Autoimmune Hemolytic Anemia

Hemolytic anemia may be caused by any one or more of several kinds of disorders. For example, contributing factors may include:

An autoimmune response in which the patient’s immune system destroys the patient’s red blood cells. The disorder is more common among people who already have an autoimmune disorder such as lupus. The taking of certain types of medication by certain people. Among such medications are penicillin, quinine, methyldopa, and sulfonamides.

Inherited enzyme deficiencies inside red blood cells may cause the cells to become fragile and subject to destruction. Most commonly, low levels of the enzymes pyruvate kinase or glucose-6-phosphate dehydrogenase are the culprits. Hemoglobin disorders such as sickle cell anemia or thalassemias (blood disorders that affect the cell’s ability to produce hemoglobin). Abnormalities of the cell membrane cause the red blood cells to take on a shape other than the normal disc shape. Such red blood cells may show up as spheres or ellipses or cup-like.

Intracorpuscular causes refer to abnormalities in the red blood cell itself. A red blood cell can be internally damaged when the solubility of hemoglobin is altered (hemoglobinopathy), the structure of the membrane or cytoskeleton is changed (embryopathy), or its metabolic abilities (enzymopathy) are decreased. Examples of hemoglobinopathies include sickle cell disease (SCD) and thalassemias. SCD is caused by a beta-globin gene mutation leading to polymerization of hemoglobin-S, sticking, and, therefore, hemolysis. Thalassemia is the most common cause of hereditary hemolytic anemia and is caused by a partial or complete lack of synthesis of one of the major alpha or beta globin chains of hemoglobin A.[rx]

Membranopathies include hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). HS is often autosomal dominant; however, non-dominant and recessive traits have been seen. It has been seen in all racial groups. HS has been documented as a rare disease, however, due to limited knowledge as the onset and severity vary considerably, as well as, the lack of specific lab tests, make it a difficult disease to study. HE is a heterogeneous red cell membrane disordered where the autosomal dominant inheritance can lead to a spectrum of presentations from asymptomatic to life-threatening.[rx][rx]

Several RBC enzymopathies alter the shape of RBCs and cause nonspherocytic hemolytic anemias.[rx] G6PD deficiency and pyruvate kinase deficiency (PKD) both fall into this category. PK is the rate-limiting enzyme in RBC energy production, whereas G6PD is involved in the processing of carbohydrates and plays a protective role against reactive oxygen species in RBCs.[rx] G6PD deficiency is an X-linked inherited disorder, almost exclusively seen in males, that causes hemolysis often with certain medications or foods such as fava beans and aspirin.[rx]

Alternatively, extracorpuscular causes refer to defects that were influenced by external factors, including mechanical, immune-mediated, or infectious. RBC transfusions can cause both acute and delayed hemolytic reactions. Mechanical trauma to RBCs is seen with microthrombi, fibrin, or valve shearing forces. Pathogens such as malaria and babesiosis are known to destroy RBCs as well as medications like dapsone, which can be used to treat these diseases, also have deleterious effects as it has oxidant potential.

Some unusual situations may lead to the destruction of red blood cells. For example, as the cells pass through oxygenating machines during open-heart surgery, they may undergo changes that lead to hemolytic anemia.