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Physician Assistant Exam: Extravascular Hemolysis or Intravascular Hemolysis

Normal red blood cells live for about 3 to 4 months. An understanding of this is important for Physician Assistant Exam (PANCE) purposes. Hemolysis is the destruction of red blood cells in the circulation way before their life span is over. Hemolysis has many causes; one easy way to think about those causes is whether you’re dealing with extravascular hemolysis or intravascular hemolysis:

  • Extravascular hemolysis: This hemolysis occurs primarily in the reticuloendothelial system (RES). The reticuloendothelial system is the part of the immune system consisting of cells whose job is to engulf and remove defective blood cells from the circulation. The liver’s Kupffer cells and the spleen are main parts of the reticuloendothelial system.

    Common causes of extravascular hemolysis include autoimmune hemolytic anemia and hereditary disorders.

  • Intravascular hemolysis: Intravascular hemolysis is the destruction of red blood cells occurring intravascularly, or within the circulation. Common causes include microangiopathic processes (such as hemolytic uremic syndrome, or HUS; thrombotic thrombocytopenic purpura, or TTP; or disseminated intravascular coagulation, or DIC), medications, hereditary conditions, tumor lysis syndrome (TLS), and autoimmune diseases.

For the PANCE, you need to be familiar with the laboratory evaluation of hemolysis. Review how the lab results for intravascular and extravascular hemolysis compare.

Lab Test Intravascular Hemolysis Extravascular Hemolysis
LDH test Lactate dehydrogenase (LDH), reticulocyte count, and total bilirubin (with an elevated unconjugated portion) are increased. LDH and haptoglobin are normal. No hemoglobin is released into the circulation because the abnormal cell contents are all completely engulfed by the reticuloendothelial system.
Peripheral smear You see schistocytes, or helmet cells, especially if there’s a microangiopathic process. You see spherocytes (sphere-shaped cells).
Urine dip The urine dips positive for blood but doesn’t show any red cells (positive for hemoglobinuria). The urine dips negative for blood (no hemoglobinuria).
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