In drug-induced nonautoimmune hemolytic anemia, red blood cells (RBC) are destroyed from various non-immune mechanisms such as direct oxidative stress from certain drugs.
[2] Drug-induced nonautoimmune hemolytic anemia can also occur due to other various mechanisms that damage RBCs such as in drug induced thrombotic microangiopathy.
[3] Individuals with drug-induced nonautoimmune hemolytic anemia often have symptoms of fatigue, pallor, shortness of breath, and abdominal pain.
Drugs commonly implicated in causing hemolytic anemia in these individuals include:[1] Methemoglobinemia may also uncommonly cause hemolytic anemia and commonly implicated drugs include topical anesthetics such as benzocaine or lidocaine, dapsone, inhaled nitric oxide, rasburicase, chloroquine, sulfasalazine and primaquine.
These oxidizing radicals can directly damage and crosslink the membrane and intracellular structures of RBCs, cause lipid peroxidation, and promote the formation of Heinz bodies that further impede RBC function.
[13] Continued oxidation and eventual precipitation of methemoglobin can cause the formation of Heinz bodies, which attach to the RBC membrane.
Non-immune DITMAs occur generally due to direct tissue injury to the small vessels of the body causing cellular damage and increased accumulation of platelets.
Since nonautoimmune hemolytic anemia occurs due to mechanisms that do not involve the creation of IgG or complement, direct antiglobulin testing will often be negative.
[16] When drug-induced nonautoimmune hemolytic anemia is suspected, stabilizing or life saving treatments should be taken aggressively prior to diagnosis.
[4] If drug-induced nonautoimmune hemolytic anemia occurs secondarily to drug induced methemoglobinemia, methylene blue can be used as a first-line therapy.