Changes in Heparin Units, Three ClotCare Editorial Board Members Comment

October, 2009

Henry I. Bussey, Pharm.D., FCCP, FAHA
New changes in the standardization of unfractionated heparin that start to take effect October 1, 2009 may be important for clinicians and laboratory personnel to know about. Several changes are designed simply to improve purity and assure that certain contaminants are not present. So, we should be getting a more pure and safe product. However, the standardization of the strength of the heparin is changing from the U.S. standard to the International Standard in order to "harmonize" the process. As I understand this change, the labeled potency may be slightly different than what we were used to using before in the United States. This may indicate that we should be aware of any perceived trends in dose-response and, if these changes occur, it may be appropriate to re-evaluate dosing protocols. Further, the adoption of the new products also would seem to indicate that our laboratories should re-assess their heparin vs aPTT curves which may require recalibration. Lastly, we should remember that the aPTT reagents have become more and more sensitive over the past several years which increases the importance of the 1995 recommendation that each laboratory should define its own therapeutic aPTT target based on a calibration curve of aPTT values vs heparin concentrations using the specific aPTT reagent being used in that laboratory. This calibration should be done with each time the lot of heparin changes.

Ann K Wittkowsky, PharmD, CACP, FASHP, FCCP
I personally feel that this change should not affect heparin standard curve for the PTT, since that is measuring heparin activity in the plasma, regardless of how the FDA defines a unit. We still want the same amount of heparin activity in the patient as we did before. The difference in heparin potency could mean that doses will need to be increased by as much as 10% compared to before, but as indicated in the release, the 10% difference is unlikely to be clinically significant compared to the wide patient-to-patient response to UFH.

Edith A. Nutescu, Pharm.D.
Dr. Nutescu conducted a webinar on this issue, which is available online at apppharma.com/usp.aspx.

For more on this issue, refer to the FDA press release at fda.gov/NewsEvents/Newsroom/
PressAnnouncements/ucm184674.htm.