followed by laboratory testing for those not deemed low risk. Laboratory testing for HIT includes screening [enzyme-linked immunosorbent assay (ELISA)] and confirmatory [serotonin release assay (SRA)] assays, wherein SRA testing can be pursued following a positive ELISA result. These tests aid diagnosis of HIT, but also introduce interpretive challenges, additional costs, and delays in clinical intervention., Methods: A retrospective review of 1011 HIT ELISA and 169 SRA tests performed over 5 years was conducted. ELISA percent inhibition and ELISA low-heparin optical density (OD) were evaluated for positive predictive value (PPV). Based on these findings, HIT ELISA reporting and management algorithm changes were implemented and metrics compared for 5 months pre- and post-intervention to assess intervention success., Results: Equivocal and positive HIT ELISA interpretation showed poor PPV based on percent inhibition (0.20 and 0.32, respectively). However, rising low-heparin OD correlated with increasing PPV (PPV of 0.00 for OD values 0.40-1.00, 0.29 for values 1.00-1.99, and 0.91 for values >2.00). Data-driven intervention decreased ELISA positivity rates (13% to 5%), decreased rates of SRA confirmatory testing overall (13% to 9%), decreased SRA testing rates for patients with non-negative ELISAs (78% to 43%), and increased heparin resumption (20% to 57%). Hematology consults remained relatively stable (78% and 86%)., Conclusions: Low-heparin OD-based HIT ELISA interpretation yielded enhanced PPV compared with percent inhibition-based interpretation. Implementation of data-driven changes improved testing stewardship and clinical management for patients with non-negative ELISAs., (© Association for Diagnostics & Laboratory Medicine 2025.)

Constitutional platelet disorders have become better understood since Bernard and Soulier first described a case in 1948. Their diagnosis can also be challenging due to overlap in clinical presentation and lab findings with platelet type von Willebrand. Bernard-Soulier syndrome is a disorder caused by GPIb receptor mutations that decrease its affinity for von Willebrand factor resulting in reduced platelet function and macrothrombocytopenia. It is associated with multiple genetic mutations in either GPIBA, GPIBB, GP9, or GP5. We present a case report of a family with a Bernard Soullier-like thrombocytopenia variant due to a heterozygous missense mutation in GPIBA., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Primary Sjogren's syndrome (pSS) typically presents with Sicca symptoms xerostomia and xeropthalmia. This study highlights atypical presentations of Primary Sjogren's syndrome posing diagnostic and therapeutic challenges. Four female patients (median age 30 years, IQR = 15.5) with atypical pSS features, confirmed by positive Anti-Ro antibodies and negative lupus or rheumatoid arthritis tests, were treated between February and August 2023. PSS presented as erythema nodosum, soft tissue swelling with medium-vessel vasculitis, palpable purpura, and severe thrombocytopenia in these cases prior to Sicca symptoms. Initial treatment included steroids and hydroxychloroquine. Azathioprine, Methotrexate, and Cyclophosphamide were added as steroid-sparing agents. Three patients achieved remission. One patient with co-existing pulmonary tuberculosis (TB) died. Atypical features can occur in SS, requiring vigilance for diagnosis and individualised treatment. Our series demonstrates the diverse atypical clinical features of Sjogren's syndrome, encompassing radiologic, histopathologic, laboratory abnormalities, and treatment guidelines, expanding the known spectrum of disease presentation and management.

Recognizing anemia and thrombpenia in acute and emergency medicine is easy. Acute (microangiopathic hemolytic) anemia and thrombopenia can be a sign of thrombotic microangiopathy (TMA). TMA syndromes are potentially life-threatening diseases. Diagnosing a TMA syndrome, causal differentiation and treatment require specialist knowledge that is not always available in acute and emergency medicine. Many differential diagnoses and examinations are usually necessary to make a correct diagnosis. Therefore, a standardized diagnostic algorithm is helpful for early diagnosis and treatment initiation., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: Gemäß den Richtlinien des Springer Medizin Verlags werden Autoren und Wissenschaftliche Leitung im Rahmen der Manuskripterstellung und Manuskriptfreigabe aufgefordert, eine vollständige Erklärung zu ihren finanziellen und nichtfinanziellen Interessen abzugeben. Autoren: S. A. Potthoff: A. Finanzielle Interessen: Referent: Sanofi-Aventis Deutschland GmbH, Alexion Pharma Germany GmbH. – Beratung: Sanofi-Aventis Deutschland GmbH, Beratung, Interne Schulung: Alexion Pharma Germany GmbH. – B. Nichtfinanzielle Interessen: Mitgliedschaft: DGIM. Wissenschaftliche Leitung: Die vollständige Erklärung zum Interessenkonflikt der Wissenschaftlichen Leitung finden Sie am Kurs der zertifizierten Fortbildung auf www.springermedizin.de/cme . Der Verlag: erklärt, dass für die Publikation dieser CME-Fortbildung keine Sponsorengelder an den Verlag fließen. Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2025. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)