Artificial Blood Platelets and Therapeutics

• Anirban Sen Gupta is developing artificial blood platelets and therapeutics to manage bleeding.
• He is leading a team to create a lab-made substitute for whole blood.
• The Defense Advanced Research Projects Agency (DARPA) is backing the project with a four-year, $46.4 million grant of $46.4 million.
• Every year more than 60,000 people in the United States and more than 2 million globally die from bleeding complications
• Millions more receive blood transfusions.
• Transfusions are among the most frequent procedures performed in U.S. hospitals.
• Donated blood is constantly in short supply.

The Promise of Platelets

• Blood contains three main types of cells, each with a different function.
• Red blood cells carry oxygen.
• White blood cells fight infection.
• Platelets are indispensable in forming clots to stop bleeding from an injury.
• Plasma, the liquid part of blood, ferries all those blood cells, as well as water, proteins, hormones, salts and nutrients.
• Plasma can be freeze-dried and stored at room temperature for a year or more.
• Red blood cells, chilled, stay functional for only 42 days.
• Platelets only last up to seven days at room temperature and possibly three weeks if chilled, making them the weakest link in the blood-transfusion chain.
• Platelets scrutinize the body for injury and bleeding.
• They jump to fix it, linking to frame a patch then plastered into place by a protein called fibrin.
• A platelet can respond to an injury within nanoseconds, with pinpoint accuracy to stop the bleed in a process called hemostasis.
• Sen Gupta first took on the problem of synthetic platelets after joining CWRU's biomedical engineering faculty in 2006.
• In 2014, Sen Gupta and his former student, Christa Pawlowski, patented the lab's artificial platelet technology.
• In 2016, they co-founded the startup Haima Therapeutics, which licensed the technology from CWRU and named it SynthoPlate.
• Haima also developed a process for freeze-drying SynthoPlate into a powder form to make it easier to store and transport.
• Dried artificial blood products are the future of resuscitation medicine
• Sen Gupta's work is the latest chapter in a pursuit that goes back hundreds of years.
• Physicians tried to cure disease and treat hemorrhage with various blood substitutes beginning in the 1600's.
• During World War I, only 4% of injured U.S. soldiers survived their wounds; in World War II, 50% did.
• In austere battlefield scenarios, more than 80% of deaths are from bleeding out.

Recreating Whole Blood

• While Sen Gupta and his campus team are focused on artificial platelets, collaborators nationally are working in parallel on fully or partially synthetic versions of other blood components.
• Their conversations ramped up in the early months of the COVID-19 pandemic, when blood donations were at a minimum, triggering a national blood-donation emergency.
• Last year, DARPA announced its planned $46.4 million investment in the project to create artificial whole blood.
• The project is led by the University of Maryland, Baltimore and includes an interdisciplinary team from CWRU, Haima Therapeutics, KaloCyte Inc., Teleflex Inc., University of Pittsburgh, The Ohio State University, University of California San Diego and several other partner organizations.
• The goal is to make a blood substitute that can be freeze-dried and kept at room temperature.
• French is leading the project's examination of the ethical, legal and social implications of the blood substitute.
• The substitute could also help save tens of thousands of civilians in the United States and more than 2 million globally who die from hemorrhage.
• Umut Gurkan studies blood disorders in low- and middle-income countries and is part of the multi-institution research team.
• "We could stockpile it for a long time and use it on demand as needed, so we don't constantly have to look for donors, look for storage, look for transport," Sen Gupta said.
• In addition to SynthoPlate, the whole blood analogue will include a red blood cell product called ErythroMer.
• The CWRU team is running lab tests on various formulations of the whole blood substitute.
• If the blood is cleared for safety in lab testing, the next phase will be testing its safety and efficacy in preclinical models of traumatic bleeding.
• If all goes well, it could be ready for clinical trials around 2028.
• Meanwhile, Sen Gupta and his campus colleagues are continuing to advance synthetic platelets as a stand-alone clotting aid for emergencies like postpartum hemorrhage and complex surgeries.