Diagnostics: Finding Blood Clots Before They Wreak Havoc

Photo: Blood clot

In the future, blood clots could be found by a urine test looking for thrombin, a key blood-clotting factor; © panthermedia.net/Sebastian Kaulitzki

A simple urine test developed by MIT engineers uses nanotechnology to detect dangerous blood clotting. Blood clots can form in anyone who sits on a plane for a long time, is confined to bed while recovering from surgery, or takes certain medications.

There is no fast and easy way to diagnose these clots, which often remain undetected until they break free and cause a stroke or heart attack. However, new technology from MIT may soon change that: A team of engineers has developed a way to detect blood clots using a simple urine test. The noninvasive diagnostic relies on nanoparticles that detect the presence of thrombin, a key blood-clotting factor. Such a system could be used to monitor patients who are at high risk for blood clots, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Biochemistry.

"Some patients are at more risk for clotting, but existing blood tests are not consistently able to detect the formation of new clots," says Bhatia. Blood clotting is produced by a complex cascade of protein interactions, culminating in the formation of fibrin, a fibrous protein that seals wounds. The last step of this process — the conversion of fibrinogen to fibrin — is controlled by an enzyme called thrombin.

Current tests for blood clotting are very indirect, Bhatia says. One, known as the D-dimer test, looks for the presence of fibrin byproducts, which indicates that a clot is being broken down, but will not detect its initial formation. Bhatia and her colleagues developed their new test based on a technology they first reported last year for early detection of colorectal cancer. "We realized the same exact technology would work for blood clots," she says. "So we took the test we had developed before, which is an injectable nanoparticle, and made it a thrombin sensor."

The system consists of iron oxide nanoparticles coated with peptides (short proteins) that are specialized to interact with thrombin. After being injected into mice, the nanoparticles travel throughout the body. When the particles encounter thrombin, the thrombin cleaves the peptides at a specific location, releasing fragments that are then excreted in the animals' urine. Once the urine is collected, the protein fragments can be identified by treating the sample with antibodies specific to peptide tags included in the fragments. The researchers showed that the amount of these tags found in the urine is directly proportional to the level of blood clotting in the mice's lungs.

Bhatia says she envisions two possible applications for this kind of test. One is to screen patients who come to the emergency room complaining of symptoms that might indicate a blood clot, allowing doctors to rapidly triage such patients and determine if more tests are needed. "Right now they just do not know how to efficiently define who to do the more extensive workup on. It is one of those things that you cannot afford to miss, so patients can get an unnecessarily expensive workup," Bhatia says.

Another application is monitoring patients who are at high risk for a clot — for example, people who have to spend a lot of time in bed recovering from surgery. Bhatia is working on a urine dipstick test, similar to a pregnancy test, that doctors could give patients when they go home after surgery. Other applications for the nanoparticle system could include monitoring and diagnosing cancer. It could also be adapted to track liver, pulmonary, and kidney fibrosis, Bhatia says.

MEDICA.de; Source: Massachusetts Institute of Technology