Tareq Abadl: Differentiating Cold Agglutination from Hemolysis
Tareq Abadl, Medical Laboratory Specialist and Director of the Blood Bank at Dr. Abdelkader Al-Mutawakkil Hospital, shared a post on LinkedIn:
“Differentiating Cold Agglutination from Hemolysis.
ย 1.Cold Agglutination
Cold agglutination is commonly associated with Cold Agglutinin Disease, a type of autoimmune hemolytic anemia caused by IgM antibodies that bind to red blood cells (RBCs) at low temperatures, leading to RBC clumping.
Specimen Appearance
- EDTA blood shows a granular or clumping appearance
- After centrifugation, the plasma remains clear and normal (not red)
CBC Findings
- Decreased RBC count (falsely low)
- Decreased hematocrit (Hct)
- Hemoglobin (Hb) remains normal or near normal
- Hb and Hct are inconsistent
- MCV falsely increased
- MCHC falsely increased
Cause: The analyzer counts clumped RBCs as a single cell, producing erroneous results.
Blood Smear Findings
- RBCs appear in irregular clumps (agglutination)
Confirmation Test
- Warm the specimen at 37ยฐC for 15โ30 minutes
Re-analyze CBC:
- CBC parameters return closer to normal
- RBC clumping disappears on smear
ย 2.Hemolysis
Hemolysis refers to the destruction of RBCs and can occur in vitro (in the tube) or in vivo (in the patient).
A. In Vitro Hemolysis (Specimen Hemolysis)
Specimen Appearance
- Plasma appears clear red after centrifugation (hemolyzed plasma)
- No granular or clumping appearance
CBC Findings
- Hb may decrease slightly
- Hct decreases proportionally
- Hb and Hct remain consistent
Blood Smear
- May see ghost cells
- No agglutination
B. In Vivo Hemolysis
Commonly seen in conditions such as:
- Autoimmune hemolytic anemia
- G6PD deficiency
- Thalassemia
Plasma Findings
- Plasma may appear pink
- Increased bilirubin
- Increased LDH
- Decreased haptoglobin
Blood Smear Findings
- Spherocytes – autoimmune hemolytic anemia
- Bite cells – G6PD deficiency
- Schistocytes – fragmentation hemolysis
Key Laboratory Points (Very Important)
Suspect Cold Agglutination if:
- Granular/clumping blood appearance
- Hb and Hct are inconsistent
- Markedly high MCHC (more than 36โ37 g/dL)
Action:
- Warm the sample at 37 degrees Celsius and repeat CBC
Suspect Hemolysis if:
- Plasma is red after centrifugation
- Hb and Hct remain consistent
- No RBC clumping on smear”
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