Hematology Chapter 23: Extrinsic Defects - Immune Causes

What is warm autoimmune hemolytic anemia (WAIHA)? What class of antibody usually causes this?

Warm autoimmune hemolytic anemia (WAIHA) is the most common type of autoimmune hemolytic anemia. In WAIHA, the patient's immune system produces autoantibodies against their own RBCs. These antibodies react best at 37°C (body temperature).

Antibody Class

✅ IgG

Mechanism

• IgG coats RBCs.

• Splenic macrophages recognize the IgG-coated cells.

• Part of the membrane is removed.

• Spherocytes form.

• RBCs are destroyed in the spleen (extravascular hemolysis).

Typical Findings

• Positive DAT for IgG

• Spherocytes

• Splenomegaly

• Increased indirect bilirubin

• Increased reticulocytes

• Decreased haptoglobin

What is Cold Agglutinin Disease? What class of antibody usually causes this?

Cold Agglutinin Disease (CAD) is an autoimmune hemolytic anemia caused by antibodies that react at cold temperatures, usually below 30°C. These antibodies bind RBCs and activate complement.

Antibody Class

✅ IgM

Mechanism

• IgM binds RBCs in cooler parts of the body.

• IgM activates complement.

• IgM may dissociate before testing, leaving complement on the RBC surface.

• DAT is often positive for C3 only.

Common Associations

• Mycoplasma pneumoniae infection

• Infectious mononucleosis (EBV)

Typical Findings

• RBC agglutination

• Acrocyanosis (blue fingers/toes in cold weather)

• Positive DAT for C3 only

What is PCH? What type of antibody causes this? This when found is more common in children following ___________.

PCH (Paroxysmal Cold Hemoglobinuria) is an autoimmune hemolytic anemia caused by the Donath-Landsteiner antibody. According to the chapter summary, PCH is one of the major forms of AIHA.

Antibody Type

✅ IgG (Donath-Landsteiner antibody)

Specificity

✅ Anti-P antibody

Mechanism

• Biphasic hemolysin

• Binds RBCs in the cold

• Activates complement when blood returns to body temperature

• Produces intravascular hemolysis and hemoglobinuria

More Common In

✅ Children following viral infections

If a patient that has a blood type of A receives blood that is type O, what will happen?

Nothing harmful should happen if the type O blood is compatible and properly prepared for transfusion.

Type O donor RBCs do not possess A or B antigens on their surface. Therefore, the anti-B antibodies naturally present in a type A patient have nothing to react against on a type O donor RBC.

Recipient	Compatible RBC Types
Type A	A or O
Type B	B or O
Type AB	A, B, AB, or O
Type O	O only

⚠ The dangerous reaction would be the reverse situation:

If a type O patient receives type A blood, the recipient's anti-A IgM antibodies can rapidly destroy donor RBCs, causing an acute hemolytic transfusion reaction. Acute ABO reactions are IgM-mediated and produce complement-mediated intravascular hemolysis.

What is HDFN? What type of antibody can cause this?

HDFN (Hemolytic Disease of the Fetus and Newborn) occurs when maternal antibodies cross the placenta and destroy fetal red blood cells. [KEY Ch 23_...Resources | Word], [KEY Ch 23_...Resources | Word]

Antibody Type

✅ IgG

Only IgG can cross the placenta.

Most Important Cause

Anti-D (Rh antibody) from an Rh-negative mother carrying an Rh-positive fetus. [KEY Ch 23_

Mechanism

1. Mother becomes sensitized to Rh-positive RBCs.

2. Mother forms IgG anti-D.

3. IgG crosses placenta.

4. Fetal RBCs are destroyed.

5. Fetal/newborn anemia and jaundice develop.

ABO HDFN

Can also occur when:

• Mother = Type O

• Baby = Type A or B

ABO HDFN is usually less severe than Rh HDFN.

Which immunoglobulin is most commonly responsible for warm autoimmune hemolytic anemia (WAIHA)?

IgM

IgA

IgG

IgE

IgG

Warm AIHA is usually caused by IgG antibodies that react at 37°C.

What type of hemolysis is most common in warm AIHA?

Extravascular

Intravascular

Mechanical

Microangiopathic

Extravascular

Explanation:IgG-coated RBCs are removed by splenic macrophages causing extravascular hemolysis.

Cold agglutinin disease is most commonly associated with which immunoglobulin?Question 3 of 15

IgG

IgM

IgA

IgD

IgM

Explanation:Cold agglutinin disease is mediated by IgM antibodies.

A DAT that is positive for C3 only is most consistent with:Question 4 of 15

Warm AIHA

Cold agglutinin disease

Iron deficiency anemia

PNH

Cold agglutinin disease

Explanation:Cold agglutinin disease often leaves complement (C3) on RBCs.

What antibody causes paroxysmal cold hemoglobinuria (PCH)?Question 5 of 15

Anti-I IgM

Donath-Landsteiner IgG

Anti-D IgG

Anti-Kell IgG

Donath-Landsteiner IgG

Explanation:PCH is caused by the Donath-Landsteiner antibody, a biphasic IgG antibody.

PCH is most commonly seen in children following:Question 6 of 15

Iron deficiency

Viral infection

Lead poisoning

Aplastic anemia

Viral infection

The Direct Antiglobulin Test (DAT) detects:Question 7 of 15

Antibodies in patient serum

Antibodies or complement attached to RBCs

Platelet antibodies

Free hemoglobin

Antibodies or complement attached to RBCs

Explanation:DAT detects immunoglobulin and/or complement coating RBCs in vivo.

Which test detects unexpected antibodies in patient serum?Question 8 of 15

DAT

IAT

Osmotic fragility

EMA

IAT

Explanation:The indirect antiglobulin test detects antibodies present in serum.

Which transfusion reaction usually occurs minutes to hours after an ABO-mismatched transfusion?Question 9 of 15

Delayed hemolytic transfusion reaction

Acute hemolytic transfusion reaction

Febrile reaction

Allergic reaction

Acute hemolytic transfusion reaction

Explanation:ABO incompatibility causes acute intravascular hemolysis.

The immunoglobulin most commonly responsible for acute ABO transfusion reactions is:Question 10 of 15

IgG

IgA

IgM

IgE

IgM

Explanation:Naturally occurring ABO antibodies are primarily IgM.

Delayed hemolytic transfusion reactions are usually caused by:Question 11 of 15

ABO antibodies

Kidd, Duffy, or Kell antibodies

Cold agglutinins

Haptoglobin deficiency

Kidd, Duffy, or Kell antibodies

What type of antibody causes hemolytic disease of the fetus and newborn (HDFN)?Question 12 of 15

IgM

IgG

IgA

IgD

IgG

Explanation:IgG crosses the placenta and destroys fetal RBCs.

Which form of HDFN is generally more severe?Question 13 of 15

ABO HDFN

Rh HDFN

Both equal

Neither causes anemia

Rh HDFN

Why can IgM agglutinate RBCs directly while IgG often cannot?Question 14 of 15

IgM is smaller

IgG is colder

IgM can span the zeta potential distance

IgG lacks specificity

IgM can span the zeta potential distance

Explanation:IgM is large enough to bridge RBCs across the zeta potential gap.

A patient has spherocytes, positive DAT, elevated indirect bilirubin, and reticulocytosis. Which diagnosis is most likely?Question 15 of 15

Warm AIHA

Cold agglutinin disease

PCH

Iron deficiency anemia

Warm AIHA