Discussion
As reported by previous study [5, 14], thrombocytosis is considered as a rare side effect of treatment of APL patients with ATRA. The result of our patient revealed that ATRA treatment combined with ATO induced bone marrow megakaryocyte differentiation and platelet production. Several mechanisms have been proposed to the regulation of platelet production [15]. Thrombopoietin (TPO), a hormone usually produced by the liver and kidneys, is known as one of major mechanisms involved in the regulation of platelet production [16]. TPO stimulates the differentiation, proliferation, and maturation of megakaryocyte, a cell precursor of platelet production [17]. Another mechanism suggested to improve megakaryocytopoiesis is the release of immune agents such as IL-1, tumor necrosis factor (TNF), IL-2, IL-3, IL-11, IL-12, IL-6, and granulocyte macrophage-colony stimulating factor (GM-CSF) [14]. During ATRA therapy, APL cell under differentiation can produce IL-1β, IL-6, IL-8, and TNF-α. IL-1 and TNF-α may participate in enhancement of platelet counts through inducing IL-6 production [18]. Although it is suggested the correlations of these factors, especially IL-6, with the serum level of TPO [15], these associations are not well explained yet.
In a study on two APL patients who were treated with interferon alpha, Losada et al. reported that platelet number was increased more than 1000× 109/L following treatment with ATRA [14]. Thrombocytosis was not accompanied by other clinical complications [14]. Subsequently, complete remission was obtained by ATRA therapy [14]. Furthermore, another study on a 20-year-old man with APL revealed a thrombocytosis on day 29 of ATRA treatment. ATRA dose was not modified and the increased number of platelet started to reduce gradually on day 33 of treatment. Finally, the patient reached to complete remission, without any complications associated with thrombocytosis [15]. The results of our case were consistent with previous studies showing thrombocytosis during ATRA therapy [11, 14, 15]. We observed an increased number of platelet (1280×103/µl) on day 32 of treatment. Thrombocytosis started to recover spontaneously on day 32 of ATRA, which is consistent with previous studies [15]. Our data were agreed with other reports pointing complete remission without any complications correlated to thrombocytosis can be achieved following ATRA treatment [12, 15].