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DOSE DEPENDENT EFFECTS OF c7E3 Fab ON MODIFIED THROMBOELASTOGRAPHY IN HEALTHY VOLUNTEERS

Greilich, PE MD; Carr, ME MD, PhD; Cooley, MV MT; Harris, DN BSEE; Carr, SL MT; Whitten, CW MD

doi: 10.1097/00000539-199802001-00064
Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Cardiovascular Anesthesia
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Department of Anesthesiology & Pain Management, UT Southwestern/VA Medical Centers, Dallas, TX & Department of Pathology, Medical College of Virginia/VCU, Richmond, VA.

Abstract S64

Introduction: A "point of care" platelet function monitor has yet to be established. Although thromboelastography (TEG) has been used clinically, [1] it lacks platelet specificity and requires 30-45 minutes to complete. Modified TEG has been shown to increase the responsiveness of this assay to platelet receptor antagonism and requires only 15 minutes to complete. [2,3] We hypothesized that: 1) modified TEG maximum amplitude (mTEG:MA) is decreased in a dose-dependent manner when exposed to the platelet glycoprotein receptor antagonist c7E3 Fab (REOPRO[trade mark sign]); 2) alterations in fibrinogen concentration significantly influences the TEG:MA.

Methods: Following IRB approval and informed consent, whole blood (WB), platelet-rich and platelet poor plasma (PPP) samples from 5 healthy volunteers were used to measure the effects of c7E3 Fab (0-10 [micro sign]g/mL) on the TEG (Haemoscope Corp., Skokie, IL), platelet contractile force (PCF)(Hemodyne Corp., Richmond, VA) and aggregometry (ADP). mTEG:MA was calculated by subtracting MA from PPP from the WB MA. The TEG:MA of purified fibrinogen (50-400mg/dL; Sigma Chem.) was also performed in duplicate. ANOVA and linear regression was used to analyze the effects of c7E3 Fab and fibrinogen on the TEG:MA. P-values <or=to 0.01 were significant.

Results: Figure 1 demonstrates the dose-dependent effects of c7E3 Fab. Figure 2 illustrates the influence of fibrinogen on the MAppp. Linear regression analysis of purified fibrinogen is inset in Figure 2. Figure 3 lists the remaining coagulation data for the volunteers.

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Discussion: This is the first reported use of modified TEG demonstrating the dose-dependent effects of c7E3 Fab on platelet function in healthy volunteers. The influence of fibrinogen on the TEG:MA can be substantial. This is illustrated by the generation of a "normal" TEG:MA using purified fibrinogen (Figure 2). Although modified TEG was not as responsive to clinical doses of c7E3 Fab (4[micro sign]/mL) as platelet contractile force or aggregometry (Figure 1), it is the only commercially available technology at this time.

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REFERENCES

1. Anesthesiology 1992;77:38
2. Anesth Analg 1997;84:31
3. Anesth Analg 1995;80:SCA141
© 1998 International Anesthesia Research Society