Lupus Anticoagulant Reflex Panel

Content Review: February 2024 Last Update:

Use to aid in the evaluation of unexplained prolonged activated partial thromboplastin time (aPTT) or for patients with a significant probability of having antiphospholipid syndrome (APS). To assess for APS, order with anticardiolipin (aCL) antibodies, IgG and IgM, and anti-beta-2 glycoprotein 1 (anti-β2GP1) antibodies, IgG and IgM.

Lupus anticoagulant (LA) is an antiphospholipid antibody (aPL) autoantibody that binds to phospholipid-binding proteins, beta-2 glycoprotein I, and prothrombin, leading to a prothrombotic state. LA is associated with a range of adverse medical events, such as thrombosis and loss of pregnancy. LA can be transient (eg, due to certain medications or infections) and may not show clinical symptoms in all cases. No single test currently exists for the detection of LA; instead, a combination of clot-based tests with appropriate reflexive steps are recommended. Persistently positive LA, anticardiolipin (aCL) IgG or IgM, or anti-beta-2 glycoprotein 1 (anti-β2GP1) IgG or IgM results (ie, consecutively positive on at least two occasions 12 weeks apart) fulfill the laboratory classification criteria for antiphospholipid syndrome (APS); they are more likely than transiently positive LA to be associated with clinical symptoms.   

Test Description

ARUP’s Lupus Anticoagulant Reflex Panel includes a combination of two clot-based screening assays (activated partial thromboplastin time [aPTT] and dilute Russell viper venom time [dRVVT]), with reflexively performed mixing and confirmation steps, as well as anticoagulant identification and neutralization (as applicable).

Anticoagulant Neutralization

Activated charcoal-based direct oral anticoagulant (DOAC) neutralizing compounds (eg, DOAC-Stop) and heparinase (eg, Hepzyme) are included in the panel in cases where screening assays suggest the presence of anticoagulant medication. However, if clinically feasible, LA testing should be performed before starting anticoagulation therapy or after its completion.

Anticoagulant Comments

Direct Xa Inhibitors

DOAC-Stop neutralizes oral direct Xa inhibitors (rivaroxaban, apixaban, edoxaban) at concentrations up to 500 ng/mL

It is recommended to wait 48-72 hrs after discontinuing an oral direct Xa inhibitor before drawing samples for LA testing

DTIs

DOAC-Stop neutralizes the oral DTI dabigatran and may neutralize parenteral DTIs (argatroban and hirudin analogues)

It is recommended to wait 4-8 hrs after discontinuing parenteral DTI infusion before drawing samples for LA testing

It is recommended to wait 48-72 hrs after discontinuing an oral DTI before drawing samples for LA testing

LMWH

Hepzyme neutralizes LMWH but may be less effective compared with its neutralization of UFH

It is recommended to wait 24-48 hrs after discontinuing LMWH injections before drawing samples for LA testing

UFH

Hepzyme neutralizes typical therapeutic concentrations (≤2 units/mL) of UFH. Higher concentrations of UFH will not be completely neutralized and will appear as an inhibitor in mixing studies

It is recommended to wait 4-8 hrs after discontinuing a UFH infusion before drawing samples for LA testing

DTI, direct thrombin inhibitor; LMWH, low molecular weight heparin; UFH, unfractionated heparin

Test Interpretation

Sensitivity/Specificity

Varies. Refer to Results for reference intervals.

Results

Panel Component Result If Performed (Reported As) Reference Interval

Prothrombin time

Time in seconds

12.0-15.5 s

PTT-LA ratio

Ratio

≤1.20

dRVVT screen ratio

Ratio

≤1.20

Anti-Xa qualitative interpretation

Present or not present

Not present

Thrombin time

Time in seconds

≤19.5 s

Anticoagulant medication neutralization

DOAC-Stop or Hepzyme

Not performed

Neutralized PTT-LA ratio

Ratio

≤1.20

Neutralized dRVVT screen ratio

Ratio

≤1.20

dRVVT 1:1 mix ratio

Ratio

≤1.20

dRVVT confirmation ratio

Ratio

≤1.20

Hexagonal phospholipid confirmation

Time in seconds (delta)

≤7.9 s

LA interpretation

LA detected or LA not detected with a narrative comment

N/A

Limitations

  • Results should be interpreted within the context of a patient’s complete clinical picture.
  • The following factors may result in test interference or spurious results:
    • Acute phase reactions due to pregnancy, malignancy, inflammatory or infectious states, or trauma
    • Liver disease
    • Anticoagulant medications in concentrations exceeding the capacity of neutralizing reagents (heparins, DOACs)
    • Warfarin effect
    • Residual platelets (≥10,000 platelets/uL) in the plasma sample
    • Specific factor antibodies directed against clotting factors involved in the intrinsic or common pathways