Successful treatment of cyclic thrombocytopenia with thrombopoietin‐mimetic agents: A report of two patients

Abstract

Previous studies have suggested that physical exercise may have an effect on the turnover of the endothelial compartment. Following a maximal exercise testing (Bruce protocol), a prompt and significant increase in the number of circulating endothelial cells (CECs) was detected (D 1 50% vs. basal; P 5 0.0001) in 12 healthy volunteers, without significant changes in the marker of myocardial ischemia; the frequency of CECs correlated significantly with systolic blood pressure (SBP) and rate-pressure product at peak exercise (r 5 0.78, P 5 0.003, and r 5 0.64, P 5 0.03, respectively). These results support the role of peak SBP during maximal exercise possibly as mechanical factor facilitating the detachment of CECs and the endothelial turnover.The endothelium is a dynamic structure maintained by a continuous selfrenewal of the endothelial cells (ECs) that in basal conditions accounts for 0.1% replications per day [1]; this rate could be affected by several physiological and pathological conditions. As the number of vital and apoptotic CECs detached from the endothelium is related to the turnover of endothelial progenitor cells (EPCs) in physiological conditions [2], the number of peripheral blood (PB) ECs has been proposed as diagnostic, therapeutic, or prognostic marker of vascular injury and neovascularization [3]. Unfortunately, PB EPCs are extremely rare, and their accurate detection and enumeration is a technical challenge especially when high sensitive techniques are used, such as flow cytometry [4,5].In patients with cardiovascular diseases, physical exercise may increase the release, mobilization, and number of PB EPCs [6,7]. In healthy subjects, dynamic exercise [8], altitude [9], or simulated [10] hypoxia seem to increase the number of PB EPCs, but the mechanism underlying this increase has not yet been clarified, although myocardial ischemia has been convincingly ruled out [11,12].The objective of this study is to clarify whether changes in blood pressure (BP) during a single session of intense physical exercise could affect the endothelial turnover in healthy subjects.The sample size was defined a priori to detect a reasonable experimental effect with an adequate power. We enrolled 12 healthy nonsmokers, nonobese (BMI 24.7 ± 2.1 kg/m 2 ), normotensive, adult volunteer males (mean age 37 ± 12 years), not currently on any medication, and who had not resided at high altitudes (>3,000 m) or performed an intense physical exercise in the 7 days preceding the test. Eligibility for the study was determined by an oral questionnaire; included subjects gave an informed consent. All study subjects underwent the same maximal exercise testing procedure according to Bruce [13], using a cyclergometer (Ec1000, Custo Med, Ottobrunn, Germany). The protocol involved a minute of unloaded exercise, followed by a progressive increase in the load (25 W every 2 min), until the achievement of 85% of the predicted maximum heart rate (220-age). During the test, the following parameters were recorded: systolic and diastolic BP (SBP...

Cyclic thrombocytopenia with statistically significant neutrophil oscillations

“…A previous report demonstrated the successful use of romiplostim (a TPO receptor agonist medication) for 2 patients: For one patient, peak platelet counts were significantly lower than the patients in our series; and for the second patient, the dose of romiplostim had to be carefully adjusted to avoid extreme thrombocytosis. 3 Patient 1 had features of classic CT, but with associated cyclical neutropenia. The synchronous cycling of neutrophils with close entrainment of the two cycles suggests a dysregulation involving a common hematopoietic progenitor cell and a shared signaling pathway.…”

“…1 Patients with ITP and thrombocytopenia for other causes respond to treatment with thrombopoietin (TPO), but there are few reports of its use in cyclic thrombocytopenia. 3 To establish a clear diagnosis of CT, therefore, platelet counts must be monitored regularly (3)(4) times weekly for at least 2-3 weeks), but the precise diagnosis depends on establishing statistical significance of periodicity of the platelet counts using mathematical methods such as Fourier analysis, or more practically the Lomb-Scargle periodogram.…”

A rare cause of thrombocytopenia: Cyclic thrombocytopenia

“…Bu olgularda trombopoietin-mimetik ilaçların kullanımı ile ilgili az sayıda olgu sunumu bildirilmitir. [10] Sonuç olarak, trombositopeni ile bavuran erikin hastalarda klasik ‹TP tedavisine yanıt alınamadı¤ında, STP olasılı¤ı akla gelmelidir. Bu hastaların trombosit sayısında bir döngü olup olmadı¤ı mutlaka kontrol edilmelidir.…”

Treatment of immune thrombocytopenic purpura: focus on eltrombopag

“…I have reported a patient with a treatment-refractory cyclic variant of ITP who responded to MGDF therapy 37. This patient has been maintained in remission for 11 years with TPO-mimetic therapy 38. Nomura treated four refractory ITP patients with MGDF, three of whom responded 39.…”