Induction of Hemolytic Anemia by Nonsteroidal Antiinflammatory Drugs

Abstract

The incidence of immune hemolytic anemia (IHA) is increasing. The proliferation of pharmaceuticals is a contributing factor to this increase. IHA is an uncommon, though significant, adverse effect of a wide variety of drugs. Several recent case reports have implicated the nonsteroidal antiinflammatory drugs (NSAIDs). Because of the extensive use of this class of drugs, a review of case reports, clinical studies, and in vitro research was conducted on NSAID-induced IHA. Mefenamic acid, ibuprofen, sulindac, naproxen, tolmetin, feprazone, and aspirin are reported to cause IHA, with mefenamic acid most frequently implicated. Mefenamic acid appears to cause hemolytic anemia by an autoimmune mechanism similar to methyldopa and aspirin by an immune complex mechanism. However, there is insufficient information concerning ibuprofen, sulindac, naproxen, tolmetin, and feprazone to assign specific mechanisms of immune hemolysis. In individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, aspirin at usual therapeutic doses is not a predisposing factor to hemolysis unless other risk factors are present. Although individuals with G-6-PD deficiency are at increased risk of developing hemolytic anemia when exposed to oxidizing stresses, the use of NSAIDs does not appear to increase this risk significantly. Because NSAID-induced IHA occurs infrequently and the sensitivity of currently used tests to detect drug-dependent antibodies is limited, routine serologic testing in patients receiving NSAIDs is not justified. If hemolytic anemia occurs in a NSAID-treated patient and the history is consistent with a drug-induced etiology, the NSAID should be discontinued. With discontinuation of the offending agent, the prognosis is good. There is a rapid hematologic recovery, with a slow resolution of abnormal serologic findings.

Autoimmune Haemolytic Anaemia Induced by Propyphenazone

“…Cases due to the immune-complexmechanism have been described in association with ibuprofen [1],diclofenac and mefenamic acid [2], diclofenac [5, 6],tolmetin [1], feprazone [1], acetylsalicylic and aceclofenac[8]. We have not found any IHA case associated with propyphenazone.…”

“…Twenty-three cases of IHA induced by NSAID havebeen published until now [1, 2, 3, 4, 5, 6, 7, 8]. Cases due to the immune-complexmechanism have been described in association with ibuprofen [1],diclofenac and mefenamic acid [2], diclofenac [5, 6],tolmetin [1], feprazone [1], acetylsalicylic and aceclofenac[8].…”

Correlation between the Physicochemical Property of Some Nonsteroidal Anti-inflammatory Drugs and Changes in Adenosine Triphosphate, Glutathione and Hemoglobin in Rat Erythrocytes

“…1,3) Of them, benzocaine, ABA-ethylester, has been reported to cause intravascular hemolysis with resulting Heinz-body formation, represented by a continuum of oxidative stress to RBCs. [8][9][10] Although NSAIDs such as ASP, DIC, IBU, and MNA have been recognized as drugs which could produce the hemolytic anemia, [1][2][3][4] their effects on the intracorpuscular components, ATP, GSH, and Hb are not well known.…”

Fatal Fulminant Autoimmune Haemolytic Anaemia Associated with Tolmetin Use and Gastric Carcinoma

“…This emphasises the importance of the clinical picture in addition to the serological results in evaluation of haemolytic anaemia. Mechanisms of these drug-induced immune haemolytic anaemias may not be as clear as previously described (Sandford-Driscoll & Knodel 1986). In light of the possibility of more than 1 mechanism being operative at one time and new methods being developed in detection of immune haemolysis, it is likely that new information regarding drug-induced immune haemaolytic anaemia will result in further elucidation of mechanisms.…”