Summary
High and low molecular weight heparin fractions obtained by gel filtration chromatography
of sodium mucosal heparin were injected subcutaneously into six healthy volunteers
and compared with the unfractionated substance in a cross-over trial. Equal doses
of 5,000 U were administered twice daily over a period of three days and heparin activity
was repeatedly controlled before and 2, 4, 8 hrs after injection by means of the APTT,
the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo
effect of subcutaneously administered fractionated heparin on platelet function was
examined on three of the volunteers. The results show that s.c. injections of the
low molecular weight fraction induced markedly higher anti-Xa activity than injections
of the other preparations. At the same time, APTT results did not significantly differ.
Unfractionated heparin and the high molecular weight fraction enhanced ADP-induced
platelet aggregation and collagen-mediated MDA production, while the low molecular
weight fraction hardly affected these assays, but potently inhibited thrombin-induced
MDA production. All heparin preparations stimulated the release of platelet Factor
4 in plasma. During the three-day treatment periods, no side-effects and no significant
changes in the response to heparin injections were detected.
Keywords
Heparin fractionation - Anti-Xa activity - Platelet function - Thrombosis prophylaxis
