Extravascular hemolysis refers to the destruction of
red blood cells (RBCs) outside the blood vessels. This process primarily occurs in the
reticuloendothelial system, which includes organs such as the
spleen,
liver, and bone marrow. These organs host macrophages that phagocytize and digest aged or abnormal RBCs, leading to their breakdown and recycling of components.
The process begins with the recognition of aged or damaged RBCs by macrophages. These cells are identified by changes in their membrane proteins or the presence of bound antibodies. Macrophages then engulf the RBCs and degrade them within phagolysosomes. The key steps in this process involve:
Recognition and binding of RBC by macrophages.
Phagocytosis and formation of a phagolysosome.
Degradation of hemoglobin into
heme and globin.
Conversion of heme into
bilirubin and iron.
The byproducts of hemolysis are efficiently recycled:
Iron: This is transported by
transferrin to the bone marrow for reuse in erythropoiesis.
Globin: The protein portion of hemoglobin is broken down into amino acids, which can be reused for protein synthesis.
Bilirubin: This is carried to the liver bound to albumin, where it is conjugated and excreted in bile.
Histological Features of Extravascular Hemolysis
In histological examinations, certain features may indicate extravascular hemolysis:
Increased macrophages: In the spleen and liver, one may observe an increased number of macrophages with ingested RBCs.
Hemosiderin deposits: Iron from degraded RBCs may accumulate as hemosiderin in macrophages, which can be visualized using special stains like Prussian blue.
Changes in spleen architecture: Chronic hemolysis can lead to splenomegaly and alterations in the splenic red pulp.
Clinical Implications of Extravascular Hemolysis
Extravascular hemolysis is a common feature in various hematologic disorders, such as
hereditary spherocytosis, autoimmune hemolytic anemia, and certain infections. Clinically, it can lead to anemia, jaundice, and splenomegaly. Laboratory findings often include elevated levels of unconjugated bilirubin, increased lactate dehydrogenase (LDH), and reticulocytosis.
Diagnosis typically involves a combination of clinical evaluation, laboratory tests, and histological examination:
Peripheral blood smear: This can show spherocytes, schistocytes, or other abnormal RBC morphologies.
Direct antiglobulin test (DAT): This detects antibodies or complement on the RBC membrane, indicating immune-mediated hemolysis.
Histopathology: Examination of splenic or hepatic tissue may reveal increased macrophage activity and hemosiderin deposits.
