Fluctuations in thrombopoietin, immature platelet fraction, and glycocalicin levels in a patient with cyclic thrombocytopenia

Abstract

Cyclic thrombocytopenia (CT) is an uncommon disorder characterized by periodic fluctuations in platelet count, resulting in alternating episodes of thrombocytopenia and normal platelet counts. Its pathogenesis remains unclear. Here, we report the case of a 65-year-old man with CT who was initially diagnosed with idiopathic thrombocytopenic purpura (ITP) concomitant with chronic thyroiditis. ITP was diagnosed 12 years ago in the absence of periodic fluctuations in platelet counts. He had been treated with corticosteroids; underwent splenectomy; and subsequently been treated with azathioprine, vincristine, high doses of dexamethasone, and herbal medicine. He had not received antibiotic eradication therapy for Helicobacter pylori because there was no evidence of infection with this organism. Since his symptoms did not improve, the treatments were discontinued, and he was placed under observation. He complained of mild bleeding symptoms, such as petechiae and purpura, which occurred intermittently for several months before he presented to us to undergo detailed investigations. His platelet count varied between 3 9 10/ll and 30 9 10/ll approximately every 3–4 weeks. His white blood cell count and hemoglobin concentration remained unchanged. To elucidate the mechanism underlying this disease, we evaluated the serum thrombopoietin (TPO) level, immature platelet fraction (IPF), plasma glycocalicin index normalized for the individual platelet count (GCI), and T helper (Th)1/Th2 ratio. The serum TPO level was measured with a human TPO ELISA kit (R&D Systems Inc., Minneapolis, MN, USA). The serum levels of TPO, a principal regulator of megakaryogenesis and thrombopoiesis, are thought to be regulated via receptor-mediated clearance by platelets and megakaryocytes. The median serum TPO concentration in healthy individuals is 51 pg/ml. The plasma glycocalicin level was measured with a Glycocalicin EIA kit (Takara Bio Inc., Ohtsu, Japan). The GCI was calculated as proposed by Steinberg et al. [1]: GCI = glycocalicin level 9 250 9 10/individual platelet count (/ll). Glycocalicin is a proteolytic fragment of the a-chain of glycoprotein Ib, a platelet membrane. The GCI reflects the rate of platelet destruction [2]. The mean GCI in healthy individuals is 1.27 (range 0.87–1.77). The IPF was determined to reliably quantify reticulated platelet counts by using a fully automated hematology analyzer XE-2100 equipped with special software IPF Master (Sysmex, Kobe, Japan). Reticulated platelets are RNA-rich immature platelets and are thought to reflect the ability of the bone marrow to produce platelets. Therefore, the IPF, as a surrogate marker of the reticulated platelet count, reflects the rate of thrombopoiesis [3]. The mean IPF in healthy individuals is 2.0% (range 0.5–5.7%). The Th1/Th2 ratio was determined by using flow cytometry analysis to measure the ratio of CD4? cells containing intracellular interferon-c to those containing interleukin-4. The fluctuations in the TPO levels, percentage of IPF, and GCI were synchronous and inversely proportional to those in the platelet counts (Fig. 1). In the thrombocytopenic phase, elevated GCI indicated platelet destruction in this patient. Thrombopoiesis was simultaneously accelerated in response to TPO. Consequently, the IPF, which is as an indicator of thrombopoiesis, increased. In the present case, CT seemed to be closely associated with cyclic increases in platelet destruction. However, the mechanism of cyclic platelet destruction remains to be elucidated. Th1/Th2 balance is T. Yujiri (&) Y. Tanaka M. Tanaka Y. Tanizawa Third Department of Internal Medicine, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan e-mail: yujirit@yamaguchi-u.ac.jp