Zeitschrift für Hämatologie und thromboembolische Erkrankungen
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Abstrakt

WHO Clinical Molecular and Pathological (WHO-CMP) Features of Congenital MPLS505N and the Acquired MPLW515l/K Mutated Essential Thrombocythemia and Myelofibrosis

Jan Jacques Michiels, Achille PIC, Hendrik de Raeve, Vitr Camp and Jiri Schwarz

We analysed the clinical and hematological features in 41 patients of seven families, including 21 ET patients with a proven MPLS505N mutation and 20 relatives with thrombocythemia reported in the medical records. Out of the 41 MPLS505N mutated individuals 15 major thrombotic episodes in 14 members (34%) were reported as Budd-Chiari syndrome age 17 in 1, deep vein thrombosis leg age 41 in 1,ecclampsia and fetal in 1, stroke at ages 43, 72, 76 and 80 in 4 and myocardial infarction at ages between 31-81 years, median 52 years. Fourteen out of 21 well documented MPLS505N mutated ET patients had no splenomegaly and were free of major thrombosis during follow-up at ages between 2 and 76 years (mean 31 years). Eight MPLS505N mutated patients had myelofibrosis (MF) from grade MF1 in 5 to grade MF2 in 3 at ages between 28-80 years (mean 48 years), which was associated with mild to moderate splenomegaly (spleen length diameter 14.5 to 18 cm). Six anemic cases at hemoglobin levels between 10 and 11.9 g/dL had platelet counts between 317 and 963 × 109 /L. Among 15 family members 9 died from thrombosis in 3, hypocellular myelofibrosis (two of them at age 76 and 80 years) in 3, and cancer or undefined in 3 cases. The maximum life expectancy of MPLS505N family members with thrombocythemia was 50% at 80 years, and 90% at 80 years of non-affected family members without thrombocythemia. The clinical presentation in 30 ET patients with acquired MPL505N mutation (9 males and 21 females, age 22-84 (mean 56 years of whom 18 had the W515L and 12 the W515K) was featured by a high incidence of major arterial event in 23%, venous thrombosis in 10%, aspirin responsive microvessel disturbances in 60%, and major hemorrhage in 7%. The only abnormal laboratory finding in MPL mutated ET was increased platelet counts, 956+331 × 109 /L in all and slight splenomegaly in 5 (17%). Bone marrow histology from patients ET carrying the MPL505N mutation consistently displayed a normocellular bone marrow with clustered small and large to giant megakaryocytes with hyperlobulated stag-horn nuclei and no features of polycythemia vera (PV) in blood and bone marrow.