Plasma fibrinogen inhibits platelet adhesion in flowing blood to immobilized fibrinogen

The influence of variations in plasma fibrinogen concentration on platelet adhesion to immobilized fibrinogen was investigated in a parallel-plate perfusion chamber. At a shear rate of 1600 s(-1) platelet adhesion decreased when increasing concentrations of purified fibrinogen were added to the plasma (IC50=1.5+/-0.2 g/L fibrinogen, n=24). Washed platelets reconstituted in a human albumin solution with red blood cells were more sensitive for soluble fibrinogen (IC50=0.4+/-0.1 g/L, n=5, P<.05). When platelet activation during circulation of the blood was minimized by using a single-passage perfusion system, an IC50 of 2.0+/-0.2 g/L was found (n=9). To exclude the possibility that the inhibition of fibrinogen was caused by irreversible changes in the fibrinogen molecule during the purification procedure, normal plasma was mixed in different ratios with plasma from a patient with congenital afibrinogenemia. Under these conditions, the plasma fibrinogen IC50 was 1.5+/-1.1 g/L. Absence of endogenous fibrinogen in the platelets of the patient resulted in an IC50 of 1.2+/-0.5 g/L for plasma fibrinogen. These results demonstrate that increased plasma fibrinogen concentrations inhibit platelet adhesion to fibrinogen under flow.