When platelets go awry

David Christiani

May 26, 2017 — David Christiani, Elkan Blout Professor of Environmental Genetics, is senior author of a study published May 8, 2017 in the American Journal of Respiratory and Critical Care Medicine that found that changes in platelet count predict acute respiratory distress syndrome mortality.

What is acute respiratory distress syndrome?

It is a life-threatening condition in which fluid and inflammation swamp the lungs and impair breathing. It’s triggered by certain critical conditions like pneumonia, pancreatitis, sepsis, severe trauma, or having major surgery, and affects around 200,000 people a year in the U.S.—a magnitude similar to that of lung cancer. Older adults are more vulnerable to ARDS, so it’s becoming more common as the population ages.

ARDS has a mortality rate of 40%, which is very high. It can be prevented by prompt treatment of its precipitating conditions, but there is no cure.

Why was platelet count the focus of your study?

Platelets are best known for their role in blood coagulation, but they are clever buggers and have a lot of other functions—like playing a part in immune response. And when their number or function is disturbed, you can have problems. In ARDS, for example, platelets gone awry have been linked to impaired coagulation and an excessive inflammatory response of the immune system.

For this study, we used a novel approach by looking at the change in platelet count from the time of developing ARDS through management of the syndrome over the first 7 or 28 days—using samples from patients in an intensive care unit who had experienced a severe infection.

We found that changes in platelet count predicted whether patients survived ARDS. With this condition, platelet numbers decline as they aggregate in mini-clots in the lungs. This impairs lung function and increases risk of death. Patients appear to do better if their platelet numbers are maintained.

This study also provided more information about a particular gene that we previously determined modulates platelet count. We identified a variant of the gene associated with better ARDS survival. It appears that ARDS patients with this variant experienced less of a decline in platelet count after ICU admission—and a better prognosis—than those who didn’t have it.

What’s the next step for this research?

We now need to investigate whether this genetic trait affects platelet function, not just number. If we can better understand how platelets function in ARDS patients, we might be able to more accurately explain variability in outcomes—and identify targets for treatment.

– Amy Roeder