Update on Clot Prevention in Patients With Antiphospholipid Antibody Syndrome

December 31, 2006

In her response to a reader’s question about clot prevention in a patient with systemiclupus erythematosus (SLE) and anticardiolipin antibody syndrome,Dr Bonnie Bermas recommends warfarin (CONSULTANT, September 15, 2003,page 1329).

In her response to a reader's question about clot prevention in a patient with systemiclupus erythematosus (SLE) and anticardiolipin antibody syndrome,Dr Bonnie Bermas recommends warfarin (CONSULTANT, September 15, 2003,page 1329). However, this recommendation is based on references that are over7 years old. Moreover, it seemed to me that too little information about the patientwas given to warrant a recommendation of warfarin. Although the reader statedthat the patient had had a previous infarct, how was it determined that this wasrelated to a hypercoagulable state rather than to the all-too-common risk factorsof hyperlipidemia, obesity, diabetes, and smoking? If the relationship can be verified,is there evidence that warfarin prevents future events as well as antiplateletagents, cholesterol-lowering agents, β-blockers, and/or angiotensin-converting enzyme(ACE) inhibitors?-- Ronald Hirsch, MD
  &nbsp Algonquin, Ill
Patients who have antiphospholipid antibodies andwho have had a major clotting event fulfill the criteriafor antiphospholipid antibody syndrome,1 forwhich the standard treatment is lifelong warfarintherapy.How was it determined that the patient's thrombosiswas related to a hypercoagulable state and not to other riskfactors? The only information the reader provided is thatthe patient has SLE and anticardiolipin antibody syndrome[sic] and had a previous infarct. Other risk factors couldcertainly have contributed to the infarct. However, becausethe peak incidence of SLE is in the second to fourth decadesof life and because risk factors such as hyperlipidemia,diabetes, and smoking are less likely to come intoplay in this age group, I assumed that this patient's majorrisk factor was the antiphospholipid antibody syndrome.There are no studies in patients with antiphospholipidantibody syndrome that compare warfarin with antiplateletagents, cholesterol-lowering agents, β-blockers,and/or ACE inhibitors. Only a handful of case reports andretrospective articles have been published on this topic. Amore recent retrospective article from a group of investigatorswhom I had referenced in my response confirmedthe recommendation that the target INR should be 3.5 inthese patients.2After my response appeared in CONSULTANT, thefirst prospective review of the topic was published.3 Thegist of these investigators' recommendation was the same:long-term anticoagulation. However, they concluded that atarget INR of 2.0 to 3.0 might be safer and just as effectiveas higher targets.Thus, the latest thinking regarding patients with antiphospholipidantibody syndrome (as manifested by athrombotic event) is that long-term anticoagulation is warranted.Hopefully, future prospective studies will elucidatethe optimal target INR to both minimize recurrent thromboticevents and ensure patient safety.-- Bonnie Lee Bermas, MD
  &nbsp Assistant Professor of Medicine
  &nbsp Division of Rheumatology
  &nbsp Harvard Medical School
  &nbsp Boston

References:

REFERENCES:1.

Wilson WA, Azzudin EG, Takos K, et al. International consensus statementon preliminary classification criteria for definite antiphospholipid syndrome: reportof an international workshop.

Arthritis Rheum.

1999;42:1309-1311.

2.

Ruiz-Irastorza G, Khamashta MA, Hunt BJ, et al. Bleeding and recurrentthrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patientstreated with oral anticoagulation to a target international normalized ratioof 3.5.

Arch Intern Med.

2002;162:1164-1169.

3.

Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities ofwarfarin for the prevention of recurrent thrombosis in patients with the antiphospholipidantibody syndrome.

N Engl J Med.

2003;349:1133-1138.