Should we worry about cold-reactive antibodies in cardiac surgery?

The following is a discussion of cold-reactive antibodies and cardiac surgery by Gerald A Hoeltge, MD, which he wrote on Feb 9, 1999, followed by a discussion among members of the CBBS e-Network.

Dr. Hoeltge, the blood banker at the Cleveland Clinic Foundation, was asked to share his opinion about the management of cold agglutinins in patients undergoing systemic hypothermia as part of a surgical procedure.

According to Dr. Hoeltge, cold reactive antibodies really are best ignored. To quote him: "We do about 4,200 hearts a year, which the marketing people tell me is more than anyone else. I don't know that for sure, but the volume has been like that for a long time. We've not looked for cold antibodies for 15 years. The surgeons haven't complained, or at least haven't noticed. Of course, systemic hypothermia is much less prevalent today than it used to be during cardiac surgery, and pump times much shorter. Interest in cold autoantibodies, such as it was, is waning. We have had two cases of cold reactive antibodies that visibly agglutinated red cells in the bypass pump tubing. Neither was detected pre-op of course because we do the same routine for heart patients as any other: MTS antibody screen at 37 deg. C., immediate spin crossmatch (and a 37 deg. C. LISS, and AHG crossmatch if indicated). The pump operators were more than a bit disconcerted. In both cases the agglutinates dispersed upon rewarming. There was no hemolysis and no lasting effects.

To blood bankers who remain emotionally attached to cold antibody detection for cardiac surgery, I can only ask, "What would you do if you found one?" Any patient who needs deep hypothermia is so sick that the cold agglutinin is the least of his problems. "

To which the following comments have been made some members of the CBBS. These comments are without attribution and do not represent an official opinion or policy of the CBBS:

Some of these comments have been excerpted from a chapter in Clinical Practice of Transfusion Medicine, third edition, pp 232-234.

Recommendations have been made in the past to perform compatibility test procedures in the cold routinely for patients undergoing surgery with induced hypothermia (Diaz et al., Arch Intern Med 1983;144:1639). However, no data are available to support the necessity of such a policy. However, if a patient has autoimmune hemolytic anemia caused by a cold antibody (cold agglutinin syndrome, CAS), it seems logical to avoid hypothermia because of the risk of exacerbating hemolysis.

Although surprisingly few complications caused by cold autoagglutinins during cardiac surgery have been reported, Bedrosian and Simel (Southern Med J 1987;80:466) reported a patient with well-compensated chronic CAS who had an acute hemolytic crisis during an elective herniorrhaphy in a cool operating room. The patient's hematocrit decreased from 36% to a low of 12.6%. Other instances of exacerbation of CAS with exposure to cold, although not associated with surgery, have been well documented (Colmers and Snavely N Engl J Med 1947;237:505; Niejadlik and Lozner Transfusion 1974;14:145). When measures have been taken to avoid the potential hematologic and cardiac consequences of cold exposure in patients with cold agglutinins, the reported results have been excellent (reviewed in Clinical Practice of Transfusion Medicine, third edition, Petz, Swisher, Kleinman, Spence and Strauss, eds., Churchill & Livingstone, 1996, pp 232-234).

In recent conversations about this topic with to a cardiac surgeon and an anesthesiologist who works with cardiovascular surgeons, these physicians stated that when autoagglutination is noted, cold crystalloid cardioplegia is performed and the systemic temperature is maintained above the thermal reactivity of the cold antibody. Ordinarily, patients are cooled to about 28 deg. C for cardiac surgery. If the procedure is expected to be uncomplicated and shunt time is predicted to be short such as a first time 1 or 2 vessel by-pass, no cooling is necessary. In the presence of striking cold agglutination, the patient is kept at a warmer temperature. The anesthesiologist commented that he had used these techniques for avoiding adverse effects of cold agglutinins in several patients in recent years. In some cardiovascular surgery, particularly when working on the aorta or doing procedures on small children, it is necessary to cool the patient to 16-18C. In these cases, an acute hemolytic episode might be expected to occur in a patient who goes into surgery with a cold antibody induced autoimmune hemolytic anemia. In such cases, plasma exchange prior to surgery would seem indicated and has been performed with a successful outcome (See Clinical Practice of Transfusion Medicine, as cited above). Since cold agglutinins may be detected in the serum of almost all individuals, the critical problem is to decide which characteristics of a given patient's cold agglutinin would warrant special precautions during surgery. This question cannot be answered precisely, but special precautions would seem important when a patient has a cold antibody-induced autoimmune hemolytic anemia.

Although cold-reactive antibodies are not routinely characterized in detail in the blood transfusion service, if the antibodies have a high enough thermal amplitude to cause autoimmune hemolytic anemia, they will ordinarily be noticed during routine compatibility test procedures. Also, significant autoagglutination will often be noticed prior to surgery because it interferes with routine laboratory tests such as the CBC.

For patients without hemolytic anemia, the thermal amplitude and titer of the antibody are probably the best guides to possible complications during surgery. Although cold agglutinins reactive at room temperature might seem to be of potential significance during hypothermic surgical procedures, there is an impressive lack of reports of complications caused by such antibodies even though they are very common. Less common are antibodies that are strongly reactive at temperatures of 30 deg. C or above. These antibodies may be associated with hemolytic anemia, and special precautions would seem to be warranted. In some cases, autoagglutination will first be noticed in the operating room.

ADDENDA Jan. 12, 2009

1. A blood bank manager at a hospital in Michigan reports that his laboratory recently started using a "solid phase automated testing instrument" and have noticed that they are not picking up as many room temperature reacting anti-M and cold autoagglutinins. While many transfusion medicine experts would consider this to be an improvement in serologic testing, some of their cardiac surgeons are concerned about missing these antibodies. They worry that these missed antibodies might cause harm to a patient when they "cool down" the patient during open heart surgery. The inquiring colleague is aware of the extensive discussions about this issue in this discussion and "Should we worry about cold-reacting antibodies in patients undergoing hypothermia for cardiac surgery? (revisited, AGAIN)" but would like an update on how other institutions who have switched to either solid phase or gel testing handle this issue.

ADDENDA Jan. 18, 2009

2. A technical supervisor at a hospital in Arizona reports that for several years they have used an automated solid phase test system to screen for unexpected red cell antibodies. They usually do NOT detect cold reacting antibodies such as anti-M with this screening system. However, since they perform immediate spin crossmatches for patients whose antibody screen by solid phase testing is negative, from time to time an open heart surgery patient will have a surprisingly reactive immediate spin crossmatch due to either an agglutinating alloantibody or autoantibody (which was missed by the solid phase screening test). When that happens they initiate a stat work up to determine if the antibody is a cold autoagglutinin or an alloantibody. If the open heart surgery patient's crossmatch is positive due to a cold autoagglutinin, they so inform the clinician. If the crossmatch is positive due to an alloantibody such as anti-M, they screen for M-antigen negative RBC units.

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