Role of Glycoprotein IIb:IIIa in the Adhesion of Platelets to Collagen Under Flow Conditions

To the Editor:

In their interesting report, Moroi et al1 studied the adhesion of platelets to a collagen-coated surface and they described, among others, the influence of anti-glycoprotein (GP) IIb:IIIa antibodies and RGD-containing peptides. Their observation was that these compounds inhibited the adhesion of platelets to collagen and their conclusion was that GPIIb:IIIa plays an important role in the adhesion of platelets with collagen types I and III. These observations are diametrically opposed to our experiments in which we have found that those compounds stimulate the adhesion to collagen.2 The increased platelet adhesion we found was due to an inhibition of the aggregate formation, platelets are not incorporated in the aggregates and an increased number of platelets is available for platelet adhesion. The reason for the discrepancy between our results and the results of Moroi et al is the used anticoagulant. We have used in our experiments blood anticoagulated with low-molecular-weight heparin (LMWH) whereas Moroi et al used citrated blood. The differences between both anticoagulants are striking, as shown in Table 1.

The influence of the anticoagulant on platelet-collagen interaction can be easily explained. Platelet adhesion to collagen is sensitive to the presence of Mg²⁺-ions.3 The adhesive properties of VLA-2 (GPIa:IIa), the major collagen receptor on the platelet membrane, are dependent on Mg²⁺. In the presence of physiologic concentrations of Mg²⁺, platelet adhesion to collagen depends on VLA-2, GPIb-von Willebrand interaction, and probably GPVI, and there is no support by other platelet membrane GPs. In the absence of cations, when VLA-2 loses its activity, other receptors like GPIIb:IIIa and GPIV may become involved in the adhesion of platelets to collagen.

In conclusion, under physiological cation concentrations platelet adhesion to collagen type I and III is not dependent on GPIIb:IIIa. However, there may be an alternative adhesive mechanism based among others on GPIIb:IIIa which functions when no Mg²⁺ is present.