Antiphospholipid Antibody Syndrome
Clinical Aspects | Lupus Anticoagulants | Lupus Testing Cascade (Interactive) | Anticardiolipin Antibodies | ß2-Glycoprotein I Antibodies
Clinical Aspects
Antiphospholipid (APL) antibodies can be detected in as many as 2% of unselected individuals,17 and they justify special consideration. These antibodies are the most common acquired cause of increased thrombotic risk.4,9-11,18-20 The term "antiphospholipid antibody syndrome" (APS) refers to a spectrum of clinical conditions that is associated with the presence of antiphospholipid antibodies. Both clinical and laboratory features must be present for the diagnosis of APS to be made.19,20 Any one or more of the conditions discussed below can occur in patients with the antiphospholipid antibody syndrome.
- Venous Thrombosis. Antiphospholipid antibody syndrome can be detected in approximately 10% of patients presenting with their first venous thrombosis.18 Studies have shown that at least one thrombotic event occurs in approximately 30% of patients with persistent antiphospholipid antibodies.18 Deep venous thrombosis (DVT) occurs in approximately 40% of individuals with primary APS. The risk is even greater in individuals with other thrombotic risk factors (ie, the second hit) such as pregnancy, prolonged immobilization, or oral contraceptive therapy.18,19
- Arterial Thrombosis. Arterial thrombosis in APS is less common than venous thrombosis but results in greater incidence of morbidity.17 More than 25% of patients with APL have evidence of arterial occlusions.17 Antiphospholipid antibodies can be detected in as many as one-third of patients with strokes prior to the age of 50, and it is observed in 7% to 10% of unselected stroke patients.17 The incidence of stroke in patients with antiphospholipid antibodies increases when other risk factors (such as hypertension, hyperlipidemia, or smoking) are present. Patients with antiphospholipid antibodies also suffer from an increased incidence of cerebral infarcts, severe vascular headaches, transient ischemic attacks, and visual disturbances.11 Arterial thrombotic events are more common in patients with antiphospholipid antibodies secondary to SLE than those with primary antiphospholipid antibodies.10
- Infertility and Complications of Pregnancy. Antiphospholipid antibodies can cause female infertility due to impaired uterine implantation of the embryo.18 In pregnancy, antiphospholipid antibodies are associated with placental-vascular thrombosis that can lead to fetal demise, fetal growth retardation, premature delivery, and neonatal thrombosis. Fetal loss associated with APS typically occurs in the second trimester. Between 5% and 15% of cases of recurrent spontaneous abortion are linked to APS.17
- Thrombocytopenia. Thrombocytopenia is reported in 30% to 50% of patients with primary APS, although this rarely causes bleeding; however, thrombocytopenia is not considered one of the primary diagnostic criteria for APS because it can be found in so many other conditions.18,19 Positive test results for antiphospholipid antibodies are increased in patients with idiopathic thrombocytopenia (ITP).18
- Other Conditions. APS is sometimes associated with symptoms that can include vasculitic rashes, dermal necrosis of digits, livedo reticularis, arthralgias, pulmonary hypertension, chorea, and migraine headaches19,22
- Catastrophic APS. Rarely, patients with antiphospholipid antibodies will suffer from multiple thrombotic occlusions simultaneously in a sometimes fatal condition that is referred to as catastrophic APS.19
Antiphospholipid antibodies can be subclassified into several clinical categories:
Primary antiphospholipid antibodies
- Represents the majority of cases
- Twice as common in women as men17,18
- Occur in individuals that are otherwise healthy with no predisposing conditions
- Often characterized by antibodies to just one phospholipid or protein10
|
Secondary antiphospholipid antibodies
Associated with:
- Systemic lupus erythematosus (SLE), other autoimmune disorders, malignancies
- Observed in approximately 50% of individuals with SLE with same female-to-male incidence ratio of 9:118
- Secondary antiphospholipid antibodies often characterized by antibodies to multiple phospholipids or proteins10
Drug-induced antiphospholipid antibodies
A variety of therapeutic drugs can induce the production of antiphospholipid antibodies
| |
calcium channel blockers |
chlorpromazine |
hydralazine |
| |
hydantoin |
isonazid |
methyldopa |
| |
procainamide |
phenothiazine |
phenytoin |
| |
quinine |
quinidine |
thorazine |
| |
various antibiotics |
|
|
| |
|
| |
Individuals with drug-induced antiphospholipid antibodies that persist after the drug treatment is ended experience an increased risk of thrombosis10 |
| |
|
| Infection-induced antiphospholipid antibodies18 |
| |
- Often observed during the convalescent phase of acute bacterial and viral infections
- Often observed in individuals with syphilis
- Generally not associated with an increased risk of clinical complications
- Usually transient
|
|
Note: Because it is not possible to distinguish infection-induced antiphospholipid antibodies from clinically significant antiphospholipid antibodies, all patients that test positive for antiphospholipid antibodies should be retested after six to eight weeks to rule out transient antibodies.18
Antiphospholipid antibodies can be detected indirectly with tests that are based on their effect on clot-based, in vitro coagulation assays (ie, lupus anticoagulants) or directly by solid-phase immunoassay.4 Due to the heterogeneity of antibodies associated with APS, both clotting and solid-phase immunoassay testing is recommend when APS is suspected.9,20
|
References
|
