320 results on '"Thrombocytosis pathology"'
Search Results
2. Thrombocytosis.
- Author
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Liaskas A and Vassilakopoulos TP
- Subjects
- Female, Humans, Thrombocytosis etiology, Thrombocytosis pathology, Thrombocytosis blood
- Published
- 2024
- Full Text
- View/download PDF
3. Red Blood Cell Contribution to Thrombosis in Polycythemia Vera and Essential Thrombocythemia.
- Author
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Grenier JMP, El Nemer W, and De Grandis M
- Subjects
- Humans, Erythrocytes pathology, Polycythemia Vera, Thrombocythemia, Essential complications, Thrombosis complications, Thrombocytosis pathology
- Abstract
Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) characterized by clonal erythrocytosis and thrombocytosis, respectively. The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. Despite a debated notion that red blood cells (RBCs) play a passive and minor role in thrombosis, there has been increasing evidence over the past decades that RBCs may play a biological and clinical role in PV and ET pathophysiology. This review summarizes the main mechanisms that suggest the involvement of PV and ET RBCs in thrombosis, including quantitative and qualitative RBC abnormalities reported in these pathologies. Among these abnormalities, we discuss increased RBC counts and hematocrit, that modulate blood rheology by increasing viscosity, as well as qualitative changes, such as deformability, aggregation, expression of adhesion proteins and phosphatidylserine and release of extracellular microvesicles. While the direct relationship between a high red cell count and thrombosis is well-known, the intrinsic defects of RBCs from PV and ET patients are new contributors that need to be investigated in depth in order to elucidate their role and pave the way for new therapeutical strategies.
- Published
- 2024
- Full Text
- View/download PDF
4. JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome.
- Author
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Krah NM, Miotke L, Li P, Patel JL, Bowen AR, Pomicter AD, and Patel AB
- Subjects
- Male, Humans, Aged, Diagnosis, Dual (Psychiatry), Mutation, Janus Kinase 2 genetics, Myelodysplastic Syndromes genetics, Leukemia, Myeloproliferative Disorders diagnosis, Myeloproliferative Disorders genetics, Myeloproliferative Disorders therapy, Thrombocytosis diagnosis, Thrombocytosis genetics, Thrombocytosis pathology, Eosinophilia
- Abstract
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.
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- 2023
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5. Myelofibrosis-type megakaryocyte dysplasia (MTMD) as a distinct category of BCR::ABL-negative myeloproliferative neoplasms. Challenges and perspectives.
- Author
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Barosi G, Rosti V, and Gale RP
- Subjects
- Humans, Megakaryocytes pathology, Fusion Proteins, bcr-abl, Bone Marrow Diseases pathology, Myeloproliferative Disorders genetics, Myeloproliferative Disorders pathology, Polycythemia Vera pathology, Primary Myelofibrosis genetics, Primary Myelofibrosis pathology, Thrombocytosis genetics, Thrombocytosis pathology
- Abstract
In this Perspective, we discuss criteria for defining a new disease entity or variant of a recognized disease or disorder. We do so in the context of the current topography of the BCR::ABL-negative myeloproliferative neoplasms (MPNs) where two new variants are reported: clonal megakaryocyte dysplasia with normal blood values (CMD-NBV) and clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). The cardinal feature of these variants is bone marrow megakaryocyte hyperplasia and atypia corresponding the WHO histological criteria for primary myelofibrosis (myelofibrosis-type megakaryocyte dysplasia-MTMD). Persons with these new variants have a different disease course and features from others in the MPN domain. In a broader context we suggest myelofibrosis-type megakaryocyte dysplasia defines a spectrum of related MPN variants including CMD-NBV, CMD-IT, pre-fibrotic myelofibrosis and overt myelofibrosis, which differ from polycythemia vera and essential thrombocythemia. Our proposal needs external validation and we stress the need for a consensus definition of the megakaryocyte dysplasia which is the hallmark of these disorders., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
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6. Pro106Leu MPL mutation is associated with thrombocytosis and a low risk of thrombosis, splenomegaly and marrow fibrosis.
- Author
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Alzahrani M, Al Turki S, Al Rajban W, Alshalati F, Almodaihsh F, Abuelgasim KA, Alahmari B, Al Bogami T, Ali O, Al Harbi T, AlBalwi MA, Alotaibi M, Aleem A, Al Asker A, and Al Mugairi A
- Subjects
- Adult, Bone Marrow pathology, Child, Female, Humans, Male, Mutation, Retrospective Studies, Splenomegaly genetics, Primary Myelofibrosis genetics, Primary Myelofibrosis pathology, Receptors, Thrombopoietin genetics, Thrombocytosis genetics, Thrombocytosis pathology, Thrombosis complications
- Abstract
The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL) was shown to be associated with hereditary thrombocythemia in Arabs. The clinical and bone marrow (BM) features of P106L mutation are unknown. Genetic databases at two tertiary hospitals in Saudi Arabia were searched to identify patients with the MPL P106L mutation. Clinical data were collected retrospectively and the BM aspirates and biopsies were independently reviewed by two hematopathologists. In total, 115 patients were included. Median age was 33 years of which 31 patients were pediatric and 65 were female. The mutation was homozygous in 87 patients. Thrombocytosis was documented in 107 patients, with a median platelet count of 667 × 10
9 /L. The homozygous genotype was associated with a higher platelet count. Thirty-three patients had an evaluable BM and clustering of megakaryocytes was observed in 30/33 patients. At the time of last follow-up, 114 patients were alive. The median follow-up was 7.8 years from the time of thrombocytosis. No patients developed disease progression to myelofibrosis. The P106L mutation was associated with marked thrombocytosis at a younger age and with a low risk of thrombosis, splenomegaly, and marrow fibrosis. The BM demonstrated normal or hypocellular marrow with megakaryocyte clusters.- Published
- 2022
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7. Platelet Count as a Prognostic Factor in Stage IV Non-Small Cell Lung Cancer.
- Author
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Saha B, Khatun N, Azim N, Islam SA, Proteek MF, Islam MR, Begum FA, Biddut MA, Khan MK, and Islam MR
- Subjects
- Adult, Aged, Bangladesh epidemiology, Female, Humans, Infant, Male, Middle Aged, Neoplasm Staging, Platelet Count, Prognosis, Retrospective Studies, Weight Loss, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms diagnosis, Thrombocytosis diagnosis, Thrombocytosis pathology
- Abstract
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.
- Published
- 2022
8. Pseudothrombocytosis due to small misshapen RBC and fragmented RBC in coexistence of beta thalassemia minor and secondary elliptocytosis.
- Author
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Luo X, Zhang H, Luo X, Geng L, and Liu K
- Subjects
- Adult, Humans, Male, Elliptocytosis, Hereditary genetics, Elliptocytosis, Hereditary metabolism, Elliptocytosis, Hereditary pathology, Erythrocytes, Abnormal metabolism, Erythrocytes, Abnormal pathology, Thrombocytosis genetics, Thrombocytosis metabolism, Thrombocytosis pathology, beta-Thalassemia genetics, beta-Thalassemia metabolism, beta-Thalassemia pathology
- Published
- 2022
- Full Text
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9. Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts, thrombocytosis, and mutated JAK2/SF3B1 without anemia.
- Author
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Neumann NM and Wen KW
- Subjects
- Aged, Female, Humans, Mutation, Myelodysplastic-Myeloproliferative Diseases complications, Myelodysplastic-Myeloproliferative Diseases genetics, Thrombocytosis complications, Thrombocytosis genetics, Janus Kinase 2 genetics, Myelodysplastic-Myeloproliferative Diseases pathology, Phosphoproteins genetics, RNA Splicing Factors genetics, Thrombocytosis pathology
- Published
- 2022
- Full Text
- View/download PDF
10. Platelet count and breast cancer stage.
- Author
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Fahdrin A, Sampepajung E, Pieter J, Kasim F, Smaradhania N, Prihantono P, Mariana N, Sampepajung D, and Faruk M
- Subjects
- Humans, Female, Platelet Count, Cross-Sectional Studies, Retrospective Studies, Prognosis, Neoplasm Staging, Breast Neoplasms pathology, Thrombocytosis pathology
- Abstract
Introduction: The relationship between increased platelet count and cancer classification stage has long been established. The prevalence of thrombocytosis varies from 10% to 57% in cancer patients. The pathogenesis of thrombocytosis in malignancy is uncertain. However, there is evidence that tumor cells secrete humoral factors that can cause thrombocytosis. Preoperative thrombocytosis is a poor prognostic variable in malignancies. This study investigated the correlation between platelet count and breast cancer stage., Methods: This cross-sectional study was conducted from February 2020 to January 2021. Patient data were collected from medical records. The study population comprised breast cancer patients at Dr. Wahidin Sudirohusodo Makassar. The staging examinations were based on the tumor, node, metastasis (TNM) classification according to the American Joint Committee on Cancer (AJCC) 8th Edition., Results: The study group comprised 171 breast cancer patients of varying ages. Metastasis was present in five (2.92%) patients and absent in 166 (97.8%) patients. Analyses found no statistically significant differences between the three staging groups based on the platelet count (p = 0.952)., Conclusion: There was no statistically significant relationship between increased platelet count and staging according to the TNM classification in breast cancer patients.
- Published
- 2022
- Full Text
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11. Thrombocytosis in COVID-19 patients without myeloproliferative neoplasms is associated with better prognosis but higher rate of venous thromboembolism.
- Author
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Lucijanic M, Krecak I, Soric E, Sedinic M, Sabljic A, Derek L, Jaksic O, and Kusec R
- Subjects
- Aged, Aged, 80 and over, Blood Platelets virology, COVID-19 transmission, COVID-19 virology, Female, Humans, Male, Middle Aged, Myeloproliferative Disorders virology, Prognosis, SARS-CoV-2 isolation & purification, Thrombocytosis pathology, Thrombocytosis virology, Venous Thromboembolism etiology, Venous Thromboembolism virology, Blood Platelets pathology, COVID-19 complications, Myeloproliferative Disorders blood, Thrombocytosis complications, Venous Thromboembolism pathology
- Published
- 2021
- Full Text
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12. A typical acute lymphoblastic leukemia JAK2 variant, R683G, causes an aggressive form of familial thrombocytosis when germline.
- Author
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Carreño-Tarragona G, Varghese LN, Sebastián E, Gálvez E, Marín-Sánchez A, López-Muñoz N, Nam-Cha S, Martínez-López J, Constantinescu SN, Sevilla J, and Ayala R
- Subjects
- Adult, Child, Female, Humans, Male, Pedigree, Thrombocytosis etiology, Thrombocytosis metabolism, Young Adult, Germ-Line Mutation, Janus Kinase 2 genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Thrombocytosis pathology
- Published
- 2021
- Full Text
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13. Extramedullary myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with ring sideroblasts and thrombocytosis.
- Author
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Kerneves P, Cornet E, and Paubelle E
- Subjects
- Aged, Bone Marrow pathology, Erythroblasts pathology, Humans, Male, Myelodysplastic-Myeloproliferative Diseases complications, Thrombocytosis complications, Hematopoiesis, Extramedullary, Myelodysplastic-Myeloproliferative Diseases pathology, Thrombocytosis pathology
- Published
- 2021
- Full Text
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14. Pediatric Chronic Myeloid Leukemia Presenting With Extreme Thrombocytosis and Acute Upper Gastrointestinal Hemorrhage: A Case Report.
- Author
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Zheng Y, Wen J, and Li J
- Subjects
- Acute Disease, Child, Gastrointestinal Hemorrhage etiology, Humans, Male, Prognosis, Thrombocytosis etiology, Gastrointestinal Hemorrhage pathology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Thrombocytosis pathology
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2021
- Full Text
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15. Treatment breaks in first line treatment of advanced colorectal cancer: An individual patient data meta-analysis.
- Author
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Adams R, Goey K, Chibaudel B, Koopman M, Punt C, Arnold D, Hinke A, Hegewisch-Becker S, de Gramont A, Labianca R, Diaz Rubio E, Magne Tveit K, Wasan H, Kaplan R, Brown L, Maughan T, and Fisher D
- Subjects
- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Colorectal Neoplasms blood, Drug Administration Schedule, Humans, Maintenance Chemotherapy, Prognosis, Randomized Controlled Trials as Topic, Thrombocytosis pathology, Colorectal Neoplasms drug therapy
- Abstract
Background: Intermittent systemic anti-cancer therapy in patients with advanced colorectal cancer (aCRC) may improve quality of life without compromising overall survival (OS). We aimed to use individual patient data meta-analysis (IPDMA) from multiple randomised controlled trials evaluating intermittent strategies to inform clinical practice. We also aimed to validate whether thrombocytosis as a predictive biomarker identified patients with significantly reduced OS receiving a complete treatment break., Patients and Methods: An IPDMA of intermittent strategy impact on survival was undertaken, including all relevant trials in which data were available. Intermittent strategies were classified into two groups: a planned stopping of all therapy ("treatment break strategy"; 6 trials; 2,907 patients) or to the same treatment omitting oxaliplatin ("maintenance strategy"; 3 trials; 1,271 patients). The primary analysis sample was of patients successfully completing induction therapy. Additionally, a pre-planned analysis of the predictive value of thrombocytosis on survival under a continuous versus an intermittent strategy was undertaken., Results: All trials had comparable inclusion criteria. The overall IPDMA of intermittent therapy versus continuous therapy demonstrated no detriment in OS (HR = 1.03 [95% CI 0.93-1.14]), whether from complete break (HR 1.04 [95% CI 0.87-1.26]) or maintenance strategies (HR 0.99 [95% CI 0.87-1.13]). Thrombocytosis was confirmed as a marker of poor prognosis in aCRC, but did not predict for OS detriment from treatment break strategies (interaction HR = 0.97 [95% CI 0.66-1.40] compared to continuous therapy)., Conclusion: The highest levels of evidence from this IPDMA indicate no detriment in survival for patients receiving an intermittent therapy strategy, either for maintenance or complete break strategies. Although, thrombocytosis is confirmed as a marker of poor prognosis, it is not predictive of poor outcome for patients treated with intermittent therapy. An intermittent chemotherapy strategy can therefore be applied irrespective of baseline platelet count and does not result in inferior OS compared to continuous chemotherapy., (Copyright © 2021. Published by Elsevier Ltd.)
- Published
- 2021
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16. Acquisition of JAK2 V617F to CALR-mutated clones accelerates disease progression and might enhance growth capacity.
- Author
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Nishimura M, Nagaharu K, Ikejiri M, Sugimoto Y, Sasao R, Ohya E, Mizutani M, Ohishi K, Tawara I, and Sekine T
- Subjects
- Disease Progression, Female, Humans, Middle Aged, Mutation, Myeloproliferative Disorders pathology, Thrombocytosis pathology, Calreticulin genetics, Janus Kinase 2 genetics, Myeloproliferative Disorders genetics, Thrombocytosis genetics
- Published
- 2021
- Full Text
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17. Evaluation of angiogenic signaling molecules associated with reactive thrombocytosis in an iron-deficient rat model.
- Author
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Garcia J, Mankin P, Gnanamony M, and de Alarcon PA
- Subjects
- Anemia, Iron-Deficiency blood, Anemia, Iron-Deficiency pathology, Animals, Disease Models, Animal, Male, Megakaryocytes pathology, Rats, Sprague-Dawley, Signal Transduction, Thrombocytosis blood, Thrombocytosis pathology, Thrombopoietin metabolism, Rats, Anemia, Iron-Deficiency complications, Bone Marrow blood supply, Megakaryocytes metabolism, Neovascularization, Pathologic, Receptors, CXCR4 metabolism, Thrombocytosis etiology, Thrombopoiesis, Vascular Endothelial Growth Factor A metabolism
- Abstract
Background: Iron deficiency anemia (IDA)-induced reactive thrombocytosis can occur in children and adults. The underlying mechanism for this phenomenon is indeterminate. Traditional cytokines such as thrombopoietin (TPO), interleukin-6 (IL-6), and IL-11 involved in megakaryopoiesis have not been shown to be the cause. Recent studies suggest that growth factors and signaling molecules involved with angiogenesis influence the proliferation and differentiation of megakaryocytes., Methods: We investigated the possible association between angiogenic cytokines with reactive thrombocytosis due to IDA in an iron-deficient (ID) rat model. Complete blood count, iron panels, and TPO levels were measured at baseline and 5 weeks later in both control (C) and ID rats. Angiogenic cytokines were evaluated in the bone marrow in all rats., Results: We successfully induced IDA in our rats by phlebotomy and reduced iron diet. We did not find an increase of TPO in ID rats. A review of the bone marrow showed an increase in the number of megakaryocytes, vascular structures, as well as increased intensity of stain for vascular endothelial growth factor (VEGF), and CXC chemokine receptor 4 (CXCR4) in rats with IDA compared to controls., Conclusions: Our results of histological bone marrow data suggest an important role for angiogenesis in the development of IDA-induced thrombocytosis., Impact: Thrombocytosis is common with IDA in both children and adults, but the mechanism is unclear. We confirmed that TPO is not the major driver of iron deficiency-associated thrombocytosis. We confirmed the increase in the number of megakaryocytes in the bone marrow despite stable TPO levels. We provided evidence supporting an important role of angiogenesis in megakaryocytopoiesis/thrombopoiesis with increased vascular structures and angiogenic cytokines in the bone marrow of iron-deficient rats. The demonstration that angiogenesis may play an important role in secondary thrombocytosis could lead to a new approach in treating symptomatic reactive thrombocytosis by targeting angiogenesis., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
- Published
- 2021
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18. New drugs for myeloid neoplasms with ring sideroblasts: Luspatercept vs imetelstat.
- Author
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Tefferi A
- Subjects
- Drug Approval, Drug Discovery, Humans, Myelodysplastic Syndromes pathology, Myelodysplastic-Myeloproliferative Diseases pathology, Thrombocytosis drug therapy, Thrombocytosis pathology, Activin Receptors, Type II therapeutic use, Immunoglobulin Fc Fragments therapeutic use, Myelodysplastic Syndromes drug therapy, Myelodysplastic-Myeloproliferative Diseases drug therapy, Oligonucleotides therapeutic use, Recombinant Fusion Proteins therapeutic use
- Published
- 2021
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19. Thrombocytosis in an infant with a TRPV4 mutation: a case report.
- Author
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Thom CS, Brandsma E, and Lambert MP
- Subjects
- Female, Humans, Infant, Thrombocytosis pathology, TRPV Cation Channels metabolism, Thrombocytosis genetics
- Abstract
Mutations in the calcium channel gene Transient Receptor Potential cation channel subfamily V member 4 ( TRPV4 ) cause autosomal dominant skeletal dysplasia, with phenotypes ranging from mild to perinatal lethality. A recent report detailed enhanced proplatelet formation and increased murine platelet count in the context of TRPV4 activation. No prior reports have described platelet count abnormalities in human TRPV4 disease. Here, we report a case of prolonged thrombocytosis in the context of TRPV4 -associated metatropic dysplasia that was lethal in the infantile period.
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- 2021
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20. Distinct effects of V617F and exon12-mutated JAK2 expressions on erythropoiesis in a human induced pluripotent stem cell (iPSC)-based model.
- Author
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Nilsri N, Jangprasert P, Pawinwongchai J, Israsena N, and Rojnuckarin P
- Subjects
- Erythropoiesis genetics, Exons, Gene Expression Regulation genetics, Humans, Induced Pluripotent Stem Cells metabolism, Mutation genetics, Myeloproliferative Disorders genetics, Myeloproliferative Disorders pathology, Polycythemia pathology, Polycythemia Vera pathology, Primary Myelofibrosis, STAT Transcription Factors genetics, Thrombocythemia, Essential genetics, Thrombocythemia, Essential pathology, Thrombocytosis genetics, Thrombocytosis pathology, Janus Kinase 2 genetics, Polycythemia genetics, Polycythemia Vera genetics, STAT1 Transcription Factor genetics, STAT3 Transcription Factor genetics
- Abstract
Activating mutations affecting the JAK-STAT signal transduction is the genetic driver of myeloproliferative neoplasms (MPNs) which comprise polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis. The JAK2p.V617F mutation can produce both erythrocytosis in PV and thrombocytosis in ET, while JAK2 exon 12 mutations cause only erythrocytosis. We hypothesized that these two mutations activated different intracellular signals. In this study, the induced pluripotent stem cells (iPSCs) were used to model JAK2-mutated MPNs. Normal iPSCs underwent lentiviral transduction to overexpress JAK2p.V617F or JAK2p.N542_E543del (JAK2exon12) under a doxycycline-inducible system. The modified iPSCs were differentiated into erythroid cells. Compared with JAK2V617F-iPSCs, JAK2exon12-iPSCs yielded more total CD71
+ GlycophorinA+ erythroid cells, displayed more mature morphology and expressed more adult hemoglobin after doxycycline induction. Capillary Western immunoassay revealed significantly higher phospho-STAT1 but lower phospho-STAT3 and lower Phospho-AKT in JAK2exon12-iPSCs compared with those of JAK2V617F-iPSCs in response to erythropoietin. Furthermore, interferon alpha and arsenic trioxide were tested on these modified iPSCs to explore their potentials for MPN therapy. Both agents preferentially inhibited proliferation and promoted apoptosis of the iPSCs expressing mutant JAK2 compared with those without doxycycline induction. In conclusion, the modified iPSC model can be used to investigate the mechanisms and search for new therapy of MPNs.- Published
- 2021
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21. Stathmin 1 deficiency induces erythro-megakaryocytic defects leading to macrocytic anemia and thrombocythemia in Stathmin 1 knock out mice.
- Author
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Ramlogan-Steel CA, Steel JC, Fathallah H, Iancu-Rubin C, and Atweh GF
- Subjects
- Anemia, Macrocytic pathology, Animals, Blood Platelets pathology, Erythropoiesis, Female, Gene Deletion, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Thrombocytosis pathology, Anemia, Macrocytic genetics, Erythroid Precursor Cells pathology, Megakaryocytes pathology, Stathmin genetics, Thrombocytosis genetics
- Abstract
Stathmin 1 (STMN1) is a cytosolic phosphoprotein that was discovered as a result of its high level of expression in leukemic cells. It plays an important role in the regulation of mitosis by promoting depolymerization of the microtubules that make up the mitotic spindle and, aging has been shown to impair STMN1 levels and change microtubule stability. We have previously demonstrated that a high level of STMN1 expression during early megakaryopoiesis is necessary for proliferation of megakaryocyte progenitors and that down-regulation of STMN1 expression during late megakaryopoiesis is important for megakaryocyte maturation and platelet production. In this report, we examined the effects of STMN1 deficiency on erythroid and megakaryocytic lineages in the mouse. Our studies show that STMN1 deficiency results in mild thrombocytopenia in young animals which converts into profound thrombocythemia as the mice age. STMN1 deficiency also lead to macrocytic changes in both erythrocytes and megakaryocytes that persisted throughout the life of STMN1 knock-out mice. Furthermore, STMN1 knock-out mice displayed a lower number of erythroid and megakaryocytic progenitor cells and had delayed recovery of their blood counts after chemotherapy. These studies show an important role for STMN1 in normal erythro-megakaryopoietic development and suggests potential implications for disorders affecting these hematopoietic lineages., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2021
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22. Clinical analysis and literature review of a case with the myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.
- Author
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Long B, Shi H, and Zhu C
- Subjects
- Aged, Antimetabolites, Antineoplastic therapeutic use, Bone Marrow drug effects, Decitabine therapeutic use, Female, Humans, Myelodysplastic-Myeloproliferative Diseases drug therapy, Myelodysplastic-Myeloproliferative Diseases genetics, Myelodysplastic-Myeloproliferative Diseases pathology, Thrombocytosis drug therapy, Thrombocytosis genetics, Thrombocytosis pathology, Bone Marrow pathology, Myelodysplastic-Myeloproliferative Diseases complications, Thrombocytosis complications
- Abstract
Objective: Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a new disease entity in the 2016 WHO classification, characterized by anemia, thrombocytosis and bone marrow ring sideroblasts. We herein reported a case of MDS/MPN-RS-T and discuss its clinical characteristics. Methods: A 69-year-old woman presented to our hospital with recurrent dizziness and fatigue. Hematologic investigations, bone marrow analysis and genomic DNA sequencing studies were performed. Results: Peripheral blood testing showed normocytes anemia and thrombocytosis, and bone marrow analysis revealed hypercellular with clusters of megakaryocytes and 95% ring sideroblasts (RS). She had a normal karyotype and was found to have SF3B1 mutations. Decitabine therapy produced a clinical response and disease remission in this patient. Conclusions: Our report provides a definite conceptual framework for a better understanding of the characteristics of MDS/MPN-RS-T.
- Published
- 2020
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23. Incorporation of pretreatment leukocytosis and thrombocytosis into the FIGO staging system for prognosis in surgically treated endometrial cancer.
- Author
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Yokoi E, Mabuchi S, Komura N, Shimura K, Matsumoto Y, and Kimura T
- Subjects
- Adult, Aged, Endometrial Neoplasms blood, Endometrial Neoplasms pathology, Endometrial Neoplasms surgery, Female, Humans, Japan epidemiology, Middle Aged, Neoplasm Recurrence, Local blood, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Neoplasm Staging, Preoperative Period, Prognosis, ROC Curve, Registries, Retrospective Studies, Survival Analysis, Endometrial Neoplasms mortality, Leukocytosis pathology, Neoplasm Recurrence, Local mortality, Thrombocytosis pathology
- Abstract
Objective: To investigate the impact of incorporating pretreatment leukocytosis and/or thrombocytosis in the FIGO staging system on prognostic prediction among women with surgically treated endometrial cancer., Methods: Retrospective review of clinical data from 900 women with endometrial cancer treated at Osaka University Hospital, Japan, between 2000 and 2016. The effect of concurrent leukocytosis and thrombocytosis on the prediction of recurrence and survival outcomes was evaluated via receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method., Results: Among 678 women with Stage I-III disease, pretreatment leukocytosis or thrombocytosis alone were not prognostic indicators, but concurrent pretreatment leukocytosis and thrombocytosis was associated with significantly shorter survival (PFS, P<0.001; OS, P=0.004). In contrast, pretreatment leukocytosis, pretreatment thrombocytosis, and concurrent pretreatment leukocytosis and thrombocytosis did not provide any prognostic information for women with Stage IV disease. In ROC curve analysis, incorporation of concurrent pretreatment leukocytosis and thrombocytosis into the FIGO staging system resulted in a higher area under the curve for predicting recurrence for women with Stages I-III disease (0.770 vs 0.755; P=0.045)., Conclusion: Incorporating concurrent pretreatment leukocytosis and thrombocytosis into the FIGO staging system might improve predictive performance and allow additional risk stratification for women with Stage I-III endometrial cancer., (© 2020 International Federation of Gynecology and Obstetrics.)
- Published
- 2020
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24. Clinicopathologic characterisation of myeloid neoplasms with concurrent spliceosome mutations and myeloproliferative-neoplasm-associated mutations.
- Author
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Liu YC, Illar GM, and Bailey NG
- Subjects
- Cohort Studies, Cytogenetics, Genotype, Humans, Leukemia genetics, Mutation, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics, Myeloproliferative Disorders diagnosis, Myeloproliferative Disorders genetics, Pathology, Molecular, Phenotype, RNA Splicing genetics, RNA Splicing Factors metabolism, Thrombocytosis diagnosis, Thrombocytosis genetics, Leukemia pathology, Myelodysplastic Syndromes pathology, Myeloproliferative Disorders pathology, RNA Splicing Factors genetics, Spliceosomes genetics, Thrombocytosis pathology
- Abstract
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.)
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- 2020
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25. A novel translocation t(10;17)(p13;q11.2) harboring two cryptic deletions identified by array-CGH and characterized by SUZ12 overexpression in a patient with chronic thrombocytosis.
- Author
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Batanian JR, Malherbe JAJ, and Erber WN
- Subjects
- Chromosome Breakpoints, Chromosomes, Human, Pair 10 genetics, Chromosomes, Human, Pair 17 genetics, Comparative Genomic Hybridization, Enhancer of Zeste Homolog 2 Protein genetics, Enhancer of Zeste Homolog 2 Protein metabolism, Female, Gene Deletion, Genetic Testing, Humans, Ki-67 Antigen genetics, Ki-67 Antigen metabolism, Middle Aged, Neoplasm Proteins metabolism, Neurofibromin 1 genetics, Thrombocytosis pathology, Transcription Factors metabolism, Neoplasm Proteins genetics, Thrombocytosis genetics, Transcription Factors genetics, Translocation, Genetic
- Abstract
No specific translocation is associated with myeloproliferative neoplasms (MPNs). However, an interstitial deletion involving subband 17q11.2 which includes the NF1 gene, although rare, is a recurrent aberration in several myeloid disorders including MPNs. For the first time, we report an acquired novel translocation involving 10p13 and 17q11.2 in a 62-year-old Caucasian female which was referred for investigation of chronic and persistent unexplained thrombocytosis. The patient had no history of hematological sequelae and genomic testing for JAK2, CALR, and MPL mutations were negative. She was subsequently diagnosed with a triple negative essential thrombocythemia. Array-CGH analysis noted that the translocation harbored two cryptic deletions, one of which involved 17q11.2 encompassing the NF1 gene. One of the junction breakpoints involved the SUZ12 gene. Immunohistochemical assessment of the marrow trephine showed increased megakaryocytic expression of the SUZ12 protein, as well as EZH2 and Ki67; biochemical abnormalities suggestive of excess megakaryocytic hyperplasia. This novel translocation may affect the expression of SUZ12 and its downstream targets, and may represent a unique pathogenomic etiology which drives chronic thrombocytosis in essential thrombocythemia., (© 2020 Wiley Periodicals LLC.)
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- 2020
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26. Platelets, Thrombocytosis, and Ovarian Cancer Prognosis: Surveying the Landscape of the Literature.
- Author
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Hufnagel DH, Cozzi GD, Crispens MA, and Beeghly-Fadiel A
- Subjects
- Female, Humans, Ovarian Neoplasms blood, Ovarian Neoplasms etiology, Prognosis, Thrombocytosis blood, Blood Platelets pathology, Ovarian Neoplasms pathology, Thrombocytosis pathology
- Abstract
Platelets are critical components of a number of physiologic processes, including tissue remodeling after injury, wound healing, and maintenance of vascular integrity. Increasing evidence suggests that platelets may also play important roles in cancer. In ovarian cancer, thrombocytosis, both at the time of initial diagnosis and at recurrence, has been associated with poorer prognosis. This review describes current evidence for associations between thrombocytosis and ovarian cancer prognosis and discusses the clinical relevance of platelet count thresholds and timing of assessment. In addition, we discuss several mechanisms from in vitro , in vivo , and clinical studies that may underlie these associations and recommend potential approaches for novel therapeutic targets for this lethal disease., Competing Interests: The authors declare no conflict of interest.
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- 2020
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27. Heavy metal.
- Author
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Dewarrat N and Blum S
- Subjects
- Aged, 80 and over, Anemia, Sideroblastic etiology, Anemia, Sideroblastic pathology, Anemia, Sideroblastic therapy, Arteriosclerosis etiology, Arteriosclerosis metabolism, Arteriosclerosis pathology, Biopsy, Blood Transfusion, Blood Vessels pathology, Bone Marrow metabolism, Bone Marrow pathology, Deferasirox therapeutic use, Female, Humans, Iron Overload diagnosis, Iron Overload drug therapy, Iron Overload etiology, Myelodysplastic-Myeloproliferative Diseases complications, Myelodysplastic-Myeloproliferative Diseases pathology, Myelodysplastic-Myeloproliferative Diseases therapy, Thrombocytosis etiology, Thrombocytosis pathology, Thrombocytosis therapy, Transfusion Reaction complications, Transfusion Reaction drug therapy, Transfusion Reaction pathology, Treatment Failure, Blood Vessels metabolism, Iron metabolism, Iron Overload pathology, Metals, Heavy metabolism
- Published
- 2020
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28. The Effect of TLR4 Blockade on Some Indicators of Systemic Inflammatory Response to Proteus mirabilis LPS in Rats.
- Author
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Sivak KV, Stosman KI, Rassokha TA, Aleksandrov AG, Kuzmich NN, Orshanskaya YR, Savateeva-Lubimova TN, and Lesiovskaya EE
- Subjects
- Alanine Transaminase blood, Alkaline Phosphatase blood, Animals, Animals, Outbred Strains, Creatinine blood, Disease Models, Animal, Gene Expression Regulation, Injections, Intravenous, Interleukin-1beta blood, Interleukin-1beta genetics, Interleukin-6 blood, Interleukin-6 genetics, Kidney drug effects, Kidney metabolism, Kidney pathology, L-Lactate Dehydrogenase blood, Leukocytosis blood, Leukocytosis pathology, Lipopolysaccharides toxicity, Liver drug effects, Liver metabolism, Liver pathology, Male, Proteus mirabilis chemistry, Rats, Sepsis blood, Sepsis pathology, Signal Transduction, Thrombocytosis blood, Thrombocytosis pathology, Toll-Like Receptor 4 blood, Toll-Like Receptor 4 genetics, Tumor Necrosis Factor-alpha blood, Tumor Necrosis Factor-alpha genetics, Urea blood, Anti-Inflammatory Agents pharmacology, Leukocytosis drug therapy, Lipopolysaccharides antagonists & inhibitors, Pyrans pharmacology, Sepsis drug therapy, Thrombocytosis drug therapy, Toll-Like Receptor 4 antagonists & inhibitors
- Abstract
The effects of TLR4 blocker on blood cell morphology, concentrations proinflammatory cytokines, and functional state of the liver and kidneys were studied in outbred male rats (n=60) after intravenous injection of 20 mg/kg LPS isolated from opportunistic Proteus mirabilis strain ATCC 51393. TLR4 blocker TLR4-IN-C34 was injected intravenously in a dose of 1 mg/kg/day over 3 days. Systemic inflammatory reaction induced by LPS was characterized by elevation of serum TNFα, IL-1β, IL-6, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis. Increased activity of hepatocyte enzymes (ALT, alkaline phosphatase, and lactate dehydrogenase), retention of nitrogen metabolites (urea and creatinine), elevated content of protein oxidation products, and enhanced protein catabolism were also observed. Administration of TLR4 blocker reduced parameters of inflammatory reaction and prevented the development of hypercatabolic syndrome; endotoxicosis and kidney function indicators approached the normal levels.
- Published
- 2020
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29. A Young Woman with Thrombocytosis.
- Author
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Bose P
- Subjects
- Adult, Age Factors, Female, Hematologic Neoplasms blood, Hematologic Neoplasms pathology, Humans, Middle Aged, Thrombocytosis pathology, Young Adult, Thrombocytosis diagnosis, Thrombocytosis drug therapy
- Abstract
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.)- Published
- 2020
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30. Diagnostic Value of the Neutrophil/Lymphocyte Ratio, Platelet/Lymphocyte Ratio, and Thrombocytosis in the Preoperative Investigation of Ovarian Masses.
- Author
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Yoshida A, Sarian LO, Marangoni M Junior, Firmano IC, and Derchain SF
- Subjects
- CA-125 Antigen blood, Female, Humans, Preoperative Period, Retrospective Studies, Lymphocyte Count, Lymphocytes cytology, Neutrophils cytology, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology, Platelet Count, Thrombocytosis pathology
- Abstract
Objective: To evaluate the diagnostic accuracy of cancer antigen 125 (CA125) and complete blood count (CBC) parameters, such as the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and thrombocytosis in patients with ovarian masses., Methods: The present is a retrospective study conducted at a single tertiary hospital from January 2010 to November 2016. We included consecutive women referred due to suspicious adnexal masses. The CBC and CA125 were measured in the serum of 528 women with ovarian masses before surgery or biopsy. We evaluated the diagnostic performance of the NLR, PLR, platelets (PLTs), CA125, and the associations between them. We tested the clinical utility of the CBC parameters and CA125 in the discrimination of ovarian masses through decision curve analysis (DCA)., Results: The best balance between sensitivity and specificity was obtained by the associations of CA125 or PLTs ≥ 350/nL, with 70.14% and 71.66%, CA125 or PLTs ≥ 400/nL, with 67.30% and 81.79%, CA125 or PLR, with 76.3% and 64.87%, and CA125 or NLR, with 71.09% and 73.89% respectively. In the DCA, no isolated CBC parameter presented a higher clinical utility than CA125 alone., Conclusion: We showed that no CBC parameter was superior to CA125 in the prediction of the malignancy of ovarian tumors in the preoperative scenario., Competing Interests: The authors have no conflict of interests to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)
- Published
- 2020
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31. Blood Platelet Count at Hospital Admission Impacts Long-Term Mortality in Patients with Acute Coronary Syndrome.
- Author
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Małyszczak A, Łukawska A, Dyląg I, Lis W, Mysiak A, and Kuliczkowski W
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Platelets pathology, Cause of Death, Female, Hospitalization, Humans, Male, Mean Platelet Volume, Middle Aged, Poland epidemiology, Prognosis, Retrospective Studies, Survival Analysis, Thrombocytopenia pathology, Thrombocytosis pathology, Time Factors, Acute Coronary Syndrome blood, Acute Coronary Syndrome mortality, Platelet Count, Thrombocytopenia blood, Thrombocytosis blood
- Abstract
Introduction: Platelets play a fundamental role in the pathogenesis of acute coronary syndrome (ACS). The platelet count (PC) at hospital admission is easy to obtain, but whether thrombocytopenia or/and thrombocytosis impact long-term mortality (LTM) after ACS is unclear., Objective: To evaluate the effect of PC at hospital admission on LTM in patients with ACS., Methods: This retrospective cohort study included patients with the ICD-10 codes for unstable angina (I.20) and acute myocardial infarction (I.21, I.22). Thrombocytopenia was defined as a blood PC <150 G/L and thrombocytosis as a PC >450 G/L. Additional platelet indices which were tested included plateletcrit (PCT), the mean platelet volume (MPV), the platelet distribution width (PDW), and the platelet larger cell ratio (P-LCR). Data on all-cause death were obtained from the National Health Fund database., Results: The study included 3,162 patients with a median follow-up of 27.2 months (interquartile range 12.5-46.8 months; max 68.7 months). Patients with thrombocytopenia and thrombocytosis yielded a higher maximal analyzed 5-year mortality rate in comparison with normal PC patients (45.8 and 47.7 vs. 24.2%, respectively; p < 0.00001) which was mainly driven by higher deaths at 1-2 years after ACS. The 5-year LTM was also significantly higher in patients with abnormal PCT and MPV levels in comparison with patients with PCT and MPV within the normal range. Other platelet indices (PDW, P-LCR) were not associated with a worse outcome. The Cox proportional hazards model revealed that thrombocytopenia at admission was independently associated with higher LTM after ACS (RR 1.83; 95% CI 1.1-3.0; p = 0.01)., Conclusions: Both thrombocytopenia and thrombocytosis at hospital admission in post-ACS patients are associated with a significant almost two times higher 5-year mortality rate., (© 2020 S. Karger AG, Basel.)
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- 2020
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32. Diagnostic workflow for hereditary erythrocytosis and thrombocytosis.
- Author
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McMullin MF
- Subjects
- Adult, Humans, Male, Genetic Diseases, Inborn diagnosis, Genetic Diseases, Inborn genetics, Genetic Diseases, Inborn pathology, Janus Kinase 2 genetics, Mutation, Polycythemia diagnosis, Polycythemia genetics, Polycythemia pathology, Receptors, Thrombopoietin genetics, Thrombocytosis diagnosis, Thrombocytosis genetics, Thrombocytosis pathology
- Abstract
In the patient presenting with an elevated blood count who does not have an acquired clonal disorder causing a myeloproliferative neoplasm, hereditary erythrocytosis or hereditary thrombocytosis needs to be considered as a possible explanation. A young patient and/or those with a family history of myeloproliferative neoplasm should specifically raise this possibility. Among the causes of hereditary erythrocytosis are mutations in the genes in the oxygen sensing pathway and high-affinity hemoglobins. Hereditary thrombocytosis has been shown to be accounted for by mutations in THPO, MPL, and JAK2 genes. In those who have a possible hereditary erythrocytosis or thrombocytosis, the investigative pathway includes specific investigation to rule out the more common acquired clonal disorders, and, if indicated, other secondary causes, measurement of specific cytokines as indicated, and search for specific identified molecular lesions that have been shown to cause these hereditary disorders. There remain individuals who appear to have a hereditary disorder in whom a genetic lesion cannot currently be identified., Competing Interests: Conflict-of-interest disclosure: M.F.M. serves on the advisory committee for Italopharma and Daiichi Sankyo and has received honoraria from, and is a member of the speakers’ bureau for, Novartis., (© 2019 by The American Society of Hematology. All rights reserved.)
- Published
- 2019
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33. JAK2 exon 12 mutation in myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis: Not an exclusive mutation to polycythaemia vera.
- Author
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Inano T, Araki M, Morishita S, Imai M, Yasuda H, Nitta H, Ito M, Edahiro Y, Ochiai T, Misawa K, Fukuda Y, Ohsaka A, and Komatsu N
- Subjects
- Anemia, Sideroblastic genetics, Anemia, Sideroblastic pathology, Humans, Myelodysplastic-Myeloproliferative Diseases pathology, Phosphoproteins genetics, Polycythemia Vera pathology, RNA Splicing Factors genetics, Thrombocytosis genetics, Thrombocytosis pathology, Tumor Stem Cell Assay, Janus Kinase 2 genetics, Mutation, Myelodysplastic-Myeloproliferative Diseases genetics, Polycythemia Vera genetics
- Published
- 2019
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34. Megakaryocytes in Peripheral Blood Smears
- Author
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Garg N, Gupta RJ, and Kumar S
- Subjects
- Adolescent, Adult, Anemia, Hypochromic pathology, Burns pathology, Child, Female, Humans, Leukocytosis pathology, Male, Thrombocytopenia pathology, Thrombocytosis pathology, Megakaryocytes pathology
- Published
- 2019
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35. Clinicopathological and molecular features of SF3B1-mutated myeloproliferative neoplasms.
- Author
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Boiocchi L, Hasserjian RP, Pozdnyakova O, Wong WJ, Lennerz JK, Le LP, Dias-Santagata D, Iafrate AJ, Hobbs GS, and Nardi V
- Subjects
- Aged, Cytogenetic Analysis, Disease Progression, Female, Humans, Male, Middle Aged, Myeloproliferative Disorders genetics, Thrombocytosis genetics, Myeloproliferative Disorders pathology, Phosphoproteins genetics, RNA Splicing Factors genetics, Thrombocytosis pathology
- Abstract
The introduction of next-generation sequencing has broadened the genetic landscape of myeloproliferative neoplasms (MPNs) beyond JAK2, MPL, and CALR. However, the biological role and clinical impact of most other mutations are not well defined. We interrogated 101 genes in 143 BCR-ABL1-negative MPNs in chronic phase from 2 large institutions. We detected SF3B1 mutations in 15 cases (10%) and set to investigate the clinical, morphologic, and molecular features of SF3B1 mutated (SF3B1+) MPNs in comparison to SF3B1 wild-type (SF3B1-) cases and to identify distinctive features with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts (RS) and thrombocytosis, which can show partial clinical and morphological overlap with MPNs. SF3B1+ cases were enriched in primary myelofibrosis in both prefibrotic and fibrotic stage, but mutations of SF3B1 seem to occur only as a late event in the fibrotic phase of essential thrombocythemia and polycythemia vera. SF3B1+ MPNs showed borderline lower hemoglobin but no other clinical or molecular differences compared to SF3B1- MPNs. Of note, RS were present only in a subset of SF3B1+ cases (4/10) without any other feature of erythroid or granulocytic dysplasia. Our results suggest that mutations in SF3B1 are not a rare event in MPNs, especially in primary myelofibrosis and during late fibrotic stages of essential thrombocythemia and polycythemia vera, but are not associated with myelodysplastic progression. Careful examination of bone marrow and peripheral blood for morphologic dysplasia is crucial to reach the correct diagnosis and avoid a misdiagnosis of myelodysplastic/myeloproliferative neoplasms with RS and thrombocytosis, a pitfall with potential prognostic and therapeutic implications., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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36. Platelet miR-28 expression level and thrombocytosis in MPN patients.
- Author
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Stolyar MA, Gorbenko AS, and Olkhovskiy IA
- Subjects
- Adult, Blood Platelets pathology, Female, Hematologic Neoplasms genetics, Hematologic Neoplasms pathology, Humans, Male, MicroRNAs genetics, Middle Aged, Myeloproliferative Disorders genetics, Myeloproliferative Disorders pathology, RNA, Neoplasm genetics, Thrombocytosis genetics, Thrombocytosis pathology, Blood Platelets metabolism, Gene Expression Regulation, Neoplastic, Hematologic Neoplasms metabolism, MicroRNAs biosynthesis, Myeloproliferative Disorders metabolism, RNA, Neoplasm biosynthesis, Thrombocytosis metabolism
- Published
- 2019
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37. The S505A thrombopoietin receptor mutation in childhood hereditary thrombocytosis and essential thrombocythemia is S505N: single letter amino acid code matters.
- Author
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Defour JP, Levy G, Leroy E, Smith SO, and Constantinescu SN
- Subjects
- Child, Humans, Thrombocythemia, Essential pathology, Thrombocytosis pathology, Amino Acids genetics, Mutation, Receptors, Thrombopoietin genetics, Thrombocythemia, Essential genetics, Thrombocytosis genetics
- Published
- 2019
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- View/download PDF
38. Management of Iron Deficiency Anaemia in Inflammatory Bowel Disease.
- Author
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Jimenez KM and Gasche C
- Subjects
- Anemia, Iron-Deficiency complications, Anemia, Iron-Deficiency pathology, Humans, Inflammatory Bowel Diseases complications, Lymphocytes cytology, Lymphocytes metabolism, Quality of Life, Severity of Illness Index, Thrombocytosis complications, Thrombocytosis pathology, Anemia, Iron-Deficiency drug therapy, Inflammatory Bowel Diseases pathology, Iron administration & dosage
- Abstract
Inflammatory bowel disease (IBD) is a group of chronic relapsing inflammatory disorders affecting the large and small intestine, with a rising worldwide incidence and prevalence. Anaemia is the most common extraintestinal manifestation of IBD, correlating with disease activity, and tending to relapse even after successful therapy. Iron deficiency is the most common cause; however, it often manifests in combination with anaemia of inflammation. As such, multiple parameters are used for the diagnosis of iron deficiency anaemia in IBD. Timely recognition and selection of appropriate therapy leads to an improvement in the quality of life and prevention of potential sequelae. Oral iron can be effective under specific circumstances; however, as luminal iron changes microbiota and bacterial metabolism, oral administration should be avoided. Intravenous iron is preferred as it bypasses the sites of inflammation. Nevertheless, the optimization of IBD treatment should occur simultaneously, as this improves both patient condition and response to iron therapy. Herein, we discuss the screening, diagnosis, selection of therapy, and follow-up for iron deficiency anaemia in IBD., (© 2019 S. Karger AG, Basel.)
- Published
- 2019
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39. Approximately 1% of chronic myeloid leukaemia cases present with isolated thrombocytosis and express common major breakpoints: a finding from a laboratory audit.
- Author
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Ng TF, Wright M, and De Kraa R
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Laboratories, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myeloid diagnosis, Male, Thrombocytosis diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukemia, Myeloid pathology, Thrombocytosis pathology
- Published
- 2019
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- View/download PDF
40. Marked rebound thrombocytosis in response to glucocorticoids in a patient with acquired amegakaryocytic thrombocytopenia.
- Author
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Nishino S, Kodaka T, Sawada Y, Goka T, Gotoh Y, Tsunemine H, and Takahashi T
- Subjects
- Adult, Autoantigens blood, Humans, Iodide Peroxidase blood, Iron-Binding Proteins blood, Male, Platelet Count, Prednisolone administration & dosage, Bone Marrow Cells metabolism, Bone Marrow Cells pathology, Megakaryocytes metabolism, Megakaryocytes pathology, Myelopoiesis drug effects, Prednisolone adverse effects, Thrombocytopenia blood, Thrombocytopenia drug therapy, Thrombocytopenia pathology, Thrombocytosis blood, Thrombocytosis chemically induced, Thrombocytosis pathology
- Abstract
Acquired amegakaryocytic thrombocytopenia (AATP) is a rare disease characterized by thrombocytopenia and the disappearance of marrow megakaryocytes. A 43-year-old man was admitted because of thrombocytopenia of 1.0×10
9 /L. Bone marrow aspirate demonstrated normal hematopoiesis lacking megakaryocytes, and AATP was diagnosed. The serum concentration of thrombopoietin (TPO) was high (7.72 fmol/mL). Prednisolone (PSL) at 60 mg/day was started and the platelet count recovered to 1,335×109 /L; however, excessive megakaryocytopoiesis and subsequent decline in platelet count were noted 14 days later. At the peak platelet count, the TPO remained at 3.79 fmol/mL and returned to a normal level of 0.40 fmol/mL during the period of normal platelet count after PSL tapering. The marked thrombocytosis in response to prednisolone may have been caused by the high TPO after the resolution of suppressed megakaryopoiesis. Marked rebound thrombocytosis beyond 1,000×109 /L after successful PSL treatment for AATP has not been previously reported.- Published
- 2018
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41. Performance and usefulness of platelet aggregation testing.
- Author
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Rivera J and Lozano ML
- Subjects
- Blood Platelets drug effects, Blood Platelets pathology, Humans, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors therapeutic use, Platelet Function Tests instrumentation, Point-of-Care Testing standards, Thrombocytopenia blood, Thrombocytopenia pathology, Thrombocytosis blood, Thrombocytosis pathology, Thrombocytosis prevention & control, Blood Platelets metabolism, Platelet Function Tests methods, Thrombocytopenia diagnosis, Thrombocytosis diagnosis
- Published
- 2018
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- View/download PDF
42. Preliminary investigation about the expression of tubulin in platelets from patients with iron deficiency anemia and thrombocytosis.
- Author
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Yung KC, Zhang ZW, Yu WJ, Qiu JF, Xu CW, He CL, Xu XR, and Yin J
- Subjects
- Adult, Anemia, Iron-Deficiency pathology, Blood Platelets pathology, Female, Humans, Male, Middle Aged, Thrombocytosis pathology, Anemia, Iron-Deficiency metabolism, Blood Platelets metabolism, Gene Expression Regulation, Thrombocytosis metabolism, Tubulin biosynthesis
- Abstract
Objective: In order to inquire into the pathogenesis of increased platelet counts in peripheral blood of patients with iron deficiency anemia (IDA), the phenomenon of thrombocytosis was confirmed, and then the expression of tubulin within platelets from IDA patients was investigated., Methods: Peripheral blood samples were collected from 79 patients with IDA and were divided into 2 groups, group of IDA with normal platelet counts (34 cases), and group of IDA with increased platelet counts (thrombocytosis) (45 cases). Additionally, 45 peripheral blood samples from healthy volunteers were enrolled as a group of healthy controls. Count of platelets in peripheral blood was detected by means of LH-780 hematology analyzer and hemocytometer under a microscope respectively, and analyzed statistically., Results: There was no statistical difference between platelet counts detected by LH-780 hematology analyzer and hemocytometer under a microscope (P > .05). The mean fluorescence intensity (MFI) of both α-tubulin and β-tubulin within platelets from IDA patients with thrombocytosis was significantly less than that from healthy volunteers and IDA patients with normal platelet counts (P < .01), and there was no statistical difference between the latter two groups (P > .05)., Conclusion: Some patients with IDA are accompanied by thrombocytosis, from which the expression of α-tubulin and β-tubulin within platelets reduced obviously compared with those with normal platelet counts and healthy controls respectively. It is implied that downregulation of tubulin probably is a part of the pathogenesis leading to increased platelet counts in IDA.
- Published
- 2018
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43. Progression to polythythemia vera from familial thrombocytosis with germline JAK2 R867Q mutation.
- Author
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Maie K, Yokoyama Y, Yano Y, Kato T, Nannya Y, Ogawa S, Noguchi M, Sakata-Yanagimoto M, and Chiba S
- Subjects
- Adult, Amino Acid Substitution, Female, Genetic Diseases, Inborn blood, Genetic Diseases, Inborn pathology, Humans, Polycythemia Vera blood, Polycythemia Vera etiology, Polycythemia Vera pathology, Thrombocytosis blood, Thrombocytosis complications, Thrombocytosis pathology, Genetic Diseases, Inborn genetics, Janus Kinase 2 genetics, Mutation, Missense, Polycythemia Vera genetics, Thrombocytosis genetics
- Published
- 2018
- Full Text
- View/download PDF
44. Thrombocytosis as a prognostic factor in inflammatory breast cancer.
- Author
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Harano K, Kogawa T, Wu J, Yuan Y, Cohen EN, Lim B, Reuben JM, and Ueno NT
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Platelets pathology, Cytokines blood, Female, Humans, Inflammatory Breast Neoplasms complications, Inflammatory Breast Neoplasms epidemiology, Inflammatory Breast Neoplasms pathology, Middle Aged, Neoplasm Staging, Prognosis, Proportional Hazards Models, Thrombocytosis complications, Thrombocytosis epidemiology, Thrombocytosis pathology, Tumor Microenvironment genetics, Chemokine CXCL1 blood, Inflammatory Breast Neoplasms blood, Thrombocytosis blood, Transforming Growth Factor beta1 blood
- Abstract
Purpose: Platelets are essential components of hemostasis and also play an important role in the tumor microenvironment. The purposes of our research were to examine the role of thrombocytosis in inflammatory breast cancer (IBC) and to know which cytokine drives thrombocytosis., Methods: We reviewed the medical records of 3654 patients with stage I-III breast cancer treated between 1998 and 2013, including 230 patients (6%) with IBC. We used Chi-squared test or Fisher's exact test to compare the variables between patients with and without thrombocytosis. Multivariate Cox regression models were used to determine the association of thrombocytosis with overall survival. We also examined baseline serum cytokine levels in 81 patients with primary IBC to determine the association of inflammatory cytokines with thrombocytosis., Results: We found that thrombocytosis was the only variable that predicted prognosis. Fifty-five patients (1.5%) had thrombocytosis. Thrombocytosis was more prevalent in patients with IBC than in those with non-IBC (3.4% vs. 1.4%, p = 0.015). In patients with IBC, thrombocytosis was associated with worse overall survival [hazard ratio 2.38, 95% confidence interval (CI) 1.05-5.4, p = 0.0378]. Circulating levels of growth-regulated oncogene (GRO) (odds ratio 1.003, 95% CI 1.001-1.005, p = 0.0019) and transforming growth factor β (TGF-β) (odds ratio 1.3, 95% CI 1.128-1.499, p = 0.0003) were associated with thrombocytosis., Conclusions: Thrombocytosis was more prevalent in patients with IBC than in those with non-IBC and it was associated with poor prognosis. GRO and TGF-β were associated with thrombocytosis in IBC.
- Published
- 2017
- Full Text
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45. Thrombocytosis in 715 Dogs (2011-2015).
- Author
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Woolcock AD, Keenan A, Cheung C, Christian JA, and Moore GE
- Subjects
- Animals, Autoimmune Diseases veterinary, Dogs, Endocrine System Diseases complications, Endocrine System Diseases veterinary, Female, Glucocorticoids adverse effects, Inflammation complications, Inflammation veterinary, Male, Neoplasms complications, Neoplasms veterinary, Retrospective Studies, Risk Factors, Thrombocytosis complications, Thrombocytosis pathology, Dog Diseases pathology, Platelet Count veterinary, Thrombocytosis veterinary
- Abstract
Background: Thrombocytosis is a hematologic abnormality in dogs that has been associated with various neoplastic, metabolic, and inflammatory conditions., Objective: To classify thrombocytosis in dogs based on severity and evaluate whether there are associations between severity and underlying disease processes., Animals: Seven hundred and fifteen dogs with thrombocytosis and 1,430 dogs with normal numbers of platelets., Methods: Retrospective study. Medical records of dogs with increased (>500 × 10
3 /μL; thrombocytosis group) and normal (300-500 × 103 /μL; control group) platelet counts between 2011 and 2015 were reviewed. Dogs were characterized by severity of platelet increase and diagnosis. Diagnostic categories included neoplasia, endocrine disease, inflammatory disease, or miscellaneous., Results: A total of 1,254 complete blood counts with thrombocytosis from 715 dogs were included in the study. Median platelet count in this population was 582 × 103 /μL (500-1,810 × 103 /μL). No correlation between severity of thrombocytosis and diagnosis was identified. Causes of secondary thrombocytosis included neoplasia (55.7%), endocrine disease (12.0%), and inflammatory disease (46.6%). Immune-mediated disease was common (22.2%), associated with frequent glucocorticoid administration, and had a significantly higher median platelet count (636 × 103 /μL [500-1,262 × 103 /μL] versus 565 × 103 /μL [500-1,810 × 103 /μL]) when compared to the other inflammatory processes (P < 0.001). The diagnoses in the thrombocytosis dogs differed significantly from the control population (P < 0.001)., Conclusions and Clinical Importance: Thrombocytosis is commonly associated with carcinoma and immune-mediated disease in dogs., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)- Published
- 2017
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46. Paraneoplastic thrombocytosis is associated with increased mortality and increased rate of lymph node metastasis in oesophageal adenocarcinoma.
- Author
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Agoston AT, Srivastava A, Zheng Y, Bueno R, Odze RD, and Szallasi Z
- Subjects
- Adenocarcinoma diagnosis, Adenocarcinoma mortality, Adenocarcinoma therapy, Aged, Chemoradiotherapy, Cohort Studies, Esophageal Neoplasms diagnosis, Esophageal Neoplasms mortality, Esophageal Neoplasms therapy, Esophagectomy, Female, Humans, Lymph Nodes pathology, Lymphatic Metastasis, Male, Middle Aged, Neoadjuvant Therapy, Paraneoplastic Syndromes diagnosis, Paraneoplastic Syndromes therapy, Platelet Count, Prognosis, Proportional Hazards Models, Thrombocytosis diagnosis, Thrombocytosis mortality, Thrombocytosis therapy, Adenocarcinoma pathology, Esophageal Neoplasms pathology, Paraneoplastic Syndromes pathology, Thrombocytosis pathology
- Abstract
Paraneoplastic thrombocytosis has been associated with adverse outcomes in several cancers, but has not been described in oesophageal adenocarcinoma. The aim of our study was to examine the prognostic value of platelet counts in patients with oesophageal adenocarcinoma. A cohort of 584 patients who underwent oesophagectomy for oesophageal adenocarcinoma was identified. Platelet counts, history of neoadjuvant chemoradiation, and clinicopathological factors such as T and N stage, and overall survival were recorded. Patients with elevated platelet count (>450,000/μL) had a higher mortality rate than patients with normal platelet count (150,000-450,000/μL) (hazard ratio = 2.60, p = 0.0013). This effect was seen in patients with and without neoadjuvant chemoradiation therapy. Paraneoplastic thrombocytosis was also associated with increased likelihood of lymph node metastasis compared to normal platelet count (69% versus 31%, p < 0.01). Paraneoplastic thrombocytosis is associated with increased rate of lymph node metastasis and mortality in oesophageal adenocarcinoma. Further studies are needed to examine the mechanisms behind this phenomenon., (Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
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47. Establishing evidence-based thresholds and laboratory practices to reduce inappropriate treatment of pseudohyperkalemia.
- Author
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Ranjitkar P, Greene DN, Baird GS, Hoofnagle AN, and Mathias PC
- Subjects
- Blood Platelets metabolism, Chelating Agents adverse effects, Diagnostic Errors, Humans, Hyperkalemia blood, Hyperkalemia etiology, Hyperkalemia pathology, Leukocyte Count, Leukocytes metabolism, Leukocytosis blood, Leukocytosis complications, Leukocytosis pathology, Linear Models, Platelet Count, Polystyrenes adverse effects, Retrospective Studies, Thrombocytosis blood, Thrombocytosis complications, Thrombocytosis pathology, Blood Platelets pathology, Hyperkalemia diagnosis, Leukocytes pathology, Leukocytosis diagnosis, Potassium blood, Thrombocytosis diagnosis
- Abstract
Background: Unrecognized pseudohyperkalemia (PHK), defined as an artificial increase in measured potassium concentration, due to thrombocytosis and leukocytosis can lead to inappropriate patient treatment. Understanding the laboratory and patient characteristics that increase risk of PHK is key to preventing diagnostic errors., Methods: Serum/plasma potassium results collected at 2 laboratories over 4years were selected based on blood cell counts collected within 24h and whole blood potassium concentrations determined within 2h of the serum/plasma sample. Differences between whole blood and serum or plasma potassium were compared as functions of platelet or leukocyte count, fit to linear models, and stratified based on leukemia diagnosis codes. Patients having a serum/plasma potassium concentration that was at least 1mEq/mL higher than the whole blood concentration were defined as having PHK. Based on this analysis, high-risk patients were prospectively identified and PHK risk was communicated to providers. Medication administration records were queried to compare rates of kayexalate use pre- and post-intervention., Results: Approximately 14% of serum samples with platelet counts >500×10
9 /L had a>1mEq/L increase relative to whole blood potassium. >25% of serum and plasma samples showed a>1mEq/L increase relative to whole blood potassium when leukocyte counts were >50×109 /L. Patients with chronic lymphocytic leukemia and high WBC count demonstrated the highest rates of PHK. The rate of kayexalate administration prior to confirmatory testing decreased from 37% to 16% after the laboratory started verbally communicating the possibility of PHK to treating providers., Conclusions: According to our data, a leukocyte count threshold for plasma samples of 50×109 /L is appropriate for indicating a high risk of PHK. Direct communication by the laboratory to the care team reduces inappropriate potassium lowering treatment in populations at high risk., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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48. Splicing factor mutations in MDS RARS and MDS/MPN-RS-T.
- Author
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Yoshimi A and Abdel-Wahab O
- Subjects
- Humans, RNA Splicing genetics, RNA, Neoplasm genetics, RNA, Neoplasm metabolism, Anemia, Refractory genetics, Anemia, Refractory metabolism, Anemia, Refractory therapy, Anemia, Sideroblastic genetics, Anemia, Sideroblastic metabolism, Anemia, Sideroblastic therapy, Mutation, Myelodysplastic-Myeloproliferative Diseases genetics, Myelodysplastic-Myeloproliferative Diseases metabolism, Myelodysplastic-Myeloproliferative Diseases therapy, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Phosphoproteins genetics, Phosphoproteins metabolism, RNA Splicing Factors genetics, RNA Splicing Factors metabolism, Thrombocytosis genetics, Thrombocytosis metabolism, Thrombocytosis pathology
- Abstract
Spliceosomal mutations, especially mutations in SF3B1, are frequently (>80%) identified in patients with refractory anemia with ringed sideroblasts (RARS) and myelodysplastic/myeloproliferative neoplasms with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T; previously known as RARS-T), and SF3B1 mutations have a high positive predictive value for disease phenotype with ringed sideroblasts. These observations suggest that SF3B1 mutations play important roles in the pathogenesis of these disorders and formation of ringed sideroblasts. Here we will review recent insights into the molecular mechanisms of mis-splicing caused by mutant SF3B1 and the pathogenesis of RSs in the context of congenital sideroblastic anemia as well as RARS with SF3B1 mutations. We will also discuss therapy of SF3B1 mutant MDS, including novel approaches.
- Published
- 2017
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49. Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota.
- Author
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Josefsdottir KS, Baldridge MT, Kadmon CS, and King KY
- Subjects
- Anemia microbiology, Anemia pathology, Anemia therapy, Animals, B-Lymphocytes drug effects, B-Lymphocytes metabolism, B-Lymphocytes pathology, Bone Marrow Cells drug effects, Bone Marrow Cells metabolism, Bone Marrow Cells pathology, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes pathology, Fecal Microbiota Transplantation, Gastrointestinal Microbiome physiology, Gene Expression, Germ-Free Life drug effects, Germ-Free Life genetics, Granulocytes drug effects, Granulocytes metabolism, Granulocytes pathology, Hematopoiesis genetics, Hematopoietic Stem Cells drug effects, Hematopoietic Stem Cells metabolism, Hematopoietic Stem Cells pathology, Leukopenia microbiology, Leukopenia pathology, Leukopenia therapy, Macrophages drug effects, Macrophages metabolism, Macrophages pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, STAT1 Transcription Factor deficiency, Signal Transduction, Thrombocytosis microbiology, Thrombocytosis pathology, Thrombocytosis therapy, Anemia chemically induced, Anti-Bacterial Agents adverse effects, Gastrointestinal Microbiome drug effects, Hematopoiesis drug effects, Leukopenia chemically induced, STAT1 Transcription Factor genetics, Thrombocytosis chemically induced
- Abstract
Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. Granulocytes and B cells were also diminished in the bone marrow, whereas the number of CD8
+ T cells increased. Reductions in progenitor activity were not observed when cells were directly incubated with antibiotics, suggesting that these effects are indirect. Hematopoietic changes were associated with a significant contraction of the fecal microbiome and were partially rescued by fecal microbiota transfer. Further, mice raised in germ-free conditions had hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and antibiotic therapy of germ-free mice caused no additional abnormalities. The effects of antibiotics were phenocopied in Stat1-deficient mice, with no additional suppression by antibiotics in these mice. We conclude that microbiome depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1 signaling and alters T-cell homeostasis, leading to impaired progenitor maintenance and granulocyte maturation. Methods to preserve the microbiome may reduce the incidence of antibiotic-associated bone marrow suppression., (© 2017 by The American Society of Hematology.)- Published
- 2017
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50. The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy.
- Author
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Holgersson G, Bergstrom S, Hallqvist A, Liv P, Nilsson J, Willen L, Nyman J, Ekman S, Henriksson R, and Bergqvist M
- Subjects
- Anemia, Carcinoma, Non-Small-Cell Lung diagnosis, Chemoradiotherapy, Clinical Trials, Phase II as Topic, Humans, Leukocytosis, Lung Neoplasms diagnosis, Neoplasm Staging, Prognosis, Retrospective Studies, Survival Analysis, Sweden, Carcinoma, Non-Small-Cell Lung therapy, Lung Neoplasms therapy, Thrombocytosis pathology
- Abstract
Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109/L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109/L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting.
- Published
- 2017
- Full Text
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