Effect of Renin Angiotensin System (RAS) Blockade on Hematological Parameters in Patients with Secondary Polycythemia (SP) Associated with Chronic Obstructive Pulmonary Disease (COPD) and Sleep Apnea (SA).
Authors: Ramanarayanan Jeyanthi , Brodzik Frank , Mehdi Syed , Pasquale Donald 
Published: October 2019

Abstract
Introduction: Erythrocytosis secondary to hypoxia is an erythropoeitin (EPO) driven physiologic mechanism to sustain tissue oxygenation. Phlebotomy is indicated to relief symptoms of hyperviscosity that occur at very high hemoglobin (Hb)/hematocrit (Hct) levels. Recent evidence suggests a causal relationship between RAS and hematopoesis in SP through either EPO related or non-EPO-related mechanisms. On that premise, angiotensin converting enzyme inhibitors (ACEI) used to treat post-transplant erythrocytosis in kidney recipients may have a beneficial effect in lowering hct levels in SP patients.
Objective: To study the effect of RAS blockade with ACEIs on Hb, Hct and EPO levels in patients with SP due to COPD/SA.
Material and methods: We retrospectively identified patients with SP or erythocytosis treated at our Institutions using the ICD code system. Search involved patients evaluated/treated between 1999 and 2006. Only patients with documented hypoxemia (diagnosis of COPD or sleep apnea), normal to elevated EPO levels, absent splenomegaly and elevated red cell mass in nuclear studies when available were included in the analysis. Demographic characteristics, pulmonary function tests results, baseline, peak Hb, Hct, serum creatinine (Cr), EPO levels at initial diagnoses and history of ACE inhibitors use were obtained. Subsequently, patients were divided into two groups based on whether or not they were on ACE inhibition for at least 2–3 months prior to the peak HgB/Hct values. Patients without documented hypoxemia were excluded as well as those with features suggestive of myeloproliferative disorder or relative polycythemia. Chi-square test was used to evaluate differences in Hct levels between groups before and after ACEI or placebo.
Results: A total of 44 patients were identified with median age 60.5 years. There were 22 patients who had received ACEIs for other co-morbid conditions, for at least 3 months prior to peak hematocrit/hemoglobin values. Serum creatinine (median 1.0 mg/dl) levels were equally balanced between two groups. About half of patients in each group had moderate to severe COPD/SA base on PFTs and sleep studies. The median peak Hct and HgB in patients receiving ACEI were 57.45% and 18.65 gr/dl (Mean peak values 56.92% and 18.96 grs/dl; range 51.3–66.9% and 17–20.8 gr/dl) respectively. Patients not on ACEIs had a median peak Hct/HgB of 56.6% and 18.95 gr/dl (Mean peak values 56.54% and 19.2 gr/dl; range 53.0–61.1% and 17.4–21.8 grs/dl). EPO levels were available in 12/44 patients at the time of initial diagnosis with mean values 13.47 MIU/ml (range 5.9–22.3 MIU/ml) without any difference between two groups. Higher percentage of patients achieved decrease in Hct levels (>/=2.5%) from baseline after starting ACEI compared to placebo p=0.017.
Discussion: Our results suggest that the use of ACEI decrease Hct levels from baseline in patients with hypoxemia induced SP. It is unclear if this decline is beneficial therapeutically in patients with chronic pulmonary disease. Further studies are warranted to determine if ACEI can decrease frequency of phlebotomies in SP due to hypoxemia.