In vitro dose-response and reversal study.
Anesthesia Research (Dallas, TX) and Special Studies Coagulation Laboratories (Washington, DC).
Nine healthy volunteers.
The addition of increasing concentrations of abciximab, 0 to 10 μg/mL, and purified fibrinogen, 50 to 400 mg/dL. The reversal of abciximab, 4 μg/mL, with the addition of fresh platelet-rich plasma (PRP) sufficient to increase the platelet concentration by approximately 10 % .
Platelet aggregation and platelet contractile force using the Hemodyne analyzer were used as platelet-specific measurements. The Thrombelastograph maximum amplitude (MA) for platelets (MAPLT) was calculated by subtracting the MA from a platelet-poor plasma (PPP) sample (MAppp) determined in one thromboelastography well from that of whole-blood MA (MAWB) run simultaneously in the second thromboelastography well. The addition of abciximab, 0 to 10 μg/mL, resulted in significant concentration-dependent reductions in platelet aggregation (p < 0.001), platelet contractile force (p < 0.001), and MAPLT (p < 0.001). Platelet contractile force (p < 0.03) and MAPLT (p < 0.05) were significantly more responsive than MAWB to the effect of abciximab, 4 μg/mL, and its reversal with the addition of fresh PRP. Purified fibrinogen concentration directly correlated with thromboelastography MA (rs = 0.97; p < 0.001), yet had no effect on platelet contractile force. The addition of abciximab had no measurable influence on the MAPPP.
This in vitro study suggests that the Hemodyne analyzer and modified Thrombelastograph might be clinically useful methods to monitor the platelet inhibitory effects of agents such as abciximab.