Blood Banking - Lecture - 13 - Autoimmune Hemolytic Anemia - Part 1 - Complete

Immune hemolytic anemia

Shortened RBC survival mediated by the humoral immune response (antibodies), which the bone marrow can not keep up with

Acquired

Immune hemolytic anemia is an (Acquired/Inherited) membrane defect

Antibodies

In Immune hemolytic anemia, destruction occurs when (antibodies/antigens) bind to RBC antigens, triggering clearance.

Alloimmune, Autoimmune, Drug-Induced

3 classifications of immune hemolysis

Alloimmune

Classification of immune hemolysis where antibodies are produced against "non-self" antigens (e.g., Transfusion, Pregnancy)

Alloimmune

Classification of immune hemolysis where the body is doing its job correctly by attacking foreign cells from a transplant or transfusion

Autoimmune

Classification of immune hemolysis where antibodies are produced against the patient's own "self" RBC antigens. The immune system loses self-tolerance and attacks its own antigens.

Drug-induced

Classification of immune hemolysis where an immune response is triggered by a drug or drug receptor complex.

Drug-induced

Classification of immune hemolysis that is unique because the RBC is often an innocent bystander caught in the crossfire of an immune reaction to a specific medication.

Extravascular hemolysis

Hemolysis where RBCs are sequestered and destroyed by macrophages in the spleen or liver

Extravascular hemolysis

Most autoimmune hemolytic anemias involve what type of hemolysis?

IgG

Antibodies that coat RBCs in Extravascular hemolysis

Splenic macrophages

These turn IgG-coated RBCs into spherocytes, before being fully destroyed, causing Extravascular hemolysis

Spherocytes

IgG-coated cells are acted on my splenic macrophages, turning them into this morphology, before causing Extravascular hemolysis

Intravascular hemolysis

Hemolysis within the blood vessels via complement activation.

Intravascular hemolysis

Between Intravascular and Extravascular hemolysis, which one is more violent?

IgM

Usual antibody seen in Intravascular hemolysis

IgM

Antibody that activates the complement cascade all the way to the Membrane attack complex, before causing Intravascular hemolysis

Free hemoglobin

This is released during Intravascular hemolysis, which is seen as red plasma in the laboratory

Spherocytes

Laboratory hallmarks for Extravascular hemolysis

Hemoglobinemia

Laboratory hallmarks for Intravascular hemolysis

Direct antiglobulin test

The primary tool used to detect in vivo sensitization of RBCs

In vivo

The Direct antiglobulin test detects (In vivo/In vitro) sensitization

Direct antiglobulin test

This test tells us if the patient's cells are currently coated with antibodies or complement proteins while still inside their body.

IgG

Antibody that reacts at body temperature

IgM

Antibody that reacts at cold temperature and in the extremities

IgG, Complement C3

Identifying the type of protein gives us the first major clue to which category of anemia we are dealing with. What are these proteins?

Thermal amplitude

Basis for distinguishing between warm and cold antibodies

Autoantibodies

Antibodies directed against "self" antigens, often high-incidence RBC antigens.

Autoantibodies

These antibodies agglutinate or sensitize the patient's own cells and most random donor cells

T

T/F

The presence of an autoantibody always equates to a disease

1,000

1 in how many health donors are DAT+?

Suppressor T-cell

Autoantibodies are theoretically caused by the loss of function of this immune cell, leading to unregulated B-cell antibody production. They fail to keep helper T-cells and B-cells in check, allowing self-attack antibodies to be produced.

Autoantibodies

Antibodies that attack the patient's own red cells

High-incidence antigens

Antigens that almost everyone has and are the usual targets of autoantibodies

False positive

ABO/Rh typing result in patients with autoantibodies

Spontaneous agglutination

Rh typing appearance of result in patients with autoantibodies

Pan-reactive

Term used to describe when a patient's serum tests positive with all screen cells, including the autocontrol. This result is also seen in patients with autoantibodies

T

T/F

It is often impossible to find a compatible blood unit for patients with autoantibodies, especially without specialized techniques

T

T/F

Autoantibodies can mask clinically significant alloantibodies

Compensated anemia

Anemia where RBC production in the bone marrow keeps pace with the destruction.

Normal Hb and Hct

Increased Reticulocyte count

Uncompensated anemia

Anemia where destruction outpaces RBC production in the bone marrow

Low Hb and Hct

Reticulocytes >3%, Indirect bilirubin, LDH

Laboratory parameters that increase in autoimmune hemolytic anemia

Spherocytes

RBC morphology in autoimmune hemolytic anemia resulting from membrane loss

Spherocytes

Classic hallmark of warm autoantibodies because the spleen removes pieces of the antibody-coated membrane

Macrocytes

RBC morphology in autoimmune hemolytic anemia that are the young RBC population

Thermal amplitude

It is the temperature at which antibodies react best and serves as the basis of classifying autoimmune hemolytic anemias

Warm-reactive AIHA

Major type of Autoimmune hemolytic anemia

70%

What % of cases are Warm-reactive AIHA?

37°C

Warm-reactive AIHA optimal reactivity temperature

IgG

Usual antibody that mediates in Warm-reactive AIHA

4-30°C

Cold-reactive AIHA optimal reactivity temperature

IgM

Usual antibody that mediates in Cold-reactive AIHA

Pre-warming

Cold-reactive antibodies are less common but require different laboratory techniques, like ___, to resolve.

18%

What % of cases are Cold-reactive AIHA?

Drug-induced AIHA

AIHA classification triggered by specific medications; involves various immune mechanisms.

12%

What % of cases are Drug-induced AIHA?

Mixed-type AIHA

AIHA classification that is rare; where both warm and cold autoantibodies are present simultaneously

Variable

Drug-induced AIHA optimal reactivity temperature

IgG

Primary protein involved in Warm-reactive AIHA

IgM or Complement

Primary protein involved in Cold-reactive AIHA

IgG or Complement

Primary protein involved in Drug-induced AIHA

4°C

Benign cold antibodies react best at this temperature

30°C or higher

Pathological cold antibodies reactivity temperature; wider range

Thermal range

Characteristic that serves as a basis to distinguish cold antibodies

<64 at 4°C

Benign cold autoantibody titers

T

T/F

Most of us have benign cold autoagglutinins. They are IgM and are in our serum and don't cause harm because they only react at 4°C.

>1000

Pathological cold autoantibody titers

T

T/F

Pathological cold autoantibody titers can start attaching to RBCs even at 37°C

IgM

Usual antibody type of Benign and Pathological cold autoantibody titers

T

T/F

Benign and Pathological cold autoantibody titers can activate complement

T

T/F

Benign cold autoantibodies are found in most healthy people.

Warm saline wash

Elute and false-positive cold autoantibody can cause false-positive pan-agglutination. These can fix be fixed by washing the antibody away with a...

AB or Rh positive

Cold agglutinins appear as ___, if RBCs are heavily coated, regardless of their true type

Cold autoadsorption technique

Cold agglutinin discrepancies are resolved using this technique to remove auto-anti I

Monospecific Anti-IgG or EDTA samples

Samples for Weak D testing to avoid false positives caused by in vitro complement binding

Prewarm technique

Technique used to prevent cold antibodies from binding and activating during testing in antibody screening.

Prewarm technique

For serum testing, this technique is a classic tool by keeping the serum, cells, and saline at 37°C throughout the process.

Warm saline wash

Laboratory solution for false positive ABO/Rh testing for cold agglutinins.

Cold autoadsorption

Laboratory solution for serum discrepancies to remove the auto-anti-I for cold agglutinins

Prewarm technique

Laboratory solution for masked alloantibodies in antibody screening for specimens suspected of cold agglutinins

Older adults

Cold hemagglutinin disease primary population affected

Acrocyanosis

Cold hemagglutinin disease clinical presentation in cold weather, where there is numbness or bluing of extremities

IgM, usually Anti-I

Cold hemagglutinin disease antibody type

Binds in cold extremities, Fixes complement, Causes hemolysis as blood returns to the core

Cold hemagglutinin disease mechanisms

Positive

Cold hemagglutinin disease DAT result

Complement C3

Cold hemagglutinin disease protein seen in DAT result

Reticulocytosis, Autoagglutination

Cold hemagglutinin disease smear finding

Secondary Cold hemagglutinin disease

Form of Cold hemagglutinin disease that can occur as a transient, self-limiting condition following Mycoplasma pneumoniae or Infectious Mononucleosis.

Cold hemagglutinin disease

It is the chronic pathological version of cold autoantibodies.

Raynaud-like symptoms

Cold hemagglutinin disease symptoms because their blood literally clumps in their fingers and toes when they get cold.

Positive, Negative

Cold hemagglutinin disease

DAT

C3: Positive/negative

IgG: Positive/negative

IgM

Antibody in Cold hemagglutinin disease that falls off the cell when it is washed, leaving the complement attached, staying behind.

Paroxysmal cold hemoglobinuria

Rarest form of autoimmune hemolytic anemia

Children following viral infections (Measles, mumps, flu)

Paroxysmal cold hemoglobinuria usually affects this population (medical emergency)

Donath-Landsteiner antibody

Paroxysmal cold hemoglobinuria antibody

IgG

Paroxysmal cold hemoglobinuria antibody class

Biphasic

Term used to describe the antibody in Paroxysmal cold hemoglobinuria because it needs 2 steps to kill the cell.

Cold

At what temperature do the antibodies in Paroxysmal cold hemoglobinuria attach to the RBC?

37°C

At what temperature do the antibodies in Paroxysmal cold hemoglobinuria cause full intravascular lysis?