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 Medicine Branch.
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 causes.
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 in time.
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 potential treatments.”
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