Download MLAB 1415-Hematology Keri Brophy

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 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
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
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.
2.
3.
RBC is hemolyzed
Free hgb released into plasma
Hgb binds to haptoglobin
–
If haptoglobin depleted,
hemopexin can step in
4. This complex goes to liver
5. Complex converted to bilirubin
6. 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 kidney
3. Hemosiderinuria
• Hemosiderin in the urine, sign of filtration of
hemoglobin thru the kidney
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
Extravascular Destruction
1. Hgb is degraded within the phagocyte to heme and globin
a.
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 bilirubin
4. 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..