Thrombocytopenia immune response

The following points should be considered in all patients receiving heparin Platelet counts should be performed frequently thrombocytopenia appearing in a time frame consistent with an immune response to heparin should be considered suspicious for HIT and any new thrombus occurring in a patient receiving heparin therapy should raise suspicion of HIT. Patients who develop HIT are treated by discontinuance of heparin and administration of a direct thrombin inhibitor or fondaparinux (see below). 

The third mechanism described for drug-induced thrombocytopenia is the innocent bystander-type immune response. The most commonly implicated drug is quinidine, and the drug-induced thrombocytopenia is frequently related to higher doses of the drug. Quinidine may also form a hapten with the platelet membrane to produce thrombocytopenia. ... 

Penicillamine (e.g., Cuprimine) Suppresses immune response. May induce remission. Mechanism unknown. GI upset, i taste perception, proteinurea, rash, thrombocytopenia, leukopenia. PO. Rapid absorption, extensive metabolism. 

Curtis BR, Divgi A, Garritty M, Aster RH (2004) Delayed thrombocytopenia after treatment with abciximab a distinct clinical entity associated with the immune response to the drag. J Thromb Haemost 2 985-992... 

Warkentin TE, Sheppard JA, Moore JC, Cook RJ, Kelton JG. Studies of the immune response in heparin-induced thrombocytopenia. Blood 2009 113(20) 4963-9. 

Pouplard C, ComOlet-Lefebvre P, Attaoua R, Leroux D, Lecocq-Lafon C, Rollin J, et al. Interleukin-10 promoter microsatellite polymorphisms influence the immune response to heparin and the risk of heparin-induced thrombocytopenia. Thromb Res 2012 129(4) 465-9. 

Heavy Metals. Some heavy metals such as gold and platinum are used pharmacologically as immunomodulators to treat rheumatoid arthritis and as antineoplastic drugs, respectively. Most heavy metals inhibit mitogenicity, antibody responses, and host resistance to bacterial or viral challenge, and tumor growth. Platinum has been shown to suppress humoral immunity, lymphocyte proliferation, and macrophage function (Lawrence, 1985). Clinically, mild to moderate myelosuppression may also be evident with transient leukopenia and thrombocytopenia. 

Large quantities of IgM are produced in response to particulate antigens like malaria, trypanosomiasis, helminths, and immune complexes and IgM malarial antibodies have been found associated with thrombocytopenia in patients with malaria infection (B4). 

The bleeding potential is similar among the agents. However, thrombocytopenia, particularly profound thrombocytopenia (platelet count <50,000 mrrT3) occurs with a two-to four-fold higher frequency with abciximab (0.4— 1.0%) compared with eptifibatide (0-0.2%) or tirofiban (0,1 —0.3%) (6), The exact mechanism of this difference is not clear, However, immune complex-mediated reaction (due to an anamnestic response to the humanized chimeric antibody) may contribute to rapid precipitation of thrombocytopenia with abciximab (6), Platelet counts should, therefore, be measured early (within the first one to four hours) after administration of these agents and followed for the duration of therapy. Platelet transfusion should be considered for profound thrombocytopenia with or without serious bleeding (6). 

This suggests that in patients with drug-induced immune thrombocytopenia, tests for metabolite-dependent antibodies can be helpful in identifying the responsible agent. 

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