Anemia Due to Destruction of Red Blood Cells
Hemolytic anemia is defined as a condition in which the life span of RBCs is shortened by premature destruction. In response to hemolysis, the kidneys increase synthesis of erythropoietin, stimulating production of RBC precursors and a subsequent rise in reticulocyte count. Peripheral blood smear evaluation may show a pattern of red cell destruction (evidenced by schistocytes or helmet cells) that reveals a potentially life-threatening disease process such as thrombotic microangiopathy associated with thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS).
The causes of hemolytic anemia are numerous and include acquired conditions as well as genetic conditions. Hemolytic anemia may be severe and life-threatening or mild and chronic. Given the numerous etiologies, it is useful to conceptualize the mechanisms of hemolysis as being either intracorpuscular (intrinsic defects of the red blood cell that lead to premature destruction) or extracorpuscular (in which the red blood cell is rendered susceptible to lysis by extrinsic factors).
Intracorpuscular defects may be caused by hemoglobinopathies, genetic membrane or cytoskeletal defects, acquired membrane disorders, or intrinsic metabolic abnormalities, such as the following:
Hereditary membrane disorders. Hereditary spherocytosis is the most common type.
Acquired membrane disorders. Paroxysmal nocturnal hemoglobinuria (PNH) manifests clinically with intravascular hemolysis, nocturnal pink or red urine, and a variable degree of jaundice and fatigue. Diagnosis of PNH is made by flow cytometry, which may incorporate fluorescent aerolysin (FLAER) assay.
Metabolic disorders. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (X-linked inheritance) and pyruvate kinase deficiency increase the susceptibility of red blood cells to oxidative stress and damage.
Antibody-mediated destruction leading to anemia (Coombs-positive hemolytic anemia) is caused by autoantibodies directed at RBC surface antigens. The condition may be assessed by direct antiglobulin testing (direct Coombs testing) for the presence of anti-IgG or anti-C3d. Other causes of antibody-mediated destruction include drug-induced autoimmune hemolytic anemia, autoimmune disease (systemic lupus erythematosus [SLE]), lymphoproliferative disorders, and transfusion-related hemolysis.
Other extracorpuscular factors leading to accelerated RBC destruction include hypersplenism with increased trapping; red blood cell pathogens like malaria, babesiosis, bartonellosis, and clostridial sepsis; mechanical heart valves; platelet microthrombi, as in TTP or HUS; or fibrin strands in blood vessels that shear the RBCs, as in disseminated intravascular coagulation. In addition, exposure to drugs that cause nonimmune (oxidative stress) destruction; trauma; and, less commonly, toxins such as snake venom, insect bites, and copper poisoning in Wilson disease are extrinsic causes of hemolytic anemia.
Evaluation and management
Hemolytic anemia may be suspected in a patient who has rapid-onset anemia in the absence of blood loss, dark urine, and jaundice, along with laboratory confirmation of hemolysis. A systematic approach to identifying the specific cause of hemolysis includes obtaining a detailed history that may, for example, reveal a recent transfusion, initiation of a new drug, or a family history of a hemoglobinopathy or other genetic disorder. Examination of the peripheral smear and flow cytometry may provide the diagnosis. Treatment of hemolytic anemia depends upon the underlying etiology, but regardless of cause, folic acid supplementation is necessary.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.