The GP IIb/IIIa inhibitor abciximab (ReoPro) decreases activation and interaction of platelets and leukocytes during in vitro cardiopulmonary bypass simulation

Abstract

Abciximab inhibits CPB-induced activation, interaction and consumption of platelets and leukocytes in vitro. GP IIb/IIIa inhibition should be considered as a promising approach not only to conserve platelet function but also to inhibit pro-inflammatory events during CPB in vivo.

Emergency coronary artery bypass grafting in patients with acute myocardial infarction treated with glycoprotein IIb/IIIa receptor inhibitors

“…Concerning abciximab, Straub and co-workers showed that abciximab treatment is associated with significantly lower number of platelet-leukocyte aggregates, lower Pselectin expression, and higher platelet and leukocyte count, using a heart-lung machine model [14]. The authors explain these results with abciximab cross-reactivity with Mac-1 and vitronectin receptors on leucocyte surface.…”

“…Moreover, it causes inhibition of platelet P-selectin expression, decreasing binding capacity of platelets with leucocytes [13]. In contrast with tirofiban and eptifibatide, abciximab cross-reacts with Mac-1 and vitronectin receptors on leucocyte surface, probably attenuating local inflammation [14]. Abciximab is administered with an i.v.…”

“…Contact of blood with cardiopulmonary bypass components is responsible of a systemic inflammatory response with many changes in blood components: rising of cytokines (IL-6 and IL-8), upregulation of P-selectin, alteration and activation of platelets and interaction with leucocytes have been observed [14,17,20]. Particularly, contact of blood with extracorporeal circuits has shown to reduce postoperative platelet count due to aggregation mediated by GP IIb/IIIa receptors [14]. Activated platelets during CABG may lead to thromboembolism, haemorrhage, and inflammation.…”

“…Unbound abciximab is rapidly cleared from circulation, and only little drug remains bound to tissues other than native platelets. Transfusion of fresh platelets rapidly reverses the inhibitory effect of abciximab, since the drug redistributes slowly onto new transfused platelets [14].…”

Immunotherapy in antiphospholipid syndrome

“…In an elegant revision, Erkan and Lockshin described the most recent studies related to inhibition of platelet aggregation [108], which included: 1) the simultaneous administration of anti-GPIIb/IIIa monoclonal antibodies and aPL in mouse models of APS, which resulted in smaller thrombus formation compared with aPL administration only [109]; 2) the prevention of aPL-mediated thrombosis in GPIIb/IIIa deficient mice [110]; and 3) the use of abciximab (a GPIIb/IIIa receptor inhibitor) in the treatment of acute thrombotic syndromes, such as myocardial infarctions and strokes [111]. No data on the use of GPIIa/ IIIb receptor inhibitors in APS patients exist, apart from limited data from an uncontrolled study of hydroxychloroquine, which might inhibit aPL-induced GPIIa/IIIB receptor expression [109].…”