Summary
This study reports on the biological activity and safety of high dose low molecular
weight (LMW) heparin therapy administered by two subcutaneous (s.C.) injections daily
for 8 days in healthy human volunteers. Group 1 received 2 × 30 aPTT units LMW heparin/kg
bodyweight, and group 2 received 2 × 50 aPTT units/kg per day.
In group 1, activated partial thromboplastin time (aPTT) and thrombin clotting time
(TCT) were uniformly prolonged by 3-5 sec 4 hrs after s.c. administration of heparin.
Heptest coagulation time values were prolonged consistently as well by 57 sec on day
1 to 68 sec on day 8. Factor Xa inhibition measured by the S 2222 chromogenic substrate
method continuously increased from 0.16 units/ml on day 1 to 0.28 units/ml on day
8.
In group 2 prolongation of a aPTT and TCT values increased from 6 sec on day 1 to
15 sec on day 8 and of Heptest time from 70 sec on day 1 to 110 sec on day 8. S 2222
method showed factor Xa inhibitory activity which increased from 0.5 units/ml on day
1 to 0.75 units/ml on day 8. The clinical tolerance of the treatment was good. No
changes in clinical chemistry parameters were detected, except for a reversible increase
of serum transaminases.
The coagulation studies demonstrate accumulation of LMW heparin when high doses are
given twice daily. The half life of LMW heparin of factor Xa inhibition increases
with increasing doses.
Heptest coagulation values were prolonged to 4-6 times the normal values during administration
of heparin. S 2222 chromogenic substrate values were in the same range as upon application
of high doses of unfractionated heparin. aPTT and thrombin clotting time values ranged
from 1.2 to 1.5 times the starting values.
Keywords
Heparin - Low molecular weight heparin - Factor Xa - Anticoagulation
