Coagulation

Acquired bleeding disorders

Lupus anticoagulation & antiphospholipid antibodies



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Last staff update: 4 March 2022

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PubMed Search: Lupus anticoagulant [title]

Jeremy C. Parsons, M.D.
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Cite this page: Parsons JC. Lupus anticoagulation & antiphospholipid antibodies. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationlupusanticoag.html. Accessed February 7th, 2023.
Definition / general
  • Also called lupus inhibitor
  • One of the 2 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, Firestein: Kelley's Textbook of Rheumatology, 9th Edition, 2012)
  • May cause increased PTT (not time dependent), increased or normal PT
  • Prolongs clotting times by binding to phospholipid cofactors in coagulation cascade; 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)
Diagnosis
  • An algorithm combining several tests is necessary
  • All are clotting time based:
    • Russell viper venom time (sensitive to abnormalities in factors X and V, diluted for screening)
    • Kaolin clotting time
    • Dilute PT (tissue thromboplastin inhibition test)
    • PTT based assays (should have low concentration of phospholipids to enhance sensitivity)
    • Less commonly Textarin (obtained from venomous Australian snake, not sensitive to abnormalities of factor X but sensitive to abnormalities of factor V
    • 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: add diluent to tube 1 and egg phosphatidylethanolamine to tube 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
  • Don’t test patients being treated with anticoagulants (or interpret with caution)
Antiphospholipid antibodies
  • Acquired antibodies against phospholipid protein complexes
  • Occurs in 3 - 5% of general population; most common cause of acquired thrombophilia
  • Rate of thrombosis per year is 1% if no history of thrombosis, 4% in systemic lupus erythematosus (SLE) patients, 5.5% in patients with a history of thrombosis, 6% if high titer of IgG anticardiolipin
  • Includes lupus anticoagulant (most patients do not have SLE), anticardiolipin antibody and anti β2 glycoprotein antibodies
  • Antibodies are against phospholipids (usually transient, secondary to infection) or various plasma protein antigenic targets (β2-glycoprotein I, protein C, protein S, annexin V, high and low molecular weight kininogens, thrombomodulin, prothrombin, factors XI and XII, complement factor H)
  • First described by Wassermann in 1906 (Wasserman test was complement fixation procedure using saline liver extracts from fetuses with congenital syphilis)
  • Associated with an increased risk of arterial or venous thrombosis, thrombocytopenia, recurrent miscarriages; causes 1 / 3 of strokes in patients younger than age 50 years (often due to mitral or aortic valve emboli), 15% of deep venous thromboses, 5 - 15% of recurrent spontaneous abortions, eclampsia, maternal DVT's; also multi infarct dementia, chorea, migraine, livedo reticularis in skin
  • Catastrophic antiphospholipid syndrome resembles TTP-HUS
  • Antiphospholipid antibody syndrome: diagnosis requires a positive lupus anticoagulant or anticardiolipin antibody on 2 separate occasions, at least 6 - 12 weeks apart and either venous or arterial thrombosis, thrombocytopenia or recurrent fetal loss
  • References: Arch Pathol Lab Med 2002;126:1424, J Thromb Haemost 2006;4:295
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