1. MLAB 1415-Hematology Keri Brophy-Martinez
Introduction to Hemolytic Anemias

2. Hemolytic anemia Anemia caused by hemolysis of red blood cells
Hemolysis is the destruction of erythrocytes resulting in the release of hemoglobin
Results in reduction of normal red cell lifespan.
Normocytic, normochromic anemia
RBC’s are prematurely destroyed

3. Classified by… Source of defect causing the hemolysis Mode of onset
Intrinsic/extrinsic
Poikilocyte present
Schistocytes/Spherocytes
Mode of onset
Inherited/acquired
Acute/Chronic
Location of hemolysis
Intravascular/Extravascular

4. Lab Features Reticulocytosis RPI> 2
Erythroid hyperplasia of bone marrow
M:E ratio decreased
Increased osmotic fragility
Peripheral blood
Normochromic,normocytic
Polychromasia
nRBCs
Tests for heme catabolism abnormal
Unconjugated/conjugated bilirubin
Haptoglobin

5. Lab Features Increased Bone Marrow Production of Erythrocytes
Increased Erythrocyte Destruction
Reticulocytosis (RPI>2)
Anemia
Leukocytosis
Spherocytes, Schistocytes, Poikilocytes
nRBCs in PB
Decreased haptoglobin
Polychromasia
Increased bilirubin
Normoblastic erythroid hyperplasia in bone marrow
Increased LDH
M:E decreased
Increased urobilinogen
Increased expired CO
Hemoglobinemia*
Hemoglobinuria*
Hemosiderinuria*
*Only with intravascular hemolysis

6. Diagnostic Approach to Hemolytic Anemias
Increased RBC Production
Increased RBC Destruction
COOMBS (DAT) test
Peripheral blood smear
RBC Morphology
Immune Hemolytic Anemias
Lab Investigation
Definitive Diagnosis

7. Clinical Findings Jaundice Pallor Fatigue Cardiac symptoms Gallstones
Dark or red urine
Splenomegaly

8. Sites of Destruction Intravascular Extravascular
Hemolysis occurs within the circulation by fragmentation
RBC’s are severely damaged
Extravascular
Hemolysis occurs within the macrophages of the spleen, liver or bone marrow
More common than intravascular

9. Intravascular Destruction
RBC is hemolyzed
Free hgb released into plasma
Hgb binds to haptoglobin
If haptoglobin depleted, hemopexin can step in
This complex goes to liver
Complex converted to bilirubin
Bilirubin excreted to intestinal tract

10. Terms
Hemoglobinemia
Occurs if hemopexin and haptoglobin is depleted. Free hgb circulates in blood.
Hemoglobinuria
Occurs if free hgb can not be absorbed by the liver and kidney
3. Hemosiderinuria
Hemosiderin in the urine, sign of filtration of hemoglobin thru the kidney

11. Causes of Intravascular Hemolysis:
Activation of Complement on RBC Membrane
Physical or Mechanical Trauma to the RBC
Toxic Microenvironment of the RBC
Paroxysmal noctural hemoglobinuria
Microangiopathic hemolytic anemia
Bacterial infections
Paroxysmal cold hemoglobinuria
Abnormalities of heart vessels
Plasmodium falciparum infection
Some transfusion reactions
Disseminated intravascular coagulation
Venoms
Some autoimmune hemolytic anemias
Thermal injury
Acute drug reaction in G6PD deficiency

12. Extravascular Destruction
Hgb is degraded within the phagocyte to heme and globin
Phagocyte locations:
Spleen: removes slightly damaged RBCs
Liver: removes severely damaged RBCs
Bone marrow: remove mature precursor cells that are intrinsically abnormal
Heme further degraded to iron, biliverdin and carbon monoxide
Biliverdin enters plasma as bilirubin
Bilirubin binds to albumin, excreted by the liver

14. Causes of Extravascular Hemolysis:
Origin
Anemias
Inherited RBC Defects
Thalassemia, Hemoglobinopathies, Enzyme deficiencies, Membrane disorder
Acquired RBC Defects
Megaloblastic anemia, Vitamin E deficiency in newborns
Immunohemolytic anemias
Autoimmune, Drug induced, Some transfusion reactions

15. Source of Defect of RBC Intrinsic Abnormality of the RBC Membrane
Cell enzymes
Hemoglobin molecule
Usually hereditary
EXCEPTION: Acquired
Paroxysymal noctural hemoglobinuria (PNH)
Site of hemolysis: extravascular

16. Source of Defect of RBC Extrinsic
Antagonist in cell’s environment causes injury to the RBC
Antagonistic plasma factors
Traumatic physical cell injury
Immune mediated cell destruction
RBC is normal
Usually acquired
Site of hemolysis: intra or extravascular

17. Referenes
Harmening, D. M. (2009). Clinical Hematology and Fundamentals of Hemostasis (5th ed.). Philadelphia, PA: F.A. Davis Company.
McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc.