Summary
Hirudin is a potent thrombin inhibitor derived from the leech Hirudo medicinalis salivary gland which has considerable potential for therapeutic use in thrombotic
disease. The major risk attendant its use is hemorrhage. This study investigates the
hypothesis that the prohemostatic effects of DDAVP infusion can curtail the hemorrhagic
effect induced by ongoing hirudin administration.
In a randomized and blinded manner, rabbits were exposed to a 15-min intravenous infusion
of DDAVP or saline midway through a continuous two-h intravenous infusion of hirudin.
Bleeding time was monitored by full thickness ear punctures performed before, during
and after hirudin exposure.
Hirudin induced a significant hemorrhagic state, manifest as a 7-10-fold prolongation
of the primary bleeding time. DDAVP reduced the mean duration of primary bleeding
from 10.8 min to 5.9 min (p = 0.001) as well as the number of sites which bled for
longer than 6 or 20 min (46% vs 27%, p = 0.002; and 18% vs 5%, p = 0.002, respectively).
Although there was no difference in the incidence of spontaneous rebleeding from these
sites (44 vs 36%, p = 0.21), rebleeding did not persist as long in animals that received
DDAVP (8 vs 16 min, p = 0.005), and fewer sites rebled for longer than 20 min (8 vs
27%, p = 0.027). Results were essentially the same for two different commercial recombinant
hirudin preparations.
DDAVP appears to attenuate the bleeding caused by continuous hirudin infusion in rabbits
and establishes a foundation for clinical assessment in patients.
