Monitoring platelet glycoprotein IIb/IIIa-fibrin interaction with tissue factor-activated thromboelastography.
Computerized thromboelastography (TEG) was used to study platelet glycoprotein IIb/IIIa function, characterize the consequences of the interaction between polymerizing fibrin and activated platelets, and establish a quantitative assay of platelet function. The ability of platelets to augment the shear elastic modulus of blood clots was measured by TEG under conditions of maximal platelet activation during ex vivo clot formation accelerated by recombinant human tissue factor (TF). Under these conditions, platelets significantly enhance clot strength eightfold (relative to platelet-free fibrin clots). This effect, inhibited by cytochalasin D and c7E3 Fab, appears to be dependent on the transmission of platelet contractile force to fibrin, through glycoprotein IIb/IIIa receptors. The c7E3 Fab dose response of TF-TEG clot strength is identical to results with platelet aggregation induced by the thrombin receptor agonist peptide (50% inhibitory concentration (IC50 = 3.6 microg/ml); adenosine diphosphate-induced aggregation is easier to inhibit (IC50 = 1.2 microg/ml). The results obtained with this system are reproducible (coefficient of variation for clot strength 4%; intraclass correlation coefficient 0.96). As a clinical assay, TF-triggered computerized TEG is easy to perform at the bedside, provides on-line results within 30 minutes, and may offer advantages over conventional measures of platelet function.
Khurana
S
S
Division of Cardiology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Mattson
J C
JC
Westley
S
S
O'Neill
W W
WW
Timmis
G C
GC
Safian
R D
RD
D000077284:Abciximab; D000199:Actins / Q000037:antagonists & inhibitors; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D009391:Nephelometry and Turbidimetry / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000819:agonists; D011994:Recombinant Proteins / Q000494:pharmacology; D013916:Thrombelastography / Q000379:methods; D013925:Thromboplastin / Q000235:genetics / Q000494:pharmacology*
D000199:Actins; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; C082835:thrombin receptor peptide (42-47); D015638:Cytochalasin D; D005337:Fibrin; D013925:Thromboplastin; D000077284:Abciximab