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BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39562.643426.80 (Published 01 May 2008) Cite this as: BMJ 2008;336:984

Heparin contaminant linked to clusters of anaphylaxis worldwide

Earlier this year, clusters of serious hypersensitivity reactions to heparin alerted regulatory authorities in the US and Germany to a possible contaminant in the supply. An unusual oversulphated form of chondroitin sulphate has since been found in heparin used in over a dozen countries, and recent experiments confirm that the contaminant can cause the kind of symptoms reported by patients worldwide.

Scientists used contaminated and clean preparations of heparin from the US Food and Drug Administration to test the biological activity of oversulphated chondroitin sulphate in human plasma and in pigs. The contaminant activated the kinin-kallikrein pathway in human plasma and induced potent anaphylotoxins derived from complement (C3a and C5a). Both could explain the hypotension and other allergic symptoms common to many cases. Intravenous infusions of contaminated heparin or synthetic oversulphated chondroitin sulphate caused hypotension in pigs. The cardiovascular changes were accompanied by an increase in kallikrein activity.

The US authorities first encountered the problem in patients having dialysis, but other cases soon came to light, including 81 potentially related deaths. One manufacturer recalled all their heparin products at the end of February. Deaths in the US associated with heparin returned to expected numbers in March.

Current treatments for intestinal worms are inadequate

Intestinal nematodes infest hundreds of millions of children and adults worldwide, and experts estimate that they cause a global burden of disease comparable to malaria. The World Health Organization wants three quarters of those at risk treated regularly by the year 2010. Four drug treatments are currently available so researchers carefully reviewed the evidence to find out which drugs were likely to be most effective against the most common soil transmitted nematodes Ascaris lumbricoides, Trichuris trichiura, and the hookworms Ancylostoma duodenale and Necator americanus.

It was hard going. Many of the 20 trials …

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