Topic 4: Autoimmune Hemolytic Anemias

Question 1

what are autoimmune hemolytic anemias?

Answer 1

patients have a low hemoglobin (anemia) because red blood cells (RBCs) are being attacked by the body’s own antibodies (autoimmune), leading to the destruction of the erythrocytes (hemolytic)

Question 2

what kind of anemia is AHA?

Answer 2

extrinsic/extracorpuscular anemias

this means that hemolysis is occuring not because of a problem with the red blood cell itself, but because of some other factor

Question 3

What are the two major classifications of AHA?

Answer 3

warm and cold

warm AHA is the majority of AHA

Question 4

what is warm autoimmune hemolytic anemia?

Answer 4

antibodies attach to RBCs in areas where the blood is warm, in the central aspects of the body, rather than the periphery

warm AHA has IgG antibodies that recognize a host’s own RBC antigens

IgG-coated RBCs eventually reach the spleen where the RBC is trapped by spleen macrophages that recognize the Fc region of the IgG antibody

RBC is phagocytosed and hemolyzed! since hemolysis is in spleen and not blood vessels, warm AHAs are characterized by extravascular hemolysis

antibodies are most reactive at 37°C = 98.6

Question 5

antigen vs. antibody

Answer 5

Antigens are molecules capable of stimulating an immune response

Antibodies (immunoglobins) are Y-shaped proteins produced by B cells of the immune system in response to exposure to antigens

Question 6

What type of antibody recognizes RBC antigens in warm AHAs?

Answer 6

IgG is the main antibody type in warm AHAs

Question 7

does complete phagocytosis in warm AHAs happen?

Answer 7

not always

usually a macrophage recognizes the IgG and takes a partial bite out of the RBC

this results in the classic RBC biconcave disk structure becoming a spherocyte

as the spherocyte circulates through the blood again, more bites are taken and eventually total hemolysis will happen

Question 8

what medications can induce warm AHA?

Answer 8

chemotherapies

B-lactamase inhibitors

alpha-methyldopa

Question 9

what is causing the body to make antibodies against RBC antigens in AHA?

Answer 9

most of the time there’s no reason = idiopathic AHA

other times antibodies are formed due to acute infections, leukemia, rheumatic disorders, solid cancers, chronic inflammatory disease and medications

Question 10

what are the symptoms of warm AHA?

Answer 10

• fatigue
• jaundice
• splenomegaly
• pallor
• tachycardia
• high-output heart failure in extreme cases

Question 11

at what temperature do cold AHA antibodies work best?

Answer 11

below 30°C

aka in the periphery of the body

Question 12

what do the antibodies in cold AHA do?

Answer 12

commonly called cold agglutinins

they can cause clumping together of RBCs in cooler regions of the body, such as the fingertips

Question 13

what antibodies are found in cold AHAs?

Answer 13

IgM antibodies

immunoglobulin M

IgG is found in warm AHA

Question 14

how many antigens can an IgM antibody bind to?

Answer 14

IgM antibodies are secreted as pentamers

so a single IgM pentamer can bind ten antigens

this high number of binding sites is what allows for RBC agglutination at colder temperatures –> RBCs can be released from IgM at warmer temperatures

Question 15

what is the complement system?

Answer 15

the complement system, once activated by IgM binding, can lead to intravascular hemolysis in cold AHA

some IgM-coated RBCs are not lysed peripherally and circulate to the spleen and undergo extravascular hemolysis

BUT the intravascular hemolysis and agglutination, though, that allows us to distinguish cold AHA from warm AHA

Question 16

What is the mechanism of intravascular hemolysis in cold AHAs?

Answer 16

In cold AHAs, intravascular hemolysis occurs secondary to IgM induced complement activation.

Question 17

what causes cold AHAs?

Answer 17

most are idiopathic

Mycoplasma and mononucleosis infections and lymphoproliferative disorders are also associated with cold AHAs

pneumonic:
IgM-induced AHA are caused by Mycoplasma and mononucleosis

Question 18

what symptoms are present with cold AHAs?

Answer 18

cyanosis and pain in the extremities

rarely, people can have red- tinged urine, signifying hemoglobinuria, after acute hemolytic episode

Question 19

what is the size of RBC in AHAs?

Answer 19

normocytic

normal cell volume

Question 20

how is the reticulocyte count in AHAs effected?

Answer 20

increase in reticulocytes in the blood, reflecting the increased production of RBCs by the bone marrow to compensate for the RBCs that are being destroyed

Question 21

how is the serum bilirubin in AHAs effected?

Answer 21

elevated because of the hemolysis

Question 22

What will the CBC show in AHAs?

Answer 22

The CBC will show a normocytic anemia with reticulocytosis

Question 23

how are free haptoglobin levels effected in cold AHAs?

Answer 23

low free haptoglobin level

haptoglobin is a protein that binds to circulating free hemoglobin

in cold AHA, the hemoglobin released from complement-mediated lysed RBCs binds to haptoglobin, thus reducing the amount of free haptoglobin

Question 24

how are free haptoglobin levels effected in warm AHAs?

Answer 24

In warm AHA, the hemolysis is extravascular, and thus the haptoglobin does not change much.

Question 25

what does the blood smear in warm AHA show?

Answer 25

spherocytes

Question 26

what does the blood smear in cold AHA show?

Answer 26

visible agglutinations of RBCs

literally it looks like clumps of RBCs

Question 27

what is hereditary spherocytosis?

Answer 27

looks the same as warm AHA on a blood smear so don’t confuse them!!

Hereditary spherocytosis is a defect
in RBC membrane proteins that result in RBCs appearing as spherocytes rather than the typical biconcave shape

the cells might look the same as warm AHA but they’re caused by different mechanisms

Question 28

what test can be used to differentiated AHAs from other hemolytic anemias?

Answer 28

direct antiglobulin test (DAT) aka direct Coombs test

Question 29

what does the DAT test do?

Answer 29

differentiates AHAs from other hemolytic anemias

patient’s RBCs are mixed with anti-human immunoglobulin (AHG)

AHG binds to the antibodies attached to the RBCs, causing agglutination of the RBCs

this reaction will only occur if RBCs have antibodies attached to them so DAT result will be negative in non-immune hemolytic anemias

Question 30

how do you treat warm AHAs?

Answer 30

transfusions don’t always work because the auto-antibodies are still there and hemolysis will still occur

instead, treat them like an autoimmune disease

glucocorticoids like prednisone or rituximab are great

last resort is splenectomy because warm AHA hemolysis occurs in splenic macrophages so if you don’t have a spleen then hemolysis won’t occur

Question 31

what does rituximab do?

Answer 31

it’s a medication used to treat warm AHAs

Rituximab is an anti-CD 20 biologic medication that stimulates destruction of B cells

CD-20 is present on B- lymphocytes, so rituximab is useful in preventing the creation of auto-antibodies

Question 32

how do you treat cold AHAs?

Answer 32

glucocorticoids and splenectomy don’t really work

rituximab can be useful

most warm AHA cases are fairly mild, and may be alleviated by avoiding cold environments

Question 33

Which of the following is the most common cause of autoimmune hemolytic anemias?

Answer 33

Idiopathic