| Translational Research:
From the laboratory bench to the patient’s bedside, the process of ‘translating’ ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. |
 |
 |
CHORI Staff Directory |
 |
CHORI Intranet |
CHORI Clinical Scientist Confirms Predictive Marker of Acute Chest Syndrome Onset in Pilot Study
| “We knew that if you were treating someone chronically with transfusions, you could prevent the symptoms of sickle cell disease – you’re basically replacing the sickle cell blood with healthy blood.” |
In a short report published at the end of the year in the British Journal of Haematology, CHORI clinical scientist Lori Styles, MD, confirmed for the first time that the inflammatory mediator, secretory phospholipase A2 (sPLA2), can be used as a predictive marker in the prevention of acute chest syndrome (ACS) in patients with sickle cell disease (SCD).
“ACS is the number one cause of death in sickle cell disease,” says Dr. Styles. “It’s like pneumonia, which can be severe in relatively well people, and in sickle cell disease it’s even more serious.”
As a result, researchers have long been searching for a way to treat or prevent ACS, which normally occurs in sickle cell patients during vaso-occlusive episodes (VOEs). The hallmark of SCD, VOEs are incredibly painful and occur when the blood vessels become clogged due to the sickle shape of the red blood cells.
In this break-through study, Dr. Styles and her colleagues were able to use a predictive marker – an elevation in the levels of sPLA2 – to determine which patients were going to develop ACS, and were then able to prevent ACS onset by pro-actively treating the at-risk patients with blood transfusions.
“It confirms that we can use sPLA2 to predict development, which we’ve never been able to do. This allows you to prevent ACS rather than simply treat it.”
While Dr. Styles’ previous research had identified sPLA2 as a potential predictive tool, this is the first study in which that theory was tested and put to use.
The results were overwhelming. Of the total number of patients with elevated sPLA2 levels, sixty-three percent of patients randomized to standard care for the treatment of their VOE developed ACS, while none of the patients randomized to transfusion did.| “No one had ever answered the question of whether or not, if you knew a day or two ahead of time, you could prevent ACS in this acute situation, while a VOE was actually occurring and not before.” |
“We knew that if you were treating someone chronically with transfusions, you could prevent all the symptoms of sickle cell disease – you’re basically replacing the sickle cell blood with healthy blood,” says Dr. Styles. “But no one had ever answered the question of whether or not, if you knew a day or two ahead of time, you could prevent it in this acute situation, while a VOE was actually occurring and not before.”
While the study provided conclusive evidence of both the predictive value of elevated sPLA2 levels and the efficacy of blood transfusions in preventing ACS under acute conditions, the number of participants for the pilot study was relatively small. Dr. Styles and her colleagues, however, already have a larger study ready to begin in 2008 to confirm the results, with over 10 different centers and 120 patients. In addition, a new study is currently underway that utilizes a sPLA2 inhibitor as a potential method of preventing ACS. Dr. Styles and her colleagues expect the results from that study by the end of 2007. |
In the mean time, Dr. Styles and her colleagues can celebrate the success of the latest study and the hope that it offers patients with SCD and their families.
“It’s really exciting not only because it adds more data to our theory that sPLA2 is a key player,” says Dr. Styles, “but also because ACS is a significant problem in sickle cell disease that we haven’t ever been able to do anything about – and now we can.”
Back
© 2005 Children's Hospital Oakland Research Institute
5700 Martin Luther King Jr Way • Oakland, California 94609
Phone 510-450-7600 • Fax 510-450-7910
Site Map • Disclaimer
• CHORI
Intranet • Email Webmaster