When skin is cut or damaged, tiny cell fragments circulating in the blood, called platelets, arrive at the injury and spread out to stop the blood from leaking out. Once enough layers of platelets accumulate, like stacks of sandbags against a flood, a blood clot is formed, trapping red blood cells. When the break occurs in a blood vessel, the clot contracts to facilitate smooth blood flow through the vessels.
Until recently, researchers believed that platelet spreading and clot contraction were controlled by the same pathway. However a recent study from Thomas Jefferson University researchers challenges that thinking, opening up a holy grail of possibilities for treatments targeting both bleeding and thrombosis or clotting.
The study, led by molecular biologist and professor at Sidney Kimmel Medical College, Ulhas Naik, PhD , showed that while the process starts from the same place, different signaling molecules were activated depending on the endpoint. Using human platelet-rich plasma, the researchers found that when certain signaling molecules were inhibited, spreading was blocked but not clot contraction and the opposite was true as well.
"This is the first time anybody has reported two different pathways playing distinct roles," says Dr. Naik.
Dr. Naik explains that in certain diseases, it may be useful to prevent clot contraction without blocking platelet spreading – this allows the loose clot to be dissolved without risking excessive blood loss. Therapies that block platelet spreading could be advantageous in implanted devices such as artificial valves and stents, where platelets adhere to these devices and form a thrombus. Current thrombotic platelet inhibitors used clinically often lead to bleeding side effects since they inhibit both processes.
The next steps would involve testing these pathways in genetically engineered mice. Dr. Naik sees promise in this discovery attracting pharmaceutical avenues in the future.
By Deborah Balthazar
