Role of ADP in platelet aggregation at high shear: studies in a patient with congenital defect of platelet responses to ADP.
The in vitro measurement of platelet aggregation (PA) at the high shear levels that can be found in the microcirculation may provide useful informations on primary haemostasis, which is usually explored in vivo with the skin bleeding time (BT). PA at high shear requires von Willebrand factor (vWf) and the platelet glycoprotein (GP) complexes Ib/IX/V and IIb/IIIa; controversial results have been reported on its requirement of released adenosine diphosphate (ADP). Due to its dependence on vWf, PA at high shear may be affected by the vasopressin analogue DDAVP, which increases the plasma vWf levels and shortens the prolonged BT of patients with congenital or acquired defects of platelet function. We studied PA at high shear, BT and plasma vWf levels in a patient with congenital impairment of platelet responses to ADP before and after the i.v. infusion of 0.3 micrograms/kg DDAVP. Two methods to study PA at high shear were used: shear-induced PA (SIPA) and the filter aggregation test. With both methods, PA at high shear of the patient was impaired. The infusion of DDAVP increased plasma vWf levels, shortened the prolonged BT and potentiated PA at high shear of the patient. In conclusion, PA at high shear is impaired in a patient with congenital defect of platelet responses to ADP and prolonged BT and is potentiated by DDAVP. Our results suggest that released ADP plays an important role in PA at high shear and that potentiation of PA at high shear by DDAVP may be one mechanism by which the drug shortens the prolonged BT of patients with congenital or acquired defects of platelet function.
Cattaneo
M
M
A. Bianchi Bonomi Haemophilia and Thrombosis Centre, Institute of Internal Medicine, IRCCS Maggiore Hospital, Milano, Italy.
Zighetti
M L
ML
Lombardi
R
R
Mannucci
P M
PM
D000244:Adenosine Diphosphate / Q000502:physiology*; D001760:Bleeding Time; D001791:Blood Platelet Disorders / Q000097:blood / Q000151:congenital*; D001792:Blood Platelets / Q000502:physiology; D002478:Cells, Cultured; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000032:analysis
D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D003894:Deamino Arginine Vasopressin