Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients

Abstract

OBJECTIVE: To determine the clinical course and influence of antithrombotic therapy in patients with lupus anticoagulant or anticardiolipin antibodies, or both, after the first thromboembolic event. DESIGN: Retrospective survey of consecutive patients treated according to their physician's best judgment. SETTING: Secondary and tertiary referral practice. PATIENTS: Seventy patients (48 women [69%]) with a mean age (+/- SD) of 45.5 +/- 17.3 years. The antiphospholipid syndrome was primary in 51 patients (73%) and secondary to systemic lupus erythematosus in 14 patients (20%) and to chronic idiopathic thrombocytopenic purpura in 5 patients (7%). MEASUREMENTS: Site of initial and recurrent thrombotic events (venous or arterial), as well as kind (aspiring, heparin, or warfarin) and intensity of anticoagulation. RESULTS: Total follow-up after the first thrombotic event was 361.0 patient-years (mean [+/- SD], 5.2 +/- 5.6 years per patient). Thirty-seven patients (53%) had 54 recurrent events, with 2 patients experiencing fatal events. Arterial events were followed by arterial events, and venous events by venous events, in 49 of 54 instances (91%). Recurrence rates during "no treatment;" aspirin therapy; or low-, intermediate-, or high-intensity warfarin therapy (international normalized ratios [INRs] less than or equal to 1.9, 2.0 to 2.9, and greater than or equal to 3.0, respectively, or rabbit brain thromboplastin prothrombin time ratios of approximately less than 1.3, 1.3 to 1.5, and greater than 1.5, respectively) were 0.19, 0.32, 0.57, 0.07 (P = 0.12), and 0.00 (P less than 0.001) per patient-year. The follow-up periods for the five types of therapy were 161.2, 37.8, 11.3, 40.9, and 110.2 patient-years, respectively. The highest INR coincident with thrombosis was 2.6. Five warfarin-treated patients had five significant bleeding events (0.031 per patient-year). CONCLUSIONS: Recurrent thrombosis is a potentially serious problem for patients with lupus anticoagulant or anticardiolipin antibodies or both. The site of the first event (arterial or venous) tended to predict the site of subsequent events. Intermediate- to high-intensity warfarin therapy may confer better antithrombotic protection than low- to intermediate-intensity warfarin therapy or aspirin therapy. Further studies are needed to define more precisely the rethrombosis rate and optimal type, intensity, and duration of antithrombotic therapy.