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Ann Rheum Dis. 2007 October; 66(10): 1407–1408.
PMCID: PMC1994325

Clinical manifestations of the anti‐phospholipid syndrome as defined by the updated Sapporo classification criteria

The antiphospholipid syndrome (APS) is characterised by thrombosis and recurrent fetal loss accompanied by the presence of lupus anticoagulant (LA) and/or anti‐cardiolipin antibodies (aCLA).1,2 Anti‐phospholipid (aPL) antibodies require a protein cofactor, β2‐glycoprotein 1 (β2‐GP1) or prothrombin, for proper binding.3,4,5 Patients may also present with antibodies to β2‐GP1, but not LA or aCLA. Originally, they were classified as having the anti‐phospholipid/cofactor syndrome,6,7 but recently the Sapporo classification criteria have been updated by including the β2‐GP1‐antibodies.8

We retrospectively evaluated the clinical manifestations of APS in 105 consecutive patients that presented with the suspicion of APS and/or systemic lupus erythematosus, and tested positive for aPL antibodies twice at least 6 weeks apart. LA was assessed by performing the LA‐screen/confirm (Gradipore dRVVT, Australia). IgM and IgG aCLA, as well as IgG antibodies to β2‐GP1, were determined by ELISA (Varelisa, Phadia, Germany).

Sixty‐eight patients (65%) fulfilled the clinical APS classification criteria; 33 patients (31%) did not. In four patients, insufficient clinical information was available. The 33 non‐APS patients were tested for aPL antibodies, because they were diagnosed as having systemic autoimmune diseases (n = 19), because they exhibited only minor APS criteria (n = 5), or for miscellaneous reasons (n = 7). According to the adjusted criteria,8 aPL‐antibody presence is categorised as follows: I, more than one aPL‐antibody; IIa, only LA; IIb, only aCLA; IIc, only anti‐β2‐GP1 antibodies. The aPL‐antibody distribution of the 68 APS patients and 33 patients not having APS are shown in table 11.. Six APS patients (categories IIb/IIc) were not tested for LA and therefore were possibly erroneously categorised. Surprisingly, 13 APS patients (19.1%) were in category IIc. This is not due to the anti‐β2‐GP1 ELISA being too sensitive, since only two non‐APS patients (6.1%) were in category IIc. That these anti‐β2‐GP1 antibodies are not detected in the β2‐GP1 dependent aCLA assay can be explained by the finding that these antibodies bind close to the phospholipids‐binding site in domain V of β2‐GP1,7 and so this epitope is blocked once β2‐GP1 has bound to cardiolipin.

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Table 1 Laboratory characteristics in relation to clinical characteristics

Clinical manifestations were scored from symptom onset until the end of inclusion. The most common events were DVT (37%), fetal loss >10 weeks of pregnancy (25%), stroke/transient ischaemic attack (21%), fetal loss <10 weeks of pregnancy (19%), pulmonary embolism (15%) and arterial thrombosis in the legs (12%). Other common findings were thrombocytopenia (28%), arthralgia (10%), epilepsy (9%) and myocardial infarction (7%). Our data are in agreement with the multicentre study of Cervera et al9 Clinical manifestations of patients categorised based on their antibody profile hardly differed between categories (table 11).). Both category IIa patients had DVT, whereas a substantial proportion of category IIc patients had stroke/transient ischaemic attack (TIA) (38%). These associations were, however, not statistically significant (p = 0.12 and p = 0.06, respectively).

Altogether, inclusion of anti‐β2‐GP1 antibodies results in a 20% increase in patients classified with APS. Clinical manifestations in APS as defined by the updated laboratory criteria8 are not different from patients with APS defined by the original Sapporo criteria.1 In addition, clinical manifestations are not predictive of a typical autoantibody profile.


aCLA - anti‐cardiolipin antibodies

aPL - anti‐phospholipid

APS - antiphospholipid syndrome

LA - lupus anticoagulant


Competing interest statement: None of the authors have any competing interest.


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