The association of in vitro arachidonic acid responsiveness and plasma thromboxane levels with early platelet deposition on the luminal surface of small-diameter grafts

Abstract

The response of canine platelets to arachidonic acid (AA) stimulation was studied as a predictor of thrombotic potential. Fifty mongrel dogs underwent in vitro platelet aggregation studies with adenosine diphosphate (ADP), collagen, and AA used as inducing agents. Thirty-two dogs were selected on the basis of their response to AA stimulation. Platelet aggregation in response to AA stimulation occurred in 16 (responders) and 16 showed no aggregatory response (nonresponders). The animals were divided into four groups. Group I received no antiplatelet agents (control); group II received U-63,557A, a specific thromboxane synthetase inhibitor (TSI); group III received aspirin; and group IV received aspirin and TSI. Polytetrafluoroethylene grafts were implanted in the carotid and femoral arteries of the dogs in all four groups. Plasma thromboxane (TxB2) levels were drawn before drug treatment and 4 weeks after surgery. Platelet deposition on the luminal surface of the implanted grafts was studied in vivo with a technique that uses both 111In-labeled platelets and 99mTc-labeled red blood cells and was expressed as percentage of indium excess (%IE). Group I (control) dogs whose platelets aggregated in response to AA stimulation had significantly higher 24-hour platelet deposition (%IE) on the luminal surface of implanted grafts (p less than 0.02), lower 4-week graft patency (p less than 0.002), and higher plasma TxB2 levels (p less than 0.01) than those dogs whose platelets did not aggregate. In contrast to the results of AA stimulation, neither ADP nor collagen responsiveness was discriminatory for the thrombotic potential of canine arteries as measured by 24-hour platelet deposition (%IE), 4-week graft patency, or plasma TxB2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Whole Blood Platelet Aggregation in Humans and Animals: A Comparative Study

“…In our study, whole dog blood PA values with 10 M ADP showed a nearly normal distribution, not two subpopulations of "responders" and "nonresponders," contrary to the observations reported by other authors using PRP [34,35]. Interestingly, Freeman and his associates [36] showed that AA was a more sensitive agonist than ADP or collagen for an optical method using PRP because it made a more distinct separation of the dog population into "responders" and "nonresponders." Although the number of dogs tested was rather small in our present study (n ϭ 19), the AA-induced PA values again showed a nearly normal distribution, and no subgroups were noted.…”

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 4—Refining and monitoring antithrombotic therapies

“…Numerous LOE 3 studies support the PICO question and suggest that platelet inhibition detectable by aggregometry is associated with reduced risk of arterial thromboembolism; however, there is considerable variation in the agonists used for aggregometry in different studies . Freeman et al reported that arachidonic acid (AA)‐stimulated platelet aggregation is a better predictor of the antithrombotic effects of aspirin in a small‐diameter graft model than when ADP or collagen were used as agonists (LOE 3, Fair) . Similarly, other authors have reported that aspirin‐inhibited AA‐induced platelet aggregation is a more useful monitoring tool for documenting the antithrombotic effect of aspirin than ADP‐induced platelet aggregation (LOE 3, Fair), and collagen‐induced platelet aggregation (LOE 3, Good) .…”

“…No LOE 1 or 2 studies directly address the PICO question. Numerous LOE 3 studies support the PICO question and suggest that platelet inhibition detectable by aggregometry is associated with reduced risk of arterial thromboembolism; however, there is considerable variation in the agonists used for aggregometry in different studies . Freeman et al reported that arachidonic acid (AA)‐stimulated platelet aggregation is a better predictor of the antithrombotic effects of aspirin in a small‐diameter graft model than when ADP or collagen were used as agonists (LOE 3, Fair) .…”

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 3—Defining antithrombotic protocols

“…A total of 47 articles were considered relevant to the PICO question, including 20 studies suggesting that protocolized aspirin therapy is more effective, or safer than, no aspirin therapy, or other thromboprophylaxis protocols. Twenty‐five studies were considered neutral to the question .…”

“…The majority of the published literature regarding the administration of aspirin in dogs involves experimental (laboratory) studies (LOE 3) of arterial thrombosis, fewer studies evaluated venous thrombosis . Most were considered of fair quality given that controls were included . Only a few studies used randomized controls, and thus were considered good quality evidence .…”