UNLABELLED: Background The 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 METHODS: We 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. RESULTS: Fifteen 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 MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy.
UNLABELLED: Background The 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 METHODS: We 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. RESULTS: Fifteen 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 MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy.
Authors: Animesh D Pardanani; Ross L Levine; Terra Lasho; Yana Pikman; Ruben A Mesa; Martha Wadleigh; David P Steensma; Michelle A Elliott; Alexandra P Wolanskyj; William J Hogan; Rebecca F McClure; Mark R Litzow; D Gary Gilliland; Ayalew Tefferi Journal: Blood Date: 2006-07-25 Impact factor: 22.113
Authors: Alexandra P Wolanskyj; Susan M Schwager; Rebecca F McClure; Dirk R Larson; Ayalew Tefferi Journal: Mayo Clin Proc Date: 2006-02 Impact factor: 7.616
Authors: Yana Pikman; Benjamin H Lee; Thomas Mercher; Elizabeth McDowell; Benjamin L Ebert; Maricel Gozo; Adam Cuker; Gerlinde Wernig; Sandra Moore; Ilene Galinsky; Daniel J DeAngelo; Jennifer J Clark; Stephanie J Lee; Todd R Golub; Martha Wadleigh; D Gary Gilliland; Ross L Levine Journal: PLoS Med Date: 2006-07 Impact factor: 11.069
Authors: Maite E Houwing; Eva A Koopman-Coenen; Rogier Kersseboom; Saskia Gooskens; Inge M Appel; Susan T C J M Arentsen-Peters; Andrica C H de Vries; Dirk Reinhardt; Jan Stary; André Baruchel; Valerie de Haas; Marjolein Blink; Rob H Lopes Cardozo; Rob Pieters; C Michel Zwaan; Marry M van den Heuvel-Eibrink Journal: Int J Hematol Date: 2015-03-03 Impact factor: 2.490