Smart Thrombosis Inhibitors Without Bleeding Side Effects

Anticoagulants, or blood thinners, break down and prevent blood clots, semi-solid clumps of blood cells, and other substances that can block blood flow. However, anticoagulants can do their job too well, preventing clotting altogether and resulting in excessive external or internal bleeding.

A new study from researchers at the University of British Columbia (UBC) and the University of Michigan introduces a new compound, MPI 8, that may one day make anticoagulants much safer.

Normally, blood clots form at the site of an internal or external injury, stop bleeding and allow the body to begin to heal. When internal clots break free, they can plug the bloodstream or block blood flow in critical areas of the body such as the brain, heart, and lungs. The result can be a stroke, pulmonary embolism, or heart attack.

The study is published in Nature Communications.

Physicians prescribe anticoagulants to people with atrial fibrillation or who have clotting conditions to avoid thrombosis. They may also be given prophylactically for surgeries that are frequently accompanied by unwanted clottings, such as heart valve, knee, or hip surgery replacement.

The problem is, he explained, “That could include things like bleeding ulcers, bleeding in the stomach, bleeding in the bone and joints, or even after minor traumas or injuries, accelerated bruising anywhere from the skin and soft tissue to even within the brain.”

The researchers focused on polyphosphate, one of a collection of molecules that are involved in blood clotting. It had been previously identified as a promising therapeutic target by one of the study’s co-authors, Dr. James Morrissey.

Nonetheless, targeting a single molecule in the bloodstream is tricky. Dr. Kizhakkedathu explained that electrically speaking, polyphosphate is a negatively charged molecule. It is polyanionic, meaning it contains multiple areas of negative charge. A molecule with a single negative charge, on the other hand, is anionic.

MPI 8 is an abbreviation for “Macromolecular Polyanion Inhibitor 8.”

In the past, researchers attempted to target polyphosphate with cations, positively charged compounds, but there are so many negatively charged anions in the blood that they bound indiscriminately with many of them and were thus toxic.

“Because [MPI 8] molecules have got a very low cationic density, or cationic charge, they circulate in the body with a very low charge,” passing harmlessly by other molecules, he explained.

“But when it finds its target, it increases the charge density. It binds very strongly [and selectively],” he added.

The researchers describe this property as “tunability.”

So far, the authors of the study have tested MPI 8 on mice and found it effective at preventing blood clots without toxicity or an increase in the risk of bleeding.

UBC and the University of Michigan have applied for a patent for MPI 8, and hope to move next to trials with larger animals, and eventually humans.

Sources:

La, C.C., Smith, S.A., Vappala, S. et al. Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design. Nat Commun 14, 2177 (2023). https://doi.org/10.1038/s41467-023-37709-0 

University of British Columbia (UBC). (2023). A safer blood thinner? This novel blood clot treatment doesn’t increase bleeding risk. MedicalNewsToday. Retrieved on May the 1st from: https://www.medicalnewstoday.com/articles/blood-thinner-potential-blood-clot-treatment-lower-bleeding-risk 

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