Humoral Immune Mediated Hemolysis, Blood Banking, Transfusions

Question 1

What are isoagglutinins?

Answer 1

Expected immunoglobulins that circulate in our blood

Do not cause disease normally

Question 2

What are alloantibodies?

Answer 2

Antibodies made against one’s own species with different genetics

Question 3

What are autoantibodies?

Answer 3

Antibodies made against your own tissues

Question 4

What is the A antigen on RBC cell membranes?

Answer 4

N-acetylgalactosamine

Question 5

What is the B antigen on RBC cell membranes?

Answer 5

D-galactose

Question 6

What blood type is the universal donor? Why?

Answer 6

O Type.

Has no A or B antigen on RBC cell surface

Question 7

What blood type is the universal recipient? Why?

Answer 7

AB Type.

Has no isoagglutinin against either A or B antigen.

Question 8

What is the most common procedure performed on hospitalized patients?

Answer 8

Blood transfusion

Question 9

What are two most common places for mistakes in blood transfusion?

Answer 9

Specimen ID

Patient ID

Question 10

What is “forward” blood typing? What reagents would you use for it?

Answer 10

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

Question 11

What is “reverse” blood typing? What reagents would you use for it?

Answer 11

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

Question 12

What is the Antibody Screen test?

Answer 12

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

Question 13

Once the patient serum and stock RBCs have been mixed, what do you add to induce agglutination if antibodies have bound antigen?

Answer 13

Anti-human globulin

Antibody made by a non-human animal against human Ig and/or complement proteins

Question 14

What is sensitization?

Answer 14

When the first antibody has bound an antigen on the cell surface of the RBC

Does not cause agglutination

Question 15

Describe the indirect agglutination test (IAT)

Answer 15

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

Question 16

What are the required pretransfusion compatibility testings?

Answer 16

Typing (ABO and Rh)

Screening (testing for clinically significant antibodies)

Question 17

What is a Type and Crossmatch?

Answer 17

Type/Screen (ABO, Rh, and antibody screening)

Crossmatch (mix patient serum with donor RBCs to see if agglutination occurs)

Question 18

When would you order a Type and Screen?

Answer 18

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

Question 19

When would you order a Type and Crossmatch?

Answer 19

High likelihood that RBC transfusion will be required

Actively bleeding patients
Surgical pts with high risk of bleeding

Question 20

How do you perform a Direct Agglutination test (DAT)?

Answer 20

In vivo test
Add anti-human globulin to the patient’s RBCs (that you suspect may be sensitized already)

Positive DATs are always abnormal

Question 21

What are methods of avoiding Acute Hemolysis from pre-formed IgM?

Answer 21

ID (Specimen and Patient)
Blood typing
Antibody Screen
Crossmatching

Question 22

Describe the pathogenesis of Acute Immune Mediated Hemolysis.

Answer 22

IgMs in serum activate complement and cause intravascular hemolysis.
Free hemoglobin will be released into circulation and bind to haptoglobin.

Occurs rapidly

Question 23

List symptoms of Acute Immune Mediated Hemolysis.

Answer 23

Fever
Constriction of chest
Lumbar pain
Hemoglobinuria
Hemolysis
Hypoalbuminemia
Hypotension
Bleeding
Renal failure

Question 24

Why is a secondary immune response of greater magnitude and speed than the primary response?

Answer 24

Plasma cells and memory B cells already exist and will be able to respond more quickly

Question 25

How are patients commonly exposed to RBC antigens they lack?

Answer 25

Pregnancy Transfusions Transplants

Question 26

List some common Lab Results you will see when you suspect Hemolysis

Answer 26

``` Falling hemoglobin and hematocrit Low haptoglobin DAT Positive Elevated LDH Peripheral blood smear findings (spherocytes, polychromasia) ```

Question 27

What are unexpected alloantibodies?

Answer 27

IgG antibodies that are made by patients who lack the corresponding antigen. They are stimulated upon exposure to RBCs from other humans

Question 28

Describe the kinetics and pathogenesis of Unexpected Alloantibodies (Delayed immune mediated hemolysis)

Answer 28

Slow kinetics (10-14 days) Most do NOT bind complement Associated with extravascular hemolysis

Question 29

How would you test for Unexpected Alloantibodies

Answer 29

Detected using the antibody screen Could cause crossmatching incompatibility DAT will be positive as long as the sensitized cells are in circulation

Question 30

When you have a patient with an Unexpected Alloantibody reaction in their history, how will you need to address in future transfusions?

Answer 30

In any future transfusions., you must provide RBCs negative for that antigen

Question 31

What is the general cause of HDN?

Answer 31

Usually due to unexpected alloantibodies (IgG) made by the mother against the fetus,

Question 32

How is the maternal immune system able to respond to the fetus?

Answer 32

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

Question 33

What is the D antigen? How is it important in HDN?

Answer 33

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

Question 34

When is the highest risk for D-alloimmunization in pregnancy?

Answer 34

3rd trimester and at delivery

Question 35

Who will have a positive DAT in HDN?

Answer 35

The fetus! The positive DAT tells you that the fetal RBCs have been sensitized by IgG made by mother

Question 36

Clinical Abnormalities and Symptoms of HDN in utero

Answer 36

``` Positive DAT for fetus Shortened RBC survival in fetus Hypoalbuminemia Hypocoagulability Hepatosplenomegaly Anasarca (whole body edema) ```

Question 37

Clinical Abnormalities and Symptoms of HDN Postpartum

Answer 37

Jaundice Severe hyperbilirubinemia High risk of kernicterus Neurological damage

Question 38

What kind of hemolysis occurs in HDN?

Answer 38

Extravascular hemolysis (of the fetal sensitized RBCs)

Question 39

What is kernicterus?

Answer 39

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

Question 40

Who is more likely to get ABO-HDN? Why?

Answer 40

Group O mothers are more likely to get ABO HDN because they have preformed anti-A, anti-B, and anti-AB in circulation

Question 41

How can we prevent HDN?

Answer 41

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

Question 42

What will be found in amniotic fluid if the fetus is undergoing hemolysis? How can this be measured?

Answer 42

Bilirubin Use Liley graph for optical density measurement

Question 43

How can fetal hematocrit be assessed in a non-invasive way?

Answer 43

Fetal ultrasound to assess speed of blood flow in the baby's cerebrum Slower speed = Higher hematocrit

Question 44

If a baby is very jaundiced and hyperbilirubinemic at birth, what is the first line therapy? Second line?

Answer 44

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

Question 45

What are the two categories of unexpected autoantibodies?

Answer 45

Warm autoimmune hemolytic anemia Cold agglutinins

Question 46

What are the common etiologies of unexpected autoantibodies?

Answer 46

Idiopathic SLE Chronic Lymphocytic Leukemia

Question 47

Describe Warm Autoimmune Hemolytic Anemias

Answer 47

Ag-AB rxns take place near body temp Typically IgG Cause extravascular clearance of RBCs

Question 48

Symptoms of Warm Autoimmune Hemolytic Anemias

Answer 48

Fatigue, pallor, exercise intolerance, weakness

Question 49

Lab features of Warm Autoimmune Hemolytic Anemias

Answer 49

Positive DAT Positive IAT Microspherocytes seen on blood smear Hyperbilirubinemia Low haptoglobin

Question 50

What are the best treatments for Warm Autoimmune Hemolytic Anemias?

Answer 50

Corticosteroids Iv gammaglobulin Splenectomy

Question 51

Describe the clinical features of Cold Agglutinin Disease

Answer 51

Moderately severe anemia | Acrocyanosis precipitated by cold exposure

Question 52

Lab Features of Cold Agglutinin Disease

Answer 52

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

Question 53

Treatments for Cold Agglutinin Disease

Answer 53

``` Supportive care (RBC transfusions) Keep the patient warm ```

Question 54

What is the pathogenesis of Drug Induced Hemolytic Anemias?

Answer 54

Drugs bind to RBC membrane and make it appear to be a neo-antigen Positive DAT is seen

Question 55

How would you treat Drug Induced Hemolytic Anemias?

Answer 55

Stop taking the drug!