Summary
A template bleeding time study in the rat was undertaken to see if it is possible
to correlate bleeding times with the molecular weight, anticoagulant activity or chemical
composition of heparin or heparin-derived compounds. Heparin from porcine intestinal
rnucosa (PM-heparin) and from bovine lung (BL-heparin) as well as heparin fragments
from these sources were compared. Heparin fragments of low anticoagulant activity
were prepared by affinity chromatography on immobilized antithrombin as well as by
chemical modification. A heparin fragment of high affinity for antithrombin (HA-fragment)
caused a marked and dose-dependent increase in bleeding time while the corresponding
heparin fragment with low affinity for antithrombin (LA-frugment) had a marginal and
non-dose dependent effect on the bleeding time. Similar results were also obtained
with PM-heparin with high and low affinity for antithrombin. A high anti-FXa activity
was not always correlated with a marked bleeding tendency. Provided that a fragment
was devoid of activated partial thromboplastin time (APTT) activity, it was not possible
to provoke a bleeding time of 20 min or longer, although the compound was administered
at a dose of 1,088 U/kg (anti-FXa activity). On the other hand, & Nacetylated chemically
oversulphated heparin fragment, with a very low anti-FXa activity (1 U/mg) and with
an APTT activity of 34UlmtB, caused a bleeding time of 20 min or longer in 70% of
the animals after injection of the same number of Aprr units, 1,088 U/kg. These data
indicate that the APTT activity is a better and more sensitive indicator of the bleeding
than is the anti-FXa activity.
