Heparin Therapeutic Range

Here is a question on how to develop the PTT therapeutic range using the Brill-Edwards method in a low-volume facility. This is from Michael D. Blechner, MD, Assistant Professor of Pathology and Laboratory Medicine, University of Kentucky Medical Center:

George,
Here at UK (University of Kentucky) we use plenty of unfractionated heparin (UFH) and it is relatively easy to identify 30+ specimens from patients on UFH with which to establish a PTT range by comparing the PTT values with anti-Xa results.
UK has recently purchased a smaller hospital across town and I have been consulted about how to establish their RR when they switch PTT reagent lots. There is very little UFH used there, making it very difficult to identify enough patients to compare PTT and anti-Xa in ex vivo samples. What is the recommended approach? Spiking? Thanks for any help.
Mike Blechner

By the way, I found a post from you from 1997 while searching the MEDLAB-L listserv on this topic…

From my 1997 post:
In response to a question about heparin therapy, the College of American Pathologists (CAP) requires the hemostasis laboratory to establish a heparin therapeutic range. See their 1997 checklist statement 0.2:3712: “The laboratory should provide recommendations concerning the test(s) to use and the range of test results that indicate control of anticoagulation.”
The traditional 1.5 to 2.5 times normal mean range for APTT results does not adjust for the varying responsiveness of individual PTT reagent-instrument combinations and results in significant under-anticoagulation, as reported by Brill-Edwards et al in 1993 where he highlights three studies conducted over nine years; or over-anticoagulation, as Lynn Quarles, Dan Kaczor, and I reported in the June, 1997 issue of Clinical Hemostasis Review comparing therapeutic ranges for four institutions.
The best way to establish the therapeutic range is to collect blood from 30-60 (now minimum of 50) patients on heparin who are not receiving simultaneous coumadin, perform PTTs and anti-Xa heparin assays on each, plot the paired data,and find the range of PTT results that corresponds to the therapeutic heparin range of 0.3-0.7 IU heparin/mL by anti-Xa assay.
The anti-Xa is fast, automatable, and reasonably priced, though not as cheap as the PTT, and there are some good reference labs prepared to do it for you if you do not offer it. The in vitro heparin response curve doesn’t work as well because the reagent heparin is variably absorbed by plasma components and flattens out at the high range (reported also by Brill-Edwards).

To continue, for low-volume institutions there are three alternatives:

Request PTT aliquots preserved by a sister institution. Though most coagulation laboratory managers choose to avoid the risks associated with sending aliquots to outside institutions, it is acceptable to distribute them to institutions within your system.
Identify local samples that meet the criteria for establishing the reference range, aliquot and save them over time. It may take weeks or months to reach a minimum, but from that point on the supply continues to be renewed and is available any time the reference range must be recalibrated.
Switch all institutions to monitoring UFH using the chromogenic anti-Xa heparin assay. This may appear to be less cost-effective, but given the increasing use of low molecular weight heparin and synthetic pentasaccharides, it may become necessary anyway. Your reagent supplier will gladly provide you with cost-effectiveness data which could reach break-even when considering adverse events traceable to inaccurate PTT results.
This issue faces most medical centers these days as they continue to acquire lower-volume institutions, so we are sure to see additional comments from others grappling with this issue. Geo