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New Data Fuels Continued Controversy About Anti-Phospholipid Antibody (APA) and Lupus Anticoagulant Management (LAC)

Henry I. Bussey, Pharm.D.
November, 2005

A prospective, randomized trial of high (INR 3 - 4) vs. moderate intensity (INR 2 - 3) anticoagulation was published in May, 2005 in the Journal of Thrombosis and Haemostasis1. This was the second such trial that failed to demonstrate an advantage of the high intensity anticoagulation over moderate anticoagulation. Both of these trials1,2 are summarized and critiqued in a handout by Amy Braun, Pharm.D. who is a Primary Care Speciality Resident at Scott & White Clinics in Temple, Texas and the Colllege of Pharmacy, The University of Texas at Austin. The handout also provides an overview of what is known about the pathophysiology, diagnosis, and management of the antiphospholipid antibody syndromes.

Because of issues of patient selection and anticoagulation control in these two more recent studies, we have not abandoned higher intensity anticoagulation for all APA patients in our clinic (Anticoagulation Clinics of North America). In two earlier reports3,4, Rosove reported that arterial (but not venous) events occurred with INRs in the 2 to 3 range (INRs < 2.6), and both studies indicated that the location (arterial vs. venous) of a recurrent thromboembolic event usually was the same as that of the preceeding thrombolic event. Because mainly recurrent arterial thromboembolic events occur at INRs in the conventional range (INR 2 - 3), and because arterial events typically occur in those with a prior arterial event, we typically set a higher target INR range for APA or LAC patients with a prior arterial thrombosis event. Within our own clinic, patients who have had only a venous thrombosis may be assigned to a conventional INR target of 2 to 3. Patients who have had a recurrent venous thromboembolic event while on warfarin (patients who were excluded from both of the more recent trials), also may be assigned to a higher target INR range in our clinic. Finally, we also rely on chromogenic factor X levels to evaluate high INRs that we feel may be falsely elevated by APA and/or LAC interference with the INR test.

Click here to download the handout from Dr. Braun.

References

  1. Finazzi G, Marchioli R, Brancaccio V, et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). Journal of Thrombosis and Haemostasis 2005; 3:848-53.

  2. Crowther MA, Ginsberg JS, Julian J, et al. A Comparison of Two Intensities of Warfarin for the Prevention of Recurrent Thrombosis in Patients with the Antiphospholipid Antibody Syndrome. N Engl J Med. 2003 Sep 18;349(12):1133-8.

  3. Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. 1992 Aug 15;117(4):303-8.

  4. Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GR. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995 Apr 13;332(15):993-7.
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