Does Codeine Affect Platelets? A Pharmacological Review

October 12, 2025 •

3 min read

Drug-induced thrombocytopenia (DITP), a condition of low platelet counts, has a cumulative incidence of 10 cases per million people annually. This raises the important question for patients and clinicians: does codeine affect platelets and contribute to this risk?

Quick Summary

Current research suggests that codeine and other opioids are not likely to heavily affect normal platelet function or count. However, rare cases of codeine-induced immune thrombocytopenia have been reported.

Key Points

General Effect: Current research indicates that codeine and other opioids are not likely to have a significant impact on normal platelet function or count.
Immune Thrombocytopenia: In very rare instances, codeine has been linked to drug-induced immune thrombocytopenia (DITP) as part of a hypersensitivity reaction.
Platelet Aggregation: Opioids like morphine generally do not inhibit platelet aggregation directly, unlike NSAIDs such as aspirin and ibuprofen.
Drug Interactions: Morphine (the active metabolite of codeine) can delay the absorption and effectiveness of certain antiplatelet medications like clopidogrel.
Mechanism: Platelets do have opioid receptors, but their stimulation by opioid agonists does not typically cause activation or interfere with the normal clotting process.
Comparison with NSAIDs: Codeine is considered a safer alternative for pain relief in people with bleeding disorders because it does not interfere with blood clotting, whereas NSAIDs do.
Platelet Count: While rare cases of codeine-induced low platelets exist, some studies in chronic opioid users have reported increased platelet counts.

Introduction to Codeine and Platelets

Codeine is an opioid medication used for pain and cough suppression, converted to morphine in the body. Platelets are blood cell fragments essential for forming clots to prevent bleeding. A normal platelet count ranges from 150,000 to 450,000 per microliter. Understanding if codeine affects these vital components is a key clinical concern.

The Direct Question: Does Codeine Affect Platelets?

Studies suggest opioids, including codeine, do not significantly impact normal platelet function or count. While platelets have opioid receptors, stimulation doesn't typically trigger activation or interfere with clotting. The Haemophilia Society confirms that paracetamol and codeine preparations do not interfere with blood clotting, making them suitable for individuals with bleeding disorders.

However, rare exceptions exist. A case report linked codeine phosphate to a hypersensitivity syndrome including immune thrombocytopenic purpura, a low platelet condition.

Mechanisms of Drug Interaction with Platelets

Drugs can cause thrombocytopenia (low platelet count) via immune-mediated destruction or suppressed production in bone marrow. Drug-induced immune thrombocytopenia (DITP) often resolves within about a week of stopping the drug. While many drugs cause DITP, opioids are not common culprits.

Research on opioid receptors on platelets is complex. Agonists didn't directly cause secretion, but studies in mice suggest a potential role for the μ-receptor in platelet function. Still, healthy platelet function is unlikely to be negatively affected during short-term use.

Codeine and Thrombocytopenia

Thrombocytopenia is defined as a platelet count below 150,000 per microliter. While very rare, codeine has been linked to this condition, typically as an idiosyncratic reaction like the case study reporting immune thrombocytopenic purpura due to codeine-induced hypersensitivity syndrome. Conversely, some studies on chronic opioid users have observed an increase in platelet counts. A case report on morphine (codeine's active form) noted severe thrombocytopenia that improved upon stopping the drug, confirmed by an anti-platelet antibody test. These findings indicate that while not a typical effect, individual adverse reactions are possible.

Codeine and Platelet Function (Aggregation)

Platelet aggregation, the clumping of platelets for clotting, is generally not significantly induced or inhibited by most opioids, including morphine, nor do they interfere with aggregation caused by natural stimulators. One study specifically found morphine to have minimal effect on aggregation.

However, indirect interactions can occur. Morphine can delay the absorption and lower the concentration of antiplatelet drugs like clopidogrel, potentially leading to higher residual platelet aggregation for a few hours. This is a drug-drug interaction, not a direct effect on the platelet itself. In contrast, NSAIDs like aspirin directly inhibit platelet function by blocking thromboxane A2, which promotes activation.

Comparison of Analgesics and Platelet Effects


Feature	Codeine/Opioids	NSAIDs (e.g., Ibuprofen, Aspirin)	Acetaminophen (Paracetamol)
Effect on Platelet Count	Generally no effect; may increase in chronic users. Rare cases of immune thrombocytopenia reported.	Generally no effect on count. Can cause thrombocytopenia, though less common than with other drugs.	Generally no effect on count, but can decrease aggregation.
Effect on Platelet Function	Not likely to have a significant direct effect on aggregation in healthy individuals.	Directly inhibit platelet aggregation, leading to a mild bleeding tendency. The effect of aspirin is irreversible for the platelet's lifespan.	Can decrease platelet aggregation. Does not interfere with blood clotting to the extent of NSAIDs.
Mechanism	Interaction with opioid receptors on platelets is complex but does not typically trigger activation or inhibition.	Inhibit the COX enzyme, preventing the production of thromboxane A2, which is essential for aggregation.	Inhibits platelet function, but the exact mechanism is less potent than that of NSAIDs.

Conclusion

Current research suggests codeine does not typically cause clinically significant effects on platelet count or function. Its action differs from NSAIDs, which are known for antiplatelet effects. However, rare idiosyncratic reactions like codeine-induced immune thrombocytopenia are possible. There is also a potential drug interaction where opioids like morphine can delay the efficacy of antiplatelet drugs such as clopidogrel.

An Authoritative Outbound Link

Frequently Asked Questions

While codeine is not known to typically lower platelet counts, you should always consult your healthcare provider. They can assess the cause of your low platelets and determine if codeine is safe for you, as very rare cases of codeine-induced thrombocytopenia have been reported.

No, codeine does not thin the blood in the same way aspirin does. Codeine preparations do not typically interfere with blood clotting, whereas aspirin and other NSAIDs inhibit platelet function, which can increase bleeding time.

Research suggests that short-term exposure to opioids like codeine is not likely to adversely affect normal platelet function during surgery. However, you must inform your surgeon and anesthesiologist of all medications you are taking.

Symptoms of a low platelet count (thrombocytopenia) can include easy or excessive bruising, frequent bleeding from the gums or nose, and the appearance of tiny red or purple spots on the skin (petechiae).

Some studies on chronic opioid-dependent individuals have noted an increase in platelet counts, while others have reported various changes in other blood parameters. The long-term effects are still being studied.

Yes, a potential interaction exists. Morphine, which is what codeine is converted to in the body, can delay the absorption and reduce the peak concentration of antiplatelet drugs like clopidogrel, potentially making it less effective for a period of time.

Codeine is generally considered safer regarding platelet function, as it does not directly inhibit platelet aggregation. Ibuprofen, an NSAID, is known to interfere with platelet function and can increase the risk of bleeding.