Introduction

Essential Thrombocythemia (ET) is a myeloproliferative Neoplasm (MPN) characterized by thrombocytosis and, like others MPNs, has complications such as thrombosis, hemorrhage, splenomegaly, bone marrow failure and a possible course to acute leukemia [1]. In addition there are reports of patients with ET that have developed from thrombosis of celiac and superior mesenteric arteries [2], thrombosis of cerebral venous sinuses [3] to pericarditis [4].

In MPNs, abnormal transient myelopoiesis and, more characteristically myelodysplastic syndrome, there is an increase in the number of dyplastic megakaryocytes, known as micromegakaryocytes (mMK). The international Working Group on Morphology of MDS (IWGM-MDS) defined them as generally diploid, mononuclear cells with a nucleus similar in size to that of a myeloblast or promyelocyte and less than 30 µm in diameter [5].

In a study conducted by Pich, it was found that the high expression of the JAK2V617F mutation in patients with ET is associated with a higher presence of mMK in bone marrow biopsies [6]. However, little is known about the relationship between the presence of mMK in peripheral blood and the occurrence of such thrombotic events.

Here we present the case of a patients diagnosed with ET, who died after successive thrombotic events, both arterial and venous, with no additional predisposing factor, in a short period of time. The large amount of mMK and the presence of the JAK2 mutation are the main peculiariaties of the case.

Case Presentation

A 55-year-old white male was admitted in November 2012 to investigate a thrombocytosis detected on a routine exam. The patient had no symptoms or any other complaint. The possible cause of thrombocytosis was identified in 2013 when the diagnosis of ET was given. The patient's diagnosis complies with the WHO criteria, which are based on clinical and laboratory characteristics [7]. Their initial platelet count was greater than 450 × 109 /L, a bone marrow biopsy (BMB) confirmed the ET. The presence of the JAK2V617F mutation was also evaluated (positive)͘

Therefor cytoreductive therapy with anagrelide (0.5 mg/2 × day), hydroxyurea (1.5 mg/day) and anti-aggressive with acetylsalicylic acid (100 mg/day) was started, which maintained his platelet count controlled. The patient did not report a history of alcohol or tobacco use and did not present any other comorbities However, within a few months, despite the standard therapy, the patient presented ulcers and thrombosis of both lower limbs, as well as ischemia of the fifth toe.

In July 2016, another BMB confimed the myeloproliferative disease, type ET, with mild fibrosis (grade 1). It was also excluded other myeloid malignancies and other causes of reactive thrombocytosis. Small, monolobular megakaryocytes with high nucleus/cytoplasm ratio were found on the slides, compatible with micromegacarocytes.

In February 2017, the patient was recruited for a quantification study of mMK in peripheral blood using flow cytometry (Figure 2) and almost 7 times the amount of these cells was observed compared to a healthy person [8]. At the same time their blood counts revealed LDH and platelet counts within the reference values, but red blood cell counts, lymphocytes, and leukocytes were reduced, as well as hemoglobin levels (Table 1). The patient died in June 2017 after an ischemic stroke associated with carotid thrombosis.

Discussion

Hitherto it is unusual for a case to report so many thrombotic events in the same patient with ET and /or to relate them to the high amount of mMK in peripheral blood. However, the medical literature is rich in the collection of thrombo-hemorrhagic events. In a systematic review of panyiotis D. Ziakas, thrombotic events were observed in 31.8% of cases positive for the JAK2 mutation [9]. While in the analysis conducted by Lussana, such thrombotic events, whether arterial or venous, occurred in 32% of patient with the JAK2 mutation [1]. In addition the literature presents a greater number of cases of thrombosis in patient with ET and mutation carriers, splanchnic veins (including the hepatic portal vein) and deep venous system, with an incidence of 11% and 23%, respectively [10].