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Clinical Review

Diagnosis and management of the antiphospholipid syndrome

BMJ 2010; 340 doi: (Published 14 May 2010) Cite this as: BMJ 2010;340:c2541

Rapid Response:

Treatment of arterial thrombosis in the antiphospholipid syndrome

Letter to the editor

Cohen et al provide an overview of the diagnosis and management of
the antiphospholipid Syndrome(APS)[1] and focus briefly on the treatment
of arterial thrombosis in patients with APS. While the treatment of a
first unprovoked venous thrombosis in the setting of persistent
antiphospholipid antibodies agreeably is long term anticoagulation at a
target INR range between 2-3, treatment of arterial thrombosis however,
has notoriously been more controversial due to lack of prospective studies
in this group. We advocate that patients with arterial thrombosis be
anticoagulated at a higher intensity long term to maintain an INR range
between 3-4.

Most of the basis of the recommendations for treatment with higher
intensity warfarin in patients with arterial events associated with
antiphospholipid antibodies comes from retrospective reviews of patient
cohorts[2-4]. These studies all come to similar conclusions – that higher
intensity warfarin is superior to standard treatment. A recent systematic
review of secondary thromboprophylaxis in patients with antiphospholipid
antibodies showed patients with arterial thrombosis treated with
higher intensity warfarin(target INR range 3-4)rarely experience recurrent
events [5]. Bleeding rates
appear to be similar in patients on higher intensity warfarin in
comparison to standard treatment[5].

There are only 2 prospective studies of higher intensity warfarin in
patients with APS and these studies have many limitations. In the APASS
study, patients with cerebral arterial events and antiphospholipid
antibodies were randomised to warfarin versus aspirin which concluded
recurrent events and bleeding episodes were similar in both
groups[6].Patients recruited to this study were only tested on one
occasion for antiphospholipid antibodies therefore did not fulfil the
criteria for APS, and patients on higher intensity warfarin had a
subtherapeutic INR for 41% of the time. The other prospective study in
patients with antiphospholipid syndrome and recurrent
thrombosis(WARSS study) involved randomisation of patients to high
intensity warfarin (INR 3-4) versus standard treatment[7]. This concluded
no difference between higher intensity warfarin and standard treatment yet
most of the patients recruited to the study had only a previous venous
thrombotic event. Unfortunately neither of these studies are of use in
clinical practise for management of patients with APS.

Although there is evidence for the use of aspirin as secondary
thromboprophylaxis in stroke in the general population, there is little
evidence for the use of aspirin alone in patients with a previous arterial
event and APS. The APASS study is the only study in this setting and has
limitations for the reasons discussed above. In particular, some recommend
aspirin in the setting of non cardio-embolic cerebral thrombosis. Again,
there is little evidence for this and eliminating a cardiac source of
cerebral thrombosis can prove particularly difficult since current
diagnostic tests have limited

Treatment of arterial events in patients with APS continues to be a
controversial subject and more
prospective studies are definitely required, but for now, we recommend
treatment with higher intensity anticoagulation in patients with APS and
a previous arterial event.


1.Cohen, D., et al., Diagnosis and management of the antiphospholipid
syndrome. BMJ.340:c2541.

2.Khamashta, M.A., et al., The management of thrombosis in the
antiphospholipid-antibody syndrome. N Engl J Med, 1995.332:993-7.

3.Ruiz-Irastorza, G., et al., Bleeding and recurrent thrombosis in
definite antiphospholipid syndrome: analysis of a series of 66 patients
treated with oral anticoagulation to a target international normalized
ratio of 3.5. Arch Intern Med, 2002. 162:1164-9.

4.Rosove, M.H. and P.M. Brewer, Antiphospholipid thrombosis: clinical
course after the first thrombotic event in 70 patients. Ann Intern Med,
1992. 117:303-8.

5.Ruiz-Irastorza, G., B.J. Hunt, and M.A. Khamashta, A systematic review
of secondary thromboprophylaxis in patients with antiphospholipid
antibodies. Arthritis Rheum, 2007. 57:1487-95.

6.Levine, S.R., et al., Antiphospholipid antibodies and subsequent thrombo
-occlusive events in patients with ischemic stroke. JAMA, 2004. 291:576-

7.Finazzi, G., 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). J Thromb Haemost, 2005. 3:848-53.

Breen KA(1,2), Khamashta M(2), Hunt B.J.(1,2)

Departments of Thrombosis and Haemostasis (1), and Lupus Unit(2),Guys and
St.Thomas’s NHS Foundation Trust, London, UK.

Correspondence to:

Competing interests:
None declared

Competing interests: No competing interests

26 May 2010
Karen A Breen
Clinical Research Fellow in Thombosis
Munther Khamashta, Beverley J. Hunt
Department of Thrombosis and Lupus Unit, Guy's and St.Thomas's NHS Foundation Trust, London, UK