|Study Finds Potential Marker To Identify Sickle
Cell Patients at High Risk of Complications
Researchers studying sickle cell disease have found that an enzyme,
which can be measured by a simple blood test, may help determine
whether a patient has a high risk of developing certain serious
complications associated with the disease.
The study, led by researchers at the National Institutes of Health
Clinical Center and the National Heart, Lung, and Blood Institute
(NHLBI), will be published in the March 15, 2006 issue of Blood,
the journal of the American Society of Hematology.
Researchers say the enzyme lactate dehydrogenase (LDH) appears
to hold promise in patients with sickle cell disease as a marker
for risk of pulmonary hypertension and other complications, including
early death. Pulmonary hypertension — abnormally high blood
pressure in the lungs — is common in sickle cell disease.
“Our findings suggest that patients with sickle cell disease and
high LDH levels should have especially careful monitoring for pulmonary
hypertension, a life-threatening complication,” says Gregory Kato,
M.D., the lead author of the study. Kato is a clinician in the
NIH Clinical Center Department of Critical Care Medicine and director
of the Sickle Cell Vascular Disease Unit in the NHLBI Vascular
Sickle cell disease is a hereditary blood disorder that, in the
United States, is most prevalent in blacks. An abnormal type of
hemoglobin inside the red blood cells distorts their shape and
interferes with blood flow.
The enzyme LDH investigated in the study is found throughout the
body, especially in red blood cells, the heart, liver, lungs and
muscle. A blood test measuring LDH levels is readily available
and commonly used to determine tissue damage due to a variety of
Researchers measured the LDH levels of 213 adults with sickle
cell disease and then categorized the patients as having low, medium
or high levels. The frequency of several complications of the disease
was determined in the three LDH groups.
The study found that patients in the highest LDH group were more
likely to experience three circulatory problems: pulmonary hypertension,
leg ulcerations, and persistent and painful penile erections called
priapism. Pulmonary hypertension was detected in 61 percent of
patients with high LDH compared to15 percent of patients in the
lowest LDH group. Thirty-nine percent of people with high LDH reported
leg ulcerations and 60 percent reported priapism at some point
Mortality rates of study participants also were examined. Patients
with high LDH levels had a nearly four-fold increased risk of early
death compared to patients with lower LDH levels.
The study also found that high LDH levels may help to explain
why pulmonary hypertension develops in sickle cell disease. High
levels of LDH appear to indirectly indicate that two other proteins,
hemoglobin and arginase, have broken out of red blood cells.
“Our recently published studies have suggested that when fragile
red blood cells rupture and release their contents into the bloodstream,
after years it may cause blood vessel walls to become diseased,” Kato
says. “Our current findings further support this theory. Learning
more about this chain of events will help us to identify additional
Researchers from the National Institutes of Health Clinical Center,
the National Heart, Lung, and Blood Institute, the Children’s Hospital
and Research Center in Oakland, California, and the University
of Pittsburgh School of Medicine participated in this study.
The NIH Clinical Center is the clinical research hospital
of the National Institutes of Health. Through clinical research,
physicians and scientists translate laboratory discoveries into
better treatments, therapies and interventions to improve the
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U. S. Department of Health
and Human Services. It is the primary Federal agency for conducting
and supporting basic, clinical, and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit http://www.nih.gov.