Thrombotic thrombocytopenic purpura associated with myelodysplastic syndrome

Abstract

Thrombotic thrombocytopenic purpura (TTP), a lifethreatening disseminated thrombotic microangiopathy (TMA) syndrome, is characterized by bicytopenias with thrombocytopenia and hemolytic anemia (HA) with schistocytes, neurological disturbances, acute renal failure, and pyrexia. It has an incidence of 2–7 per million person per year with a peak incidence between the ages of 30 and 40 [1, 2]. Myelodysplastic syndrome (MDS) is also characterized by multilineage cytopenias due to ineffective hematopoiesis, and predominantly affects the elderly with a peak incidence between the ages of 60 and 75. Compared with other disorders, such as aplastic anemia, phenomena secondary to leukemias, autoimmune disorders, such as systemic lupus erythematosus or Evans syndrome, viral infection, or adverse drug effects, both MDS and TTP are less common as causatives for multilineage cytopenias in young patients. This report describes a rare case of MDS associated with TTP in a young female presented with multilineage cytopenias. A 21-year-old female was referred to our hospital with complaints of purpura, petechiae, headache, numbness and pancytopenia. She was not pregnant, showed no sign of recent infection and had no recent history of drug exposure. Peripheral blood count findings were pancytopenia with white blood cells at 2.4 9 10/L (3.4–7.3 9 10) (neutrophils 47%, lymphocytes 44%, abnormal cells 0%), red blood cells at 2.21 9 10/L (3.62–4.99 9 10), hemoglobin at 7.3 g/dL (11.7–15.1) and platelet count of 20.0 9 10/L (160–327 9 10). Blood examination also demonstrated the presence of HA, shown by elevated serum levels of total bilirubin 2.2 mg/dL (0.2–1.0), and lactate dehydrogenase 453 IU/L (114–243), serum haptoglobin reduced to below detectable levels and the presence of schistocytes. Serum vitamin B12 and folic acid were normal, 384 ng/L (180–914) and 3.9 lg/L ([3.1), respectively. Coombs test, Ham test, and the cell surface expression of glycosyl phosphatidilinositol-anchored proteins were all negative. Other examinations showed no evidence of autoimmune disorders. Bone marrow (BM) examination revealed hypercellular marrow with 300 9 10/L BM nucleated cell counts, and multilineage dysplasia, such as pseudo-Pelger neutrophils or micromegakaryocytes, but with no abnormal increase of myeloblasts at 1.6% of all BM nucleated cells (Fig. 1). Chromosome aberration was not identified by either Gbanding or spectral karyotyping analysis. According to the WHO classification criteria, the patient was diagnosed as MDS, comprising refractory cytopenia with multilineage dysplasia (RCMD) [3]. One month later, she suddenly showed various neuropsychological symptoms, such as disorientation, aphypnia, and anxiety neurosis. Serum urea nitrogen and creatinine levels were normal, 21.1 mg/dL (8.0–23.0) and 0.7 mg/dL (0.4–1.2), respectively. Coagulation tests, such as prothrombin time, activated partial thromboplastin time, or plasma levels of fibrinogen or fibrin degradation product, were normal (data not shown), while a decrease in ADAMTS13 activity (\0.5%) and an increase in the autoantibody for ADAMTS13 (14 Bethesda unit/ml), which functions as an inhibitor of ADAMTS13, were detected in her serum. We diagnosed her as having N. Sasaki J. Kuroda (&) M. Taniwaki Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan e-mail: junkuro@koto.kpu-m.ac.jp