Medicine – Essential Features of Antiphospholipid Antibody Syndrome

Antiphospholipid antibody syndrome (APS) is an acquired autoimmune thrombophilic disorder characterised by the presence of persistent antiphospholipid antibodies together with recurrent arterial or venous thrombosis and/or characteristic pregnancy complications. The syndrome may occur as a primary disorder or in association with another autoimmune disease, particularly systemic lupus erythematosus (SLE). An important feature of APS is the apparent paradox that some antiphospholipid antibodies produce an anticoagulant effect in laboratory tests but promote thrombosis within the body.

1. Antiphospholipid Antibodies

Patients with APS have circulating autoantibodies directed against phospholipid-binding proteins. Clinically important laboratory antibodies include lupus anticoagulant, anticardiolipin IgG or IgM antibodies, and anti-β2-glycoprotein I antibodies. These antibodies interfere with normal phospholipid-dependent coagulation reactions and are responsible for many of the characteristic laboratory and clinical findings of the syndrome.

2. False-Positive VDRL Test

Antiphospholipid antibodies can produce a false-positive Venereal Disease Research Laboratory (VDRL) test for syphilis. The VDRL test uses cardiolipin-containing antigen, and anticardiolipin antibodies present in APS may therefore react with the test despite the absence of syphilis. A positive VDRL result in this setting should consequently be confirmed with an appropriate specific treponemal test.

3. Anticoagulant Effect In Vitro

In laboratory testing, the lupus anticoagulant can interfere with phospholipid-dependent coagulation assays and cause prolongation of the activated partial thromboplastin time (APTT). When a mixing study is performed by adding normal plasma to the patient’s plasma, the prolonged clotting time may fail to correct, suggesting the presence of an inhibitor rather than a simple clotting-factor deficiency.

This produces an important apparent paradox. Although the lupus anticoagulant can prolong clotting tests in vitro, patients are generally not anticoagulated clinically. Instead, these antibodies are associated with an increased tendency to develop thrombosis in vivo.

4. Recurrent Thrombosis In Vivo

The major clinical consequence of APS is a predisposition to recurrent thrombosis. Thrombotic events can involve either the venous or arterial circulation and may affect vessels of different sizes. Recurrent episodes are particularly suggestive when thrombosis occurs in younger patients or in the absence of conventional thrombotic risk factors.

Clinical Features

1. Venous Thrombosis

Venous thromboembolism is one of the most common manifestations of APS. Deep vein thrombosis (DVT) of the lower limbs is particularly characteristic and may present with unilateral leg pain, swelling, warmth, and tenderness. A thrombus may embolise to the pulmonary circulation and cause a pulmonary embolism, resulting in acute breathlessness, chest pain, or haemodynamic compromise.

2. Arterial Thrombosis

APS can also produce arterial thrombosis, potentially affecting the cerebral, coronary, or peripheral circulation. Cerebral arterial thrombosis may result in a stroke (cerebrovascular accident) or transient ischaemic attack, while coronary artery thrombosis can contribute to myocardial infarction. The precise clinical manifestation depends on the artery involved and the degree of vascular obstruction.

3. Recurrent Miscarriage and Pregnancy Complications

Pregnancy morbidity is an important manifestation of APS. Placental vascular thrombosis and abnormal placental function can contribute to recurrent miscarriage, fetal loss, placental insufficiency, fetal growth restriction, and premature delivery. The combination of recurrent pregnancy loss and persistent antiphospholipid antibodies should therefore raise suspicion of obstetric APS.

4. Thrombocytopenia

Patients may develop thrombocytopenia, usually as a result of increased platelet activation and consumption associated with the autoimmune process. The reduction in platelet count is often mild to moderate. Despite the thrombocytopenia, the predominant clinical problem in APS is generally thrombosis rather than spontaneous bleeding.

5. Livedo Reticularis

Livedo reticularis is a vascular skin manifestation that produces a characteristic mottled, violaceous, net-like pattern on the skin. It results from abnormalities in the cutaneous circulation and may provide an external clue to the underlying vascular abnormalities associated with APS.

6. Pulmonary Hypertension

Pulmonary hypertension may occur in patients with APS, particularly as a consequence of recurrent pulmonary thromboembolism or chronic thromboembolic obstruction of the pulmonary vessels. Progressive elevation of pulmonary arterial pressure can produce exertional breathlessness, fatigue, chest discomfort, syncope, and eventually right-sided heart failure.

Key Clinical Concept

Antiphospholipid antibody syndrome is characterised by the important paradox of prolonged phospholipid-dependent clotting tests in vitro but an increased risk of thrombosis in vivo. The major clinical manifestations are recurrent venous or arterial thrombosis and pregnancy morbidity, while associated findings can include thrombocytopenia, livedo reticularis, and pulmonary hypertension.