Hemolytic Anemias (RBC desturction)

What are hemolytic anemias? What RBC type will increase in PB? What does the lifespan of an RBC look like?

Anemias caused by increased RBC destruction → causes BM to accelerate production (retics will increase in PB)

RBC production is normal with very short lifespan → anemia develops b/c destruction is faster than RBC proliferation

What do RBCs usually look like in hemolytic anemias? What is the process called for premature RBC destruction?

RBCs will be normocytic, normochromic

• hemolysis

What 3 things classify the type of hemolytic anemia?

• Defect source: intrinsic or extrinsic to RBC

• Mode of onset (cause): inherited or acquired

• Location of hemolysis: intravascular or extravascular

Where does extravascular hemolysis occur? What will RBCs look like in PB?

RBCs are destroyed outside blood vessels (ex. in spleen, liver, BM) → macros in spleen & liver phagocytose RBCs

RBCs: spherocytes

Where does intravascular hemolysis occur? What will RBCs look like?

Defective RBCs destroyed as they circulate → lyse in circulation

RBCs: fragmented RBCs → schistocytes

What is the pathway of normal RBC destruction (catabolism) - due to RBC old-age?

Hemolgobin degraded (globin is returned to AA pool, iron separated & stored

What hemolysis is more common? Intravascular or extravascular? What is the pathway of extravascular RBC destruction?

What increases in extravascular hemolysis and where? What is NOT present in extravascular hemolysis?

Increased:

• unconjugated bilirubin in serum

• urobilinogen in urine and stool

Not present:

• No hemoglobinuria, hemosiderinuira, free Hgb

What happens to an intravascularly hemolyzed RBC? What happens if there is excess Hgb present in kidneys? What will appear in urine if the kidney successfully absorbed a lot of Hgb?

On death RBC releases free Hgb into plasma → Hgb binds to haptoglobin (plasma protein) → free Hgb removed by liver, some into kidneys → reabsorbed by kidney

• IF excess free Hgb in kidney, hemoglobinuria (will appear in urine)

• Hemosiderinuria: iron is converted to hemosiderin in kidney & excreted in urine

What increases in intravascular hemolysis? What else is present in the body due to intravascular hemolysis?

Increased

• unconjugated bilirubin

Present:

• Free Hgb in plasma

• Hemoglobinuria

• Hemosiderinuria

What is the normal Hgb concentration in plasma? What is the name of the anemia caused by excess free Hgb bound to haptoglobin?

Normal Hbg in plasma: 5mg/dL

Excess Hgb in plasma w/ haptoglobin: hemoglobinemia

What two types of hemolytic anemias are there? Where does the anemia occur in the RBC (intrinsic or extrinsic)? What are their subtypes?

• Hereditary hemolytic anemias → intrinsic & extravascular hemolysis

  • Membrane defects

  • Enzyme defects

• Acquired hemolytic anemias → extrinsic & extravas. or intravasc. hemolysis

  • Non-immune

  • immune

  • membrane defects

In general, what are signs of hemolytic anemia? What will the RBCs look like?

Signs:

• Jaundice (yellowing skin & eyes due to bilirubin)

  • Elevated unconjugated (indirect) bilirubin

• Gallstones (made of bilirubin)

• Dark/red urine due to plasma Hgb excretion

• Splenomegaly

• Reticulocytosis (more retics in PB)

RBCs: Normochromic, normocytic anemia

• Schistocytes (intravascular hemolysis) or spherocytes (extravascular hemolysis)

Hereditary anemias happen intrinsically. What does this mean? What kind of hemolysis do the RBCs undergo?

Intrinsic: defects within an RBC (abnormality within an RBC themself)

• Undergo extravascular hemolysis

Acquired anemias happen extrinsically. What does this mean? What kind of hemolysis do RBCs undergo?

Extrinsic: defects caused by external agents (ex. something causes injury to RBC)

• Undergoes extravascular or intravascular hemolysis

Hereditary hemolytic anemias occur intrinsically. They often undergo extravascular hemolysis. What are the 2 types of membrane defects that can occur on an RBC? What are the 2 enzyme defects? The 2 globin defects?

Membrane defects:

1. Hereditary spherocytosis

2. Hereditary elliptocytosis

Enzyme defects:

1. G6PD deficiency

2. Pyruvate Kinase deficiency

Globin defects:

1. Hemoglobinopathies

2. Thalassemias

One of the hereditary anemia defects is the membrane defect: Hereditary spherocytosis (HS).

What causes this defect and what does it result in the loss of?

What clears these cells from the body?

How does this lead to anemia (pathogenesis)?

What are the symptoms of hereditary spherocytosis (HS) anemia? How will RBCs appear and how does it effect MCHC & retics?

What is the confirmatory test for hereditary spherocytosis (HS) anemia and how does it work? What is the treatment for this anemia and how does it effect the RBCs after?

One of the hereditary anemia defects is the membrane defect: Hereditary elliptocytosis (HE).

What causes this defect and what does it cause RBCs to look like?

What percent of patients have this but don’t suffer from anemia?

What is the treatment of this anemia?

One of the hereditary anemia defects is an enzyme defect: Glucose-6-phosphate dihydrogen deficiency (G6PD). How is it inherited and what gender is effected? Where does this deficiency occur most often in the world (3 places)?

What causes a deficiency in G6PD? How do these exposures lead to anemia?

One of the hereditary anemia defects is an enzyme defect: Glucose-6-phosphate dihydrogen deficiency (G6PD). What does this enzyme do? What leads to this anemia (pathogenesis)? How are RBCs removed or “fixed” and what does it cause the RBCs to look like?

Although the hereditary enzyme defect anemia: G6PD is usually intravascular hemolysis, it can also become extravascular hemolysis. Explain how both of these hemolysis occur.

What test(s) or RBC appearance is checked to identify hereditary enzyme G6PD deficiency? What is the treatment for G6PD anemia?

Another hereditary enzyme defect anemia is by deficiency of: Pyruvate Kinase (PK).