The effect of ex vivo anticoagulants on whole blood platelet aggregation

Abstract

Pre- and intraoperative platelet function monitoring is increasingly recommended in order to detect risk factors for bleeding and to target coagulation management. The ideal anticoagulant for accurate platelet aggregometry remains controversial. The aim of this experimental trial was to compare platelet aggregability in whole blood stored in citrate, heparin and direct thrombin inhibitors. Whole blood was drawn from 11 healthy adult volunteers who had not taken any medication in the previous 14 days. Blood was stored in trisodium citrate, unfractionated heparin, melagatran, lepirudin and argatroban. Platelet aggregation was performed using the impedance aggregometer Multiplate (Dynabyte, Munich, Germany) with adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP), collagen, arachidonic acid and ristocetin as agonists. Samples were analysed immediately after blood sampling (baseline), as well as 30 and 120 min afterwards. At baseline there were no significant differences in aggregability between samples containing direct thrombin inhibitors and heparin. In contrast, aggregation in response to all agonists except for ristocetin was significantly impaired in citrated blood. During storage the response to arachidonic acid and collagen was maintained by direct thrombin inhibitors and heparin, whereas ADP-, TRAP- and ristocetin-induced aggregation varied considerably over time in all ex vivo anticoagulants tested. Pre-analytical procedures should be standardized because storage duration and anticoagulants significantly affect platelet aggregability in whole blood. For point-of-care monitoring with immediate analysis after blood withdrawal all tested direct thrombin inhibitors as well as unfractionated heparin can be used as anticoagulants whereas citrate is not recommended.

Sex differences of leukocyte–platelet interactions and on-treatment platelet reactivity in patients with atherosclerosis

“…Recently, Kalb et al compared platelet aggregability by MEA in whole blood stored in citrate, heparin and direct thrombin inhibitors [20]. They found no significant differences in aggregability between samples containing direct thrombin inhibitors and samples containing heparin, whereas aggregation by MEA was significantly impaired in citrate-anticoagulated blood.…”

First direct comparison of platelet reactivity and thrombolytic status between Japanese and Western volunteers: Possible relationship to the “Japanese paradox”

“…Citrate significantly interferes with platelets, distorting their reaction to physiological stimuli [36,37]. Further, the assessment of the response of platelets to common agonists (epinephrine, collagen and ADP) does not have direct relevance to the most important pathophysiological processes that take place in vivo and results show wide interindividual variability [38][39][40].…”

Precision and Reliability of 5 Platelet Function Tests in Healthy Volunteers and Donors on Daily Antiplatelet Agent Therapy

“…Interpreting changes in platelet function over several days, whether to titrate antiplatelet therapy during MCS or monitor therapy for other acutely ill patients, requires knowledge of assay precision over short periods of time. Because platelet activation during blood collection (a source of preanalytic variability) is a function of collection tube type (15,16 ); temperature and time of blood storage and processing (14 -16 ); amount of vacuum in collection tube (17 ); and other factors, it is not possible to independently measure analytic and biologic variability for tests of platelet function.…”