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

• 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.

• 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.

• 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.

• 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), and coagulation tests for the lupus anticoagulant.

• The diagnosis of antiphospholipid syndrome is based on consensual (research) criteria, as presented in Table 85–2.

• Vasculitis may cause vascular occlusion in patients with autoimmune diseases.

• The catastrophic antiphospholipid syndrome should be differentiated from thrombotic microangiopathies (including thrombotic thrombocytopenic purpura (see Chaps. 21 and 91), disseminated vasculitis, or disseminated intravascular coagulation (see Chap. 86).

• The "lupus anticoagulant" as the cause of prolongation of the activated partial thromboplastin time should be differentiated from specific coagulation factor deficiencies or other inhibitors by using appropriate laboratory procedures.

• Antiphospholipid antibody levels may be elevated artifactually or because of specific infections, such as syphilis, Lyme disease, HIV, or hepatitis C.

Thrombosis

• Acute thrombosis in the antiphospholipid syndrome is treated the same as thrombosis from any cause.

• Patients with the antiphospholipid syndrome who develop spontaneous thromboembolism should receive long-term, possibly lifelong, oral anticoagulation. Clinical studies have not shown conclusive evidence that a higher intensity of anticoagulant therapy should be maintained.

• Hydroxychloroquine therapy appears to have an antithrombotic effect in patients with the antiphospholipid syndrome and SLE.

• Patients with the catastrophic antiphospholipid syndrome may benefit from treatment with anticoagulants, glucocorticoids, and plasma exchange or intravenous gamma-globulin. There is anecdotal successful experience with rituximab.

• Antiphospholipid antibodies may spontaneously disappear and its presence should be monitored.

Pregnancy Loss

• Pregnant patients who have antiphospholipid antibodies but have no history of clinical problems do not require treatment.

• Women who have antiphospholipid antibodies, and who have spontaneously lost three or more pregnancies should receive aspirin and heparin during the pregnancy and after delivery. For example, one suggested regimen calls for treatment with aspirin (80 mg) daily and unfractionated heparin (5000 U subcutaneously every 12 hours) beginning with diagnosis of the pregnancy and continuing until 1 month prior to the expected delivery date if no complications develop. Unfractionated heparin (5000 U subcutaneously every 12 hours) is then restarted 4 to 6 hours after delivery if bleeding has stopped, and is continued until the patient is fully ambulatory.

• Low-molecular-weight heparin is most probably as effective as unfractionated heparin in this setting and allows for once daily injection.

• Patients who have had systemic thromboembolism should be considered for oral anticoagulation for 6 to 12 weeks after delivery. Breastfeeding is possible if the baby is administered usual vitamin K treatment.