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Hematology – Coagulation and autoimmune diseases

Circulating lupus anticoagulants

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Lupus anticoagulants (LACs), also referred to by the English term Lupus anticoagulant (LA) are autoantibodies directed against phospholipid-protein complexes involved in the coagulation cascade. Their name is confusing: although they prolong measured coagulation times in vitro, they are associated, in vivo, to a marked procoagulant state, favoring venous and arterial thrombosis. They constitute one of the three biological criteria for antiphospholipid syndrome (APS), alongside anticardiolipin IgG/IgM and anti-beta-2-glycoprotein I IgG/IgM antibodies. First described in patients with systemic lupus erythematosus (SLE), they can also occur in isolation, without identifiable connective tissue disease, or transiently following an infection or medication. Their detection relies on a structured multi-step biological algorithm, due to the absence of a single test that is sufficiently sensitive and specific. As a diagnostic criterion for APS, their presence must be confirmed on two separate samples taken at least 12 weeks apart.
Medical emergencies

Any suspicion of deep vein thrombosis, pulmonary embolism, or stroke in a patient carrying lupus anticoagulants represents a medical emergency requiring immediate hospital evaluation.

Mechanism of action and biological paradox

Lupus anticoagulant antibodies bind to anionic phospholipids and associated plasma proteins, notably beta-2-glycoprotein I and prothrombin. This binding interferes with the assembly of coagulation enzyme complexes on phospholipid surfaces, thereby prolonging the coagulation times measured in laboratory-based biological tests.

Paradoxically, this inhibition in vitro does not translate to an anticoagulant effect in vivo. On the contrary, aCL disrupt natural anticoagulant mechanisms, activate platelets and endothelial cells, and promote a prothrombotic state. This paradox is the reason for the misleading name of these antibodies, and it is important to understand it to correctly interpret coagulation results in a patient with aCL.

ℹ️ A patient with lupus anticoagulants may present with a prolonged activated partial thromboplastin time (aPTT) in laboratory tests, without clinical bleeding. This prolongation does not reflect an increased bleeding risk, but rather a high thrombotic risk. This distinction is clinically fundamental.

Screening indications

The search for ACL is indicated in several clinical contexts, particularly when an autoimmune thrombophilia or antiphospholipid syndrome is suspected.

  • Deep vein thrombosis or pulmonary embolism, especially in a young patient or one without obvious triggering factors
  • Ischemic stroke or transient ischemic attack (TIA) in a patient under 55 years of age
  • Arterial thrombosis in an unusual territory (mesenteric, renal, adrenal)
  • Recurrent spontaneous miscarriages or unexplained stillbirth
  • Unexplained prolonged aPTT not corrected by adding normal plasma (mixing study)
  • Systemic lupus erythematosus or other known connective tissue disease, in initial immunological assessment
  • Immune thrombocytopenia without other identified cause

Laboratory detection algorithm

ACL detection does not rely on a single test. The International Society on Thrombosis and Haemostasis (ISTH) international guidelines recommend a three-step sequential algorithm, performed on platelet-poor plasma obtained by double centrifugation.

Step Test completed Principle
Screening tests TCA sensitive, diluted Russell viper venom time (dRVVT screen) Highlighting a lengthening of phospholipid-dependent clotting times
2. Mixer test Patient plasma and normal plasma mix (1:1) Verify that the prolongation is not corrected, confirming the presence of a circulating inhibitor rather than a deficient factor
3. Confirmation test dRVVT confirm (excess phospholipids), hexagonalization test Demonstrate the phospholipid dependence of ACL-specific inhibition

A result is considered positive for ACLA only if all three steps are conclusive according to ISTH criteria. A single abnormal test is not sufficient to confirm their presence.

ℹ️ ACL detection is significantly disrupted by the presence of therapeutic anticoagulants: heparin, warfarin, and direct oral anticoagulants (rivaroxaban, apixaban, dabigatran). Whenever possible, the sample should be collected at a distance from anticoagulant treatment, or specific neutralizers should be used in the laboratory.

Results Interpretation

Result Meaning Usual conduct
Confirmed positive (2 times, at 12 weeks) Biological criterion for SAPL established Complete clinical evaluation, antiphospholipid panel, specialized follow-up
Positive on a single sample Possible transient positivity (infection, medication) Mandatory check at 12 weeks before any diagnostic conclusion
Negative ACL absent at the time of sampling Do not rule out APS if anticardiolipin or anti-beta2GPI are positive
Uninterpretable Interference by therapeutic anticoagulants or inadequate collection Repeat under optimal conditions; mention current treatments

Risk profiles in antiphospholipid syndrome

The prognostic value of ACLA varies depending on their association with other antiphospholipid antibodies. Thrombotic risk is stratified according to the number of positive markers and their persistence.

Serological profile Thrombotic risk level
ACL isolated, positive Moderate risk; to be contextualized clinically
ACL + anticardiolipin antibodies (double positivity) High risk
ACL + anti-beta2GPI (double positivity) High risk
Triple positivity (aCL + anticardiolipin + anti-beta2GPI) Very high risk; profile associated with the most significant rate of thrombotic recurrence
ℹ️ Among the three biological criteria for APS (Antiphospholipid Syndrome), lupus anticoagulants are considered the marker most strongly associated with thrombotic risk, ahead of anticardiolipins and anti-beta-2-glycoprotein I, according to data from large international cohorts.

Causes of transient or non-SAPL-related positivity

The presence of ACLs is not always synonymous with APS. Several situations can lead to a transient or non-pathological positive result, hence the importance of systematically confirming the result at 12 weeks.

  • Acute viral infections: HIV, hepatitis C, Epstein-Barr virus, cytomegalovirus
  • Bacterial infections: syphilis, borreliosis, tuberculosis
  • Medications: phenothiazines, hydralazine, procainamide, certain antibiotics
  • Hematologic neoplasms and solid tumors
  • Connective tissue diseases other than lupus: Sjögren's syndrome, rheumatoid arthritis
  • Elderly subject with no history of thrombosis or identifiable connective tissue disease

Additional balance sheet

The detection of positive ACL is part of a complete antiphospholipid antibody syndrome workup, which may include other immunological and thrombophilic investigations depending on the clinical context.

  • Anticardiolipin IgG and IgM by ELISA
  • Anti-beta-2-glycoprotein I IgG and IgM
  • Antinuclear antibodies (ANA) with immunofluorescence profile
  • Complement C3, C4, and CH50 in the context of suspected lupus
  • FSC with platelet count (possible associated thrombocytopenia)
  • Genetic thrombophilia assessment based on clinical presentation: Factor V Leiden, prothrombin G20210A mutation
  • Imaging according to the suspected location of thrombosis

Consult at Clinique Omicron

Clinique Omicron has service locations in Quebec where patients can receive a medical evaluation and biological assessment, including screening for lupus anticoagulants. The clinic's physicians and nurse practitioners (NPs) prescribe the appropriate tests and refer to specialists based on the clinical presentation. To make an appointment at one of their Quebec locations, visit cliniqueomicron.ca or contact the clinic directly.

The content of this page is provided for informational purposes only and is not intended to replace the advice of a qualified healthcare professional. Consult a physician for any symptoms, questions or decisions you may have regarding your health.

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