Sustained granulocyte recovery after G‐CSF in a patient with ticlopidine‐induced severe aplastic anemia

Abstract

The use of ticlopidine as an antiplatelet drug has been associated with agranulocytosis (I-2%) and thrombocytopenia (O.l%), and in a few cases (8 cases have been described) with severe aplastic anemia (SAA) [ 1-31, Patients with aplastic anemia and residual myeloid progenitors can respond to pharmacologic doses of growth factors such as granulocyte colony-stimulating factor (G-CSF). However, all patients who show an increase in neutrophil counts with G-CSF return to baseline values 2-10 days after discontinuation of the drug [4]. We describe here the first case of sustained granulocyte recovery after G-CSF in a patient with ticlopidineinduced SAA.A 78-year-old-man was admitted with a 48-hr history of fever. He had been taking amiodarone for 1 year for supraventricular tachycardia, and ticlopidine 500 mg/day for 6 weeks for peripheral arteriopathy. He suffered from chronic renal failure due to obstructive uropathy and recurrent urinary tract infections. For months, he had presented a normocytic normochromic anemia with hemoglobin levels near 10 g/dl and a creatinine clearance of 30 mlhin. On admission, physical examination revealed a temperature of 39°C. The lungs were clear. No lymphadenopathy or hepatosplenomegaly were found. Peripheral blood counts were WBC 0.9 X 109/L (10% neutrophils, 90% lymphocytes), hemoglobin 8.3 g/dl, and platelets 12 X 109/L. Biochemical parameters (except from creatinine 3.2 mg/dl); immunoglobulin levels, complement, and autoantibodies were normal. Serological studies for hepatitis B and C viruses, human immunodeficiency virus (HIV), parvovirus, and Epstein-Ban virus (EBV) were negative.Serrutiu marcenses was identified in blood and urine cultures. A bone marrow biopsy showed a picture of SAA without cytogenetic abnormalities. Ticlopidine was stopped. Treatment included IV antibiotics, red cell and platelet support, and G-CSF at a daily dose of 5 p,g/kg subcutaneously. Twelve days after G-CSF was begun, WBC was 1.9 X 109/L with 32% of neutrophils. Two days later, WBC was 6.6 X 109/L with 70% neutrophils and remained within the normal range thereafter, although G-CSF was discontinued on day 14. Hemoglobin and platelet counts remained at admis-0 1995 Wiley-Liss, Inc.sion values with high transfusion requirements. High-dose immunoglobulins and recombinant erythropoietin were given without results. The clinical course was stormy, and death occurred 5 months later from massive gastrointestinal bleeding.In six of the eight reported cases of ticlopidine-related SAA bone marrow completely recovered in 15 days to 1 year after discontinuation of the drug. The sustained neutrophil recovery after G-CSF in our case and the persistence of low hemoglobin and platelet counts might suggest that ticlopidine-related SAA is not immunologically mediated, as described by other studies [5]. Thus a trial with myeloid growth factors such as G-CSF or GM-CSF is warranted.Aplastic anemia is one of the most dreaded adverse drug reactions. Monitoring of the blood counts during ticlopidine therapy should he performe...

Ticlopidine-induced aplastic anemia and quick recovery with G-CSF: Case report and literature review

“…However, its use in the literature, though limited, is not very encouraging, as many patients had persistence of bone marrow suppression [6][7][8][9]11], leading to death in a few instances [6][7][8]11]. This patient responded dramatically to G-CSF with quick recovery of granulocytes and platelets.…”

“…In general, treatment was mostly supportive and colony stimulating factor was tried in eight reported cases with variable success [6][7][8][9][11][12][13]. Four of those patients recovered 4 to more than 13 weeks after stopping ticlopidine [9,12,13], and four patients died after 1-21 weeks [6][7][8]11] following cessation of ticlopidine therapy despite administration of colony stimulating factor.…”

“…The time to recovery was as short as three weeks [12,13] and as protracted as 52 weeks [5]. Death was not infrequent and occurred in seven patients one day to 21 weeks after presentation and drug discontinuation [6][7][8]10,11,16,17]. In general, treatment was mostly supportive and colony stimulating factor was tried in eight reported cases with variable success [6][7][8][9][11][12][13].…”