PULMONARY HYPERTENSION IN SICKLE CELL DISEASE: LOOKING BEYOND THE USUAL SUSPECT

Abstract

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pulmonary hypertension (PH) is common in sickle cell disease (SCD) and is a major risk factor for death with 2-year mortality 40-50%. Autoimmune disease (AID) is an established cause of pulmonary hypertension. Patients with SCD present a defective alternate complement pathway that increases risk of infection and autoimmune diseases. However, coexisting AID and SCD is rarely reported, suggesting possible under-diagnosis due to overlapping symptoms. CASE PRESENTATION: 20 year old male with sickle cell S/O Arab presented with 2 days of hip pain, fever, dyspnea and reproducible, non-exertional chest pain. Admitted for management of acute chest syndrome. He was found to have nephrotic-range proteinuria (protein-creatinine ratio 3.65 mg/mg). Serology markers were positive for ANA titer 1:2560 (speckled pattern), positive RNP (> 8.0) and Smith antibodies (1.9). Echocardiogram revealed right ventricular systolic pressure (RVSP) of 75 mmHg. Patient was diagnosed with mixed connective tissue disease (MCTD) with systemic lupus erythematosus (SLE) predominant features. He underwent kidney biopsy which was consistent with focal segmental and global glomerulosclerosis (FSGS). Right heart catheterization (RHC) showed mean pulmonary artery pressure of 31 mmHg, pulmonary capillary wedge pressure of 5 mmHg, cardiac output/cardiac index 7.95L/min/4.69L/min/m2 respectively, pulmonary vascular resistance of 5.7 Wood units. Patient was initiated on hydroxychloroquine, losartan, and ambrisentan. DISCUSSION: Hemoglobin O Arab is an uncommon hemoglobinopathy due to substitution of lysine for glutamic acid at a position 121 of beta globin chain. Homozygotes are clinically asympatomatic. Compound heterozygous condition in combination with sickle hemoglobin results in Hb S/O Arab , which resembles homozygous sickle cell anemia and manifests with severe hemolytic anemia and recurrent painful crisis (Reference #1). Pulmonary hypertension in SCD is multifactorial, classified as Group V; pre-capillary PH due to hemolysis, impaired nitric oxide bioavailability, asplenia, chronic hypoxemia and thromboembolism; as well as post-capillary PH due to left ventricular dysfunction. Despite the prevalence and negative impact on mortality, there are few data to guide management of PH in SCD. A small number of clinical trials (Walk-PHaSST, ASSET-1 and ASSET-2 trials) failed to prove success with PAH specific therapies, thus it is not recommended for routine use in PH-SCD patients (Reference #2 and #3). Based on RHC data of our patient, he has PAH of combined etiology associated with SCD as well as MCTD with SLE features and therefore we chose to treat him with PAH-targeted therapy. CONCLUSIONS: This case demonstrates importance of increased awareness of coexisting etiologies for PAH leading to a rapid progression and increased morbidity. Reference #1: Hemoglobin S/OARAB: Thirteen New Cases and Review of the Literature. American Journal of Hematology 60:279–284 (1999) Reference #2: Machado RF, Martyr S, Kato GJ, et al. Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Br J Haematol. 2005;130:445–453. Reference #3: Br J Haematol. 2010 May;149(3):426-35. https://doi.org/10.1111/j.1365-2141.2010.08097.x. Epub 2010 Feb 17. DISCLOSURES: No relevant relationships by Sandi Khin, source=Web Response No relevant relationships by Ruth Minkin, source=Web Response