Clinical and serological characterization of cold agglutinin syndrome in a Tertiary Care Hospital in Eastern India

Abstract

Background and Aim:Cold agglutinin syndrome (CAS) primary or secondary represents approximately 16-32% of autoimmune hemolytic anemia cases. Most patients present with mild, chronic hemolytic anemia with exacerbation of the condition in the cold environment. Red cell transfusions are only indicated when there is a life-threatening anemia causing crisis. We studied the clinical and serological characterization of CAS with the aim that the information gained from this study would help in proper diagnosis and management of these patients.Materials and Methods:The prospective study included nine patients who were admitted with severe anemia. Detailed work-up were conducted to establish the diagnosis, severity of in vivo hemolysis and transfusion management.Results:All patients presented with pallor, weakness, fatigue and painful fingers and toes with exacerbation of symptoms in winter months. Secondary CAS was observed in three patients suffering from malignant lymphoma. Red cells of all patients were coated with complements (C3) more specifically C3d. In one patient suffering from malignant lymphoma, the cold autoagglutinin titer was as high as 4096. Autoantibody in seven patients was specific to “I” antigen and one to “i” antigen.Conclusions:We conclude that detailed clinical and serological characterization is needed to diagnose and manage CAS. Whereas avoidance of cold exposure is the primary therapy, but no critical patient should be denied blood transfusion due to serological complications. All transfusion services should follow the correct protocol to maximize blood safety in CAS.

Systematic review for the serological testing for cold agglutinins: The BEST collaborative study

“…Otherwise, most articles describe large variation in the CA titer between individual patients with CAD/CAS, but an evaluation of a correlation between the titer and the hemolytic degree in vivo is missing 43,50–52 . Pla et al showed a titer range of 32–2048 in patients with CAD/CAS, in comparison with a titer of 16 in healthy donors, without a reported correlation titers and the degree of hemolysis 53…”

“…To what extent the antibody specificity indicates severity of the disease, remains unknown. In only 6/13 case series performing testing on CA specificity, the CA specificity was described as either being correlative or used to confirm the diagnosis in patients with CAD/CAS 43,45,48,51,56,57 . In the case series by Sokol et al, with 121 patients, the most common autoantibody specificity was anti‐I 57 .…”

“…44 Wilen et al reported that a positive DAT with complement deposition can be used as an acceptance criterion for further CA testing, as a negative DAT using anti-C3 has a negative predictive value of 98% for CA titers that may be associated with clinically significant CAD/CAS. 45 The DAT strength might reflect the concentration and avidity of CA, but only two case series reported on the association of agglutination strength with presence and severity of cAIHA 46,47 Studies that used a titer as part of definition for inclusion 43,45,48,50,51,63,64 Thermal Amplitude Case Series Described: 7 Described [48][49][50][51]56,57,64 Indicative of clinical significance: 3…”

“…Indicative of clinical significance: 52,54,65 Antibody specificity Case Series 6 Indicative 43,45,48,51,56,57…”

A case report of perioperative managements for a patient with gastric cancer and cold agglutinin syndrome

“…[ 2 ] Under some circumstances, the exacerbations of CAS could lead to acute hemolysis, jaundice, and even acute renal dysfunction when the patients are in a cold environment. [ 3 ] Most cases of CAS are complicated with lymphoma, and some other hematological malignancies and cases of CAS with solid tumors have been seldom reported. [ 4 ] Surgical resection is always the unique way to achieve curative outcome for the solid tumor patients.…”