Antiphospholipids & SLE: A Clinical Overview

Dr. Graham R.V. Hughes, MD FRCP
The Rayne Institute
St. Thomas' Hospital, London.

(Societa' Italiana Di Reumatologia: 35° Congresso Nazional Genova, 25-28 novembre 1998)


A 35 year old woman presents with severe headaches, memory difficulties and occasional slurred speech. She has had 2 spontaneous abortions and a past history in her late teens and early 20s of arthralgia.

Investigations include a positive ANA, positive anti-Ro (and a dry Schrimer's test), a strongly positive IgG anticardiolipin (aCL) test and a negative anticoagulant screen. Further investigations include a negative MRI brain scan.

She is in medical difficulties. She has a probable diagnosis - Antiphospholipid (Hughes') Syndrome, associated with Sjogren's and has an even chance of successful treatment. With aspirin? With warfarin? With steroids?

Let us start with imagining, MRI, as it stands, often lets us down in these patients. Often normal in "classical" APS patients with cerebral features, and sometimes abnormal in individuals without clinical problems.

Preliminary studies with SPECT and PET have not increased diagnostic precision as yet in this area.

In practical terms, an abnormal MRI is helpful. It supports a strong clinical impression. The presence of antiphospholipid antibodies is important in the neurological world.

The brain is the most conspicuously affected organ in the APS. APS is the underlying mechanism in up to 30% of strokes in the under 40s (1).

In the clinical example discussed here, the choice of treatment is between aspirin and warfarin (Coumadin). In practical terms, I think the majority decision would favour aspirin. the patient has never suffered an overt thrombosis, the MRI is normal and the headaches may be unrelated to the presence of anticardiolipin antibodies.

However, the evidence is building up to suggest that untreated, the prognosis in this group of patients is grave.

In this 15 years since we described the syndrome (2). and its tendency to arterial (especially the brain) thrombosis, we have become increasingly concerned about the continuing dangers of APS. We recently reviewed a cohort of patients seen 10 years ago in our unit - "the class of 1988". These patients were selected as having positive antibodies tests but without a history of clinical thrombosis.

The outcome was sobering. No Less than one half went on to thrombosis (including strokes) - and this in the clinical environment of a teaching hospital unit (3).

Such data lead to the conclusion that possibly in these individuals the benefits of warfarin outweigh the problems.

The study led by Dr. Munther Khamashta and colleagues in the unit showed that over a 10 year period, neither aspirin nor low dose warfarin (INR <3) WERE EFFECTIVE IN PREVENTING FURTHER THROMBOSIS IN APS PATIENTS (4).

Nearly half of the patients in each group suffered recurrences. Only those anticoagulated to an INR of 3 over was re-thrombosis significantly reduced - at a cost. There were a number of bleeds, some major. The study was retrospective and included patients with both venous and arterial thrombosis.

It has been reasonably suggested that possibly those with venous thrombosis could be treated less aggressively and we and others are prospectively studying different anticoagulant régimes.

Clinically, there is an impression that patients stay "true to form" - those with venous thrombosis to onto further venous thrombosis, those with arterial clots develop further arterial clots.

Indeed, it may be said that there are distinct sub-groups with Hughes' Syndrome - those with venous or arterial thrombosis, idiopathic thrombocytopenic purpura, recurrent pregnancy loss - most interesting of all - those with accelerated atheroma.

The race is on to devise laboratory tests to try to distinguish these clinical subsets.

To date, antiphospholipid profile has not distinguished these subsets, neither have antibodies against prothrombin.

However, we have recently found associations between anti-Beta-2 glycoprotein antibodies and possibly with antioxidised LDL antibodies and arterial disease in lupus and secondary antiphospholipid syndrome (5,6).

If confirmed, such observations might begin to make inroads into the differentiation of clinical subjects of the antiphospholipid syndrome.

References

1. Hughes, GRV 1998.
Hughes' Syndrome. The Antiphospholipid Syndrome.
J Royal Coll Physic. Vol 32: No.3, p 260-3.

2. Hughes, GRV 1998.
The history of the antiphospholipid syndrome.
LUPUS 7: p 427-9.

3. Shah NM, Khamashta MA, Atsumi T, Hughes, GRV 1998.
Outcome of patients with anticardiolipin antibodies. A ten year follow up of 52 patients.
LUPUS 7: p 3-6.

4. Khamashta MA, Cuadrado MJ, Mujic F, Taub N, Hunt BJ, Hughes, GRV 1985
The management of thrombosis in the antiphospholipid antibody syndrome.
New Eng J Med. 332: p 993-7.

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