HEPARIN, CONTAMINATED HEPARIN and HEPARIN-INDUCED THROMBOCYTOPENIA
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I have been discussing in my recent blogs Heparin, Heparin contaminated products and HIT. The FDA has come up with the following helpful Q & A to help educate the public. The following are some important questions posted by the FDA:
1. What is the contaminant?
Oversulfated chondroitin sulfate (OSCS), a substance that mimics the biological activity of heparin, was identified as the contaminant.
2. Where is the contaminant found?
The contaminant was found in samples of heparin crude materials, heparin active pharmaceutical ingredients (API), and finished heparin drug products.
3. Is oversulfated chondroitin sulfate unsafe by itself or in combination with heparin?
The adverse events were reported in patients who received heparin contaminated with oversulfated chondroitin sulfate. The lab studies suggest that when oversulfated chondroitin sulfate is given alone or in combination to animals, similar adverse events occur (N Engl J Med 358;23 June 5, 2008 p2457) .
4. Have all heparin products used in the U.S. been tested for the contaminant?
The active pharmaceutical ingredient (API) used for products in the U.S. market has been tested for the contaminant. FDA has been working with manufacturers to analyze the heparin API used to manufacture the existing finished products. This testing will assure that no contaminated finished heparin products are available to the U.S. market.
5. How did the contaminant get into the product?
At this point, FDA does not know how the contaminant got into the heparin active pharmaceutical ingredient (API). The agency is continuing to aggressively investigate the situation.
6. Why does the contaminant cause serious adverse events?
The contaminant activates chemicals in the body called enzymes. These enzymes cause the body to make inflammatory mediators (chemicals that are released by immune cells). Inflammatory mediators can lead to some of the symptoms such as low blood pressure, abdominal symptoms and shortness of breath. This mechanism can explain many of the serious adverse events that occurred immediately after patients were given the contaminated heparin.
7. Has all contaminated heparin been removed from the U.S. market?
Since March 10, FDA has been screening and reviewing all imported heparin products. This gives FDA the opportunity to sample and test products that pose a significant risk to U.S. consumers. FDA can ultimately refuse and request the destruction of products that appear to be contaminated based on the testing. In addition, FDA has been working with manufacturers to retrospectively analyze heparin sodium API. These measures have resulted in a number of recalls to remove contaminated heparin products from the U.S. market.
8. I received the Baxter product in the past. Am I still at risk for a serious reaction?
The serious reactions have generally occurred rapidly; usually within minutes of when heparin was given. However, some patients undergoing cardiac procedures have developed very low blood pressures as late as an hour following the start of the heparin bolus. Other reports have noted adverse events of one kind or another that occurred even later than that. In this case, it is more likely that the adverse events that occurred right away were related to the heparin. So it is unlikely that an adverse event of this type will happen a long time after the heparin was given.
9. Are there any long-term health effects from exposure to the contaminant?
We do not know whether there could be long term health effects of the contaminant, since the contaminant was only recently discovered. The FDA is in the process of having this question investigated.
There is a distinct difference between contaminated heparin products and heparin inducted thrombocytopenia. There are two types of HIT, non-immune HIT and immune-mediated (HIT type II). Non-immune HIT occurs more frequently and is distinguishable by a mild decrease in platelet count but is not harmful to the patient. Immune-mediated HIT (HIT type II) causes a very low platelet count, is less common and patients who develop this are at risk for major clotting problems which can result in deep vein thrombosis (DVT), pulmonary embolism, heart attack or stroke. HIT usually occurs from five to 14 days after the start of heparin. For more information on HIT type II the following website is very informative: http://ndt.oxfordjournals.org/cgi/content/full/21/6/1721 .