Cardiac surgery in a patient with paroxysmal nocturnal hemoglobinuria. (2002)

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia associated with thrombocytopenia and an abnormal susceptibility to venous thromboses. The major mechanism of hemolysis consists of unregulated complement activation. In cardiac surgery, PNH-induced granulocytopenia increases the risk of postoperative infection. PNH-induced complement activation is further exaggerated by extracorporeal circulation in cardiac surgery leading to potential hemolytic crises. In addition, resulting thrombocytopenia would lead to an increase risk of bleeding. Here, we report for the first time on a patient who developed PNH after severe aplastic anemia (SAA) undergoing aortic valve replacement and coronary revascularization using extracorporeal circulation. Paroxysmal nocturnal hemoglobinuria (PNH) is based on a clonal defect of hematopoietic stem cells characterized by deficiency in glycosyl-phosphatidylinositol-(GPI)-anchored surface proteins due to mutations within the X-chromosomal PIG-A gene. 1-4 Due to the lack of GPI-linked complement regulating surface proteins such as CD59 (membrane inhibitor of reactive lysis), erythrocytes become abnormally sensitive to the activation of especially the autologous complement. 5-8 As a result, PNH is an acquired hemolytic anemia associated with an increased risk of developing thrombocytopenia, atypical venous thrombosis and hypoplastic bone marrow. 4 Hemolytic crises and venous thrombosis are known to precipitate in clinical conditions associated with complement activation such as systemic infections. Here, we report for the first time on a patient with a severe aortic valve regurgitation undergoing prosthetic aortic valve replacement with extracorporeal circulation who suffers from PNH developed after aplastic anemia. Case report. A 72-year old man was admitted to hospital due to acute shortness of breath without typical angina. The patients' history included treatment for severe aplastic anemia with anti-thymocyte globulin, prednisone and cyclosporine 8 years ago. Two years later he developed paroxysmal nocturnal hemoglobinuria (PNH) with increasing hemolytic activity. Furthermore he suffered compensated renal insufficiency, and arterial hypertension. Echocardiography revealed reduced left ventricular function and a severe combined aortic vitium with leading aortic valve regurgitation (III-IV°) with aortic annulus measuring 26 mm. Angiography and right heart catheter confirmed severe aortic regurgitation, and moderate pulmonary hypertension. Coronary angiography revealed significant stenosis of the left anterior descending artery. Therefore, aortic valve replacement and coronary revascularization was scheduled. On admission, laboratory tests exhibited leukocytopenia (1.9 g/L), hemoglobin 5.27 mmol/L, thrombocytopenia 89 g/L, complete-bilirubin 22 µmol/L [<17 µmol/L], haptoglobin <0.06 g/L [0.3-2.0 g/L], LDH 1215U/L [80-240 U/L]. Differential blood count revealed 26% neutrophils [50-70%], 46% lymphocytes [25-40%], 27% monocytes [2-8%], and 1% eosinophils [2-4%]. Flow cytometric analysis resulted in a marked GPI-anchoring defect on different cell lineages including neutrophils (about 75 % deficient cells), monocytes (about 96% deficient cells), and erythrocytes (about 25%