Criteria

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)[1]

There are no diagnostic criteria for APS. However, the classification criteria (originally formulated in Sapporo, Japan) is often used as a guide for APS diagnosis.[1][3]​​​​ The Sapporo criteria have a specificity of 86% and a sensitivity of 99%.[1]​ The diagnosis of APS requires at least 1 of the following clinical criteria and 1 of the following laboratory criteria. Laboratory criteria must be positive on 2 or more occasions, at least 12 weeks apart.

Clinical criteria

  • Vascular thrombosis: 1 or more clinical episodes of arterial, venous, or small-vessel thrombosis in any tissue or organ. Thrombosis must be confirmed by objective validated criteria. For histopathological confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wall. This can be further subclassified as being in the presence or the absence of additional risk factors for thrombosis.

  • Pregnancy morbidity: 1 or more unexplained deaths of morphologically normal fetuses at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus; 1 or more premature births of morphologically normal neonates before the 34th week of gestation because of eclampsia, severe pre-eclampsia, intrauterine growth restriction, or placental insufficiency defined according to standard definitions or recognised features of placental insufficiency; 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomical or hormonal abnormalities and paternal and maternal chromosomal causes excluded.

Laboratory criteria

  • Lupus anticoagulant is present in the plasma on 2 or more occasions, at least 12 weeks apart.

  • Anticardiolipin antibody of IgG or IgM isotype in serum or plasma is present in medium or high titre (>40 IgG phospholipid [GPL] units or IgM phospholipid [MPL] units, or >99th percentile) on 2 or more occasions, at least 12 weeks apart, by enzyme-linked immunosorbent assay (ELISA).

  • Anti-beta2-glycoprotein I antibody of IgG and/or IgM isotype in serum or plasma (in titre >90th percentile) on 2 or more occasions, at least 12 weeks apart, measured by ELISA.

  • It must be emphasised that about one third of patients with APS have a lupus anticoagulant, anticardiolipin, and anti-beta2-glycoprotein I antibodies (i.e., they are triple-positive). However, many patients may be positive for only a lupus anticoagulant or anticardiolipin antibody alone. Thus, it is important to offer all the assays in a patient's work-up.

Non-criteria manifestations include thrombocytopenia, heart valve abnormalities, livedo reticularis, seizures, chorea, and nephropathy.[42]

American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) antiphospholipid syndrome classification criteria[2]

The ACR/EULAR classification criteria update the Sapporo criteria above, by widening the scope of symptoms and clinical signs to include hierarchically clustered and weighted independent clinical and laboratory domains.[2] ​The criteria have a specificity of 99% and sensitivity of 84%.[2]​ Those with at least one positive antiphospholipid antibody (aPL) test within 3 years of an aPL-associated clinical criterion can be classified with the following criteria.

Clinical criteria

  • Macrovascular venous thromboembolism: an otherwise unexplained venous thromboembolism (e.g., pulmonary embolism, deep vein thrombosis, splanchnic and renal vein thrombosis, cerebral venous thrombosis, and retinal vein occlusion) that has been confirmed by appropriate testing (e.g., imaging or pathology). Criterion weighting depends on whether the individual has a high-risk profile for venous thromboembolism (e.g., active malignancy, recent emergency hospitalisation, major trauma, or recent surgical procedure).

  • Macrovascular arterial thrombosis: an otherwise unexplained arterial thromboembolism (e.g., myocardial infarction, thrombosis of the peripheral, splanchnic, or retinal artery, stroke, and other organ infarcts [e.g., kidney, liver, or spleen] in the absence of a visualised thrombus) that has been confirmed by appropriate testing (e.g., imaging or pathology). Criterion weighting depends on whether the individual has a high-risk profile for cardiovascular disease (e.g., arterial hypertension, chronic kidney disease, diabetes, or hyperlipidaemia) at the time of the event.

  • Microvascular manifestations: livedo racemosa, livedoid vasculopathy lesions, aPL nephropathy, pulmonary haemorrhage, adrenal haemorrhage or microthrombosis, or myocardial disease. Criterion weighting depends on whether the diagnosis is suspected or confirmed (e.g., by imaging or pathology).

  • Pregnancy morbidity: three or more consecutive prefetal (before the 10th week of gestation) or early fetal (between the 10th week of gestation and the 16th week of gestation) deaths, a fetal death between the 16th week of gestation and the 34th week of gestation in the absence of severe pre-eclampsia or placental insufficiency, or severe pre-eclampsia or placental insufficiency before the 34th week of gestation with or without fetal death.

  • Cardiac-valve abnormalities: otherwise unexplained valve thickening or vegetations.

  • Haematological abnormalities: otherwise unexplained thrombocytopenia confirmed on peripheral blood smear and repeat testing.

Laboratory criteria

  • aPL test by coagulation-based assay (lupus anticoagulant test): criterion weighting depends whether the test is positive once or persistently positive (positive on two or more occasions, at least 12 weeks apart).

  • aPL test by solid-phase assay (anticardiolipin and/or anti-beta2-glycoprotein I antibodies): tests must be positive on two or more occasions, at least 12 weeks apart. Criterion weighting depends on whether the test result is moderate or high and whether one or both antibodies are present.

Items in each of these eight domains receive a score between 1 and 7. People who score at least 3 points in both the clinical and the laboratory domains are classified as having APS.[2]

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