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 Table of Contents  
Year : 2023  |  Volume : 13  |  Issue : 1  |  Page : 40-42

Congenital cardiac surgery in a patient with cold agglutinins

Department of Pediatric Cardiac Sciences, Sir Ganaga Ram Hospital, New Delhi, India

Date of Submission23-Jul-2021
Date of Decision10-Dec-2022
Date of Acceptance10-Jan-2023
Date of Web Publication24-Feb-2023

Correspondence Address:
Dr. Mridul Agarwal
F-57, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi - 110 060
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmrp.cmrp_73_21

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Cold agglutinin disease is a type of autoimmune haemolytic anaemia caused by autoantibodies that bind to red blood cell antigens at a cold temperature and causes extravascular haemolysis and sometimes thrombosis also. Due to exposure to a lower temperature during open-heart surgery, the activation of haemolysis may occur in the presence of cold agglutinin antibodies. We present the management of a cyanotic child who has undergone open-heart surgery after the detection of high cold agglutinin titres during routine pre-transfusion screening.

Keywords: Cold agglutinin, congenital cardiac surgery, cyanotic

How to cite this article:
Agarwal M, Joshi RK, Aggarwal N, Joshi R. Congenital cardiac surgery in a patient with cold agglutinins. Curr Med Res Pract 2023;13:40-2

How to cite this URL:
Agarwal M, Joshi RK, Aggarwal N, Joshi R. Congenital cardiac surgery in a patient with cold agglutinins. Curr Med Res Pract [serial online] 2023 [cited 2023 Apr 2];13:40-2. Available from: http://www.cmrpjournal.org/text.asp?2023/13/1/40/370516

  Introduction Top

Cold agglutinin disease (CAD) is characterised by the presence of circulating antibodies which binds to red blood cell antigens at temperatures below normal core body temperature which cause agglutination and extravascular haemolysis.[1],[2] The temperature range at which these antibodies are active is referred to as the thermal amplitude. The typical thermal amplitude for normally occurring cold agglutinins is in the range of 3°C–4°C, but many antibodies are active at higher temperatures such as occur in colder peripheries of the body. The person could be asymptomatic or may have anaemia or may have a history of acrocyanosis or may have raised haemolytic markers during screening.

During the surgery for a congenital heart defect, there is the possibility of cold exposure to the child. This may occur from shifting to the operation theatre, prepping for surgery, scrubbing the child or during the insertion of monitoring lines. Open-heart surgeries are usually performed with cardiopulmonary bypass (CPB) with controlled hypothermia and the cardioplegia to arrest the heart is mixed with autologous blood and delivered at a temperature of 4°C and targeted to cause myocardial cooling to <15°C. These exposures to low temperature in the presence of CAD may lead to haemolysis and thus intraoperative and post-operative complications. We present a case of a child who underwent tetralogy of Fallot repair with positive screening for cold agglutinin antibodies.

  Case Report Top

A 4-year-old, 15 kg boy diagnosed with tetralogy of Fallot with deep cyanosis and clubbing, was scheduled for a complete repair. During the blood cross-match testing, screening for cold agglutination antibodies showed the presence of a higher titre for these antibodies. The thermal amplitude of these agglutinins was 4°C (+1) and was negative at 22, 30 and 37°C. Titres at 4°C were 1/64. Other routine pre-operative tests, including blood count, liver and kidney function tests and coagulation profile, were normal.

The surgery was postponed and a haematology opinion was sought. There was no history of recent respiratory infection, exposure to a cold environment or any symptomatology suggestive of hypercoagulability and haemolytic anaemia or family history directing towards cold agglutinin. Reticulocyte count and peripheral smears were normal. Mycoplasma immunoglobulin G titres were not raised.

Although the cold agglutinin's thermal amplitude was 4°C, considering the presence of these antibodies, precautions were taken to avoid hypothermia by preventing any drift in ambient operating room temperature, infusing pre-warmed intravenous fluids and keeping the patient warm using the Cincinnati Sub-Zero heating cooling blanket roll. After induction of general anaesthesia, a median sternotomy was performed. About 3mg/kg of heparin was administered and target-activated clotting time was maintained greater than 480 s. CPB was initiated after aorto-bicaval cannulation. As discussed with haematology experts, the perfusate was kept warm at 37° C, and more importantly, the cardioplegia strategy had to be modified to antegrade warm cardioplegia induction at 37°C rather than at 4°C. After satisfactory diastolic cardioplegic arrest trans right, atrial closure of the ventricular septal defect and infundibular resection was performed. The patient was weaned successfully from CPB with no inotropic support. Aortic cross-clamp and CPB times were 85 and 142 min, respectively. A strict vigil was kept on the colour of the urine and for the development of clots in the CPB circuit.

The patient was extubated in the operating room and was shifted to the intensive care unit. The post-operative course was uneventful with no evidence of haemolysis. He was discharged on the 5th post-operative day. The patient was re-evaluated on 6-month follow-up and had no clinical or investigational evidence of haemolysis.

  Discussion Top

Cold agglutinin antibodies are not uncommon in normal healthy individuals and cold autoantibodies usually do not cause any problems if the titres are extremely low and pose no threat above the threshold temperature. The overall incidence of cold agglutinins in patients subjected to CPB is not well documented. A study by Agarwal et al.[3] have shown an incidence of 0.8% in their subset of adult patients undergoing CBP. The incidence is even rarer in the paediatric population undergoing CPB.[4],[5],[6]

At our institution before blood transfusion, screening for detection of thermally triggered antibody formation is done. When the screening test is positive, a thermal amplitude test as described by Hopkins and Walters,[7] is performed to determine the reactivity of cold autoantibodies at temperatures: 4°C, 22°C, 30°C and 37°C. Thermal amplitude test is especially helpful to determine whether systemic hypothermia, deep hypothermic circulatory arrest or cold cardioplegia will be tolerated or not. Management of these patients depends on thermal amplitude and levels of CA. Although our patient had no risk under mild hypothermic CPB, agglutination would have occurred in coronary arteries with the use of cold crystalloid cardioplegia delivered at 4°. Thus, the conduct of CPB was performed utilising normothermia with antegrade delivery of warm cardioplegia.[8],[9] Corticosteroids were not used, as it has not been proven to be of any benefit in such patients.[10],[11] The goal of management in the intraoperative period and on bypass is to maintain the temperature above the threshold temperature.

This case is presented here as it is unusual to have cold agglutinins in paediatric patients undergoing CPB and it was timely detected due to routine screening of all blood before transfusion. Centres that do not routinely screen for cold agglutinin (CA) can have unexplained morbidity and mortality due to perioperative myocardial infarction, cerebral infarction, haemolysis or renal failure. Interdepartmental coordination is essential for the detection and management of patients with such coexisting diseases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Park JV, Weiss CI. Cardiopulmonary bypass and myocardial protection: Management problems in cardiac surgical patients with cold autoimmune disease. Anesth Analg 1988;67:75-8.  Back to cited text no. 1
Fischer GD, Claypoole V, Collard CD. Increased pressures in the retrograde blood cardioplegia line: An unusual presentation of cold agglutinins during cardiopulmonary bypass. Anesth Analg 1997;84:454-6.  Back to cited text no. 2
Agarwal SK, Ghosh PK, Gupta D. Cardiac surgery and cold-reactive proteins. Ann Thorac Surg 1995;60:1143-50.  Back to cited text no. 3
Schubothe H. The cold hemagglutinin disease. Semin Hematol 1966;3:27-47.  Back to cited text no. 4
Hoashi T, Kagisaki K, Moon J, Takahashi Y, Hayashi T, Ichikawa H. Suspected cold agglutination during mild hypothermic pediatric open heart surgery: A report of two cases. J Artif Organs 2015;18:370-2.  Back to cited text no. 5
Hasegawa T, Oshima Y, Maruo A, Matsuhisa H. Paediatric cardiac surgery in a patient with cold agglutinins. Interact Cardiovasc Thorac Surg 2012;14:333-4.  Back to cited text no. 6
Hopkins C, Walters TK. Thermal amplitude test. Immunohematology 2013;29:49-50.  Back to cited text no. 7
Muehrcke DD, Torchiana DF. Warm heart surgery in patients with cold autoimmune disorders. Ann Thorac Surg 1993;55:532-3.  Back to cited text no. 8
Gokhale AG, Suhasini T, Saraswati V, Chandrasekhar N, Rajagopal P. Cold agglutinins and warm heart surgery. J Thorac Cardiovasc Surg 1993;105:557.  Back to cited text no. 9
Shah S, Gilliland H, Benson G. Agglutinins and cardiac surgery: A web based survey of cardiac anaesthetic practice; questions raised and possible solutions. Heart Lung Vessel 2014;6:187-96.  Back to cited text no. 10
Berentsen S, Tjønnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev 2012;26:107-15.  Back to cited text no. 11


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