A modified thromboelastographic method for monitoring c7E3 Fab in heparinized patients.
The monoclonal antibody, c7E3 Fab, binds to the platelet surface fibrinogen receptor (GPIIb/IIIa), inhibiting platelet aggregation and clot retraction. We performed an in vitro study to assess the ability of a modification of the thromboelastograph (MTEG) to detect inhibition of clot strength by c7E3 Fab and its reversal with platelet-rich plasma (PRP). In the modified assay (MTEG), thrombin was added to whole blood (WB) and platelet-poor plasma (PPP) and the resultant maximum amplitude (MA) was measured, MAWB and MAPPP, respectively. Anticoagulated blood samples from 17 patients scheduled for cardiac surgery were collected for a dose response (Part I; n = 5) and c7E3 Fab reversal (Part II; n = 12) study. Clot strength was reduced in a dose-dependent manner by c7E3 Fab. Ecteola cellulose effectively reversed the effect of heparin on the thrombin time and the addition of PRP significantly increased the MAWB (P < 0.0001) and MAWP-PPP (P < 0.0001). Subtracting the MAPPP from MAWB significantly magnified the response of MA to the addition of c7E3 Fab (P = 0.002) and its reversal with PRP (P = 0.005). This in vitro study indicates that the MTEG is a responsive assay demonstrating that inhibition by the antiplatelet c7E3 Fab is reversible with PRP.
Greilich
P E
PE
Anesthesia and Operative Services, Walter Reed Army Medical Center, Washington, DC, USA.
Alving
B M
BM
O'Neill
K L
KL
Chang
A S
AS
Reid
T J
TJ
D000077284:Abciximab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D003018:Clot Retraction; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013916:Thrombelastography / Q000379:methods*
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D000077284:Abciximab