THE EFFECT OF MOLECULAR-WEIGHT ON HEPARIN BINDING TO PLATELETS

Low molecular weight heparin is reported to be less reactive with platelets than larger heparins. We probed the molecular basis for this pattern of reactivity by characterizing the saturable platelet binding of [3H]heparin in plasma using heparins of different molecular weights (Mr˜ 3000, ˜ 5000, ˜ 10 000, ˜ 15000). Binding affinity increased with increasing molecular weight, as expressed by decreasing apparent dissociation constants (Kdapp˜ 1.3 μM for Mr˜ 3000, to Kdapp˜ 0.31 μM for Mr˜ 15000). After adjusting for the effect of antithrombin III in the plasma, true dissociation constants (Kd) could be calculated and these showed the same trend with molecular weight (Kd˜ 1.1 μM for Mr ˜ 3000 to Kd˜ 0.096 μM for Mr˜ 15 000). Platelet binding capacity for the different heparin fractions also increased with molecular weight, although this correlation appeared to lessen with the largest species. Heparin antithrombin III affinity was shown not to affect heparin binding to platelets. We propose a model in which heparin binding to platelets is mediated by charge interaction. Larger molecules with more charge bind with greater affinity and to sites with a broader range of electronegativity than do smaller, less Copyright © 1990, Wiley Blackwell. All rights reserved