MLAB 1415-Hematology Keri Brophy-Martinez Chapter 14: Introduction to Hemolytic Anemias

MLAB 1415-Hematology

Keri Brophy-Martinez

Chapter 14: Introduction to Hemolytic Anemias

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

Classified by…

• Source of defect causing the hemolysis– Intrinsic/extrinsic• Poikilocyte present

– Schistocytes/Spherocytes

• Mode of onset– Inherited/acquired

• Location of hemolysis– Intravascular/Extravascular

Lab Features• Reticulocytosis– RPI> 2

• Erythroid hyperplasia of bone marrow• M:E ratio decreased• Peripheral blood– Normochromic,normocytic– Polychromasia– nRBCs

• Tests for heme catabolism abnormal– Unconjugated/conjugated bilirubin– Haptoglobin

Lab FeaturesIncreased 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

Diagnostic Approach to Hemolytic Anemias

Increased RBC ProductionIncreased RBC Destruction

COOMBS (DAT) test

Immune Hemolytic Anemias

Peripheral blood smearRBC Morphology

Lab Investigation

Definitive Diagnosis

Clinical Findings

• Jaundice• Pallor• Fatigue• Cardiac symptoms• Gallstones• Dark or red urine• Splenomegaly

Sites of Destruction

• Intravascular– Hemolysis occurs within the circulation– RBC’s are severely damaged

• Extravascular– Hemolysis occurs within the macrophages of the

spleen, liver or bone marrow– More common than intravascular

Intravascular Destruction

1. RBC is hemolyzed2. Free hgb released into plasma3. Hgb binds to haptoglobin

– If haptoglobin depleted, hemopexin can step in

4. This complex goes to liver 5. Complex converted to bilirubin6. Bilirubin excreted to intestinal

tract

Terms

1. Hemoglobinemia– Occurs if hemopexin and haptoglobin is depleted.

Free hgb circulates in blood.2. Hemoglobinuria– Occurs if free hgb can not be absorbed by the

liver and kidney3. Hemosiderinuria• Hemosiderin in the urine, sign of filtration of

hemoglobin thru the kidney

Causes ofIntravascular 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

Extravascular Destruction

1. Hgb is degraded within the phagocyte to heme and globina. Phagocyte locations:• Spleen: removes slightly damaged RBCs• Liver: removes severely damaged RBCs• Bone marrow: remove mature precursor cells that are

intrinsically abnormal

2. Heme further degraded to iron, biliverdin and carbon monoxide

3. Biliverdin enters plasma as bilirubin4. Bilirubin binds to albumin, excreted by the liver

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

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

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

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..