Topic 4: Autoimmune Hemolytic Anemias Flashcards
what are autoimmune hemolytic anemias?
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)
what kind of anemia is AHA?
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
What are the two major classifications of AHA?
warm and cold
warm AHA is the majority of AHA
what is warm autoimmune hemolytic anemia?
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
antigen vs. antibody
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
What type of antibody recognizes RBC antigens in warm AHAs?
IgG is the main antibody type in warm AHAs
does complete phagocytosis in warm AHAs happen?
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
what medications can induce warm AHA?
chemotherapies
B-lactamase inhibitors
alpha-methyldopa
what is causing the body to make antibodies against RBC antigens in AHA?
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
what are the symptoms of warm AHA?
- fatigue
- jaundice
- splenomegaly
- pallor
- tachycardia
- high-output heart failure in extreme cases
at what temperature do cold AHA antibodies work best?
below 30°C
aka in the periphery of the body
what do the antibodies in cold AHA do?
commonly called cold agglutinins
they can cause clumping together of RBCs in cooler regions of the body, such as the fingertips
what antibodies are found in cold AHAs?
IgM antibodies
immunoglobulin M
IgG is found in warm AHA
how many antigens can an IgM antibody bind to?
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
what is the complement system?
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
What is the mechanism of intravascular hemolysis in cold AHAs?
In cold AHAs, intravascular hemolysis occurs secondary to IgM induced complement activation.
what causes cold AHAs?
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
what symptoms are present with cold AHAs?
cyanosis and pain in the extremities
rarely, people can have red- tinged urine, signifying hemoglobinuria, after acute hemolytic episode
what is the size of RBC in AHAs?
normocytic
normal cell volume
how is the reticulocyte count in AHAs effected?
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
how is the serum bilirubin in AHAs effected?
elevated because of the hemolysis
What will the CBC show in AHAs?
The CBC will show a normocytic anemia with reticulocytosis
how are free haptoglobin levels effected in cold AHAs?
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
how are free haptoglobin levels effected in warm AHAs?
In warm AHA, the hemolysis is extravascular, and thus the haptoglobin does not change much.
what does the blood smear in warm AHA show?
spherocytes
what does the blood smear in cold AHA show?
visible agglutinations of RBCs
literally it looks like clumps of RBCs
what is hereditary spherocytosis?
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
what test can be used to differentiated AHAs from other hemolytic anemias?
direct antiglobulin test (DAT) aka direct Coombs test
what does the DAT test do?
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
how do you treat warm AHAs?
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
what does rituximab do?
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
how do you treat cold AHAs?
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
Which of the following is the most common cause of autoimmune hemolytic anemias?
Idiopathic
