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Coagulation

Coagulation laboratory tests

Lupus anticoagulant


Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 10 February 2013, last major update November 2012
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.

General
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● Also called lupus inhibitor
● One of the two main types of antiphospholipid antibodies (other is anticardiolipin antibodies)
● Common in patients with systemic lupus erythematosus, but most cases occur in patients without SLE (Arch Pathol Lab Med 2002;126:1424, Kelley's Textbook of Rheumatology (9th ed, 2012))
● May cause increased PTT (not time dependent), increased or normal PT
● Prolongs clotting times by binding to phospholipid cofactors in coagulation cascade (note: often not true for HIV+ patients, Arch Pathol Lab Med 1993;117:595)
Indications: patients with venous thromboembolism (particularly if no family history or associated with autoimmune disease); unexplained stroke (young person or autoimmune disease), cerebral venous thrombosis, recurrent or late pregnancy loss; may be considered for arterial thrombosis (particularly in young patient or no documented atherosclerosis)
Specimen: plasma (citrate tube)

Methodology
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● An algorithm combining several tests is necessary
● All are clotting time based: (a) Russell viper venom time (sensitive to abnormalities in factors X and V, diluted for screening), (b) kaolin clotting time, (c) dilute PT (tissue thromboplastin inhibition test), (d) PTT-based assays (should have low concentration of phospholipids to enhance sensitivity), (e) less commonly Textarin (obtained from venomous Australian snake, not sensitive to abnormalities of factor X but sensitive to abnormalities of factor V) and (f) less commonly Taipan venom (insensitive to abnormalities of factors X or V)
Note: all venom assays are sensitive to abnormalities in factor II, calcium and platelets
● Use of commercially available integrated test systems is recommended: Staclot procedure - (1) add diluent to tube 1 and egg phosphatidylethanolamine to tube 2; (2) add platelet poor plasma with polybrene (neutralizes heparin) to both tubes, incubate and add PTT reagent; PTT in tube 2 should be 12+ seconds shorter than tube 1 to be a positive test for lupus anticoagulant
● To demonstrate persistence, positive test must be confirmed by repeat testing after 6-12 weeks
● Screening assay has low concentration of phospholipids to enhance sensitivity; should have platelet count less than 10K
● Abnormal (prolonged) PTT results may be repeated after mixing with equal amount of normal platelet-poor plasma
● Continued prolongation of clotting time indicates an inhibitor (not a factor deficiency)
● Confirmed by adding excess phospholipids, which should shorten clotting time towards normal; must also rule out factor VIII inhibitors, heparin and other coagulopathies
● Values prolonged by bivalirudin, lepirudin, argatroban and fondaparinux (Arch Pathol Lab Med 2004;128:1142)
● Results vary based on dilutions in factor XII, XI, IX and VIII assays
● May be mistaken for a factor VIII inhibitor if dilutions to abnormal factor assays are not done
● Donít test patients being treated with anticoagulants (or interpret with caution)

End of Coagulation > Coagulation laboratory tests > Lupus anticoagulant


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