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‘Cold Agglutinin-Induced Haemolytic Anemia’ - Challenges in Immunohaematology Clameo Chimfombo Frances O’Shea St Vincent’s Hospital Sydney SydPath Pathology Moree Hospital, NSW
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‘Cold Agglutinin-Induced Haemolytic Anemia’

Jan 15, 2023

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PowerPoint PresentationSt Vincent’s Hospital Sydney SydPath Pathology
Moree Hospital, NSW
“Fatal cold agglutinin - induced haemolytic anaemia - a case report”, Lodi et al. Journal of Medical Case Reports 2010, 4:252
Hb 38g/L
Dramatic haemolysis
Cardiovascular Shock
Pre-transfusion testing found presence of cold agglutinins High cold agglutinins titre levels with anti-H antibodies in the patient’s blood
reacted with H antigen in universal O red cells. Concluded risk of emergency transfusion should be assessed against risk of
delaying transfusion until pre-transfusion tests are completed.
AIM Present two cases of Cold Agglutinin Induced Haemolytic Anaemia
Discuss and learn from peers - challenges that can be posed by cold agglutinins
Always happy to learn….
Cold Agglutinins Cold antibodies, which are often IgM, can cause both red cell
agglutination and complement mediated haemolysis
Cold Exposure
Body Temperature Decreases (as low as 28 degrees in the extremities)
Cold Autoantibody Activated
Clinical features such as cyanosis and ischaemia due to haemolysis or red cell agglutination
Infections, eg Mononucleosis, Mycoplasma pneumoniae may also result in cold antibody production
Warming blood at 37 C usually resolves cold agglutinins. However some severe cases are unresolved.
CASE 1 52 yr old female
hypothyroid , SOB on exertion for 2 months, previous Vit B12 deficiency
FBC - Cold Agglutinins flagged by analyser
- Hb 55 (previously 145, 4 months prior)
- WCC 4.1, Plt’s 286
- Sampled warmed, cold agglutinins not resolved MCHC =432 (RR 320-360)
- Spun Hct 0.23 (no change from automated result)
- LDH 1004 (RR 0 - 430)
Dr notified, patient admitted to emergency department Repeat FBC - similar results
Haemolysis screen requested - Reticulocytes (unable to perform)
- Haptoglobin - DAT (+ve, polyspecific) Blood Film : Polychromasia, auto agglutination, occasional spherocytes
Group and Hold - O Positive
- Autoantibody detected with pan reactivity UNABLE TO CROSSMATCH COMPATIBLE UNITS
Haematologist advice‘TRANSFER PATIENT TO LARGER INSTITUTION’
Patient transferred to a larger institution Similar results on arrival - Hb = 40
- Haptogloblin = <0.10 (RR: 0.30-2.00) Mycoplasma Pneumoniae identified as causing the the cold antibody induced
haemolytic anaemia Cold Agglutinins not resolved Transfused incompatible crossmatched
blood Rh and K matched Blood warmer OUTCOME : Patient recovered well as infection resolved
CASE 2 76 yr old Female
No clinical notes
20/06/17 : INR - 3.5
- Cold Agglutinin Flag MCHC=377 (RR 320-360)
- Cold Agglutinins resolved on warming, MCHC 345
Blood Film : Polychromasia, occasional spherocytes, agglutination
DAT : +ve, polyspecific
GP notified GI bleed ? over warfarinised ?dark stools
INR no > 3.5 recorded no FOB’s received Laboratory Findings Cold Antibody Induced Haemolytic Anaemia
Subsequent laboratory testing : Full haemolysis screen together with Mycoplasma pneumoniae
Haematologist advice TRANSFER PATIENT TO LARGER INSTITUTION
GP Continued to investigate GI bleed Colonoscopy
Intravenous Iron Infusion per Surgeon
Crossmatch 3 units requested by Anaesthetist VERY RISK
- Increased risk of bleeding during surgery - Limited Blood Stock - Limited Laboratory Resources - Severity of haemolysis - lab findings -Remote Location and Retrieval if required
Cold agglutinins resolved on warming Pre-warmed technique tubes and BioVue No Antibody Detected 3 compatible units found Patient transfused using blood warmer
OUTCOMES: Cause of cold agglutinins never investigated Faecal Occult Blood was never determined No evidence of a GI bleed No immediate follow up of Hb post transfusion and surgery
DISCUSSION Always room for improvement
? Protocols for resolving cold agglutinins
Unresolved cases BUT urgent results needed eg. Blood Transfusion
Laboratory findings vs. Clinicians diagnosis
Acknowledgements Ms Rosemary Marando, Senior Scientist, Transfusion, SydPath, St Vincent’s
Hospital, Sydney
Dr Joanne Joseph, Staff Specialist Haematology, SydPath, St Vincent’s Hospital, Sydney
Moree SydPath staff
References 1. Berentsen, Sigbjørn, Ulla Randen, and Geir E. Tjønnfjord. "Cold agglutinin-mediated
autoimmune hemolytic anemia." Hematology/oncology clinics of North America 29.3 (2015): 455-471.
2. Berentsen, Sigbjørn, and Geir E. Tjønnfjord. "Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia." Blood reviews 26.3 (2012): 107- 115.
3. Lodi G, Resca D, Reverberi R. Fatal cold agglutinin-induced haemolytic anaemia: a case report. Journal of Medical Case Reports. 2010;4:252. doi:10.1186/1752-1947-4- 252
4. Jain, Michael D., et al. "Seek and you shall find—but then what do you do? Cold agglutinins in cardiopulmonary bypass and a single-center experience with cold agglutinin screening before cardiac surgery." Transfusion medicine reviews 27.2 (2013): 65-73.
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