Guidelines on the investigation and management of antiphospholipid syndrome

his guidance updates and replaces previous BSH guidelines.^1, 2 Antiphospholipid syndrome (APS) is an autoimmune disease characterised by thrombosis (venous, arterial and/or microvascular) and/or pregnancy morbidity in association with persistently positive antiphospholipid antibodies (aPL). APS can occur in isolation (primary APS) or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE) and rheumatoid arthritis (secondary APS).

The diagnosis of APS requires the presence of at least one clinical event (either an objectively confirmed thrombotic event and/or pregnancy complication) and detection of one or more aPL (lupus anticoagulant [LA], IgG/IgM anticardiolipin [aCL] and/or IgG/IgM anti-β₂ glycoprotein-1 [aβ₂GPI]) on two or more occasions at least 12 weeks apart.³ Thrombosis in APS can occur in any organ or tissue. Deep vein thrombosis (DVT) with or without pulmonary embolism (PE) is the most common venous thrombosis (VTE) while transient ischaemic attack (TIA) and stroke are the most common arterial thromboses.³ APS may also present with unusual site thrombosis such as portal, renal, mesenteric and cerebral venous sinus thrombosis. Microvascular thrombosis in APS is uncommon but may manifest as the potentially lethal catastrophic antiphospholipid syndrome (CAPS), which develops in <1% of patients with APS and where there is evidence of multiorgan failure commonly affecting the heart, lungs, brain and/or kidneys.³

In the updated Sapporo classification criteria, non-thrombotic clinical manifestations such as thrombocytopenia and heart valve disease were not included as diagnostic or defining features of definite APS.³ However, recent American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) Antiphospholipid Syndrome Classification Criteria,⁴ designed for uniformity of patient risk profiles in clinical studies, include several features not described in the revised Sapporo criteria.³ The ACR/EULAR criteria (Table 1)⁴ include a scoring system (score range 1–7 points each) divided into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular thrombosis, obstetric, cardiac valve and haematological) and two laboratory domains similar to the revised Sapporo criteria. Patients are classified as having APS if they score ≥3 points in clinical domains and ≥3 points in laboratory domains (Table 1). The definition of aPL persistence has not altered, but the maximum time between a clinical event and persistently positive aPL has been shortened from 5 to 3 years (Table 1). Diagnosis of APS in routine clinical practice is less restrictive than the ACR/EULAR APS classification criteria; their strict application in routine practice to diagnose individual patients should be avoided. The diagnosis of APS should depend on careful clinical assessment, paying attention to alternative causes of thrombosis or pregnancy morbidity and critical evaluation of laboratory results considering the limitations of the laboratory assays. Current clinical practice is based on the evidence derived from the clinical studies from patients with APS diagnosed as per revised Sapporo criteria.³