Higher hemoglobin levels tied to lower end-organ damage risk

Risk of any damage in SCD was greater with levels below 7 g/dL

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Higher levels of hemoglobin — the protein in red blood cells responsible for oxygen transport — were associated with a lower risk of end-organ damage with sickle cell disease (SCD), a retrospective study has found.

The risk was higher for patients with hemoglobin levels below 7 g/dL and increased with age. End-organ damage refers to damage in major organs, such as the heart, lungs, kidneys, and brain.

Generally, men had a higher chance of developing end-organ-damage than women, except for stroke.

“Therapeutic strategies that result in higher [hemoglobin] levels may offer clinical and economic value for patients with SCD,” the researchers wrote in “Hemoglobin and End-Organ Damage in Individuals With Sickle Cell Disease,” which was published in Current Therapeutic Research.

SCD patients produce a faulty version of hemoglobin due to mutations in the beta-globin (HBB) gene that encodes for one of its subunits. The defective protein causes red blood cells to become rigid and acquire a sickle-like shape.

These sickled cells can slow or block blood flow to certain parts of the body, as it’s more difficult for them to pass through small blood vessels. They also die much quicker than healthy red blood cells, often leaving patients with a shortage of them and low hemoglobin levels, a condition known as anemia.

This can compromise the delivery of oxygen to organs, causing damage and leading to sudden episodes of severe pain — so-called vaso-occlusive crises (VOCs). Other forms of end-organ damage include acute chest syndrome (a severe SCD-related lung condition), kidney failure, pulmonary hypertension, stroke, and leg ulcers.

To characterize the relationship between hemoglobin levels and end-organ damage in adults and adolescents (ages 12 and older) with SCD, researchers conducted a large retrospective observational study using a U.S. healthcare database.

A total of 16,043 SCD patients contributed with 44,913 observations for a mean duration of 358 days (almost one year). Patients had a mean age of 37.9, with more than half (64.5%) being young adults (ages 18-49). Most (63.1%) were female.

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Role of hemoglobin levels in end-organ damage

At baseline (study’s start), mean hemoglobin levels were at 9.7 g/dL. Around a quarter of the patients (25.6%) had a history of end-organ damage, including chronic kidney disease (16.5%), pulmonary hypertension (7.0%), stroke (5.5%), and leg ulcers (3.1%).

The risk of any type of end-organ damage was higher for those with a hemoglobin level below 7 g/dL. The probability of developing any type of end-organ damage decreased consistently with higher hemoglobin levels. For instance, those with hemoglobin levels equal to or higher than 12 g/dL were 68.8% less likely to develop any type of end-organ damage than those with hemoglobin levels below 7 g/dL.

Patients with hemoglobin levels equal to or higher than 12 g/dL were 71.9% less likely to develop chronic kidney disease, 81.5% less likely to develop pulmonary hypertension, 83.5% less likely to have leg ulcers, and 31% less likely to have a stroke than those with hemoglobin below 7 g/dL.

The probability of having a stroke was 30% higher among female patients, but the probability of developing other types of end-organ damage was 16-53% lower for females.

The probability of end-organ damage generally increased with age — by 4.1 times for patients 18-34 and by 11.3 times for those 65 and older compared with patients under 18.

A history of end-organ damage was also associated with a higher likelihood of new end-organ damage events.

The results of this analysis “provide further evidence of an association between [hemoglobin] and risks of [end-organ damage] in patients with SCD and suggest that new treatments for SCD that result in higher [hemoglobin] levels may reduce the risk of these adverse outcomes,” wrote the researchers, who called it essential that healthcare providers be “aware of the association between anemia and [end-organ damage], and the related morbidity, mortality, and health care costs, to improve the overall management of this patient population according to evidence-based guidelines.”