Laura C. Gennari

Antibodies directed to protein S in patients with systemic lupus erythematosus: prevalence and clinical significance

Antibodies directed against protein S (anti-ProtS) may be involved in the development of thrombosis in patients with the antiphospholipid syndrome. We assessed the prevalence and clinical significance of anti-ProtS and evaluated their immunological characteristics in 184 patients with SLE and 99 healthy donors. All patients were tested for IgG anti-ProtS by an in-house ELISA. Plasma levels and functional activity of protein S were also tested. Anti-ProtS were found in 57 patients (31%) and 4 healthy controls (4%). Patients with thrombosis had anti-ProtS more frequently than controls (29% vs 4%, OR 9.5 [95% CI 3.07-29.3], p<0.0001). Anti-ProtS were more frequent in patients with venous thrombosis and in those with arterial thrombosis, than in controls (41% vs. 4%, OR 16.5 [95% CI 5-54], p<0.0001 and 23% vs. 4%, OR 7 [95%CI 2.1-23.5], p=0.0008, respectively). Patients with prematurity, preeclampsia and intrauterine growth restriction had anti-ProtS more frequently than the control group (36%, 47% and 44% vs. 4%; OR 13.6 [95% CI 2.8-66], p=0.003, OR 21 [95% CI 5-86], p<0.0001 and OR 19 [95% CI 4-99], p=0.0014, respectively). Plasma levels of free protein S were not statistically different between patients with and without anti-ProtS and controls (77.9% [20.7-100] vs. 83.7% [52.7-100] vs. 89% [62-101], respectively). Free protein S functional activity was no different between subgroups (105% [48-230] in anti-ProtS positive vs. 123% [95-283] in anti-ProtS negative vs. 136% [60-174] in controls). Anti-ProtS are frequent in SLE patients with thrombosis and pregnancy morbidity. These antibodies do not interfere with free protein S in plasma since its level and/or functional activity are not impaired.

Antiphospholipid antibodies and hyperhomocysteinaemia in patients with vascular occlusive disease

Hyperhomocysteinemia (HHcy), lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are independent risk factors for thrombosis. Even though risks are cumulative, the clinical impact of the association is unknown. Preliminary data suggested that HHcy might be associated with transient LA and ACA, disappearing after lowering HHcy. We prospectively evaluated the association of HHcy and LA/ACA, the effect of lowering HHcy with folic acid in LA behavior, and the correlation of the initial dRVVT with LA behavior after folic acid in 210 patients with thrombosis and adverse pregnancy outcomes. Prevalence of HHcy among patients with LA/ACA was 40%. Thirty-one patients exhibited only HHcy (15%; Group 1), 106 (50%; Group 2) had only LA/ACA, while 73 (35%; Group 3) had both. After therapy, 63% and 64% of LA/ACA remained positive in Group 3 and 2, respectively. We observed a trend towards a more positive dRVVT in persistent LA after lowering HHcy. No differences in clinical presentation or in outcomes after two years of followup were observed among the groups. Even though the association of HHcy and LA/ACA is common in patients with thrombosis, it might have no prognostic implications if Hcy levels are lowered. Currently, no laboratory findings correlate with LA behavior, which is independent of homocysteine levels and vitamin treatment.

Mechanical heart valve prostheses and persistent lupus anticoagulant: is the thrombotic risk increased?

The risk of thrombosis in patients with mechanical heart valve prostheses in spite of life-long adequate anticoagulation is 1–2% per year. Current recommendations for anticoagulation take into account the prosthesis itself and the co-morbid conditions that enhance the thrombotic risk. Lupus anticoagulant is diagnosed in many thrombotic recurrences.We designed an ambispective case–control study to evaluate thrombotic events in patients with mechanical heart valve prostheses and persistent lupus anticoagulant. Our objectives were to determine whether persistent lupus anticoagulant increased the risk of embolism in that population and thus, if a more intense anticoagulation would be recommended, even at the risk of increasing bleeding episodes.We included 16 patients and 16 controls with more than 80 patient-years of follow-up and with other risk factors for embolism. We observed no increased rate of thromboembolic events in patients than in controls, even during high-risk situations (i.e. bacterial endocarditis). Our population spent most of the time within the intended anticoagulation range.We conclude that adequate anticoagulation is the most important issue to prevent events, protecting against thrombosis without increasing the bleeding risk.