Background: 
Azacitidine, an hypomethylating agent, is currently used in patients with high-risk myelodysplastic syndrome. Early platelet increase under azacitidine has been described as an independent positive predictive factor of response to treatment (1). However, even if extreme thrombocytosis is described (2), it is rarely observed. 
Methods: 
This report describes the case of a 58-year-old caucasian woman with a myelodysplastic syndrome (MDS) following an essential thrombocythemia (ET), who developed extreme thrombocytosis under subcutaneous azacitidine. 
Results: 
This 58-year-old woman has been diagnosed in 2014 with ET (CALR 1 mutation positive) and treated by hydroxyurea and low-dose aspirin. In March 2018, a bone marrow aspiration and biopsy were performed for pancytopenia under hydroxyurea. The histological and cytogenetics results showed a  high-risk myelodysplastic syndrome (R-IPSS 5.5) with a very poor and complex caryotype (including complete or partial loss of chromosomes 5, 7 and 17). Treatment with subcutaneous azacitidine was initiated on April 2018. After 2 cycles of azacitidine (7 days/28 days), the patient was hospitalized with thrombocytosis that reached to 4 036 000/µL. The mean platelet volume was low (correlated to the high platelet count) and the level of von Willebrand factor was normal. During hospitalization, 3 thrombopheresis, high dose hydroxyurea (up to 1500mg daily) and anagrelide (up to 2.5mg daily) were needed to lower platelet count under 1 000 000/µL. Azacitidine was stopped. Aspirin was temporary discontinued to avoid bleeding. In October 2018, platelet count was 166 000/µL but treatment with azacytidine was not resumed. 
Discussion and conclusions:
We report an original case of extreme thrombocytosis observed under azacitidine in treatment of MDS with underlying TE, which was controlled by thrombopheresis, anagrelide, hydroxyurea and azacitidine discontinuation, without occurrence of thrombotic or hemorrhagic complications.
In this case, the treatment by azacitidine has promoted the recurrence of the initial myeloproliferative disease feature, especially the thrombocytosis. This effect has been previously described with azacitidine, in patients treated for progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome (or acute myeloid leukemia) (2). The action mechanism could be an epigenetic regulation of the drivers of the ET clone by hypomethylating agents, leading to the relapse of the underlying myeloproliferative disorder with megakaryocytic proliferation (3). It was also described that Decitabine (2-deoxy-5-azacitidine) increases platelet count by enhancing platelet release and megakaryocytes maturation. However, the mechanism is unclear (4). Further investigations would be interesting.

Extreme thrombocytosis under azacitidine in a patient with secondary high-risk myelodysplastic syndrome: a case report.