Thursday December 18, 2008
Prothrombin Time for Detection of Contaminated Heparins


Editors' note: Interesting correspondence published this week in The New England Journal of Medicine. It is available as free text. Click on reference below to obtain authors and related references. We are reproducing few important parts.


"The recent "heparin scandal" resulted from the use of contaminated heparin that caused serious adverse events including death. The contaminant was identified as synthetically oversulfated chondroitin sulfate (OSCS). Despite the missing final proof of a cause-and-effect relationship, OSCS was shown to have pharmacologic effects that may contribute to the observed allergic-type reactions. Furthermore, OSCS is suspected to be responsible for an observed increased incidence of heparin-induced thrombocytopenia type 2. ...........

We report on the use of prothrombin time to detect OSCS contamination in both unfractionated heparin and low-molecular-weight heparins. As expected, only plasma concentrations of 5 µg per milliliter (about 1 IU per milliliter) or greater of unfractionated heparin and 10 µg per milliliter of unfractionated heparin contaminated with 17.4% OSCS (contaminated unfractionated heparin) slightly prolonged the prothrombin time (by 9% and 12%, respectively)........

Highly sulfated polysaccharides such as OSCS are known to act as anticoagulants, but they also induce contact activation promoting in vitro coagulation. However, with activated partial-thromboplastin time assays (also used for the assay of heparin in the U.S. and European pharmacopeias) in which the coagulation is initiated by contact activators, such effects cannot be recognized. In contrast, the prothrombin time is suitable for determining such procoagulant effects for two reasons. First, the coagulation is induced by thromboplastin. Second, the prothrombin time is quite insensitive to heparins, so that any procoagulant effect of OSCS is not obscured.

In conclusion, the prothrombin time could be used in a validated form as a sensitive screening test for the quality control of heparins. In clinical practice it could serve as a simple and fast assay to check the applied heparin when heparin-induced thrombocytopenia type 2 or allergic-type reactions develop in a patient who is receiving heparin..."



Reference: click to get abstract

Prothrombin Time for Detection of Contaminated Heparins - The New England Journal of Medicine, Volume 359:2732-2734, Number 25, December 18, 2008