Washington: A recent study has found that it may be possible to disrupt harmful blood clots in people at risk for heart attack or stroke without increasing their risk of bleeding.
The research from University Hospitals (UH) Cleveland Medical Centre, Case Western Reserve University School of Medicine and the Cleveland Clinic revealed a previously unknown cell receptor interaction that, when manipulated with therapeutic molecules, safely prevents blood clots.
"We have found a new thrombosis target that does not increase bleeding risk," said senior author Daniel I. Simon. "Our discovery indicates that you can identify a new pathway and target that mediates blood clotting, but does not affect our body's natural processes to stop bleeding, called hemostasis."
The new pathway centres around a pair of protein receptors that help certain cells interact in inflammation and thrombosis. One receptor-Mac-1-is found on the surfaces of white blood cells recruited to sites of blood vessel injury, and the other-GPIb alpha-resides on the surfaces of platelets that form clots.
When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting. Mac-1 binding to GPIb alpha also broadly regulates inflammation in laboratory models of kidney disease, vasculitis and multiple sclerosis.
Simon and colleagues discovered the interaction causes large and small artery clots in mice, but can be blocked by an antibody or a new, therapeutic small molecule that binds to the Mac-1 receptor.
The researchers showed genetically engineered mice either without the Mac-1 receptor or with a mutant form could not bind GPIb alpha on platelets. As a result, the mice had delayed blood clot formation in response to artery injury. Mice exposed to the interfering antibody or small molecule were also unable to form the kinds of blood clots that can lead to stroke or heart attack.
While the results showed the Mac-1-GPIb alpha receptor duo is required for harmful clots, the researchers discovered blocking their interaction with the small molecule had no effect on bleeding risk. Mice exposed to the molecule were still able to successfully stop minor bleeding, like tail cuts, and maintain normal blood coagulation and platelet function.
The findings could lead to new medications that stave off heart attacks and strokes without harmful side effects, like excessive bleeding.
"Current anti-clotting drugs (anticoagulants, such as warfarin, Xarelto/rivaroxaban, Eliquis/apixaban) and antiplatelet agents (aspirin, Plavix/clopdigorel, Brilinta/ticagrelor) are effective in reducing heart attack and stroke, but are associated with increased bleeding and transfusion," said Simon, adding, "We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke."
The study is published in Nature Communications....