Inhibition of ticlopidine of platelet adhesion to human venous subendothelium in patients with diabetes.
To elucidate the bleeding tendency that follows the administration of ticlopidine, we investigated the skin bleeding time and some ex vivo functions of platelets from nine patients with insulin-dependent diabetes before and 2 weeks after daily doses of 500 mg ticlopidine. Ticlopidine significantly prolonged bleeding time and reduced platelet reactivity to fixed, relatively high concentrations of aggregating agents, without interfering with thromboxane B2 formation. We used a rotating probe device at a relatively low shear rate (570 sec-1) to measure platelet adhesion to human subendothelium. This system was able to detect an impairment of platelet adhesion dependent on glycoprotein (GP) Ib defect (Bernard Soulier syndrome) or on low platelet von Willebrand factor content, but was insensitive to platelet GPIIb-IIIa defect (Glanzmann's thrombasthenia). In our patients, platelet adhesion was consistently reduced after the administration of ticlopidine. We conclude that ticlopidine is an inhibitor of platelet function that modulates the interaction between platelets. The drug also appears to interfere with mechanisms that modulate platelet-subendothelium interaction at relatively low shear rates. This double action could be relevant in the prevention of vasculopathy in patients with diabetes.
Orlando
E
E
Department of Hematology, Ospedali Riuniti di Bergamo, Italy.
Cortelazzo
S
S
Nosari
I
I
Lepore
G
G
Pagani
G
G
de Gaetano
G
G
Barbui
T
T
D000328:Adult; D001760:Bleeding Time; D003920:Diabetes Mellitus / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D013929:Thromboxane B2 / Q000096:biosynthesis; D013988:Ticlopidine / Q000494:pharmacology*
D005353:Fibronectins; D013929:Thromboxane B2; D013988:Ticlopidine