Mechanisms of drug-induced thrombocytopenias
| Mechanism . | Description . | Drugs . |
|---|---|---|
| Most frequent | ||
| Bone marrow depression | Toxic bone marrow depression | Chemotherapeutics, linezolid, nonsteroidal anti-inflammatory drugs, azathioprine, and valproic acid |
| Immune mediated | ||
| Classic drug-dependent antibodies | Drug, platelet glycoproteins, and antibodies form a 3-molecular complex, which results in increased platelet destruction by the reticuloendothelial system; onset typically 7 to 20 d after start of a new drug or immediately in case of re-exposure; platelet nadir <20 × 109/L | Quinine, quinidine, antibiotics (sulfamethoxazole trimethoprim, vancomycin, rifampicin cephalosporins), antiepileptics (valproate, carbamazepine, phenytoin), diuretics (furosemide, thiazides), ranitidine, nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen), |
| Hapten-induced antibodies | Drug acts as a hapten that binds to large molecules (eg, proteins) on the platelet surface and stimulates antibody production; onset typically 7 to 20 d after start of an antibiotic; platelet nadir variable, often >20 × 109/L | Penicillin, and cephalosporins |
| Fiban-induced antibodies | Drug binds to epitopes on GPIIbIIIa on platelets, causing a conformational change that enhances affinity of preexisting antiplatelet antibodies; onset within hours after start of the drug or 7 to 10 d in a subset of patients after start of the drug, even if the drug is no longer present (antibodies cross-react with native GPIIbIIIa; platelet nadir often <20 × 109/L; exclude pseudothrombocytopenia | Tirofiban and eptifibatide |
| Drug-specific antibodies | Fab fragments of a monoclonal antibody bind to GPIIbIIIa on platelets and become targets of naturally occurring antibodies, provoking increased platelet destruction; onset within hours after start of the drug; platelet nadir often <20 × 109/L; exclude pseudothrombocytopenia | Abciximab |
| Autoantibodies | Production of platelet-specific autoantibodies is induced and maintained by a drug (exact mechanism unknown) | Procainamide, levodopa, and gold |
| Prothrombotic | ||
| Heparin-induced thrombocytopenia | IgG antibodies against PF4/polyanion complexes activate platelets via the platelet Fc-receptor, inducing thrombin generation | Heparin, low-molecular-weight heparin, and potentially other polyanionic drugs (eg, aptamers) |
| Thrombotic microangiopathy | Autoantibodies against ADAMTS13 are produced in the presence of the drug, causing ADAMTS13 deficiency; onset 5 to 20 d after start of a new drug; platelet count nadir 10 to 30 × 109/L | Quinine, cyclosporine, tacrolimus, and gemcitabine |
| Mechanism . | Description . | Drugs . |
|---|---|---|
| Most frequent | ||
| Bone marrow depression | Toxic bone marrow depression | Chemotherapeutics, linezolid, nonsteroidal anti-inflammatory drugs, azathioprine, and valproic acid |
| Immune mediated | ||
| Classic drug-dependent antibodies | Drug, platelet glycoproteins, and antibodies form a 3-molecular complex, which results in increased platelet destruction by the reticuloendothelial system; onset typically 7 to 20 d after start of a new drug or immediately in case of re-exposure; platelet nadir <20 × 109/L | Quinine, quinidine, antibiotics (sulfamethoxazole trimethoprim, vancomycin, rifampicin cephalosporins), antiepileptics (valproate, carbamazepine, phenytoin), diuretics (furosemide, thiazides), ranitidine, nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen), |
| Hapten-induced antibodies | Drug acts as a hapten that binds to large molecules (eg, proteins) on the platelet surface and stimulates antibody production; onset typically 7 to 20 d after start of an antibiotic; platelet nadir variable, often >20 × 109/L | Penicillin, and cephalosporins |
| Fiban-induced antibodies | Drug binds to epitopes on GPIIbIIIa on platelets, causing a conformational change that enhances affinity of preexisting antiplatelet antibodies; onset within hours after start of the drug or 7 to 10 d in a subset of patients after start of the drug, even if the drug is no longer present (antibodies cross-react with native GPIIbIIIa; platelet nadir often <20 × 109/L; exclude pseudothrombocytopenia | Tirofiban and eptifibatide |
| Drug-specific antibodies | Fab fragments of a monoclonal antibody bind to GPIIbIIIa on platelets and become targets of naturally occurring antibodies, provoking increased platelet destruction; onset within hours after start of the drug; platelet nadir often <20 × 109/L; exclude pseudothrombocytopenia | Abciximab |
| Autoantibodies | Production of platelet-specific autoantibodies is induced and maintained by a drug (exact mechanism unknown) | Procainamide, levodopa, and gold |
| Prothrombotic | ||
| Heparin-induced thrombocytopenia | IgG antibodies against PF4/polyanion complexes activate platelets via the platelet Fc-receptor, inducing thrombin generation | Heparin, low-molecular-weight heparin, and potentially other polyanionic drugs (eg, aptamers) |
| Thrombotic microangiopathy | Autoantibodies against ADAMTS13 are produced in the presence of the drug, causing ADAMTS13 deficiency; onset 5 to 20 d after start of a new drug; platelet count nadir 10 to 30 × 109/L | Quinine, cyclosporine, tacrolimus, and gemcitabine |