AIHA

lecture 2

What is immune hemolytic anemia?

the shortened RBC survival mediated by an immune response → humoral

What are the three categories of immune hemolytic anemia?

1. alloimmune

2. autoimmune

3. Drug inducted

What is the alloimmune response from a transfusion?

the recipient produces antibodies to foreign antigens introduced by transfusion, transplants, or pregnancy

What is intravascular hemolysis?

complement fixation and lysis OR RBC mechanical damage

What is extravascular hemolysis?

antibody coated RBC that is carried out of circulation into the liver or spleen

What is the autoimmune response?

When we make antibodies against self

If auto antibodies are present, what testing can be complicated?

ABO/Rh reverse typing, antibody screens, autocontrol positive, compatibility testing will almost always show incompatible

How can we confirm autoimmune hemolytic anemia?

increased RBC destruction, dec. hgb and hct, increased reticulocytes and NRBCs, increased LDH, decreased haptoglobin, macrocytes

How can we identify auto antibodies?

DAT with polyspecific and monospecific to ID if it is antibody based

What are the types of auto antibodies?

cold

warm

drug dependent

drug independent

What are cold reactive auto antibodies?

auto antibodies that react at cold temperatures (4C), usually not significant

What are two types of cold reactive auto antibodies?

1. benign

2. pathologic

Benign cold auto antibodies have a thermal amplitude of __ C, and a titer of __

4C, 64

Pathologic cold auto antibodies react at __ C and have a titer of ____

4C, 1000

a common cold autoantibody (either benign or pathologic) is?

anti-I

What infection can cause anti-I formation?

M. pneumonia infection

What tests are complicated with cold agglutinins?

ABO fwd/rev type, IAT, antibody ID, RBC phenotyping

How can we resolve auto cold reactions?

auto adsorption → plate specimen in fridge and let antibody settle out

• remove adsorbed plasma with prewarming

• REST enzyme to destroy antibody

• use monoclonal IgG

pre-warm your serum, cells, saline, media

anti-H and anti-IH cold auto antibodies can be found in what RBC groups?

A1 and A1B

What is the concentration of H antigen in RBC groups from most to least?

O > A2 > B > A2B > A1 > A1B > Oh

anti-i is very rare because?

most of the adult population is I

Mycoplasma pneumoniae is associated with what auto antibody?

anti-I

EBV is associated with what cold auto antibody?

anti-i

Cold auto antibodies are typically what isotype?

IgM

The presence of cold auto antibodies like anti-I and anti-i can cause what disease?

cold hemolytic disease OR cold agglutinin disease

What is the clinical picture of cold agglutinin disease?

seen in older people around the winter months

What are symptoms of cold agglutinin disease?

acrocyanosis of the hands, feet, ears, and nose, numbness, hemoglobinuria

can anti-I and anti-i bind complement?

yes

How do we treat cold agglutinin disease?

transfusions with blood warmers and blankets

What are the labs of cold agglutinin disease?

increased reticulocytes, positive DAT for C3d, WBC/PLT normal, rouleaux, polychromasia, anisocytosis, poikilocytosis

What is paroxysmal cold hemoglobinuria?

autoimmune hemolytic anemia caused by viral illness with mumps, measles, chickenpox, IM, flu

PCH was first associated with what disease?

Syphilis

PCH is caused by what antibody?

anti-P IgG

What kind of hemolysis occurs with PCH?

intravascular

What are the signs of PCH?

fever, shakes, chills, malaise, cramping, hemoglobinemia/uria, bilirubinemia

What temperature do warm auto antibodies react at?

37C

What can cause warm autoimmune hemolytic anemia?

infection, trauma, surgery, pregnancy, underlying disease

What are the symptoms of warm autoimmune hemolytic anemia?

significant anemia, pall, weakness, dizziness, dyspnea, jaundice, fever

What does the blood smear of warm autoimmune hemolytic anemia look like?

polychromatic cells, macrocytes, reticulocytosis, NRBCs, spherocytes, RBC fragments

How do we treat warm autoimmune hemolytic anemia?

give corticosteroids, remove spleen, immunosuppressive drugs, plasma exchange, plasma filtration

What is the preferred method to treat warm autoimmune hemolytic anemia?

corticosteroids to stop Ab synthesis

What are some diseases associated with warm autoimmune hemolytic anemia?

reticuloendothelial neoplasms (Cancer), SLE, viruses, hypogammaglobulinemia, ulcerative colitis, ovarian cysts

What tests are complicated with warm autoantibody presence?

Rh type false positive, DAT positive, masking alloantibody presence, elutions

If a patient has warm autoantibodies, what can we treat their cells with to get an accurate Rh type?

EGA and CDP to remove IgG

How can we detect alloantibodies if we have autoantibody presence?

1. if the autoantibody demonstrates specificity, use test cells that are negative for those antigens

2. perform auto adsorptions

3. antigen type with reticulocytes

4. multiple adsorption rounds

Who is ineligible for adsorption procedures?

people who have been transfused in the past 3 months, severe anemia

What is the most important thing to identify in a person who has autoimmune hemolytic anemia?

if any alloantibodies are being masked