Eptifibatide can inhibit new platelets in both active and inactive states. Also, detecting platelet factor-4 (PF-4) assay in HIT can help differentiate it from eptifibatide-induced thrombocytopenia. Thus thrombocytopenia develops within the first day, or severe thrombocytopenia favors thrombocytopenia secondary to eptifibatide. HIT-1 occurs within one and five days, whereas HIT-2 occurs within 4 to 20 days following heparin administration. Compared to heparin-induced thrombocytopenia (HIT), eptifibatide usually causes a steep decline in platelet count (less than 30000 cells/ uL). Heparin and eptifibatide are administered simultaneously during PCI and in ACS treatment. Among the Gp IIb/IIIa inhibitors, only abciximab has reportedly shown an association with pseudo-thrombocytopenia. The absence of platelet clumping on peripheral smear rules out pseudo-thrombocytopenia. Pseudothrombocytopenia is detectable using complete blood cell analysis when blood samples are collected in EDTA- containing tubes. It is also clinically relevant to distinguish eptifibatide-induced thrombocytopenia from other etiologies. Tirofiban-induced thrombocytopenia (secondary to eptifibatide) occurs because the naturally occurring drug-dependent antibodies specific for eptifibatide occupy Gp IIb/IIIa receptor site. The risk of thrombocytopenia associated with eptifibatide (0.1 to 0.2%) and tirofiban (0.1 to 0.3%) is lesser compared to abciximab (0.4 to 1.1%). Thrombocytopenia infrequently occurs with Gp IIb/IIIa inhibitors but sometimes may be profound. Thrombocytopenia is another side effect of eptifibatide reported in several case reports. However, there is increased bleeding following abciximab administration compared to eptifibatide or tirofiban because of the rapid reversibility of these latter two agents. More red cell transfusions were required in the eptifibatide group than placebo to counteract anemia. In most cases, bleeding was mild and occurred at femoral access sites. The significant side effect of eptifibatide described in the PURSUIT trial was bleeding. Glanzmann thrombasthenia is an autosomal recessive disease with platelet receptor deficiency similar to the site of action of eptifibatide. Furthermore, high doses of eptifibatide provide additional antithrombotic benefits by blocking the vitronectin binding site, the ligand for alpha-beta in vascular cells, which may offer other antithrombotic benefits. The low affinity for direct binding with GP IIb/IIIa is responsible for rapid states. Eptifibatide can competitively inhibit the KGD (Lys-Gly-Asp) sequence binding site in active and inactive states. Higher plasma levels of eptifibatide are needed to competitively inhibit the target of over 80% block of KGD binding sites. Eptifibatide binds to the KGD binding sites on Gp IIb/IIIa receptor and competitively fights against the receptor's binding with fibrinogen, von Willebrand factor (vWF), and prothrombin. It has a highly specific binding to the Gp IIb/IIIa receptor because of the structural resemblance of the KGD (Lys-Gly-Asp) sequence. The eptifibatide is a natural disintegrin from snake venom. The binding sites of GP IIb/IIIa are hidden as latent and become active on the surface by undergoing a conformational change via inside-out signaling. The beta-subunit comprises disulfide bonds, binding sites including lysine-glycine-aspartic acid (KGD) bindings binding sites, or arginine-glycine-aspartic acid (RGD) for attachment of fibrinogen, von Willebrand factor (vWF) and prothrombin. The alpha-subunit is characterized by three or four divalent Ca- or Mn-binding domains crucial in the GP IIb/IIIa heterodimer. The Gp IIb/IIIa receptor is a calcium and manganese-dependent heterodimer protein with an alpha- and a beta-subunit. GP IIb/IIIa heterodimer contains a large extracellular region, a transmembrane domain, and a short intracellular cytoplasmic tail. The glycoprotein IIb/IIIa receptor inhibitors, including abciximab, eptifibatide, sibrafiban, and tirofiban, block the activation of Gp IIb/IIIa receptors, ultimately preventing clot formation/progression. The secondary platelet plug is essential for the progression and stability of the clot. The activation of Gp IIb/IIIa receptors leads to cross-linking of fibrinogen to attach multiple platelets to form a durable secondary platelet plug. This event triggers a platelet signaling cascade that leads to the activation of the glycoprotein IIb/IIIa receptor (GpIIb/IIIa). Rupture of atherosclerotic plaque or injury to the vessel wall exposes the subendothelial matrix of the coronary blood vessel to circulating platelets.
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