A new study describes how sickled red blood cells get stuck in tiny blood vessels of patients with sickle-cell disease. The findings may help researchers predict more accurately when such a vaso-occlusive pain crisis might occur.

One of the most common causes of sickle-cell disease occurs when deformed red blood cells clump together, blocking tiny blood vessels and causing severe pain and swelling in the affected body parts.

A new study from MIT sheds light on how these events, known as vaso-occlusive pain crises, arise. The findings also represent a step to being able to predict when such a crisis might occur.

"Estos painful crises are very much unpredictable. In a sense, we understand why they happen, but we do not have a good way to predict them yet, "says Ming Dao, a leading research scientist in MIT's Department of Science and Engineering and one of the senior authors of the study.

The researchers found that these painful events are most likely to be produced by immature red blood cells, called reticulocytes, which are more prone to stick to blood vessel walls.

Subra Suresh, president of Singapore's Nanyang Technological University, former dean of engineering at MIT, and the Vannevar Bush Professor Emeritus of Engineering, is also a senior author of the study, which appears in  Proceedings of the National Academy of Sciences the week of Sept. 3. The paper's lead authors are MIT postdoc Dimitrios Papageorgiou and former postdoc Sabia Abidi.

Simulating blood flow

Patients with a sickle cell disease have a single mutation in the gene that encodes hemoglobin, the protein that allows red blood cells to carry oxygen. Esteproduces misshapen red blood cells: Instead of the characteristic disc shape, cells become sickle-shaped, especially in low-oxygen conditions.

Patients often suffer from anemia because the abnormal hemoglobin cannot carry as much oxygen, as well as from vaso-occlusive pain crises, which are usually treated with opioids or other drugs.

To probe how blood cells interact with blood vessels to set off a vaso-occlusive crisis, the researchers built a specialized microfluidic system that mimics the post-capillary vessels, which carry deoxygenated blood away from the capillaries. These vessels, about 10-20 microns in diameter, are where vaso-occlusions are most likely to occur.

The microfluidic system is designed to allow the researchers to control the oxygen level. They found that when oxygen is very low, or under hypoxia, similar to what is seen in post-capillary vessels, sickle red cells are two to four times more likely to get stuck to the blood vessel walls than they are at normal oxygen levels.

When oxygen is low, hemoglobin inside the sickle cells forms stiff fibers that grow and push the cell membrane outward. These fibers also help the cells stick more firmly to the lining of the blood vessel.