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Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with 'triple-negative thrombocytosis', we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology ('myeloproliferative neoplasm-definite/probable', 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real-world 'triple-negative' ET diagnosis currently depends heavily on histology; we advocate caution in MGP-negative cases and that specific guidelines are needed., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Context.—: In the Sysmex DI-60 digital morphology system, a platelet estimate factor (PEF) is used to calculate the estimated platelet count (PLT)., Objective.—: To determine the most accurate PEF by analyzing various specimens, including those with abnormal flag alerts, using both impedance (PLT-I) and optical fluorescent (PLT-F) PLT methods. A validation study was then conducted using random specimens to evaluate the accuracy of the PEF., Design.—: This study included 120 blood specimens without flag alerts, and 120 blood specimens with flag alerts related to platelet abnormalities to determine the PEF. Each group was equally divided into thrombocytopenia, normal count, and thrombocytosis specimens. The PEF values obtained from the PLT-I and PLT-F methods were analyzed. An additional 120 specimens were used to compare the estimated PLT from PEF with the PLT-F count. Unadjusted PEF disregarded platelet ranges and flag alerts, whereas adjusted PEF incorporated them., Results.—: The mean PEF values ranged within 9.95 to 12.99 for PLT-I-obtained values (PEF-I) and within 10.32 to 11.69 for PLT-F-obtained values (PEF-F) across different PLT ranges. The mean PEF values were significantly higher in specimens with flags compared with those without flags. The values were 12.43 compared with 10.19 for PEF-I and 11.45 compared with 10.4 for PEF-F. A significant difference was found between PEF-I and PEF-F in flagged specimens, with respective values of 12.43 and 11.45. There was excellent agreement between estimated PLTs using adjusted PEF and PLT-F. However, proportional biases were observed between estimated PLT using unadjusted PEF and PLT-F., Conclusions.—: Adjustment of PEF values according to specific platelet ranges and flag alert presence was shown to enhance the accuracy of PLT estimation using the Sysmex DI-60 system., Competing Interests: The author has no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: The most ordered laboratory test worldwide is the complete blood count (CBC)., Content: In this primer, an introduction to platelet testing in the context of the CBC is provided with a discussion of the laboratory evaluation of platelet abnormalities including thrombocytopenia and thrombocytosis., Summary: As clinical chemists continue to be tasked to direct laboratories outside of the traditional clinical chemistry sections such as hematology, expertise must be developed. This primer is dedicated to that effort., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This case report describes a case of pseudonormokalemia, true hypokalemia. Often, only laboratory values outside the normal range gain attention and false normal results are at risk of not being noticed. However, a disease state may be masked by another pathological process. Here, a 50-year old male was admitted to the Department of Internal Medicine due to sepsis from a dental infection. Initially, serum potassium measurement revealed a normal value of 4 mmol/L (reference interval 3.8-5.1 mmol/L). Thrombocyte number was above 500x10 9 /L. Due to our policy to recommend a repeated measurement of potassium in whole blood or heparin plasma if a patient has thrombocytosis, pseudonormokalemia was identified because the heparin plasma potassium value was only 2.9 mmol/L (reference interval 3.5-4.8 mmol/L). The physiological difference between serum and plasma concentration is no more than 0.3 mmol/L. In this case, potassium concentration were falsely elevated in the serum sample, probably caused by the high number of platelets releasing potassium during clotting. Interpretative comments in patients with thrombocytosis over 500x10 9 /L recommending plasma potassium measurement are helpful. The best way to eliminate pseudohyperkalemia and pseudonormokalemia phenomena caused by thrombocytosis is to completely change towards heparin plasma as the standard material., Competing Interests: Potential conflicts of interest None declared, (Copyright Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Platelet counts in reactive thrombocytosis rarely exceed 1000 × 10 9 /L. We present the case of a male patient, aged 80 years, with quiescent rheumatoid arthritis who was found to have a platelet count of 1011 × 10 9 /L on routine laboratory testing. The patient was initially asymptomatic but developed leukocytosis to 23.1 × 10 9 /L on hospital day 2. Diagnostic work-up revealed obstructive nephrolithiasis and pyelonephritis, and the thrombocytosis and leukocytosis gradually resolved with empiric antibiotic treatment and ureteral stent placement. Tests for myeloproliferative disorders, including JAK-2V617F mutation, BCR-ABL for chronic myeloid leukemia and acute lymphocytic leukemia, and myeloproliferative neoplasms (MPL/CALR), were negative. Physicians should be aware that in rare cases reactive thrombocytosis can exceed 1000 × 10 9 /L, and that markedly elevated platelet counts in the setting of urinary tract infections may be an early sign of obstructive uropathy., (Copyright © 2024 Marshfield Clinic Health System.)

Overview: Essential thrombocythemia is a Janus kinase 2 (JAK2) mutation-prevalent myeloproliferative neoplasm characterized by clonal thrombocytosis; clinical course is often indolent but might be interrupted by thrombotic or hemorrhagic complications, microcirculatory symptoms (e.g., headaches, lightheadedness, and acral paresthesias), and, less frequently, by disease transformation into myelofibrosis (MF) or acute myeloid leukemia., Diagnosis: In addition to thrombocytosis (platelets ≥450 × 10 9 /L), formal diagnosis requires the exclusion of other myeloid neoplasms, including prefibrotic MF, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes with ring sideroblasts and thrombocytosis. Bone marrow morphology typically shows increased number of mature-appearing megakaryocytes distributed in loose clusters., Genetics: Approximately 80% of patients express myeloproliferative neoplasm driver mutations (JAK2, CALR, MPL), in a mutually exclusive manner; in addition, about 50% harbor other mutations, the most frequent being TET2 (9%-11%), ASXL1 (7%-20%), DNMT3A (7%), and SF3B1 (5%). Abnormal karyotype is seen in <10% of patients and includes +9/20q-/13q-., Survival and Prognosis: Life expectancy is less than that of the control population. Median survival is approximately 18 years but exceeds >35 years in younger patients. The triple A survival risk model, based on Age, Absolute neutrophil count, and Absolute lymphocyte count, effectively delineates high-, intermediate-1-, intermediate-2-, and low-risk disease with corresponding median survivals of 8, 14, 21, and 47 years., Risk Factors for Thrombosis: Four risk categories are considered: very low (age ≤60 years, no thrombosis history, JAK2 wild-type), low (same as very low but JAK2 mutation present), intermediate (same as low but age >60 years), and high (thrombosis history or age >60 years with JAK2 mutation)., Mutations and Prognosis: MPL and CALR-1 mutations have been associated with increased risk of MF transformation; spliceosome with inferior overall and MF-free survival; TP53 with leukemic transformation, and JAK2V617F with thrombosis. Leukemic transformation rate at 10 years is <1% but might be higher in JAK2-mutated patients with extreme thrombocytosis and those with abnormal karyotype., Treatment: The main goal of therapy is to prevent thrombosis. In this regard, once-daily low-dose aspirin is advised for all patients and twice daily for low-risk disease. Cytoreductive therapy is advised for high-risk and optional for intermediate-risk disease. First-line cytoreductive drugs of choice are hydroxyurea and pegylated interferon-α and second-line busulfan., Additional Content: The current review includes specific treatment strategies in the context of extreme thrombocytosis, pregnancy, splanchnic vein thrombosis, perioperative care, and post-essential thrombocythemia MF, as well as new investigational drugs., (© 2024 Wiley Periodicals LLC.)

Abstract: Acute megakaryoblastic leukemia (AML-M7) is rarely seen in adult patients and patients usually present with cytopenias. Here we discuss diagnostic challenges and pathologic features in a patient with AML-M7 who presented with thrombocytosis and diarrhea. A 63-year-old male patient presented with persistent diarrhea lasting for 2 months, fatigue, and thrombocytosis. The diagnostic workup included a stool analysis, endoscopy colonoscopy, and imaging studies; however, these studies did not reveal any possible etiology. The hematologic evaluation included peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry, and cytogenetic analysis. Eventually, according to pathologic and flow cytometric findings, a diagnosis of AML-M7 was made. Diagnosis of AML-M7 may be challenging, especially in adult patients with atypical presentation. Patients with megakaryoblastic leukemia respond poorly to standard induction regimens and they should be advised to participate in a clinical trial., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Hydroxyuria is a common medication for treating blood system diseases, but ulcers in the lower limbs caused by this medication are often rare and not often suspected. We reported an elderly patient with lower limb ulcers caused by hydroxyurea treatment for primary thrombocytosis. When hydroxide is used, close observation of skin lesions and prompt handling of any skin disruption should prevent ulcers., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Platelet count increases are typically a reactionary response to one of a variety of pathophysiological events. We present here a case of microcytic hypochromic red blood cells and thrombocytosis in an adolescent female that we have monitored for three years. The patient was positive for alpha thalassemia trait; negative for mutation in Janus kinase 2, calreticulin, or myeloproliferative leukemia virus oncogene; and negative for reactive causes of thrombocytosis. Noticeably, a variant in atypical chemokine receptor 1 ( ACKR1 ) (c.-67T>C, rs2814778) was found to be homozygous. Accordingly, the case was diagnosed as idiopathic thrombocytosis, and treatment was given to restore platelet levels to normal. Our findings highlight the possibility of an unknown association between alpha thalassemia trait and idiopathic thrombocytosis in the presence of ACKR1 mutation, which could be implicated in disease pathogenesis., (© 2024 by the Association of Clinical Scientists, Inc.)

A 66-year-old male presented with hypereosinophilia, thrombocytosis, extensive thrombosis refractory to direct oral anticoagulant therapy, and evidence of end-organ damage, including rash, splenic infarcts, and pulmonary infiltrates. Bone marrow biopsy revealed myeloid malignancy consistent with both chronic eosinophilic leukemia and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with SF3B1 mutation and thrombocytosis. Next-generation sequencing of the patient's eosinophils and neutrophil compartments revealed pathologic variants in EZH2 and SF3B1 in addition to a noncanonical JAK2 R683S mutation that has not been previously described in myeloproliferative disorders or other chronic myeloid neoplasms. These mutations were not present in the patient's lymphoid cell fraction, suggesting that the hematopoietic malignancy arose in a myeloid-committed progenitor cell. Based on this case and previous work from our group, we propose that noncanonical JAK2 mutations may permit signal transduction that biases toward eosinophilic differentiation in chronic myeloid neoplasms. Although the patient's blood counts initially responded to ruxolitinib and hydroxyurea, the response was not durable. Early referral for allogenic bone marrow transplant appears necessary to prevent long-term complications and disease progression in myeloid neoplasms with clonal hypereosinophilia driven by noncanonical JAK2 mutations.

This case report presents the clinical evaluation and management of a female patient from a rural background who presented with leg pain, headache, weakness and irritability. Initial investigations revealed iron deficiency anaemia accompanied by a significantly elevated platelet count, prompting suspicion of an underlying myeloproliferative neoplastic disorder. However, subsequent genetic testing ruled out these mutations, suggesting a reactive response to iron deficiency anaemia rather than an independent neoplastic process. Treatment was focused on addressing the underlying iron deficiency anaemia, resulting in significant improvement in the patient's blood profile and resolution of symptoms. Follow-up assessments demonstrated a complete normalisation of the blood profile and platelet counts, further supporting the efficacy of the treatment. This case highlights the importance of considering reactive thrombocytosis in the context of iron deficiency anaemia and emphasises the favourable response achieved through appropriate management strategies., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND Essential thrombocytosis (ET) is a myeloproliferative neoplasm variant that leads to excessive platelet production in the bone marrow. Janus kinase 2 (JAK2) mutation is observed in 60% of ET cases. The risk of thrombosis increases with the presence of this mutation. ET can cause systemic thrombosis, including extra-portal vein thrombosis (EHPVT). In patients with ET-induced EHPVT, varied symptoms generally occur. However, our case was asymptomatic. This condition is relatively rare. CASE REPORT A 49-year-old woman presented to our hospital for a detailed clinical examination 1 month after a health examination, and blood tests revealed microcytic anemia and thrombocytosis. The patient had no current concerns and had no relevant medical or alcohol consumption history. Esophagogastroduodenoscopy demonstrated esophageal varices, with portal hypertension suspected as the underlying cause. Contrast-enhanced computed tomography scans revealed a thrombus in the portal vein, but liver cirrhosis and a tumor were ruled out. JAK2 mutation was positive, which led to myeloproliferative neoplasms being considered as the differential diagnosis. Bone marrow biopsy demonstrated many mature megakaryocytes with large and irregular nuclei and platelet aggregation in the field of view, leading to the diagnosis of ET. CONCLUSIONS This case study describes a patient with EHPVT caused by JAK2-positive ET. This case report emphasizes that physicians should consider myeloproliferative neoplasms as part of their differential diagnosis when presented with EHPVT.

Introduction: The management to reduce risk of thromboembolic complications in polycythemia vera and essential thrombocythemia are well established, but for other conditions with elevated hemoglobin, hematocrit, or platelets there are no consensus regarding treatment and follow up., Aims: To assess frequency of elevated blood values in patients with thromboembolic event, how many of these should be investigated further regarding myeloproliferative neoplasm and if the risk of recurrent event is depending on underlying condition., Methods: Retrospective cohort study of 3931 adult patients in the county of Norrbotten, Sweden, with thromboembolism during 2017 and 2018., Results: Of the 3931 patients, 1195 had either elevated Hb, HCT, or platelets fulfilling the 2016 revised WHO criteria for PV and ET, and out of these 411 should be evaluated regarding underlying myeloproliferative neoplasms. Unexplained thrombocytosis and secondary erythrocytosis were associated with the highest rate of recurrent event as well as the most inferior restricted mean survival time., Conclusion: Elevated blood values are common in patients with thromboembolic event and the high risk of recurrent event and inferior restricted mean survival time in patients with unexplained thrombocytosis and secondary erythrocytosis implicates the importance of finding and managing the underlying condition., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objective: We aimed to investigate the frequency and causes of thrombocytosis in patients admitted to the Department of Pediatric Hematology and Oncology of Elazig Fethi Sekin City Hospital, Elazig, Turkey., Methods: Between 2019 and 2021, the laboratory parameters of 2,500 patients admitted to the Hematology Department were studied. During this examination, 319 (12.76%) patients were found to have thrombocytosis. Demographic characteristics (age and gender), hematologic parameters (hemoglobin, white blood cells, and platelets), and ultimate diagnoses ot the cases were recorded from their files., Results: Of these 319 patients with thrombocytosis, 197 (1.8%) were male and 122 (38.2%) were female, and the mean age was 72.0±69.0 (1-216) months. The median platelet count of the patients was 590.43±280.12/μL (450,000-750,000). The most common cause of secondary thrombocytosis was infection, accounting for 37.9% of all patients. Other common causes were sickle cell anemia (21%), iron deficiency anemia (15.4%), colloid tissue disease (6.6%), hemolytic anemia (5.0%), splenectomy (4.5%), and other causes (9.7%)., Conclusion: In our study, infections were the most common cause of thrombocytosis. In addition to infections, sickle cell anemia and iron deficiency anemia should also be considered in the differential diagnosis of thrombocytosis.

Increase platelet count can accompany various cancers including lung cancer. This finding has recently been suggested to indicate poor prognosis. In patients with malignancies, thrombocytosis has previously been related disease stage, histological type and survival. In this study, the prevalence of thrombocytosis and the prognostic information provided by platelet count were analyzed in patients with stage IV Non-Small Cell Lung Cancer (NSCLC) with an aim to assess elevated platelet count as a prognostic factor in patients with stage IV NSCLC and to investigate whether there is relationship between thrombocytosis, other clinico-pathologic factors and median survival. This prospective observational study was conducted in National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh from September 2019 to August 2020. A total of 108 patients were enrolled purposively. Detail history taking, thorough physical examination was done along with relevant investigations. Data were collected by semi structured questionnaire and analysis was done with the help of Statistical Package for Social Science (SPSS), version 21.0. The mean age of the patients was found 56.4±12.2 years with range from 35 to 75 years. Majority (79.6%) patients were male, 52.8% patients came from low income and 36.1% were farmer. Majority (40.7%) were symptomatic; in bed >50.0% of day. Almost two third (59.3%) had <5.0% weight loss. Almost three fourth (69.4%) had squamous cell carcinoma. At the time of first assessment 75(69.4%) patients had normal and 33(30.6%) had elevated platelet count level. Age, sex and histological type were statistically not significant between normal and elevated platelet count level groups. But performance status, weight loss were statistically significant (p<0.05) between two groups. According to univariate analysis, age, performance status at presentation, weight loss more than 10.0% for 3 months and platelet count prior the start of treatment were all significant predictors for the overall survival. In multivariate analysis age, performance status at presentation and initial thrombocytosis were independent prognostic determinants for overall survival. Median survival time was significantly higher for the normal platelet count group and elevated platelet count group (7.5 months versus 5.5 months) respectively (95% CI, 5.5-7.5), p<0.001. The frequency of thrombocytosis in patients with stage-IV NSCLC at first presentation was 30.6% and median survival time in these patients was significantly shorter compared in patients without thrombocytosis. These results concluded that an elevated platelet count could be a useful prognostic factor for survival in patients with stage-IV NSCLC.

Background: Pediatric splenic torsion is a rare entity, and the most common cause is wandering spleen. This study aimed to summarize our clinical experience in the diagnosis and surgical treatment pediatric patients with splenic torsion, and to use preoperative thrombocytosis as a preoperative predictive factor for splenic infarction., Methods: From January 1st, 2016 to December 31st, 2021, 6 children diagnosed as splenic torsion were included. All patients were surgically treated and followed up. The clinical data was collected including clinical presentations, laboratory tests, imaging results, surgical procedures, and prognosis. Clinical experience of diagnosis and surgical treatment were summarized., Results: There were 4 females and 2 males, with median age at surgery 102.6 (range 9.4-170.7) months. Abdominal pain and abdominal mass were the most common presentations. The diagnosis of splenic torsion depended on imaging studies, and adjacent organ involvement (gastric and pancreas torsion) was observed on contrast CT in one patient. Five patients were diagnosed as torsion of wandering spleen, and one was torsion of wandering accessory spleen. Emergent laparoscopic or open splenectomy was performed in all patients. Pathology revealed total splenic infarction in 4 patients, partial infarction in 1 patient, and viable spleen with congestion and hemorrhage in 1 patient. Preoperative platelet counts were elevated in all 4 patients with splenic infarction, but normal in the rest 2 with viable spleen. Postoperative transient portal vein branch thromboembolism occurred in one patient., Conclusions: Imaging modalities are crucial for the diagnosis of pediatric splenic torsion and adjacent organ involvement. Preoperative thrombocytosis may predict splenic infarction. Spleen preserving surgery should be seriously considered over splenectomy in patients with a viable spleen., (© 2022. The Author(s).)

Background: Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/ MPN-RS-T) was newly introduced as a full entity in the 2016 revision of the WHO classification. In this study, we investigated the morphologic, laboratory, and clinical features of MDS/MPN-RS-T., Methods: We reviewed the bone marrow and genetic studies of patients whose diagnoses were coded as "refractory anemia with ring sideroblasts (RARS)" or "MDS/MPN, unclassifiable" between January 2008 and April 2018., Results: A total of 8 cases fulfilled the criteria for a diagnosis of MDS/MPN-RS-T. All of them had no specific symptoms. Half of the cases had less than 450 × 109/L platelet counts by an automated hematology analyzer; however, all platelet counts exceeded 450 × 109/L when performed manually. JAK2 mutation tests were performed in 7 cases, and a heterozygous mutation was detected in 1 case. SF3B1 mutations were present in 3 of the 4 cases tested., Conclusions: When RARS is suspected in patients without thrombocytopenia, manual platelet counts should be performed. For patients with suspected essential thrombocythemia, RS evaluation through careful observation of an iron-stained slide is crucial. Since the independent evaluation of RS was reflected in the revised classification, the ambiguous disease classification becomes clearer and more consistent.

Introduction: Essential thrombocythemia (ET) is an entity of classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by thrombocytosis with megakaryocytic hyperplasia where in the thrombocytes are increased with abnormal function.Thrombotic events are seen frequently and represent the main cause of morbidity and mortality in patients with MPNs, mainly polycythemia vera and ET. This study has aimed to research the effects of clonally increased thrombocytes on plasma viscosity (PV) levels among patients with ET and the relationship between PV and thromboembolism history, according to the hypotheses about the effects of PV in thromboembolic events among patients with ET., Methods: A total of 55 patients were enrolled in the study group, 18 of who had been newly diagnosed with ET according to 2016 World Health Organization criteria and had not previously been treated. 37 of them had already been diagnosed with ET and had been treated. There were 47 healthy volunteers in the control group. 5 cc blood samples were taken from the patients into tubes including an anticoagulant to measure their PV levels., Results: PV of the control group was found to be lower than in the study group and both each patient groups (p < 0.05). No relationship was found between the patient groups in terms of PV (p = 0.404). The mean PV levels of the 16 patients with a history of thromboembolism and the 39 patients with no such history were 2.42±0.17 cP and 2.33±0.20 cP, respectively. The mean PV levels were found to be similar according to their history of thromboembolism in all patient groups and in treated patients (p = 0.572 vs p = 0.991)., Conclusion: We have found that PV levels were increased in clonally increased thrombocytes in patients with ET when compared with the control group. This is the first study in this field according to our knowledge.

Background: Total pancreatectomy with islet autotransplantation (TPIAT) involves pancreatectomy, splenectomy, and reinjection of the patient's pancreatic islets into the portal vein. This process triggers a local inflammatory reaction and increase in portal pressure, threatening islet survival and potentially causing portal vein thrombosis. Recent research has highlighted a high frequency of extreme thrombocytosis (platelets ≥1000 × 109/L) after TPIAT, but its cause and association with thrombotic risk remain unclear., Methods: This retrospective single-site study of a contemporary cohort of 409 pediatric and adult patients analyzed the frequency of thrombocytosis, risk factors for thrombosis, and antiplatelet and anticoagulation strategies., Results: Of 409 patients, 67% developed extreme thrombocytosis, peaking around postoperative day 16. Extreme thrombocytosis was significantly associated with infused islet volumes. Thromboembolic events occurred in 12.2% of patients, with portal vein thromboses occurring significantly earlier than peripheral thromboses. Portal vein thromboses were associated with infused islet volumes and portal pressures but not platelet counts or other measures. Most thromboembolic events (82.7%) occurred before the postoperative day of maximum platelet count. Only 4 of 27 (14.8%) of portal vein thromboses occurred at platelet counts ≥500 × 109/L. Perioperative heparin was given to all patients. Treatment of reactive thrombocytosis using aspirin in adults and hydroxyurea in children was not associated with significantly decreased thromboembolic risk., Conclusions: These results suggest that post-TPIAT thrombocytosis and portal vein thromboses may be linked to the islet infusion inflammation, not directly to each other, and further reducing this inflammation may reduce thrombosis and thrombocytosis frequencies simultaneously., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

During a blood test, the discovery of thrombocytosis is a frequent phenomenon with multiple origins. False thrombocytosis linked to analytical interferences is rare but must be eliminated before confirming the anomaly. The reaction origin, often very easily demonstrated by the context and/or the presence of a biological inflammatory syndrome, is the most frequent. More rarely, the diagnosis is oriented towards a clonal hematological pathology not limited to essential thrombocythemia. Currently, many biological tools, which have largely contributed to the recommendations of the latest WHO classification of chronic myeloid neoplasms, are available to classify these pathologies as precisely as possible, allowing optimal management.

Familial thrombocytosis (FT) is a rare hereditary haematological disorder characterised by increased platelet count, usually caused by germ-line mutations in thrombopoietin (THPO), myeloproliferative leukaemia virus oncogene (MPL) or Janus kinase 2 (JAK2) genes, and can be associated with increased risk of thrombosis. We aimed to determine the yield of diagnostic tests, assess treatment received and describe the clinical course of MPL-associated FT. We retrospectively reviewed all paediatric and adult haematology patients diagnosed with MPL-related FT, who were seen in our clinics from March 2013 to February 2021. Of 64 eligible patients, 26 (41%) were aged <14 years, while the remaining 38 (59%) patients were adults. The median (interquartile range) age at diagnosis was 20 (33·5) years. In all, 26 tribes were represented in this cohort of 64 patients, out of which 31 (48%) patients belonged to two tribes. A total of 60 patients (94%) had thrombocytosis on blood count. Additional genetic tests, including myelodysplastic syndrome (MDS) gene panel, Philadelphia gene breakpoint cluster region-Abelson (BCR-ABL) and JAK2, were carried out for 52 patients and only one patient was positive for JAK2 mutation. In all, 21 (33%) patients were prescribed aspirin and seven (11%) were prescribed hydroxyurea. Overall, 63 (98%) patients did not develop any thrombotic or haemorrhagic event. There was no significant association of MPL-mutated FT with thrombosis or haemorrhage., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with coexistent APS and MPN has not been defined. A single centre and systematic literature review of patients with coexistent APS and MPN was performed. Cases were divided into two groups based on whether they met international consensus criteria for APS. Of the 12 studies identified, eight were excluded (leaving five of a total 54 patients), as although antiphospholipid antibodies (aPL) were documented, the diagnosis of APS was not conclusively demonstrated. Another ten patients with definite APS were identified at our centre. Fifteen patients (ten females, five males) were therefore included in this analysis (eleven definite APS and four highly likely), median age 44 (range: 13-71) years. Nine had polycythaemia vera and six, essential thrombocythaemia. Thirteen of the 15 patients (86.7%) had thrombotic APS (seven with initial venous events and six arterial) and two (13.3%) had obstetric APS. Nine patients were single-positive, and six double-positive for aPL. None were triple aPL-positive. Four patients at our centre had recurrent thrombotic/obstetric events, including while on anticoagulation/antiplatelet treatment.

Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation. Primary hereditary thrombocytosis may be caused by germline mutations within the genes encoding key regulators of thrombopoiesis, i.e., thrombopoietin (THPO) and its receptor c-MPL (MPL) or the receptor's effector kinase Januskinase2 (JAK2). Furthermore, somatic mutations in JAK2, MPL, and in the gene-encoding calreticulin (CALR) have been described to act as driver mutations within the so-called Philadelphia-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Increasing knowledge on the molecular mechanisms and on the clinical complications of these diseases is reflected by the WHO diagnostic criteria and European LeukemiaNet (ELN) recommendations on the management of adult MPN. However, data on childhood thrombocytosis are rare, and no consensus guidelines for pediatric thrombocytosis exist. Current literature has highlighted differences in the epidemiology and molecular pathogenesis of childhood thrombocytosis as compared to adults. Furthermore, age-dependent complications and pharmacological specificities suggest that recommendations tailored to the pediatric population are necessary in clinical practice. Here we summarize literature on classification, diagnostics, and clinical management of childhood thrombocytosis.

Objective/hypothesis: Early and objective prediction of complications in head and neck reconstructive surgery could decrease morbidity and prolonged hospital stays but unfortunately most complications are not identified until their effect is fully realized. There are limited data regarding the association of platelet levels and post-operative complications. Post-operative thrombocytosis (POTCT) is proposed as a possible indicator for complications following free-flap reconstruction., Study Design: Retrospective review., Methods: A multisite retrospective chart review of patients undergoing free tissue transfer between 2013 and 2018 was undertaken. POTCT was recorded and data normalized between institutions. Data were compared between groups using t-tests and logistic regression (P < .05). A lag-1 difference was used to compare the rate of change in platelet values., Results: A total of 398 patients were included. POTCT and a rate of change of 30 K between POD5 and POD6 was significantly associated with the presence of post-operative complication (P = .007). Additionally, lag-1 difference demonstrated a significant association of change in daily platelet counts and complication rates., Conclusions: Isolated POTCT may be an early predictor of complications in HNC patients undergoing free-flap reconstruction., Level of Evidence: 4 Laryngoscope, 131:1542-1547, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Hyperkalemia is common in medicine and requires rapid management. Besides the easily evoked causes such as renal failure, adrenal insufficiency, cell lysis or iatrogenic causes, false or pseudo-hyperkalemia should not be forgotten., Observations: Three patients (1 man, 2 women, aged 78, 84, 88) were managed for thrombocytosis (between 1306 and 2404 G/L) and non-symptomatic hyperkalemia (between 6.1 and 7.7mmol/L) are reported. Kalemia on blood collected in heparin tube was normal (4.4-4.6mmol/L). Therefore, no specific treatment for this pseudohyperkalemia was required., Conclusion: The combination of thrombocytosis and non-symptomatic hyperkalemia should suggest the diagnosis of pseudohyperkalemia and should prompt for a control of kalemia on blood collected in heparin tube. The recognition of this diagnosis is important in order to avoid unnecessary and potentially deleterious treatment of hyperkalemia., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9 years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22-4·60, P = 0·01] and thrombocytosis> 400 × 10 9 /l at RUX start (HR:1·98, 95%CI: 1·10-4·60, P = 0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24-7·92, P = 0·02) and duration of hydroxycarbamide and RUX therapy > 5 years (HR: 3·20, 95%CI: 1·17-8·75, P = 0·02 and HR: 2·93, 95%CI: 1·39-6·17, P = 0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11-5·25, P = 0·03), platelet > 400 × 10 9 /l (HR: 3·30, 95%CI: 1·67-6·50, P = 0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48-8·14, P = 0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Disease Overview: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include myelodysplastic syndromes with RS (MDS-RS) and MDS/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T)., Diagnosis: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (MDS-RS-SLD/MLD), <5% bone marrow (BM) blasts, <1% peripheral blood blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations). MDS/MPN-RS-T, now a formal entity in the MDS/MPN overlap syndromes, has diagnostic features of MDS-RS-SLD, along with a platelet count ≥450 × 10 9 /L and large atypical megakaryocytes., Mutations and Karyotype: Mutations in SF3B1 are seen in ≥80% of patients with MDS-RS-SLD and MDS/MPN-RS-T, and strongly correlate with the presence of BM RS; MDS/MPN-RS-T patients also demonstrate JAK2V617F (50%), DNMT3A, TET2 and ASXL1 mutations. Cytogenetic abnormalities are uncommon in both., Risk Stratification: Most patients with MDS-RS-SLD are stratified into lower risk groups by the revised-IPSS. Disease outcome in MDS/MPN-RS-T is better than that of MDS-RS-SLD, but worse than that of essential thrombocythemia (MPN). Both diseases are associated with a low risk of leukemic transformation., Treatment: Anemia and iron overload are complications seen in both and are managed similar to lower risk MDS and MPN. Luspatercept, a first-in-class erythroid maturation agent is now approved for the management of anemia in patients with MDS-RS and MDS/MPN-RS-T. Aspirin therapy is reasonable in MDS/MPN-RS-T, especially in the presence of JAK2V617F, but the value of platelet-lowering drugs remains to be defined., (© 2021 Wiley Periodicals LLC.)

Background: Extreme thrombocytosis (EXT, platelet count > 1000 × 10 3 /μL) is an uncommon but potentially clinically significant finding. Primary EXT in the setting of myeloproliferative disorders is linked to thrombotic and/or bleeding complications more frequently than secondary EXT, which typically occurs in reaction to infection, inflammation, or iron deficiency. However, comorbidities have been reported in adults with secondary EXT. Clinical implications of EXT in children are not well defined, as prior studies targeted small and/or specialized pediatric populations., Objectives: Our objectives were to determine etiologies and sequelae of EXT in a hospitalized general pediatric patient population., Patients and Methods: We retrospectively analyzed EXT cases from a single-center pediatric cohort of ~80 000 patients over 8 years., Results: Virtually all cases (99.8%) were secondary in nature, and most were multifactorial. Many cases of EXT occurred in children under 2 years old (47%) and/or during critical illness (55%). No thrombotic or bleeding events directly resulted from EXT, confirming a paucity of clinical complications associated with EXT in pediatric patients. There were indications that neonatal hematopoiesis and individual genetic variation influenced some cases, in addition to certain diagnoses (eg, sickle cell anemia) and clinical contexts (eg, asplenia)., Conclusion: Our findings confirm that thrombotic events related to EXT are rare in pediatric patients, which can inform the use of empiric anti-platelet therapy., (© 2020 International Society on Thrombosis and Haemostasis.)

Childhood essential thrombocythemia (ET) is a rare chronic myeloproliferative disorder. The quality of life of ET patients may decrease as a result of ischemic and hemorrhagic complications of unclear origin. Our goal was to characterize the hemostatic system in children with ET. We genotyped and investigated blood samples from 20 children with ET in a prospective case series study using platelet aggregation, functional flow cytometry (FC) assay and standard clotting assays. Three children had a JAK2V617F mutation, 4 had mutations in CALR and 13 were triple-negative. Myelofibrosis in stage 1-2 was detected in 3 children. Three patients had bleeding episodes and seven had ischemic events. Aggregation in response to collagen, adenosine diphosphate, and ristomycin was decreased in all patients. In FC, significant changes in the whole patient group compared to the healthy children control group were decrease in the resting forward scatter and PAC1 binding (activated GPIIb/IIIa) level. For the activated platelets, dense granules release (by mepacrine), PAC1, and GPIIb/IIIa levels were significantly decreased. GPIb/V/IX, P -selectin, and phosphatidylserine levels manifested only moderate differences. Forward and side scatter changes in response to stimulation (representing shape change) and dense granules release were significantly lower in the 3 patients with bleeding than in the 17 patients without hemorrhage. Activated partial thromboplastin time was slightly prolonged, prothrombin index was slightly shortened and thrombin time was normal, while fibrinogen was mildly decreased in the ET patients. It could be concluded that the observed platelet function defects could be related to bleeding in ET, and be potentially used as a marker.

Aims: Spliceosome genes ( SF3B1 , SRSF2 , U2AF1 and ZRSR2 ) are commonly mutated in myeloid neoplasms, particularly in myelodysplastic syndromes (MDS). JAK2 , MPL and CALR mutations are associated with myeloproliferative neoplasms (MPN). Although SF3B1 and MPN-associated mutations frequently co-occur in the rare entity MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), myeloid neoplasms with concurrent spliceosome and MPN-associated mutations encompass many disease entities and are not well characterised., Methods: Specimens from 2016 to 2019 with concurrent spliceosome and MPN-associated mutations were identified, and the clinicopathologic features were assessed., Results: The 36 cases were divided into mutational categories based on their spliceosome mutation. At diagnosis, cases with concurrent U2AF1 and MPN-associated mutations had lower leucocyte counts and platelet counts than did the other groups. Cases with mutant SRSF2 were more likely to have ASXL1 and IDH2 mutations, while U2AF1- mutated neoplasms were more likely to have an abnormal karyotype. The most common SF3B1 K700 and U2AF1 S34 mutational hotspots were underrepresented in our cohort of myeloid neoplasms with concurrent spliceosome and MPN-associated mutations, as SF3B1 and U2AF1 mutations tended to involve other codons. Numerous WHO-defined disease entities were represented in each spliceosome gene category; although MDS/MPN-RS-T were only identified in the group with SF3B1 mutations, they constituted only 1/4 of the neoplasms in the category., Conclusions: Myeloid neoplasms with different mutant splicing factor and concurrent MPN-associated mutations demonstrate somewhat different clinical and pathologic features, but t he association between genotypes and phenotypes in these overlapping neoplasms is not straightforward., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An association was shown between thrombocytosis and future development of several cancers., Objectives: To investigate whether pre-treatment platelet counts correlated with clinical outcomes of patients with breast cancer., Methods: This retrospective study included 22 patients who had been diagnosed with stage I breast cancer and were 66.8 ± 13.2 years of age. Of these, 22 with stage II were 61.6 ± 12.3 years old and 9 with stage III and IV were 64.4 ± 15.3 years old. Clinical and hematological data from the first visit to the oncology clinic were collected. The follow-up period was 12 months to 5 years., Results: A significant difference in platelet counts was found between patients who died (187,000 ± 4000 µ/L) and those who were disease free for 5 years (248,000 ± 83,000 µ/L, P = 0.0001). A significant difference in platelet-to-lymphocyte ratio was found between patients who died and those with recurrence (192 ± 81 vs. 124 ± 71, P = 0.01). A negative correlation was found between age and lymph nodes (Ps = -0.305, P = 0.02) and staging and white blood cells count (Ps = -0.280, P = 0.04). A positive correlation was found between clinical staging and lymph nodes (Ps = 0.443, P = 0.001) and clinical staging and metastases (P = 0.308, P = 0.02)., Conclusions: Platelet counts may be a prognostic marker for breast cancer. Patients who died within 1 year had lower pre-treatment platelet count, which could represent an insidious disseminated intravascular coagulopathy cancer related consumption process.

The diagnostic approach to thrombocytosis involves consideration of reactive, hereditary, and neoplastic causes. Once reactive causes of thrombocytosis, such as iron deficiency, infections, solid tumors, and other obvious causes such as post-splenectomy thrombocytosis, have been ruled out, the focus shifts to myeloid malignancies, such as chronic myeloid leukemia (CML), the classic Philadelphia chromosome-negative (Ph - ) myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), primary myelofibrosis (PMF), polycythemia vera (PV), myelodysplastic syndrome (MDS) with isolated deletion 5q and the rare MDS/MPN "overlap" syndrome, MDS/MPN with ring sideroblasts, and thrombocytosis (MDS/MPN-RS-T)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are a heterogenous group of myeloid malignancies hallmarked by clinicopathologic features that overlap with myelodysplastic syndromes and myeloproliferative neoplasms. Formally recognized by the World Health Organization, this group includes the entities chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN with ring sideroblasts and thrombocytosis and MDS/MPN, unclassifiable. Advancements in next generation sequencing have begun to unravel the molecular underpinnings of these diseases, identifying an array of recurrently mutated genes involved in epigenetic regulation, RNA splicing, transcription, and cell signaling. Despite molecular overlap with other myeloid malignancies, each entity displays a unique spectrum of somatic mutations supporting their unique pathobiology and clinical features. Importantly, molecular profiling is becoming an integral tool utilized in routine clinical practice. This review summarizes our current understanding of the molecular pathogenesis of overlap syndromes and details the impact of somatic mutations in diagnostic, prognostic, and therapeutic decision-making., (Copyright © 2020. Published by Elsevier Ltd.)

Studies have suggested a possible association between inflammatory bowel disease (IBD) and the Philadelphia-negative chronic myeloproliferative neoplasms (MPNs). The mechanisms behind this association have not been investigated yet, but in this review, we find it most likely to involve complex interactions between genetic, treatment-related and inflammation- and immune-mediated factors. When patients with IBD present with persistent leukocytosis and/or thrombocytosis, it may reflect concomitant MPN, and early detection and treatment of MPNs may prevent some of the complications related to these diseases.

A considerable proportion of patients with chronic myeloid leukaemia (CML) may present at diagnosis with high platelet counts. This may result in thrombosis or bleeding complications due to binding of von Willebrand factor (VWF) multimers to platelets. Paediatric CML is very rare and no systematic investigation on clinical complications of elevated platelets has been reported. Data on platelet count and associated haemostaseological complications were retrospectively analysed in a cohort of 156 children with CML. Fifty-one percent (81/156) patients presented with thrombocytosis (platelet count> 500 × 10 9 /l), and were extreme (>1 000 × 10 9 /l) in 23/156 (16%). There were no cases of thrombosis but mild bleeding signs were present in 12% (n = 9) children with thrombocytosis. Bleeding occurred without correlation to elevated platelet counts and was associated with reduced large VWF multimers, indicating a diagnosis of acquired von Willebrand syndrome (AVWS), which resolved after initiation of CML treatment. Patients with paediatric CML frequently exhibit high platelet counts not resulting in thrombosis. In patients with thrombocytosis mild bleeding signs due to a low percentage of large VWF multimers can be demonstrated. AVWS may be underdiagnosed in paediatric CML (Clinical-Trials.gov NCT00445822, 9 March 2007)., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)