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The effect of molecular weight on heparin binding to platelets
Author(s) -
Horne McDonald K.,
Chad Elizabeth S.
Publication year - 1990
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1990.tb02588.x
Subject(s) - chemistry , platelet , antithrombin , dissociation constant , heparin , low molecular weight heparin , molecular mass , electronegativity , dissociation (chemistry) , stereochemistry , biophysics , biochemistry , enzyme , immunology , receptor , organic chemistry , biology
Summary 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 [ 3 H]heparin in plasma using heparins of different molecular weights (M r ˜ 3000, ˜ 5000, ˜ 10 000, ˜ 15000). Binding affinity increased with increasing molecular weight, as expressed by decreasing apparent dissociation constants ( K dapp ˜ 1.3 μM for M r ˜ 3000, to K dapp ˜ 0.31 μM for M r ˜ 15000). After adjusting for the effect of antithrombin III in the plasma, true dissociation constants ( K d ) could be calculated and these showed the same trend with molecular weight ( K d ˜ 1.1 μM for Mr ˜ 3000 to K d ˜ 0.096 μM for M r ˜ 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