Effects of SolCD39, a novel inhibitor of Platelet Aggregation, on Platelet Deposition and Aggregation after PTCA in a Porcine Model

This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP. A recombinant soluble form of CD39 (solCD39) giv...

Full description

Saved in:
Bibliographic Details
Published in:Journal of thrombosis and thrombolysis 2005-04, Vol.19 (2), p.115-122
Main Authors: Buergler, John M, Maliszewski, Charles R, Broekman, M Johan, Kaluza, Grzegorz L, Schulz, Daryl G, Marcus, Aaron J, Raizner, Albert E, Kleiman, Neal S, Ali, Nadir M
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - pharmacology
Angioplasty, Balloon, Coronary - adverse effects
Animals
Antigens, CD - pharmacology
Antigens, CD - therapeutic use
Apyrase - pharmacokinetics
Apyrase - pharmacology
Apyrase - therapeutic use
Blood Coagulation Tests
Collagen - pharmacology
Drug Evaluation, Preclinical
Half-Life
Humans
Models, Animal
Platelet Adhesiveness - drug effects
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - pharmacology
Receptors, Thrombin
Solubility
Swine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP. A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5--7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by>90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7+/-1.4 versus 11.7+/- 3.4) and fibrin (3.5+/- 0.4 versus 4.2+/- 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAP(SFLLRN)) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel. SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study. ABBREVIATED ABSTRACT: E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5-7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.
ISSN:0929-5305
1573-742X
DOI:10.1007/s11239-005-1381-y