Can aspirin (acetylsalicylic acid) cause thrombocytopenia (low platelet count)?

Does Aspirin Cause Thrombocytopenia?

Aspirin does not typically cause thrombocytopenia in the vast majority of patients, and the incidence of aspirin-induced thrombocytopenia is extremely rare. 1

Evidence from Large Clinical Trials

The most definitive evidence comes from the CAPRIE trial, which directly compared clopidogrel (75 mg/day) with aspirin (325 mg/day) in 19,185 high-risk patients. The incidence of thrombocytopenia was identical in both the aspirin and clopidogrel groups, demonstrating no increased risk of low platelet counts with aspirin therapy. 1 Additionally, no excess neutropenia was found in either group. 1

Multiple other large-scale trials involving tens of thousands of patients have consistently shown that aspirin does not cause clinically significant thrombocytopenia:

• The ISIS-2 trial involving over 17,000 patients showed aspirin reduced mortality by approximately 20% with no reports of thrombocytopenia as a safety concern. 1
• The COMMIT trial of 45,852 STEMI patients treated with aspirin showed no thrombocytopenia signal. 1
• The CURE trial of 12,562 patients on aspirin therapy documented no thrombocytopenia issues. 1

Rare Case Reports vs. Clinical Reality

While isolated case reports exist documenting aspirin-induced thrombocytopenia, these represent extraordinarily rare occurrences:

• One case report described a 73-year-old woman who developed severe thrombocytopenia on both clopidogrel and subsequently aspirin, suggesting a rare idiosyncratic reaction to antiplatelet agents in general. 2
• Another case report documented aspirin "allergy"-induced thrombocytopenia involving both IgG and IgE antibodies, representing a hypersensitivity reaction rather than a direct drug effect. 3

These case reports represent exceptional circumstances and should not alter clinical practice for the overwhelming majority of patients. 2, 3

Critical Clinical Context: Aspirin Use in Thrombocytopenia

Importantly, the evidence demonstrates that aspirin can and should be used safely even in patients who already have thrombocytopenia from other causes, provided the clinical indication is strong enough:

• In cancer patients with ACS and thrombocytopenia (platelet count ≤100,000 cells/µL), those who received aspirin had a 7-day survival rate of 90% compared to only 6% in those who did not receive aspirin (P < 0.0001), with no severe bleeding complications. 1, 4
• Even in cancer patients with platelet counts >100,000 cells/µL, aspirin improved 7-day survival from 45% to 88% (P = 0.0096). 4

Mechanism of Action

Aspirin works by irreversibly acetylating platelet cyclooxygenase (COX-1) at serine529, preventing thromboxane A2 formation and inhibiting platelet aggregation. 5 This mechanism affects platelet function, not platelet production or destruction, which explains why thrombocytopenia is not a typical adverse effect. 5

Studies examining aspirin's effects on platelet parameters show that while aspirin reduces platelet adhesiveness and increases bleeding time (its intended therapeutic effects), it does not change platelet count. 6

Practical Recommendations

• Do not withhold aspirin due to concerns about causing thrombocytopenia in patients with clear cardiovascular indications. 1, 4
• If unexplained thrombocytopenia develops in a patient taking aspirin, consider aspirin hypersensitivity as a rare possibility, but investigate other more common causes first. 3
• The standard therapeutic doses (75-162 mg daily for cardiovascular prevention) have been extensively studied and do not cause thrombocytopenia. 1
• True aspirin-induced thrombocytopenia, when it occurs, typically resolves within months of drug withdrawal. 2