Thrombocytosis and essential thrombocythaemia

2020 ◽  
pp. 5239-5247
Author(s):  
Daniel Aruch ◽  
Ronald Hoffman
Keyword(s):  
Platelet Count ◽  
Myeloproliferative Neoplasms ◽  
Receptor Gene ◽  
Jak2 V617f ◽  
Prior History ◽  
Polycythaemia Vera ◽  
Essential Thrombocythaemia ◽  
Minor Criterion ◽  
History Of ◽  
The One

The term thrombocytosis refers to a platelet count elevated above 450 × 109/litre, which can be (1) primary—including essential thrombocythaemia, chronic myeloid leukaemia, polycythaemia vera, and myelodysplastic syndromes; or (2) secondary—including iron deficiency, infection, blood loss, and malignancy. Essential thrombocythaemia: aetiology—the JAK2 V617F missense mutation typical of polycythaemia vera is found in about 50% of cases. In addition, 10% of patients have a mutation in the thrombopoietin receptor gene, MPL, and 30% have a mutation in calreticulin (CALR). Approximately 10% of patients have none of these mutations and are referred to as ‘triple negative’ essential thrombocythaemia. Diagnosis requires all of the following four major criteria: (1) platelet count greater than 450 × 109/litre; (2) bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei without a significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibres; (3) failure to meet the criteria for other myeloproliferative neoplasms; and (4) presence of JAK2, CALR, or MPL mutations. Alternatively, diagnosis can be met when the first three major criteria are present and the one minor criterion, namely the presence of another clonal marker or absence of evidence for reactive thrombocytosis. Treatment requires risk stratification based on the age of the patient and any prior history of thrombosis, with treatment being reserved for those at a high risk of developing complications and not introduced simply on the basis of platelet counts alone unless there is extreme thrombocytosis (>1500 × 109/litre). Therapies include low-dose aspirin and cytoreduction.

Cultivation of Megakaryocytes On a Collagen Matrix: A More Sensitive and Reproducible Test for the Diagnosis of Patients with Essential Thrombocythaemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4970-4970
Author(s):  
Adrian Emanuel Schmidt ◽  
Patricia Darlington ◽  
Lucie Kopfstein ◽  
Elisabeth Ischi ◽  
Elisabeth Oppliger Leibundgut ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Healthy Subjects ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Essential Thrombocythaemia ◽  
Jak2 Mutation ◽  
Spontaneous Proliferation

Abstract Abstract 4970 Background Essential thrombocythaemia (ET) is one of the chronic myeloproliferative neoplasms (MPN), along with polycythaemia vera (PV), primary myelofibrosis (PMF) and chronic myeloid leukaemia (CML). Their common feature is excessive proliferation of a certain stem or progenitor cell in the bone marrow; in the case of ET, the megakaryocytic lineage is affected. Clinical manifestations include thrombotic events and haemorrhage. Diagnosis of ET according to new WHO-criteria requires a sustained high platelet count, bone marrow biopsy showing proliferation of the megakaryocytic lineage with large and mature morphology, demonstration of JAK2 V617F (although only present in about 50% of patients with ET) or another clonal marker and explicit exclusion of other myeloid and myeloproliferative neoplasms as well as signs of reactive thrombocytosis. Additionally, spontaneous proliferation of megakaryocytes obtained from peripheral blood can be detected in in vitro culture assays. Presently, we use agar as a matrix for megakaryocyte cultivation, although this assay has never been validated in connection with ET. The identification of megakaryocytic colonies grown on agar can sometimes be quite difficult. Our aims were therefore to technically evaluate the use of a collagen based matrix and to investigate its suitability to identify patients with ET. Patients and Methods We have examined 63 patients (26 with ET, 21 with PV, 8 with myelofibrosis [MF; including PMF and post-ET/PV-MF], 6 with secondary or idiopathic erythrocytosis and 2 with secondary thrombocytosis; mean age=59.8, male=33, female=30, mean platelet count 457 G/l) and 5 healthy subjects. Following informed consent, both clinical and laboratory data was collected. Medication intake, phlebotomies, smoking habits and regular haemogram results were noted in order to recognise possible confounding factors influencing laboratory results. Results of megakaryocyte cultivation on both agar and collagen matrixes were recorded, considering both spontaneous growth and growth stimulated by megakaryocyte derived growth factor (MDGF). Results Based on our collagen culture results we were able to define 2 or more spontaneously grown megakaryocyte colonies as the most optimal cut-off for the identification of patients with MPN (sensitivity 71%, specificity 100% with positive and negative predictive values of 100% and 45%, respectively). Compared to the agar culture results (where a specificity and a positive predictive value of 100% were demonstrated at a cut-off value of ≥ 10 CFU-Mega) we found a higher accuracy and better reproducibility. In addition, we observed an improved negative predictive value (45% with collagen versus 25% with agar cultures) reducing false negative results. Healthy subjects and patients with secondary thrombocytosis showed no significant spontaneous megakaryocyte proliferation. In patients with MF, we observed strong spontaneous and MDGF-stimulated growth of megakaryocytic colonies. At a cut-off value of ≥ 50 CFU-Mega (after stimulation with MDGF), the collagen assay showed a sensitivity of 100% and a specifity of 70% for this special form of MPN, resulting in a negative predictive value of 100%. We found no confounding clinical or laboratory parameters such as medication intake (particularly cytoreductive treatment with hydroxyurea) or phlebotomies influencing our culture results, and no significant effect of the Jak2-V617F mutation on the growth behaviour of megakaryocytic colonies. Conclusion The results of this ongoing study imply that the collagen based assay is more sensitive, specific, time efficient and user friendly regarding the detection of spontaneous proliferation of megakaryocytes than the currently used agar based culture assay. In addition, the collagen based assay also has the great advantage that it allows isolation of single megakaryocytic colonies for further analyses, for example PCR-based identification of a JAK2 mutation. Furthermore, the collagen based assay facilitates the diagnosis of patients with MPN, especially in cases where conventional diagnostic criteria are lacking, such as in ET without a JAK2 mutation. Ultimately, the new assay may well be able to detect transformation from PV/ET to MF. Disclosures No relevant conflicts of interest to declare.

scholarly journals How I treat polycythemia vera

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 275-284 ◽  
Author(s):  
Francesco Passamonti
Keyword(s):  
Polycythemia Vera ◽  
Myeloproliferative Neoplasms ◽  
Phase 1 ◽  
Signal Transduction Pathway ◽  
Jak2 V617f ◽  
Prior History ◽  
Oncogenic Mutations ◽  
Clinical Presentations ◽  
History Of ◽  
Disease Stratification

Abstract Polycythemia vera (PV) is a clonal disorder characterized by unwarranted production of red blood cells. In the majority of cases, PV is driven by oncogenic mutations that constitutively activate the JAK-STAT signal transduction pathway, such as JAK2 V617F, or exon 12 mutations or LNK mutations. Diagnosis of PV is based on the WHO criteria. Diagnosis of post-PV myelofibrosis is established according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria. Different clinical presentations of PV are discussed. Prognostication of PV is tailored to the most frequent complication during follow-up, namely, thrombosis. Age older than 60 years and prior history of thrombosis are the 2 main risk factors for disease stratification. Correlations are emerging between leukocytosis, JAK2(V617F) mutation, BM fibrosis, and different outcomes of PV, which need to be confirmed in prospective studies. In my practice, hydroxyurea is still the “gold standard” when cytoreduction is needed, even though pegylated IFN-alfa-2a and ruxolitinib might be useful in particular settings. Results of phase 1 or 2 studies concerning these latter agents should however be confirmed by the ongoing randomized phase 3 clinical trials. In this paper, I discuss the main problems encountered in daily clinical practice with PV patients regarding diagnosis, prognostication, and therapy.

Myeloproliferative neoplasms

2015 ◽  
Author(s):  
Drew Provan ◽  
Trevor Baglin ◽  
Inderjeet Dokal ◽  
Johannes de Vos
Keyword(s):  
Systemic Mastocytosis ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Polycythaemia Vera ◽  
Essential Thrombocythaemia ◽  
Cell Disease ◽  
Reactive Thrombocytosis ◽  
History Of ◽  
Mast Cell Disease ◽  
Idiopathic Erythrocytosis

Myeloproliferative neoplasms (MPNs) - Pathogenesis of the MPNs - Polycythaemia vera (PV) - Natural history of PV - Management of PV - Secondary erythrocytosis - Relative erythrocytosis - Idiopathic erythrocytosis - Essential thrombocythaemia - Reactive thrombocytosis - Primary myelofibrosis - Chronic neutrophilic leukaemia - Eosinophilic syndromes and neoplasms - Mastocytosis (mast cell disease) - Systemic mastocytosis - MPN—unclassifiable

Myeloproliferative neoplasms

2018 ◽  
Author(s):  
Drew Provan ◽  
Trevor Baglin ◽  
Inderjeet Dokal ◽  
Johannes de Vos ◽  
Mammit Kaur
Keyword(s):  
Systemic Mastocytosis ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Polycythaemia Vera ◽  
Essential Thrombocythaemia ◽  
Cell Disease ◽  
Reactive Thrombocytosis ◽  
History Of ◽  
Mast Cell Disease ◽  
Idiopathic Erythrocytosis

Myeloproliferative neoplasms (MPNs) - Pathogenesis of the MPNs - Polycythaemia vera (PV) - Natural history of PV - Management of PV - Secondary erythrocytosis - Relative erythrocytosis - Idiopathic erythrocytosis - Essential thrombocythaemia - Reactive thrombocytosis - Primary myelofibrosis - Chronic neutrophilic leukaemia - Eosinophilic syndromes and neoplasms - Mastocytosis (mast cell disease) - Systemic mastocytosis - MPN—unclassifiable

Thrombocytosis

2010 ◽  
pp. 4280-4287
Author(s):  
Stefan O. Ciurea ◽  
Ronald Hoffman
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Iron Deficiency ◽  
Blood Loss ◽  
Haematopoietic Stem Cell ◽  
Polycythaemia Vera ◽  
Essential Thrombocythaemia ◽  
Platelet Production ◽  
The Many ◽  
Different Levels

Thrombocytosis describes a platelet count elevated above 450 × 109/litre, which can be (1) primary—including essential thrombocythaemia, chronic myeloid leukaemia, polycythaemia vera and myelodysplastic syndromes; or (2) secondary—including iron deficiency, infection, blood loss, malignancy. Platelets are released from megakaryocytes, whose development is principally regulated by thrombopoietin. This is chiefly produced in the liver and binds to its receptor (c-Mpl) to cause activation via the JAK-STAT signalling pathway at different levels of the platelet production pathway, ranging from the proliferation and survival of haematopoietic stem cell/progenitor cells to megakaryocyte maturation. Thrombopoietin production is increased by a wide variety of stimuli, which explains the many causes of secondary thrombocytosis....

scholarly journals Thrombocytapheresis in Patient with Essential Thrombocythemia: A Case Report

2020 ◽  
Vol 13 (2) ◽  
pp. 675-679
Author(s):  
Afra M. Elhassan ◽  
Arwa Alsaud ◽  
Mohamed A. Yassin ◽  
Mahmood Aldapt ◽  
Lubna Riaz ◽  
...  
Keyword(s):  
Platelet Count ◽  
Case Report ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Favorable Outcome ◽  
Who Criteria ◽  
Icu Admission ◽  
Calr Mutation ◽  
Clonal Abnormalities

Essential thrombocythemia (ET) is one of the myeloproliferative neoplasms, characterized by persistent thrombocytosis, platelets >450,000/μL, and evident clonal abnormalities like JAK2 V617F, MPL, CALR mutation and not fulfilling WHO criteria for MDS, CML, PV, and IDA. Here we report a 24-year-old female who presented with headache and was found to have thrombocytosis with a platelet count of 2,141 × 103/μL, diagnosed as ET as per WHO criteria 2008; she required ICU admission and thrombocytapheresis with a favorable outcome.

Evaluation of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) in Patients with Non-Hodgkin’s Lymphoma (NHL) Having Previously Received Autologous Stem Cell Transplant (ASCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5238-5238 ◽  
Author(s):  
Samuel A. Jacobs ◽  
Barry McCook ◽  
Frank Torok ◽  
Norbert Avril ◽  
Nick Vidnovic ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prior History ◽  
Ibritumomab Tiuxetan ◽  
Heavily Pretreated ◽  
History Of ◽  
Lymphomatous Involvement ◽  
Yttrium 90

Abstract Background: As the first radioimmunotherapeutic (RIT) agent approved for the treatment of relapsed or refractory B-cell NHL, yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) has been shown to achieve durable responses in heavily pretreated NHL patients. In phase 1–2, the eligibility criteria for 90Y ibritumomab tiuxetan therapy excluded patients with hypocellular bone marrow (<15%), lymphomatous involvement >25%, or prior ASCT due to concern of depleting the bone marrow reserve. However, Kaminski et al previously demonstrated that a parallel RIT agent, 131I tositumomab, was safe and efficacious when administered after ASCT (Blood2000; 96:1259–66). We report our experience of using ibritumomab tiuxetan in NHL patients with a prior history of ASCT. Methods: Patients with histologically confirmed relapsed or refractory B-cell NHL, ≥18 years, platelet counts >100,000/mm3, bone marrow cellularity >15%, and lymphomatous involvement <25% were eligible for treatment. In a series of 40 patients treated with ibritumomab tiuxetan at the UPMC Cancer Center, 6 patients with prior ASCT were treated. A standard course of ibritumomab tiuxetan was given, with the therapeutic dose of 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg (the initial patient, and another with platelet count ≥150,000/mm3) or the standard dose of 0.4 mCi/kg 90Y in the 4 remaining cases (baseline platelet count >150,000/mm3). Pretreatment diagnostic PET/CT scans were taken for all patients and evaluated for areas of lymphomatous involvement. Follow-up scans were performed approximately 12 weeks after treatment to assess patient response. Maximum toxicities were monitored weekly over a 12-week period after therapy and classified according to CTCAE v. 3.0 toxicity criteria. Results: Patients with a prior history of ASCT had received a minimum of 4 previous regimens (range, 4–7). Subjects presented with follicular NHL (n = 3), transformed NHL (n = 1), large cell lymphoma (n = 1), and mantle cell lymphoma (n = 1). Six patients were evaluable for toxicity and 5 patients were evaluable for response. Observed toxicities were consistent with those expected in this patient population, with 33% (2/6) and 17% (1/6) of patients experiencing grade 4 thrombocytopenia and grade 3 neutropenia, respectively. Episodes of bleeding or neutropenic fever were not observed. Of the 5 patients evaluable for response, 1 patient with follicular lymphoma had a complete response to ibritumomab tiuxetan as determined by FDG-PET imaging. Conclusions: Ibritumomab tiuxetan therapy is feasible and safe in NHL patients who have previously received ASCT. Heavily pretreated patients can benefit from the administration of ibritumomab tiuxetan although additional data are needed to further characterize the degree of clinical response after ASCT.

Risperidone-Induced Neuroleptic Malignant Syndrome: A Case Report and Review

1996 ◽  
Vol 41 (1) ◽  
pp. 52-54 ◽  
Author(s):  
Gb Meterissian
Keyword(s):  
Case Report ◽  
Side Effects ◽  
Neuroleptic Malignant Syndrome ◽  
Clinical Features ◽  
Prior History ◽  
Extrapyramidal Side Effects ◽  
Life Threatening ◽  
History Of ◽  
Life Threatening Complication ◽  
The One

Objectives: 1. To report the case of a 53-year-old patient who developed neuroleptic malignant syndrome (NMS) — a rare but potentially life-threatening complication of neuroleptic therapy — 4 days after treatment with risperidone was initiated. 2. To review previously reported cases of NMS associated with risperidone. Methods: A computerized search of several databases, including MEDLINE, was conducted to find all previously reported cases of NMS with risperidone. Results: Five reported cases of risperidone-induced NMS were found in the literature. All cases including the one reported here displayed typical clinical features of NMS and all 6 patients had a prior history of extrapyramidal side effects and/or NMS. Age and duration of exposure to risperidone did not seem to be of significance. Conclusions: These cases illustrate that clinicians should be on the lookout for risperidone-induced NMS.

scholarly journals SARS-COV-2 infection in a patient with Evans syndrome: A silent enemy or an ally?

2020 ◽  
pp. 115-115
Author(s):  
Nikola Pantic ◽  
Mirjana Mitrovic ◽  
Marijana Virijevic ◽  
Nikica Sabljic ◽  
Zlatko Pravdic ◽  
...  
Keyword(s):  
Platelet Count ◽  
Case Report ◽  
Autoimmune Diseases ◽  
Reference Range ◽  
Prior History ◽  
Limited Data ◽  
Evans Syndrome ◽  
History Of ◽  
Current Outbreak ◽  
Platelet Count Monitoring

During the current outbreak of Coronavirus disease 2019 (COVID-19), the way to manage patients with autoimmune diseases remains elusive due to limited data available. Case report: Addressing this issue we report a case of a COVID-19 positive 20-year-old female with prior history of Evans syndrome. She remained asymptomatic even though she had been treated with immunosuppressants (prednisolone and azathioprine) together with romiplostim. Moreover, her course of infection was accompanied by thrombocytosis, although her platelet count was mostly below the reference range before the infection. The patient was monitored vigilantly, with special regard to platelet count and signs of thrombotic events. Conclusion: Platelet count monitoring and romiplostim administration should be performed more cautiously in ITP patients infected by SARS-CoV-2.

Myeloid Blastic Transformation of Myeloproliferative Neoplasms – A Review of 113 Cases.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3113-3113
Author(s):  
Syed Noor ◽  
Wei Tan ◽  
Gregory Wilding ◽  
Laurie Ann Ford ◽  
Maurice Barcos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Polycythemia Vera ◽  
Myeloproliferative Neoplasms ◽  
Alkylating Agents ◽  
Allogeneic Transplantation ◽  
Prior History ◽  
Complex Karyotype ◽  
Blastic Transformation ◽  
Frequent Use ◽  
History Of

Abstract Abstract 3113 Poster Board III-50 Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. Mutations of JAK2V617F were described in the majority of MPN patients but only about half of those undergoing blastic transformation continue to harbor that mutation. We describe a cohort of 23 patients from Roswell Park Cancer Institute (RPCI) and discuss 90 additional cases from the English literature for whom biologic features were described. We also screened our cases for JAK2V617F, JAK2T875N and MPL515L/K. We initially compared our 23 patients to the 90 cases from the literature. Our population had significantly less patients with prior history of polycythemia vera (22% vs. 53%; P<0.0001), shorter time from MPN diagnosis to blastic transformation (<5 years to transformation in 68% vs. 40%; p=0.0296), <3 prior therapies (100% vs. 16%; p<0.0001), more frequent use of hydroxyurea (63% vs. 27%; p=0.0056), less frequent use of alkylating agents (5% vs. 54%; p<0.0001) and more frequent use of erythropoietin (11% vs. 0%; p=0.0332). Detection of normal karyotype at the time of blastic transformation was more common in the RPCI population (35% vs. 7%; p=0.0033). The two populations did not differ in regards to age at diagnosis of MPN or blastic transformation, gender, prior use of interferon or karyotype aberrations. Interestingly, the overall survival of the two cohorts from the time of blastic transformation was similar [3 vs. 5 months; 95% confidence interval (CI) 2 to 5 vs. 3 to 9; p=0.1639]. We therefore looked at the outcome of the entire cohort (n=113). Patients with prior history of essential thrombocythemia survived longer (8.6 months; 95% CI 4.3, 24) than patients with prior history of myelofibrosis (4.5 months; 95% CI 2, 11) or polycythemia vera (3 months; 95% CI 2, 5) (p=0.0224). Further, patients with <3 prior therapies had significantly longer survival (8 vs. 3 months; 95% CI 4 to 11 vs. 2 to 5; p=0.0212). Finally, patients with complex karyotype had significantly shorter survival (3 vs. 5 months; 95% CI 2 to 5 vs. 3 to 10); p=0.0272). No difference in survival was detected based on time from MPN diagnosis to blastic transformation, age, prior hydroxyurea treatment, prior alkylating agents, erythropoietin, or interferon, or presence of non-complex karyotype aberrations. We then evaluated the treatment response among the PRCI patients (n=23). A total of 20/23 patients underwent induction treatment with cytarabine and an anthracycline containing regimens; 12 achieved remission and eight did not. The overall survival of those achieving remission was significantly longer than those who did not [13 vs. 3 months; 95% CI 8 to 25 vs. 2 to 4); p<0.0001]. Three patients underwent an allogeneic transplantation and their survival was significantly longer that those who did not [11 vs. 4 months; 95% CI 8 to 57 vs. 3 to 5; p=0.0119]. Samples were available for eight of the patients at disease transformation; JAK2V617F was detected in two and none had T875N or MPL515K/L. In summary, patients with less than three prior therapies and lack of complex karyotype have longer survival following blastic transformation. Finally, allogeneic transplantation represents the only chance for long term survival in these patients. Disclosures No relevant conflicts of interest to declare.

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