The pharmacological inhibition of platelets has always been regarded as a double-edged sword: the challenge of balancing the antithrombotic effect against the
bleeding risk. Potent
antiplatelet agents and novel oral
anticoagulants, sometimes in combination, are increasingly used in the treatment of
cardiovascular disease and for thromboprophylaxis in
atrial fibrillation. Although such treatment has reduced the risk of thrombotic events, the potential for major
bleeding has increased, and a technique to identify those at increased
bleeding risk is greatly needed. Platelet function tests (PFTs), most frequently VerifyNow and also the
vasodilator-stimulated phosphoprotein -phosphorylation assay, have been used to identify low on-treatment platelet reactivity, to identify individuals who may be at increased
bleeding risk. Such results predict nuisance
bleeding, but many individuals have low on-treatment platelet reactivity and yet do not exhibit major or even minor
bleeding. Although PFTs may be useful in assessing populations, they do not allow identification of individual patients at risk of
bleeding on either antiplatelet or novel oral
anticoagulant therapy, nor do they allow the tailoring of such
therapy to optimize the risk:benefit ratio.
Thrombin plays a cardinal role in both arterial
thrombus formation and hemostasis, yet most PFTs fail to assess the contribution of
thrombin, because they employ anticoagulated blood. Techniques such as the calibrated automated thrombogram and the point-of-care global
thrombosis test, performed on native blood, which measure endogenous
thrombin potential, seem to show the most promise for profiling
bleeding risk, as tests that most physiologically assess the effects of medications on
thrombin.