Immune Hemolytic Anemias

Question 1

immune hemolytic anemia

Answer 1

shortening of RBC survival due to antibodies coating the red cells
anemia of increased destruction

Question 2

Immune Hemolytic Anemias requiring transfusion support (3 categories)

Answer 2

1. Alloimmune hemolytic anemia
2. Autoimmune hemolytic anemia
3. Drug-induced hemolytic anemia

Question 3

Lab indicators of immune hemolysis

Answer 3

positive DAT
increased retics
increased LDH-intravascular hemolysis
increased indirect bilirubin
decreased hemoglobin & hematocrit
decreased haptoglobin
spherocytes -extravascular

Question 4

Intravascular hemolysis

Answer 4

increased bilirubin
hemoglobinuria, hemoglobinemia
positive DAT
schistocytes

Question 5

Extravascular hemolysis

Answer 5

increased bilirubin
no hemoglobinuria, no hemoglobinemia
positive DAT
spherocytes

Question 6

Extravascular targeting of Coated RBCs

Answer 6

A. reticular endothelial system (RES) can ‘pluck’ IgG-coated RBCs & create spherocytes
B. RES can engulf & phagocytize RBCs IgG-coated RBCs in the spleen
C. RES can remove IgG & Complement coated RBCs in the liver

Question 7

Direct Antiglobulin Test

Answer 7

detect IgG &/or complement attached to the red cell surface
up to 90 molecules of IgG may be present normally

Question 8

threshold for positive DAT

Answer 8

100-500 molecules of IgG

400-1100 molecules of C3d

Question 9

reasons for positive DAT besides the obvious

Answer 9

0.3-1.0% of hospitalized pts will have a positive DAT w/o clinical hemolysis
IVIG!!!
recent transfusion
drug associated w/ immune hemolytic anemias
organ transplant
septicemia-bc of constant complement activation

Question 10

DAT tips for accuracy

Answer 10

RBCs must be washed thoroughly = false negative
RBCs must be tested immediately after washing to avoid false negatives
used EDTA sample to avoid false positive

Question 11

Additional testing when autoantibodies are present

Answer 11

1. elution when DAT IgG is positive

2. absorption: remove warm/cold autoantibody

Question 12

Autoantibodies general

Answer 12

must resolve cold autos in order to ABO type
must resolve warm autos in order to screen for alloantibodies
serologic findings DO NOT always imply hemolytic anemias
clinical significance varies

Question 13

how to predict if autoantibodies are clinically significant

Answer 13

thermal range - high range cold autos & warm autos
ability of antibody to fix complement
titer of antibody bound to RBCs
underlying disease

Question 14

Cold Autoagglutinin Disease

Answer 14

hemolytic anemia associated w/ autoantibodies reacting in the cold
18% of all AIHAs
acute & chronic

Question 15

Acute CAD

Answer 15

usually fairly mild anemia
anti-I: can happen in mycoplasma pneumonia & other bacterial infections
anti-i: CMV, infectious mononucleosis etc

usually do not require any transfusion support

Question 16

chronic CAD

Answer 16

most serious clinically
more common in the elderly, lymphoma, chronoic lymphocytic leukemia
most severe cases in younger individuals w/ no known underlying cause

Question 17

CAD clinical features

Answer 17

anemia 
jaundice
acrocyanosis
Raynaud's phenomenon
therapy: avoid cold

Question 18

CAD manifestation/mechanism

Answer 18

1. IgM antibody binds to RBC in lower temps of peripheral circulation causing complement to attach to RBCs
2. as RBCs move to warmer areas, IgM dissociates but complement remains
3. intravascular hemolysis

Question 19

CAD serologic testing

Answer 19

can interfere with serologic testing- wash cells
usually can skip this step for antibody screen/panel/crossmatch
prewarming techniques

Question 20

typical reactivity seen with CAD

Answer 20

4C= 3-4+
15-18C= 1-2+
20-24C = 0-1+
37C = 0
IgG = 0

Question 21

CAD lab results

Answer 21

positive DAT - anti-C3d
reticulocytosis
agglutination in peripheral smear- have to warm up sample before testing

Question 22

Anti-I: pathologic

Answer 22

greater thermal amplitude >30C

titer >1000 @ 4C (always titer at 4C)

Question 23

other cold autoantibodies

Answer 23

anti-H & anti-IH: present in only A1 & A1B individuals at low levels
clinically insignificant unless in a BOMBAY phenotype
anti-M

Question 24

anti-M cold autoantibody

Answer 24

not uncommon in children less than 1 year old

Question 25

Paroxysmal Cold Hemoglobinuria (PCH)

Answer 25

uncommon; occurs in children after viral illnesses biphasic hemolysin (anti-P): binds at low temps & causes hemolysis @ 37C DONATH-LANDSTEINER TEST

Question 26

PCH treatment

Answer 26

normally self-limiting after virus passes anti-P negative blood is rare-> transfuse w/ ABO compatible blood w/ blood warmer treat w/ steroids

Question 27

Warm autoimmune hemolytic anemia

Answer 27

majority of AIHA most detected are not clinically significant (no hemolysis) important because they can mask an underlying alloantibody & will make crossmatches incompatible

Question 28

WAIHA serologic reactions

Answer 28

``` IS - 0 37C - 0 AHG - 2-4+ polyspecific DAT - 2-4+ IgG DAT - 2-4+ C3b/d DAT- 0-2+ ```

Question 29

most common warm autoantibody

Answer 29

anti-e

Question 30

work around warm autoantibodies

Answer 30

perform an autoadsorption- cannot have had a transfusion recently

Question 31

mixed-type autoimmune hemolytic anemia

Answer 31

features similar to both warm & cold | DAT - both IgG & C3d/b

Question 32

Drug Induced Immune Hemolytic anemia

Answer 32

rare; first seen in penicillin & methyldopa | >100 drugs could cause IHA &/or positive DAT

Question 33

DIIHA mechanisms (4)

Answer 33

1. penicillin-type (drug adsorption) 2. immune complex 3. membrane modification 4. drug-independent

Question 34

Penicillin type DIIHA

Answer 34

penicillin or its metabolites are adsorbed onto the RBCs antibodies attach to the drug causing a positive DAT (IgG) & may increase RBC destruction hemolysis is extravascular elute should be tested w/ RBCs sensitized w/ penicillin

Question 35

immune complex DIIHA

Answer 35

after patient receives a drug, an antibody to the drug forms drug-antibody complex absorbs to the RBCs complement is activated intravascular hemolysis w/ hemoglobinemia & hemoglobinuria

Question 36

classic drugs that cause immune complex DIIHA

Answer 36

quinine | quinidine

Question 37

non-immunologic protein adsorption (Membrane modification)

Answer 37

drugs that MODIFY THE CELL MEMBRANE of RBCs by making the membrane 'sticky' positive DAT may demonstrate IgG, IgM, IgA, C3 rarely associated with RBC destruction eluates are non-reactive bc there is no drug antibody present

Question 38

unique feature of drug-independent DIIHA

Answer 38

the drug does NOT have to be present to have a positive DAT

Question 39

methyldopa

Answer 39

anti-hypertensive drug; interferes with suppressor T cell function, leading to the production of autoantibodies

Question 40

Drug Independent features DIIHA

Answer 40

positive DAT - IgG; after 3-6 months of discontinuing the drug eluate is reactive against all panel cells! looks exactly like a warm autoantibody hemolysis RARELY occurs