MPL-Positive Essential Thrombocytosis Presenting as Budd-Chiari Syndrome in a Middle-Aged Woman with an Initially Normal Platelet Count

Budd-Chiari syndrome (BCS) results from an occlusion of the hepatic venous flow which in turn leads to portal hypertension causing ascites and other signs of liver dysfunction. Here, we present the case of a 43-year-old woman with recurrent ascites who was found to have BCS secondary to an inferior vena cava thrombosis extending into the hepatic veins. Although she had a normal platelet count on admission, additional laboratory investigations revealed an MPL mutation. She was discharged on anticoagulation with apixaban and later found to have thrombocytosis on repeat blood work, confirming the diagnosis of essential thrombocytosis, following which she was started on myelosuppressive therapy with hydroxyurea.

Designing a Scoring System for Differential Diagnosis From Reactive Thrombocytosis and Essential Thrombocytosis

Background: Thrombocytosis is a common finding in hospitalized patients and is of two main types, essential thrombocytosis (ET) and reactive thrombocytosis (RT). It is important to distinguish the two due to increased risk of developing marrow fibrosis, acute leukemia, and thrombosis in the former. Molecular studies are the main tools to differentiate the two but are not available in all hospitals. We aimed to design a highly sensitive scoring system using routine lab data to classify thrombocytosis as essential or reactive.Methods: A total of 145 patients were enrolled in this study. Potential predictors included patient demographics and clinical laboratory parameters. Receiver operating characteristic curve analysis was used to decide the optimal cutoff level. Multivariate logistic regression with forward model selection method was performed to decide the predictors.Results: The risk scores by multivariate analysis were as follows: 1 point for WBC > 13,500/μL; 2.5 points for Hb > 10.9 g/dL; 3 points for platelet count > 659,000/μL; and 2 points for MPV > 9.3 fL. The cut off value was set as 4.5 points, and sensitivity of 91.1% and specificity of 75.8% were noted.Conclusion: In this study, we investigated lab data and developed a high-sensitivity convenient-to-use scoring system to differentiate ET from RT. The scoring system was assigned to the resulting model to make it more economical, simple, and convenient for clinical practice.

Acute Limb Ischemia in the Young: A Rare Case of Essential Thrombocytosis

Acute limb ischemia (ALI) is rarely observed in young populations. The hypercoagulable state is a notable cause of ALI other than artery disease progression and cardiac embolization. A hypercoagulable state occurs in essential thrombocytosis because of the overproduction of hematopoietic cells secondary to the mutation of the JAK2, CALR, or MPL genes. We report a rare case of a 37-year-old woman presenting with Rutherford IIA ALI in the left lower extremity. Laboratory data revealed she had a platelet count reaching up to 1.38 mil/μL, with other blood profiles being normal. A JAK2 mutation examination was later performed and proved positive. After careful management with catheter-directed thrombolysis, surgical thrombectomy, and cytoreductive therapy using hydroxyurea, the symptoms subsided and eventually restored the patient to physical activity in less than one month.

Essential Thrombocytosis and Hepatocellular Carcinoma: A Mechanistic Challenge

Introduction/Objective Thrombocytosis has been reported in 8.2% of patients with Hepatocellular carcinoma [HCC] and has been attributed to increased Thrombopoietin [TPO] production by the tumor. Methods/Case Report We present a case of a 68-year-old male with a history of Hepatitis C and ethanol abuse presented with complaints of headache and chills. Imaging studies revealed a large mass in the liver [right lobe] suggesting an HCC of fibrolamellar type. His platelet count [PC] was 965 K/mcL. The serum AFP [Alpha feto protein] concentration was >51,800 ng/ml. There was no evidence of metastatic disease and the patient was started on Capecitabine and radiation therapy targeting the liver mass. Lung metastasis became evident and Sorafenib was added. His PCs and AFP concentrations however continued decreasing to 306 K/mcL and 460.7 ng/ml respectively. His PC then increased to a peak of 1.32 million/mcL 10 months later. The molecular workup done at our reference lab was positive for CALR [Calreticulin] mutation. The patient was started on Hydroxyurea and his PC decreased to 323 K/mcL at the time of writing. His AFP has remained stable. This case illuminates the complicated relationship between HCC and thrombocytosis. The therapy directed against the HCC did decrease PC and AFP concentration in our case. The second wave of thrombocytosis led to the discovery of CALR mutation, and the patient was diagnosed with Essential Thrombocytosis [ET]. Treatment with Hydroxyurea again decreased the PC while AFP concentration was increased but stable. Thrombopoietin levels have remained stable for the patient after treatment with Hydroxyurea. Results (if a Case Study enter NA) NA Conclusion Although the question of which mechanism(or possibly both) was at work in this case cannot be resolved definitely, two points are worth noting. The first is that- the assumption that the thrombocytosis was related to the HCC delayed testing for mutations associated with Essential Thrombocytosis. The second is that the TPO assay that may have yielded useful information in sorting out the alternatives was not ordered early enough before starting hydroxyurea.

Essential thrombocytosis: review of literature with a rare presentation of cerebral thrombosis treated with endovascular therapy

Essential thrombocytosis (ET) is a clonal hematopoietic stem cell disorder. Clinically there is an over-production of platelets without a definable cause. ET is a myeloproliferative neoplasm (MPN). It has an incidence of 1 to 2 per 100,000 population and a distinct female predominance. Once considered a disease of the elderly and responsible for significant morbidity due to haemorrhage or thrombosis, it is now clear that ET can occur at any age in adults and often without symptoms or disturbances of hemostasis. ET can cause both thrombosis or haemorrhage and carries a risk of acute leukemic transformation. Being an MPN, in some cases, polycythemia vera (PV) or primary myelo-fibrosis (PMF) can present as ET. Though the average life expectancy only slightly deviates from the standard expected for age-matched individuals, a thorough understanding of its etiopathogenesis, clinical presentation, complication and management can make a world of difference to patients. Thrombosis is one such complication that has a significant impact on the mortality and morbidity of ET. We proposed using endovascular therapy (EVT) as a treatment modality for cerebral venous sinus thrombosis.

The Role of Neutrophilic Granulocytes in Philadelphia Chromosome Negative Myeloproliferative Neoplasms

Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are composed of polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The clinical picture is determined by constitutional symptoms and complications, including arterial and venous thromboembolic or hemorrhagic events. MPNs are characterized by mutations in JAK2, MPL, or CALR, with additional mutations leading to an expansion of myeloid cell lineages and, in PMF, to marrow fibrosis and cytopenias. Chronic inflammation impacting the initiation and expansion of disease in a major way has been described. Neutrophilic granulocytes play a major role in the pathogenesis of thromboembolic events via the secretion of inflammatory markers, as well as via interaction with thrombocytes and the endothelium. In this review, we discuss the molecular biology underlying myeloproliferative neoplasms and point out the central role of leukocytosis and, specifically, neutrophilic granulocytes in this group of disorders.