Large-scale simulation of human blood is boon to personalized medicine

ScienceDaily (May 2, 2012) Having a virtual copy of a patient's blood in a computer would be a boon to researchers and doctors. They could examine a simulated heart attack caused by blood clotting in a diseased coronary artery and see if a drug like aspirin would be effective in reducing the size of such a clot.

Now, a team of biomedical engineers and hematologists at the University of Pennsylvania has made large-scale, patient-specific simulations of blood function under the flow conditions found in blood vessels, using robots to run hundreds of tests on human platelets responding to combinations of activating agents that cause clotting.

Their work was published in the journal Blood.

Patient-specific information on how platelets form blood clots can be a vital part of care. Normally, clots prevent bleeding, but they can also cause heart attacks when they form in plaque-laden coronary arteries. Several drugs, including aspirin, are used to reduce the size of such clots and prevent heart attacks, but, as platelets differ from person to person, the efficacy of such drugs differs as well.

"Blood platelets are like computers in that they integrate many signals and make a complex decision of what to do," said senior author Scott Diamond, professor of chemical and biomolecular engineering in the School of Engineering and Applied Science. "We were interested to learn if we could make enough measurements in the lab to detect the small differences that make each of us unique. It would be impossible to do this with the cells of the liver, heart or brain. But we can easily obtain a tube of blood from each donor and run tests of platelet calcium release."

When blood platelets are exposed to the conditions of a cut or, in a more dangerous situation, a ruptured atherosclerotic plaque, they respond by elevating their internal calcium, which causes release of two chemicals, thromboxane and ADP. These two activating agents further enhance calcium levels and are the targets of common anti-platelet drugs such as aspirin or clopidogrel, also known as Plavix. By preventing platelets from increasing their calcium levels, these drugs make them less able to stick together and block blood vessels, decreasing the likelihood of a heart attack.

Since blood is a liquid, the liquid-handling robots originally developed for drug screening tests were ideal to test platelet function.

"We used a technique developed in our lab called 'pairwise agonist scanning' on platelets from three different donors to generate a massive data set of how their cells responded to all different pairs of these activating agents," Diamond said. "Then we trained neural network models for each donor based on this data to simulate how each and every cell in a blood clot is responding."

Neural networks are a way of looking at the relationship between inputs and outputs for very complex processes, rather than at the details of the process.

"They summarize the overall function of all the chemical reaction networks that are occurring within a single platelet," Diamond said.

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Large-scale simulation of human blood is boon to personalized medicine