Chapter 85: The Antiphospholipid Syndrome (Lupus Anticoagulant and Related Disorders)

INTRODUCTION

• The antiphospholipid syndrome is an acquired thrombotic disorder associated with circulating autoantibodies to anionic phospholipid-protein complexes.

• These antibodies were first detected as inhibitors of the partial thromboplastin time in patients with systemic lupus erythematosus (SLE) and, for this reason, were called "lupus anticoagulant," although this finding is not limited to patients with lupus.

PATHOGENESIS

• The disorder is generally considered to be autoimmune, although a direct causal relationship between antiphospholipid antibodies and thrombosis or pregnancy problems has not been demonstrated.

• The antiphospholipid antibodies found in the syndrome usually react with phospholipid bound to a plasma protein.

• A number of pathogenetic mechanisms have been proposed for the antiphospholipid syndrome, and it is possible that several of these act in concert to cause the disorder.

CLINICAL FEATURES

• Patients usually present with manifestations of thrombosis and/or pregnancy complications or loss.

• The disease usually presents in patients between ages 35 and 45 years. Both sexes are equally susceptible.

• The disorder is considered "secondary antiphospholipid syndrome" if the patient has a recognizable autoimmune disease, or "primary antiphospholipid syndrome" if there is no associated disorder.

• Table 85–1 summarizes the clinical manifestations of the antiphospholipid syndrome.

• The antiphospholipid syndrome should be considered in patients with recurrent thromboses in unusual locations.

• Venous and/or arterial thromboses may occur at any site but are most frequent in the lower extremities.

• Patients with concurrent inherited thrombophilia who develop antiphospholipid antibodies are at increased risk for thrombosis.

• Immune thrombocytopenia, usually of mild to moderate severity, occurs frequently in patients with antiphospholipid syndrome.

• Rarely, patients may develop a catastrophic form of the antiphospholipid syndrome, with severe, widespread vascular occlusions, despite intense anticoagulant treatment, often leading to death.

• Recurrent pregnancy loss occurs often in women with the antiphospholipid syndrome. About one-half of the abortions occur after the first trimester.

• Some patients develop a bleeding disorder because of a concurrent coagulopathy, such as acquired hypoprothrombinemia, or because of acquired inhibitors of factor VIII.

LABORATORY FEATURES

• Diagnosis of the antiphospholipid syndrome requires demonstration of antibodies against phospholipids and/or relevant protein cofactors.

• No single test is sufficient for diagnosis, and usually a panel of tests is used, including assays for antibodies against cardiolipin, phosphatidylserine, and β₂-glycoprotein I (β₂-GPI), ...