TY - JOUR
T1 - Shear-induced global thrombosis test of native blood: Pivotal role of ADP allows monitoring of P2Y12 antagonist therapy
AU - Saraf, S.
AU - Wellsted, D.
AU - Sharma, S.
AU - Gorog, D.A.
N1 - Original article can be found at: http://www.sciencedirect.com/science/journal/00493848 Copyright Elsevier Ireland Ltd. [Full text of this article is not available in the UHRA]
PY - 2009
Y1 - 2009
N2 - Background: It is claimed that in shear-induced platelet function tests, shear-stress is the sole agonist causing platelet activation and resultant thrombosis. However, the fact that red blood cells (RBC) are essential to achieve platelet aggregation in these tests supports recent evidence that ADP makes an important contribution to shear-induced platelet reaction. Aim: To establish the role of ADP in shear-induced thrombosis, and investigate whether a shear-induced thrombosis test can assess ADP-receptor (P2Y12) antagonist medication. Methods: Blood from healthy volunteers was tested using the Global Thrombosis Test (GTT), before and after clopidogrel. To investigate the importance of contact of blood with plastic, the reactive part of the tube was primed with saline. We also investigated the effect of priming the tube with water, to cause localised haemolysis and ADP release. Results: Saline-priming prolonged occlusion times (OT) by 25% (p < 0.01) confirming ADP release from platelets and RBC as a result of contact. Water-priming shortened OT, accelerating the thrombotic reaction (accelerated GTT; aGTT) (OT 379 vs. 177s, p < 0.01). Clopidogrel increased OT (379 vs. 477s, p < 0.01), preventing the shortening of aGTT-OT (177 vs. 362s, pre- and post-clopidogrel; p < 0.01). Conclusion: In addition to thrombin formation, ADP released from platelets and RBC in native blood subjected to high shear-stress makes an important contribution to the resultant thrombotic occlusion. The described aGTT sensitively detected the effect of clopidogrel and thus seems suitable for monitoring and individualizing ADP-receptor antagonist therapy. Parallel measurement of GTT and aGTT would allow assessment of both global thrombotic status and response to P2Y12 antagonist therapy.
AB - Background: It is claimed that in shear-induced platelet function tests, shear-stress is the sole agonist causing platelet activation and resultant thrombosis. However, the fact that red blood cells (RBC) are essential to achieve platelet aggregation in these tests supports recent evidence that ADP makes an important contribution to shear-induced platelet reaction. Aim: To establish the role of ADP in shear-induced thrombosis, and investigate whether a shear-induced thrombosis test can assess ADP-receptor (P2Y12) antagonist medication. Methods: Blood from healthy volunteers was tested using the Global Thrombosis Test (GTT), before and after clopidogrel. To investigate the importance of contact of blood with plastic, the reactive part of the tube was primed with saline. We also investigated the effect of priming the tube with water, to cause localised haemolysis and ADP release. Results: Saline-priming prolonged occlusion times (OT) by 25% (p < 0.01) confirming ADP release from platelets and RBC as a result of contact. Water-priming shortened OT, accelerating the thrombotic reaction (accelerated GTT; aGTT) (OT 379 vs. 177s, p < 0.01). Clopidogrel increased OT (379 vs. 477s, p < 0.01), preventing the shortening of aGTT-OT (177 vs. 362s, pre- and post-clopidogrel; p < 0.01). Conclusion: In addition to thrombin formation, ADP released from platelets and RBC in native blood subjected to high shear-stress makes an important contribution to the resultant thrombotic occlusion. The described aGTT sensitively detected the effect of clopidogrel and thus seems suitable for monitoring and individualizing ADP-receptor antagonist therapy. Parallel measurement of GTT and aGTT would allow assessment of both global thrombotic status and response to P2Y12 antagonist therapy.
KW - clopidogrel
U2 - 10.1016/j.thromres.2009.04.013
DO - 10.1016/j.thromres.2009.04.013
M3 - Article
SN - 0049-3848
VL - 124
SP - 447
EP - 451
JO - Thrombosis Research: Vascular Obstruction, Hemorrhage and Hemostasis
JF - Thrombosis Research: Vascular Obstruction, Hemorrhage and Hemostasis
IS - 4
ER -