Lupus Anticoagulant (LA): A Laboratory Testing Algorithm [Utilization Spotlight]
Since 2012, we have been publishing a Utilization Spotlight in every issue of the Communiqué. Each Spotlight offers a quick view of utilization management best practices in action. This Spotlight is from November 2014.
Laboratory testing for the presence of a lupus anticoagulant (LA) is challenging. The Mayo Clinic Special Coagulation Laboratory performs LA testing (LUPPR / Lupus Anticoagulant Profile) in an algorithmic fashion in accordance with the International Society on Thrombosis and Haemostasis (ISTH) published guidelines.
Laboratory testing for the presence of a lupus anticoagulant (LA) is challenging. At present, the available laboratory assays and methods exhibit substantial differences in
their ability to detect LAs, and no single laboratory test is capable of detecting all LAs. The variability is attributable not only to analytical factors but also to preanalytic and postanalytic considerations. Preanalytic variables, such as effects of anticoagulation therapies or specific factor inhibitors, add complexity to testing and its interpretation, and must be carefully evaluated.
The International Society on Thrombosis and Haemostasis (ISTH) published updated testing guidelines in 2009 that include performing the following:
- At least two screening tests using different assay principles to demonstrate prolongation of a phospholipid-dependent clotting time
- A mixing study to evaluate for the presence of an inhibitor
- A confirmatory test that demonstrates phospholipid-dependent inhibitory activity. The guidelines also suggest evaluating for other coagulopathies that can interfere with LA testing.1
The Mayo Clinic Special Coagulation Laboratory performs LA testing (LUPPR / Lupus Anticoagulant Profile) in an algorithmic fashion in accordance with the ISTH guidelines.
Initial testing includes: prothrombin time (PT), activated partial thromboplastin time (APTT), and dilute Russell’s viper venom time (DRVVT). If the PT, APTT, and DRVVT are normal, no additional testing is performed and the results indicate no evidence of LA.
Prolongation beyond the established reference range of the PT, APTT, or DRVVT will trigger a mixing study in that particular assay system as well as performance of
a thrombin time (TT). Prolongation of the TT will initiate a reptilase clotting time.
Confirmatory LA testing is initiated in the following situations:
- If the APTT mixing study does not demonstrate correction of the clotting time and there is no evidence of heparin in the sample (ie, normal TT), the platelet neutralization procedure (PNP) will be performed.
- If the DRVVT mix ratio is >1.2, the DRVVT confirmatory test will be performed.
Additional testing may be performed to address differential diagnosis for certain patterns of abnormal test results including identifying effects of therapeutic anticoagulants or the presence of a specific coagulation factor inhibitor. Supplemental testing may include selected coagulation factor assays, Staclot LA, fibrinogen, D-dimer, and soluble fibrin monomer; note that not all supplemental assays are always performed. If the factor VIII activity is significantly decreased, a screening test may be performed to look for specific factor VIII inhibition. If specific inhibition is apparent, the titer of the inhibitor will be determined.
It is important to identify the presence of heparin and warfarin anticoagulation therapy effects in a specimen submitted for LA testing, since sensitivity and specificity may be compromised. Direct-acting thrombin or activated factor X (factor Xa) inhibitor anticoagulants are also increasingly used for prevention and treatment of thrombosis and it is important to recognize their effects on LA testing. In most situations, LA testing cannot be reliably performed to detect or exclude LA when these anticoagulants are present, and there is risk of false-positive results.
Laboratory testing for the presence of a lupus anticoagulant is challenging and interpretation must be carefully evaluated. The available laboratory assays and methods exhibit differences in their ability to detect a lupus anticoagulant, and no single laboratory test is capable of detecting them all.
- Pengo V, Tripodi A, Reber G, et al: Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committeeof the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009;7(10):1737–1740