### Neutropenia

Neutropenia may occur suddenly. Bone-marrow examination typically shows a reduction in white blood cell precursors. After withdrawal of ticlopidine, the neutrophil count usually rises to >1200/mm within 1 to 3 weeks. 3

### Thrombocytopenia

Rarely, thrombocytopenia may occur in isolation or together with neutropenia.

### Thrombotic Thrombocytopenic Purpura (TTP)

TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragmented RBCs] seen on peripheral smear), neurological findings, renal dysfunction, and fever. The signs and symptoms can occur in any order, in particular, clinical symptoms may precede laboratory findings by hours or days. With treatment (often including plasmapheresis), 70% to 80% of patients will survive with minimal or no sequelae. Because platelet transfusions may accelerate thrombosis in patients with TTP on ticlopidine, they should, if possible, be avoided. prompt

### Aplastic Anemia

Aplastic anemia is characterized by anemia, thrombocytopenia and neutropenia together with a bone marrow examination that shows decreases in the precursor cells for red blood cells, white blood cells, and platelets. Patients may present with signs or symptoms suggestive of infection, in association with low white blood cell and platelet counts. treatment, which may include the use of drugs to stimulate the bone marrow, can minimize the mortality associated with aplastic anemia. Prompt

### Monitoring for Hematologic Adverse Reactions

Starting just before initiating treatment and continuing through the third month of therapy, patients receiving ticlopidine must be monitored every 2 weeks. Because of ticlopidine’s long plasma half-life, patients who discontinue ticlopidine during this 3-month period should continue to be monitored for 2 weeks after discontinuation. More frequent monitoring, and monitoring after the first 3 months of therapy, is necessary only in patients with clinical signs (eg, signs or symptoms suggestive of infection) or laboratory signs (eg, neutrophil count less than 70% of the baseline count, decrease in hematocrit or platelet count) that suggest incipient hematological adverse reactions.

Clinically, fever might suggest neutropenia, TTP, or aplastic anemia; TTP might also be suggested by weakness, pallor, petechiae or purpura, dark urine (due to blood, bile pigments, or hemoglobin) or jaundice, or neurological changes. Patients should be told to discontinue ticlopidine and to contact the physician immediately upon the occurrence of any of these findings.

Laboratory monitoring should include a complete blood count, with special attention to the absolute neutrophil count (WBC x % neutrophils), platelet count, and the appearance of the peripheral smear. Ticlopidine is occasionally associated with thrombocytopenia unrelated to TTP or aplastic anemia. Any acute, unexplained reduction in or platelet count should prompt further investigation for a diagnosis of TTP, and the appearance of (fragmented RBCs) on the smear should be treated as presumptive evidence of TTP. A simultaneous decrease in platelet count and WBC count should prompt further investigation for a diagnosis of aplastic anemia. If there are laboratory signs of TTP or aplastic anemia, or if the neutrophil count is confirmed to be <1200/mm , then ticlopidine should be discontinued immediately. hemoglobinschistocytes3