Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension

Panagiota Xanthouli,Eduardo Bossone,Martina U Muckenthaler,Benjamin Egenlauf,Nicola Benjamin,Cao Ding,Christina A Eichstaedt,Memoona Shaukat,Maria Kögler,Anna D’Agostino,Ekkehard Grünig,Antonio Cittadini,Vivienne Theobald,Alberto M Marra

doi:10.1186/s12931-021-01884-9

Abstract

BackgroundIron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet. The aim of this study was to identify a new marker for iron deficiency and clinical outcome in PAH patients.MethodsIn this single-center, retrospective study we assessed indicators of iron status and clinical parameters specifying the time to clinical worsening (TTCW) and survival in PAH patients at time of initial diagnosis and at 1-year follow-up using univariable and multivariable analysis.ResultsIn total, 150 patients were included with an invasively confirmed PAH and complete data on iron metabolism. The proportion of hypochromic erythrocytes > 2% at initial diagnosis was identified as an independent predictor for a shorter TTCW (p = 0.0001) and worse survival (p = 0.002) at initial diagnosis as well as worse survival (p = 0.016) at 1-year follow-up. Only a subset of these patients (64%) suffered from iron deficiency. Low ferritin or low serum iron neither correlated with TTCW nor survival. Severe hemoglobin deficiency at baseline was significantly associated with a shorter TTCW (p = 0.001).ConclusionsThe presence of hypochromic erythrocytes > 2% was a strong and independent predictor of mortality and shorter TTCW in this cohort of PAH patients. Thus, it can serve as a valuable indicator of iron homeostasis and prognosis even in patients without iron deficiency or anemia. Further studies are needed to confirm the results and to investigate therapeutic implications.

Highlights

Iron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet
Patient characteristics Among 1522 right heart catheterizations performed at the Center for Pulmonary Hypertension, Thoraxklinik Heidelberg between April 2013 and August 2017, 150 patients had an invasively confirmed PAH diagnosis and a concomitant iron metabolism assessment
Ferritin and low serum iron were not able to predict mortality in PAH patients, these parameters are commonly used in clinical routine to assess iron metabolism and to indicate iron supplementation therapy

Summary

Introduction

Iron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet. Xanthouli et al Respiratory Research (2021) 22:288 such as quality of life [10], exercise endurance time [6] or right ventricular fractional area change [11] In these studies, the definition of iron deficiency was based on the three parameters each, including serum ferritin, transferrin saturation (TSAT), and serum iron or hemoglobin concentration. Iron deficiency diagnosis relies on the TSAT and serum ferritin levels. These parameters can be altered by concomitant conditions such as inflammation and infections and, not always accurately reflect the iron status [12]. The measurement of serum iron levels depends on the daytime and food intake [13] These parameters are unreliable if not recorded under standardized conditions such as fasting. Readily available, new iron deficiency indices which mirror the clinical status of the patient and which are less affected by inflammation are needed to facilitate therapeutic decisions

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