ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Surendra K. Agarwal
Probal K. Ghosh
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Agarwal, S. K.
Right arrow Articles by Gupta, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Agarwal, S. K.
Right arrow Articles by Gupta, D.

Ann Thorac Surg 1995;60:1143-1150
© 1995 The Society of Thoracic Surgeons

Collective Review

Cardiac Surgery and Cold-Reactive Proteins

Surendra K. Agarwal, MCh, Probal K. Ghosh, FRCSEd, Debashish Gupta, MD

Departments of Cardiovascular and Thoracic Surgery and Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India


   Abstract
Top
 Footnotes
 Abstract
Introduction
 Incidence
 What Are Cold-Reactive Proteins?
 References
 
Cold agglutinins are commonly found in sera of healthy persons. They rarely become clinically apparent due to their activity at low temperatures. In these patients, cardiovascular operations requiring hypothermia can result in complications such as hemolysis, renal failure, and myocardial damage and can cause unexpected morbidity and mortality. The literature on cold-reactive proteins is reviewed, and methods of diagnosis and management related to cardiac surgery are suggested. Ideally all patients should be routinely tested preoperatively for the antibodies, and appropriate changes in cardiopulmonary bypass and myocardial management plans should be made in positive patients. Preoperative plasmapheresis may be a useful adjunct, especially in patients requiring operation under profound hypothermia and circulatory arrest. Currently, warm heart surgery appears to be the most expedient method. Unexpected detection of agglutination during operation or hemolysis after operation requires a specific treatment plan.


   Introduction
Top
 Footnotes
 Abstract
 Introduction
Incidence
 What Are Cold-Reactive Proteins?
 References
 
Open heart operation (OHO) with hypothermia in patients with cold-reactive proteins can cause hemolysis, inadequate cardioplegic distribution, myocardial infarction, renal and hepatic insufficiency, and cerebral damage. Persistent intravascular hemolysis caused by these proteins in a patient undergoing hypothermic cardiopulmonary bypass (CPB) was reported first by Wertlake and colleagues in 1969 [1]. Various case reports of detection, complications, and management of these patients during cardiac as well as noncardiac operations [2–25] followed. Our recent experience with a number of these patients prompted this review. We outline the physiology, analyze the available reports, and provide guidelines for detection and management of this uncommon, but probably not rare clinical problem to prevent unwarranted perioperative morbidity and mortality.


   Incidence
Top
 Footnotes
 Abstract
 Introduction
 Incidence
What Are Cold-Reactive Proteins?
 References
 
The overall clinical incidence of cold reactive proteins in the OHO population is difficult to estimate. Most publications are anecdotal case reports without any mention of incidence. The cold agglutinin syndrome accounts for about one third of all cases of autoimmune hemolytic anemia [26]. Moore and colleagues [8] reported 7 of 832 OHO patients to be positive for cold agglutinins. In a study of patients with acquired immunodeficiency syndrome and related disorders, Pruzanski and associates [27] reported 12 of 81 patients to be positive for these antibodies. In 1993, Bracken and co-workers [20] reported an incidence of 4% (19/504) from Albany Medical College, Albany, NY, of which only 3 patients had agglutination at higher than 4°C. The same report mentioned an incidence of 0.4% (4/1,000) at the University of Texas Health Science Center, San Antonio, TX. We encountered 13 patients in approximately 1,500 consecutive patients undergoing OHO at our center, for an incidence of approximately 0.8%. Chronic idiopathic cold agglutinin disease is predominantly a disease of the elderly, with a clear peak incidence in the seventh and eighth decades [26, 28]. The same appears to be the experience with the cardiac surgical patients (Table 1Go). Patients have been reported to have a mean age of 60 years (range, 6 months to 77 years) and a male to female ratio of 3:2. All patients except 2 [7, 14] had acquired heart disease of coronary arteries and valves. Congenital lesions were noticed in 2 of 13 patients in our experience, but all patients were adults. The exact role played by age as a factor in the manifestation in these patients remains to be defined.


View this table:
[in this window]
[in a new window]
  		Table 1. . Historical Review: Cardiovascular Surgical Patients With Cold-Reactive Proteins
 

   What Are Cold-Reactive Proteins?
Top
 Footnotes
 Abstract
 Introduction
 Incidence
 What Are Cold-Reactive Proteins?
References
 
Cold-reactive proteins can be classified into four categories: (1) Cryoglobulins are serum proteins or protein complexes that undergo reversible precipitation at low temperatures [29]. (2) Cold agglutinins are antibodies that react more effectively with red cells and also with other cells at low temperatures, resulting in cold hemagglutinin disease characterized by agglutination of red cells with resultant microvascular occlusion and hemolysis (26). (3) Donath-Landsteiner antibodies are rare immunoglobulin G (IgG), anti-P proteins seen in patients with paroxysmal cold hemoglobinuria. They are potent hemolysins. They are not active at 20°C in saline solution or at 30°C in albumin and may not be detected during crossmatching. There is no clinical report of OHO in patients with this cold-reactive protein [26]. (4) The fourth category is cryofibrinogen [10].

Cryoglobulins
Although the phenomenon of cryoprecipitation was first described in vitro in 1929 [29, 30], its clinical significance was reported for the first time in 1933 by Wintrobe and Buell [31] in a 56-year-old woman with multiple myeloma presenting with progressive Raynaud's phenomenon, purpura, hepatosplenomegaly, and renal vein thrombosis. The first systematic study of these antibodies came in 1947 from Lerner and Watson [29].

The cryoglobulins have been classified into three main groups. Type I cryoglobulins consist of monoclonal proteins. The antibody in multiple myeloma is usually IgG, whereas in Waldenstrom's macroglobulinemia and lymphoreticular disease, it is immunoglobulin M (IgM). The presence of these proteins in absence of plasma cell dyscrasia is termed ``essential monoclonal cryoglobulinemia'' [29]. Type II cryoglobulins consist of mixed immunoglobulin complexes in which the monoclonal component, usually IgM but occasionally IgG or immunoglobulin A, has antibody specificity for polyclonal IgG [32]. These antibodies are associated with autoimmune, infectious, or lymphoproliferative disorders [32, 33]. Essential mixed cryoglobulinemia encompasses the cases where no cause is detected. Type III cryoglobulins are composed of one or more classes of polyclonal immunoglobulins and sometimes nonimmunoglobulin substances, eg, complement components, polynucleotides, viral antigens, and other materials [29, 32, 34]. One of the polyclonal molecules, usually IgM, has antibody activity against polyclonal IgG molecules. Usually they are associated with infections (viral, bacterial, parasitic) or autoimmune diseases or may be familial. But they sometimes occur in the absence of any discernible cause (essential mixed cryoglobulinemia).

CLINICAL MANIFESTATIONS.
Most patients with single-component monoclonal cryoglobulins have no symptoms. Common symptoms result from cryoprecipitation within capillaries of skin with resultant impaired blood flow [32], eg, Raynaud's phenomenon, necrosis of tip of nose, ears, fingers, toes, or legs, acrocyanosis, vascular purpura, urticaria, supramalleolar leg ulcers, and livedo reticularis. Massive endomembranous deposits of cryoglobulins or diffuse glomerulonephritis with endomembranous deposits of complexes constitute renal manifestations. Hemorrhages, peripheral neuropathies, articular manifestations, and thrombosis of major visceral vessels have also been described [29]. In patients undergoing cardiovascular operations these features should alert the clinician about associated cryoglobulinemia.

In mixed disease, the cryoprecipitate behaves as immune complex [29], resulting in various typical manifestations of immune complex disease such as vascular purpura [35], livedo reticularis, arthralgia, and hepatosplenomegaly, renal disease (azotemia, edema or hypertension), intraabdominal vasculitis and generalized lymphadenopathies. In association with these manifestations the features of the primary disease causing cryoglobulinemia may be present.

LABORATORY DETECTION.
Blood is collected in warm syringes and clotted at 37°C. After centrifugation at ambient room or higher temperature, serum is promptly harvested and stored at 4°C. Monoclonal cryoglobulins appear within 24 hours, whereas polyclonal mixed cryoglobulins may take 72 hours or more to appear. Cryocrit (volume of cryoglobulin/total serum) can be estimated by centrifuging the capillary tube in which the serum is stored [32]. Then cryoglobulins are washed in cold saline solution and dissolved, and the components are identified by immunoelectrophoresis or by double diffusion techniques at 37°C using antisera to whole human serum and antisera specific for alpha, gamma, mu, kappa, and lambda chains. They should also be tested for rheumatoid factor activity and the presence of nonimmunoglobulin protein, especially complement components. The normal values are less than 0.08 g/L. The patients with cryoglobulinemia have values of more than 0.2 g/L (may be as high as 5 g/L). The cryocrit ranges from 1% to 35% in these patients.

HYPOTHERMIA, OPEN HEART OPERATION, AND CRYOGLOBULINS.
A review of literature revealed only four surgical reports in patients with cryoglobulins. Carloss and Tavassoli [25] described a 60-year-old woman with lymphoma and cryoglobulins in whom acute renal failure developed after gastrectomy in a cold operating room. Kotsuka and colleagues [15] reported coronary artery bypass grafting in a 58-year-old woman with Sjögren's syndrome and cryoglobulins. Muehrcke and Torchiana [16] reported coronary artery bypass grafting with normothermic CPB and warm blood cardioplegia in a 69-year-old man with primary cryoglobulinemia presenting with cutaneous vasculitis after cardiac catheterization. Osada and associates [21] reported one 57-year-old woman with thoracic aortic aneurysm who had cryoglobulins associated with rheumatoid arthritis. She underwent successful replacement of ascending aorta and arch under hypothermic CPB.

Cold Agglutinins
Elliotson [36] described a patient with heart disease and cold fits in 1832 who passed bloody urine ``whenever the eastwind blew.'' But it took almost a century to implicate cold agglutinins in disease [37]. Iwai and Mei Sai [38] gave the first clinical description of cold-hemagglutinin disease.

Many theories ranging from genetic predisposition to the fundamental disorder of immunologic regulation [26] have been proposed to explain the production of activated cell antibodies. The cold agglutinins occur more commonly in association with infectious or malignant disease [39–41] but sometimes form in the absence of known underlying cause. For the polyclonal antibodies the most common infectious agent is Mycoplasma pneumoniae [40]. No obvious common antigenic stimulus accounts for the predominant I specificity of polyclonal cold agglutinins. A variety of stimuli apparently can trigger their formation [39, 40], perhaps by interfering with specific suppressor cell functions. Some evidence exists, however, that Mycoplasma pneumoniae, Listeriea monocytogenes, and Streptococcus MG possess antigens related to the red cell I antigen. Interaction of red cells with infectious agents leading to sufficient alteration of I antigen to make it autoimmunogenic has been suggested [26]. Monoclonal antibodies occur mostly in idiopathic form or with hematologic neoplasms, such as lymphomas. Unlike the polyclonal antibodies, monoclonal ones can have either I or i specificity [39].

Almost all cold agglutinins are IgM, although a few cases of immunoglobulin A or IgG have been reported [39]. Cold agglutinins are assigned I specificity when they react more strongly with adult red cells than with umbilical cord cells, whereas i specificity is assigned when the agglutinin reacts more strongly with cord cells than with the adult cells [39]. Normal persons have low titers of autoanti-I antibodies [42, 43], which react only at low temperatures and are not clinically significant. The pathogenic anti-I antibodies appear to have the same specificities as normal anti-I antibodies except the range of temperatures over which they react with red cells [39]. This difference is known as thermal amplitude of the cold agglutinin in question. Anti-i antibody is not detected in serum of normal individuals. Uncommonly found cold agglutinins that react equally with cord and adult cells [44] are termed anti-not-I or protease sensitive. Anti-A, anti-B, anti-H IgM anti-P, anti-F1 anti-N-like autoantibodies have also been reported [39]. At least one third of anti-i cold agglutinins are cryoprecipitable, whereas anti-I cold agglutinins are rarely cryoprecipitable [26].

Thermal amplitude is the highest temperature at which antibody binds to red cells [28] and is most important in assessing the clinical significance of these antibodies. The antibody binding and complement fixation are optimal at low temperature (0°C), whereas complement is most lytic at higher temperatures (40°C). Thus, hemolysis occurs only in the temperature range of 10° to 30°C where these two activities overlap (Fig 1Go). The higher thermal amplitude of antibody, broadening the triangle to right, indicates a more serious form of the disease. Other proteins protecting red cells from lysis (eg, plasma enzyme factor I, membrane-bound decay acclerating factor, and homologous restricting factors) in addition to the dissociation of cold-reactive antibody from red cells at higher temperatures ensure that intravascular hemolysis occurs rarely [26]. Evidence suggests that thermal dependency results from either temperature-related changes in antibody molecule itself or room temperature-dependent changes in red cell membrane [26]. Clinically, the titer of the antibody is less important than its thermal amplitude [45].



View larger version (40K):
[in this window]
[in a new window]
  		Fig 1. . Temperature ranges for cold agglutination effects. (Inspired by Reference 28.)

 
Cells other than red cells that possess Ii or Ii-like surface antigens can be affected by cold agglutinin in the form of agglutination and cell death in the presence of complement. Such cells include B and T lymphocytes [40], polymorphonuclear leukocytes, monocytes and macrophages, platelets, and a variety of other cells such as fibroblasts, HeLa cells, intestinal mucosal cells, and even some human malignant cell lines maintained in in vitro culture [26].

DIAGNOSIS.
The effect of cold on intravascular hemolysis can be demonstrated by the Ehrlich finger test [8, 26]. After the venous return of one finger is occluded with a rubber band, the digit is immersed in cold water (20°C) for 15 minutes. As a control, another occluded digit is immersed in warm water (37°C) at the same time. The capillary blood obtained from the finger immersed in cold water is centrifuged. It usually demonstrates marked hemolysis as compared with the control sample.

The ice cube test [26] may produce a circumscribed area of intravascular agglutination and acrocyanosis in hyperemic palm. It is a useful test.

The cold agglutinins are detected in serum by the indirect hemagglutination test at various temperatures to determine the titer and thermal amplitude. Immunoglobulin M cold agglutinin itself is rarely detected because it elutes readily from the cell, especially during warming. In addition, most antiglobulin sera do not contain much anti-IgM [40]. Hemolysis by cold agglutinins is rarely demonstrated in vitro, possibly due to the inefficient fixation of C4 by such antibodies [26]. The methods of detection can be summarized as follows:

At the Sanjay Gandhi Postgraduate Institute of Medical Sciences, all patients undergoing cardiopulmonary bypass were evaluated for the presence of cold agglutinins. Serum was separated from 10 mL of whole blood and a 5% cell suspension was prepared. In three test tubes two drops of the patient's serum were placed along with one drop of cell suspension. These test tubes were incubated at 4°, 22°, and 37°C and after 1 hour were observed for agglutination, which was graded from 0 (no agglutination) to 1+ to 4+ agglutination. Titration was carried out at the temperatures showing agglutination. Five percent cell suspension of group ``O'' cells from the donor pool was titrated against a double dilution of patient's serum in saline solution. The last dilution with visible agglutination was taken as end-point of titration. Thus both the thermal amplitude and the titer of these antibodies were determined.

COLD AGGLUTININS IN CARDIAC SURGERY.
In the first reported case [1] persistent intravascular hemolysis developed after operation. All subsequently reported patients were also adults with cold agglutinins and acquired heart diseases except 2 [7, 14]. A 6-month-old boy with ventricular septal defect who had anti-H antibodies was reported by Leach and associates [7]. Anti-I antibody reacting at 37°C was present in another 8-year-old girl who underwent closure of a ventricular septal defect with use of the total washout method during OHO [14]. Klein and colleagues [2] in 1980 discussed cold agglutinin in relation to cardiac surgery for the first time. Most authors had noted these antibodies in routine preoperative testing [2–8, 10–14, 17, 19, 22–24], whereas a few were surprised by unexpected finding of agglutination in the CPB [20] or cardioplegia circuit [9, 13, 18, 20] during operation or persistent hemolysis after operation [1, 25]. Moore and co-workers [8] were the first group to use routine preoperative clinical testing with the Ehrlich finger test and palm ice cube test. Most reports with preoperative detection of antibodies also documented the titer and thermal amplitude. Advocacy of aggressive screening for cold agglutinins in all patients requiring hypothermic operations by Diaz and colleagues in 1984 [9] stirred up some controversy. Schmidt [46] believed that in his 15-year experience, this aggressive screening was neither justified nor necessary. Diaz and co-workers [47] rebutted that routine use of hypothermia and cold crystalloid cardioplegia justified their conclusions. Subsequently, most other authors have reported a routine preoperative testing for these antibodies in cardiac surgical patients. A few reports of complications arising from known [10, 20] or unknown [1, 9, 18] cold antibodies have further stressed the importance of routine preoperative screening. Bracken and associates [20] described a simple technique of screening for these antibodies in blood cardioplegia circuit during setup. The same method was earlier suggested by Dake and colleagues [13] after they detected unexpected agglutination in a patient. In this technique, 5 mL of the patient's blood was added to the cold chamber of the cardioplegia infusion device, thus allowing detection of precipitation in the cold chamber before the institution of cooling or cardioplegia. Bracken and colleagues [20] identified 2 additional patients with this technique who were not previously identified by their blood bank during routine testing.

SANJAY GANDHI POSTGRADUATE INSTITUTE OF MEDICAL SCIENCES EXPERIENCE.
Of about 1,500 consecutive OHO patients, 13 patients were found to be positive. Table 2Go summarizes our data. Seven of these had a thermal amplitude of 4°C; although they had no risk for hypothermic CPB, agglutination could have developed in coronary arteries with use of cold crystalloid cardioplegia, which is used at 4°C. In the earlier part of the series 7 patients were managed with moderate hypothermia and crystalloid cardioplegia. Six subsequent patients were operated on under normothermic CPB with antegrade continuous warm blood cardioplegia. All the patients tolerated the procedure well. There was a lone death in the early experience of this center (who died of an unrelated cause). One other patient died about 3 months after operation due to early prosthetic valve endocarditis. All other patients are well without any complication.


View this table:
[in this window]
[in a new window]
  		Table 2. . Sanjay Gandhi Postgraduate Institute of Medical Sciences Experience
 
MANAGEMENT.
Various approaches for management of cold agglutinins during OHO have been described (Table 3Go). Earlier, preoperative plasma exchange was the preferred method [2, 10, 12, 15]. The total washout method described by Lee and associates [14] is theoretically appealing but has the disadvantages of massive transfusion. Other authors have employed normothermia or moderate hypothermia depending on thermal amplitude of antibody [1, 3–10, 13, 16, 21–24].


View this table:
[in this window]
[in a new window]
  		Table 3. . Approaches to Management
 
For myocardial protection the most common technique in the past has been crystalloid/blood cardioplegia at higher temperature [5]. Hypothermic circulatory arrest [7] technique depends on noncoronary collaterals for myocardial protection and may be inadequate. Hypothermic ventricular fibrillation [13, 15] or intermittent cross-clamping with or without fibrillation [3, 9, 11] is useful only for coronary artery operations. The warm crystalloid washout technique [4, 6, 10] is theoretically attractive but requires isolation of the heart from the remaining circulation, which may not be achieved due to noncoronary collaterals. The use of retrograde cardioplegia [18] may flush out the agglutinated particles in the aortic root but also is cumbersome and less effective. The recently introduced technique of normothermic operation with warm blood cardioplegia delivered antegradely [12, 16, 19, 21] or retrogradely [17, 22] obviates the need for hypothermia and prevents activation of these proteins while at the same time providing excellent myocardial protection, which may be better than any other technique of myocardial management in these patients. We recommend warm heart operation as the method of choice.

Taking all these factors into account, an operative strategy to manage the patients with cold-reactive proteins is outlined in Figure 2Go. All the patients should undergo routine preoperative testing for cold-reactive proteins. The patients with low-titer, low-thermal-amplitude antibodies may undergo operation without any change in routine management plan, whereas patients with high-titer, high-thermal-amplitude antibodies need a change in management according to the procedures planned. The cases requiring no cardiotomy may be managed by normothermic CPB with antegrade/retrograde warm blood cardioplegia or intermittent cross-clamping or induced ventricular fibrillation. The patients requiring cardiotomy and aortic cross-clamping are managed with normothermic CPB with warm blood cardioplegia. In patients in whom deep hypothermia and circulatory arrest are required, preoperative plasmapharesis followed by hypothermia above the thermal amplitude and low-flow CPB may be the alternative.



View larger version (27K):
[in this window]
[in a new window]
  		Fig 2. . Algorithm for management. (ACC = aortic cross-clamp; CABG = coronary artery bypass grafting; CCPG = cold crystalloid cardioplegia; CPB = cardiopulmonary bypass; INTRAOP = intraoperative; POSTOP = postoperative; PREOP = preoperative; VF = ventricular fibrillation; WBC = warm blood cardioplegia.)

 
If the cold-reactive proteins are not detected preoperatively and manifest with agglutination during the operation, immediate raising of the temperature to a safe level followed by cardioplegic washout by the retrograde route is an effective way to control damage. If the problem goes undetected during the operation and manifests itself in the postoperative period with hemolysis or low cardiac output due to inadequate myocardial protection, renal damage, or other organ dysfunction, then plasma exchange, steroids, maintenance of good urine output by use of diuretics, inotropes, and ventricular assist devices for low cardiac output may be required. These patients, however, carry a high risk of increased morbidity and mortality despite all efforts. Obviously general precautions such as a warm operating room and warming of anaesthetic gases, intravenous fluids, blood, and blood products cannot be overemphasized.

To conclude, with a proper screening and management plan, this uncommon but not rare problem encountered by cardiac surgeons may be treated successfully without untoward morbidity and mortality.


   Footnotes
Top
 Footnotes
Abstract
 Introduction
 Incidence
 What Are Cold-Reactive Proteins?
 References
 
Address reprint requests to Dr Ghosh, Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Rd, Lucknow 226 014, India.


   References
Top
 Footnotes
 Abstract
 Introduction
 Incidence
 What Are Cold-Reactive Proteins?
 References
 

  1. Wertlake PT, McGinniss MH, Schmidt PJ. Cold antibody and persistent intravascular hemolysis after surgery under hypothermia. Transfusion 1969;9:70–3.[Medline]
  2. Klein HG, Faltz LL, McIntosh CL, Appelbaum FR, Deisseroth AB, Holland PV. Surgical hypothermia in a patient with a cold agglutinin: management by plasma exchange. Transfusion 1980;20:354–7.[Medline]
  3. Williams AC. Cold agglutinins: cause for concern? Anaesthesia 1980;35:887–9.[Medline]
  4. Berreklouw E, Moulijn AC, Pegels JG, Meijne NG. Myocardial protection with cold cardioplegia in a patient with cold autoagglutinins and hemolysins. Ann Thorac Surg 1982;33:521–2.[Abstract]
  5. Landymore R, Isom OW, Barlam B. Management of patients with cold agglutinins who require open heart surgery. Can J Surg 1983;26:79–80.[Medline]
  6. Blumberg N, Hicks G, Woll J, et al. Successful cardiac bypass surgery in the presence of a potent cold agglutinin without plasma exchange [Letter]. Transfusion 1983;23:363–4.
  7. Leach AB, Van Hasselt GL, Edwards JC. Cold agglutinins and deep hypothermia. Anaesthesia 1983;38:140–3.[Medline]
  8. Moore RA, Geller EA, Mathews ES, Botros SB, Jose AB, Clark DL. The effect of hypothermic cardiopulmonary bypass on patients with low titer, nonspecific cold agglutinins. Ann Thorac Surg 1984;37:233–8.[Abstract]
  9. Diaz JH, Cooper ES, Ochsner JL. Cardiac surgery in patients with cold autoimmune diseases. Anesth Analg 1984;63: 349–52.[Abstract/Free Full Text]
  10. Shahian DM, Wallach SR, Bern MM. Open heart surgery in patients with cold-reactive proteins. Surg Clin North Am 1985;65:315–22.[Medline]
  11. 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.[Free Full Text]
  12. Paccagnella A, Simini G, Nieri A, Da Col U, Frugoni C, Valfre C. Cardiopulmonary bypass and cold agglutinin [Letter]. J Thorac Cardiovasc Surg 1988;95:543.
  13. Dake SB, Johnston MFM, Brueggeman P, Barner HB. Detection of cold hemagglutination in a blood cardioplegia unit before systemic cooling of a patient with unsuspected cold agglutinin disease. Ann Thorac Surg 1989;47:914–5.[Abstract]
  14. Lee MC, Chang CH, Heish MJ. Use of a total wash-out method in an open heart operation. Ann Thorac Surg 1989;47:57–8.[Abstract]
  15. Kotsuka Y, Nakajima J, Miyairi T, et al. Coronary artery bypass grafting in a patient with cryoglobulinemia. J Cardiovasc Surg 1991;32:53–5.[Medline]
  16. Muehrcke DD, Torchiana DF. Warm heart surgery in patients with cold autoimmune disorders. Ann Thorac Surg 1993;55:532–3.[Abstract]
  17. Hearnsberger J, Ziomek S, Tobler G, Maxson T, Van Devanter S, Harrell JE. Management of cold agglutinemia with warm heart surgical intervention: a case report [Letter]. J Thorac Cardiovasc Surg 1993;106:756–7.[Medline]
  18. Izzat MB, Rajesh PB, Smith GH. Use of retrograde cold crystalloid cardioplegia in a patient with unexpected cold agglutination. Ann Thorac Surg 1993;56:1395–7.[Abstract]
  19. Gokhale AGK, Suhasini T, Saraswati V, Chandrasekhar N, Rajagopal P. Cold agglutinins and warm heart surgery [Letter]. J Thorac Cardiovasc Surg 1993;105:557.
  20. Bracken CA, Gurkowski MA, Naples JJ, et al. Cardiopulmonary bypass in two patients with previously undetected cold agglutinins. J Cardiothorac Vasc Anesth 1993;7:743–9.[Medline]
  21. Osada T, Kawachi K, Uchino T, Hirayama T, Ishimaru S, Furukawa K. A successful case of thoracic aortic aneurysm with mixed cryoglobulinemia. Nippon Kyobu Geka Gakkai Zasshi 1992;40:1100–4.[Medline]
  22. Aoki A, Kay GL, Zubiate P, Ruggio J, Kay JH. Cardiac operation without hypothermia for the patient with cold agglutinin. Chest 1993;104:1627–9.[Abstract/Free Full Text]
  23. Saldanha R, Srikrishna SV, Ross C. Mitral valve replacement in the presence of cold agglutinins [Letter]. Ann Thorac Surg 1994;57:1370.
  24. Koppula AS, Jagannath BR, Kanhere AS, Das M, Gupta CM. Management of cold agglutinemia using normothermic intermittent fibrillatory arrest [Letter]. Ann Thorac Surg 1994;58:1566.
  25. Carloss HW, Tavassoli M. Acute renal failure from precipitation of cryoglobulins in a cold operating room. JAMA 1980;244:1472–3.[Medline]
  26. Foerster J. Autoimmune hemolytic anemias. In: Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN, eds. Wintrobe's clinical haematology. Philadelphia: Lea & Febiger, 1993:1170-96.
  27. Pruzanski W, Roelcke D, Donnelly E, Lui LC. Persistent cold agglutinins in AIDS and related disorders. Acta Haematol 1986;75:171–3.[Medline]
  28. Schubothe H. The cold hemagglutinin disease. Semin Hematol 1966;3:27–46.[Medline]
  29. Foerster J. Cryoglobulins and cryoglobulinemias. In: Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN, eds. Wintrobe's clinical haematology. Philadelphia: Lea & Febiger, 1993:2284-96.
  30. Heidelberger M, Kendal FE. A quantitative study of the precipitin reaction between type III Pneumococcus polysaccharide and purified homologous antibody. J Exp Med 1929;50:819–23.
  31. Wintrobe MM, Buell MV. Hyperproteinemia associated with multiple myeloma. Bull Johns Hopkins Hosp 1933;52:156–65.
  32. Grey HM, Kohler PF. Cryoimmunoglobulins. Semin Hematol 1973;10:87–112.[Medline]
  33. Abramsky O, Slavin S. Neurologic manifestations in patients with mixed cryoglobulinemia. Neurology 1974;24:245–9.[Abstract/Free Full Text]
  34. Moroz LA, Rose B. The cryopathies. In: Samter M, ed. Immunological diseases. 3rd ed. Boston: Little, Brown, 1978:570-91.
  35. Mantagnino G. Reappraisal of the clinical expression of mixed cryoglobulinemia. Springer Semin Immunopathol 1988;10:1.[Medline]
  36. Elliotson J. Diseases of the heart united with ague. Lancet 1832;1:500–1.
  37. Clough MC, Richter IM. A study of an autoagglutinin occurring in a human serum. Johns Hopkins Hosp Bull 1918;29:86–93.
  38. Iwai S, Mei Sai N. Etiology of Raynaud's disease (preliminary report). Jpn Med World 1925;5:119–21.
  39. Pruzanski W, Shumak KH. Biologic activity of cold-reacting autoantibodies. I. N Engl J Med 1977;297:538–42.[Medline]
  40. Pruzanski W, Shumak KH. Biologic activity of cold-reacting autoantibodies II. N Engl J Med 1977;297:583–9.[Medline]
  41. Crisp D, Pruzanski W. B-cell neoplasms with homogenous cold-reacting antibodies (cold agglutinins). Am J Med 1982;72:915–22.[Medline]
  42. Williams RC Jr. Cold agglutinins. Studies of primary structure, serologic activity and antigenic uniqueness. Ann NY Acad Sci 1971;190:330–41.[Medline]
  43. Adinolfi M. Anti-I antibody in normal human newborn infants. Immunology 1965;9:43–52.[Medline]
  44. Marsh WL, Jenkins WJ. Anti-i: a new cold antibody. Nature 1960;188:753.[Medline]
  45. Rosse WF, Adams JP. The variability of hemolysis in the cold agglutinin syndrome. Blood 1980;56:409–16.[Abstract/Free Full Text]
  46. Schmidt PJ. Cold agglutinins and hypothermia [Letter]. Arch Intern Med 1985;145:578–9.
  47. Diaz JH, Cooper ES, Ochsner JL. Cold agglutinins and hypothermia. Reply [Letter]. Arch Intern Med 1985;145:579.



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
V. P. Atkinson, P. Soeding, G. Horne, and J. Tatoulis
Cold Agglutinins in Cardiac Surgery: Management of Myocardial Protection and Cardiopulmonary Bypass
Ann. Thorac. Surg., January 1, 2008; 85(1): 310 - 311.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
A. Panos, N. Murith, P. O. Myers, and A. Kalangos
Aortic Arch Repair and Cold-Reactive Agglutinins: What to Do?
Ann. Thorac. Surg., October 1, 2007; 84(4): 1403 - 1404.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
A. P. Kypson, J. J. Warner, M. J. Telen, and C. A. Milano
Paroxysmal cold hemoglobinuria and cardiopulmonary bypass
Ann. Thorac. Surg., February 1, 2003; 75(2): 579 - 581.
[Abstract] [Full Text] [PDF]

Home page
 PerfusionHome page
J W Hoffman Jr, T B Gilbert, and M L Hyder
Cold agglutinins complicating repair of aortic dissection using cardiopulmonary bypass and hypothermic circulatory arrest: case report and review
Perfusion, September 1, 2002; 17(5): 391 - 394.
[Abstract] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. Onoe, T. Magara, and Y. Yamamoto
Cardiac operation for a patient with autoimmune hemolytic anemia with warm-reactive antibodies
Ann. Thorac. Surg., January 1, 2001; 71(1): 351 - 352.
[Abstract] [Full Text] [PDF]

Home page
 PerfusionHome page
J. Schaadt
Oxygenator thrombosis: an international phenomenon
Perfusion, December 1, 1999; 14(6): 425 - 435.
[Abstract] [PDF]

Home page
 PerfusionHome page
S. Svenmarker, S. Haggmark, E. Jansson, R. Lindholm, M. Appelblad, and T. Aberg
The relative safety of an oxygenator
Perfusion, September 1, 1997; 12(5): 289 - 292.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Surendra K. Agarwal
Probal K. Ghosh
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Agarwal, S. K.
Right arrow Articles by Gupta, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Agarwal, S. K.
Right arrow Articles by Gupta, D.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS