A new study published in Nature Communications led by Versiti Blood Research Institute senior investigator Prithu Sundd, PhD, his past and current trainees (Tomasz Brzoska, PhD and Tomasz Kaminski, PhD) and collaborators across the country, sheds light on a long-standing and life-threatening question in sickle cell disease: Why do only some sickle cell patients develop dangerous blood clots in their lungs?
Sickle cell disease is the most common inherited blood disorder affecting people of African ancestry. The red blood cells of sickle cell patients are shaped like sickles or crescents, which can cause serious problems with the body’s oxygen and blood flow. Among sickle cell patients hospitalized for acute respiratory failure, lung thrombosis (the formation of blood clots in the lungs) accounts for approximately 20% of cases. However, clinicians and researchers haven’t understood why this dangerous health complication develops in some patients and not in others.
In the new article “CD39 polymorphism enables lung thrombosis in sickle cell disease,” Sundd and colleagues uncovered a key biological mechanism that normally protects patients from lung thrombosis and how a genetic variance disrupts this protection to increase the incidence of lung thrombosis.
Extracellular vesicles, tiny particles released by blood-vessel wall cells, were found to play a role in preventing clot formation in the lungs of people with sickle cell disease. The research team identified a small, specific genetic variation in the CD39 gene that interferes with the release of extracellular vesicles. Patients who carry variation, called the CD39 polymorphism, are more likely to develop lung thrombosis, which explains why the condition only affects a subset of sickle cell patients.
“This study has the potential to inform future therapies and treatments for sickle cell patients by reporting why only a subset but not every sickle cell patient may develop lung thrombosis,” said Sundd.
Knowing the “why” behind this life-threatening complication is the first step in figuring out new and better treatments for it, and more information allows healthcare providers to help their patients more effectively.
“The study’s findings also promote a precision medicine approach and may inspire future clinical trials by suggesting that sickle cell patients carrying this CD39 polymorphism may actually benefit from purinergic signaling inhibitors,” said Sundd.
Beyond its scientific impact, the study highlights the true power of scientific collaboration at the national scale. The study brought together investigators from Versiti Blood Research Institute, University of Pittsburgh, Medical College of Wisconsin, University of Maryland, as well as Walk-PHaSST study investigators, and NHLBI TOPMed program venous thrombo-embolism working group investigators.
“This level of collaboration and teamwork provides all the necessary resources to enable a study like this,” Sundd said.
And for patients living with sickle cell disease, the study offers hope that future therapies could prevent one of the condition’s most dangerous complications. By identifying who is most at risk, clinicians may one day intervene earlier and more effectively, ultimately saving lives.