Red Blood Cells With Lower Hemoglobin May Help Predict PAH Outcomes

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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A new study highlights the predictive utility of hypochromic erythrocytes — red blood cells that have decreased levels of hemoglobin (the oxygen carrier) — in patients with pulmonary arterial hypertension (PAH).

The increased presence of these erythrocytes was shown to be an independent predictor of both mortality and shorter time to clinical worsening (TTCW) in PAH, serving as a potential indicator of disease prognosis, as well as iron homeostasis — the regulation of the import and export of iron from the body’s tissues and organs (iron is an important component of hemoglobin).

The study, titled “Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension,” was published in the journal Respiratory Research.

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Studies within the last decade have shown that iron deficiency in PAH patients is indicative of more severe disease and worse outcomes. However, iron supplementation has not been decisively shown to change such poor outcomes.

Iron deficiency was determined in these previous studies through blood tests for: serum ferritin (a blood protein that contains iron), iron or hemoglobin concentration, and transferrin saturation (TSAT; the value of blood iron divided by the total iron-binding capacity of the available transferrin, the protein that binds iron in the blood). These tests can however be affected by inflammation and infection, thus they may not always accurately define a person’s iron status. New tests to assess iron deficiency are therefore needed.

In the new study, a team led by researchers in Germany looked at 150 patients who had a confirmed PAH diagnosis and a concomitant iron metabolism assessment from between April 2013 and August 2017. All participants were treated at the Center for Pulmonary Hypertension, Thoraxklinik Heidelberg, in Germany.

“The aim of this study was to identify a new marker for iron deficiency and clinical outcome in PAH patients,” the team wrote.

Out of the 150 PAH patients, the mean average age was 63.3 years, and 62% were female. Of the disease subtypes, 3% had heritable PAH, 29% had idiopathic PAH, 33% had associated PAH, and 35% had PAH associated with comorbidities (33 with cardiac comorbidities and 19 with pulmonary comorbidities).

Right heart catheterization — a test to measure heart function and often used as a diagnostic tool — showed a severely increased pressure in the pulmonary arteries (those that take blood from the heart to the lungs) along with high vascular resistance, meaning increased resistance to blood flow, in PAH patients.

Patients also showed enlarged right hearts with mild impairment of the right ventricular function, the part of the heart that pumps blood to the lungs to get oxygenated. All patients displayed normal kidney function and were followed for one year.

In total, 10.7% of the patients had anemia (decreased hemoglobin) at diagnosis, and that number nearly doubled to 21.1% at the one-year follow-up. Low levels of iron in the blood were unchanged between the baseline (study start; 54.1%) and the one-year follow-up (50.5%).

Similarly, hypochromic erythrocytes and serum ferritin levels were also unchanged between baseline and follow-up — 33.9% versus 36.5% after one year for hypochromic erythrocytes levels, and 16.0% versus 15.7% for serum ferritin levels.

The researchers then conducted survival analyses and found that iron levels had no predictive value for disease outcomes on either survival rates or TTCW. In contrast, hemoglobin deficiency at the time of diagnosis was significantly associated with a shorter TTCW; furthermore, patients who had low hemoglobin displayed a trend towards increased mortality.

However, hemoglobin levels at the one-year follow-up indicated no association with survival rates.

The team found that a presence greater than 2% of hypochromic erythrocytes in the blood at baseline was a strong, independent predictor of a shorter TTCW and worse survival. At one year after diagnosis, it was also associated with decreased survival.

In a multivariable analysis, where more than one variable is assessed at a given time, the increased presence of these red blood cells was the only variable that had a significant predictive value for TTCW and survival.

Low hemoglobin levels and a red cell distribution width (RDW, a measurement of the variation in red blood cell volume) of 15.7% or greater were the two strongest predictors at baseline for survival. At the one-year follow-up, hypochromic erythrocytes were the only significant predictor of survival.

Moreover, patients with a higher rate of hypochromic erythrocytes (more than 2%) displayed a greater impairment of renal function and of lung diffusion capacity (a measurement of how well oxygen and carbon dioxide are exchanged between the lungs and the blood). These patients also had increased anemia.

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There also seemed to be a significant association between increased hypochromic erythrocytes and worse World Health Organization functional class.

No correlation was identified for hypochromic erythrocytes and age, gender, mean pulmonary arterial pressure, pulmonary vascular resistance, or right ventricular systolic pressure.

Overall, the team suggested that, although ferritin and low blood iron levels are often used to assess iron homeostasis and the need for iron supplementation, these parameters were unable to predict mortality in PAH patients, unlike hypochromic erythrocyte measurements. The researchers believe that ferritin measurements may not correlate with TTCW or mortality due to the effects of inflammation and chronic kidney failure, which often occur in PAH patients.

Given that hypochromic erythrocytes are less affected by inflammation, their levels may provide valuable insight into iron deficiency and be a more reliable marker than serum ferritin.

“The presence of hypochromic erythrocytes [at levels greater than] 2% was a strong and independent predictor of mortality and shorter TTCW in this cohort of PAH patients,” the researchers wrote. “Thus, it can serve as a valuable indicator of iron homeostasis and prognosis even in patients without iron deficiency or anemia.”

The team noted, however, that “further studies are needed to confirm the results and to investigate therapeutic implications.”