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Antiphospholipid Antibody Syndrome

Antiphospholipid antibody syndrome is perhaps one of the most confounding immunologic disorders. It's an acquired autoimmune disorder defined by the presence of antibodies against phospholipids. It's characterized by vascular thrombosis and recurrent pregnancy loss.

Primary antiphospholipid antibody syndrome occurs when the syndrome exists in the absence of other major autoimmune disorders such as systemic lupus erythematosus (SLE). Antiphospholipid antibody syndrome is classified as secondary when it occurs in the presence of such a disorder as SLE. One-third of patients with SLE also have antiphospholipid antibodies, and approximately one-third of those with antibodies have clinical signs of antiphospholipid antibody syndrome. Rarely, a patient will have catastrophic antiphospholipid antibody syndrome, or multiorgan system failure resulting from widespread formation of micro thrombi.

Because antiphospholipid antibodies are known to occur more frequently in women, one must be especially alert to the concerns of thromboembolism. Women are more likely to experience periods of higher risk for thromboembolism in their lifetime, such as through hormonal therapy
and pregnancy. Combine these factors with the presence of antiphospholipid antibodies, and the risks increase even more.

Signs and symptoms of Antiphospholipid antibody syndrome

In antiphospholipid antibody syndrome, blood clots can affect any part of the body. Clinical features may include:

  • stroke and transient ischemic attack
  • myocardial infarction
  • kidney disease
  • livedo reticularis (red-blue, netlike mottling of the skin)
  • pulmonary hypertension
  • leg ulcers
  • recurrent spontaneous abortion.

Other features include:

  • labile hypertension
  • migraine
  • epilepsy
  • transverse myelopathy
  • thrombocytopenia
  • valvular heart disease
  • ocular ischemia.

Causes of Antiphospholipid antibody syndrome

The lupus anticoagulant and anticardiolipin antibodies are types of antiphospholipid antibodies that are present in antiphospholipid antibody syndrome. These antibodies target platelets and vascular endothelium, causing thrombosis. The antibodies also block the formation of pro stacyclin, which leads to thrombosis and vasoconstriction.

The mechanism of pregnancy loss and thrombosis in the antiphospholipid antibody syndrome remains unclear, although several theories do exist. The consensus is that thrombosis leading to placental insufficiency is the central mechanism. Placental vessel thrombosis and ischemia, a process that almost certainly starts from the very earliest time in pregnancy and leads to a progressive decrease in fetal circulation, is the most common belief. Early pregnancy loss may also be due to uteroplacental thrombosis and vasoconstriction that results from binding of the innnunogiobulins to both platelet and endothelial membrane phospholipids.

Antiphospholipid antibodies are also considered by some to be cytotoxic to the trophoblast or fetus tissues when passing through the placenta.This mechanism could explain a relationship between antiphospholipid antibodies and neonate thrombocytopenia, congenital heart block, and neonatal lupus syndrome.

Diagnosis

Currently, no single test is available to diagnosis antiphospholipid antibody syndrome. The diagnosis is difficult because a patient may show isolated, transient, or borderline laboratory changes. Testing should include evaluating for the presence of lupus anticoagulant or specified levels of anticardiolipin antibodies, in combination with one or more characteristic clinical events.

Forms of lupus anticoagulant testing include:

  • dilute Russell's viper venom time (dRVVT)
  • partial thromboplastin time (PTT)
  • kaolin clotting time
  • tissue thromboplastin inhibition test
  • hexagonal phase phospholipid
  • textarin/ ecarin test.

The presence of anticardiolipin antibodies is determined by an enzymelinked innnunosorbent assay (ELISA). Antiphospholipid antibody syndrome has been seen mainly with elevated levels of immunoglobulin G. Other laboratory testing may include evaluation of phosphatidylserine and beta2glycoprotein (B2GPI).

Antiphospholipid antibody syndrome treatment

Available studies recommend treatment of acute thrombosis in the same way as thrombosis resulting from other etiologies. This treatment may include anticoagulation with heparin or warfarin. Treatment of asymptomatic patients may be considered for those with SLE, family history of thromboembolism, or significant laboratory abnormalities.

Patients with catastrophic antiphospholipid antibody syndrome may benefit from aggressive treatment with immunosuppression via plasmapheresis and I.V. cyclophosphamide. Immediate supportive therapy is crucial in these patients for resolution of organ failure.

Several investigators have proposed various treatments for the treatment of antiphospholipid antibodysyndrome during pregnancy. Treatment alternatives have included prednisone, aspirin, heparin, immunoglobulins, azathioprine, plasma exchange, and others. These treatments are thought to affect the immune and coagulation systems to counteract the adverse actions of antiphospholipid antibodies. A favored therapeutic option consists of combining antiplatelet therapy (low-dose aspirin) with either immunosuppression (prednisone) or anticoagulation (heparin). Low-dose aspirin therapy is considered safe in pregnancy and generally free of adverse effects, but prednisone and heparin can cause serious maternal complications, such as cataract formation, osteoporosis, bleeding, and peptic ulcer disease. Therefore, demonstration of a measurable benefit of combination therapy is necessary to justify prednisone or heparin administration.

Special considerations

Primary care providers must be aware that antiphospholipid antibody syndrome exists. Screening for antiphospholipid antibodies should be part of the investigation of women with recurrent spontaneous abortions. Awareness of available treatment options and patient education is also critical.

The decision to screen for antiphospholipid antibodies is sometimes difficult as they can be present in the normal population. However, by identifying the patient with this condition, treatment options can be offered to aid in the prevention of a thromboembolic episode or a miscarriage.
PREVENTING RECURRENT FETAL LOSS
According to a recent report, the standard of care for preventing recurrent fetal loss due to antiphos­pholipid antibody syndrome should be low-molecular-weight heparin plus low-dose aspirin. Investigators have found that this combination is substantially more effective than I.V. immunoglobulin and recommend that it be considered a standard therapy.

For women considering hormonal contraceptive use, counseling should be provided to explore other methods that are highly effective and don't carry the risk of thrombosis. For women considering hormone replacement therapy (HRT), the risks of thrombosis versus the benefits of HRT must be assessed.


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