Cyclic Thrombocytopenia: A Case Report

Introduction

Cyclic thrombocytopenia (CTP) is a rare disorder characterized by episodes of oscillating platelet counts. It is usually associated with another primary hematologic disorder but there are idiopathic cases in the literature. Patients with CTP have similar clinical features and symptoms with idiopathic thrombocytopenic purpura (ITP), so they are often misdiagnosed as ITP and treated accordingly. In general, CTP does not respond to ITP therapies, so it should always be considered when treatments are not effective. It is more common in females. However, in our case report we present a 93-year-old male with CTP who was initially mistaken for ITP.

Case description

A 93-year-old male patient with a past medical history of hypertension was initially thought to have idiopathic thrombocytopenia (ITP) presenting with mucosal gum bleeding and a petechial rash. He was found to have isolated thrombocytopenia, and no evidence of other cytopenias. He did trials of multiple medications such as corticosteroids and intravenous immunoglobulin (IVIG) with no response. He was not a surgical candidate for splenectomy. He also deferred a bone marrow biopsy, though peripheral blood testing with flow cytometry showed a small monoclonal B cell population. Peripheral blood myeloid sequencing panel showing ASXL1 and EZH2. He was started on Eltrombopag, a thrombopoietin (TPO) agonist with significant lability in the platelet count, from 8,000 per microliter (mcL) to over 1,000,000 per mcL. Romiplostim, another TPO agonist also gave similar results. A diagnosis of cyclic thrombocytopenia was suspected. A Helicobacter pylori antibody was positive, and treated with antibiotics with no improvement in platelet count oscillations. Thyroid function was within normal limits. T-cell gene rearrangement was negative. Thrombopoetin (TPO) levels were checked and these were found to be in discordance with the platelet count, consistent with a CTP diagnosis. He was started on cyclosporine 150 milligrams twice daily with significant improvement in fluctuations of platelet counts.

Discussion

Cyclic hematopoietic disorders are rare and have regular predictable oscillations of one or more cellular components of the blood. Physiologically, there is a complex interplay between thrombopoietic stimulation and feedback inhibition in order to maintain the circulating platelets within the normal range. An error in any of these steps results in oscillation of the platelet counts (cyclic thrombocytopenia). Many mechanisms are behind the pathophysiology of this disease, such as: autoimmune destruction of platelets, hypoplasia of megakaryocytes, a defect in regulating platelet formation and an infectious or hormonal etiology. There are many reports linking T-lymphocytes proliferation and clonal TCR gene rearrangement to cyclic thrombocytopenia.

We noticed in the literature that there can be variable responses to TPO agonists, but often can result in very high platelet counts. Due to its rarity, there are only case reports which show reports of remission after hormone therapy with danazol and immune suppressant therapies, such as cyclosporine. Further studies are needed to determine the mechanism responsible for cycling phenomena and optimal treatments for this disorder.

In conclusion, any presumed ITP case that does not respond well to the standard therapy of ITP should be reevaluated for the possibility of cyclic thrombocytopenia.

No relevant conflicts of interest to declare.