What a new way to potentially stop profuse bleeding quickly means

The sight of a fresh wound or cut with blood spurting out uncontrollably could be quite disturbing. But what could be more traumatic or debilitating or sometimes even fatal is when that bleeding doesn’t stop.

Our body repairs minor cuts and wounds by forming a clot at the wound site. However, when there is profuse bleeding in traumatic injuries like accidents, war wounds or surgeries, the repair action takes a long time. In the meantime, excessive blood loss may soon turn fatal.

In such medical emergencies, external blood clotting agents called hemostats are handy in arresting the bleeding quickly. It is a continuous goal of medicine to find highly efficient and biocompatible hemostats.

A team of researchers led by Dr Rituparna Sinha Roy from the Indian Institutes of Science Education and Research (IISER) collaborated with Professor Samit Kumar Nandi’s team at the West Bengal University of Fishery and Animal Sciences, both from Kolkata, to engineer a gel-like hemostat that shows promise to stop bleeding, and quickly form a clot.

The sealing agent is biocompatible and does not interfere with the body’s natural clotting process. The clot so formed gets eliminated naturally by body mechanisms. The study is published in the journal ACS Biomaterials, Science and Engineering, and their product’s patent is pending for approval.

How blood clots

When there is a bleeding injury in the body, the blood begins to coagulate quickly to form a clot to stop the bleeding. The clot formation process is a complex cascade of events involving the stepwise release of enzymes, ions, blood components and proteins.

When a blood vessel ruptures and gets exposed, platelets in the blood begin to aggregate and stick to the blood vessel walls. The platelets activate a protein called factor X, which combines with calcium ions to trigger a prothrombin activator.

The enzyme facilitates the conversion of a blood plasma protein called prothrombin into thrombin. Thrombin helps to convert a protein called fibrinogen into a fibrous form called fibrin.

Fibrin then acts as the weaver, and the strands stick to the platelets and blood cells enmeshing them into a blood clot.

The clot plugs the wound area, preventing further bleeding and also forming a bridge across the wound where new cells can grow for repair. Over time, another enzyme called plasmin gradually dissolves the clot and flushes it away.

Nature-inspired

An effective external blood clotting agent should quickly form a clot and not cause any adverse effects. The clot should also stay adhered to the wound site without drowning in the excess blood; else the very purpose is defeated.

Although several hemostats are currently in use, many are not biocompatible. They have to be removed after soaking up the blood. Others adhere poorly to the wound site, exposing the wound before healing.

The present study addresses these two problems by engineering a biomaterial that mimics two natural proteins’ structural and functional properties. One is the basic thread-like fibrin, and the other called DOPA is present in the footpads of mussels (marine animals).

Mussels have specialised footpads that help them anchor to surfaces under water. DOPA is a specific amino acid that makes the footpads sticky, helping them stay on surfaces without getting affected by the water turbulence.

The study of the mussel footpad mechanism is an active research area for biomedical applications.

The researchers constructed a synthetic hybrid by utilising artificial peptides — short chains of amino acids — as building blocks to design the novel material. They developed a series of peptides of different combinations of the hybrid material.

The optimised version called sealant 5 exhibited biocompatibility, thermal stability with improved strength and adhesion. It quickly formed a crisscross, dense mesh around blood platelets to form a clot. They stabilised the material ionically and chemically to react with blood components.

Besides, it works independently of the natural clotting process and complies with clinical requirements. The designed sealant creates a physical barrier at the wound site and absorbs fluid from the blood. It concentrates the clotting factors to enhance the blood coagulation mechanism.

Experiments and results

The team tested the sealant 5 on internal as well as external wounds in rabbits. “Our sealant exhibits a four-fold improved performance than fibrin in arresting blood loss in the heparinised system (an induced condition where thrombin is inactivated thereby disrupting the body’s natural coagulation events),” says Dr Sinha Roy.

The bleeding stops 82 seconds faster than fibrin, and 113 seconds faster than RADA-16, a conventional hemostat in use developed by a team of researchers from MIT, USA, she adds.

Moreover, the material works independently of the natural blood clotting process, thereby quickening the clotting.

The researchers opine that the sealant will be useful for people with haemophilia — a blood defect where the clotting factors are missing, wherein even a minor cut or wound can soon turn fatal.

Sealant 5 was tested for external skin wound closure and compared with suture, stapling and natural fibrin-based adhesive.

The reports indicate that the novel material shows minimal inflammation and a thick growth of collagen fibre that accelerates wound healing, superior to the conventional methods. Besides, it exhibits antibacterial properties on two strains of bacteria.

“The sealant has potential use as a sutureless wound closure material. Next, we plan to incorporate wound healing elements to our peptide-based sealant material to make it a total wound-care material. It can be useful for chronic diabetic wounds, burns or leprosy wounds,” sums up Dr Sinha Roy.