Blood, 1 April 2002, Vol. 99, No. 7, pp. 2434-2441
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
A hereditary bleeding disorder of dogs caused by a lack of
platelet procoagulant activity
Marjory B. Brooks,
James L. Catalfamo,
H. Alex Brown,
Pavlina Ivanova, and
Jamie Lovaglio
From the Department of Population Medicine and
Diagnostic Sciences and the Department of Molecular Medicine, College
of Veterinary Medicine, Cornell University, Ithaca, NY.
We have discovered a novel canine hereditary bleeding disorder with
the characteristic features of Scott syndrome, a rare defect of
platelet procoagulant activity. Affected dogs were from a single,
inbred colony and experienced clinical signs of epistaxis, hyphema,
intramuscular hematoma, and prolonged bleeding with cutaneous bruising
after surgery. The hemostatic abnormalities identified were restricted
to tests of platelet procoagulant activity, whereas platelet count,
platelet morphology under light microscopy, bleeding time, clot
retraction, and platelet aggregation and secretion in response to
thrombin, collagen, and adenosine diphosphate stimulation were all
within normal limits. Washed platelets from the affected dogs
demonstrated approximately twice normal clotting times in a platelet
factor 3 availability assay and, in a prothrombinase assay, generated
only background levels of thrombin in response to calcium ionophore,
thrombin, or combined thrombin plus collagen stimulation. While
platelet phospholipid content was normal, flow cytometric analyses
revealed diminished phosphatidylserine exposure and a failure of
microvesiculation in response to calcium ionophore, thrombin, and
collagen stimulation. Pedigree studies indicate a likely homozygous
recessive inheritance pattern of the defect. These findings confirm the
importance of platelet procoagulant activity for in vivo hemostasis and
provide a large animal model for studying agonist-induced signal
transduction, calcium mobilization, and effector pathways involved in
the late platelet response of transmembrane phospholipid movement and
membrane vesiculation.
