Authored by Steve Sutton, LP, CCP
Steve Sutton is well known and highly regarded into today’s Perfusion community. He is a strong proponent for advancing Perfusion education and in pursuing that goal, he has given numerous presentations at some of the most premier Perfusion meetings held each year.
Along with his dedication to Perfusion as a science, Steve is tremendously compassionate in his work as a perfusionist, as a patient advocate, and as a friend and supporter to his coworkers.
He has graciously offered to assist the community by sharing some of his work with us online. This is his second submission of a series of authored posts that he is offering on a weekly basis.
To see a list of all of Steve Sutton’s work – click here.
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By Steve Sutton, LP, CCP
Heparin Alternatives are Scarce It is Difficult to Replace Something Taken for Granted Over 70 Years
Introduced into clinical use over 70 years ago, heparin is the most commonly used anticoagulant today. In all that time there were no quality or supply issues, and as a result it was not especially critical to find a viable alternative. Of the currently available alternatives, only a couple can be considered, but none compare to heparin.
Saline, for example, is a suitable alternative for maintaining patency of total parenteral nutrition (TPN) catheters and can be used to flush two-way valve catheters. The blood thinner pharmaceutical Warfarin, a synthetic derivative of coumarin, is an oral anticoagulant often used to prevent thromboembolic disorders. However, Warfarin probably is not suitable as a heparin substitute.
Heparin Widely Used in Diverse Settings
Heparin, which is produced naturally by the liver and lungs and can be synthesized in a laboratory setting, is injected in hospital settings when there is a danger of clot formation. The substance is also used for dialysis so that clots do not form in the hemodialysis lines or dialyzer. Other medical devices such as cardiac catheters, recommend heparin to flush the devices to reduce clot formation within the device’s lumen. Clots forming in these devices could be deadly if they disengage from the catheter wall and enter the patient’s circulatory system.
One of heparin’s primary manufacturers, Baxter International, had begun monitoring reports of adverse reactions in December, and stopped producing multiple-dose heparin vials on Feb. 11 after four deaths were reported. To date, over 800 cases of adverse effects have been reported, including 21 deaths. A large-scale recall of the product was not ordered, as the FDA feared problems associated with a sudden shortage. Baxter supplies approximately half of the heparin used in the U.S.
Problems Thought to Originate in China
Changzhou Scientific Protein Laboratories supplied the ingredients for injectable heparin that Baxter manufactured. The FDA believes the Chinese-made ingredients are at fault, and the manufacturing facility thought to be at fault was not routinely inspected. The facility’s name resembles that of another manufacturing facility that was inspected regularly. Equally significant, a substance that mimics heparin was used rather than the correct active ingredient, whether accidently or purposely has not yet been determined.
For the companies that manufacture medical devices that require heparin flushing, the problem is what should replace heparin and how to communicate this to their customers. For the hospitals which use heparin on a regular basis especially with dialysis patients who need the blood thinning pharmaceutical, there is a critical demand problem.
Alternatives Not Always Available
Hospital administrators and medical device manufacturers are left searching for alternative sources for “clean” heparin or adequate substitutes. Offshore sources are unlikely to fill the need as Japanese and German companies also have recalled heparin containing active ingredients from China. For the time being, the FDA recommends using another product when possible or to use very low doses of heparin and closely monitor the patient for adverse effects.
Of the new anticoagulants currently in clinical development, Hirudin, a protein cloned from a leech, inhibits thrombin, and Danaparoid (Orgaran), which is structured like heparin and requires less monitoring than heparin, are in the final stages of approval for use. But those are not yet available to meet the present crisis.
A thought-provoking issue is how prepared pharmaceutical companies must be to find substitutes quickly when reliable substances or their ingredients suddenly become less than reliable. Consumer trust in the quality the drugs they are given or the medical devices they use is critical to the health care system.
This heparin issue brings to light critical quality issues in imported medical devices and pharmaceuticals. Pharmaceutical manufacturers increasingly rely on offshore manufacturers for critical ingredients. For example, China currently supplies more pharmaceutical ingredients than any other country in the world. Companies must take care that alternative supplies are readily available to support a substantial global medical need.