Conference: 2012 International PHA Conference and Scientific Sessions
Release Date: 06.22.2012
Presentation Type: Abstracts
George MP, Novelli E, Simon M, Feingold B, Krishnamurti L, Morrell MR, Gries CG, Haider S, Johnson BA, Crespo MM, Pipeling MR, McDyer JF, Shigemura N, Bhama JK, Toyoda Y, Yousem S, Bermudez C, Pilewski JP, Champion HC, Gladwin MT
University of Pittsburgh, Pittsburgh, Pennsylvania, USA
BACKGROUND: Sickle-cell disease (SCD) is an inherited, multisystem disease, associated with episodes of acute illness and progressive organ damage. Pulmonary hypertension is a known complication in patients with SCD, affecting 6-10% of all patients with this disorder, and elevating mortality risk up to ten-fold in patients with significant disease. Medical treatment of sickle-cell disease-associated pulmonary hypertension (SCD-PAH) can be quite complicated, and to date there is no cure. Little is known about the use of lung transplantation in the management of SCD-associated pulmonary vascular complications. We report the first successful outcome of bilateral lung transplantation in a patient with severe SCD-PAH.
METHODS: The recipient was a 17-year-old man with SCD (S/β0 thalassemia) and Protein S deficiency, diagnosed after an episode of syncope with SCD-PAH and inoperable chronic thromboembolic pulmonary hypertension. Despite aggressive treatment with biweekly transfusions, sildenafil, bosentan, and inhaled treprostinil, he continued to suffer episodes of presyncope severe decompensation associated with an acute chest syndrome event. At that time his right heart catheterization demonstrated pulmonary arterial pressure of 102/30, mean 59 mmHg, right atrial pressure 15 mmHg and pulmonary vascular resistance 7.3 Wood units. Given these findings, the patient was transitioned from inhaled to subcutaneous treprostinil, and when he continued to worsen was listed for transplant. The patient was managed with aggressive transfusions pre- and post-transplant to maintain his hemoglobin S level less than 10%, and transplant was performed off cardiopulmonary bypass.
RESULTS: Over one year post-transplant, the patient continues to do well. He remains off oxygen and all pulmonary hypertension medications. He has had resolution of radiographic findings associated with his SCD-PAH. Pathology from the explanted lungs revealed pulmonary arterial vasculopathy as well as veno-occlusive disease. He discontinued oxygen and vasodilator therapy soon after transplant. Although he had an episode of primary graft dysfunction, and had acute cellular rejection in the first year, he has had no sickle cell vaso-occlusive pain crises or SCD-related complications, and continues to do well. Notably, he has discontinued opiates, likely related to aggressive q3 week phenotype-matched simple RBC transfusions and immunosuppression.
CONCLUSIONS: This case report discusses the complexities of management of patients with SCD-PAH pre- and post-transplant, and provides rationale for ongoing transplantation in this patient population on a case-by-case basis.