Hemolysis refers to the shortened survival of erythrocytes (red blood cells; RBCs) in the blood circulation before the normal expected lifespan of the RBC has been reached. In this situation, RBCs are typically produced in the bone marrow but are destroyed after they enter the blood stream.
When there is an increased rate of RBC destruction, the bone marrow is able to increase production in an attempt to compensate for the losses. Bone marrow has the capacity to increase RBC production 6 – 8 times normal, a process that involves an increase in erythropoietin production.
Anemia is the term used to define when the amount of RBCs, measured as hemoglobin or hematocrit, is below the lower limit of the normal value for the population being examined. There are many potential causes of anemia which do not involve hemolysis. Likewise, due to the ability of a normal bone marrow to increase production in response to increased destruction of RBCs, hemolysis can occur in the absence of anemia when the bone marrow is able to compensate for the rate of RBC loss with an equivalent level of RBC production. Anemia occurs when RBC production cannot match the rate of RBC loss.
Causes of Hemolysis
Hemolysis is due to both inherited abnormalities of RBCs and acquired causes introduced after birth. Acquired mechanisms of hemolysis include those that involve the immune system, physical damage to RBCs, infectious agents which damage RBCs, and medications/drugs. In addition, there is an acquired genetic disease that results in the clonal proliferation of RBCs that have an inherent predisposition for hemolysis (i.e., paroxysmal nocturnal hemoglobinuria; PNH).
Immune – mediated hemolysis Warm antibody autoimmune hemolytic anemia (AIHA) | Cold antibody AIHA | Cold agglutinin disease | Donath – Landsteiner AIHA | Paroxysmal cold hemoglobinuria
Drug – induced hemolysis Hapten mechanism | Immune complex mechanism | Autoantibody mechanism | Immunogenic drug – RBC complex mechanism
Non – immune hemolysis Fragmentation hemolysis (aka microangiopathic hemolysis) | Hypersplenism | Infection | Liver disease | Hypophosphatemia | Severe burns | Copper excess (Wilson’s disease) | Drug – induced oxidative damage | Vitamin E deficiency
RBC transfusion – associated hemolysis Acute hemolytic reactions | Delayed hemolytic reactions
Paroxysmal nocturnal hemoglobinuria
Location of where hemolysis occurs
1. Extravascular: (a) Tissue macrophages in the spleen (most common) or liver. (b) Laboratory features often include unconjugated hyperbilirubinemia (indirect bilirubin) and normal to slightly decreased haptoglobin (an α – globulin produced in the liver that binds free hemoglobin and is decreased in hemolysis and in severe liver disease).
2. Intravascular: (a) Within the blood circulation (blood vessels). (b) Laboratory features often include hemoglobinemia (i.e., pink plasma due to free hemoglobin in the blood), hemoglobinuria (i.e., free hemoglobin observed in voided urine), hemosiderinuria (i.e., water soluble hemosiderin in urine), and decreased serum haptoglobin.
1. Anemia (these are not specific for hemolysis): Fatigue. Dyspnea. Pallor.
2. Symptoms and signs that may be related to hemolysis: Jaundice. Gallstones (pigmented; bilirubin). Splenomegaly.
3. Extravascular: Often associated with jaundice, splenomegaly.
4. Intravascular: (a) Often associated with fever, chills, tachycardia, backache, renal failure.