Survival Disorders (Hemolytic Anemias)

What does the membrane do for RBCs?

maintains deformability and permeability

What is the RBC membrane made of?

50% protein, 40% phospholipid, 10% cholesterol

What is the mean volume of an RBC?

90 fL

Integral proteins

provide anion channels thru the membrane (Band3, glycophorins)

Peripheral proteins

provide the structural network on the inner surface (actin, spectrin, akyrin)

Senescence

the natural physical decline brought about by aging
- dec flexibility/inc rigidity
- splenic trapping

Extravascular hemolysis

90%, reticuloendothelial system (mostly spleen), Ab complexes or defects of cells

Intravascular hemolysis

10%, in the vessel, activated complement, trauma, or toxic substances

What is heme broken into?

Protoporphyrin (bilirubin) and iron

Where is the largest body pool of iron found?

in circulating RBCs and precursors in the bone marrow

Other than in the RBCs and precursors, where can the rest of stored iron be found?

in the splenic macrophage or the NRBCs as ferritin or hemosiderin

What does the globin portion of hemoglobin turn into when degraded?

amino acids (recycled into the protein pool)

In intravascular hemolysis, what does haptoglobin bind?

a1B1 hemoglobin dimers (prevents renal excretion of hgb, stabilizes heme-globin bond, moved to liver)

What happens if there is a sudden release of several grams of hgb?

exceeds/overwhelms the haptoglobin-binding capacity (acute renal failure bc hgb is filtered by glomerulus)

What are the lab findings for hemolysis?

- normocytic/chromic
- ellipto, acantho, sickle, sphere, schistocytes
- leukocytosis w/ left shift (more immature)
- INC serum bili
- DEC serum haptoglobin

What would the bone marrow look like in aplastic crisis?

pts present w/ reticulocytopenia and erythroid hypoplasia (dec in all cell lines)

Bone marrow in hemolytic crisis

pts present w/ reticulocytosis and erythroid hyperplasia

Hereditary spherocytosis

- autosomal dominant
- mutation in one or multiple structural proteins (a and B spectrin)
- 1:3500 whites (N europeans)

Hereditary spherocytosis lab findings

- spherocytes
- INC autohemolysis test
- INC osmotic fragility
- flow (most recent tech)

What conditions are common with HS?

splenomegaly, chronic refractory hemolytic anemia (corrected with splenectomy)

Hereditary elliptocytosis

- autosomal dominant
- spectrin a chain mutation
- 90% non-anemic
- splenomegaly, inc autohemolysis test

Hereditary Pyropoikilocytosis

- autosomal RECESSIVE
- severe hemolytic anemia
- African Americans
- Microcytosis, lots of fragments

What is hereditary pyropoikilocytosis a more severe version of?

Hereditary elliptocytosis (defective spectrin function)

Hereditary stomatocytosis

- mild hemolytic anemia
- deficiency of stomatin
- over-hydrated, inc cation flux
- less flexible, shorter lifespan

Spur cell hemolytic anemia

- chronic alcoholic cirrhosis
- fatal hemolytic anemia develops in 5-10% of cases (most don't make it this far)

What is the RBC survival in acanthocyte associated hemolytic anemia?

5-6 days

In what age group is PNH commonly seen? What is the prognosis?

age: 30-60
prognosis: 10-20 years

What is paroxysmal nocturnal hemoglobinuria?

- intrinsic defect (PIG-A mutation)
- deficiency of GPI-Aps preventing CD55 and 59 from binding RBC surface
- over sensitive to complement mediated lysis

What is the leading cause of death in PNH?

thrombosis

What percent of PNH cases are associated with nocturnal hemoglobinuria, aplastic anemia, and AML?

25% nocturnal hemoglobinuria
25% aplastic anemia
5-10% AML

PNH lab tests and results

autohemolysis test: increased
sucrose hemolysis: higher degree of hemolysis
Ham's test: darker serum when acidified

G6PD deficiency

- sex-linked, higher in African American/Mediterranean
- hemolytic episodes induced (fava, primaquine, infection)
- Heinz bodies

What tests can be used to find a G6PD deficiency?

fluorescent spot test: no fluorescence = deficiency
dye reduction test: dye stays blue = deficiency
ascorbate cyanide test: HGBM is oxidized more quickly

Pyruvate kinase deficiency

- autosomal recessive
- Embden-Meyerhof pathway produces ATP (needed for membrane stability)
- can't produce ATP

What would the fluorescent spot test look like for a pt with PK deficiency?

it would fluoresce

Methemoglobin reductase deficiency

- autosomal recessive
- can't reduce HGBM so conc. is increased
- HgbM can't carry O2

Hemolysis due to physical forces

lots of fragmentation, could be from severe burns

Cardiovascular disease and prosthetic heart valves causing hemolysis

- mechanical damage to RBC
- microangiopathic hemolytic anemia (TTP, DIC, HUS)
- poikilocytosis

What causes immune hemolytic anemia? what test would be positive?

- Immunoglobulin binds RBC and spleen removes it
- DAT would be positive

Autoimmune hemolytic anemia (AIHA)

- hemolysis is EXTRAvascular
- IgG: Warm usu. Rh antigens
- IgM: cold usu. big i-antigen

Isoimmune hemolytic anemia

- hemolysis is INTRAvascular
- HTR and HDFN
- foreign antigen exposure

What is a major cause of acute renal failure in children?

HUS caused by E. coli O157

How does anemia of blood loss progress?

Hypovolemia w/o signs of anemia > fluid pulled from tissues inc plasma volume > anemia signs bc cells have not been replaced

What are the lab findings for anemia of blood loss?

- brief thrombocytopenia
- moderate leukocytosis w/ left shift (more immature)
- H+H falls after volume is inc
- normocytic/chromic

Chronic posthemorrhagic anemia

- slow, sustained blood loss
- IDA develops
- retic count drops
- thrombocytosis