Laboratory Studies
The hallmark result from laboratory tests that defines antiphospholipid syndrome (APS) is the presence of antiphospholipid (aPL) antibodies or abnormalities in phospholipid-dependent tests of coagulation. In addition to the clinical criteria listed in History, at least one of the following laboratory criteria is necessary for the classification of APS:
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Presence of lupus anticoagulant (LA) in plasma on two or more occasions at least 12 weeks apart (see below)
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Presence of moderate to high levels of anticardiolipin (aCL) (IgG or IgM) in serum or plasma (ie, > 40 IgG phospholipid units (GPL)/mL or IgM phospholipid units (MPL)/mL or > 99th percentile) on two or more occasions at least 12 weeks apart
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Presence of moderate to high levels of anti–beta-2 glycoprotein I antibodies (IgG or IgM) in serum or plasma (> 99th percentile) on two or more occasions at least 12 weeks apart
aCL antibodies react primarily to membrane phospholipids, such as cardiolipin and phosphatidylserine. Of the 3 known isotypes of aCL (ie, IgG, IgM, immunoglobulin A [IgA]), IgG correlates most strongly with thrombotic events. Cardiolipin is the dominant antigen used in most serologic tests for syphilis; consequently, these patients may have a false-positive test result for syphilis.
The literature suggests that an abnormal LA finding is the laboratory test result that confers the strongest risk for thrombosis. [8, 21] LA is directed against plasma coagulation molecules. In vitro, this interaction results in the paradoxical prolongation of clotting assays, such as activated partial thromboplastin time (aPTT), kaolin clotting time, and dilute Russell viper venom time (DRVVT). The presence of LA is confirmed by mixing normal platelet-poor plasma with the patient's plasma. If a clotting factor is deficient, the addition of normal plasma corrects the prolonged clotting time. If the clotting time does not normalize during mixing studies, an inhibitor is present; the absence of a specific clotting factor inhibitor confirms that a LA is present.
Currently, there is much investigation into risk-stratifying patients based on aPL profile, aPL titers, associated autoimmune disease, and other cardiovascular risk factors. "Triple-positive" patients (LA, anti-beta-2 glycoprotein antibodies, AC antibodies) are at highest risk for thrombosis or abnormal pregnancy, and possibly for recurrence. [8] Standardized scoring systems such as the Global Antiphospholipid Syndrome Score (GAPSS) are being developed.
Patients with APS may have one or more abnormal results from these laboratory tests; the following laboratory tests should be considered in a patient suspected of having APS:
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aCL antibodies (IgG, IgM)
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Anti–beta-2 glycoprotein I antibodies (IgG, IgM)
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Activated partial thromboplastin time (aPTT)
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LA tests such as DRVVT (A threshold of approximately 1.6 for the DRVVT ratio has been recommended for helping discriminate APS from non-APS. [22] )
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Serologic test for syphilis (false-positive result)
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CBC count (thrombocytopenia, hemolytic anemia)
A study of 97 pregnancies in women with a past history of APS concluded that aPL antibodiy profiling to determine obstetric risk is best performed during the first trimester of pregnancy. Latino et al reported that risk categorization performed during pregnancy predicted pregnancy outcome more accurately than categorization performed before pregnancy (91.8% vs 82.5%, respectively). [23]
Thrombocytopenia is fairly common in persons with APS (22% at presentation, 30% cumulatively) and is therefore associated with paradoxical thrombosis. However, patients with platelet counts of less than 50,000/µL may have an increased risk of bleeding. Hemolytic anemia has been well described in patients with APS and is associated with the presence of IgM aCL antibodies.
A low antinuclear antibody level may be present and does not necessarily imply coexisting SLE.
Additional antibodies directed against phospholipid/phospholipid-protein complexes for which testing may be useful in selected cases (seronegative APS, because they are not part of the 2006 consensus criteria) include the following [24, 25, 16, 26] :
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IgA aCL
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IgA beta-2 glycoprotein I
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Anti-phosphatidylserine antibodies
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Anti-phosphatidylethanolamine antibodies
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Anti-prothrombin antibodies
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Antibodies against the phosphatidylserine-prothrombin complex
For further information, see Antiphospholipid Antibodies.
Imaging Studies
Imaging studies are helpful for confirming a thrombotic event. Doppler ultrasound studies are recommended for possible detection of DVT. Computed tomography (CT) or magnetic resonance imaging (MRI) scans of the following may be used:
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Brain (for stroke)
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Chest (for pulmonary embolism)
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Abdomen (for Budd-Chiari syndrome)
Two-dimensional echocardiography findings may demonstrate asymptomatic valve thickening, vegetations, or valvular insufficiency. Aortic or mitral insufficiency is the most common valvular defect found in persons with Libman-Sacks endocarditis.
Histologic Findings
Unlike inflammatory autoimmune diseases, histologic studies of skin or other involved tissue reveal a noninflammatory bland thrombosis with no signs of perivascular inflammation or leukocytoclastic vasculitis. Similarly, biopsy samples from affected kidneys demonstrate glomerular and small arterial microthrombi.
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Antiphospholipid syndrome. Livedo reticularis.
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Antiphospholipid syndrome. Arterial thrombosis resulting in ischemia and necrosis of the foot.
