Summary
The bolus intravenous infusion of factor Xa in combination with phosphatidylcholine/phosphatidylserine
(PCPS) vesicles, at a dose of 2.6 × 10-11 moles and 4.0 × 10-8 moles/kg body weight respectively, has previously been shown to correct the bleeding
diathesis of haemophilic (factor VIII deficient) dogs (Br J Haematol 1988; 69: 491-7).
The cuticle bleeding time (CBT) was used as the test to evaluate objectively this
response. Transmission electron microscopy was performed to document the evolution
of haemostatic plugs forming in the vascular bed of the injured cuticles of both normal
and factor VIII deficient dogs with and without treatment with factor Xa/PCPS. The
dosage previously shown to normalize the CBT in haemophilic and significantly shorten
it in normal animals was used. Subjective and objective observations, using morphometric
techniques, were made over a period of 25 min following injury induction. The administration
of factor Xa/PCPS was associated with complete and sustained normalization of haemostatic
plug development in the haemophiliacs including platelet recruitment, activation and
compaction and subsequently fibrinous transformation. In the case of the normals,
platelet activation, etc., was exaggerated and fibrinous transformation appeared to
be accelerated. The haemostatic plugs forming in the treated haemophiliacs were indistinguishable
from those forming in the normals and significantly different, with regard to all
parameters measured, from the morphological appearances noted in the untreated haemophiliacs.
These data suggest that the correction of the haemostatic defect previously observed
results from the normalization of haemostatic plug formation and that this is sustained
despite the promotion of systemic fibrinolysis that is also known to occur.
