Search for a rare disease
Other search option(s)
Familial thrombocytosis
Disease definition
Familial thrombocytosis is a type of thrombocytosis, a sustained elevation of platelet numbers, which affects the platelet/megakaryocyte lineage and may create a tendency for thrombosis and hemorrhage but does not cause myeloproliferation.
ORPHA:71493
Classification level: DisorderSummary
Epidemiology
The prevalence of familial thrombocytosis is not known.
Clinical description
The disease usually presents at birth but can be discovered at any time during life and thus can affect all ages. Patients present with thrombocytosis which is often discovered on a routine blood test. The clinical presentation is similar to sporadic essential thrombocythemia (ET; see this term) and may include impaired microcirculation resulting in brief episodes of fainting and dizziness, an increased risk of thrombotic events, hemorrhage, and mild splenomegaly. Patients with mutations in the MPL gene also experience frequent development of bone marrow fibrosis and seem to be free of hemorrhagic complications. The course of the disease is milder than sporadic ET and is devoid of the risk of leukemic transformation or progression toward myelofibrosis with myeloid metaplasia.
Etiology
Familial thrombocytosis is caused by germline mutations in the THPO gene (3q26.3-q27) or in the MPL (MPL S505N) gene (1p34)
Diagnostic methods
Diagnosis is based on the observation of elevated levels of platelets (over 450 x 109/L) and the elimination of secondary causes of thrombocythemia. Genetic testing is required to confirm the diagnosis.
Differential diagnosis
Differential diagnoses include causes of thrombocytosis with myeloproliferative neoplasm including chronic myeloid leukemia, polycythemia vera, primary myelofibrosis, sporadic or familial ET and myelodysplasic disorders with thrombocytosis including sideroblastic anemia or 5q- syndrome (see these terms), although these can be excluded by the presence of myeloproliferation. Differential diagnoses also include causes of secondary thrombocytosis including iron deficiency, malignancy, chronic inflammatory disease, splenectomy or aspleny and protracted marrow regeneration.
Genetic counseling
Transmission is autosomal dominant with high penetrance.
Management and treatment
Treatment is based on low dose aspirin at diagnosis. There is no consensus for using platelet lowering therapy despite an increased risk of thrombosis. Patients may have an increased risk of thrombotic events and hemorrhage.
Prognosis
The predominant clinical feature is impaired microcirculation resulting in brief episodes of fainting and dizziness responding well to aspirin when the THPO gene is mutated and an increased risk of thrombosis and a frequent development of marrow fibrosis when MPL gene is mutated. All these may affect life expectancy.
A summary on this disease is available in Español (2010) Français (2010) Nederlands (2010)
Detailed information
Genetic Testing
- Guidance for genetic testing
- English (2013) - Eur J Hum Genet


Additional information