Is primary haemostasis controlled by a ‘platelet delay time’? Formulation of a new hypothesis

Abstract

A simple physical model is able to adequately describe platelet thrombus formation during primary haemostasis ex vivo, under the assumption of a ‘platelet delay time’ (P_del), which is defined as the difference between the moment of platelet adhesion (to collagen or to another adherent platelet) and the time when the newly adherent platelet allows another platelet to adhere. P_del was estimated with an ex vivo model of primary haemostasis (modified PFA-100™, Dade Behring, Marburg). ADP and epinephrine test cartridges were perfused with human anticoagulated blood of control persons using a pressure/flow clamp technique (Kretschmer V, et al. Platelets 2001; 12: 462–9). Platelets gradually occluded the aperture in the test system. Pressure ( p) across and flow (Q) through the aperture were measured versus time. The change of the aperture radius versus time (dr/dt) was calculated from p and Q using the Law of Hagen–Poiseuille. The surprising result was a constant decay of dr/dt (R_squ ˜0.996), in spite of a 5-fold increase in the shear- and transport-rates of platelets. This can be explained by postulating the existence of a P_del, which was estimated as 2.89 s for collagen/ADP and 4.62 s in collagen/epinephrine test cartridges. This new hypothesis explains for the first time the relative independence of in vivo and ex vivo bleeding time on blood platelet concentrations, a well known observation at platelet counts higher than 40 000/μl. If the described physical model is correct, platelet thrombus growth rate is strongly decreased as a consequence of P_del in extreme arterial flow conditions. A preliminary report of these experiments has been published (Kratzer MAA, Platelets 2002; 13: 344).