Synthetic Heparin Shows Promise for Safe, Effective Anticoagulant Therapy

Anticoagulants are used to treat patients with clotting disorders and those undergoing certain surgeries. The anticoagulant heparin is widely used, but is derived from pig intestines and could pose risks to certain patients.

A synthetic form of low molecular weight (LMW) heparin may pose less risks for contamination during manufacturing, unlike traditional heparin. The synthetic drug was found to be safer for patients with poor kidney function, and can be reversible in the event of uncontrolled bleeding, according to a new study published by Science Translational Medicine.

In the study, the authors explored the safety and efficacy of synthetic LMW heparin in sheep models of deep vein thrombosis and sickle cell disease.

Previously, the team of researchers developed and manufactured a synthetic form of LMW heparin, which allowed them to improve the traditional drug.

Up to 5% of patients receiving the traditional form of LMW heparin experience uncontrolled bleeding. The drug does not respond to an antidote to unfractionated heparin, which highlights potential dangers associated with treatment, according to the study. The authors altered LMW heparin’s molecular structure to respond to the FDA-approved heparin antidote, protamine.

While traditional heparin is cleared through the kidneys, the synthetic drug was altered to clear through alternative pathways, which may increase safety for patients with poor renal function, according to the study.

"We streamlined and altered the molecular structure of low molecular weight heparin in ways that vastly improve the function of the drug, and make it more cost-effective to synthesize, but also make it more of a challenge to analyze," said Xing Zhang, PhD. "At Rensselaer [Center for Biotechnology and Interdisciplinary Studies], we developed sophisticated NMR [nuclear magnetic resonance] and mass spectrometry techniques that ensure the high quality and purity of synthesis."

Natural heparin was under scrutiny in 2008 when a contamination in the drug resulted in more than 80 deaths and hundreds of adverse reactions. The researchers set out to develop a safer alternative to prevent future contamination events, according to the study.

The authors noted that the synthetic form of the drug was significantly safer for patients with renal impairment and may prevent the widespread contamination hazards associated with animal-derived products.

The synthetic drug is headed for clinical trials for patients with clotting disorders and those undergoing kidney dialysis, heart bypass surgery, stent implantation, and knee or hip replacements, according to the study.

"This is at the cusp of clinical trials and commercial use. There is no question about the science; we have proven that this is a safer, more effective alternative to its natural counterpart, and what now determines its success or failure is the marketplace," said researcher Robert Linhardt, PhD.