Summary
To gain insight into the contribution of platelet-dependent thrombin formation in
haemostasis and thrombosis, we investigated under flow conditions the haemostatic
functions of platelets from a patient with Scott syndrome. Scott platelets are characterised
by a diminished platelet-dependent thrombin generation. Thrombin generation was determined
by calibrated automated thrombography and flow-based experiments were performed to
reveal collagen-mediated platelet activation and fibrin deposition. Our studies indicate
that adherent Scott platelets do not differ from control platelets in the formation
of stable platelet aggregates under static and flow conditions. While for adherent
control platelets a shape change, e.g. balloon formation, and externalisation of phosphatidylserine
(PS) is associated with an increase in intracellular calcium concentration, this is
not the case for Scott platelets. The calcium-induced morphological changes in control
platelets are accompanied with a diminished recruitment of free flowing platelets.
Scott platelets, not showing a calcium-induced shape change, also lost the ability
to recruit free flowing platelets. These findings rebut the hypothesis that the mild
bleeding tendency of Scott syndrome patients is due to a preserved adhesive activity
of patient’s platelets. Perfusion of tissue factor (TF)-activated control blood over
immobilised collagen results in the formation of fibrin fibers that radiate from platelet
aggregates. Although platelet aggregates were also observed after perfusion with TF-activated
Scott blood, fibrin deposition was not observed. In conclusion, our findings indicate
that platelet adhesion and spreading on a collagen matrix in the absence of fibrin
formation is sufficient to sustain haemostasis under non-traumatic conditions.
Keywords
Haemostasis - platelet physiology - thrombin - fibrinogen / fibrin - Scott syndrome
