Guidelines on the investigation and management of antiphospholipid syndrome

Abstract

This guideline was compiled according to the British Society for Haematology (BSH) process at (https://b-s-h.org.uk/media/16732/bsh-guidance-development-process-dec-5-18.pdf). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate the levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. A literature search was carried out using the terms given in the appendix up to April 2024. Review of the guideline followed the standard BSH guidelines procedure. Following review of the draft guideline by the BSH Haemostasis and Thrombosis Task Force and the BSH Guidelines Committee, it was placed on the members' section of the BSH website for comment (sounding board) and these comments were addressed and incorporated appropriately. The guideline was reviewed by the Royal College of Obstetricians and Gynaecologists, Thrombosis UK and APS Support UK. These organizations do not necessarily approve or endorse the contents. This 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 ≥1 episode of arterial, venous or small vessel thrombosis in any organ or tissue confirmed objectively (imaging/histology) Where histology used, thrombosis should be present without overt vessel wall inflammation Although the supplementary guidance notes to the modified Sapporo criteria do suggest taking other risk factors for thrombosis into account, there is no formal downgrading in the presence of risk factors for CVD or VTE The Sapporo criteria provide no weighting to thrombotic manifestations (any thrombotic manifestation counts as towards the diagnosis equally in the appropriate clinical context) Both guidelines emphasise the need to confirm thrombosis objectively ≥1 unexplained death of a morphologically normal fetus at ≥10 ≥1 of a morphologically normal ≥3 with alternative factors positive according to positive IgG/IgM at or by 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most in with thrombocytopenia or manifestations of In of the of the to the of in the can be and has been used with in with a thrombotic The should be where with a and with 2 weeks in in with guidance where may be to clinical and of the laboratory features of the thrombotic in the of thrombosis may be and it be to in the evidence the of from on but a Patients with with or without present a of clinical In to by with the time there is a risk of and systemic thrombosis to the presence of In the with the by and not the of for of of Although the of levels is more than the for the anticoagulant of may not be in a in for patients and studies used to in patients with with or without In a of patients with with or without it was the between and the was The and to of were and was no thrombosis or or death 12 patients standard or if the patients a confirmed diagnosis of APS to In of patients with APS thrombosis,

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