Antiphospholipid antibody syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis, complications during pregnancy, and the presence of antiphospholipid antibodies (APL) in plasma.
Revised Sapporo classification criteria for the APS
1. Vascular thrombosis*
One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ. Thrombosis must be confirmed by imaging or Doppler studies or histopathology, with the exception of superficial venous thrombosis. For histopathologic confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wall.
2. Pregnancy morbidity
- One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus, or
- One or more premature births of a morphologically normal neonate before the 34th week of gestation because of: (i) eclampsia or severe preeclampsia defined according to standard definitions, or (ii) recognised features of placental insufficiency**, or
- Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.
In studies of populations of patients who have more than one type of pregnancy morbidity, investigators are strongly encouraged to stratify groups of subjects according to a, b, or c above.
1. Anticardiolipin antibody of IgG and/or IgM isotype in serum or plasma, present in medium or high titer (i.e. >40 IgG phospholipid units (GPL) or IgM phospholipid units (MPL), or >the 99th percentile, or > mean + 3SD of 40 healthy controls), on 2 or more occasions, at least 12 weeks apart, measured by a standardized enzyme-linked immunosorbent assay (ELISA).
2. Lupus anticoagulant present in plasma, on 2 or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Hemostasis (Scientific Subcommittee on Lupus Anticoagulants/Phospholipid-Dependent Antibodies).
3. Anti-β2 glycoprotein-I antibody of IgG and/or IgM isotype in serum or plasma, present on 2 or more occasions, at least 12 weeks apart, measured by a standardized enzyme-linked immunosorbent assay, according to recommended procedures.
Definite APS is present if at least one of the clinical criteria and one 3 of the laboratory criteria are met, with the first measurement of the laboratory test performed at least 12 weeks from the clinical manifestation****.
*Coexisting inherited or acquired factors for thrombosis are not reason for excluding patients from APS trials. However, two subgroups of APS patients should be recognized, according to: (a) the presence, and (b) the absence of additional risk factors for thrombosis. Indicative (but not exhaustive) such cases include: age (>55 in men, and >65 in women), and the presence of any of the established risk factors for cardiovascular disease (hypertension, diabetes mellitus, elevated LDL or low HDL cholesterol, cigarette smoking, family history of premature cardiovascular disease, body mass index ≥30 kg/m2, microalbuminuria, estimated GFR <60 mL/min), inherited thrombophilias, oral contraceptives, nephrotic syndrome, malignancy, immobilization, surgery. Thus, patients who fulfill criteria should be stratified according to contributing causes of thrombosis.
**Generally accepted features of placental insufficiency include: (1) abnormal or non-reassuring fetal surveillance test(s), e.g., a non-reactive non-stress test, suggestive of fetal hypoxemia, (2) abnormal Doppler flow velocimetry waveform analysis suggestive of fetal hypoxemia, e.g., absent end-diastolic flow in the umbilical artery, (3) oligohydramnios, e.g., an amniotic fluid index of 5 cm or less, or (4) a post natal birth weight less than the 10th percentile for the gestational age.
***Investigators are strongly advised to classify APS patients in studies into one of the following categories:
I: More than one Laboratory criteria present (any combination)
IIa: Anti-cardiolipin antibody present alone
IIb: Lupus Anticoagulant present alone
IIc: Anti-β2 glycoprotein-I antibody present alone
****Classification of APS should be avoided if less than 12 weeks or more than 5 years separate the positive aPL test and the clinical manifestation.
Major Clinical Manifestations of the Antiphospholipid Syndrome That Are Not Included in the Revised Sapporo Classification Criteria
- More common: mild (platelet count, 50,000–150,000 per mm3), asymptomatic
- Less common: severe (platelet count, <20,000 per mm3), with or without thrombotic microangiopathy
2- Hemolytic anemia
- Without schistocytes, suggesting immune-mediated hemolytic anemia
- With schistocytes, suggesting thrombotic microangiopathy
- Acute thrombotic microangiopathy
- Chronic vaso-occlusive lesions (cortical ischemia or infarction with arteriosclerosis, arteriolosclerosis, arterial fibrous intimal hyperplasia, glomerular
ischemia, interstitial fibrosis, tubular thyroidization, tubular atrophy, organized thrombi with or without recanalization, or a combination of such lesions)
- Valve vegetations or thickening (valve thickness >3 mm, thickening of the proximal or middle portion of the leaflet, or irregular nodules on the atrial face of the edge of the mitral valve, the vascular face of the aortic valve, or both)
- Livedo reticularis or racemosa
- Livedoid vasculopathy (recurrent, painful skin ulcerations)
- Cognitive dysfunction (in the absence of stroke)
- Subcortical white-matter changes
- Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018 May 24;378(21):2010-2021. [Medline]
- Chaturvedi S, McCrae KR. Diagnosis and management of the antiphospholipid syndrome. Blood Rev. 2017 Nov;31(6):406-417. [Medline]
- Cervera R. Antiphospholipid syndrome. Thromb Res. 2017 Mar;151 Suppl 1:S43-S47. [Medline]
Created Apr 12, 2019.