LA Test Stability and Thrombosis Risk Examined

Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies directed against anionic phospholipids and phospholipid-binding plasma proteins. Patients with persistent aPL with or without antiphospholipid syndrome are at increased risk of future thrombotic events, lupus anticoagulant (LA) positivity having the strongest association with these events.

The presence of one or more of these aPL for 12 or more weeks constitutes the laboratory criteria for antiphospholipid syndrome (APS), an autoimmune disorder defined clinically by arterial and venous thrombotic events and/or pregnancy complications. Additional antibodies, most notably anti-cardiolipin antibodies (aCL) and anti–glycoprotein-I antibodies (aβ2GPI), have been identified and associated with thrombosis and recurrent spontaneous abortions.

Hematologists at the Medical University of Vienna (Vienna, Austria) and their colleagues investigated the rate and predictors of a negative LA test and whether experiencing a negative test affected a patient’s risk of future thrombotic events or death in a prospective observational study of persistently LA+ patients. They followed 164 patients (84% women) for a median of 9.2 years and a total of 1,438 follow-up visits. During the observation period, 50 thrombotic events (23 arterial and 27 venous events) occurred, and 24 patients died.

Blood samples were drawn with a 21-gauge butterfly needle into vacuette tubes containing trisodium citrate for the determination of LA and containing Z Serum Sep Clot Activator for the determination of aCL and aβ2GPI antibodies. A lupus-sensitive activated partial thromboplastin time (PTT-LA, Diagnostica Stago, Asniere-sur-Seine, France) and a dilute Russell’s viper venom time (dRVVT, Life Diagnostics, Clarkston, GA, USA) were used as screening tests. Immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against cardiolipin and β2-GPI were determined using commercially available indirect solid-phase enzyme immunoassays.

Between 2001 and September 2005, IgG and IgM aCL were determined using the Varelisa Cardiolipin test (Pharmacia [Phadia AB], Uppsala, Sweden) performed semi-automatically on the Tecan Genesis liquid handling system (Tecan Group Ltd., Männedorf, Switzerland). From October 2005, the Orgentec Cardiolipin, and from October 2006, the Orgentec aβ2GPI tests (Orgentec, Mainz, Germany), were performed on a fully automated BEP2000 Advanced System (Siemens Healthcare Diagnostics, Marbury, Germany).

The scientists reported that 46 of the patients had at least one negative LA test during the observation period, corresponding to a 10-year cumulative incidence of a negative LA test of 28%. The majority of patients (41/46, 89%) with available follow-up after a negative LA test had at least one subsequent positive test for LA (n = 28/41, 68%). Vitamin K antagonist (VKA) treatment at baseline was associated with a negative LA test during follow-up. Using a multistate time-to-event model with multivariable adjustment, a negative LA test had no impact on a patient’s prospective risk of thrombosis or mortality. Median time to a first subsequent positive LA test for those who turned LA negative was one year.

The authors concluded that the decision for duration of anticoagulation cannot be based on a negative LA test if a patient has previously been persistently positive. Additionally, based on their findings, there is no evidence for the clinical utility of routine monitoring of LA status in persistently positive patients. The study was published on May 13, 2022 in the journal Blood Advances.

Related Links:
Medical University of Vienna 
Diagnostica Stago
Life Diagnostics 
Pharmacia 
Tecan Group Ltd 
Orgentec 
Siemens Healthcare Diagnostics