Low-molecular-weight heparin is commonly used in surgeries to prevent dangerous blood clots. But when patients experience the other extreme – uncontrolled bleeding – in response to low-molecular-weight heparin, there is no antidote.
Now researchers at the University of North Carolina at Chapel Hill and Rensselaer Polytechnic Institute have created a synthetic form of low-molecular-weight heparin that can be reversed if things go wrong and would be safer for patients with poor kidney function.
“When doctors talk to me about the kind of heparin they want to use during and after surgery, they want it reversible, and they want it to not go through the kidneys,” said Jian Liu, the John A. and Deborah S. McNeill Jr. Distinguished Professor in the UNC Eshelman School of Pharmacy, and one of the inventors of the new drug.
While unfractionated heparin is the type commonly used in procedures such as dialysis, the more-refined low-molecular-weight heparins are the drugs of choice for preventing dangerous blood clots in hospitalized patients. However, low-molecular-weight heparin doesn’t have an antidote and it is also cleared from the body by the kidneys, which can make it unsuitable for patients with a weakened kidney function, a relatively common condition among hospitalized patients.
Liu and RPI’s Robert Lindhardt and their teams created a synthetic version of low-molecular-weight heparin that can be counteracted by an existing drug and can be cleared by the liver, not the kidneys. Their creation is described in Nature Chemical Biology this week.
Up to 5 percent of patients receiving heparin experience some form of uncontrolled bleeding, explained Liu. Patients receiving unfractionated heparin are in less danger because there is an existing FDA-approved antidote available. The antidote, called protamine, is not as effective in reversing low-molecular-weight heparin so Liu and Lindhardt tweaked the drug’s molecular structure so that protamine is able to deactivate it.
“If a person’s kidneys aren’t effectively clearing heparin from the blood, the drug stays active in the body for longer than expected,” said Nigel Key, a hematologist with UNC Health Care and the UNC School of Medicine and one of the paper’s coauthors. “That can represent a potentially dangerous situation for the physician, pharmacist and patient.”
Heparin prevents blood clots from forming and is most often used during and after such procedures as kidney dialysis, heart bypass surgery, stent implantation, indwelling catheters and knee and hip replacement. Its side effects can include uncontrolled bleeding and thrombocytopenia (too few platelets in the blood). The worldwide sales of heparin are estimated at $4 billion annually.
The natural form of the drug was in the spotlight in spring 2008 when more than eighty people died and hundreds of others suffered adverse reactions to it, leading to recalls of heparin in countries around the world. Authorities linked the problems to a contaminant in raw natural heparin from China. Natural heparin is most commonly extracted from the linings of pig intestines.
“The pig stuff has served us well for fifty years and is very inexpensive, but if we cannot control the supply chain, we cannot ensure the safety of the drug,” Liu said. “I am working for the day when synthetic heparin can be brewed in large laboratories at a low cost.”
School of Pharmacy contact: David Etchison, (919) 966-7744, firstname.lastname@example.org
News Services contact: Thania Benios, (919) 962-8596, email@example.com
Thania Benios | EurekAlert!
27.03.2015 | Oak Ridge National Laboratory
How did the chicken cross the sea?
27.03.2015 | Michigan State University
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences
27.03.2015 | Ecology, The Environment and Conservation