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

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(TM), 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 similar to 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/mul. 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).