Autoimmune hemolytic anemia the annual incidence of which is estimated between 1/80 000 and 1/35 000 in North America and Western Europe. It may be primitive (idiopathic) or, more often, secondary to an underlying disease, such as an infection to Mycoplasma pneumoniae, HIV or Ebstein-Barr, a lymphoproliferative syndrome , a systemic autoimmune disease or a neoplasia (lymphoma). The majority of cases are secondary with the presence of a monoclonal IgM (usually kappa subtype) antibody with cold agglutinin activity. Idiopathic or cases secondary to lymphoma are usually chronic, while those of infections cause rather present as acute forms.

These cold agglutinins are  anti-erythrocytic antibodies causing agglutination of the red blood cells at temperatures below 37 ° C and their fixation to the C1 complex of complement. Their agglutination is maximal at 4 ° C but may be observed up to 20-25 ° C. Hemolysis occurs during the rewarming.

It is important to know the thermal amplitude of the agglutinins (temperature at which agglutination is observed) as well as their titer (concentration: < 1/32 = low titer, > 1/128 = high titer).

Clinical manifestations are similar to acute or chronic hemolytic anemia, with pallor and fatigue. During the hemolytic episodes, symptomatology can include severe back and leg pain, headaches, vomiting, diarrhea, dark urines and hepatosplenomegaly. The disease can be triggered or worsened by a cold atmosphere or intercurrent infection; the episodes of acute hemolysis with hemoglobinuria and hemoglobinemia are more frequent in winter. It can start brutally, with anemia and hemoglobinuria, or progress more gradually and insidiously. Sometimes, the pathology is discovered fortuitously, on a routine total blood count showing abnormal red blood cells agglutination.

Management is based on global rewarming with avoidance of cold exposure. It may be the only treatment in patients with few symptoms and slight anemia alone. The disease is generally resistant to corticosteroids. Rituximab may be a therapeutic option.

Anesthetic implications: 

prevention of hypothermia; rewarming of blood products; in case of surgery under extracorporeal circulation, a normothermic cardioplegia must be used; in case of organ transplantation, the organ must be rewarmed to at least 30 ° C before being implanted.

References : 

-        Young S, Haldane G.
Major colorectal surgery in a patient with cold agglutinin disease.
Anaesthesia 2006; 61: 593-6

-        Gentili M.
Gestion périopératoire des patients avec un syndrome des agglutinines froides.
Le Praticien en Anesthésie-Réanimation 2017; 21: 317-8

-        Cho S-H, Kim DH, Kwak YT.
Normothermic cardiac surgery with warm blood cardioplegia in patient with cold  agglutinins.
Korean J Thorac Cardiovasc Surg 2014;47:133-6

Updated: May 2022