Cold Agglutinin Hemolytic Anemia

1. Hematology:
CaseStudy
Hanisha EricaV. Hernandez, RMT

2. CASESTUDY
 Leslie’s blood upon extraction showed macroagglutination on the
evacuated test tube when she had her annual check-up. Her urine
gives dark color in which her clinician suspected that indicates
intravascular hemolysis. Her laboratory results information
showed the following:
 Hgb : 9.0 g/L MCV : 102 fL
 Hct : 29 L/L MCH : 25 pg
 RBC : 3.0 x 1012 L MCHC : 31 %
 RDW : 11.9 WBC : 4.6 x 109/L
 RPI: 3.4 x basal Platelet Count : 88 x 109 L
 Her clinician suspected that Leslie had an “Idiopathic Cold
Hemmaglutinin Syndrome” based on her recent infection with
Mycoplasma pneumonia.
 After several weeks her blood lab results returns to normal level.

3. LAB RESULTS LaboratoryTest
Normal Female
Values
Leslie’s Findings
Hemoglobin 12 – 16 g/L 9.0 g/L
Hematocrit 35 – 45 % 29 L/L
RBC Count 3.8 – 5.5 x 12 /L 3.0 x 1012 /L
RDW 11.5 – 14 % 11.9 Normal
Reticulocyte Production Index 0.5 – 2.5 % 3.4 %
MCV 82 – 100 fL 102 fL
MCH 27 – 32 pg 25 pg
MCHC 31 – 35 % 31 % Normal
WBC Count 4.0 - 11 x 109/L 4.6 x 109/L Normal
Platelet Count 150 - 450 x 109/L 88 x 109/L
Macrocytic
Anemia
Reticulocytosis

4. ANEMIA
MORPHOLOGICALCLASSIFICATION
 MeanCellVolume
 MeanCell Hemoglobin Concentration
= MACROCYTIC NORMOCHROMICANEMIA
1. MegaloblasticAnemia
1. Vitamin B12 Deficiency
2. Folic Acid Deficiency
2. Non-MegaloblasticAnemia
1. Hepatic Disease
2. Alcoholism
3. Hypothyroidism – e.g. myelodysplastic
4. AplasticAnemia
****Hemolytic Anemia
= NORMAL
RETICULOCYTOSIS

5. HEMOLYTIC
ANEMIA TWOTYPES OF HEMOLYTICANEMIA
1. Extravascular Hemolysis (most common)
 Splenic and hepatic clearance of defective RBCs
2. INTRAVASCULAR HEMOLYSIS
 RBC membrane injury (Trauma, autoimmune, infection)
Macroagglutination
Dark colored Urine
Recent infection with Mycoplasma pneumoniae
AUTO-IMMUNE
Hemolytic Anemia
COLD AGGULITININ HEMOLYTIC
DISEASE

6. COLD
AGGLUTININ
HEMOLYTIC
ANEMIA
 a form of autoimmune hemolytic anemia caused by cold-reacting
autoantibodies or cold agglutinins
 Autoantibodies that bind to the erythrocyte membrane at low
temperatures leading to premature erythrocyte destruction
(hemolysis)
 RBC are normocytic but our findings show they are MACROCYTIC
 Correlated with doublet erythrocytes
 Two clinical forms:
1. Acute Form
- Less common and always self-limited
- Occurs during recovery phase of infectious disease such as:
- Mycoplasma pneumonia, infectious mononucleosis, influenza, HIV
2. Chronic Form
- May develop in association with B-cell lymphoid neoplasms or as
idiopathic condition

7. COLD
AGGLUTININ
HEMOLYTIC
ANEMIA dueto
Mycoplasma
pneumoniae
Infection
 Cold agglutinins or cold antibodies are naturally occurring
 Occur at low titers, less than 1:64 measured at 4º C.
 Increase on cold agglutinins titer is usually observed during
Mycoplasma pneumonia infection
 Have no activity at higher temperatures
 USUALLY OFTHE IgMVARIETY
 Only activated by cold temperatures wherein they attached to the
red blood cell antigen
= MACRO-AGGLUTINATION

8.  Binding of autoantibodies or
the cold agglutinins to the
antigen in RBCs activates
CLASSICAL PATHWAYOF
THE COMPLEMENT
SYSTEM
 attack the antigen on the
surface of red blood cells
causing the cells to burst
open and release
hemoglobin (hemolysis)
DARK URINE =
HEMOGLOBINURIA

9. COLD
AGGLUTININ
HEMOLYTIC
ANEMIA due to
Mycoplasma
pneumoniae
Infection
 Cold agglutinins belonging mainly to IgM are specific for “I”
antigen of the red blood cell surface
 “I” antigen is usually present in most adults
 Not present on the RBC membranes of fetuses – “i” antigen
 Cold reactivity of the IgM class is attributed to “I” antigen where as
the temperature drops it is presumed to move itself to more
accessible positions on the red blood cell membrane

10. PATHOGENESIS
Ab/Ag
Complex
• High levels of Antigen I on RBC membrane binds
to anti-I IgM antibody
Complement
Activation
• Classical Pathway paved way to activation of
complement pathway
C3b
Production
• Once complement sequence complete, C3b
attached to RBC membrane
Pitting of RBC
• Mononuclear phagocytic cells of liver and spleen
have special receptors for C3b
Microspherocy
tes
• Sequestered by spleen and target for
phagocytosis and pre-mature hemolysis

11. DIAGNOSIS  Peripheral Blood Smear
 Hemoglobin and Hematocrit
 ReticulocyteCount
 Mean CellVolume
 Appear as macrocytic due to doublet erythrocytes counted as single
cell
 Direct AntiglobulinTest
 also known as the direct Coombs test, is used primarily to help
determine whether the cause of hemolytic anemia, a condition in
which red blood cells (RBCs) are destroyed more quickly than they
can be replaced, is due to antibodies attached to RBCs.
 Positive results indicate cold agglutinins present

12. TREATMENT
 Avoidanc e of cold – exposure (Idiopathic Cold Agglutinin
Hemolytic Anemia)
 Use mittens and warm clothes
 Treat the underlying cause of Cold Agglutinin Hemolytic Anemia
 Infection with Mycoplasma pneumonia
 Plasmapheresis
 Reduce antibody titer

13. PROGNOSIS
 Leslie’s Case
 Laboratory Results returned to normal after several weeks due to:
 Acute type of Cold Agglutinin Hemolytic Anemia
 Cause of the increase in antibody titer was successfully treated
 Due to high reticulocyte production, RBC level returned to normal

14. Thank You!