Abstract
We treated a 68-year-old woman with warm-reactive type of autoimmune hemolytic anemia (AIHA) who underwent aortic valve replacement. In consideration of the different hemolytic mechanisms between cardiopulmonary bypass and warm-reactive AIHA, conventional surgical procedures could be performed after the discontinuation of steroid therapy.
1 Introduction
Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic anemia caused by an autoantibody reaction against an antigens on the surface of patient's own erythrocytes at normal temperature, resulting in severe anemia due to extravascular hemolysis [1,2]. Hemolysis itself is one of the cardiopulmonary bypass (CPB)-induced critical adverse effects [3,4], and in particular, CPB is reported to weaken the erythrocyte membrane and reduce an erythrocyte life span [5]. Therefore, perioperative hemolysis often represents a serious problem during open-heart operation, especially in AIHA patients. Although previous reports suggested the various kinds of perioperative management for hemolytic anemia such as cold hemagglutinemia and hereditary spherocytosis [6–9], there have been very few reports on open-heart operations for AIHA patients with warm-reactive antibodies [10]. Herein, we report a patient with warm-reactive type of AIHA who underwent aortic valve replacement (AVR) for severe aortic stenosis (AS), and refer to some of the important issues related to perioperative management for warm-reactive AIHA.
2 Case report
A 68-year-old woman, who had suffered from effort dyspnea for 4 years, was admitted to our hospital because of frequent severe general malaise, palpitation and dyspnea. Clinical examinations suggested chronic congestive cardiac failure due to severe AS. Blood analysis revealed severe normocytic-normochromic anemia with a hemoglobin concentration of 5.3 g/dl, a hematocrit value of 17.9% and reticulocyte count of 27.0%. Microscopic examination did not indicate red blood cell fragmentation. Urinary analysis demonstrated that only a slight occult blood reaction and no occult blood were detected in the patient's stool. The plasma total bilirubin level was 3.5 mg/dl and plasma lactate dehydrogenase was 1537 IU/l. Both direct and indirect Coombs’ tests were positive and no cold agglutinin was detected. Detailed results for differential diagnosis are presented in Table 1 . The patient had not been given any drugs possibly inducing AIHA. Virus infections such as myoplasma, which are considered to induce sequential AIHA, appeared negative judging from her clinical course and blood analysis. Therefore, the patient was diagnosed as having idiopathic AIHA with warm-reactive antibodies, and 40 mg/day of prednisolone was given after definitive diagnosis.
Blood analysis data
Anemia improved in response to the oral steroid administration therapy, and the Coombs test changed to negative 30 days after the initiation of steroid therapy. The dose of prednisolone was gradually tapered to zero 5 months after the initiation of steroid therapy. The hemoglobin concentration remained around 10 g/dl without any rebound phenomena, and the rapid adrenocorticotropic hormone (ACTH) test did not show hypoadrenalism. After the evaluation of AIHA 1 month after the discontinuation of steroid administration (Table 1), the patient was subsequently introduced to us for cardiac operation. Echocardiography revealed severe calcified aortic valve cusps, 0.38 cm2 of aortic valve area (AVA) and 126 mmHg of the pressure gradient between the left ventricle (LV) and ascending aorta (Ao). Cardiac catheterization and angiography revealed 0.50 cm2 of AVA, 124 mmHg of the pressure gradient between LV and Ao, and indicated poor LV function (ejection fraction 35%). Autologous blood donation was not done in spite of her stable anemic condition, because the patient was considered to be in severe chronic cardiac failure.
The patient underwent AVR using a 21-mm bioprosthesis (Carpentier-Edwards, Pericardial Valve; Edwards Life Sciences Co. Ltd., Irvine, CA) 12 days after admission. To prevent possible hemolytic deterioration, a centrifugal pump (Capio system; Termo Co. Ltd, Tokyo, Japan) was used as a main perfusion pump. The components of the CPB circuits were heparin-coated. Myocardial protection during aortic cross-clamping was performed with continuous and intermittent bolus infusion of minimally-diluted blood cardioplegia supplemented with potassium-chloride and magnesium-sulfate. No apparent sign of hemolytic or vaso-occlusive complication was observed, and haptoglobin was not given during and after CPB. No homologous blood components were transfused. Postoperative rapid ACTH test did not show hypoadrenalism, and no recurrence of hemolytic anemia was observed without resuming steroid therapy, The postoperative course was uneventful, and the patient was discharged from our institution 28 days after operation.
3 Discussion
Recent popularity in warm cardiac operation may deteriorate intraoperative hemolytic reaction especially in patients with warm-reactive AIHA, and the perioperative management for warm-reactive AIHA appears complicated. However, we suppose that it is not so intricate in consideration of the hemolytic mechanism of warm-reactive AIHA.
The hemolytic mechanism of AIHA differs according to the type of antibodies; warm-reactive or cold-reactive. The reticuloendothelial system is thought to play a role in the extravascular hemolytic reaction due to warm-reactive AIHA, and sensitized erythrocytes bound to antierythrocyte autoantibodies (IgG) are phagocytosed by macrophages after recognition through IgG-Fc receptors [1,2]. On the other hand, cold-reactive AIHA, such as cold hemagglutinemia and paroxysmal cold hemoglobinuria, shows intravascular hemolysis under hypothermic conditions [1,2,8,9]. CPB also induces intravascular hemolysis mainly due to mechanical destruction of erythrocytes [3,4]. Furthermore, complement activation, which is highly associated with the development of cold-reactive AIHA, is considered not to play a pivotal role in the development of warm-reactive AIHA [1,2]. These above facts suggest that CPB may not deteriorate warm-reactive AIHA. However, the actual mechanism of the hemolytic reaction due to warm-reactive AIHA under CPB has been unclear. Therefore, some efforts should be applied to attenuate CPB-induced hemolytic reactions and avoid possible hemolytic crisis. A centrifugal pump for systemic perfusion provides a smaller degree of hemolysis than a roller pump does [3,6,7]. The heparin-coated circuit is thought to attenuate CPB-induced complement activation. The use of anti-inflammatory agents, such as nafamostat mesilate and aprotinin, is also recommended.
Preoperative steroid administration was discontinued and an operation was electively performed in the present case. In an emergency or urgent case, however, two important issues have been raised: (1) the possibility of deteriorating hemolysis by homologous blood transfusion, and (2) the necessity of postoperative steroid administration therapy.
Generally in case of blood requirement for AIHA patients, washed red blood cell transfusion is recommended in order to prevent hemolytic crisis due to complement activation [1,2]. Complement activation does not play a pivotal role in the development of hemolytic warm-reactive AIHA as mentioned above, and we suppose that intraoperative homologous blood transfusion can be performed in a conventional style without inducing hemolytic crisis. As for the postoperative steroid administration, we used the postoperative rapid ACTH test as an indicator of the possibility of steroid rebound phenomenon. Although steroid was not administered after operation in the present case, further studies should be done to elucidate whether the rapid ACTH test is adequate and useful for investigating the necessity of postoperative steroid administration therapy.
In summary, we experienced a successful AVR in a patient with warm-reactive AIHA. In consideration of different hemolytic mechanisms between CPB and warm-reactive AIHA, conventional surgical procedures could be performed after the discontinuation of steroid administration therapy. Although important issues related to homologous blood transfusion and steroid therapy have been raised, perioperative management for warm-reactive AIHA is considered not to be complicated even under normothermic or tepid-thermic CPB.
