Essential thrombocythaemia in children

Dror, Yigal; Blanchette, Victor S.

doi:10.1046/j.1365-2141.1999.01545.x

Cited by 42 publications

(29 citation statements)

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“…Thus, in the light of the evidence that the MPL Ser505Asn mutation affects both overall and thrombosis-free survival, patients with this mutation would probably benefit from treatment with low dose aspirin. The increased thrombotic risk in patients with the MPL Ser505Asn mutation is in accordance with the detection of functionally similar mutations in both essential thrombocythemia and primary myelofibrosis [9][10][11][12][13][14][15][16][17][18][19][20][21][22] and suggests that this defect, like the JAK2 V617F mutation, is able to induce platelet or leukocyte activation. 14,17 In accordance with this hypothesis, the expression of CD11b in granulocytes of three patients with the MPL Ser505Asn was similar to that observed in patients with essential thrombocythemia and significantly higher than in normal controls.…”

Section: Discussionsupporting

confidence: 69%

“…18 This finding is in agreement with the results of a recent study by Liu et al in patients with hereditary thrombocytosis, 9 whereas in this set of patients microcirculatory disturbances rather than major thromboses were mostly reported. 9 It is noteworthy that in our series of patients the thrombotic disease was fatal in nine cases and that most patients were not receiving antiplatelet therapy at the time of the thrombosis. Thus, in the light of the evidence that the MPL Ser505Asn mutation affects both overall and thrombosis-free survival, patients with this mutation would probably benefit from treatment with low dose aspirin.…”

Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis

et al. 2009

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The online version of this article has a supplementary appendix. BackgroundThe MPL Ser505Asn mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL Ser505Asn mutation could be underestimated. Design and MethodsWe extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL Ser505Asn mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis. ResultsFifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). Conclusions Patients with familial thrombocytosis caused by a MPLSer505Asn mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy. Key words: MPL Ser505Asn, hereditary thrombocytosis, splenomegaly, bone marrow fibrosis. Citation: Teofili L, Giona F, Torti L, Cenci T, Ricerca BM, Rumi C, Nunes V, Foà R, Leone G, Martini M, and Larocca LM. Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Haematologica. 2010; 95:65-70. doi:10.3324/haematol.2009 This is an open-access paper. Hereditary thrombocytosis caused by MPL

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis

et al. 2009

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“…Kawasaki disease, rheumatoid arthritis, and inflammatory bowel disease, are commonly associated with reactive thrombocytosis, as are hypoxia, trauma, blood loss, and malignancy. 19,21,22 Iron deficiency also seems to be a frequent cause of secondary thrombocytosis. 20 It is believed that underlying mechanisms of secondary thrombocytosis can be explained by upregulation of TPO expression and resultant increased TPO levels.…”

Section: Causes Of Reactive Thrombocytosis In Childrenmentioning

confidence: 99%

Primary thrombocytosis in children

et al. 2014

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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. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o ngenerally on control at the transcriptional level. 13 This rate depends upon TPO binding to its receptor, which in turn depends upon how many TPO-R bearing cells are accessible, as well as how many receptors they express.14 Low platelet counts will lead to decreased TPO clearance (less receptors in the circulation) and therefore increased levels of TPO; the reverse occurs with higher platelet counts, i.e. thrombocytosis. There are variations to this basic principal, for example in the setting of idiopathic thrombocytopenia (thrombocytopenia due to destruction). In these cases, the number of megakaryocytes and megakaryocyte mass may also influence TPO regulation and circulating levels. 15,16 Causes of reactive thrombocytosis in childrenSecondary, or reactive, thrombocytosis is a common occurrence in children. It has been reported to occur in 6-15% of hospitalized children, with variations based on age. Most of these children had thrombocytosis that could be characterized as mild, but others transiently reached levels over 900,000. [17][18][19][20] Causes of secondary thrombocytosis are many and varied (Table 1). Infection is the most common, including viral and bacterial pathogens, and both acute and chronic infections. Especially in children under one year of age, any infection seems capable of triggering a high platelet count. Inflammatory diseases, e.g. Kawasaki disease, rheumatoid arthritis, and inflammatory bowel disease, are commonly associated with reactive thrombocytosis, as are hypoxia, trauma, blood loss, and malignancy. 19,21,22 Iron deficiency also seems to be a frequent cause of secondary thrombocytosis. 20 It is believed that underlying mechanisms of secondary thrombocytosis can be explained by upregulation of TPO expression and resultant increased TPO levels. Hepatic TPO mRNA expression is increased with inflammation. Figure 1 shows our groups' proposed diagnostic algorithm for approaching patients with elevated platelets. Evaluation for secondary causes, such as iron deficiency or inflammatory or infectious disorders is conducted. Iron deficiency and othe...

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“…Patients carrying mutations of the 5'-untranslated region have a high platelet count due to the elevated serum levels of thrombopoietin [2][3][4][5][6][7] but are not usually considered at high thrombotic risk. 9 Nevertheless, Liu et al recently reported that patients with thrombocytosis due to a G to C transversion in the splice donor of intron 3 of THPO have a risk of vascular complications similar to that of patients with essential thrombocythemia. 8 In 2004, Ding et al described the pedigree of a Japanese family with thrombocythemia caused by a G to A nucleotide substitution at position 1073 in exon 10 of MPL, leading to the exchange of serine for asparagine at position 505 (MPL Ser505Asn ).…”

Section: Introductionmentioning

confidence: 99%

Acknowledgments / The Authors

Glasner¹,

Ott²

2013

Wonder Wood

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The online version of this article has a supplementary appendix. BackgroundThe MPL Ser505Asn mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL Ser505Asn mutation could be underestimated. Design and MethodsWe extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL Ser505Asn mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis. ResultsFifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). ConclusionsPatients with familial thrombocytosis caused by a MPL Ser505Asn mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy.Key words: MPL Ser505Asn , hereditary thrombocytosis, splenomegaly, bone marrow fibrosis. Giona F, Torti L, Cenci T, Ricerca BM, Rumi C, Nunes V, Foà R, Leone G, Martini M, and Larocca LM. Hereditary thrombocytosis caused by MPL Ser505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Haematologica. 2010; 95:65-70. doi:10.3324/haematol.2009 Hereditary thrombocytosis caused by MPL Ser505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis

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Essential thrombocythaemia in children

Cited by 42 publications

References 84 publications

Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis

Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis

Primary thrombocytosis in children

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