Causation Link Provided in Heparin Deaths and Allergic Reactions

Posted on 28th April 2008 by gjohnson in Uncategorized

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The New England Journal of Medicine last week published a study out of MIT which establishes a clear causal link between the contaminant identified by the FDA to have been found in the tainted Heparin and allergic reactions/anaphylactic shock. See the New England Journal of Medicine, April 23, 2008: “Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System” Takashi Kei Kishimoto, Ph.D., et. al. The full text of this research can be found at http://content.nejm.org/cgi/content/full/NEJMoa0803200v2#F2 See also an excellent article discussing this research at the Science Daily: http://www.sciencedaily.com/releases/2008/04/080423171529.htm

As indicated in the title, this research establishes that the contaminants identified by the FDA in the tainted lots of Heparin, could in fact cause the anaphylactic shock and severe hypotensive events. To understand the full scope of this poisoning, it is important to understand what is described in highly technical terms in this article. Therefore, we have provided a glossary to help the concerned reader to understand the basic terms used therein. While this is far from a primer in organic chemistry, this glossary has been useful for us, in grasping the technical aspects of these findings. Go to http://heparin-law.com/glossary.html

As said in such paper:

“The OSCS found in contaminated lots of unfractionated heparin, as well as a synthetically generated OSCS reference standard, directly activated the kinin–kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins.”

What does this mean? It means that there is no question that the contaminant in Heparin has the potential to cause hypotension (a drop in blood pressure) and anaphylactic shock. Both can kill. The research essentially concluded that this contaminant, OSCS, is an anaphylatoxins – a chemical that can trigger anaphylactic shock and allergic reactions. In addition to testing the effect of this contaminant on blood in the laboratory, it was also tested it on pigs. Such findings included:

“Two of six animals treated with OSCS-contaminated heparin had at least a 30% drop in blood pressure over the first 30 minutes after infusion (Figure 5B). One animal remained in a hypotensive state for more than 15 minutes. In contrast, none of the four animals treated with control heparin showed any substantive changes in blood pressure. … Thus, intravenous infusion of OSCS is capable of recapitulating the hallmark cardiovascular features of the reaction in swine.”

Most of those identified by the FDA as having died while on the contaminated Heparin died from some type of hypotensive or anaphylactoid event. The continuing mystery will now primarily focus on:

How far back did this OSCS begin to show up in heparin;
What are the keys to determining the precise mechanism of death in those suspected of having been killed by this poison; and
What organ damage could have been done to the survivors as a result of the drop in blood pressure.

One of the intriguing findings which I believe should receive additional study is that the toxic cascade of events apparently continued “even after the vital functions returned to normal.”

Clearly, this study is not the end of the line in terms of determining the potential toxic effects on the human body from this toxin. All it establishes is that the contaminant will cause a gross allergic reaction. But what other damage can it do? Is its chemical similarity to the Heparin which we use to reduce clotting, limit its adverse effects to blood reactive type events, or can the toxin actually do direct damage?

The FDA warning letter we detailed last week makes it clear that the Heparin purity issues at the Changzhou SPL China facility could involve considerably more problems than just apparent intentional dilution of Heparin with OSCS. We cannot stop this inquiry with the period of September 2007 to present. We can’t assume the only problem with this horrific breakdown in the supply of Heparin is limited allergic reactions.