Worldwide, over 13 million people suffer from sickle cell disease, for which few treatment options exist. Over six decades ago, scientists discovered the cause of sickle cell disease. They established that individuals with sickle cell disease produce crescent-shaped red blood cells that unlike typical disc-shaped red blood cells, clog the capillaries instead of flowing smoothly, which can result in severe pain, major organ damage and a substantially shorter life-span.

Later discoveries demonstrated that the disease is caused by a single mutation in the hemoglobin protein, and that the sickle shape, which is more prevalent in people who come from tropical climates, is in fact an evolutionary adaptation that can prove beneficial in protecting against malaria.

Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT declares:

“We still don’t have effective enough therapies and we don’t have a good feel for how the disease manifests itself differently in different people.”

Bhatia, and her team from Harvard University, Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital, have come up with a simple blood test, which is able to predict if a sickle cell patient has a high risk of developing painful complications of the disease.

The test is conducted by researchers measuring the blood samples’ efficiency of flowing through a microfluidic device, which could assist doctors in monitoring sickle cell patients and determine their optimum course of treatment, but also help scientists to develop new drugs for the disease. The device is described in the March issue of Science Translational Medicine.

Because the abnormal red blood cells of sickle cell patients are usually not long in circulation, patients often suffer from anemia, although the disease is mostly linked to vaso-occlusive crises that occur when the stiffer and stickier sickle-shaped cells obstruct blood vessels and prevent the flow of blood. The frequency and severity of these crises is different from patient to patient and nobody is able to predict when a crisis occurs.

Bhatia explains:

“When a patient has high cholesterol, you can monitor their risk for heart disease and response to therapy with a blood test. With sickle cell disease, despite patients having the same underlying genetic change, some suffer tremendously while others don’t – and we still don’t have a test that can guide physicians in making therapeutic decisions.”

Bhatia and L. Mahadevan, a Harvard professor of applied mathematics who studies natural and biological phenomena, started collaborating in 2007 to gain insight of how sickle cells move through capillaries.

In this study, the researchers recreated conditions that can lead to a vaso-occlusive crisis by directing blood through a microchannel and lowering its oxygen concentration. This triggers a bottleneck of sickle cells and prevents the flow of blood. They measured each blood sample to establish the duration it would take to stop the blood flow after being deoxygenized.

John Higgins, of MGH and Harvard Medical School, subsequently compared the sickle cell patients’ blood samples of those who did or did not visit the hospital’s emergency department or who received a blood transfusion within the last 12 months. Higgins discovered that patients’ blood of those with a less severe form of the disease did not slow down as rapidly, compared with the blood of those who were more severely affected.

According to Bathia, there are no other existing measures of blood properties, which include measuring the concentration of red blood cells or a fraction of altered hemoglobin or white blood cell count that are capable of making this kind of prediction. She says that the results emphasize that it is important to consider vaso-occlusion as a result of many factors interacting instead of just a single molecular measurement.

To demonstrate the device’s benefits for developing new drugs, the researchers also evaluated a potential sickle cell disease drug named 5-hydroxymethyl furfural. The drug has been designed to improve hemoglobin’s ability to bind to oxygen and by adding the drug to blood they discovered a drastic improvement in the blood’s flow through the device. A patent application for the device is pending with researchers currently working on developing the device as a diagnostic and research tool.

Written by Petra Rattue