trimethoprim--sulfamethoxazole-drug-combination and Anemia--Macrocytic

A 50-year-old woman was admitted to our emergency room because of progressive weakness. She collapsed the night before admission. Skin and mucosa were pale, she denied major infections or bleedings. An alcohol abuse was known for many years. Because of edema she received a therapy with triamteren, an infection of the urinary tract was treated with cotrimoxacol.. In addition to thrombocytopenia (50 Gpt/l) and leukocytopenia (1,51 10 (9)/l) we diagnosed a hyperchromic and macrocytic anemia (Hb 3,6 mmol/l [5,8 g/dl], Hk 0,17, MCH 2.52 fmol, 116,8 fl). Folic acid was decreased to 0.677 ng/ml, whereas levels of cobalamin, ferritin and iron were normal. Examination of bone marrow showed a hypercellular marrow with typical megaloblastic features of erythropoiesis and granulopoiesis. A systemic hematological disorder could be ruled out. The folic acid deficiency in our patient was the result of a long time alcohol abuse and a simultaneous therapy with mild folate antagonists (triamteren and cotrimoxacol).. The patient received folic acid (5 mg/d orally). Within one week the peripheral blood counts increased to normal, the follow up bone marrow examination showed a hyperplastic marrow with normal hematopoietic maturation.. Folic acid deficiency can be aggravated because of simultaneous therapy with mild folate antagonists. In addition to megaloblastic anemia this can lead to thrombocytopenia and/or leukocytopenia. Therefore in patients with pancytopenia a deficiency of folic acid should be ruled out.

Topics: Alcoholism; Anemia, Macrocytic; Anti-Infective Agents, Urinary; Diagnosis, Differential; Diuretics; Edema; Female; Folic Acid; Folic Acid Antagonists; Folic Acid Deficiency; Humans; Middle Aged; Pancytopenia; Triamterene; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Trimethoprim-sulfamethoxazole (TMP-SMX), commonly used for prophylaxis of Pneumocystis carinii pneumonia (PCP) in AIDS patients, often produces a high incidence of treatment-limiting reactions. We investigated the effect of oral administration of TMP-SMX alone or in combination with the antiretroviral drug zidovudine (ZDV) on hematopoiesis and cellular immunity in BALB/c mice. Daily treatment for 28 days with TMP-SMX (160:800 mg/kg) had no effect on hematopoiesis or the ex vivo proliferative response of splenic T lymphocytes to allogeneic tumor cells (EL-4) or to concanavalin A (ConA), or that of splenic B cells to lipopolysaccharide (LPS). ZDV at 240 mg/kg/day was not immunosuppressive but caused a mild macrocytic anemia. Combined treatment produced severe pancytopenia, a significant drop in splenic cellularity, and a 61% decrease in the percentage of splenic macrophages. The percentage of splenic CD3+ lymphocytes increased 150% in the TMP-SMX + ZDV group, but the ratios of T-cell subsets and the frequency of B cells remained unchanged. Combined drug treatment did not impair the proliferative response of B cells to LPS or that of T cells to EL-4 cells. In concert with the reduction in the percentage of macrophages, the proliferative response of T lymphocytes to ConA decreased significantly. Optimal ConA-induced T-cell proliferation requires the participation of accessory cells (AC) (e.g., macrophages); EL-4 cells are able to function as AC. These data indicate that ZDV synergizes with TMP-SMX, causing severe hematotoxicity and suppressing AC-dependent immune function, and suggest that this therapeutic regimen may contribute to the immune deterioration in AIDS patients.

Topics: Administration, Oral; Anemia, Macrocytic; Animals; Anti-HIV Agents; Anti-Infective Agents; Antigen-Presenting Cells; Concanavalin A; Drug Combinations; Female; Hematopoiesis; Immunity, Cellular; Immunosuppression Therapy; Lipopolysaccharides; Lymphocyte Activation; Lymphocyte Count; Mice; Mice, Inbred BALB C; Pancytopenia; Spleen; T-Lymphocytes; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Cells, Cultured; Zidovudine

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Drug Combinations; Female; Folic Acid Antagonists; Humans; Male; Megaloblasts; Middle Aged; Pyrimethamine; Sulfamethoxazole; Triamterene; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Combinations; Female; Humans; Leucovorin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination