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Quick Question: Unfractionated Heparin Management

The results of our December 20 Quick Question are a little surprising:

How do you produce your PTT therapeutic range for monitoring unfractionated heparin?

a. Spike a normal plasma with measured heparin and perform PTTs: 6 (32%)
b. Use 1.5 to 2.5 X the mean of normal: 1 (5%)
c. Brill-Edwards ex-vivo curve using anti-Xa as the reference: 9 (47%)
d. We use the anti-Xa for assay for all heparin monitoring: 3 (16%)

Comments appear below…

We’ll get some debate on this, however I’ve checked with CAP officials and colleagues to confirm the spiking method is not acceptable because the curve tends to flatten and lose sensitivity at the high end. CAP requires we use the Brill-Edwards technique: collect at least 50 unfractionated heparin patient specimens from patients not simultaneously taking coumadin and 20 normals, assay them for the PTT and chromogenic anti-Xa heparin assay, and select PTT results in seconds that correspond to 0.3 to 0.7 heparin units/mL for the unfractionated heparin therapeutic range. The lab manager publishes the therapeutic range to clients and updates it when there is a new lot of PTT reagent or an instrument calibration.

For those of us who reference old or poorly researched textbooks and use 1.5 to 2.5 × the mean of normal, we are exposing our heparin patients to the risk of a new thrombotic event as the resulting dose is too low. See Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med 1993;119:104-9. We not only must terminate this practice, we must go to all the units in our institution and dig out printed algorithms that use this approach.

The weakness in the Brill-Edwards curve is its scatter. Any time we develop a new curve we’ll have several specimens whose PTT results don’t match up with the chromogenic anti-Xa. We see PTTs that are significantly above the range in which the anti-Xa is within or even below range, and vice-versa. This can be traced to the inherent variability of the PTT, which is influenced by fibrinogen concentration, factor VIII activity, and antithrombin activity.

The answer is to convert to the chromogenic anti-Xa which is unaffected by fibrinogen and factor VIII levels and is rock-solid reproducible. In the US at least, the only barrier to this reasonable conversion is the cost per test, which may not be reimbursed by insurance carriers. I’d like to get responses from those who have made the conversion to learn if they are getting reasonable reimbursement and also if they have recorded better in-range and adverse event results. Geo

Comments (1)
Jan 19, 2011 9:13pm

Agreeing with your assessment of test of choice for heparin
Agreeing with your assessment of test of choice for heparin monitoring in the anti-Xa, I must point out a specific on reimbursement. As heparin is administered via IV or bolus, the patient must be admitted and kept in the facility. Reimbursement for such diagnoses as MI, AT, VT or DVT will not be done on a per test basis. Payments are issued per diagnosis as a bundle regardless of total length of stay, heparin administered or tests performed. This is the underlying factor and reason hospitals are trying to find ways to reduce length of stay. Reducing a patient’s stay in days will decrease monetary losses and may even lead to profit. Anti-Xa monitoring of unfractionated heparin has been proven to provide these results as noted in Clin Pharm 1987;6:216-222.

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