CH 17 Hemolytic Anemia - Membrane Defects

What are the 3 hereditary defects of RBC membrane involving protein defects?

Hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis

What are the 2 hereditary defects of RBC membrane involving lipid bilayer composition?

Hereditary stomatocytosis (overhydrated/dehydrated), Acanthocytosis

What is the primary pathophysiology of hereditary spherocytosis?

Protein defect → deformability problems → decrease SA/volume ratio → spherocytes → extravascular hemolysis

What is the classic triad of hereditary spheroytosis?

jaundice, splenomegaly, bile stones

What is the primary screening test for hereditary spherocytosis? Describe how the test works.

Osmotic fragility test: Measures RBC resistance to osmotic stress

RBC’s incubated in varying [ ] of NaCl @37C for 24 hours. Spherocytes cannot expand as normal RBCs do

What results of the osmotic fragility test give a positive for hereditary spherocytosis?

Increased [ ] of NaCl causes lysing

What are the 2 other tests used to measure/determine hereditary spherocytosis?

Autohemolysis test: measures degree of spontaneous hemolysis

DAT: used to differentiate immune HA for HS (- DAT)

What is the protein that is deficient/defective in hereditary spherocytosis?

Eosin-5-maleimide (EMA)

What are the 3 distinct classifications of hereditary elliptocytosis?

Common: biconcave elliptocytes

Spherocytic: hemolytic ovalocytes

Southeast Asian Ovalocytosis: SAO

What are the 2 pathophysiological effects of hereditary elliptocytosis?

RBC’s abnormally permeable to cations

Elliptocytosis w/ membrane fragmentation

What is the distinct etiology of hereditary pyro-poikilocytosis? What does it cause?

Disintegrates when incubated @37C for >6 hours

severe anemia and extreme poikilocytosis

What is the pathophysiology of hereditary pyro-poikilocytosis?

deficiency or mutation of spectrin (2 defects, 1 from each parent)

What is hereditary stomatocytosis characterized by?

alteration of membrane permeability to cations

What is the pathophysiology of over-hydrated hereditary stomatocytosis?

deficiency of stomatin → abnormally permeable to Na+ and K+ → water entering the cells

What is the pathophysiology of dehydrated hereditary stomatocytosis?

net loss of K+ → dehydrated cells

What are the following lab findings of OHS vs DHS?

1. MCHC and MCV

2. osmotic fragility

1. Decreased MCHC vs Increased MCHC. Increased MCV vs. slightly increased MCV

2. Increased osmotic fragility vs decreased osmotic fragility

What is the pathophysiology of hereditary acanthocytosis (abetalipoproteinemia)?

Absence of serum B-lipoprotein → decreased cholesterol, triglyceride, phospholipid → decreased membrane fluidity

What differentiates acanthocytes from spherocytes or stomatocytes?

They have normal osmotic fragility

What is acquired spur cell anemia associated with?

severe hepatocellular disease

What is Paroxysmal Nocturnal Hemoglobinuria (PNH)? What are the 2 possible etiologies of PNH?

acquired stem cell disorder of RBC membrane

1. Abnormal clone of differentiated hematopoietic cells

2. Uncontrolled complement activation (CD55,CD59)

What are the 2 primary clinical presentations of PNH?

Acute intravascular hemolysis associated with sleep

venous thrombosis → common cause of death

What are the 3 lab tests to screen/determine PNH?

AHG DAT: - for IgG but + for complement

Sucrose hemolysis test: sucrose promotes complement binding to RBCs → hemolysis

Ham test: RBC’s incubated in acidified serum → complement lyses PNH cells