Mutations in calreticulin have been identified as driver mutations in BCR-ABL1-negative myeloproliferative neoplasms (MPNs) and are especially important for diagnostics and prognosis in primary myelofibrosis and essential thrombocythemia. The vast majority of pathogenic variants are insertions or deletions in exon 9 that result in a mutant C-terminal sequence that activates the signaling of the thrombopoietin receptor, which in turn promotes megakaryocytic proliferation. This review examines the potential clinical utility of calreticulin mutations as laboratory biomarkers in essential thrombocythemia (ET) and primary myelofibrosis (PMF). It emphasizes their role in confirming clonality in JAK2/MPL-unmutated cases, distinguishing a clonal myeloproliferative disease from reactive thrombocytosis, clarifying the molecular interpretation, and guiding molecular diagnostic workflows. Special focus is placed on practical laboratory challenges, such as choosing assays, detecting rare and non-canonical variants in exon 9, analytical sensitivity, molecular reporting, and the integration of bone marrow morphology, cytogenetics, co-mutations, and next-generation sequencing. Overall, clinical information gained from calreticulin testing is greatest when it is used in an integrated clinicopathologic and molecular testing context rather than as a standalone test. To make calreticulin mutations more effectively used for diagnosis or prognosis in routine hematology practice, we need standardization of testing, harmonization of reporting, and prospective validation of risk-models based on both the subtypes and the burden of the mutation.

We report a 51-year-old female with rheumatoid arthritis (RA) on long-term methotrexate, hydroxychloroquine, and sulfasalazine, who self-administered multiple medications, including diclofenac 50 mg, without medical supervision. She presented with acute-onset shortness of breath, generalized pruritus, angioedema, and palpitations, and was found to be in severe anaphylaxis with cardiovascular collapse, with a blood pressure of 60/nil mmHg and a heart rate of 143 beats per minute. Diclofenac was considered the most likely trigger based on temporal association and known nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity risk; however, causality cannot be definitively proven as several medications were taken within the same exposure window. Investigations revealed leukocytosis, microcytic anemia, reactive thrombocytosis, and elevated alkaline phosphatase. The electrocardiogram showed no ischemic ST-segment changes or conduction abnormalities. Prompt resuscitation with intramuscular epinephrine resulted in hemodynamic stabilization within 15 minutes of the first dose, with complete angioedema resolution within 30 minutes. The patient was managed without intensive care unit admission and discharged in stable condition on day three. This case highlights the diagnostic and management challenges of severe hypersensitivity reactions occurring in the setting of polypharmacy and emphasizes the importance of individualized analgesic planning and careful medication counseling in patients with RA receiving chronic therapy.

This review characterizes VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) as a prototype of adult-onset autoinflammation that challenges traditional autoimmune paradigms. Driven by constitutive activation of innate myeloid cells via Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1) mutations, VEXAS affects the nervous system in approximately 6-10% of cases. We identify the peripheral nervous system as the primary target (70%), typically manifesting as refractory axonal polyneuropathy, while central involvement may present as neutrophilic meningoencephalitis. Crucially, we highlight the "hematologic paradox"-hyperinflammation co-occurring with macrocytic anemia rather than thrombocytosis-as the key biomarker distinguishing VEXAS from vasculitic mimics, necessitating early genetic sequencing for targeted clone suppression.

Lipid-lowering drugs are currently widely used by clinicians in clinical practice; numerous related studies have confirmed the pivotal role of the lipid pathway in regulating platelet function. Lipid-lowering drugs, represented by statins, have been found to have an improving effect on platelet-related diseases. However, there is a lack of large-scale population studies at present, and the causal explanation of traditional observational design studies is easily limited by confounding variables. The impact of lipid-lowering drugs on the risk of essential hemorrhagic thrombocythemia is not clearly understood. Our study sought to investigate the causal association between essential hemorrhagic thrombocythemia and lipid-lowering drugs through a drug-target Mendelian randomization (MR) analysis. We utilized the data from the Global Lipid Genetics Consortium to identify instrumental variables for 3 types of lipid-lowering drugs (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and NPC1-like intracellular cholesterol transporter 1 [NPC1L1] inhibitors). We obtained the genome-wide association study data for essential hemorrhagic thrombocythemia from the FinnGen study. We employed the MR method based on aggregated data and the inverse variance weighted method for the analysis. Sensitivity analyses were conducted using the conventional MR method. By analyzing data from 1171 patients with essential hemorrhagic thrombocythemia and about 1.3 million individuals with low-density lipoprotein (LDL) testing, PCSK9 inhibition was associated with a significantly increased risk of essential hemorrhagic thrombocythemia (odds ratio [OR], LDL ratio of 1.87 for every 1 standard deviation increased; 95% confidence interval [CI] = 1.2-2.91; P = .02). NPC1L1 inhibition was associated with a reduced risk of essential hemorrhagic thrombocythemia (OR, LDL 0.19 for every 1 standard deviation reduction; 95% CI = 0.05-0.73; P = .03). No association was found between 3-hydroxy-3-methylglutaryl-CoA reductase inhibition and essential hemorrhagic thrombocythemia (OR = 0.76, 95% CI = 0.34-1.69, P = .51). The results of this MR study suggest that NPC1L1 inhibition is causally associated with a reduction in primary hemorrhagic thrombocythemia, whereas PCSK9 inhibition was positively correlated with the occurrence of the disease, which provided a new clue for the future treatment of essential hemorrhagic thrombocythemia.

Sickle cell disease (SCD) is a complex thrombo-inflammatory disorder in which haemolysis, platelet activation, thrombocytosis, inflammation and endothelial activation operate as an intricate network creating a perpetual cycle of cellular injury and vascular dysfunction that drives vaso-occlusive crises, tissue ischaemia and progressive end-organ damage. Thrombocytosis is common in SCD, especially in response to acute chest syndrome, vaso-occlusive crises and chronic haemolysis. Increased platelet activity contributes to the proinflammatory and prothrombotic environment. Activated platelets release platelet-derived microparticles (PMPs) containing phospholipids and inflammatory mediators, which enhance thrombin generation, entrap leucocytes and promote cellular adhesions leading to endothelial dysfunction and vaso-occlusion within the microvasculature. This review provides insights into the mechanisms underlying thrombocytosis and PMP formation in SCD and discusses therapeutic strategies targeting platelet activation to mitigate inflammation and vascular complications.

Primary Epstein-Barr virus (EBV) infection in children exhibits substantial clinical heterogeneity, often complicating early diagnosis and leading to unnecessary antibiotic use. This retrospective study evaluated 695 children (0-18 years) diagnosed with primary EBV infection at a tertiary pediatric center between 2010 and 2015, defined by positive viral capsid antigen (VCA) IgM and negative Epstein-Barr nuclear antigen (EBNA) IgG. Clinical, laboratory, and ultrasonographic findings were compared according to age group (≤4 vs. >4 years) and clinical setting (inpatient vs. outpatient). The median age was 3.75 years (IQR: 2-6.25), and more than half of the patients were ≤4 years. Younger children more frequently presented with nonspecific respiratory and gastrointestinal symptoms, whereas older children more commonly exhibited the classic infectious mononucleosis (IM) phenotype, including sore throat, dysphagia, lymphadenopathy, and hepatosplenomegaly (p < 0.001). Antibiotics were prescribed in 64.2% of patients, while 21.7% required hospitalization. Multivariable logistic regression analyses demonstrated that age was not an independent predictor of hospitalization, classic IM phenotype, or antibiotic use. Instead, specific clinical and laboratory findings-such as lymphopenia, lymphadenopathy, vomiting, thrombocytosis, and tonsillar hypertrophy-emerged as the key determinants of clinical outcomes. To enhance diagnostic discrimination, receiver operating characteristic (ROC) analysis of ANC/ALC and AST/ALT ratios was performed, and a composite risk score (0-2) was derived. Although both markers showed modest discriminative ability (AUC 0.607 and 0.575), their high negative predictive values (>90%) suggest potential utility as rule-out tools. The composite score demonstrated a stepwise increase in the probability of classic IM presentation across age groups. In conclusion, primary EBV infection demonstrates a clear age-related clinical spectrum; however, clinical and laboratory features rather than age alone drive key outcomes. These findings highlight the need for age-specific diagnostic strategies and improved antimicrobial stewardship, while the proposed risk score provides a foundation for future validation studies.

Background/Objectives: Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals, with a highly heterogeneous clinical presentation encompassing both intestinal and extraintestinal manifestations. Despite growing clinical awareness, diagnostic delay remains a significant challenge, and the evolution of clinical and histopathological features following gluten-free diet (GFD) initiation remains incompletely characterized. This study aimed to compare the clinical, serological, and histopathological profile of adults with newly diagnosed CD and those maintained on a long-term GFD. Methods: This prospective observational study enrolled 50 adult patients with biopsy-confirmed CD: 16 at the time of diagnosis (gluten-consuming) and 34 on a GFD for at least one year. All participants underwent standardized clinical assessment, serological testing (IgA anti-tissue transglutaminase [tTG] and/or IgA anti-endomysial antibodies [EMAs]), upper digestive endoscopy with duodenal biopsies graded according to the Marsh-Oberhuber classification, and evaluation for Helicobacter pylori co-infection. Between-group comparisons were performed using the Mann-Whitney U test, Fisher's exact test, and chi-square test, as appropriate. Results: Newly diagnosed patients exhibited a significantly longer median duration from symptom onset to diagnosis compared to the GFD group (p = 0.03). Histopathological severity was greater in the newly diagnosed group, with more advanced Marsh-Oberhuber grades (p = 0.03). Among individual symptoms, bloating was significantly more frequent in newly diagnosed patients (p = 0.02). Notably, thrombocytosis was identified significantly more often in the newly diagnosed group compared to GFD patients (p = 0.02), representing a potentially underrecognized extraintestinal marker of active CD. Overall rates of intestinal and extraintestinal manifestations and CD-specific seropositivity did not differ significantly between groups. Conclusions: The clinical and histopathological profile of adults with celiac disease differs meaningfully between the time of diagnosis and during GFD adherence. Bloating and thrombocytosis were significantly more prevalent at diagnosis, with thrombocytosis emerging as a potentially underrecognized marker of active disease. Conversely, several manifestations persisted despite dietary treatment, underscoring the heterogeneous nature of CD across its clinical course. These findings may support earlier disease recognition and more individualized follow-up strategies in routine clinical practice.

We present the case of a woman in her early nineties who was admitted after recurrent falls and a short history of respiratory symptoms. She was diagnosed with influenza A lower respiratory tract infection (LRTI) complicated by hospital-acquired pneumonia (HAP). Despite clinical and radiological recovery, inflammatory markers remained persistently elevated, including neutrophilic leucocytosis, thrombocytosis, and elevated C-reactive protein (CRP), without residual symptoms or objective evidence of infection. Extensive investigation and multidisciplinary input failed to identify an infective, autoimmune, or malignant cause. This case illustrates the challenge of interpreting persistent biochemical abnormalities in older adults, highlights the importance of clinical context, and cautions against over-investigation and unnecessary antibiotic use in asymptomatic patients.

A 29-year-old primigravida woman (G1P0) with a BMI of 35.2 presented at 38+3 weeks with severe edema extending from lower abdomen to her thighs, and vulval edema predominantly right-sided, and associated with difficulty mobilizing. Her BP was 160/94 mmHg. She had a prior diagnosis of gestational hypertension that progressed to preeclampsia.