AIHA Flashcards
Exam 4
What is an autoimmune hemolytic anemia?
Shortened RBC survival mediated through the immune response where antibodies are produced against self RBC antigens.
What are the frequencies of warm autoantibodies vs. cold autoantibodies?
Warm autoantibodies (70%), Cold autoantibodies (18%)
What lab results would you expect to see for a patient with autoantibodies?
Positive DAT, positive autocontrol, all panel cells reactive
Does a positive DAT always result in hemolytic anemia?
No, some positive DATs have no evidence of hemolytic anemia
Describe the difference between a compensated and uncompensated anemia.
Destruction of red cells is equal to the production of red cells in compensated anemia. In uncompensated anemia, destruction of red cells is greater than production of red cells. Macrocytosis, spherocytosis, increased reticulocytes, increased unconjugated bilirubin, and increased LDH are also seen.
List reasons why some individuals may be affected by autoantibodies and others are not.
Thermal amplitude of antibody reactivity, IgG subclass, ability of antibody to fix complement, activity of individual’s macrophages, difference in RBC structure
What is the most common cold autoantibody specificity?
Autoanti-I
What is the biggest problem with benign cold autoantibodies?
Interfere with testing masking significant alloantibodies
In what individuals will an anti-IH most commonly be found?
A1 and A1B individuals because they have the least amount of H
What are the common presentations of Cold Hemagglutinin Disease (CHD)?
Individuals >50 years of age, usually anti-I specificity, lower the temp the stronger the antibody reactivity, seasonal (more symptoms in winter months), acrocyanosis, numbness of extremities, hemoglobinuria, weakness, pallor, weight loss, jaundice, Raynaud’s disease.
What are the common lab findings for Cold Hemagglutinin Disease?
Reticulocytosis, positive DAT due to complement only, autoagglutination of anti-coagulated whole blood samples
What is secondary cold autoimmune hemolytic anemia?
Cold autoimmune hemolytic anemia that occurs secondary to another illness. Usually caused by infection of Mycoplasma pneumonia (anti-I) and infectious mono (anti-i).
What is the presentation of Paroxysmal Cold Hemoglobinuria (PCH)?
Usually in children with viral illnesses, biphasic autohemolysin that fixes complement and low temperatures and hemolyzes at warmer temperatures, anti-P specificity, episodes occur on exposure to cold, sudden onset fever, shaking/chills, abdominal cramps, back pain, hemoglobinemia, hemoglobinuria, bilirubinemia, severe and rapidly progressing anemia.
Describe the basic steps and results of the Donath Landsteiner Test.
Patient serum is incubated with P positive red cells and complement. One tube is incubated at 4C, then 37C. The other only at 37C. The set incubated at cold then warm showing hemolysis, while the 37C only tube showing no hemolysis is a positive result.
What are diseases that are associated with warm autoimmune hemolytic anemia (WAIHA)?
Lymphoma/leukemia, collagen disease (lupus/rheumatoid arthritis), infectious disease (viral), immunologic disease, gastrointestinal disease (ulcerative colitis), carcinoma, pregnancy, chronic renal failure, trauma/surgery
What are symptoms of WAIHA?
Pallor, weakness, dizziness, dyspnea, jaundice, unexplained fever, anemia
What are the lab findings of WAIHA?
Positive DAT, blood smear with polychromasia, macrocytosis, reticulocytosis, reticulocytopenia, increased bilirubin and urobilinogen, hemoglobinemia, hemoglobinuria, increased LDH
What is the strength of the DAT reactions correlated with?
Correlates with the presence of multiple IgG subclasses. Multiple IgG subclasses correlates with the severity of hemolysis.
How are corticosteroids used to treat WAIHA?
They reduce antibody synthesis, alter antibody activity, and alter macrophage receptors for IgG and C3 to reduce the clearance of RBCs.
How will a splenectomy treat WAIHA?
Removes a potent site of RBC damage and destruction and decreases production of antibody.
How will immunosuppressive drugs treat WAIHA?
This is a last approach that interferes with antibody synthesis by destroying dividing cells
What is the first treatment considered for patients with symptomatic WAIHA?
Corticosteroids
What blood bank testing can autoantibodies interfere with?
ABORh, antibody screen, crossmatch
How can cold autoantibodies interfere with a blood type and how can this be resolved?
In the front type, the patient RBCs can become heavily coated with cold agglutinin and will agglutinate with reagents regardless of their type. This can be resolved by washing the patient red cells with warm saline to disassociate the cold agglutinins and then repeat testing. In the back type, the cold agglutinins in the serum will react with the reagent A and B cells. To resolve this, perform the prewarming technique (or settled reading) on the back type.
How can autoantibodies interfere with antibody screens and what methods are used to resolve this?
The autoantibody in the serum reacts with the reagent red cells causing agglutination which can mask clnically significant alloantibodies. Methods to resolve a cold autoantibody include prewarm, cold autoadsorption, and cold alloadsorption. Methods to resolve a warm autoantibody include warm autoadsorption and warm alloadsorption (triple adsorption).
Describe the process of an autoadsorption.
The patient’s red cells are treated to remove any autoantibody already coating the red cell. Patient plasma is then mixed with the patient treated red cells and incubated at warm or cold temperatures depending on the antibody. The plasma is then separated from the red cells. This is repeated until all of the autoantibody is removed by being adsorbed onto the patient’s red cells.
Describe the process of an alloadsorption and how this might differ from autoadsorptions.
Reagent red cells are used with known antigens. Patient plasma is then added to all of these tubes to adsorb out the autoantibody as well as some alloantibodies depending on the reagent red cells in the tube. The plasma is then removed. This process is repeated 2-3 times to remove all autoantibody. The major difference is that reagent red cells are used instead of the patient’s red cells.
How might cold autoantibodies interfere with compatibility testing (crossmatches) and how can this be resolved?
They will interfere at immediate spin readings at possibly IgG if the antibody is strong enough. The solution is to perform a prewarmed crossmatch.
How can warm autoantibodies interfere with compatibility testing (crossmatches) and how can this be resolved?
They will interfere at AHG testing as well as 37 sometimes. This reactivity will remain no matter what is done. The least incompatible unit should be given to the patient.
How does the drug adsorption (hapten) mechanism for drug-induced immune hemolytic anemia work?
The drug binds to proteins on the red cell membrane. An antibody is then formed to the drug coating the red cell.
How does the drug-dependent or immune complex mechanism work?
IgM antibodies will bind with the drug forming a complex. The complex loosely attaches to the red cell membrane which initiates the complement cascade.
How does the membrane modification mechanism work?
The drug modifies the red cell membrane so plasma proteins (immunoglobulins and complement) can bind to the membrane.
How does the autoantibody formation mechanism for drug-induced immune hemolytic anemia work?
The drug induces production of an autoantibody which recognizes red cell antigens.
What type of drugs may cause drug-induced hemolytic anemia due to drug adsorption?
penicillin, cephalosporin
What type of drugs may cause drug-induced hemolytic anemia due to immune complex formation?
Quinidine, Phenacetin
What type of drugs may cause drug-induced hemolytic anemia due to membrane modification?
Cephalosporin
What type of drugs may cause drug-induced hemolytic anemia due to the production of an autoantibody?
Methyldopa (Aldomet)
Which drug-induced mechanisms are caused by IgG antibodies?
Drug adsorption and methyldopa induced
Which drug-induced mechanisms are caused by plasma proteins?
Membrane modifications
Which drug-induced mechanisms are caused by mainly IgM antibodies?
Immune complex
Describe how the DAT and eluate results will differ between each type of drug-induced hemolytic anemia mechanism.
The DAT is positive for all of them, but often only with C3 for the immune complex. The eluate is negative for all mechanisms except the methyldopa induced mechanism.
At what age is Cold Hemagglutinin Disease usually seen?
> 50 years old
What antibody specificity is associated with Cold Hemagglutinin Disease?
usually anti-I specificity, lower the temp the stronger the antibody reactivity
At what age is PCH usually seen?
Usually in children following viral illnesses
What antibody specificity is associated with PCH?
Anti-P
Is Cold Hemagglutinin Disease due to an IgM or IgG antibody?
IgM
Is PCH due to an IgM or IgG antibody?
IgG - biphasic hemolysin
