Among adults with sickle cell disease, early mortality is associated with increasing tricuspid regurgitant jet velocity on ECG, reticulocyte count, brain natriuretic peptide levels, and patient age, and with decreasing fetal hemoglobin levels, according to a report published in Haematologica.
Although survival improved among children with sickle cell disease (SCD) following the Food and Drug Administration approval of hydroxyurea treatment in 1998, mortality remains high among adult patients. To examine the clinical and laboratory factors underlying early mortality in this patient population, researchers combined the findings from their single-center cohort study of 161 clinic patients and a meta-analysis of nine studies in the literature, for a total of 3,257 participants. This is “the largest number of SCD patients in whom risk factors for mortality have been evaluated in the hydroxyurea era,” said Poulami Maitra, PhD, of the department of biostatistics at the University of North Carolina, Chapel Hill, and her associates.
The clinic cohort had a median age of 36 years (range, 18-71 years), and there were 29 deaths during a median follow-up of 7.2 years. The median age at death was 48 years. Similarly, the median age at death ranged from 39.7 to 53 years in the meta-analysis.
In the combined cohort, patients who had a tricuspid regurgitant jet velocity of 2.5 m/s or more had three times greater risk of dying than did patients who had lower values, and the risk of dying was approximately doubled for every 1-U elevation in log(N-terminal pro-B type natriuretic peptide), which reflects increasing ventricular strain. Both links have been reported before. The findings confirm that recent clinical practice guidelines recommending periodic echocardiographic screening for these patients is warranted, the investigators said (Haematologica. 2017 Jan 19. doi: 10.3324/haematol.2016.153791).
The hazard of dying was 5% higher for every 1% increase in reticulocyte count, which suggests that hemolysis contributes to early mortality in these patients. The hazard of dying also was 3% lower for every 1% increase in fetal hemoglobin. This association with fetal hemoglobin is the basis for the development of drugs that raise that level, such as hydroxyurea.
Mortality was 30% higher for every 10-year increase in patient age, reflecting the fact that people with SCD show increasing end-organ damage over time that contributes to their mortality, Dr. Maitra and her associates said.
This work was supported by the National Institutes of Health and the North Carolina Sickle Cell Program. Dr. Maitra reported having no relevant financial disclosures; one of her associates reported serving as a consultant to Pfizer and Global Blood Therapeutics.