(2) Path - EB Viral Infections and Autoimmune Hemolytic Anemia

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What virus causes infectious mononucleosis?

Epstein-Barr virus (Herpesvirus 4)

The mechanism of action of EBV in infectious mononucleosis is to attach to what kind of complement receptors on B lymphoctyes?

C3d complement receptors

In infectious mononucleosis, EBV enters a B lymphocyte and induces the formation of several new antigens. These antigens evoke what kind of response by the body's immune system?

T-killer lymphocyte response (activated to destroy
infected B cells).

Fever, sore throat (that doesn't get better with antibiotics) and enlarged cervical lymph nodes (often posterior), tenderness over the liver, splenomegaly, and fatigue are all symptoms of what disease?

Infectious mononucleosis

In this disease, there are increased circulating lymphocytes (often between 60-90% of the total white cells) of which greater than 10% are atypical (transformed) lymphocytes (T-killer).

Infectious mononucleosis

This disease will give a positive monospot test.

Infectious mononucleosis

How does it take to recover from infectious mononucleosis?

3-4 weeks

Which are more common: warm or cold autoimmune hemolytic anemias?

Warm autoimmune hemolytic anemias

At what temperature are antibodies maximally active in warm autoimmune hemolytic anemia?

37 degrees C

In 90% of cases, what type of antibodies are involved in warm autoimmune hemolytic anemia?

IgG

In this disease, IgG-coated red cells are bound to Fc receptors on monocytes and splenic macrophages and undergo spheroidal transformation (i.e. the macrophages phagocytize fragments of the antibody coated membrane, thereby reducing the size of the cell surface and causing spherocytosis.) This leads to erythrocyte entrapment and eventual destruction in the spleen. Splenomegaly is therefore present in 50%. If the red cells are heavily coated with antibodies, the liver also participates in the destruction.

Warm autoimmune hemolytic anemia

Which type of autoimmune hemolytic anemia causes extravascular hemolysis?

Warm autoimmune hemolytic anemia

This type of autoimmune hemolytic anemia is characterized by weakness, fever, dizziness, jaundice, and anemia.

Warm autoimmune hemolytic anemia

This type of autoimmune hemolytic anemia responds to steroid treatment.

Warm autoimmune hemolytic anemia

This type of autoimmune hemolytic anemia is resistant to steroid treatment.

Cold Hemagglutinin Disease

At what temperature are antibodies maximally active in cold autoimmune hemolytic anemia?

4 degrees C

What kind of activity do the antibodies in cold autoimmune hemolytic anemia display at 37 degrees C?

Little to no reactivity

What type of antibodies are involved in cold autoimmune hemolytic anemia?

IgM

Which type of autoimmune hemolytic anemia binds complement and causes intravascular hemolysis?

Cold Hemagglutinin Disease

Some classic causes of this type of autoimmune hemolytic anemia include microplasma pneumonia, infectious mononucleosis, lymphocytic leukemia, and lymphoma.

Cold Hemagglutinin Disease

Treatment for this form of autoimmune hemolytic anemia includes transfusions with washed red cells to decrease complement.

Cold Hemagglutinin Disease

This form of autoimmune hemolytic anemia exhibits IgG complement-fixing antibody with anti-P specificity.

Paroxysmal Cold Hemoglobinuria

Which gender is affected more by warm autoimmune hemolytic anemia?

Females, age >40

Acute, intermittent, massive hemolysis after exposure to cold is seen in this form of autoimmune hemolytic anemia. It often follows a viral disease (measles, mumps). May be associated with syphilis.

Paroxysmal Cold Hemoglobinuria

Which gender is affected more by warm cold hemagglutinin disease?

Females, age >50

Which gender is affected more by warm Paroxysmal Cold Hemoglobinuria?

Both males and females equally

A biphasic mode of action is seen in this autoimmune hemolytic anemia. The antibody attaches to red blood cells at low temperature. When temperature rises, the hemolytic action is mediated by the complement sequence.

Paroxysmal Cold Hemoglobinuria

These are drugs that bind firmly to the red cell membrane. These drugs, which are usually of a small molecular weight, join plasma proteins and attach to rbcs...then become immunogenic. Antibodies are then produced which are directed against the red cell-drug complexes.

Penicillin, cephalosporins

What type of antibodies are involved hemolytic anemias that are caused by drugs that bind tightly to the red cell membrane?

IgG

What kind of antibody causes largely extravascular hemolysis by macrophages in the spleen?

IgG

What type of hemolysis is seen in hemolytic anemias that are caused by drugs that bind tightly to the red cell membrane?

Extravascular hemolysis by macrophages in the spleen

These drugs bind to plasma proteins and the drug-protein complex evokes antibodies. Once on the red cells, the complex promotes complement fixation and hemolysis.

Quinine, Quinidine, and Phenacetin

What type of antibodies are involved hemolytic anemias that are caused by drugs that form immune 'ternary'complexes?

IgM

What kind of antibody causes intravascular hemolysis?

IgM

What type of hemolysis is seen in hemolytic anemias that are caused by drugs that form immune 'ternary'complexes?

Intravascular hemolysis

This drug alters the red cell membrane by an unknown mechanism that enables antibodies to react with red blood cells even when the drug is no longer present. (Autoantibody model)

Aldomet (methyldopa)

What type of antibodies are involved in the autoantibody model of drug induced hemolysis?

IgG

What percentage of those with the autoantibody model of drug induced hemolysis develop clinically significant hemolysis?

1%

Hyperventilation, tachycardia, urticaria, flushing, and deep back pain are common symptoms of what?

Red blood cell incompatibility reaction

What type of hemoysis is seen in an ABO transfusion reaction?

Intravascular hemolysis

What type of hemoysis is seen in an Rh incompatibility?

Extravascular hemolysis

What is the most commonly occuring type of hemolytic disease of the newborn?

ABO incompatibility (20-25%)

Why is the immune reaction is much less severe than expected in hemolytic disease of the newborn due to ABO incompatibility?

1. Most antibodies produced against A and B cell antigens are IgM and can't cross the placenta.
2. A and B antigens are not fully developed on fetal red cells.
3. A and B antigens are not confined to red cells alone but are present on other cells

Which is more serious: hemolytic disease of the newborn caused by ABO incompatibility or Rh incompatibility?

Rh incompatibility

In which type of hemolytic disease of the newborn is the firstborn child more likely to be affected?

ABO incompatibility

In Rh incompatible hemolytic disease of the newborn, how much fetal blood is needed to initiate maternal antibody formation?

1 cc

In Rh incompatible hemolytic disease of the newborn, does the baby show a positive direct or indirect Coombs test?

Positive direct Coombs test

In Rh incompatible hemolytic disease of the newborn, does the mother show a positive direct or indirect Coombs test?

Positive indirect Coombs test

The best preventive treatment for Rh- mothers with Rh+ fetuses is to give anti-D immunoglobulin (Rhogam) within how many hours of delivery to prevent sensitization?

72 hours

Rhogam prophylaxis is recommended at how many weeks gestation for Rh(-) mothers whose spouse is Rh(+)?

28 weeks

Infants with a bilirubin greater than this should receive exchange transfusion for the infant with blood compatible with the mother's serum (usually O negative).

7

What type of antibodies cause hemolytic disease of the newborn?

IgG (crosses placenta)

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