Clonal T cell‐mediated cyclic thrombocytopenia

Abstract

Summary. Cyclic thrombocytopenia is a rare disorder characterized by periodic platelet count fluctuations of unknown aetiology. We report on a female patient with cyclic changes of platelet counts ranging from 6 · 10 9 /l to 753 · 10 9 /l in 4-week intervals. Platelet counts were inversely correlated to thrombopoietin levels suggesting production failure. Reticulocyte counts and neutrophil counts showed similar, but less prominent, fluctuations. Clonal T-cell receptor rearrangement was detected in bone marrow samples as well as in peripheral blood. Cell typing of blood lymphocytes revealed a relative increase in CD3 + T cells. Treatment with cyclosporine A resulted in a substantial improvement of platelet counts. Taken together, we provide evidence for clonal T-cell mediated bone marrow failure with cyclic impairment of thrombopoiesis responsive to cyclosporine therapy.

Large granular lymphocytic proliferation-associated cyclic thrombocytopenia

“…In a previous report, a clonal TCR gene rearrangement in a patient with cyclic thrombocytopenia was observed, though LGLs were absent on microscopic examination of peripheral blood and bone marrow specimens [1]. Some patients with LGL lymphoproliferative disease are known to exhibit a relative, rather than absolute, lymphocytosis [6], and it is possible that a small clonal expansion of LGLs in that patient escaped detection by histologic inspection.…”

“…CsA, which is used to treat LGL lymphoproliferative disorders [6] and has decreased the severity of platelet count nadir in some patients with cyclic thrombocytopenia [1,5,8], was ineffective. Because a dramatic reduction in LGLs in the peripheral blood was observed in this case following use of CsA, is not known what degree of interruption of the lymphoproliferative process (if any) would be required to achieve clinical remission of platelet count fluctuations.…”

“…Cyclic thrombocytopenia is a rare condition characterized by periodic and, often chronologically regular, fluctuations in the platelet count, leading to symptomatic bleeding at the time of platelet nadir, with normal or even elevated platelet counts between nadirs [1]. The pathophysiologic mechanisms producing cyclic thrombocytopenia remain elusive.…”

Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder

“…[6][7][8] Whereas patients with the lymphocytic variant of HES can present with intermittent angioedema and/or urticaria, 9 the regular periodicity of eosinophilia and symptoms in EAE is a distinguishing feature that is reminiscent of other cyclic hematologic disorders, such as cyclic neutropenia 10,11 and cyclic thrombocytopenia. 12,13 Of note, cycling of multiple additional cell lineages, including eosinophils, platelets, monocytes and lymphocytes, has been reported in patients with these disorders. 10,13 Furthermore, populations of abnormal lymphocytes, specifically large granular lymphocytes, are often present in patients with the adult onset form of cyclic neutropenia 11 and have been described in cyclic thrombocytopenia.…”

“…12,13 Of note, cycling of multiple additional cell lineages, including eosinophils, platelets, monocytes and lymphocytes, has been reported in patients with these disorders. 10,13 Furthermore, populations of abnormal lymphocytes, specifically large granular lymphocytes, are often present in patients with the adult onset form of cyclic neutropenia 11 and have been described in cyclic thrombocytopenia. 12 Although mutations in neutrophil elastase (ELANE) 14 have been identified in many patients with cyclic neutropenia, the role of these mutations in neutrophil cycling remains controversial.…”