L.G.
Melton, C.M. Thompson, D.A. Gabriel
Abstract
Hemorrhage associated with uremia remains
a significant clinical problem.
Although guanidinosuccinic acid has
been implicated in the platelet dysfunction,
other factors such as the hematocrit
and platelet count are also important.
Current therapeutic intervention includes
transfusion of red blood cells and platelets,
which may enhance the rheophoretic effect
and increase the platelet number at
the vessel surface.
Alternatively, fresh frozen plasma,
cryoprecipitate and DDAVP are sometimes
infused to improve platelet adhesion.
These therapies have disadvantages of
volume expansion, allo-immunization,
and the risk of viral exposure.
In this pilot study, we have examined
the efficacy of rhFVIIa on improving
hemostasis in uremic patients as evaluated
by a flow device (Clot Signature Analyzer).
rhFVIIa may be effective in improving
platelet activation through thrombin
generation since rhFVIIa has the advantage
of activating both zymogens FIX and
FX. The CSA flow device can assess the
effects of rhFVIIa on functional hemostasis
with three quantitative parameters,
Platelet Hemostasis Time (PHT), Clotting
(CT), and Collagen-Induced Thrombus
Formation (CITF).
These parameters are determined using
unanticoagulated whole blood under a
defined shear field with minimal manipulation
of blood.
Unanticoagulated whole blood from four
dialysis patients was doped with increasing
concentrations of rhFVIIa (0, 75, 150
and 300 nM) and then immediately examined
on the flow device.
As expected the baseline parameters
(PHT, CT and CITF) were prolonged compared
to normal blood donors.
The concentration effect of rhFVIIa
on uremic blood (oDonor 1, ¡ Donor 2,
o Donor 3 and n Donor 4) is shown below.
The addition of 150 nM rhFVIIa to uremic
blood corrects all three parameters
to normal values, except for Donor 4
who had a more severe coagulopathy that
required higher concentrations of rhFVIIa
for correction.
These preliminary data show a potential
benefit of rhFVIIa infusion in the treatment
of hemorrhage in patients.
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