Pulmonary thromboendarterectomy in a patient with cryoagglutinins

Pulmonary Thromboendarterectomy in a Patient With Cryoagglutinins Nicoletta Barzaghi, MD, Marco Maurelli, MD, Vincenzo Emmi, MD, Gaetano Minzioni, MD, Andrea Maria D’Armini, MD, Carlomaurizio Montecucco, MD, Laura Salvaneschi, MD, Marisa Barone, MD, and Franco Piovella, MD

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ATIENTS with undiagnosed cold-reactive protein (CRP) disease undergoing hypothermia are at high risk of major morbidity and mortality if they are not identified and treated before surgery.1 Chronic thromboembolic pulmonary hypertension may be cured by pulmonary thromboendarterectomy (PTE), for which deep hypothermia and circulatory arrest (DHCA) are recommended.2 Because of hypothermia, PTE is a challenging procedure in patients with sickle cell and CRP disease. Successful PTE in patients with sickle cell disease has been reported by Yung et al.3 A patient is described with a preoperative diagnosis of cold agglutinins (CA) in whom successful PTE was also performed. CASE REPORT

A New York Heart Association class IV, 47-year-old man was admitted for PTE in March 1998. The history was positive for arterial and venous thrombosis, recurrent pulmonary embolism, and pulmonary hypertension (cardiac index of 2.6 L/min/m2, total pulmonary resistance of 600 dynes · sec · cm⫺5 ). The patient had painful skin rashes after subcutaneous heparin and finger paresthesias during cold exposure. Mycoplasma and virus infection were excluded. The patient’s hypercoagulable state was related to the antiphospholipid antibody syndrome,4 and a high titer of IgM and IgG class anticardiolipin and lupus-like anticoagulant antibodies were detected in the serum. At preoperative assessment, CA had a titer of 1:32 at 4°C and thermal amplitude—the highest temperature at which antibodies bind to red cells—of 30°C. Hemoagglutination was due to, at least in part, IgM class anticardiolipin antibodies, which were detected by an enzymelinked immunosorbent assay. After switching from warfarin to low-molecular-weight heparin, the patient underwent 3 uneventful plasma exchanges, the last being performed 12 hours before surgery. Plamapheresis was carried out by removing over 3 cycles a total of 10.8 L of the patient’s plasma and replacing it with 3.2 L of fresh frozen plasma and 7.6 L of 4% albumin. At operation, hemoagglutinin titer was 1:2 at 4°C, whereas agglutinins were not detectable at higher temperatures. Surgery was performed according to Jamieson’s technique,2 with minor modifications. To reduce the likelihood of side effects related to hypothermia, the temperature in the heat exchanger of the pump circuit was maintained at greater than 18°C, and the core temperature was kept at 21°C. Cardioplegia was not given. The patient’s head was not packed in ice during DHCA. Total extracorporeal and circulatory arrest times were 3.2 hours and 20 minutes. Surgery was followed by immediate hemodynamic improvement. The patient recovered from anesthesia within 12 hours. No sign of brain damage was detected by clinical examination, and blood laboratory tests for liver and kidney function were within the normal range. The postoperative period was complicated by early-onset pneumonia with Haemophilus influenzae bacteremia. Antibiotic therapy was successful after 5 days. The patient was discharged on postoperative day 20 on warfarin and calcium channel

blockers. At 3-month follow-up, right heart catheterization confirmed good hemodynamics (cardiac index, 3.0 L/min/m2; total pulmonary resistance, 361 dynes · sec · cm⫺5 ). DISCUSSION

The actual incidence of CRP in patients requiring cardiac surgery is 0.4% to 4%.1,5 Patients with CRP show increased perioperative morbidity and mortality after hypothermic surgery if they are not identified before operation. Today, for most procedures, the risk for CRP-related complications is trivial because of the possibility of using normothermic cardiopulmonary bypass and warm cardioplegia without further preoperative treatments. Although normothermic cardiopulmonary bypass with a beating heart for PTE has been described in 4 patients, the safety of this approach remains to be established, and DHCA is still considered the gold standard for this procedure.6 The likelihood of CRP being present in patients requiring PTE is probably low, a finding that explains the lack of agreement on the best approach for the preoperative identification of these patients. Because PTE is usually an elective operation and laboratory investigations to detect CRP are readily available and relatively inexpensive, contraindications to hypothermia should be actively searched for in all PTE candidates. CAs always should be investigated in patients with antiphospholipid syndrome. Anticardiolipin antibodies may adhere to red blood cell membranes, leading to positive Coombs’ tests or hemolytic anemia (or both) by acting as anti–red blood cell autoantibodies.7 In the patient of this case study, anticardiolipin antibody adhesiveness occurred at temperatures less than 37°C, and they acted as CA. Available literature on cardiac surgery in subjects with CA is confined largely to patients undergoing moderate hypothermia (ⱖ30°C). Low titers (ⱕ1:32) of CA reacting only at 4°C are considered clinically irrelevant.8 Even patients with high thermal amplitude CA may undergo safe hypothermia if systemic temperature can be maintained above the thermal amplitude.9 In this patient, hemoagglutination occurred at 30°C. PTE could not be scheduled unless CA had been removed before operation. Suggested therapeutic strategies for perioperative management of patients with CRP include steroid treatment, the total blood washout method described by Lee et al10; and plasma exchange, which involve a definite risk for complications.1,8,10,11

From the Department of Anesthesiology, Division of Cardiac Surgery, Division of Rheumatology, Department of Transfusion Medicine and Immunohematology, and Thromboembolism Unit, I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. Address reprint requests to Nicoletta Barzaghi, MD, Servizio di Anestesia e Rianimazione I—Direzione, Policlinico San Matteo, Piazzale Golgi no. 2, 27100 Pavia, Italy. Copyright r 2000 by W.B. Saunders Company 1053-0770/00/1404-0018$10.00 doi:10.1053/jcan.2000.7947 Key words: cryoagglutinins, deep hypothermia, pulmonary thromboendarterectomy

Journal of Cardiothoracic and Vascular Anesthesia, Vol 14, No 4 (August), 2000: pp 447-448

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In the present case, plasma exchange was thought to be the least risky and time-consuming of the remaining therapeutic options. It cannot be excluded that early infection in the postoperative period could be related to transient immunocompromise, as a consequence of extracorporeal circulation, hypothermia, or the plasma exchange itself. At operation, hemoagglutinin titer was 1:2 at 4°C. The authors considered a low titer of agglutinins detectable only at 4°C the target to be obtained to submit the patient to the operation, provided that the exposure of the patient or his organs to temperatures near 4°C could be avoided. The patient’s head was not packed in ice because of the possible risk for red blood cell agglutination in the microvasculature of the scalp. To exclude the possibility of coronary artery occlusion resulting from blood agglutination, cardioplegia, which is usually delivered at 4°C, was not given. In this respect, in patients undergoing PTE, cardioplegia administration is not required to protect the myocardium. In fact, its metabolic requirements may be satisfied equally by leaving the decompressed (vented) and fibrillating (or asystolic) left ventricle perfused while performing PTE. To date, at this center, 41 patients have been submitted to PTE, and cardioplegia has been given only in 3 patients. With respect to the 38 patients in whom cardioplegia was not given,

severe but transient right ventricular failure developed only in 1 case, whereas the remaining subjects were weaned from extracorporeal circulation without drugs to treat right ventricular failure. Anticoagulation was switched from warfarin to lowmolecular-weight heparin before plasma exchange. Because of the risk for sudden thrombosis, patients scheduled for PTE always should have adequate anticoagulation. It may be difficult, however, to maintain therapeutic anticoagulation with warfarin or drugs with high protein binding, such as unfractionated heparin, during plasma exchanges, which involve alteration in the plasma protein content. Compared with unfractionated heparin, low-molecular-weight heparin has negligible protein binding,12 and its effect is less likely to be affected by plasmapheresis. In conclusion, although the possibility of CRP being present in patients scheduled for elective surgery under DHCA is probably low, it should be excluded by laboratory investigations, especially in patients with the antiphospholipid syndrome. If high titer or high thermal amplitude CA is detected, antibody removal before hypothermic surgery is imperative, and plasma exchange may be a valuable approach.

REFERENCES 1. Agarwal SK, Ghosh PK, Gupta D: Cardiac surgery and coldreactive proteins. Ann Thorac Surg 60:1143-1150, 1995 2. Jamieson SW, Auger WR, Fedullo PF, et al: Experience and results with 150 pulmonary thromboendarterectomy operations over a 29-month period. J Thorac Cardiovasc Surg 106:116-127, 1993 3. Yung GL, Channick RN, Fedullo FP, et al: Successful pulmonary thromboendarterectomy in two patients with sickle cell disease. Am J Respir Crit Care Med 157:1690-1693, 1998 4. Robbins P, Forrest M, Royston D: Hypercoagulable states. Semin Cardiothorac Vasc Anesth 1:295-318, 1997 5. Bracken CA, Gurkowski MA, Naples JJ, et al: Cardiopulmonary bypass in two patients with previously undetected cold agglutinins. J Cardiothorac Vasc Anesth 7:743-749, 1993 6. Zund G, Pretre R, Niederhauser U, et al: Improved exposure of the pulmonary arteries for thromboendarterectomy. Ann Thorac Surg 66:1821-1823, 1998

7. Sthoeger Z, Sthoeger D, Green L, Geltner D: The role of anticardiolipin autoantibodies in the pathogenesis of autoimmune hemolytic anemia in systemic lupus erythematosus. J Rheumatol 20:2058-2061, 1993 8. Moore RA, Geller EA, Mathews ES, et al: The effect of hypothermic cardiopulmonary bypass on patients with low-titer, nonspecific cold agglutinins. Ann Thorac Surg 37:233-238, 1984 9. Leach AB, Van Hasselt GL, Edwards JC: Cold agglutinins and deep hypothermia. Anaesthesia 38:140-143, 1983 10. Lee M-C, Chang C-H, Hsieh M-J: Use of total wash-out method in an open heart operation. Ann Thorac Surg 47:57-58, 1989 11. Schreiber AD, Herskovitz BS, Goldwein M: Low-titer coldhemagglutinin disease. N Engl J Med 296:1490-1494, 1977 12. Cummins D, Hill E: Heparin-induced thrombocytopenia. Semin Cardiothorac Vasc Anesth 1:349-365, 1997