Anemia due to Hemolysis II

Question 1

List some of the major foods, drugs, or other chemicals which can induce hemolytic anemia in patients with G6PD deficiency.

Answer 1

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Question 2

Describe the pathophysiology and site of RBC destruction of immune-mediated hemlysis

Answer 2

a. Antibodies to universal red cell antigens can cause hemolysis by either intravascular or extravascular destruction. Production of these antibodies can be in response to infection, can be associated with a malignancy or autoimmune disease, or can be drug-induced.
b. Cold antibodies (referring to a 4°C temperature for maximal in vitro effect), typically of the IgM class, transiently bind red cell membrane in cooler areas of the body (fingers, toes, ears, skin). As they move back to central circulation, they avidly activate complement through the C5-9 attack complex which creates holes in the membrane. When they move more centrally, the antibody dissociates itself because of low affinity at higher temperatures, and complement is left to destroy the cell (intravascular hemolysis).
c. Warm (maximal effect at 37°C) antibodies, usually IgG, bind the red cell with high affinity and have no or poor complement activating capacity, inciting the splenic macrophage to antibody-mediated phagocytosis through its Fc receptor.
d. Occasionally, the small amount of C3 also induces phagocytosis through complement receptors. Clearance by phagocytosis results in extravascular hemolysis

Question 3

Describe the direct antiglobulin test (DAT or direct Coombs)

Answer 3

used to detect IgG and/or complement on the surface of the cell. The direct antiglobulin test (DAT), also known as the direct Coombs test, evaluates the presence of either IgG or C3d or C4d on the surface of the red cell by the addition of Coombs reagent which has antibodies for IgG, C3d and C4d, causing agglutination

Question 4

Describe the the indirect antiglobulin test (IAT or indirect Coombs)

Answer 4

detects the ability of patient’s serum to bind IgG and/or complement to test (normal) red blood cells. By definition, autoimmune hemolytic anemia should have a positive DAT.

Question 5

Distinguish warm antibody-induced autoimmune hemolytic anemia (AIHA) from cold antibody-induced autoimmune hemolytic anemia (AIHA).

Answer 5

+ Patients with COLD AIHA have a positive DAT (complement only, no IgG), maximal reactivity at 4˚C and antigen specificity for I or i.
+ Patients with WARM AIHA exhibit a positive DAT (strong IgG +/- weak complement) with maximal reactivity at 4˚ C and panagglutin without antigen specificity.

Question 6

List and describe some of the indications of splenectomy.

Answer 6

The spleen is critical for clearance of intravascular microbes and in children, is critical to the development of the adaptive humoral response (and is the origin of IgM agglutinins, especially for encapsulated organisms).

Question 7

List and describe some of the risks of splenectomy.

Answer 7

Most significant complication of splenectomy is overwhelming bacterial sepsis, particularly associated with S. pneumoniae. The risk is greatest in children < 5 years of age.
In adults mortality from sepsis is 200 times that of the general population

Question 8

List and describe some of the benefits of splenectomy.

Answer 8

amelioration of symptoms associated with hemolytic anemia

Question 9

Explain when prophylactic antibiotics are indicated post-splenectomy and the role of vaccination.

Answer 9

• Pre-surgery vaccination protocol: to avoid complication of splenectomy, vaccination against H. influenza b, S. pneumoniae, and Meningococcus takes place before surgery.
• Prophylactic antibiotics: should be given daily atleast during childhood; and the instruction to see a physician immediately for a febrile illness > 38.5˚ C is imperative