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It may be possible to disrupt thrombosis without increasing the risk of bleeding, according to preclinical research published in Nature Communications.
“We have found a new thrombosis target that does not increase bleeding risk,” said study author Daniel I. Simon, MD, of University Hospitals Cleveland Medical Center in Cleveland, Ohio.
“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.”
The new pathway centers around a pair of protein receptors. One—Mac-1—is found on the surface of leukocytes recruited to sites of blood vessel injury, and the other—GPIbα—resides on the surface of platelets.
When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting.
The researchers found that genetically engineered mice, either without the Mac-1 receptor or with a mutant form of the receptor, could not bind GPIbα on platelets. As a result, the mice had delayed clot formation in response to artery injury.
However, these mice had similar platelet counts, platelet activation, plasma coagulation activity, and bleeding time as wild-type mice.
Additional experiments in mice showed that an antibody targeting Mac-1:GPIba inhibits thrombus formation.
And glucosamine, a small-molecule inhibitor of Mac-1:GPIba binding, inhibits thrombus formation without increasing bleeding risk.
Mice exposed to glucosamine were still able to successfully stop minor bleeding, like tail cuts, and maintain normal coagulation and platelet function.
The researchers believe these findings could lead to the development of better antithrombotic agents, as “the interaction between leukocyte Mac-1 and platelet GPIba is positioned as a novel and targetable mediator of thrombosis but not hemostasis.”
“Current anticlotting drugs and antiplatelet agents are effective in reducing heart attack and stroke but are associated with increased bleeding and transfusion,” Dr Simon said. “We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke.” 
It may be possible to disrupt thrombosis without increasing the risk of bleeding, according to preclinical research published in Nature Communications.
“We have found a new thrombosis target that does not increase bleeding risk,” said study author Daniel I. Simon, MD, of University Hospitals Cleveland Medical Center in Cleveland, Ohio.
“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.”
The new pathway centers around a pair of protein receptors. One—Mac-1—is found on the surface of leukocytes recruited to sites of blood vessel injury, and the other—GPIbα—resides on the surface of platelets.
When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting.
The researchers found that genetically engineered mice, either without the Mac-1 receptor or with a mutant form of the receptor, could not bind GPIbα on platelets. As a result, the mice had delayed clot formation in response to artery injury.
However, these mice had similar platelet counts, platelet activation, plasma coagulation activity, and bleeding time as wild-type mice.
Additional experiments in mice showed that an antibody targeting Mac-1:GPIba inhibits thrombus formation.
And glucosamine, a small-molecule inhibitor of Mac-1:GPIba binding, inhibits thrombus formation without increasing bleeding risk.
Mice exposed to glucosamine were still able to successfully stop minor bleeding, like tail cuts, and maintain normal coagulation and platelet function.
The researchers believe these findings could lead to the development of better antithrombotic agents, as “the interaction between leukocyte Mac-1 and platelet GPIba is positioned as a novel and targetable mediator of thrombosis but not hemostasis.”
“Current anticlotting drugs and antiplatelet agents are effective in reducing heart attack and stroke but are associated with increased bleeding and transfusion,” Dr Simon said. “We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke.”
It may be possible to disrupt thrombosis without increasing the risk of bleeding, according to preclinical research published in Nature Communications.
“We have found a new thrombosis target that does not increase bleeding risk,” said study author Daniel I. Simon, MD, of University Hospitals Cleveland Medical Center in Cleveland, Ohio.
“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.”
The new pathway centers around a pair of protein receptors. One—Mac-1—is found on the surface of leukocytes recruited to sites of blood vessel injury, and the other—GPIbα—resides on the surface of platelets.
When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting.
The researchers found that genetically engineered mice, either without the Mac-1 receptor or with a mutant form of the receptor, could not bind GPIbα on platelets. As a result, the mice had delayed clot formation in response to artery injury.
However, these mice had similar platelet counts, platelet activation, plasma coagulation activity, and bleeding time as wild-type mice.
Additional experiments in mice showed that an antibody targeting Mac-1:GPIba inhibits thrombus formation.
And glucosamine, a small-molecule inhibitor of Mac-1:GPIba binding, inhibits thrombus formation without increasing bleeding risk.
Mice exposed to glucosamine were still able to successfully stop minor bleeding, like tail cuts, and maintain normal coagulation and platelet function.
The researchers believe these findings could lead to the development of better antithrombotic agents, as “the interaction between leukocyte Mac-1 and platelet GPIba is positioned as a novel and targetable mediator of thrombosis but not hemostasis.”
“Current anticlotting drugs and antiplatelet agents are effective in reducing heart attack and stroke but are associated with increased bleeding and transfusion,” Dr Simon said. “We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke.”