Summary
The non-specific binding of anticoagulantly-active heparin to plasma proteins may
influence its anticoagulant effect. We used low affinity heparin (LAH) essentially
devoid of anti-factor Xa activity to investigate the extent and possible mechanism
of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing
a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably
because it displaces anticoagulantly-active heparin from plasma proteins. Although
dextran sulfates of varying molecular weights also increased the anti-factor Xa activity,
less sulfated heparin-like polysaccharides had no effect. These findings suggest that
the ability to displace active heparin from plasma protein binding sites is related
to charge and may be independent of molecular size. In contrast to its effect in plasma
containing unfractionated heparin, there was little augmentation in anti-factor Xa
activity when LAH was added to plasma containing low molecular weight heparin (LMWH),
indicating that LMWH binds less to plasma proteins than unfractionated heparin. This
concept is supported by studies comparing the anticoagulant activity of unfractionated
heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor
Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified
system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and
buffer, respectively. These findings may be clinically relevant because the recovered
anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients
with suspected venous thrombosis than in plasma from healthy volunteers. The reduced
heparin recovery in patient plasma reflects increased heparin binding to plasma proteins
because the addition of LAH augmented the anti-factor Xa activity. In contrast to
unfractionated heparin, there was complete recovery of LMWH added to patient plasma
and little increase of anti-factor Xa activity after the addition of LAH. These findings
may explain why LMWH gives a more predictable dose response than unfractionated heparin.
