Autoimmune Hemolytic Anemias (Final Exam)

What are the three types of immune hemolytic anemias?

- Alloimmune (HTR)

- Autoimmune Hemolytic Anemia (AIHA)

- Drug-Induced Immune Hemolytic Anemia

Hemolysis is the lysis of ______ resulting in the release of hemoglobin.

RBCs

Antibodies directed against the individual's own RBCs are called ______.

autoantibodies/autoagglutinins

Autoantibodies don't always cause shortened RBC ______.

survival

A positive DAT does not always signify an ______ is present.

autoantibody

_______ is a disease caused by autoantibodies doing direct damage.

Myasthenia gravis

______ is an example of autoantibody clumping, causing damage.

Lupus

In some diseases, the cause is unknown if the autoantibodies cause damage or are a byproduct of uncontrolled ______.

inflammation

An example of this is the disease ______.

Juvenile Myositis

If a patient's RBCs are coated with autoantibody, the patient may present with discrepancies with what tests?

- Serological ABO discrepancy

- Positive Rh control

- Positive DAT

If a patient's plasma contains autoantibody, what tests are affected?

- ABSCN

- Compatibility testing

- Reverse ABO typing

A positive DAT, auto control, or serum autoantibody does not necessarily mean the patient has ______.

AIHA

In order to diagnose AIHA, the presence of ______ must be verified.

hemolysis

Compensated Anemia

RBC production = RBC destruction

What are some hallmarks of Compensated Anemia?

- Increased reticulocytes

- Mild decrease in Hgb/Hct

Uncompensated Anemia

RBC production < RBC destruction

What are some hallmarks of Uncompensated Anemia?

- Macrocytosis

- Spherocytosis

- Increased unconjugated bilirubin

- Increased LDH

- Decreased haptoglobin

Diagnostic tests for an AIHA in a symptomatic patients include the ______.

DAT (poly and monospecific)

In these patients the autoantibody is identified in the ______.

serum/eluate

What are the types of AIHA?

Cold (18%), warm (70%), drug-induced (12%)

Autoantibodies are characterized by their optimal ______ of reactivity.

temperature

Most cold reactive autoantibodies are not ______.

clinically significant

The distinction between benign and significant cold autoantibodies is determined through ______.

Thermal Amplitude

Typically, cold agglutinins have a relatively ______ (low/high) titer.

low

What tests can cold agglutinins interfere with at room temperature?

- ABO typing

- DAT

- Antibody detection and ID

- Compatibility testing

AIHA under the microscope

Most cold autoantibodies have ______ specificity.

anti-I

The I antigen is expressed strongly on ______ RBCs and weakly on ______ RBCs.

adult, cord

______ is a relatively uncommon autoantibody.

Anti-i

Cold agglutinins in group A1 and A1B individuals may have ______ specificity.

anti-H

Groups A1 and A1B cells have the least ______ so they react weakly.

H antigen

Group ______ and ______ cells react best because they have the largest amount of H antigen.

O, A2

Auto anti-H and anti-IH react only with the auto control at ______C.

4C

Cold Agglutinin Disease (CAD) is often associated with ______.

Mycoplasma pneumoniae

In CAD, moderate chronic hemolytic anemia is produced by a cold autoantibody that optimally reacts at 4C but also reacts at ______C.

25-30C

The antibody responsible for causing CAD is usually ______, which efficiently activates complement.

IgM

CAD occurs predominantly in ______ individuals.

older

CAD antibody specificity is almost always ______.

anti-I

Lab findings for CAD include ______ and a positive ______.

reticulocytosis, DAT (for complement only)

What are some other things seen in a blood smear for a CAD patient?

- Agglutinated RBCs

- Polychromasia

- Anisocytosis

- Poikilocytosis

- May look clotted in the tube

What is the most common fix for CAD?

To move to a warmer climate (steroids may be used)

Paroxysmal Cold Hemoglobinuria (PCH) is very rare, most often seen in children associated with ______.

viral illnesses

PCH is caused by a ______.

biphasic autohemolysin

Biphasic autohemolysins bind to patient RBCs at ______ temperatures and fixes complement.

low

At 37C, biphasic autohemolysins cause ______.

complement-mediated intravascular lysis

PCH involves ______ autoantibodies.

Donath-Landsteiner

Donath-Landsteiner autoantibodies have ______ and ______ specificity.

anti-P, IgG

Warm autoantibodies react best at ______C with ______ specificity at IAT.

37C, IgG

Harmless warm autoantibodies are ______ indistinguishable from the harmful ones.

serologically

Warm autoantibodies are ______ common in the population as the cold autoantibody-i.

less

A lot of warm autoantibody patients suffer from an anemia severe enough to require ______.

transfusion

Most patients with Warm Autoimmune Hemolytic Anemia (WAIHA) have ______ and ______ on their RBCs (67%).

IgG, C3d

In WAIHA, extravascular immune RBC destruction occurs in the ...

liver and spleen

WAIHA could potentially interfere with ______.

Rh(D) typing

With WAIHA, the DAT is expected to be ______.

positive

In WAIHA antibody screening and ID, if there is more autoantibody than antigen sites on the RBCs, the autoantibody will be detected in ______ too.

plasma

With WAIHA, during antibody screening and ID, the MLS must determine if underlying ______ are present.

alloantibodies

Drug-Induced Immune Hemolytic Anemia (DIIHA) can cause immune destruction of ...

RBCs, WBCs, PLTs

DIIHA is often a diagnosis of ______.

exclusion

What are the three mechanisms of DIIHA?

- Drug : RBC membrane, Ab directed at the drug

- Drug : drug Ab

- Drug --> immune response, Ab directed at RBC membrane

Drugs operating through the drug-adsorption mechanism bind firmly to ______, including those on the RBC membrane.

proteins

Antibodies to the drug ______ is the most commonly associated with the Drug-Adsorption (Hapten) Mechanism.

Penicillin

Most penicillin antibodies are ______, not detected by the DAT.

IgM

DAT results for Drug-Adsorption (Hapten) Mechanism

+ DAT

+ IgG

+/- C3d

Eluate results for Drug-Adsorption (Hapten) Mechanism

Nonreactive with random donor cells

ABSCN results for Drug-Adsorption (Hapten) Mechanism

Negative

Crossmatch results for Drug-Adsorption (Hapten) Mechanism

Compatible

Plasma and eluate tested for the Drug-Adsorption (Hapten) Mechanism must involve ______ cells.

drug-coated

The Drug-Independent or Immune Complex (Innocent Bystander) Mechanism functions via ______ interactions with membrane components.

non-covalent

This causes the formation of a new ______.

antigen (neoantigen)

With the Innocent Bystander Mechanism, ______ often activates complement and sensitizes the cell, causing lysis.

IgM

Confirmation of the Innocent Bystander Mechanism must demonstrate the antibody in the patient's serum reacts only if the ______ is added to the system.

drug

With Membrane Modification (Nonimmunologic Protein Adsorption), it is suspected that ______ demonstrates the drug-adsorption mechanism and can modify RBCs so that plasma proteins can bind to the membrane.

cephalosporins

Membrane Modification (Nonimmunologic Protein Adsorption) is not a result of ______ interactions.

antigen-antibody (nonimmunogenic)

With Membrane Modification (Nonimmunologic Protein Adsorption), it is suspected that ______ demostrates the drug-adsorption mechanism and can modify RBCs so that plasma proteins can bind to the membrane.

With Membrane Modification (Nonimmunologic Protein Adsorption), it is suspected that ______