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Antiphospholipid/cofactor antibodies are detected in only 60% of patients with systemic lupus erythematosus (SLE) with thrombosis.1 Therefore, we studied thrombophilia factors and their relation with thrombosis in patients with SLE.
METHODS AND RESULTS
Forty eight consecutive patients with SLE were included (39 women, 9 men), 15 with and 33 without past thrombosis (Th and NTh group, respectively). Twenty thrombotic events were identified: 17 deep venous and 1 arterial thrombosis, 2 osteonecrosis. Both groups had comparable clinical, biological, therapeutic data, and mean (SD) SLE disease activity index (SLEDAI) (5 (4.6) v 5.3 (4.8)).
Patients were examined at least one month after thrombosis (>3 months in 11 out of 15). The following parameters were determined: protein C, total and free protein S (in 43 patients because five had antivitamin K treatment), antithrombin, activated protein C resistance (APCR), the R506Q mutation of the factor V gene and the G20210A allele of the prothrombin gene, lupus anticoagulant (LAC) (activated partial thromboplastin time, tissue thromboplastin inhibition test, and platelet neutralisation procedure), IgG anticardiolipin antibodies (aCL), IgG and IgM anti-β2-glycoprotein I (anti-β2GPI) antibodies, IgG and IgM antiprothrombin antibodies. Homocysteinaemia (fasting and after oral methionine load (100 mg/kg)) was measured in 38 patients (9 Th, 29 NTh patients).
Table 1 gives the main results. LAC and aCL >30 GPL units were associated with thrombosis, unlike anti-cofactor antibodies. Anti-β2GPI was detected only in positive LAC subjects. Free protein S levels were negatively correlated with the SLEDAI (r=−0.33, p=0.025), and anti-DNA levels (r=−0.31, p=0.04), but not with C reactive protein or ESR. Antiphospholipid/cofactor antibodies were present in 6/8 patients with low free protein S and in 12/35 patients with normal free protein S (p=0.05). One of the two patients with APCR was negative for factor V Leiden. G20210A prothrombin gene mutation was present in one NTh patient. Homocysteinaemia was highly correlated with creatininaemia (r=0.64, p<0.0001), but not with current or cumulative steroid dose (p=0.08).
The patient with arterial thrombosis had neither antiphospholipid/cofactor antibodies nor thrombophilic factor.
Our results confirm that LAC and aCL (>30 GPL) are closely associated with thrombosis in SLE.2,3 Anti-β2GPI antibodies do not add any information to LAC, and anti-β2GPI and antiprothrombin are not associated with thrombosis. Transiently negative results are unlikely because patients were sampled at least one month after the thrombosis.
As in previous studies,4 decreased free protein S is common (19%) but not associated with thrombosis. Antiphospholipid/cofactor antibodies are more prevalent in patients with protein S deficiency, suggesting an autoimmune mechanism that might involve antiprotein S antibodies.5 The negative correlation between free protein S level and SLE activity suggests a link between disease activity and coagulation activation,6,7 although we were unable to demonstrate an association between thrombosis and protein S level.
Mild hyperhomocysteinaemia was common (37%) and closely correlated with mild renal function impairment but not with the steroid regimen.8,9 Hyperhomocysteinaemia is an arterial thrombosis risk factor in SLE,8 and it was not associated with the mainly venous thrombosis in our sample.
Genetic thrombophilia was no more prevalent than in the general population.
Finally, we confirm that LAC and aCL >30 GPL units are the main thrombophilic factors associated with thrombosis in SLE. The role of free protein S and homocysteinaemia remains unclear. Prospective studies, with serial sampling, are needed to elucidate which others factors may play a part.
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