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].