AIHA & DIIHA

Immune Hemolytic Anemia

Shortened RBC survival mediated through the immune response, specifically by the humoral antibody

Immune Hemolytic Anemia

What does IHA stand for?

1. Alloimmune

2. Autoimmune Hemolytic Anemia

3. Drug-Induced Immune Hemolytic Anemia

List the 3 categories that IHA falls under

Alloimmune

What is the most come type of IHA?

ABO discrepancy

Positive Rh control

Positive DAT

What 3 discrepancies can you see in your workup if patients' RBC are coated with an antibody?

autoantibodies

Antibodies directed against your own RBCs

aka autoagglutinins

1. Compensated anemia

2. Uncomponsated anemia

What are the 2 types of anemia caused by the destruction of RBCs?

Compensated anemia

The rate of RBC production will nearly equal the rate of RBC destruction

- common in elderly patients

Uncompensated anemia

The rate of RBC destruction is > the rate of RBC production

DAT

Antibody ID

Cold autoantibody

What are the 3 diagnostic tests performed in symptomatic patients?

Warm Autoimmune Hemolytic Anemia

What does WAIHA stand for?

70%

WAIHA are what % of IHA?

IgG

What antibody is seen in WAIHA?

37C

What is the optimal temperature for reactivity in WAIHA?

protein antigen on RBC surface

In WAIHA, IgG reacts against what?

spherocytes

In WAIHA, we see in increase in what type of erythrocyte?

18%

Cold reactive autoantibodies are what % of IHA?

IgM

What antibody is seen in cold reactive autoantibodies?

< 30C

What is the optimal temp for reactivity for cold reactive autoantibodies?

polysaccharide antigens

In cold reactive autoantibodies, IgG reacts against what?

RBC agglutination

In cold reactive autoantibodies, we see in increase in what?

12%

Drug-Induced is what % of IHA?

4C

What temperature do most of the cold autoantibodies react best at?

benign cold agglutinin

When testing is performed at 4C, what is the most common autoantibody found in normal healthy people?

interfere with routine testing being performed at room temperature

Even though most cold agglutinins are clinically insignificant, what problem do they pose?

ABO typing

DAT

Ab detection and ID

Compatibility testing

Cold agglutinins can potentially affect what tests (4)?

false-positives

ABO typing affected by Cold Autoagglutinins

RBCs heavily coated with cold agglutinins may directly agglutinate causing false __________ with routine ABO reagents

warm washing RBCs

When ABO typing is affected by cold autoagglutinins, how can we solve this problem?

true

True or False

When cold autoagglutinins are interfering with ABO typing, you should warm wash every reagent that is performed at room temperature

true

True or False

Cold autogglutinins frequently cause discrepancies in ABO reverse typing too

Cold auto adsorption

When cold autoagglutinins cause discrepancies in ABO reverse typing, how should we resolve this problem?

warm washing & monoclonal reagents

When cold autoagglutinins cause discrepancies in Rh typing, how should we resolve this problem?

thiol reagents

When cold autoagglutinins cause discrepancies in Rh typing, and warm washing doesn't work, what should we use?

Dithiothreitol

aka Thiol Reagent used when warm wahing with saline is ineffective

warm washing

When cold autoagglutinins cause discrepancies in DAT, how should we resolve this problem?

negative

DAT of patient with benign cold autoagglutinins will usually come out positive/negative

Cold auto adsorption

When cold autoagglutinins cause discrepancies in Antibody Detection and ID, how should we resolve this problem?

clinically significant alloantibodies

Cold autoagglutinins can mask the presence of what in an antibody detection and ID

prewarm

auto adsorbed serum

allogenic adsorbed serum

anti-IgG antiglobulin reagent

When cold autoagglutinins cause discrepancies in compatibility testing, what 4 things can we do/use?

RBC blood warmer

When infusing patients with cold agglutinins, what should we use?

reactive at ≤ 20-24C

Normal (Benign) Cold Autoantibody

What is the thermal range

**hint: reactive at immediate spin (RT)

≤ 64

Normal (Benign) Cold Autoantibody

What is the titer at 4C

marginally enhanced

Normal (Benign) Cold Autoantibody

Reactivity marginally / strongly enhanced with albumin

anti-I or anti-IH

Normal (Benign) Cold Autoantibody

Common specifcity (common antibodies)

0-1+

Normal (Benign) Cold Autoantibody

Capable of binding complement (in vitro) due to being IgM

DAT will show what type of agglutination?

no

Normal (Benign) Cold Autoantibody

Are they clinically significant?

no

Normal (Benign) Cold Autoantibody

Are they assocaited with disease

reactive at ≥ 30C

Pathological Cold Autoantibody

What is the thermal range?

**hint: 37C

≥ 1000

Pathological Cold Autoantibody

What is the titer at 4C?

strongly

Pathological Cold Autoantibody

Reactivity marginally / strongly enhanced with albumin

anti-I or anti-i (in babies)

Pathological Cold Autoantibody

Common specificity (common antibody)

2-4+

Pathological Cold Autoantibody

Capable of binding complement (in vitro) due to being IgM

DAT will show what type of agglutination?

yes

Pathological Cold Autoantibody

Are they clinically significant?

yes

Pathological Cold Autoantibody

Are they associated with diseases?

secondary infection to viral infections or Mycoplasma pneumoniae

Pathological Cold Autoantibody

Can cause what type of disease?

anti-I

What is the most commonly encountered

adults

the I antigen is fully expressed in the RBCs of adults or children?

anti-i

Which antibody is relatively uncommon autoantibody, but common in babies?

anti-H and anti-IH

Cold agglutinins found in the sera of group A1 and A1B individuals (& occasionally group B)

Group O and A2 cells

Which cells react best because they have the largest amount of H antigen?

Group A1 and A1B cells

Which cells react weakly because they have the least amount of H antigen?

Cold Hemagglutinin Disease

Occurs predominantly in older individuals

- peaking in those older than 50 years old

anti-I

What antibody is almost always in CHD?

- less common: anti-i

- rarely anti-Pr

reticulocytes

positive DAT at complement

Lab findings in CHD (2)

agglutinated RBCs

polychrommasia

mild to mod anisocytosis (size)

poikilocytosis (shape)

Peripheral smear of CHD may show (4)

avoid cold, keep warm or move to a milder climate

Most patients with CHD do not require no treatment, but are instructed to do what?

plae

hard time breathing

What are the #1 symptoms of CHD

**hint: lack of O2

Idiopathic cold AIHA

Cold Hemagglutinin Disease is also known as?

Secondary Cold AIHA

Transient disorder secondary to infection

- often occur after upper respirtoy infection

Mycoplasma pneumoniae

~ 50% of patients suffering from pneumonia caused by what bacteria?

> 64

~ 50% of patients suffering from pneumonia caused by M. pneumonia to have cold agglutin titers higher than?

infection subsides

Secondary cold AIHA resolves when?

infectious mononucleosis

an infection that also may be associated with hemolytic anemia resulting form cold autoantibody

moderate chronic hemolytic anemia

Produced by a cold autoantibody that optimally reacts at 4C but also reacts at between 25-30C

IgM

antibody in Secondary Cold AIHA

**hint: efficient activates complement

Paroxysmal Cold Hemoglobinuria

- least common type of AIHA with incidence between 1-2%

- most often seen in children in association with viral

- classic antibody produced: anti-P

Donath-Landsteiner test

What test is used to determine anti-P

**hint: its the only test

anti-P

Donath-Landsteiner antibody

protection from cold exposure

Treatment for Chronic Paroxysmal Cold Hemoglobinuria

steroids & transfusion (depending on the severity)

Treatment for Acute Paroxysmal Cold Hemoglobinuria

Warm Autimmune Hemolytic Anemia

What does WAIHA stand for?

Warm Autoantibodies

- reacts best at 37C and are usually enhanced by enzymes techniques

- not as common as cold autoanti-I

true

True or False

More of the true AIHAs are warm type (70%) than of the cold-reactive type (18%)

transfusion

A significant percent of Warm Autoantibody cases suffering from anemia of sufficient severity require what?

polychromasia and macrocytosis

NRBCs

spherocytosis, occasional RBC fragmentation, indicating extravascular hemolysis

Peripheral blood smear for Warm Autoantibodies

↑ LDH, bilirubin (mainly unconjugated), urine urobilinogen

↓ depleted haptoglobin

hemoglibinemia and hemoglobinuria

Chemistry results of Warm Autoantibodies due to hemolysis

67%

RBC Hemolysis

% of patients with warm autoimmune hemolytic anemia have both IgG and complement on RBCs

20%

RBC Hemolysis

% of patients with warm autoimmune hemolytic anemia have IgG only on RBCs

13%

RBC Hemolysis

% of patients with warm autoimmune hemolytic anemia have complement only on RBCs

liver and spleen

What organ is involved in removing sensitized RBCs?

**hint:

ABO typing

What routine testing performed that warm agglutinins has shown not to interfere?

Rh typing

DAT

antibody detection and ID

evaulation of autoantibody

What lab tests are affected by warm agglutinins?

Rh typing

Warm autoagglutinins affected test

Most of the warm autoantibodies react with a high-incidence RBC ag, often with a general specificity within the Rh blood group system -- use monospecific

False positive Rh typing can occur when the patient's cells are coated with immunoglobulins

DAT

Warm autoagglutinins affected test

Positive results expected

In rare cases, may be negative or cells may be coated only with IgA or IgM

antibody detection and ID

Warm autoagglutinins affected test

Clinically significant alloantibodies & the autoantibodies themselves react best at the indirect antiglobulin phase; therefore, more complicated and time-consuming procedures for resolving the problems may have to be used

-- doing autoadsoprtion

never

Many patients with WAIHA _______ require transfusion, they can be managed with medical treatment

true

True or False

Occasionally, anemia from WAIHA pose problems when blood is needed for surgical procedures

treat underlying disease

Treatment of WAIHA

First thing to do?

accelerate hemolysis

Treatment of WAIHA

Transfusion should be avoided, if possible, because it may only do what?

Corticosteroid administration & use of IVIG

Splenectomy

Immunosuppressive Drugs

What 3 other treatments can be used for WAIHA