Elevated RDW linked to significantly higher mortality risk

Elevated red blood cell distribution width (RDW) measured at hospital admission, and rising RDW during hospitalization were both linked to significantly higher death rates from Covid-19 in a study involving more than 1,600 patients treated at 4 Boston hospitals.

A RDW of greater than 14.5% at the time of hospital admission for illness due to SARS-CoV-2 infection was associated with an almost 3-fold increase in risk for death in the cohort (relative risk [RR] 2.73), with a mortality rate of 31% in these patients, compared to 11% in those with normal RDW.

Among patients younger than 50 years of age, a RDW greater than 14.5% at admission increased the risk for death from Covid-19 more than 5-fold (RR, 5.25), with a mortality rate of 8% vs. 1%, respectively, associated with elevated and normal RDW.

And patients with elevated RDW at hospital admission were more than 6-times more likely to die within 48 hours of admission.

Study findings were published online Sept. 23 in JAMA Network Open.

Red blood distribution width is determined as part of a routine complete blood count test, and elevated RDW, which corresponds to decreased mean red blood cell volume, has been shown in previous studies to be a risk factor for death from all causes, as well as death from heart disease, pulmonary disease, sepsis, cancer, and other life-threatening conditions.

“Previous studies have found evidence in some specific conditions that RDW elevation is caused by delayed clearance of older red blood cells,” wrote researcher John M. Higgins, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

They noted that since red blood cells characteristically decrease in cellular volume across their lifespan, “persistence of these older, smaller cells thus increases volume variance, and this clearance delay coincides with and offsets a net decrease in red blood cell production.”

“These reports suggest the possibility that an elevated RDW in some circumstances may reflect a clinical state in which red blood cell production and turnover have slowed in the setting of increased production and turnover of leukocytes or platelets such as would occur in inflammation.”

With this background in mind, the researchers examined whether elevated RDW was associated with an increased risk for death among patients hospitalized with Covid-19.

The study included adults admitted for symptoms related to SARS-CoV-2 infection at four Boston hospitals (Massachusetts General Hospital, Brigham and Women’s Hospital, North Sore Medical Center or Newton-Wellesley Hospital) between early March and late April of this year.

Measures included RDW at admission and during hospitalization, with an elevated RDW defined as greater than 14.5%. Relative risk (RR) of mortality was estimated by dividing deaths of those with an elevated RDW by deaths among those without an elevated RDW. Mortality hazard ratios (HRs) and 95% CIs were estimated using a Cox proportional hazards model.

The study population included 1,641 patients (mean [SD] age, 62 [18] years; 886 men [54%]; 740 whites [45%] and 497 Hispanic [30%]; 276 non survivors [17%]).

Elevated RDW (>14.5%) was associated with an increased mortality risk in patients of all ages. A total of 1,173 patients had normal RDW and 468 had elevated RDW. Among patients younger than age 50 years, 341 had normal RDW and 65 had elevated RDW.

Among the main study findings:

  • The relative risk for death associated with elevated RDW compared to normal RDW was 2.73 among the entire cohort, 5.25 among patients younger than age 50 years, 2.90 among patients between the ages of 50 and 59-years, 3.96 among patients between the ages of 60- and 69-years of age, 1.45 among patients who were age 70- to 79, and 1.59 among patients who were age 80 years or older.
  • RDW was associated with mortality risk in Cox proportional hazards models adjusted for age, D-dimer (dimerized plasmin fragment D) level, absolute lymphocyte count, and common comorbidities such as diabetes and hypertension (hazard ratio of 1.09 per 0.5% RDW increase and 2.01 for an RDW >14.5% versus ≤14.5%; P<0.001).
  • Patients whose RDW increased during hospitalization had higher mortality compared with those whose RDW did not change; for those with normal RDW, mortality increased from 6% to 24%, and for those with an elevated RDW at admission, mortality increased from 22% to 40%.

Relative risk for death was particularly elevated within 48 hours of admission, with just 9 of 1,175 patients with normal RDW dying during this time frame (mortality rate, 0.8%) compared to 23 of 479 patients with elevated RDW (morality rate, 4.9%, RR, 6.12).

In addition, risk ratios for different age groups were significantly different compared with each other, suggesting an effect modification, with an elevated RDW having a larger effect on mortality for younger patients (<70 years) than it had for older patients.

Mortality risk associated with RDW remained statistically significant after adjustment for patient age, race, ethnicity, D-dimer level, absolute lymphocyte count, other blood count measures, and 5 major comorbidities.

The researchers concluded that RDW is “a routine laboratory test that may be useful in risk stratification of hospitalized patients with Covid-19.”

  1. Elevated red blood cell distribution width measured at hospital admission, and rising red blood cell distribution width during hospitalization were both linked to significantly higher death rates from Covid-19.
  2. Patients with elevated RDW at hospital admission were more than 6-times more likely to die within 48 hours of admission.

Salynn Boyles, Contributing Writer, BreakingMED™

Funding for this research was provided by the One BraveIdea Initiative, Fast Grants and the Mercatus Center, George Mason University, and others.

Researcher Brandon Westover reported grants from the National Institutes of Health during the conduct of the study. Aaron D. Aguirre reported grants from the CRICO Risk Management Foundation during the conduct of the study. John M. Higgins reported grants from the One Brave Idea Initiative and grants from Fast Grants at the Mercatus Center, George Mason University during the conduct of the study. .

 

Cat ID: 190

Topic ID: 79,190,254,930,570,190,926,192,927,151,928,925,934