Researchers Detect Blood-Clotting Mechanism

Ever wonder how your blood miraculously stops flowing and forms a scab after a cut? Researchers have now pinpointed the mechanism down to the molecular level.

"The human body has an incredible ability to heal from life's scrapes and bruises," study co-author Wesley P. Wong, a principal investigator at the Rowland Institute at Harvard University, said in a university news release.

"A central aspect of this response to damage is the ability to bring bleeding to an end, a process known as hemostasis," Wong said. "Yet regulating hemostasis is a complex balancing act."

If people have too much hemostatic activity, they can develop an excess of blood clots, resulting in thrombosis, which is a potentially deadly condition. On the other hand, if there is too little hemostatic activity, people could bleed to death, according to background information in the news release.

To achieve and maintain the right hemostatic balance, the body has a feedback system controlled by miniscule forces in the circulation system. The forces are applied to the highly-sensitive A2 domain of the blood-clotting protein called von Willebrand factor (VWF), which acts as a "force sensor," the researchers explained.

By manipulating single molecules, the researchers found that the tiniest force causes A2 molecules to unfold and lose much of their complex, three-dimensional organization. After the unfolding, the enzyme ADAMTS13 comes into play. The enzyme cuts the molecule, hence controlling the size of the blood clot, according to the study, in the June 5 issue ofScience.

"In the body, these cutting events decrease hemostatic potential and also enable blood clots to be trimmed in size," Wong said. "The system is so finely tuned that the A2 shear sensor is able to regulate the size of VWF within the bloodstream, maintaining the optimal size for responding properly to traumas."

To manipulate molecules, the researchers used "optical tweezers" developed in Wong's lab, which can apply miniscule forces to individual molecules while observing tiny changes in their length.

A better understanding of the mechanism of blot clotting could lead to new treatments for injuries or bleeding disorders, such as type 2A von Willebrand disease, the researchers noted.