Chapter 9: Hemolytic Anemias

Why is the RBC membrane important?

• structure / flexibility

  • withstand forces of circulatory pressure

• RBC deformability

  • ability of the RBC to repeatedly bend, stretch, destroy and return to normal shape

What happens if a RBC membrane is defected?

• alter the shape/deformability of cell

• leads to premature destruction / hemolysis

What are Intrinsic Hemolytic Anemias?

• intracorpuscular, defect within the cell

  • usually genetic / inherited

  • membrane defects - shape or structure abnormalities

  • enzyme deficiencies

  • faulty hemoglobin

What are Extrinsic Hemolytic Anemias?

• extracorpsule, outside of the cell

  • usually acquired

  • normal cells in a hostile environment

  • immune response

  • infections, parasites, toxins, trauma

What is Hemolysis?

• lysis of RBC resulting in the release of hemoglobin

How is Hemolysis Diagnosed

• increased destruction

  • ↑ indirect bilirubin

  • ↓ Haptoglobin - binds excess hgb

  • ↑ LDH

• increased production

  • BM response

  • reticulocytes

What does a positive DAT (Coombs test) mean about Hemolysis?

• body destroying cells in vivo

What does a negative DAT (Coombs test) mean about Hemolysis?

• other factors are destroying cells

How are morphological abnormalities of RBC’s classified?

• Hereditary spherocytosis

• Hereditary elliptocytosis

  • Hereditary pyropoikilocytosis

  • SE Asian ovalocytosis

• Hereditary stomatocytosis

• Hereditary xerocytosis

What are Vertical Interactions between the red cell membrane components?

• between membrane skeleton and the bilayer

• spectrin-ankyrin associations

What are Horizontal Interactions between the red cell membrane components?

• within lipid bilayer

• spectrin dimer self-association to produce tetramers

• spectrin-actin complex formation

What is Hereditary Spherocytosis?

• vertical defect

• heterogenous group of hemolytic anemia

• protein defects disrupting vertical interactions

• autosomal dominant - common in european ancestry

• RBC stay round

What defects occur in Hereditary Spherocytosis?

• spektrin

• ankyrin

• band 3

• protein 4.2

What is the pathophysiology of Hereditary Spherocytosis?

1. primary membrane cytoskeletal defect

2. loss of membrane due to decreased stability

3. decreased surface to volume ratio

4. spherocytes (decreased deformability)

5. erythrostasis due to splenic trapping

6. phagocytosis (extravascular hemolysis)

What are symptoms of Hereditary Spherocytosis?

• anemia

• jaundice

• splenomegaly

  • affects half of young children

  • 75-95% of older children / adults

• presents in infancy, childhood, adulthood

What lab findings indicate Hereditary Spherocytosis?

• Spherocytes

• Polychromasia

• reticulocytes

• ↑ MCHC and RDW

• ↑ osmotic fragility

What is used to treat Hereditary Spherocytosis?

• splenectomy

What is Hereditary Elliptocytosis (HE)?

• heterogenous group of hemolytic anemias

• presence of elliptical (oval) RBC

• more common in Africa/Mediterranean

• autosomal dominant

• abnormality: membrane skeleton

What are the different HE Groups?

• Common HE - most prevalent

• SE Asia Ovalocytosis

  • SE Asian population

  • spoon shaped ovalocytes

  • resistant to malaria

  • two distinct ridges/transverse bars

• Hereditary pyropoikilocytosis

  • a and B disorder

  • Microspherocytosis

  • Micropeikilocytosis

  • Fragments

  • Few elliptocytes

What mutations can occur in HE?

• Alpha Spectrin (65% of cases)

• Beta Spectrin (30% of cases)

• Protein 4.1 (5% of cases)

• disruption of spectrin destabilizes the cytoskeleton

• horizontal defect

What clinical manifestations are associated with HE?

• most patients are asymptomatic

• mild compensated hemolysis

• MCV: norm/↑

• Reticulocytosis

• Elliptocytosis , not oval, like cigars

• norm/ ↑ osmotic fragility

Describe the Hereditary Pyropoikilocytosis variety of Hereditary Elliptocytosis.

• has extreme poikilocytosis

• many fragment RBC

• microspherocytes

• low fluorescence with eosin 5 ‘ maleimide

• MCV: 50-65 fL

• thermal sensitivity

  • RBC fragment 41 - 45C

What is used to treat HE?

Mild

• no therapeutic intervention

Severe (HPP)

• splenectomy

• RBC transfusions to treat anemia

What is Hereditary Hydrocytosis and Xerocytosis?

• rare, autosomal dominant

• defect in cation permeability of RBC

  • effects hydration

• H. hydrocytosis

  • Na+ leaks

  • RBC swollen

  • macrocytosis

  • decrease in protein stomatin

• H. xerocytosis

  • K+ leak

  • RBC dehydrated

What are clinical findings of H. hydrocytosis?

• mod-severe anemia

• jaundice

• splenomegaly

• iron overload

What are clinical findings of H. xerocytosis?

• mild-mod compensated anemia

• splenomegaly

• iron overload

What lab findings indicate H.hydrocytosis?

↓ MCHC

↑ ↑ MCV - macrocytes

stomatocytes

occasional spherocytes

What lab findings indicate H.xerocytosis?

↑ MCHC - dehydration

mild ↑ MCV

target cells

burr cells

puddled cells - hgb concentration in one part of cell

↓ osmotic fragility

What is used to treat H. hydrocytosis?

• Splenectomy

What is used to treat H. xerocytosis?

• none