Simple test could predict major complications in sickle cell patients

Researchers have found that a simple test for an enzyme called LDH may have significant importance for determining major risk factors in adults with sickle cell disease. The study results will be published in the March 15, 2006, issue of Blood, the official journal of the American Society of Hematology.

“This study suggests that LDH testing may be a worthwhile addition to ’well adult’ visits for individuals with sickle cell anemia, though the significance in children and adolescents, remains unclear,” said Zora Rogers, MD, Associate Professor of Pediatrics at The University of Texas Southwestern Medical Center in Dallas, who is not affiliated with the study.

LDH, or lactate dehydrogenase, is found in many different types of cells in the body, but is particularly rich in the red blood cells, heart, kidney, liver, and muscles. When these organs become diseased, the cells containing LDH release the enzyme, resulting in elevated LDH levels in the bloodstream.

In this study, patients with all forms of sickle cell disease – 213 adults in all – had their LDH levels measured with a blood test. Based on these values, the patients were categorized into three groups – low, medium, and high LDH. The LDH values were then reviewed in light of each patient’s medical history.

Typically, the upper limit of LDH in healthy adults is 200 IU/L (international units per liter). The 31 patients in the high group had LDH values of 512-1171 IU/L, correlating to a history of medical complications, in particular, leg ulcerations and priapism. The patients’ LDH values were also compared to their rates and severity of pulmonary hypertension, a build-up of pressure in the arteries that supply the lungs and a common complication of sickle cell disease. The researchers found that LDH values rise with severity of pulmonary hypertension.

In addition, mortality rates for the study participants were examined over a follow-up period of 49 months. Researchers found that patients with LDH values higher than the median had reduced survival compared to those with LDH values lower than the median. These data suggest that high LDH values may predict early mortality in patients with sickle cell disease.

The results of the study indicate that high LDH levels can define a subgroup of sickle cell patients who are significantly more likely to have serious complications such as pulmonary hypertension, leg ulcerations, and priapism, and are at increased risk of early mortality. Interestingly, these correlations held whether or not patients were taking hydroxyurea, the standard treatment for the disease, and LDH values were not associated with episodes of pain crisis, the hallmark of sickle cell anemia.

The source of LDH in these patients appears to be primarily from the breakdown of fragile red blood cells, consistent with recent published findings suggesting that red blood cell contents released into the bloodstream over a period of years may cause diseased blood vessel walls.

“LDH levels illuminate a pattern of pathology in sickle cell disease patients,” said Gregory Kato, MD, of the National Institutes of Health and lead study author. “As a result, LDH appears to hold great promise as an effective indicator for identifying patients most at risk and in need of possible preventive care and careful monitoring.”