Gastrointestinal
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Aspirin use has been shown to increase the risk of gastrointestinal bleeding.[92] Although some enteric coated formulations of aspirin are advertised as being "gentle to the stomach", in one study enteric coating did not seem to reduce this risk.[92] Combining aspirin with other NSAIDs has also been shown to further increase this risk.[92] Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.[93]
Mitigation of gastrointestinal bleeding
In addition to enteric coating, "buffering" is the other main method companies have used to try to mitigate the problem of gastrointestinal bleeding. Buffering agents are intended to work by preventing the aspirin from concentrating in the walls of the stomach, although the benefits of buffered aspirin are disputed. Almost any buffering agent that is used in antacids can be used; Bufferin, for example, uses MgO. Other preparations use CaCO3.[94]
Taking with Vitamin C is a more recently investigated method of protecting the stomach lining. According to research done at a German university taking equal doses of vitamin C and aspirin decreases the amount of stomach damage that occurs when compared to taking aspirin alone.[95][96]
DGL, Deglycyrrhizinated licorice, an extract of the popular herb licorice reportedly helps relieve the symptoms of gastritis. In a 1979 research study a dose of 350 milligrams of DGL was shown to decrease the amount of gastrointestinal bleeding induced by 3 adult-strength aspirin tablets (750 milligrams).[97]
A dose of 500 milligrams of SAMe (S-adenosyl-methionine,is an amino acid naturally formed in the body) given together with a large dose of aspirin (1300 milligrams) in a research study reduced the amount of stomach damage by 90 percent.[98]
Central effects
Large doses of salicylate, a metabolite of aspirin, have been proposed to cause tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.[99]
Reye's syndrome
Reye's syndrome, a severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illnesses or infections. From 1981 through 1997, 1207 cases of Reye's syndrome in under-18 patients were reported to the U.S. Centers for Disease Control and Prevention. Of these, 93% reported being ill in the three weeks preceding onset of Reye's syndrome, most commonly with a respiratory infection, chickenpox, or diarrhea. Salicylates were detectable in 81.9% of children for whom test results were reported.[100] After the association between Reye's syndrome and aspirin was reported and safety measures to prevent it (including a Surgeon General's warning and changes to the labeling of aspirin-containing drugs) were implemented, aspirin taken by children declined considerably in the United States, as did the number of reported cases of Reye's syndrome; a similar decline was found in the United Kingdom after warnings against pediatric aspirin use were issued.[100] The United States Food and Drug Administration now recommends that aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever,[4] and the British Medicines and Healthcare products Regulatory Agency (MHRA) recommends that children who are under 16 years of age should not take aspirin, unless it is on the advice of a doctor.[101]
Hives and swelling
For a small number of people, aspirin can result in symptoms that resemble an allergic reaction and include hives, swelling, and headache. The reaction is caused by salicylate intolerance and is not a true allergy, but rather an inability to metabolize even small amounts of aspirin, resulting in an overdose.
Other effects
Aspirin can induce angioedema in some people. In one study, angioedema appeared 1–6 hours after ingesting aspirin in some of the patients participating in the study. However, when the aspirin was taken alone it did not cause angioedema in these patients; the aspirin had been taken in combination with another NSAID-induced drug when angioedema appeared.[102]
Aspirin causes an increased risk of cerebral microbleeds that has the appearance on MRI scans of 5–10 mm or smaller hypointense (dark holes) patches.[103][104] Such cerebral microbleeds are important since they often occur prior to ischemic stroke or intracerebral hemorrhage, Binswanger disease and Alzheimers Disease.
Aspirin can cause prolonged bleeding after operations for up to 10 days. In one study, 30 of 6499 elective surgical patients required reoperations to control bleeding. 20 had diffuse bleeding and 10 bleeding from a site. Diffuse, but not discrete, bleeding was associated with the preoperative use of aspirin alone or in combination with other NSAIDS in 19 of the 20 diffuse bleeding patients.[105]
