25th February 2025

Antiphospholipid syndrome (APLS)

Overview of antiphospholipid syndrome

Antiphospholipid syndrome is a chronic autoimmune condition which increases the risk of thrombus. It can be primary or associated with another autoimmune condition such as SLE.

Diagnosis is usually made either following thrombus or pregnancy complications, in combination with positive antiphospholipid antibodies.

Clinical features of antiphospholipid syndrome

Antiphospholipid syndrome can cause arterial, venous or microvascular thrombosis. DVT is the most common vascular manifestation, although pulmonary emboli and ischaemic strokes are also common. Cardiac valve abnormalities are seen in 30-50% of patients. Skin manifestations, such as livedo reticularis, can also be associated with antiphospholipid syndrome. Diagnosis is commonly made due to obstetric complications, such as recurrent early miscarriage, fetal loss, intrauterine growth restriction, pre-eclampsia or placental insufficiency.

Investigations in antiphospholipid syndrome

Routine blood tests will usually be normal in primary APLS; however, a prolonged APTT can be seen. Additionally, thrombocytopenia can be seen in around 30% of patients, particularly around the time of a thrombotic event.

Diagnosis of APLS requires at least one of the antiphospholipid antibodies to be positive on two occasions within 5 years of the thrombotic event. These are anti-2 glycoprotein-1 antibodies, anti-cardiolipin antibodies and lupus anticoagulant. Those with more than one positive antibody have a higher risk for thrombotic events.

Patients can have false positive syphilis results, as non-treponemal tests such as VDRL use cardiolipin antigens.

Management of antiphospholipid syndrome

Decisions surrounding use of antiplatelet agents and anticoagulation are complex and depend on whether there has been a previous clot, whether there is concomitant SLE and whether the thrombotic event was provoked.

• Hydroxychloroquine is used in patients with concomitant SLE, as it has anticoagulant and anti-inflammatory activity.
• Those who have had unprovoked thrombotic events are usually treated with warfarin (target INR 3-4). DOACs are not generally used as there is limited evidence regarding their safety and efficacy in APLS.
• In pregnancy, mothers are usually given low-dose aspirin and low-molecular-weight heparin (LMWH) – treatment dose with previous thrombosis, otherwise prophylactic dose.
• In refractory cases, rituximab (anti-CD20 B cell-depleting monoclonal antibody) can be used.

References

• Clunie GPR, Wilkinson N, Nikiphorou E, Deepak Jadon. Oxford handbook of rheumatology. Oxford: Oxford University Press; 2018.
• Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Annals of the Rheumatic Diseases [Internet]. 2019 Oct 1 [cited 2022 Feb 3];78(10):1296–304. Available from: https://ard.bmj.com/content/78/10/1296
• de Larrañaga G, Trombetta L, Wingeyer SP, Remondino G. False positive reactions in confirmatory tests for syphilis in presence of antiphospholipid antibodies: misdiagnosis with prognostic and social consequences. Dermatology Online Journal [Internet]. 2006 May 30 [cited 2022 Feb 3];12(4):22. Available from: https://pubmed.ncbi.nlm.nih.gov/17083877/
• Schreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastorza G, et al. Antiphospholipid syndrome. Nature Reviews Disease Primers [Internet]. 2018 Jan 11 [cited 2022 Feb 2];4(1). Available from: https://www.nature.com/articles/nrdp2017103