The glycoprotein IIb/IIIa antagonist c7E3 inhibits platelet aggregation in the presence of heparin-associated antibodies

Liem, Timothy K.; Teel, Rosemary; Shukla, Shivendra D.; Silver, Donald

doi:10.1016/s0741-5214(97)70328-8

Cited by 12 publications

(3 citation statements)

References 19 publications

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“…5 Platelet function inhibitors such as aspirin and dipyridamole protect patients with HAAbs from thromboembolic complications during brief exposures to heparin, but not from thrombocytopenia. 6 The glycoprotein IIb/IIIa inhibitor abciximab inhibits HAAb-induced platelet aggregation, 7 but the glycoprotein IIb/IIIa inhibitors have not been shown to provide adequate anticoagulation as the sole agent in patients with HAAbs. Certain glycoproteins IIb/IIIa inhibitors, such as abciximab, have been associated with thrombocytopenia and hemorrhagic complications.…”

Section: Discussionmentioning

confidence: 99%

Lepirudin is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies

Mudaliar

Liem

Nichols

et al. 2001

Journal of Vascular Surgery

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Section: Discussionmentioning

confidence: 99%

Lepirudin is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies

Mudaliar

Liem

Nichols

et al. 2001

Journal of Vascular Surgery

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“…More than 66% of patients with HAAb will not cross-react to enoxaparin, 21 and 74% will not cross-react to dalteparin. 22 If the LMWH caus-es platelet aggregation and heparin-like anticoagulation therapy is required, we consider blocking the platelet glycoprotein IIb/IIIa receptor with a monoclonal antibody 23 or alternatively using a heparin substitute. A few patients with HIT have been treated with heparin substitutes (i.e., LMWHs, 21 heparinoids, 24 hirudin, 25 ancrod).…”

Section: Discussionmentioning

confidence: 99%

Reduced morbidity and mortality rates of the heparin-induced thrombocytopenia syndrome

Almeida

Coats

Liem

et al. 1998

Journal of Vascular Surgery

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“…Stimulation of the production of tissue factor at the surface of endothelial cells by serum samples from HIT patients suggested that immune injury to endothelial cells may have a role in the development of thrombosis in some patients after heparin therapy (7). To date, attempts to treat HIT with platelet function inhibiting agents such as aspirin, dipyridamole and iloprost have met with variable success and it is only recently that agents that bind to the GP IIb-IIIa receptor have been shown to inhibit platelet aggregation in the presence of heparin and heparin-associated antibodies (8)(9)(10). These data described that GP IIb-IIIa inhibitors can potently block in vitro platelet activation and aggregation induced by HIT serum/heparin and suggested that they can be used for the treatment of patients with HIT or as prophylaxis for HIT in those who are likely to produce a HIT response.…”

Section: Introductionmentioning

confidence: 99%

Effect of SR121566A, a Potent GP IIb-IIIa Antagonist, on the HIT Serum/heparin-Induced Platelet Mediated Activation of Human Endothelial Cells

Savi¹,

Jeske²,

Walenga³

et al. 1998

Thromb Haemost

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SummaryHeparin-induced thrombocytopenia (HIT) is a common adverse effect of heparin therapy that carries a risk of serious thrombotic events. This condition is caused by platelet aggregation, which is mediated by anti-heparin/platelet factor 4 antibodies. Sera from patients with HIT in the presence of platelets, induced the expression of E-selectin, VCAM, ICAM-1 and tissue factor and the release of IL1β, IL6, TNFα and PAI-1 by human umbilical vein endothelial cells (HUVECs) in vitro and initiated platelet adhesion to activated HUVECs. These effects which occurred in a time-dependent manner were significant in the first 1-2 h of incubation and reached a maximum after 6 to 9 h. The GP IIb-IIIa receptor antagonist SR121566A which has been shown to block platelet aggregation induced by a wide variety of agonists including HIT serum/heparin, reduced in a dose-dependent manner the HIT serum/heparin-induced, platelet mediated expression and release of the above mentioned proteins. The IC50 for inhibition of HIT serum/ heparin-induced platelet dependent HUVEC activation by SR121566A was approximately 10-20 nM. ADP, but not serotonin release, also appeared to be involved as apyrase and ATPγS blocked platelet-dependent, HIT serum/heparin-induced cell surface protein expression and cytokine release by HUVECs. Increased platelet adherence to HIT serum/heparin-activated HUVECs was inhibited by SR121566A and, to a lesser extent, by apyrase and ATPγS, showing that platelet activation and release was at the origin of the HIT serum/heparin-induced expression of these proteins by HUVECs.Thus, sera from patients with HIT induced the expression of adhesive and coagulation proteins and the release of cytokines by HUVECs through the activation of platelets which occurred in a GP IIb-IIIa-dependent manner, a process that could be selectively blocked by SR121566A.

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The glycoprotein IIb/IIIa antagonist c7E3 inhibits platelet aggregation in the presence of heparin-associated antibodies

Cited by 12 publications

References 19 publications

Lepirudin is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies

Lepirudin is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies

Reduced morbidity and mortality rates of the heparin-induced thrombocytopenia syndrome

Effect of SR121566A, a Potent GP IIb-IIIa Antagonist, on the HIT Serum/heparin-Induced Platelet Mediated Activation of Human Endothelial Cells

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