Beverley J Hunt^1
1Kings Healthcare Partners

Antiphospholipid syndrome (APS) is a difficult condition to diagnose and treat and the aim of my lecture is to bring the audience up-to date with current management and highlight the controversial areas.

Diagnosis is dependent on a patient having a thrombotic episode (unlike the inherited thrombophilias, APS can affect any vessel -arterial venous or microvascular) and/or defined obstetric morbidity/mortality associated with persistent antiphospholipid antibodies i.e antibodies present on two occasions more than 12 weeks apart. Currently testing is required for lupus anticoagulant, anticardiolipin and anti beta-2 glycoprotein I antibodies. Testing for all three is required as a significant minority of in those with APS are only positive for one assay and while triple positivity conveys the highest risk of thrombosis, serious thrombotic issues can occur in those with only single positivity.

The principle of managing those with unprovoked thrombotic events is to prescribe long-term anticoagulation usually with a vitamin K antagonist (VKAs) although DOACs are used in those who are not triple positive and don’t have a previous arterial event. For those with issue with VKAs we have been trialling fondaparinux successfully long term. A special group is those with a monoclonal gammopathy, it appears the antiphospholipid effect lies within the gammopathy, and they may have recurrent thrombosis despite good anticoagulation. 

Management of women with antiphospholipid antibodies during pregnancy is getting increasingly complex depending on their past obstetric and thrombotic history and current management pathways will be discussed.

Schreiber K, Hunt BJ. Managing antiphospholipid syndrome in pregnancy. Thromb Res. 2019 Sep;181 Suppl 1:S41-S46. 

Schreiber K, Breen K, Cohen H, Jacobsen S, Middeldorp S, Pavord S, Regan L, Roccatello D, Robinson SE, Sciascia S, Seed PT, Watkins L, Hunt BJ. HYdroxychloroquine to Improve Pregnancy Outcome in Women with AnTIphospholipid Antibodies (HYPATIA) Protocol: A Multinational Randomized Controlled Trial of Hydroxychloroquine versus Placebo in Addition to Standard Treatment in Pregnant Women with Antiphospholipid Syndrome or Antibodies. Semin Thromb Hemost. 2017 Sep;43(6):562-571. 

Schreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastorza G, Salmon JE, Shoenfeld Y, Shovman O, Hunt BJ. Antiphospholipid syndrome. Nat Rev Dis Primers. 2018 Jan 25;4:18005. doi: 10.1038/nrdp.2018.5. Erratum for: Nat Rev Dis Primers. 2018 Jan 11;4:17103. 

Schreiber K, Graversgaard C, Hunt BJ, Wason JMS, Costedoat-Chalumeau N, Aguilera S, Guerra MM, Salmon JE. Challenges of designing and conducting cohort studies and clinical trials in populations of pregnant people. Lancet Rheumatol. 2024 Aug;6(8):e560-e572. 

Bor B, Doyle AJ, Bartoli-Abdou JK, Hackett A, Collings V, Omrani F, Foskett C, Wareing A, Young J, Breen KA, Hunt BJ. Clinical outcomes of patients receiving long-term fondaparinux for thrombotic antiphospholipid syndrome. Lupus. 2024 Nov;33(13):1446-1454..

Doyle AJ, Breen KA, Hunt BJ. Antiphospholipid Syndrome with Monoclonal Gammopathy-A Mechanism for Recurrent Thrombosis? Thromb Haemost. 2021 Oct;121(10):1387-1390. 

Joseph Rigano¹

¹Department of Haematology, Northern Health, Melbourne, Australia

Antiphospholipid syndrome (APS) is characterised by the persistent detection of antiphospholipid antibodies (aPLs). Lupus anticoagulant (LA) is one of the three criteria aPLs used in the laboratory identification of APS. Two phospholipid dependant assays utilising different principles should be used to detected LA. One being dRVVT and the other a LA sensitive aPTT both paired with low and high phospholipoid concentration. Initial prolonged screening assays should be followed up with mixing and confirmatory assays. Often testing is requested when patients are anticoagulated leading to interference with false positive and false negative results. To overcome anticoagulant interference, commercial DOAC removal agents are available in the form of activated charcoal and filters. Alternatively, Taipan snake venom time/ecarin time (TSVT/ET) can be used in patients on VKA and anti-Xa DOACs. Interpretation of LA testing is dependant on cut-off values which should be established in each laboratory based on reagent and instrument combination. Repeat testing should be performed to exclude transient antibodies produced by infection and drugs and elevated acute phase proteins yielding equivocal results. Results should be reported as positive (presence) or negative (absence) for LA. Re-testing should be performed on a second occasion 12 weeks from initial LA detection to confirm persistent positivity.

A review of current and novel antibody testing in APLS