The Antiphospholipid syndrome an often overlooked and under diagnosed condition

The Antiphospholipid (APLS) syndrome/Hughes syndrome is one of the most common acquired causes of a hypercoagulable state with incidences ranging from 1 to 6 % of the general population ². Despite this the average time of diagnosis of this condition is around 3 years and the average number of specialists seen before diagnosis is 2 with a maximum of 19 ³. It is therefore not commonly thought of and rarely investigated.

The APLS is an autoimmune condition which can occur on its own (primary) or in association with other diseases like systemic lupus erythematosus (secondary). It presents with recurrent thrombotic events and pregnancy losses in the in the presence of persistent anticardiolipin antibodies and or lupus anticoagulant antibodies.

The thrombotic events can be either arterial (30%) or venous (70%) and can affect any organ. Between 4 and 14% of venous thromboembolism are APLS related ¹. The mechanism of thrombosis is thought to be initiated by complement in association with auto antibodies with secondary involvement of the coagulation system. It can occur in unusual sites such as the retinal vein, portal vein and dural sinuses. Thrombosis in these sites or in a patient with no risk factors should prompt the search for APLS.

In arterial thrombosis the usual manifestation is the occurrence in young individuals with myocardial infarction, avascular necrosis, strokes, peripheral gangrene and adrenal insufficiency. The commonest site for arterial thrombosis is the brain and in young strokes 46% are due to the APLS ². Other common central nervous system symptoms which are not thrombotic include cognitive dysfunction, dementia, migraine and chorea⁵.

Pregnancy morbidity is the second commonest manifestation and presents with recurrent miscarriages or premature birth secondary to eclampsia. Other common associated presentations include livedo reticularis, thrombocytopenia, valvular heart disease, nephropathy, hypertension and proteinuria.

Once diagnosed the therapy consists of anticoagulation with wafarin. For venous events treatment is lifelong with a target INR of between 2 to 3. In arterial events there are no randomized controlled trials and therapy varies from the use of aspirin to warfarin with a high target INR. In patients with recurrent events on warfarin some may benefit with the use of immunosuppressive therapy ⁴.

The APLS is a condition which is easily diagnosed by antibody testing (anticardiolipin antibodies, lupus anticoagulant and  beta 2 - glycoprotein 1) but requires a high index of suspicion in the appropriate clinical context.

References:

1.) Alonso S JE, Inglada G L, Perez P G. The antiphospholipid syndrome, an update.        An Med Interna 2007 May;24(5): 242-248. 4.

2.) Asherson RA, Cervera R, Piette JC, Shoenfeld Y, eds. The antiphospholipid syndrome. Boca Rajon, FL CRC Press;1996:13-28.

3.) Donnan PT, McDonald MJ. Patients experiences of a diagnosis of Hughes syndrome. Clinical Rheumatology 2009 May; 21: (Epub ahead of print).

4.) Michael D, Lockshin M D. Update on antiphospholipid syndrome. Bulletin of the NYU for Joint Diseases 2008;66(3):195–7.

5.) Pasquali J-L, Poindron V, Martin T.The antiphospholipid syndrome. Best Practice and Research Clinical Rheumatology 2008; 22 (5): 831-845.

Dr A Solomon

Bsc (Med), BSc (Hon), MSc (Med), M.B.ChB. (WITS), F.C.P. (SA), Cert. Rheumatology (SA)

Clinical Head Department of Rheumatology,

Charlotte Maxeke Academic hospital,

Tel: (011) 488 3215

Fax: ( 086) 553 3648

e-mail ahmed.solomon@wits.ac.za