How I use laboratory monitoring of antiplatelet therapy

Abstract

Antiplatelet therapy is of proven benefit in coronary artery disease and a number of other clinical settings. This article reviews platelet function, molecular targets of antiplatelet agents, and clinical indications for antiplatelet therapy before focusing on a frequent question to hematologists about the 2 most commonly used antiplatelet therapies: Could the patient be aspirin “resistant” or clopidogrel “resistant”? If so, should results of a platelet function test be used to guide the dose or type of antiplatelet therapy? Whether such guided therapy is of clinical benefit to patients has been a source of controversy. The present article reviews this subject in the context of 2 prototypical clinical cases. Available evidence does not support the use of laboratory tests to guide the dose of aspirin or clopidogrel in patients with so-called aspirin or clopidogrel “resistance.”

Cyclic nucleotide‐dependent inhibitory signaling interweaves with activating pathways to determine platelet responses

“…The clinical relevance of crosstalk between activating and cyclic nucleotide‐dependent inhibitory pathways is further highlighted by the success of drugs targeting either the Gi‐coupled P2Y12 receptor or PDEs 3A and 5A,12, 104, 105 which prevent the blockade of cyclic nucleotide production or degradation, respectively 106. Stimulators of the cGMP pathway are commonly used to treat vascular disease due to their ability to lower vascular tone by acting on smooth muscle cells, however, simultaneous platelet inhibition might contribute to their beneficial effects.…”

“…On the other hand, platelet activation requires active blockage of endothelium‐dependent inhibitory pathways,8, 9, 10, 11 including ADP‐mediated inhibition of cAMP production via P2Y12 and thrombin‐mediated cAMP degradation via PDE type 3A. Interestingly, both P2Y12 and PDE3A are targets of multiple clinically used drugs which reduce thrombosis 12. Once initiated, cyclic nucleotides are also able to reverse platelet aggregation leading to complete disaggregation of already formed platelet aggregates 13, 14, 15, 16.…”

Point of care testing in general haematology

“…Thromboelastography is not a substitute for conventional laboratory testing, such as INR, but it offers additional information and may guide blood transfusion at the POC (Michelson & Bhatt, ). The use of viscoelastic assays during major haemorrhage in obstetrics, liver disease, cardiac surgery and trauma is covered in detail in the recent BSH guideline; ‘ The use of viscoelastic haemostatic assays in the management of major bleeding ’ (Curry et al , ).…”

“…The increasing use of aspirin and oral P2Y inhibitors in the prevention and management of arterial thrombosis, and whether or not a patient is aspirin "resistant" or clopidogrel "resistant", has promoted extensive research into development of POC devices for measurement of platelet inhibition by said anti‐platelet medications (Dionizovik‐Dimanovski et al , ). However, many studies have failed to show a true benefit, therefore the clinical utility of POC systems in this area is yet to confirmed (Ebner et al , ; Michelson & Bhatt, ).…”

Evaluation of AggreGuide A‐100 for monitoring of antiplatelet therapy

“…1,2 Other factors that may contribute to the variable anti-platelet effect of clopidogrel are differences in absorption (diet, polymorphisms in the ABCB1 transporter molecule), smoking, drug interactions, inherent variations in platelet function before clopidogrel administration and other patient-related factors (obesity, diabetes mellitus, renal dysfunction, inflammation, age…). 3 Similarly, an unpredictable response of platelets to ASA has been reported and has been related to poor clinical outcome, although described prevalence of aspirin resistance varies from <1% to 57% according to different publications. [4][5][6] A recent review of Michelson et al 3 focused on the clinical benefit for monitoring of antiplatelet therapy and found that available evidence is not sufficiently strong to support routine use of laboratory tests for monitoring platelet function in patients with so-called aspirin or clopidogrel resistance.…”