Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism

Abstract

It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-β2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions ∼6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% confidence interval [CI], 0.9-3.7; P = .09) in the 25.9% of patients with an APA on ≥1 occasions, 2.7 (95% CI, 1.1-.7; P = .03) in the 9.0% of patients with the same APA on 2 occasions, and 4.5 (95% CI, 1.5-13.0; P = .006) in the 3.8% of patients with 2 or 3 different APA types on either the same or different occasions. There was no association between having an APA and D-dimer levels. We conclude that having the same type of APA on 2 occasions or having >1 type of APA on the same or different occasions is associated with recurrent thrombosis in patients with a first unprovoked VTE who stop anticoagulant therapy in response to negative D-dimer tests. APA and D-dimer levels seem to be independent predictors of recurrence in patients with an unprovoked VTE. This trial was registered at www.clinicaltrials.gov as #NCT00720915.

Graphical abstract

Figure 1.

Patient flow and when APA testing was performed. At enrollment, all patients were receiving anticoagulants. At 1 month, patients with a positive D-dimer at enrollment remained on anticoagulants. At 7 months, patients with a positive D-dimer at enrollment or 1 month were receiving anticoagulants, and patients with a negative D-dimer at enrollment and at 1 month were not receiving anticoagulants.

Figure 2.

Association between quantitative APA assay results and recurrent VTE after stopping anticoagulant therapy. Results of APA assays in individual patients according to whether they did or did not have recurrent VTE during follow-up after stopping anticoagulant therapy. The cutoff values used to define whether a result was within the normal range are shown for each type of APA assay. When an APA was measured on 2 occasions in the same patient, the higher of the 2 values was used in these figures. The median values in patients with and without recurrent VTE are shown; the P values (2-sided median test) associated with each of these differences were: ACA IgG, P = .15; ACA IgM, P = .041; anti-β2GP1, P = .70; LA APTT, P = .17; and LA dilute Russell viper venom time (DRVVT), P = .70. GPL, IgG phospholipid units; MPL, IgM phospholipid units.

Figure 3.

Recurrent VTE after stopping anticoagulant therapy in patients with different APA findings. The cumulative proportion for recurrent VTE during follow-up after stopping anticoagulant therapy according to the APA findings in different groups of patients. No APA means no positive APA test on all occasions tested, and any APA means ≥1 positive APA tests on ≥1 occasions; these 2 groups are mutually exclusive. Same APA means that the same type of APA was positive on 2 occasions; these patients are a subgroup of the any APA group. Different APA means that at least 2 different types of APAs were positive, either on the same or different occasions; these patients are a subgroup of the any APA group.