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Annals of Hematology Jul 2021Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation. Primary hereditary thrombocytosis may be caused by germline mutations... (Review)
Review
Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation. Primary hereditary thrombocytosis may be caused by germline mutations within the genes encoding key regulators of thrombopoiesis, i.e., thrombopoietin (THPO) and its receptor c-MPL (MPL) or the receptor's effector kinase Januskinase2 (JAK2). Furthermore, somatic mutations in JAK2, MPL, and in the gene-encoding calreticulin (CALR) have been described to act as driver mutations within the so-called Philadelphia-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Increasing knowledge on the molecular mechanisms and on the clinical complications of these diseases is reflected by the WHO diagnostic criteria and European LeukemiaNet (ELN) recommendations on the management of adult MPN. However, data on childhood thrombocytosis are rare, and no consensus guidelines for pediatric thrombocytosis exist. Current literature has highlighted differences in the epidemiology and molecular pathogenesis of childhood thrombocytosis as compared to adults. Furthermore, age-dependent complications and pharmacological specificities suggest that recommendations tailored to the pediatric population are necessary in clinical practice. Here we summarize literature on classification, diagnostics, and clinical management of childhood thrombocytosis.
Topics: Adolescent; Adult; Age of Onset; Algorithms; Anticoagulants; Calreticulin; Child; Disease Management; Female; Germ-Line Mutation; Humans; Hydroxyurea; Interferon-alpha; Janus Kinase 2; Male; Myelodysplastic-Myeloproliferative Diseases; Platelet Count; Quinazolines; Receptors, Thrombopoietin; Severity of Illness Index; Thrombocythemia, Essential; Thrombocytosis; Thrombophilia
PubMed: 33712866
DOI: 10.1007/s00277-021-04485-0 -
American Journal of Hematology Mar 2021Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include... (Review)
Review
Myelodysplastic syndromes with ring sideroblasts (MDS-RS) and MDS/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T) - "2021 update on diagnosis, risk-stratification, and management".
DISEASE OVERVIEW
Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include myelodysplastic syndromes with RS (MDS-RS) and MDS/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).
DIAGNOSIS
MDS-RS is a lower risk MDS, with single or multilineage dysplasia (MDS-RS-SLD/MLD), <5% bone marrow (BM) blasts, <1% peripheral blood blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations). MDS/MPN-RS-T, now a formal entity in the MDS/MPN overlap syndromes, has diagnostic features of MDS-RS-SLD, along with a platelet count ≥450 × 10 /L and large atypical megakaryocytes.
MUTATIONS AND KARYOTYPE
Mutations in SF3B1 are seen in ≥80% of patients with MDS-RS-SLD and MDS/MPN-RS-T, and strongly correlate with the presence of BM RS; MDS/MPN-RS-T patients also demonstrate JAK2V617F (50%), DNMT3A, TET2 and ASXL1 mutations. Cytogenetic abnormalities are uncommon in both.
RISK STRATIFICATION
Most patients with MDS-RS-SLD are stratified into lower risk groups by the revised-IPSS. Disease outcome in MDS/MPN-RS-T is better than that of MDS-RS-SLD, but worse than that of essential thrombocythemia (MPN). Both diseases are associated with a low risk of leukemic transformation.
TREATMENT
Anemia and iron overload are complications seen in both and are managed similar to lower risk MDS and MPN. Luspatercept, a first-in-class erythroid maturation agent is now approved for the management of anemia in patients with MDS-RS and MDS/MPN-RS-T. Aspirin therapy is reasonable in MDS/MPN-RS-T, especially in the presence of JAK2V617F, but the value of platelet-lowering drugs remains to be defined.
Topics: Allografts; Anemia, Sideroblastic; Bone Marrow; Cell Lineage; Clone Cells; Combined Modality Therapy; DNA Methylation; Disease Management; Erythroblasts; Ferritins; Hematinics; Hematopoietic Stem Cell Transplantation; Humans; Iron Chelating Agents; Mitochondria; Mutation; Myelodysplastic-Myeloproliferative Diseases; Phosphoproteins; Prognosis; RNA Splicing Factors; Risk Assessment; Thrombocytosis
PubMed: 33428785
DOI: 10.1002/ajh.26090 -
Cancer Cell Jun 2018Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of... (Review)
Review
Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of tumorigenesis including tumor growth, tumor cell extravasation, and metastasis. Additionally, thrombocytosis in cancer patients is associated with adverse patient survival. Due to the secretion of large amounts of microparticles and exosomes, platelets are well positioned to coordinate both local and distant tumor-host crosstalk. Here, we present a review of recent discoveries in the field of platelet biology and the role of platelets in cancer progression as well as challenges in targeting platelets for cancer treatment.
Topics: Animals; Blood Platelets; Cell-Derived Microparticles; Disease Progression; Exosomes; Humans; Neoplasm Metastasis; Neoplasms; Thrombocytosis; Tumor Burden
PubMed: 29657130
DOI: 10.1016/j.ccell.2018.03.002 -
Mayo Clinic Proceedings Jul 2005A complete blood cell count (CBC) is one of the most common laboratory tests in medicine. For example, at our institution alone, approximately 1800 CBCs are ordered... (Review)
Review
A complete blood cell count (CBC) is one of the most common laboratory tests in medicine. For example, at our institution alone, approximately 1800 CBCs are ordered every day, and 10% to 20% of results are reported as abnormal. Therefore, it is in every clinician's interest to have some understanding of the specific test basics as well as a structured action plan when confronted with abnormal CBC results. In this article, we provide practical diagnostic algorithms that address frequently encountered conditions associated with CBC abnormalities including anemia, thrombocytopenia, leukopenia, polycythemia, thrombocytosis, and leukocytosis. The objective is to help the nonhematologist recognize when a subspecialty consultation is reasonable and when it may be circumvented, thus allowing a cost-effective and intellectually rewarding practice.
Topics: Adult; Algorithms; Anemia; Blood Cell Count; Cost-Benefit Analysis; Diagnosis, Differential; Hematologic Diseases; Hematology; Humans; Leukocytosis; Leukopenia; Polycythemia; Practice Patterns, Physicians'; Referral and Consultation; Thrombocytopenia; Thrombocytosis
PubMed: 16007898
DOI: 10.4065/80.7.923 -
Revista Da Associacao Medica Brasileira... 2023We aimed to investigate the frequency and causes of thrombocytosis in patients admitted to the Department of Pediatric Hematology and Oncology of Elazig Fethi Sekin City...
OBJECTIVE
We aimed to investigate the frequency and causes of thrombocytosis in patients admitted to the Department of Pediatric Hematology and Oncology of Elazig Fethi Sekin City Hospital, Elazig, Turkey.
METHODS
Between 2019 and 2021, the laboratory parameters of 2,500 patients admitted to the Hematology Department were studied. During this examination, 319 (12.76%) patients were found to have thrombocytosis. Demographic characteristics (age and gender), hematologic parameters (hemoglobin, white blood cells, and platelets), and ultimate diagnoses ot the cases were recorded from their files.
RESULTS
Of these 319 patients with thrombocytosis, 197 (1.8%) were male and 122 (38.2%) were female, and the mean age was 72.0±69.0 (1-216) months. The median platelet count of the patients was 590.43±280.12/μL (450,000-750,000). The most common cause of secondary thrombocytosis was infection, accounting for 37.9% of all patients. Other common causes were sickle cell anemia (21%), iron deficiency anemia (15.4%), colloid tissue disease (6.6%), hemolytic anemia (5.0%), splenectomy (4.5%), and other causes (9.7%).
CONCLUSION
In our study, infections were the most common cause of thrombocytosis. In addition to infections, sickle cell anemia and iron deficiency anemia should also be considered in the differential diagnosis of thrombocytosis.
Topics: Humans; Male; Child; Female; Child, Preschool; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Thrombocytosis; Platelet Count; Blood Platelets; Anemia, Sickle Cell
PubMed: 37255084
DOI: 10.1590/1806-9282.20230020 -
Blood Cancer Journal Feb 2022The current World Health Organization (WHO) classification of myeloid malignancies includes myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and...
The current World Health Organization (WHO) classification of myeloid malignancies includes myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) as a distinct entity. Previous literature on predictors of survival was based on the provisional category of refractory anemia with ring sideroblast and thrombocytosis (RARS-T), which was not subject to MDS/MPN-RS-T exclusionary criteria such as PB blast% ≥1, BM blast% ≥5 or cytogenetic abnormalities such as t(3;3)(q21.2;q26.2), inv(3)(q21.23q26.2) or isolated del(5q). We examined overall (OS) and leukemia-free (LFS) survival and its predictors, among 158 patients with WHO-defined MDS/MPN-RS-T. In univariate analysis, age ≥70 years (P = 0.006), hemoglobin (Hb) ≤10 g/dL (P = 0.03) and abnormal karyotype (excluding -Y, P = 0.008) were associated with shortened OS, which was otherwise not affected by either ASXL1 (P = 0.7), SF3B1 (P = 0.4) or JAK2 V617F (P = 0.7) mutations; in multivariable analysis, Hb ≤ 10 g/dL (P = 0.03) and abnormal karyotype (P = 0.001) remained significant, and thus allowed the development of an operational survival model with low (0 risk factors, median OS 10.5 years), intermediate (1 risk factor, median OS 4.8 years) and high risk (2 risk factors, median OS 1.4 years) categories (P = 0.0009). Comparison of MDS/MPN-RS-T (n = 158) and MDS/MPN-U with BM RS ≥ 15% (MDS/MPN-U-RS; n = 25) did not reveal significant differences in frequency of thrombosis, OS, or LFS, although SF3B1 mutation frequency was higher in the former (93% versus 59%; P = 0.0005). These data suggest limited survival impact for molecular abnormalities and the morphological distinction between MDS/MPN-RS-T and MDS/MPN-U-RS.
Topics: Aged; Anemia, Sideroblastic; Humans; Mutation; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; Neoplasms; Thrombocytosis
PubMed: 35105856
DOI: 10.1038/s41408-022-00622-8 -
Haematologica Apr 2014Myeloproliferative neoplasms are uncommon disorders in children, for which we have limited understanding of the pathogenesis and optimal management. JAK2 and MPL... (Review)
Review
Myeloproliferative neoplasms are uncommon disorders in children, for which we have limited understanding of the pathogenesis and optimal management. JAK2 and MPL mutations, while common drivers of myeloproliferative neoplasms in adult patients, are not clearly linked to pediatric disease. Management and clinical outcomes in adults have been well delineated with defined recommendations for risk stratification and treatment. This is not the case for pediatric patients, for whom there is neither a standard approach to workup nor any consensus regarding management. This review will discuss thrombocytosis in children, including causes of thrombocytosis in children, the limited knowledge we have regarding pediatric primary thrombocytosis, and our thoughts on potential risk stratification and management, and future questions to be answered by laboratory research and collaborative clinical study.
Topics: Child; Child, Preschool; Humans; Thrombocythemia, Essential
PubMed: 24688110
DOI: 10.3324/haematol.2013.092684 -
Journal of Veterinary Internal Medicine Jan 2022Carcinoma-associated thrombocytosis involves tumor production of mediators such as interleukin-6 (IL-6) and thrombopoietin (TPO) that increase thrombopoiesis and may...
BACKGROUND
Carcinoma-associated thrombocytosis involves tumor production of mediators such as interleukin-6 (IL-6) and thrombopoietin (TPO) that increase thrombopoiesis and may play a role in tumor evasion and metastasis. Carcinoma-associated thrombocytosis is described in people, but has not been described in dogs.
HYPOTHESIS/OBJECTIVES
Evaluate the concentrations of IL-6 and TPO in dogs diagnosed with carcinoma with or without thrombocytosis. We hypothesized that IL-6 and TPO concentrations would be higher in dogs with carcinoma compared to healthy dogs, and that IL-6 and TPO concentrations would be higher in dogs with carcinoma and thrombocytosis when compared to dogs with carcinoma and normal platelet counts.
ANIMALS
One-hundred sixteen dogs: 63 with carcinoma and 53 healthy control dogs.
METHODS
Complete blood count was performed in all dogs, and they were stratified for sub-group analysis based on the presence or absence of thrombocytosis (platelet count > 500 103/µL). Serum TPO and IL-6 concentrations were measured by ELISA. Results of selected numeric variables were compared using Wilcoxon rank sum tests for pairwise comparisons. A value of P < .05 was considered significant.
RESULTS
Twelve of the dogs with carcinoma (12/63, 19.0%) and none of the healthy control dogs (0%) had thrombocytosis. Thrombopoietin concentrations (median [range]) were significantly higher in dogs with carcinoma when compared to controls (87.42 pg/mL [0 to >600] vs 15.99 pg/mL [0 to >600], P < .001). Interleukin-6 concentrations (median [range]) were not different between dogs with carcinoma and healthy control dogs (9.70 pg/mL [0-181.53] vs 3.03 pg/mL [0-280.77], P = .15). In dogs with carcinoma, the TPO and IL-6 concentrations were not different between dogs with thrombocytosis and dogs with normal platelet count.
CONCLUSIONS AND CLINICAL IMPORTANCE
Thrombopoietin concentrations were significantly higher in dogs with carcinoma, regardless of platelet count. Thrombopoietin is likely to be 1 of multiple factors that can impact platelet number, production, and consumption in dogs with carcinoma.
Topics: Animals; Carcinoma; Case-Control Studies; Dog Diseases; Dogs; Interleukin-6; Platelet Count; Thrombocytosis; Thrombopoietin
PubMed: 34881459
DOI: 10.1111/jvim.16317 -
Journal of Cancer Research and... 2017Thrombocytosis has been suggested to be a poor prognostic indicator in malignancies. Studies have shown that thrombocytosis is associated with a poor prognosis in... (Review)
Review
Thrombocytosis has been suggested to be a poor prognostic indicator in malignancies. Studies have shown that thrombocytosis is associated with a poor prognosis in various gynecological malignancies such as carcinoma ovary, cervical cancer, and endometrial cancer. The aim of this study is to analyze the impact of thrombocytosis on the prognosis of gynecological cancer. All the relevant data were retrieved by PubMed, MEDLINE, and Web of Science, and then studies were chosen in this analysis of association between thrombocytosis and gynecological malignancy. Thrombocytosis is common in advanced disease in patients with ovarian cancer, endometrial cancer, and cervical cancer. Therefore, it may be a marker of tumor burden or biologically more aggressive disease. Thrombocytosis is bad prognostic factor and associated with poorer outcomes.
Topics: Blood Platelets; Female; Genital Neoplasms, Female; Humans; Thrombocytosis
PubMed: 28643732
DOI: 10.4103/0973-1482.189234 -
PloS One 2022Thrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy,...
BACKGROUND
Thrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy, guidelines for investigating thrombocytosis in the absence of red flag symptoms remain unclear. A novel automated system of laboratory analysis, intelligent Liver Function Testing (iLFT), launched in Tayside in 2018 and has identified a patient group with thrombocytosis and abnormal liver test (LFT) results. This study analysed the outcome of these patients and investigated the use of thrombocytosis combined with LFTs in predicting risk of cancer.
METHODS AND FINDINGS
Between August 2018 and August 2020, 6792 patients underwent iLFT, with 246 found to have both thrombocytosis and at least one abnormal LFT. A random case-matched control group of 492 iLFT patients with normal platelet count and at least one abnormal LFT was created. 7.7% (95% CI 4.7-11.8%) of patients with thrombocytosis had cancer compared to 2.0% (1.0-3.7%) of controls. Patients <40 years or with pre-existing causes of thrombocytosis were then excluded. Subsequent analysis revealed a 10.8% (6.6-16.3%) incidence of cancer in thrombocytosis patients (n = 176) compared to 2.5% (1.2-4.6%, p = 0.00014) in patients with normal platelet count (PLT) (n = 398). When thrombocytosis is combined with elevated alkaline phosphatase (ALP), there is a positive predictive value (PPV) of 20% for cancer. These rules were subsequently applied to a validation cohort of 71,652 patients, of whom 458 had thrombocytosis and elevated ALP. There was a 30.6% cancer incidence, confirming the strong predictive value of the combined test of PLT and ALP.
CONCLUSIONS
These findings suggest a substantial increased risk of cancer in patients with thrombocytosis and raised ALP. This could be developed as an adjunct to current investigation algorithms, highlighting high-risk patients and prompting further investigation (such as computed tomography scans) where indicated.
Topics: Humans; Liver Diseases; Liver Function Tests; Neoplasms; Thrombocytosis
PubMed: 35482741
DOI: 10.1371/journal.pone.0267124