Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and
plasminogen activator from the vascular endothelium. An infusion of exogenous factor
VIII given to haemophiliacs causes an increase in platelet activation. This activation
does not occur after stimulating a rise in the patient's own factor VIII level caused
by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial
release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor
VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release,
as measured by its stable metabolite 6-oxo-PGFla, in vitro and in vivo. Rabbit aortic
rings were incubated with different concentrations of DDAVP using saline as control.
The supernatant was assayed for 6-oxo-PGFlct by radioimmunoassay. All concentrations
of DDAVP gave a significant release of 6-oxo-PGF1α. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients
there was a significant increase in circulating 6-oxo-PGF1α levels immediately after the infusion. The facial flushing observed as a side-effect
of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing
the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin
which inhibits PGI2 formation.
Key words
DDAVP - Prostacyclin - Platelet aggregation - Factor VIII
