Chapter 6-9: Hemolysis

TEXTBOOK PRESENTATION

A classic presentation of hemolytic anemia is a previously healthy patient presenting with relatively acute onset of mild jaundice associated with fatigue, exertional dyspnea, and dizziness, and a moderate to severe degree of anemia.

DISEASE HIGHLIGHTS

1. In macroangiopathic and microangiopathic hemolytic anemia and some complement-induced lysis, RBCs are destroyed in the intravascular space.

   1. Completely destroyed cells release free Hb into the plasma, which then binds to haptoglobin, reducing the plasma haptoglobin level.

   2. Some Hb is filtered by the glomerulus, causing hemoglobinuria, which darkens the urine.

   3. Some filtered Hb is taken up by renal tubular cells, stored as hemosiderin; hemosiderinuria occurs about a week later, when the tubular cells are sloughed into the urine.

   4. Damaged but incompletely hemolyzed cells are destroyed in the spleen.

2. Deformed RBCs and those coated with complement are usually destroyed in the extravascular space, in the liver or spleen.

   1. Most of the Hb is degraded into biliverdin, iron, and carbon monoxide.

   2. Biliverdin is converted to unconjugated bilirubin and released into the plasma, increasing the unconjugated bilirubin level.

   3. Some free Hb is released, which then binds to haptoglobin, again reducing the plasma haptoglobin level.

EVIDENCE-BASED DIAGNOSIS

1. The reticulocyte count is usually at least 4–5%; in 1 study of autoimmune hemolytic anemia, the median was 9%.

2. The serum haptoglobin should be < 25 mg/dL.

   1. Sensitivity = 83%, specificity = 96% for hemolysis; LR+ = 21, LR– = 0.18

   2. Haptoglobin is an acute phase reactant.

3. The LD is often increased.

   1. Finding an increased LD and a decreased haptoglobin is 90% specific for the diagnosis of hemolysis.

   2. Finding a normal LD and a normal serum haptoglobin (> 25 mg/dL) is 92% sensitive for the absence of hemolysis.

4. The unconjugated bilirubin may be increased.

5. Plasma and urine Hb should be elevated if the hemolysis is intravascular.

TREATMENT

Treatment depends on the underlying cause. In an autoimmune condition, immunosuppressive therapy, especially prednisone, is used. Rituximab and splenectomy are options in refractory cases. If hemolysis is associated with TTP and HUS, the treatment is plasmapheresis and immunosuppressive therapy.