Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 54. Antiphospholipid Antibody Syndrome

Antiphospholipid antibodies are antibodies that are directed against negatively charged phospholipids and include lupus anticoagulant and anticardiolipin antibodies. The antiphospholipid antibody syndrome is an autoimmune condition characterized by recurrent arterial or venous thrombosis (or both), thrombocytopenia, and fetal losses, especially stillbirths during the second half of pregnancy. There is a strong association between the presence of the lupus anticoagulant and anticardiolipin antibodies with decidual vasculopathy, placental infarction, fetal growth restriction, early-onset preeclampsia, and recurrent fetal death. Some of these women, like those with lupus, also have a high incidence of venous and arterial thromboses, cerebral thrombosis, hemolytic anemia, thrombocytopenia, and pulmonary hypertension. The syndrome may occur alone (“primary”) or in association with systemic lupus erythematosus or other autoimmune disorders (“secondary”).

Contrary to what its name implies, the lupus anticoagulant is powerfully thrombotic in vivo. Its name is derived from the observation that it prolongs all phospholipid-dependent coagulation tests, including the prothrombin time, partial thromboplastin time, and Russell viper venom time. Tests considered most specific are the dilute Russell viper venom test and the platelet neutralization procedure. There is currently disagreement as to which of these is best for screening; but, if any of the tests are positive after adding normal plasma, the diagnosis is confirmed.

The anticardiolipin antibody is detected serologically using enzyme-linked immunosorbent assays (ELISA). Values are reported in units and expressed as either negative or low, medium, or high positive. They may be of IgG, IgM, and IgA classes, alone or in combination. Most often IgM anticardiolipin antibodies found alone are stimulated by infections or drugs and are innocuous. Approximately 5 percent of all otherwise healthy pregnant patients screened have nonspecific antiphospholipid antibodies in low titers, the same as normal non-pregnant individuals.

DIAGNOSIS

Because only approximately 20 percent of patients with the antiphospholipid antibody syndrome have a positive lupus anticoagulant reaction alone, both the clotting test to identify the lupus anticoagulant and the anticardiolipin ELISA test must be performed. The clinical and laboratory criteria for diagnosis of the antiphospholipid antibody syndrome are summarized in Table 54-1. Shown in Table 54-2 are the indications for laboratory testing for the antiphospholipid syndrome.

TABLE 54-1. Clinical and Laboratory Criteria for the Diagnosis of Antiphospholipid Syndromea

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TABLE 54-2. Indications for Testing for Antiphospholipid Antibodies

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MANAGEMENT

Proposed management for women with antiphospholipid antibodies is summarized in Table 54-3. A number of treatments for women with antiphospholipid antibodies have been evaluated and are thought to counteract the adverse action of these antibodies by affecting both the immune and coagulation systems. The most efficacious therapy is low-dose heparin (7500 to 10,000 units administered subcutaneously, twice daily), given along with low-dose aspirin (60 to 80 mg, once daily). The rationale for heparin therapy is to prevent thrombotic episodes. Heparin therapy is also thought to prevent thrombosis in the decidual–trophoblastic interface of the placenta. However, heparin therapy is associated with a number of complications, which include bleeding, thrombocytopenia, osteopenia, and osteoporosis.

TABLE 54-3. Some Proposed Managements for Women with Antiphospholipid Antibodies

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Low-dose aspirin blocks the conversion of arachidonic acid to thromboxane A2 while allegedly sparing prostacyclin production. This is thought to reduce thromboxane A2, which aggregates platelets and causes vasoconstriction, while sparing prostacyclin, which has the opposite effect. There appear to be no major side effects from low-dose aspirin other than a slight risk of small vessel bleeding during surgical procedures.

Glucocorticoid Steroids

Glucocorticoids are not widely used for treatment of “primary” antiphospholipid antibody syndrome. In cases of “secondary” antiphospholipid antibody syndrome (e.g., lupus erythematosus), the dose of prednisone should be maintained at the lowest effect level to prevent pregnancy flares. Steroid therapy has significant adverse effects, including osteopenia, osteoporosis, and pathological fractures; impaired wound healing; and the induction of gestational and overt diabetes. Azathioprine and cyclosporine do not appear to improve standard therapies. Methotrexate and cyclophosphamide are contraindicated because of teratogenic potential.

Immunoglobulin Therapy

This therapy is used when other first-line therapies have failed, especially when preeclampsia and fetal growth restriction have been associated with these prior failures. Immunoglobulin is administered intravenously in doses of 0.4 g/kg daily for 5 days (total dose of 2 g/kg). This is repeated monthly, or it is given as a single dose of 1 g/kg each month. The drug costs the provider $5000 to $8000 for each 5-day course, and it may cause anaphylactic reactions.

Results with Treatment

Although improved outcomes are reported with some of the preceding treatments, we caution that fetal growth restriction and preeclampsia still are common. Low-dose aspirin and corticosteroid therapy are not universally successful, and some women with lupus and antiphospholipid antibodies have normal pregnancy outcomes without treatment. It has been reported that 72 percent of women with a prior fetal death and antiphospholipid antibody greater than 40 IgG units, have had a recurrent fetal death despite treatment with prednisone or aspirin, or both.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 54, “Connective Tissue Disorders.”