Ticlopidine‐induced aplastic anemia: Two new case reports, review, and meta‐analysis of 55 additional cases

Abstract

Ticlopidine-induced aplastic anemia (TIAA) is considered very uncommon. We present two new cases, and we review 55 additional cases from the literature. The first case concerns a 70-year-old man who developed severe aplastic anemia 7 weeks after treatment with 500 mg of ticlopidine daily. The patient sustained a severe septic episode, was treated with antibiotics and GM-CSF, and recovered the 14 th day after ticlopidine withdrawal. The second was an 82-year-old man receiving ticlopidine for 2 years when, during a febrile episode, he was found neutropenic with marrow aplasia. Ticlopidine withdrawal and treatment with antibiotics, transfusions, and G-CSF helped him to recover. When the data of the 57 patients are evaluated, a reversible direct cytotoxic effect of ticlopidine on the pluripotent/bipotent hematopoietic progenitor stem cell is proposed. It is estimated that the real incidence if TIAA is higher, and many cases, initially presented as agranulocytosis ± thrombocytopenia, might be true aplastic anemias, not proven by marrow aspiration or trephine biopsy. There is no effective monitoring to prevent this side effect. Recombinant growth factors appear not to help in shortening the neutropenic period.

Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy-systematic review and meta-analysis

“…Of them, 19 trials were excluded for various reasons 3,7,[10][11][12]14,15,18,19,[22][23][24][25][26][27][28][29][30][31] (Figure 1). Six trials performed between 1991-2007 and randomizing 414 patients fulfilled inclusion criteria.…”

“…Design incompatible with inclusion criteria -13 trials 3,7,[10][11][12]14,15,18,[22][23][24][25][26] Randomization according to genetics: allo-HSCT vs. immunosuppressive therapy -1 trial 27…”

“…Furthermore, their use may also improve response to IST, as they may act in concert with endogenous HGF to stimulate hematopoietic stem cells. 5,[9][10][11][12] The addition of erythropoiesis stimulating agents to hematopoietic colony stimulating factors is aimed at encouraging hemoglobin production and synergizing the stimulation of other lineage precursors.…”

Prasugrel: Newest Antiplatelet Agent and Its Emerging Role in Management of Acute Coronary Syndrome and Percutaneous Coronary Intervention

“…An older drug in this class was ticlopidine, and although it was used to display the remarkable advantage of these agents in conjunction with aspirin [2][3][4] its use has been hampered by significant adverse reactions, particularly hematologic abnormalities including aplastic anemia and trombotic thrombo cytopenic purpura (TTP) [5]. Clopidogrel, the most widely used thienopyridine, has shown significant improvement in outcomes in patients treated for acute coronary syndromes (ACS) and in those who have undergone percutaneous coronary intervention (PCI), whether elective or urgent [6][7][8][9].…”

Current Oral Antiplatelets: Focus Update on Prasugrel

“…Ticlopidine, the first thienopyridine to be introduced, stepped out of the limelight largely because of its unacceptable side effects (aplastic anemia and thrombotic thrombocytopenic purpura). 6 Clopidogrel, which has a better side-effect profile, soon replaced ticlopidine as the preferred antiplatelet agent in dual antiplatelet therapy with aspirin. Clopidogrel therapy has been shown to improve outcomes in patients with ACS and in those undergoing emergent or elective PCI.…”