What does low Adenosine Diphosphate (ADP) on platelet mapping indicate in a patient's platelet function?

Low ADP on Platelet Mapping: Clinical Interpretation

Low ADP inhibition on platelet mapping indicates either inadequate antiplatelet therapy (if the patient is on a P2Y12 inhibitor like clopidogrel) or trauma-induced platelet dysfunction independent of medication use, and critically, ADP inhibition performs poorly for detecting antiplatelet agent use in trauma patients. 1

Understanding ADP Measurement on Platelet Mapping

What the Test Measures

• Platelet mapping using thromboelastography (TEG-PM) measures the percentage inhibition of the platelet P2Y12 receptor pathway, which is the specific target of ADP and medications like clopidogrel, prasugrel, and ticagrelor 1
• The test uses ADP as an agonist to stimulate platelet aggregation, and the degree of inhibition reflects how well the P2Y12 receptor pathway is blocked 1
• Low ADP inhibition means platelets are responding normally to ADP stimulation, suggesting the P2Y12 pathway is functional and not adequately blocked 1

Clinical Context Matters Critically

In patients on P2Y12 inhibitors (clopidogrel/prasugrel/ticagrelor):

• Low ADP inhibition suggests inadequate platelet inhibition or "clopidogrel resistance", with various cut-off values proposed: >60% aggregation with 20 µM ADP, >50% with 5 µM ADP, or >70% with 10 µM ADP 1
• This finding has been associated with 2-4 fold higher risk of myocardial infarction, stroke, or death in patients with cardiovascular disease 1
• However, the clinical utility of routine testing remains controversial because cut-off values are not standardized and vary widely between studies 2

In trauma patients (especially traumatic brain injury):

• Low ADP inhibition (or paradoxically, increased ADP inhibition) can occur independent of antiplatelet medication use, representing trauma-induced platelet dysfunction 1
• ADP inhibition on TEG-PM performed poorly (AUROC 0.58) for detecting pre-injury antiplatelet agent use in a prospective study of 824 trauma patients, meaning it cannot reliably distinguish medication effect from trauma-induced dysfunction 1
• The European trauma guidelines (2023) recommend against routine use of POC platelet function devices including TEG-PM for monitoring trauma patients (Grade 1C recommendation) 1

Key Limitations and Pitfalls

Test Performance Issues

• Different platelet function tests are not interchangeable and measure different parameters of platelet activation with different sensitivities 1
• Results may be of limited value if platelet counts are low, as the test requires adequate platelet numbers to function properly 1
• Correlation between different testing methods is only modest (66-78% agreement), meaning a patient may be classified as resistant by one method but responsive by another 2

Clinical Decision-Making Caveats

• Diagnostic cut-offs for pathologic platelet dysfunction after traumatic injury have not been established, making it impossible to distinguish pharmacologic from trauma-induced platelet receptor hypofunction 1
• The in vivo platelet response to ADP used in POC tests may not adequately detect traumatic platelet dysfunction 1
• Multiple pathways exist for platelet activation beyond the P2Y12/ADP pathway (including thromboxane A2, collagen, serotonin, and fibrin), so normal ADP response doesn't guarantee normal overall platelet function 1

Management Algorithm Based on Clinical Context

If patient is on clopidogrel with low ADP inhibition:

• Verify medication compliance first before assuming pharmacologic resistance 1
• Check for drug interactions, particularly NSAIDs like ibuprofen which can interfere with antiplatelet effects 1, 3
• Consider dose-dependent effects: resistance rates are lower with 600 mg loading doses versus 300 mg, and with 150 mg/day maintenance versus 75 mg/day 2
• CYP2C19 poor metabolizers (2% of Whites, 4% of Blacks, 14% of Chinese) will show inadequate response and genetic testing may be warranted 4

If patient is a trauma patient:

• Do not rely on ADP inhibition results to guide platelet transfusion decisions given the poor performance and lack of established cut-offs 1
• Consider that both low and high ADP inhibition can occur in traumatic brain injury independent of medication history 1
• Focus on clinical bleeding assessment and standard coagulation parameters rather than platelet function testing 1

If patient has no clear indication for antiplatelet therapy:

• Low ADP inhibition is the expected normal finding and requires no intervention 1