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Heparin and Mixing Studies

From colleague Brenda Goforth, Senior CLS Hematology, Coagulation, and Urinalysis | Clinical Laboratory, Antelope Valley Medical Center

Hi George, When using Hepzyme on patients who are on heparin and a mixing study is ordered, what is the standard for when neutralization is complete? If the PTT is normal after one neutralization, then proceed to 37ºC incubation, but what if the PTT is still increased after two neutralization?  Is this due to residual heparin, a factor deficiency, or an inhibitor? It seems that there would be a cutoff value for when the PTT is increased in which direction to proceed. Again any information would be helpful. Thank you, Brenda

Hello, Brenda, and thank you for your thoughtful question. I checked with my coagulation colleague Dave McGlasson, who responded, “If there is a question of unfractionated heparin [UFH] present, do a chromogenic anti-FXa heparin assay. That will verify the presence of residual UFH.” I’ll add that Hepzyme should clear ~1.0 mg/dL UFH and that if the anti-FXa is not readily available, a time-honored approach is to run a thrombin time, which will be sensitive to any residual UFH.

If you’ve confirmed UFH removal and the PTT remains prolonged past the upper limit of the reference interval [or a locally agreed-upon limit], proceed with the mixing study. Uncorrected prolongation in the immediate mix implies a lupus anticoagulant [LAC]. If after UFH removal and the PTT is normal, there remains a possibility of a specific inhibitor such as anti-FVIII, for instance, if the patient is experiencing a bleed, proceed with the incubated mixing study. It’s unlikely, however, that a bleeding patient would be receiving UFH.

A confounding circumstance is that ~15% of specific inhibitors are revealed by a lack of correction in the immediate mix, and ~15% of LACs appear only after incubation. For this reason, some facilities bypass the immediate mix altogether.

Mixing studies often generates discussion about cutoff points and interpretation, and I invite comments to this entry.

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