Resident working at The Townsville Hospital with interest in General Medicine, Endocrinology and Neurology
An Unusual Association Of Cold Agglutinin Haemolytic Anaemia (CAHA) And Streptococcus Pneumoniae Sepsis In A Young Male
Case: A previously healthy 34 year old Fijian gentleman presented with five day history of cough, breathlessness and haematuria. Clinical examination revealed signs of anaemia, jaundice and left lobar pneumonia. Both blood culture and urinary antigen were positive for Streptococcus pneumoniae. Haemolytic screening was consistent with autoimmune intravascular haemolysis with positive coombs for C3D and red cell agglutination <37 ⁰C. M.pneumoniae, EBV, CMV, Hepatitis A, B,C ,HIV and autoimmune studies were negative. There was no evidence of clonally restricted B-cell population or PNH. Protein serum electrophoresis and cyroproteins were normal. Iron studies reflected acute phase reaction with normal Vitamin B12, folate and renal function. Treatment with intravenous Benzylpenicillin 2.4g QID was initiated. Hospital course was complicated with autoimmune haemolytic anaemia (AIHA cold agglutinin) requiring multiple blood transfusions and left parapneumonic effusion treated with intercoastal drainage. Patient was discharged in a stable condition after two weeks.
Discussion: Cold agglutinins constitutes for 15-20% of AIHA cases affecting primarily female and middle aged or elderly population1.Secondary Cold agglutinin syndrome is commonly associated with M.pneumoniae, Epstein-Barr virus, Rubella, HIV and Influenza. 2Linkage with autoimmune disorders like Rheumatoid Arthritis and lymphoid malignancies presents in elderly. Cases of S.pneumoniae induced haemolytic uremic syndrome resulting in MAHA have been published however association with CAHA is not reported. Management of CAHA is dependent on cause and severity of haemolysis and involves a multidisciplinary approach. Intravenous antibiotics and blood transfusions are effective for clinical stabilisation. In refractory cases, Ritixumab can be used to reduce IgM production and IVIG or Plasmapheresis to remove IgM. Newer agents like Sutimlimab targeting complement pathway is currently under clinical trial.2
Conclusion: This case illustrates an uncommon association of secondary cold agglutinin haemolytic anaemia with Streptococcus pneumoniae. Evaluation for an underlying cause contributing to CAHA must be explored for effective therapeutic management. Despite cause, blood transfusions or ,in severe cases, consideration of plasmapheresis or IVIG would be beneficial to prevent clinical deterioration.
Berentsen, S., Röth, A., Randen, U., Jilma, B. and Tjønnfjord, G. (2019). Cold agglutinin disease: current challenges and future prospects. J Blood Med https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497508/
Swiecicki, P., Hegerova, L. and Gertz, M. (2013). Cold agglutinin disease. Blood. https://ashpublications.org/blood/article/122/7/1114/32390/Cold-agglutinin-disease