From the Guidelines
Low platelet aggregation in response to adrenaline (epinephrine) is most likely caused by the use of antiplatelet medications, such as aspirin, which inhibit platelet function, as evidenced by studies showing variable responses to aspirin in patients with vascular disease 1.
Mechanism of Action
The decreased aggregation occurs because epinephrine normally activates platelets through alpha-2 adrenergic receptors, triggering a signaling cascade that leads to platelet activation and aggregation. When this pathway is disrupted by medications or certain medical conditions, the laboratory test shows reduced aggregation.
Clinical Implications
If this is an incidental finding in an asymptomatic patient, no specific treatment is typically required. However, if the patient is experiencing bleeding symptoms or is scheduled for surgery, temporary discontinuation of antiplatelet medications may be necessary. For patients on aspirin, stopping the medication 7-10 days before elective procedures is often recommended, based on studies such as those by Helgason et al, which showed that 25% of patients exhibited only partial inhibition of platelet aggregation 1.
Key Considerations
- Aspirin resistance, defined as the failure of aspirin to inhibit platelet aggregation, is a significant concern, with studies suggesting that up to 30% of patients may be nonresponders 1.
- The use of alternative or additive platelet therapy may be necessary in patients who are nonresponders to aspirin, as suggested by studies such as those by Mueller et al, which showed that patients who did not respond to aspirin had a higher risk of complications 1.
- Further hematologic evaluation may be warranted to identify underlying platelet function disorders in cases where the finding is not medication-related.
From the Research
Causes of Low Platelet Aggregation in Response to Adrenaline (Epinephrine)
- The low initial response of platelets to epinephrine in vitro might be due to reduced secretion of ADP, i.e., limited adaptive response, as established in a study on patients with chronic cerebral ischemia 2.
- Inherited heterogeneous defects of platelet function can cause impairment of platelet responses to weak agonists such as ADP and epinephrine, leading to low platelet aggregation 3.
- Epinephrine-induced platelet aggregation can be influenced by the presence of other agonists, such as collagen, and the potency of epinephrine can vary depending on the species, as seen in a study on rat platelet-rich plasma 4.
- Desensitization of epinephrine-initiated platelet aggregation can occur without altering binding to the alpha 2-adrenergic receptor or receptor coupling to adenylate cyclase, as demonstrated in a study on aspirin-treated platelets 5.
- Epinephrine can induce a late thromboxane-dependent platelet shape change and enhance synergistically the shape change induced by other platelet agonists, which may contribute to low platelet aggregation in response to epinephrine alone 6.
Key Factors Influencing Platelet Aggregation
- ADP secretion: reduced secretion of ADP can limit the adaptive response of platelets to epinephrine 2.
- Presence of other agonists: collagen and other agonists can influence epinephrine-induced platelet aggregation 4, 6.
- Alpha 2-adrenergic receptors: desensitization of these receptors can occur without altering their binding or coupling to adenylate cyclase 5.
- Thromboxane generation: slow generation of TXA(2) may contribute to the inability of epinephrine to induce a shape change that precedes aggregation 6.