Both chemical and physical effects of red cells are known to play a role in the adenosine diphosphate (ADP)-induced aggregation of human platelets in sheared blood. Using a previously described double infusion technique (Bell et al., 1989a), we studied the effect of increasing hematocrit from 10 to 60% on the rate and extent of platelet aggregation with 0.2 microM ADP in citrated whole blood undergoing tube flow. Blood and agonist were rapidly mixed in a small chamber and the suspensions flowed through lengths of 1.19 mm-diameter polyethylene tubing at mean transit times from 0.2 to 42.8 s at a mean tube shear rate = 335 s-1. Effluent was collected into 0.5% glutaraldehyde, the red cells removed by centrifugation through Percoll, and all single platelets and aggregates in the volume range 1-10(5) microns3 counted and sized using an aperture impedance counter. Both the initial rate (over the first 8.6 s) and the extent of aggregation with time increased with increasing mean hematocrit up to 35.8%, being significantly greater than in citrated plasma (cPRP). However, at 61.5% hematocrit, the extent of aggregation decreased markedly to a level close to that in cPRP. We also studied the effect of washed red cells at 39% hematocrit on the aggregation of washed platelets in Tyrodes-albumin fibrinogen-free suspensions. It had previously been shown that, at > or = 335 s-1, washed platelets in platelet-rich Tyrodes (PRT) aggregated with 0.7 microM ADP. We found that red cells markedly increased the extent of aggregation from that in PRT, and promoted the formation of large aggregates, absent in PRT. Spontaneous aggregation in whole blood or washed cell suspensions in the absence of added ADP at = 42.8 s was < 10% of that in the presence of ADP. The results indicate that a physical effect of red cells, likely manifested as an increase in the efficiency of aggregate formation (Goldsmith et al., 1995), plays an important role at low and normal hematocrits; however, at high hematocrits, particle crowding impedes the formation of aggregates.
