The role of platelets in blood coagulation--effects of platelet agonists and GPIIb/IIIa inhibitors studied by free oscillation rheometry.
We have studied the contribution of platelets to the coagulation of plasma and the effects of activation or inhibition of platelets on the coagulation process in unanticoagulated fresh whole blood (subsequently termed native blood). For this purpose, we have used a free oscillation rheometer (FOR), the ReoRox4, a new instrument that enables noninvasive viscoelastic measurements of clot formation in plasma and whole blood. Platelets appear essential for the initiation of coagulation if no activating surface is present. We prepared platelet-free plasma by quick centrifugation and filtration of native blood, which did not coagulate if stored in plastic containers at 37 degrees C but clotted if transferred to glass containers. Addition of platelet agonists, such as collagen or the thrombin receptor agonist peptide, SFLLRN, significantly accelerated the clotting of native blood and also changed the rheometer curve appearance, accelerating both onset and completion of clot formation (i.e. fibrin gel formation). Inhibition of platelet glycoprotein (GP) IIb/IIIa with the peptide-derived compound MK-852 or the antibody-derived abciximab (Reopro) prevented clot retraction and prolonged the clotting time with SFLLRN. In collagen-stimulated samples, MK-852 accelerated clotting but delayed completion of clotting while abciximab prolonged both clotting time and completion of clotting. To our knowledge, this is the first report showing that activation of platelets in native whole blood shortens the coagulation time ex vivo. It also describes a new instrument that enables studies of the viscoelastic properties of a forming whole blood clot.
Ramström
Sofia
S
Department of Biomedicine and Surgery, Division of Clinical Chemistry, University Hospital, SE-581 85 Linköping, Sweden. sofra@ifm.liu.se
Rånby
Mats
M
Lindahl
Tomas L
TL
D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000295:instrumentation; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D004867:Equipment Design; D018056:Hemorheology / Q000295:instrumentation; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000295:instrumentation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors
D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C082835:thrombin receptor peptide (42-47); D003094:Collagen