Antiphospholipid Antibody Syndrome
At a Glance
Antiphospholipid antibodies include anticardiolipin antibodies, the lupus anticoagulant, and antibeta-2 glycoprotein 1 antibodies. The current classification criteria for antiphospholipid syndrome include both laboratory criteria and clinical criteria.
The laboratory criteria are the presence of an elevated concentration of antiphospholipid antibodies, which includes a positive test for the lupus anticoagulant, present on 2 or more occasions at least 12 weeks apart. The antiphospholipid antibody tests considered in this analysis are lupus anticoagulant, the anticardiolipin antibody, and the antibeta-2 glycoprotein 1 antibody.
The clinical criteria involving thrombosis are at least 1 episode of arterial, venous, or small vessel thrombosis in any tissue or organ. Superficial vein thrombosis is not included. Clinical criteria involving pregnancy morbidity are 1 or more unexplained death of a morphologically normal fetus at or beyond the 10th week of gestation; 1 or more premature births of a morphologically normal neonate before the 34th week of gestation in a woman with eclampsia or severe preeclampsia or with placental insufficiency; or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation with anatomic and hormonal abnormalities of the mother and paternal and maternal chromosomal causes excluded.
For patients manifesting antiphospholipid syndrome as thrombosis, venous thrombosis is more common than arterial. Venous thrombosis is most common in the calf, whereas arterial thrombosis is most common in the cerebral circulation. Initial bouts of venous thrombosis are typically followed by venous recurrences, and the same is true for arterial thrombotic events. Thus, the site of the first event as venous or arterial can predict with high likelihood the sight of any subsequent thrombotic events.
In patients with systemic lupus, the presence of an antiphospholipid antibody increases the incidence of thromboembolic events 2- to 3-fold. Patients who develop multiple thromboses over days, despite appropriate anticoagulation, and experience adrenal failure, myocardial infarction, stroke, or liver failure may be suffering from catastrophic antiphospholipid syndrome. There are many disease associations with antiphospholipid antibodies. Common associations include thrombosis, obstetrical complications, and thrombocytopenia. Nonthrombotic manifestations of antiphospholipid syndrome include a host of cardiovascular diseases, neurologic disorders, hematologic disorders, renal dysfunction, and cutaneous changes.
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
The lupus anticoagulant is identified from its inhibitory effect on the clotting cascade, which prolongs the partial thromboplastin time (PTT) commonly and the prothrombin time (PT) rarely. Prolongation of the PT can occur if the patient is also deficient in prothrombin (factor II) as a result of neutralizing antiprothrombin antibodies uncommonly present along with the lupus anticoagulant. In this setting, if there is a deficiency of prothrombin significant enough to prolong the PT, the patient may have more of a bleeding risk than a thrombotic risk. The lupus anticoagulant is an anticoagulant only in vitro, but, in the body, it is prothrombotic. Most individuals with the lupus anticoagulant do not have the disease lupus, making the term lupus anticoagulant poorly reflective of a disorder that most often affects patients without lupus and has a procoagulant effect.
Anticardiolipin antibodies are actually antibodies that bind to a protein, called beta-2 glycoprotein 1. It was previously thought that these antibodies bound to the phospholipid known as cardiolipin. These antibodies are identified by detecting their binding to beta-2 glycoprotein 1 in association with cardiolipin. Antibeta-2 glycoprotein 1 antibodies are identified by their binding directly to the antibeta-2 glycoprotein 1 protein. In general, the more antiphospholipid antibody tests that are positive and the greater the positivity of the test, the greater the risk is for thrombosis and for pregnancy complications.
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?
Antiphospholipid antibodies can be detected in the general population with a frequency of 3-5%, with higher percentages in older populations. The antibodies also appear with a much higher incidence in patients with infections or autoimmune disease. Patients with antiphospholipid antibodies may also demonstrate false positive tests for syphilis in the VDRL assay.
A number of mechanisms have been suggested to explain how antiphospholipid antibodies are prothrombotic. This is still a matter of great controversy. In general, patients with antiphospholipid syndrome who develop venous or arterial thrombosis are treated for thrombosis just as patients who suffer thrombosis from other causes. Patients who have antiphospholipid syndrome and wish to become pregnant or who are pregnant are often treated with anticoagulants to limit the risk of fetal loss.
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