Extreme Reactive Thrombocytosis Caused by Obstructive Nephrolithiasis and Pyelonephritis.

Platelet counts in reactive thrombocytosis rarely exceed 1000 × 109/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 × 109/L on routine laboratory testing. The patient was initially asymptomatic but developed leukocytosis to 23.1 × 109/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 × 109/L, and that markedly elevated platelet counts in the setting of urinary tract infections may be an early sign of obstructive uropathy.

Clinical utility of investigations in triple-negative thrombocytosis: A real-world, multicentre evaluation of UK practice.

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.

Pseudonormokalemia case report - What does it mean to have normal blood potassium?

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 500x109/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 500x109/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.

An Introduction to the Complete Blood Count for Clinical Chemists: Platelets.

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.

Idiopathic Thrombocytosis in Alpha Thalassemia Trait Patient.

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.

Adult acute megakaryoblastic leukemia with persistent diarrhea and extreme thrombocytosis: A very unusual case.

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.

Essential thrombocythemia: 2024 update on diagnosis, risk stratification, and management.

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 × 109 /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.

A case of lower limb ulcer caused by hydroxyurea in treating primary thrombocytosis.

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.

Extreme thrombocytosis with an aggressive evolution harboring a novel variant of calreticulin (CALR) in exon 3.

We describe the case of a patient with extreme thrombocytosis whose evolution was rapidly fatal. No cause of secondary thrombocytosis was found. There was no sign of myelofibrosis but the megakaryocytes were small and dysplastic. The patient presented a calreticulin (CALR) variant in exon 3 (C105S), as well as concomitant mutations of ASXL1, U2AF1, and EZH2. This variant of CALR has never been described before, and after sorting, all identified mutations were found in myeloid cells but not in lymphoid cells. Therefore, the diagnosis of a frontier case of myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) was made. A treatment with hydroxycarbamide was started because of a high risk of thrombosis. Upon worsening of the hematological status two new mutations appeared, SETBP1 and ETV6, and the CALR mutation was still detectable, as well as the three other mutations found in the chronic stage. Our results show that this variant could contribute to MDS/MPN pathogenesis in that patient.

JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome.

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.

Marked reactive thrombocytosis in a female with iron deficiency anaemia.

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.

Asymptomatic Essential Thrombocytosis Presenting with Extrahepatic Portal Vein Thrombosis: A Case Report.

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.

Thrombocytosis in children.

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.

Erythrocytosis, thrombocytosis, and rate of recurrent thromboembolic event-A population based cohort study.

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.

Platelet Count as a Prognostic Factor in Stage IV Non-Small Cell Lung Cancer.

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.