In-vitro efficacy of different platelet glycoprotein IIb/IIIa antagonists and thrombolytics on platelet/fibrin-mediated clot dynamics in human whole blood using thrombelastography

Abstract

Suppressing platelet activation improves efficacy of thrombolytic therapy for stroke and acute myocardial infarction. Combination treatment with recombinant tissue plasminogen activator (r-tPA) and glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor that binds with high affinity to platelets may therefore improve the efficacy of thrombolytic therapy. The effect of platelet GPIIb/IIIa antagonists and/or r-tPA on the dynamics of platelet/fibrin clot formation, strength, and lysis was determined using thrombelastography in human blood under thrombin or tissue factor stimulation. The study utilized platelet GPIIb/IIIa antagonists with high affinity and slow off-rate (Class I) from resting and activated platelets in comparison with Class II antagonists (lower affinity and fast off-rate from platelet GPIIb/IIIa receptors). The combination of the active form of roxifiban (XV459; Class I) or the active form of orbofiban (Class II) with a subeffective concentration of r-tPA resulted in a synergistic effect in clot lysis with roxifiban active form XV459 but not with that of orbofiban at therapeutically achievable concentrations that inhibit human platelet aggregation. These data indicate differential enhanced thrombolysis of low levels of r-tPA with high-affinity Class I but not with low-affinity Class II GPIIb/IIIa antagonists in the absence of anticoagulants.

Mechanisms of hydroxyethyl starch‐induced dilutional coagulopathy

“…In addition, low levels of FXIII [26] or excessive fibrinolysis may be associated with reduced MCF [27]. Finally, inhibition of glycoprotein IIb/IIIa receptors diminishes the MCF [28]. In the present study, the most likely explanation for reduced MCF was reduced level of fibrinogen.…”

Adjunctive and Alternative Approaches to Current Reperfusion Therapy

“…21 In vitro and in vivo experimental studies suggest that combination therapy (fibrinolytic agent plus GPIIB/IIIA inhibitor) provide more complete lysis than fibrinolytics alone. 22, 23 The combination was evaluated in a multicenter phase 2 study, The Combined Approach to Lysis Utilizing Eptifibatide and tPA in Acute (CLEAR trial). 24 Ninety-four 0–3 hour ischemic stroke patients were randomized into 3 different arms: IV-tPA (0.9mg/kg) alone or two different combination arms of low-dose IV-tPA (0.3mg/kg and 0.45mg/kg)+eptifibatide (75 μg/kg bolus followed by 0.75μg/kg/minute infusion for 2 hours) with combination treatment given in 69 patients (3:1 randomization to combination arms).…”

Evaluation of coagulation kinetics using thromboelastometry—methodologic influence of activator and test medium

“…The MCF remained unaffected by increasing concentrations of phospholipids, and similar to observations gained from other experimental conditions the amplitude was independent of the type and concentration of activator. [7], the effect of vasoactive agents, platelet agonists, and anticoagulants [22,23], as well as assessment of storage of donor platelets [24]. Some studies have revealed that different types of activators provide different results in various clinical scenarios, such as e.g.…”