Scientists solve the mystery of heparin death

Scientists have explained how recently in the United States and Germany, a batch of contaminated blood thinner heparin passed through the traditional safety barrier, resulting in the death of dozens of patients.

Posted 3 months ago in Science and Technology.

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Scientists have explained how recently in the United States and Germany, a batch of contaminated blood thinner heparin passed through the traditional safety barrier, resulting in the death of dozens of patients.

An international research team led by the Massachusetts Institute of Technology explained how the contaminated blood thinner heparin recently killed dozens of patients in the United States and Germany through traditional safety screening.

The research team led by Professor Ram Sasisekharan of Massachusetts Institute of Technology has determined the chemical structure of this pollutant, namely chondroitin supersulfate (OSCS). In a report published in the online edition of Nature Biotechnology on April 23, researchers introduced their findings and provided new methods for detecting pollutants.

Another team led by Sasisekharan has accurately demonstrated how OSCS can cause death - especially by triggering allergic reactions. A report published online on April 23 in the New England Journal of Medicine outlined the biological effects of this pollutant.

"Advanced analytical technology can fully characterize the pollutants in heparin. In addition, this research also provides a scientific basis for the key improvement of screening practice, and can now be applied to monitor heparin to ensure patient safety," said Sasisekharan, senior author of the paper and Professor Underwood Prescott of Bioengineering and Health Science and Technology of Massachusetts Institute of Technology.

Heparin is a blood thinner, commonly used in kidney dialysis or heart surgery, and usually made from pig intestines. FDA officials said that the contaminated heparin came from the Chinese factory that produced the drug for Baite International.

Since November last year, after reporting dozens of deaths of heparin, Baxter recalled heparin in February this year. So far, contaminated heparin has killed 81 Americans. Earlier this week, FDA announced that contaminated batches were also found in 10 other countries.

The study in the New England Journal of Medicine provides for the first time a potential link between pollutants and reported deaths. Researchers found that contaminated heparin could activate two inflammatory pathways, leading to severe allergic reactions and hypotension.

"These results provide a potential link between the presence of chemical pollutants in heparin and the clinical symptoms of affected patients. Our research results also show that a simple bioassay method can help protect the global supply chain of heparin. By screening the polysulfate pollutants in heparin batches, these pollutants may have unexpected pharmacological consequences," Sasisekharan said.

Heparin is composed of a long chain of complex repeating sugar molecules. This contaminant comes from animal cartilage, and its structure is very similar to heparin, so it cannot be identified by the test normally used to check heparin batches.

At present, it is not clear whether the pollutants enter heparin during the production process, or how and where the pollution occurs. More investigations are needed to solve this problem.

Traditional heparin safety screening only detects pollutants such as protein, lipid or DNA, so it cannot detect sugar chains that do not belong to these pollutants. Sasisekharan's laboratory has played a key role in developing new technologies for the analysis of complex sugars. Using this new technology, the research team can detect the presence of problematic sugar.

"In addition to being vital to public health, the discovery of the latest impurities in heparin is also a chemical victory," said Jeremy M. Berg, director of the National Institute of General Medical Science, which supported the work. "The research team completed this arduous task by using a unique combination of science and technology, which may be used to detect other impurities in drug materials in the future."

More than 100 patients had adverse reactions after receiving contaminated heparin. Symptoms include extremely low blood pressure, swelling of skin and mucous membranes, shortness of breath and abdominal pain.

Researchers found that this pollutant can activate two inflammatory pathways: one is to activate blood coagulation and vasodilation, and the other is to produce allergic toxins. The first can cause dangerous blood pressure drop, and the second can cause serious allergic reaction. In the laboratory blind test, the contaminated heparin activated the biological pathway, while the normal heparin did not.

Sasisekharan stressed the extraordinary will of dozens of scientists around the world, who are willing to work together to quickly solve problems that may cause serious uncertainty about drug safety.

"The generosity and willingness of people to do their best to help solve this problem is different from anything I have experienced before. It is very gratifying to see how teamwork leads to the application of strict, peer-reviewed science and helps to ensure our drug safety," he said.

Sasisekharan said that he hoped that this effective team cooperation would extend to other areas of public health. In these areas, strict team-based science would not only lead to safer drugs, but also lead to safer food and safer environment.

FDA researcher from Momenta Pharmaceutical Company, Cambridge, Massachusetts. The Rensler Institute of Technology in the United States and the Institute of Biochemistry in Milan, Italy also contributed to the paper of Natural Biotechnology.

Researchers from FDA, Momenta Pharmaceuticals, Virginia Tech University's Virginian-Mariland Regional Veterinary College and Brigham Women's Hospital contributed to the paper in the New England Journal of Medicine.