Team develops bioengineered material to quickly stop bleeding in patients taking blood thinners

In the United States, more than 11 million people take anticoagulant or antiplatelet medications, such as heparin or aspirin, to treat serious illnesses like heart attacks and strokes. However, these medications also put patients at risk of life-threatening bleeding if injured or during surgery.

To improve strategies for reducing blood loss, a team led by researchers at Brigham and Women’s Hospital developed a porous material that maximizes blood absorption and effectively activates clotting mechanisms, even in patients on anticoagulation or antiplatelets.

The results, published in PNASshow that the bleeding-stopping material, or “hemostatic,” stopped bleeding in an average of five minutes in patients on blood thinners who underwent cardiac catheterization, a dramatic reduction from traditional compression methods which can take more than two hours .

“This is a next-generation hemostat that effectively stops bleeding, even in patients who are taking anticoagulant or antiplatelet medications,” said corresponding author Hae Lin Jang, Ph.D., of the Center for Engineered Therapeutics. “We used an exciting interdisciplinary approach that combines engineering principles, materials science and understanding of molecular biology to overcome the limitations of existing therapies and address a real clinical need.”

More than 5 million people worldwide die from trauma each year, with more than a third attributed to uncontrolled hemorrhage. The researchers used what is called a “rational engineering” approach to develop a more effective hemostat. They began by simulating blood flow through the pores to determine which microscopic design would optimize absorption. They were inspired by the architecture of human lungs, which contain spherical “air sacs” called alveoli that allow a high rate of interaction with blood in a short time.

The alveoli have a large surface area due to their tortuous porous structure, which led researchers to engineer a highly interconnected spherical microporous structure into their material to rapidly absorb blood and accumulate clotting components such as platelets in a highly concentrated manner. , which facilitates blood clotting.

The researchers developed the honeycomb-like structure using chitosan, which can be extracted from shellfish. Chitosan is already used in certain hemostatics; its positively charged surface is known to strongly attract negatively charged platelets and fibrinogen, the two main components of a blood clot. However, contrary to previous hypotheses, researchers found that chitosan also directly stimulates blood clotting by activating the TLR-2 clotting pathway, making it a viable mechanism for increasing blood clotting, even in patients on anticoagulants.

Researchers demonstrated the material’s effectiveness in 70 patients who underwent cardiovascular catheterization procedures while on the anticoagulant heparin, with bleeding stopping after an average time of about five minutes for patients on low-dose heparin. and in less than about nine minutes in patients. on heparin doses up to 12,500 IU.

Other benefits of hemostatic material include its ease of application and removal. The chitosan pad eliminates the need for strong, prolonged compression, which can take several hours and requires extensive nursing care. Additionally, removal of gauze can cause severe pain in patients and is frequently associated with recurrence of bleeding; in contrast, the more absorbent chitosan hemostatic was removed relatively cleanly from wounds and received high patient comfort scores.

Researchers continue to study the healing process after application of chitosan hemostat. Additionally, they are investigating other next-generation dressings, which may be able to deliver medications or improve the cleanliness of the wound environment, reducing the need for frequent changes.

“This hemostat can save valuable time in emergency situations,” said first author Vivian K. Lee, Ph.D., of the Center for Engineered Therapeutics. “In an emergency, it can be extremely difficult to verify a patient’s prescribing information in order to provide appropriate anticoagulant therapy to patients on anticoagulants. If a hemostat can bypass the anticoagulant mechanisms of a medication, it may be used in a wide range of patients, saving time and potentially saving lives.

Co-authors of the study include Taewoo Lee (BWH), Amrit Ghosh (BWH), Tanmoy Saha (BWH), Manish V. Bais (BWH), Kala Kumar Bharani, Milan Chag, Keyur Parikh, Parloop Bhatt, Bumseok Namgung (BWH). ), Geethapriya Venkataramanan (BWH), Animesh Agrawal, Kiran Sonaje, Leo Mavely, Shiladitya Sengupta (BWH) and Raghunath Anant Mashelkar.