13. Hemolysis

Hemolysis Overview

  • Hemolysis refers to the destruction of red blood cells (RBCs).

  • Heme I 1304 (April 2026) - Reference document page identification.

Types of Hemolysis

Extravascular Hemolysis

  • Definition: A process by which RBCs are destroyed outside the bloodstream, primarily by macrophages in the spleen, liver, lymph nodes, and bone marrow.

  • Statistics: Approximately 90% of hemolysis is extravascular.

  • Mechanism:
      - RBCs are phagocytized by macrophages.
      - Hemoglobin within the RBC is released into macrophages.
      - Hemoglobin is broken down into heme and globin.
      - Globin Chain Recycling: Amino acids from globin chains are recycled into the amino acid pool.
      - Heme Breakdown: Heme undergoes conversion through various pathways.
      - Iron Transport: Iron is transported via transferrin to either:
        - Bone marrow for erythropoiesis.
        - Storage sites for future use.

  • Bilirubin Production:
      - Hemoglobin reacts with heme oxygenase producing biliverdin, which is then reduced to unconjugated bilirubin.
      - Bilirubin binds to albumin and is transported to the liver.

  • Clinical Indicators of Increased Extravascular Hemolysis:
      - Complete Blood Count (CBC) shows reduced red blood cell count, hemoglobin, and hematocrit.
      - Elevated reticulocyte count, evidenced by polychromasia in peripheral smear.

Intravascular Hemolysis

  • Definition: A process where RBCs are destroyed directly within the blood vessels.

  • Mechanism:
      - RBCs burst, releasing alpha and beta dimers of hemoglobin into the plasma.
      - Free hemoglobin binds to haptoglobin, creating a complex that is too large for renal filtration; this complex is transported to the liver.

  • Clinical Indicators of Increased Intravascular Hemolysis:
      - Low RBC count, hemoglobin, and hematocrit.
      - Decreased haptoglobin levels due to binding with free hemoglobin.
      - Increases in reticulocyte count, indicating erythroid hyperplasia in the bone marrow.
      - Elevated lactate dehydrogenase (LDH) in the plasma due to premature RBC lysis.

  • Disease Activators:
      - Conditions that lead to rapid hemolysis may activate the complement system (e.g., ABO transfusion reactions), promoting further RBC damage.

Laboratory Evidence of Hemolysis

  • Hemolysis can be tracked through various laboratory methods:
      - Evidence appears in the bone marrow, peripheral circulation, and blood plasma.
      - Bone Marrow Findings:
        - Shows erythroid hyperplasia, meaning a rise in RBC precursors and early release of reticulocytes.
        - Normal myeloid:erythroid (M:E) ratio of 3:1 to 4:1 shifts to a 1:2 ratio due to increased RBC precursors.
      - Peripheral Smear Findings:
        - Polychromasia indicates increased reticulocytes.
        - Nucleated RBCs may also be observed.
        - Spherocytes may form if antibody-coated RBCs are processed by the spleen.

  • Plasma Findings:
      - Haptoglobin levels are low during hemolytic events due to binding with free hemoglobin.
      - Distinction between intravascular and extravascular hemolysis can often be made by careful laboratory analysis.
      - Spleen Changes: Spleen may become enlarged in cases of extravascular hemolysis due to sequestered damaged RBCs.

Hemoglobinuria and Hemoglobinemia

  • Hemoglobinemia: Presence of free hemoglobin in the plasma, causing red or pink-tinted plasma post-centrifugation.

  • Hemoglobinuria: Free hemoglobin filtered by kidneys appears in the urine, causing reddish urine; indicates intravascular hemolysis.

  • Clinical Implications: If hemoglobinemia and hemoglobinuria are present, it suggests a serious condition that requires immediate intervention.

Summary of Hemolytic Events

Shared Conditions in Hemolysis

  • Common Lab Findings:
      - Decreased levels of hemoglobin (Hgb), hematocrit (Hct), and RBC count are indicative of anemia (pallor, fatigue, tachycardia).
      - Serum bilirubin levels are elevated, leading to jaundice.
      - Reticulocyte count is increased.
      - Serum haptoglobin is markedly decreased.
      - Lactate dehydrogenase (LDH) levels are elevated.

Classifications Relevant to Hemolytic Anemias

  • Hemolytic anemias can arise from either intrinsic defects of the RBC or extrinsic factors.

Intrinsic Defects

  • Related to inherited deficiencies affecting:
      - RBC membrane.
      - Hemoglobin structure or synthesis.
      - Other biochemical components.

Extrinsic Defects

  • Secondary factors that affect RBC performance leading to hemolysis, such as autoimmune disorders or environmental agents.

Classification by Defect Types

Intrinsic Defects Leading to Hemolysis

  • Hemoglobinopathies: Structural and synthetic defects in hemoglobin.

  • RBC Membrane Defects: May include hereditary spherocytosis and elliptocytosis.

  • RBC Enzyme Defects: Such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase deficiencies.

  • Stem Cell Defects: Affect the precursor cells in the bone marrow.

Extrinsic Defects Leading to Hemolysis

  • Autoimmune hemolytic anemias.

  • Parasitic infections (e.g., malaria, babesiosis).

  • Acute hemolytic transfusion reactions (HTR).

  • Environmental toxins including venoms and chemical agents.

Summary Diagram of Hemolysis

  • Extravascular Hemolysis: Mediated by the spleen and reticuloendothelial system.

  • Intravascular Hemolysis: Occurs within circulation.

  • Conditions Affecting Hemolysis:
      - Immune-mediated hemolysis (e.g., Warm AIHA, Cold AIHA).
      - Complement-mediated (e.g., PCH, PNH).
      - Mechanical shearing (e.g., prosthetic heart valves, MAHA conditions like TTP, DIC, HUS).