Hyperacute Rejection After Single Lung Transplantation: A Case Report J. de Jesus Peixoto Camargo, S. Marcantonio Camargo, S. Marcelo Schio, T. Noguchi Machuca, and F. Adélia Perin ABSTRACT Hyperacute rejection is a well-known complication in kidney and heart transplantations. However, its occurrence in lung transplantation is extremely rare, with only 4 cases previously described. A 53-year-old female patient blood type O with end-stage chronic obstructive pulmonary disease underwent left lung transplantation. She had 2 negative pretransplantation evaluations for panel-reactive antibodies. One hour after the vascular clamps were released, progressive hypoxia developed. Fiberoptic bronchoscopy revealed an optimal bronchial anastomosis; an abundant pink frothy fluid was observed on the allograft side. Chest X ray sevealed a completely opacified left lung. Due to the low-compliance of the transplanted lung and the risk for native lung hyperinsufflation, independent mechanical ventilation was employed. Despite all measures, multiple organ failure developed and the patient died 24 hours after the procedure. A necropsy evaluation for confirmed the patency of all anastomoses and no signs of ischemia. Retrospectively, a new evaluation for panel-reactive antibodies was performed, with 24% reactivity. Complementdependent cytotoxicity crossmatch was negative, however, a flow cytometric analysis was positive for both HLA-I (56%) and HLA-II (45%). Further investigation detected an anti-A2 in the recipient serum and the donor had an A2 antigen. Hyperacute rejection is a rare posttransplantation complication highlighted by its precocity and lethality. With the increased number of lung transplantations performed yearly, it is believed that its incidence will also rise. Therefore, prompt diagnosis and familiarity with management strategies are fundamental.
L
UNG TRANSPLANTATION is considered an effective therapeutic modality for patients with end-stage lung disease. A variety of complications can jeopardize the allograft in the postoperative period, however, only few are manifested immediately after completion of the procedure. Among them, hyperacute rejection (HAR) represents a recently described cause. Due to its rarity and immunological pitfalls, this case warrants description.
CASE REPORT A 53-year-old Caucasian woman, blood group O, with end-stage chronic obstructive pulmonary disease due to tobacco smoking was admitted for lung transplantation. She had been listed for 13 months, she was O2 and corticosteroid-dependent and, in addition, obese (body mass index 35.1 kg/m2). She had no associated illnesses. Cytomegalovirus (CMV) status was IgG positive and IgM negative. She had 2 negative pretransplantation evaluations for panel-reactive © 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 40, 867– 869 (2008)
antibodies (PRA) for both HLA-I and HLA-II antibodies (ELISA — LS1-PRA ONE LAMBDA, LS2-PRA ONE LAMBDA). There was no blood transfusion history and the patient was gravida 3 for 3. The patient underwent left lung transplantation which was uneventful. Ischemic time was 160 minutes and no extracorporeal support was required (preclamping, clamping, and postclamping pulmonary artery mean pressures were 30, 33, and 17 mm Hg, respectively). The donor was a 24-year-old male, type O blood group, CMV status negative, with declared brain death due to cranioencephalic trauma. Both antegrade and retrograde preserFrom the Thoracic Surgery Service and Lung Transplantation Unit, Pavilhao Pereira Filho/Hospital Dom Vicente Scherer– Santa Casa de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. Address reprint requests to Dr José Camargo, Irmandade da Santa Casa de Misericórdia de Porto Alegre–Pavilhão Pereira Filho, Annes Dias Street St 285, 90020-090, Porto Alegre, Rio Grande do Sul, Brazil. E-mail:
[email protected] 0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.02.052 867
868
CAMARGO, CAMARGO, SCHIO ET AL
vations were done with 4 L of Perfadex solution. The recipient was prescribed standard immunosuppression with intraoperative methylprednisolone. We do not perform preoperative conditioning at our institution. One hour after completion of the anastomoses, severe hypoxia developed, with an O2 saturation of 79% on 100% FIO2. Bronchoscopy revealed abundant pink frothy fluid draining from the allograft. Chest radiograph displayed a completely opacified left lung, with homogeneous infiltrates. On arrival in the intensive care unit, the patient’s temperature was 40°C. Hemodynamic instability developed, requiring increasing higher levels of norepinephrine. Anuric acute renal failure was rapidly observed, with a creatinine level, which was normal in the pretransplantation evaluation, to 2.7 mg/dL. Mean pulmonary artery pressure increased to 29 mm Hg. Two pretransplantation PRAs were negative and, due to technical barriers, crossmatch data were not available at this time. Reperfusion injury was assumed; due to decreasing allograft compliance and the risk for hyperinflation of the native lung, independent lung ventilation was started. In the former: 100% FIO2, 24 mm Hg PEEP, 42 mm Hg peak pressure; and in the latter: 100% FIO2, 0 mm Hg PEEP, 30 mm Hg peak pressure. The patient’s condition was clearly unstable, hence no biopsy was performed. Despite all measures, the patient died at 24 hours after the procedure. An autopsy revealed both vascular and bronchial anastomoses to be patent without signs of injury. Macroscopically, the transplanted lung displayed red hepatization, with a firm consistency. Microscopically, signs of acute lung injury were evident. HLA and crossmatch analysis were available retrospectively. Donor HLA profile was A1, A2, B8, B60, DR11, DR17. A flow cytometric PRA (FL1-30-ONE LAMBDA) revealed 24% reactivity against anti-HLA class I antigens. Although the, complementdependent cytotoxicity crossmatch was negative, however, a more sensitive flow cytometric test revealed 56% and 45% reactivity against HLA class I and class II, respectively. Among the preformed antibodies, anti-A2 was detected and, we believe, played an overwhelming role in the adverse outcome.
DISCUSSION
HAR is a well-known phenomenon afflicting solid organ transplants, particularly kidney, heart, and liver. It shares universal morphologic features, characterized macroscopically by gross edema and cyanosis of the graft. Histologically, platelet thrombi, neutrophilic infiltration, and fibrin thrombi are observed. Endothelial damage and edema subsequently follow, leading to graft loss.1,2 Nevertheless, HAR is an extremely rare condition among lung transplant recipients, with, to the best of our knowledge, only 4 cases previously reported (Table 1). In the first case, a positive pretransplantation PRA (16% and 33%)
was present.3 Posttransplantation crossmatch revealed an anti-B8 against the donor. The patient underwent transplant pneumonectomy and died after 10 days since no donor became available. In the second case, HAR developed after retransplantation, with the first graft clearly representing an immunological stimulus.1 A fulminant course was observed and the posttransplantation crossmatch was positive; however, no specific antibody was identified. In the third case, the pretransplantation PRA was positive (33%) and the recipient was known to have an anti-A2.4 The donor was A2, but the pretransplantation crosmatch was negative. The authors implemented an aggressive protocol adapted from successful HAR management in heart transplant recipients. The patient was discharged on the 17th postoperative day. And lastly, in the fourth case, the patient had a negative PRA but retrospective analysis revealed a mismatched anti-DR11 (the pretransplantation flow cytometric PRA was designed to detect only T-cell antibodies).5 The patient died after 48 hours. Few studies have addressed the impact of PRA in solid organ transplantation. Regarding heart transplantation, Lavee et al6 detected 18 of 463 cases of HAR and, surprisingly, only 2 of them had positive PRA. Among kidney recipients, PRA has not shown a secure correlation with crossmatch, with 7.2% and 13.7% positive crossmatches in patients with 0% and 1% to 10% PRA, respectively, when using the IgG ELISA method.7 In order to evaluate the significance of preformed antibodies among recipients of lung allografts, one large cohort study observed an important correlation between PRA and survival.8 Six patients (30%) with high PRA levels died within 30 days after transplantation; all of them had evidence of acute lung injury. Furthermore, positive crossmatches were observed more frequently among patients with high PRA (30%), although it is noteworthy that 17 of 636 patients with low PRA had positive crossmatches. Regarding the rarity of HAR in lung recipients, it is stated that the smaller number of transplantations performed yearly, along with the particularities of end-stage pulmonary disease patients such as fewer requirements for blood transfusions, play important roles. However, we believe that as lung transplantation becomes a more widespread procedure, the number of cases will increase requiring more effective screening methods. After this dramatic HAR episode, we have substituted the ELISA PRA for flow cytometric PRA and have only judiciously admitted patients with high presensitization levels. Due to the limitations
Table 1. Cases Reported of Hyperacute Rejection in Lung Transplantation Author 3
Frost et al Choi et al1 Bittner et al4 Scornik et al5 Camargo
Sex/Age (y)
Cause
PRA
F/48 F/50 F/57 F/NA F/53
Emphysema Emphysema Emphysema NA Emphysema
33% Negative 33% Negative Negative
PRA, panel-reactive antibodies; POD, postoperative day; NA, not available.
Crossmatch
⫹ ⫹ ⫹ ⫹ ⫹
Anti-B8 ND Anti-A2 Anti-DR11 Anti-A2
Outcome
Death Death Alive Death Death
13 in 4 hours in 48 hours in 24 hours
HAR AFTER SINGLE LUNG TRANSPLANTATION
posed by short ischemia times, the performance of pretransplantation crossmatches is far from a routine step and only possible in a fully commited environment. In a few cases we have accomplished this, especially when recipient presensitization was present and, more importantly, when the donor center geographically allowed. The impact of these measures is still unknown. In summary, this report added another case of HAR, a rare life-threatening complication in lung transplantation. Previous studies and immunological aspects were reviewed, with special attention to sensitization screening. PRA shows high false-negative rates and pretranspantation crossmatch is not often possible. Thus, the ideal tool is still not available. REFERENCES 1. Choi JK, Kearns J, Palevsky HI, et al: Hyperacute rejection of pulmonary allograft. Am J Respir Crit Care Med 160:1015, 1999
869 2. Whelan TPM, Hertz MI: Allograft rejection after lung transplantation. Clin Chest Med 26:599, 2005 3. Frost AE, Jammal CT, Cagle PT: Hyperacute rejection following lung transplantation. Chest 110:559, 1996 4. Bittner HB, Dunitz J, Hertz M, et al: Hyperacute rejection in single lung transplantation: case report of successful management by means of plasmapheresis and antithymocyte globulin treatment. Transplantation 71:649, 2001 5. Scornik JC, Zander DS, Baz MA, et al: Susceptibility of lung transplants to preformed donor-specific HLA antibodies as detected by flow cytometry. Transplantation 68:1542, 1999 6. Lavee J, Kormos RL, Duquesnoy RJ, et al: Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation. J Heart Lung Transplant 10:921, 1991 7. Lieber SR, Perez FVT, Tabossi MR, et al: Effect of panelreactive antibody in predicting crossmatch selection of cadaveric kidney recipients. Transplant Proc 39:429, 2007 8. Hadjiliadis D, Chaparro C, Reinsmoen NL, et al: Pretransplant panel reactive antibody in lung transplant recipients is associated with significantly worse post-transplant survival in a multicenter study. J Heart Lung Transplant 24:S249, 2005
