Humoral Immune Mediated Hemolysis, Blood Banking, Transfusions Flashcards
What are isoagglutinins?
Expected immunoglobulins that circulate in our blood
Do not cause disease normally
What are alloantibodies?
Antibodies made against one’s own species with different genetics
What are autoantibodies?
Antibodies made against your own tissues
What is the A antigen on RBC cell membranes?
N-acetylgalactosamine
What is the B antigen on RBC cell membranes?
D-galactose
What blood type is the universal donor? Why?
O Type.
Has no A or B antigen on RBC cell surface
What blood type is the universal recipient? Why?
AB Type.
Has no isoagglutinin against either A or B antigen.
What is the most common procedure performed on hospitalized patients?
Blood transfusion
What are two most common places for mistakes in blood transfusion?
Specimen ID
Patient ID
What is “forward” blood typing? What reagents would you use for it?
Used to determine ABO and D blood type of individual.
Take the patient’s RBCs and coat with anti-A, anti-B, and anti-D
What is “reverse” blood typing? What reagents would you use for it?
Used to determine what isoagglutinins are present in a patient’s serum
Use stock Type A and stock Type B RBCs to test for isoagglutinins in patient serum
What is the Antibody Screen test?
Screening for antibodies in patient serum that are against other common antigens (Not ABO type).
Mix patient serum with these RBCs and perform an IAT to see if they have antibodies
Once the patient serum and stock RBCs have been mixed, what do you add to induce agglutination if antibodies have bound antigen?
Anti-human globulin
Antibody made by a non-human animal against human Ig and/or complement proteins
What is sensitization?
When the first antibody has bound an antigen on the cell surface of the RBC
Does not cause agglutination
Describe the indirect agglutination test (IAT)
In vitro test = Antibody Screen
Given a stock of RBCs, add the patient’s serum and let any antibodies bind to RBC membrane. Then add anti-human globulin and see if agglutination occurs. This will tell you whether the patient has any alloantibodies against your sample of RBCs
What are the required pretransfusion compatibility testings?
Typing (ABO and Rh)
Screening (testing for clinically significant antibodies)
What is a Type and Crossmatch?
Type/Screen (ABO, Rh, and antibody screening)
Crossmatch (mix patient serum with donor RBCs to see if agglutination occurs)
When would you order a Type and Screen?
When the need for transfusion is remote (5% or lower)
Asymptomatic with chronic anemia
Surgical pts with low risk of bleeding
Prior positive antibody screens
When would you order a Type and Crossmatch?
High likelihood that RBC transfusion will be required
Actively bleeding patients
Surgical pts with high risk of bleeding
How do you perform a Direct Agglutination test (DAT)?
In vivo test
Add anti-human globulin to the patient’s RBCs (that you suspect may be sensitized already)
Positive DATs are always abnormal
What are methods of avoiding Acute Hemolysis from pre-formed IgM?
ID (Specimen and Patient)
Blood typing
Antibody Screen
Crossmatching
Describe the pathogenesis of Acute Immune Mediated Hemolysis.
IgMs in serum activate complement and cause intravascular hemolysis.
Free hemoglobin will be released into circulation and bind to haptoglobin.
Occurs rapidly
List symptoms of Acute Immune Mediated Hemolysis.
Fever Constriction of chest Lumbar pain Hemoglobinuria Hemolysis Hypoalbuminemia Hypotension Bleeding Renal failure
Why is a secondary immune response of greater magnitude and speed than the primary response?
Plasma cells and memory B cells already exist and will be able to respond more quickly
How are patients commonly exposed to RBC antigens they lack?
Pregnancy
Transfusions
Transplants
List some common Lab Results you will see when you suspect Hemolysis
Falling hemoglobin and hematocrit Low haptoglobin DAT Positive Elevated LDH Peripheral blood smear findings (spherocytes, polychromasia)
What are unexpected alloantibodies?
IgG antibodies that are made by patients who lack the corresponding antigen.
They are stimulated upon exposure to RBCs from other humans
Describe the kinetics and pathogenesis of Unexpected Alloantibodies (Delayed immune mediated hemolysis)
Slow kinetics (10-14 days)
Most do NOT bind complement
Associated with extravascular hemolysis
How would you test for Unexpected Alloantibodies
Detected using the antibody screen
Could cause crossmatching incompatibility
DAT will be positive as long as the sensitized cells are in circulation
When you have a patient with an Unexpected Alloantibody reaction in their history, how will you need to address in future transfusions?
In any future transfusions., you must provide RBCs negative for that antigen
What is the general cause of HDN?
Usually due to unexpected alloantibodies (IgG) made by the mother against the fetus,
How is the maternal immune system able to respond to the fetus?
Mom should become immunomodulated to the fetus. The placenta is an incomplete barrier between mother and child and there is bilateral transfer of maternal and fetal cells
What is the D antigen? How is it important in HDN?
D antigen = Rh antigen
When mom is Rh- and dad is Rh+, the mother may become alloimmunized for the D antigen in the first pregnancy, which could cause HDN in the second pregnancy
When is the highest risk for D-alloimmunization in pregnancy?
3rd trimester and at delivery
Who will have a positive DAT in HDN?
The fetus! The positive DAT tells you that the fetal RBCs have been sensitized by IgG made by mother
Clinical Abnormalities and Symptoms of HDN in utero
Positive DAT for fetus Shortened RBC survival in fetus Hypoalbuminemia Hypocoagulability Hepatosplenomegaly Anasarca (whole body edema)
Clinical Abnormalities and Symptoms of HDN Postpartum
Jaundice
Severe hyperbilirubinemia
High risk of kernicterus
Neurological damage
What kind of hemolysis occurs in HDN?
Extravascular hemolysis (of the fetal sensitized RBCs)
What is kernicterus?
Severe hyperbilirubinemia can cause neuronal damage.
Can lead to visual/auditory problems, cerebral palsy-like effects.
Get yellow stain to the deep white matter of the brain
Who is more likely to get ABO-HDN? Why?
Group O mothers are more likely to get ABO HDN because they have preformed anti-A, anti-B, and anti-AB in circulation
How can we prevent HDN?
Prophylaxis is only available for the Rh “D” Antigen.
We can give protein concentrate of Anti-D prepared from serum pools of previously sensitized females. Given to the mothers postpartum after first delivery
Nobody knows why this works
What will be found in amniotic fluid if the fetus is undergoing hemolysis? How can this be measured?
Bilirubin
Use Liley graph for optical density measurement
How can fetal hematocrit be assessed in a non-invasive way?
Fetal ultrasound to assess speed of blood flow in the baby’s cerebrum
Slower speed = Higher hematocrit
If a baby is very jaundiced and hyperbilirubinemic at birth, what is the first line therapy? Second line?
Phototherapy with UV light to solubilize unconjugated bilirubin. The baby will then urinate out water soluble bilirubin
If phototherapy doesn’t work, try an exchange transfusion through the umbilical vein
What are the two categories of unexpected autoantibodies?
Warm autoimmune hemolytic anemia
Cold agglutinins
What are the common etiologies of unexpected autoantibodies?
Idiopathic
SLE
Chronic Lymphocytic Leukemia
Describe Warm Autoimmune Hemolytic Anemias
Ag-AB rxns take place near body temp
Typically IgG
Cause extravascular clearance of RBCs
Symptoms of Warm Autoimmune Hemolytic Anemias
Fatigue, pallor, exercise intolerance, weakness
Lab features of Warm Autoimmune Hemolytic Anemias
Positive DAT
Positive IAT
Microspherocytes seen on blood smear
Hyperbilirubinemia
Low haptoglobin
What are the best treatments for Warm Autoimmune Hemolytic Anemias?
Corticosteroids
Iv gammaglobulin
Splenectomy
Describe the clinical features of Cold Agglutinin Disease
Moderately severe anemia
Acrocyanosis precipitated by cold exposure
Lab Features of Cold Agglutinin Disease
Ag-Ab rxns take place only at 25 celsius or lower
Positive DAT due to anti-complement only (Typically, the IgM molecule falls off)
Spherocytes and polychromasia on blood smear
Hyperbilirubinemia
Treatments for Cold Agglutinin Disease
Supportive care (RBC transfusions) Keep the patient warm
What is the pathogenesis of Drug Induced Hemolytic Anemias?
Drugs bind to RBC membrane and make it appear to be a neo-antigen
Positive DAT is seen
How would you treat Drug Induced Hemolytic Anemias?
Stop taking the drug!
