VCU news

By Lorraine Cichowski and Marcus Carr, Jr.

RICHMOND, Va. – Researchers at Virginia Commonwealth University have developed an innovative laboratory test that quickly measures the amount and speed at which the enzyme, thrombin, is produced in a patient’s blood. The new tool could help clinicians target drugs to control a range of blood-clotting problems – from hemorrhaging in accident victims to uncontrolled bleeding in hemophiliacs to excessive clotting that could lead to life-threatening thrombosis.

Finding a way to accurately and easily mark the moment that thrombin generation begins following surgery or injury to a blood vessel and measure the rate and amount of thrombin produced in a patient’s blood is “the holy grail of coagulation,” says VCU blood-clotting expert Marcus E. Carr Jr., M.D., Ph.D., professor of internal medicine and pathology.  Current methods to assess the function of the haemostatic system are relatively crude.

“Thrombin generation increasingly is recognized as the critical component of normal hemostatic function,” says Carr. “If thrombin generation is delayed or deficient, as it might be in a hemophiliac, the patient is at risk for excessive bleeding. If thrombin generation is not controlled, the patient is at risk for recurrent thrombosis, which could cause stroke, coronary infarction, circulatory problems in the legs or other serious diseases. Physicians who want to treat any of these cases with some of the new therapies being introduced need much more information about thrombin than they can get today.”

Thrombin is a key enzyme in the blood that activates the tiny blood cells called blood platelets to begin the blood-clotting process.

In an article published online this week by the Journal of Thrombosis and Haemostasis, Carr and his team of researchers describe a blood analysis process that uses technology Carr developed at VCU to measure how long it takes for thrombin to form in normal blood, in blood from patients with coronary artery disease and in blood from hemophiliacs.

Their study of 40 patients showed that blood taken from normal, healthy volunteers, average age 45, took on average between six and seven minutes to begin clotting. Blood from patients with hemophilia took as much as three times longer to clot -- between 10 and 19 minutes -- and produced very weak clots compared with clots formed in normal blood.  In patients with coronary artery disease, clotting began very quickly – in about four minutes – and clots were twice as rigid as those formed in normal blood. The study also tracked how long it takes for blood from hemophiliacs or those with coronary artery disease to clot normally after treatment with either hemostatic agents to speed up clotting or anticoagulants to slow it down.

“It makes it exquisitely a potentially useful test for diagnosing and assessing risk and monitoring drug therapies to reverse abnormal thrombin generation,” said Carr. “The continuing development of potent antiplatelet and anticoagulant agents and their combined application in settings such as acute coronary syndromes and cerebrovascular attacks have emphasized the need for a global measure of thrombin generation which could reflect the combined effects of these agents.”

The test takes about 10 minutes and uses 700 micro liters of whole blood, an advantage over many existing tests which require that the blood be separated first into plasma and cells.

The article will be published in the August print edition of the Journal of Thrombosis and Haemostasis.  Editors published the article in the Early Edition section of their web site at www.JournalTH.com because of its potential interest to other researchers.