Antiphospholipid syndrome

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Antiphospholipid syndrome or antiphospholipid antibody syndrome is a disorder of coagulation, and causes thrombosis in both arteries and veins, as well as recurrent miscarriage. It is due to the autoimmune production of antibodies against cell membrane constituents. It is occasionally referred to as Hughes' syndrome after the rheumatologist Dr Graham R.V. Hughes (St Thomas' Hospital, London, UK).

A very rare form is the catastrophic antiphospholipid syndrome, in which there is rapid organ dysfunction and arterial hypertension. It carries a high mortality.

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Signs and symptoms

The presence of antiphospholipid antibodies (APLAs) is suggested by thrombosis (arterial or venous) and recurrent miscarriage (especially in the second trimester, but often earlier). Other common findings, although not part of the classification, are thrombocytopenia (low platelet count) and livedo reticularis (a skin condition). Many patients report headaches.

APLAs occur in the context of a number of diseases, most notably systemic lupus erythematosus (SLE). One can only speak of antiphospolipid syndrome when there are no other symptoms of one of these diseases (e.g. arthritis suggestive of SLE). A number of patients with the syndrome (about 10%) will eventually develop SLE, but most never get signs of this disease.

Laboratory

The diagnosis is often entertained in cases of thrombophilia (recurrent thrombosis) or recurrent miscarriage. Tests that are often run at the same time are a full blood count, liver enzymes and renal function.

Thrombophilia studies consist of:

Screening coagulation studies: APTT, PT and TT.
Further studies for Factor V Leiden variant and the prothrombin mutation, Factor VIII levels, MTHFR mutation.
Levels of protein C, protein S and antithrombin

Antiphospholipid syndrome is tested for in the laboratory by two tests of coagulation. The person will occasionally have a prolonged APTT, that will not be corrected with a 50:50 mixture with normal plasma. This result is known as lupus anticoagulant; further studies can confirm the presence of this antibody (the dillute Russell viper venom time test, DRVVT). A second antibody can be detected with an immunological test; these are the cardiolipin antibodies.

Low platelet count and positivity for antibodies against β₂-glycoprotein may be indicative of the syndrome.

Definition

The diagnosis is made in case of a clinical event (thrombosis or miscarriage after 10 weeks gestation) and positivity of lupus anticoagulant and/or anticardiolipin antibodies 6-8 weeks apart. Other antibodies, although implicated, are not sufficient for the diagnosis.

Pathogenesis

Antiphospholipid syndrome is an autoimmune disease, in which antibodies react against anionic phospholipids on cell membranes. Being an autoimmune disease, it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident.

Treatment

Often, this disease is treated by giving aspirin to inhibit platelet activation, and/or warfarin as an anticoagulant. During pregnancy, heparin is used during because of warfarin's teratogenicity.

Women with recurrent miscarriage are often advised to take aspirin and to start heparin (or low molecular weight heparin) treatment after missing a period. This is the most effective treatment at the moment.