Androgen-induced erythrocytosis

Abstract

Ticlopidine hydrochloride, a potent inhibitor of platelet aggregation, is widely used for secondary stroke prophylaxis [1]. The most common adverse effects reported with ticlopidine include diarrhea (22%), skin rash (15%), bleeding disorders (7%), hepatic dysfunction (4%), and neutropenia (2%) [1]. In 1994, 16% of the cases were fatal among 645 patients with ticlopidin-induced aplastic anemia, bone morrow suppression, and pancytopenia [2].A 68-year-old woman was admitted to the emergency department with a three-day history of fever and skin rash. On admission, her temperature was 39°C; blood pressure, 150/80 mmHg; white blood count (WBC), 2.2 × 10 9 /L (8% band, 18% monocytes, 74% lymphocytes), platelets, 95 × 10 9 /L, hemoglobin (Hb) levels, 13.3 g/dL. Physical examination revealed no lymphadenopathy and hepatosplenomegaly. Liver function tests were as follows: serum aspartate aminotransferase, 423 U/L; serum alanine aminotransferase, 423 U/L, serum alanine aminotransferase, 338 U/L; gama glutamil transpeptidase, 204 U/L; alkaline phosphatase, 317 U/L; total bilirubin, 3.7 mg/dL; and direct biluribin, 2.4 mg/dL. Fourteen days before hospitalization, the patient underwent percutaneous transluminal coronary angioplasty and stenting and 500 mg ticlopidine was administered daily. At this time, complete blood count and other biochemical parameters were normal. On the eighteenth day of ticlopidine therapy, investigations disclosed a WBC of 0.4 × 10 9 /L, a platelet count of 2.0 × 10 9 /L, an Hb level of 9.7 g/dL with a reticulocyte count of 0.8%. Coagulation tests were normal. Diagnostic information could not be obtained by sternal bone marrow aspirate. A trephone bone marrow biopsy displayed extremely hypoplastic cellularity (5-10%) and severe aplastic anemia. In the skin biopsy, superficial perivascular dermatitis was observed. Immunoglobulin levels, autoantibodies, and hepatitis markers were normal. Repeated blood cultures wer negative. In spite of the antibiotic modifications performed to control neutropenic fever, the patient died of septic shock and multiorgan dysfunction. Postmortem percutaneous liver biopsy disclosed cholestasis.Ticlopidine-induced severe aplastic anemia, neutropenia, and thrombocytopenia have been reported frequently. The adverse effects mentioned above are usually reversible and appear after 4-5 weeks of administration of ticlopidine [2]. Yunis et al. [3], claim that the effects of ticlopidine on bone marrow is caused by direct toxic effects other than idiosyncrasy. On the other hand, Ona et al. [4] mentioned that immunological processes could have a role in the pathogenesis. Furthermore, hepatic dysfunction was observed in patients receiving ticlopidine [1,5]. Interestingly, in our case we have observed a combination of superficial perivascular dermatitis, aplastic anemia, and hepatic dysfunction; and we have noticed that the previous ticlopidine-induced aplastic anemia cases could not have been diagnosed in a such short period of time after the therapy. Hematologic disorders caused by ti...

Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors

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Testosterone action on erythropoiesis does not require its aromatization to estrogen: Insights from the testosterone and estrogen treatment of two aromatase-deficient men

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