PMC:2778502 / 11270-15221 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2778502","sourcedb":"PMC","sourceid":"2778502","source_url":"http://www.ncbi.nlm.nih.gov/pmc/2778502","text":"9. Immune Thrombocytopenia\nIn immune thrombocytopenia purpura (ITP), platelet destruction is caused as antibodies bind to platelets leading to their clearance by the reticuloendothelial system (RES), as well as by some degree of decreased production. ITP can be idiopathic, or related to viral infections, autoimmune disorders, lymphoproliferative disorders, or drugs [34, 35].\nClassical causes of drug-induced thrombocytopenia are the quinine and quinine-like drugs [36]. The thrombocytopenia is typically sudden, severe, and may be accompanied by bleeding. The thrombocytopenia induced by these drugs is caused by antibody that is nonreactive in the absence of drug, but binds to epitopes on platelet membrane, glycoproteins IIb/IIIa or Ib/IX, when the sensitizing drug is present. Vancomycin can also be associated with marked thrombocytopenia and demonstrable drug-dependent antibodies in the serum [37]. Prolonged thrombocytopenia may occur in patients with renal insufficiency, likely due to delayed drug clearance. Other drugs associated with immune thrombocytopenia include include antimicrobials (sulfanomides, rifampin, linezolid), anti-inflammatory drugs, antineoplastics, antidepressants, benzodiazepines, anticonvulsants (carbamazepine, phenytoin, valproic acid) as well as cardiac and antihypertensive drugs [34, 35]. Although the ITP generally develops rapidly, it usually resolves upon cessation of treatment and is drug-specific.\nHeparin is well known to be associated with thrombocytopenia, sometimes with arterial or venous thrombosis, which is generally a far greater threat than the risk of bleeding [38, 39]. Heparin-induced immune thrombocytopenia is caused by antibodies against complex of heparin and platelet factor 4 (PF4), which can lead to platelet activation and the initiation of thromboses. Although heparin can also induce a milder, nonimmune mediated thrombocytopenia, the immune version is potentially more severe. Heparin-induced thrombocytopenia follows exposure to both unfractionated and low molecular weight heparins, but is less common with the latter. There is usually a delay of 5–10 days for newly exposed patients, but thrombocytopenia can occur within hours in patients with a recent heparin exposure who still have PF4 antibodies, or within a few days for those with prior exposure who develop an anamnestic response. Occasionally venous gangrene, skin necrosis, and acute anaphylactic-type reactions to heparin can occur. In the appropriate clinical setting, the diagnosis is supported by evidence of antiheparin antibodies, which can be detected by a number of assays. These include the more sensitive serologic assays (e.g., by ELISA) and the functional, more specific assays such as measuring C-14 serotonin platelet release in the presence of heparin and serum. In addition to cessation of heparin use, treatment involves anticoagulation to reduce the risk of thrombosis, typically with argatroban, bivalrudin, or lepirudin initially, with transition to warfarin. Anticoagulation should be continued for several weeks even after the platelet count returns to normal due to the high risk of thrombosis during that time.\nAbciximab (a chimeric Fab fragment) and eptifibatide and tirofiban (ligand mimetic inhibitors) are frequently used following coronary angioplasty to reduce thrombosis by impairing platelet function through the inhibition of GP IIb/IIIa-fibrinogen interaction. In addition to inducing the desired platelet dysfunction, however, they can induce a severe thrombocytopenia in a small percentage of patients, likely through a drug- dependent antibody-mediated mechanism [40]. This may begin within hours to days and typically resolves spontaneously in 2–5 days. It may occur on the initial or subsequent infusions. The majority of patients recover without complications though severe bleeding may occasionally occur. Platelet transfusions can be given if there is significant 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