A question from “Bmolpus:”
Hello, I am an emergency physician who has started an urgent care practice and find myself reviewing more patient records and getting more exposure to laboratory tests which were out of the scope of my previous ER practice. I have been reviewing the site and am curious to see if you could answer the following question:
Knowing that heparin and low molecular weight heparin (but not coumadin) can cause a false positive lupus anticoagulant (LA) assay, my question is as follows: Does treatment with heparin/heparin substitutes cause a false positive LA screening assay only, or can it also cause a false positive hexagonal phase confirmatory test? Thanks much.
Hello, and thank you for your question. Yes, heparin, particularly standard unfractionated heparin, does interfere with both the partial thromboplastin time (PTT) assay, which is the preliminary screening assay, and the confirmatory hexagonal phase phospholipid assay. Low molecular weight heparin may also interfere, though to a lesser degree. When the initial screening PTT is prolonged, perform a thrombin time test, which is significantly prolonged by unfractionated heparin. If heparin is confirmed by the thrombin time, neutralize the heparin with Heparinase, then proceed with the remainder of the lupus anticoagulant profile.
By the way, it is possible, though less frequent, for Coumadin to also interfere, particularly with the dilute Russell viper venom time (DRVVT). This should be considered, and there is no method available for neutralizing the effect of Coumadin in vitro.
For detailed information on lupus anticoagulant testing, please see my audio modules,Lupus Anticoagulant I and Lupus Anticoagulant II. Thank you. Geo.
Hey guys, I think I will add my 2 cents to this conversation
Hey guys, I think I will add my 2 cents to this conversation.
In our laboratory, we use 3 tests to help identify a lupus anticoagulant (LA). They are the STA-Clot LA (Diagnostica Stago), LA Check and LA Sure (commonly called DRVVT, Precision BioLogic) and the Dilute PT Index (also know by various other names such as Tissue Thromboplastin Inhibition Test). Our testing scheme includes the PTT, PT and possibly a thrombin time and Hepzyme treatment of the plasma as necessary.
According to the package insert for the STA-Clot LA (SLA), reagent 3 contains normal human plasma and a heparin inhibitor. The “heparin inhibitor” is useful in test plasmas that contain less than 1 IU/mL, which is significantly higher than the recommended therapeutic heparin levels. I can tell you that this test system does a very good job of eliminating any interference from heparin.
The Staclot LA package insert also states, “thrombin inhibitors (eg hirudin, argatroban…) present in the sample to be tested may interfere in the test and lead to falsely positive results.” We have received samples at various times from referring facilities and I can tell you that the results from such samples are unreliable and technically unreportable and should be handled as such.
The package insert for the LA Check and LA Sure (DRVVT) from Precision BioLogic also states that the reagent contains “antiheparin agents” sufficient to “neutralize heparin up to 1.0 unit/mL.” I have not seen therapeutic doses of heparin interfere with this test system.
The Dilute PT-Index (DPTI) is a different issue. While this test is not included in the current ISTH subcommittee recommendations, it is a valuable tool in detecting a lupus anticoagulant. The DPTI is highly sensitive to heparin contamination and will almost always (I hesitate to say “always”) gives a false positive. Plasmas that test positive using the DPTI and show a significantly elevated thrombin time (indicating heparin contamination) are treated with Hepzyme and retested and footnoted as such. Most generally these plasmas will turn negative upon retesting.
Coumadin is a different issue altogether. The Staclot LA uses a 50/50 mix with normal human plasma. This effectively removes the factor deficiency issue caused by coumadin. The LA Check is sensitive to coumadin therapy. We add a 50/50 mixing strategy and repeat the LA Sure, eliminating any issues with factor deficiencies. I have rarely seen a prolonged PT and a normal LA Check. The DPTI is insensitive to oral anticoagulation therapy.
I am surprised that our doctor would be seeing interference from heparin. Current testing systems have mechanisms to deal with heparin. Potentially, samples from heparinized lines, could contain more heparin than could be neutralized by the reagents. If it is suspected that heparin is present to the levels to cause interference with the testing, it should be verified that it was a venous draw and that the patient is therapeutic.
I hope this helps.
Regards
Herb Crown
St. Louis University Hospital Coagulation Reference Laboratory