Antiphospholipid Syndrome and Pregnancy Workup

As previously mentioned, the 1999 “international consensus statement for the diagnosis of antiphospholipid syndrome” provided a set of criteria for the diagnosis of APS. These were updated in 2006 to reflect new insights into the disease.

The diagnosis of APS requires that the patient have at least 1 clinical criterion and 1 laboratory criterion. The criteria for laboratory testing, which are consistent with current clinical management guidelines from the American Congress of Obstetricians and Gynecologists (ACOG), include the following ^{[7, 8, 9]} :

• Anticardiolipin antibodies - Anticardiolipin (aCL) IgG or IgM antibodies present at moderate or high levels (ie, >40 GPL or MPL or >99th percentile) in the blood on 2 or more occasions at least 12 weeks apart

• Lupus anticoagulant - LAC detected in the blood on 2 or more occasions at least 12 weeks apart, according to the guidelines of the International Society on Thrombosis and Hemostasis

• Anti-beta₂ -glycoprotein I antibodies IgG or IgM - In titer above the 99th percentile for normal as defined by the laboratory performing the test, on 2 or more occasions at least 12 weeks apart

In a 3-year retrospective analysis by the European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS), the investigators indicated that all relevant laboratory studies should be obtained to avoid false-negative diagnoses and that levels may act as serologic markers for some cases. ^[2]

Imaging studies

Appropriate neurologic or imaging studies should be performed based on clinical findings; ie, a computed tomography (CT) or magnetic resonance imaging (MRI) scan can be carried out in the presence of central nervous system (CNS) symptoms.

Antiphospholipid (aPL) antibodies are detected by conventional and specific solid-phase or enzyme-linked immunoassays. Results are measured as GPL (IgG aCL), MPL (IgM aCL), or aPL (IgA aCL) units and reported in semiquantitative terms such as negative, low positive, medium positive, or high positive.

Systemic lupus erythematosus (SLE) is associated with lower serum complement levels, measured either as total hemolytic complement activity CH50 or as levels of the third and fourth components of complement C3 and C4, respectively. Decreased levels of these are indicative of consumption by immune complexes. However, preeclampsia, however, is associated with an increased serum complement level.

LAC, aCL, anti-b2GPI, and aPS/PT studies

LAC is detected by phospholipid (PL)-dependent clotting assays, without correction with normal plasma. Results are confirmed by demonstrating PL dependency. The activated partial thromboplastin time (aPTT) is prolonged. Sera are screened for anticoagulant activity by mixing them with platelet-pool normal sera and assaying the aPTT. Several laboratory measurements are available for the assessment of LAC.

For aCL or anti-beta₂ -glycoprotein I antibodies, an IgG isotype greater than 12-20 GPL units (medium to high positive) detected in a standardized assay using standard serum calibrators is indicative.

Anti-beta₂ -glycoprotein I IgG or IgM isotype in serum or plasma that is greater than the 99th percentile for a normal population as defined by the laboratory performing the test.

In a study of 230 patients with SLE, Sciascia et al determined that combining tests for LAC, anti-beta₂ -glycoprotein I, and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies provided greater diagnostic accuracy for APS than did other combinations of laboratory tests. The investigators also found that patients in whom all 3 tests were positive were at greater risk for clinical events, such as thrombosis or pregnancy loss, than were patients in whom only 1 or 2 of the tests were positive. ^[10]

Hematologic and serologic characteristics of APS

All studies need to be repeated in at least 12 weeks for confirmation before the diagnosis of APS is appropriate.

Lupus anticoagulant

Prolonged clotting times occur with any of the following:

• aPTT

• Kaolin clotting time

• Dilute Russell viper venom time

• Plasma clotting time

These prolongations should be confirmed with one of the following:

• Mixing studies with normal plasma, clotting time will remain prolonged with LA

• Platelet neutralization test (recommended by some authorities)

Anticardiolipin antibodies

Many aCL antibodies correlate poorly with the clinical manifestations of APS. At present, only IgG and IgM in moderate and high levels are recommended to be used in the diagnosis of APS.

VDRL test

False-positive results from the venereal disease research laboratory (VDRL) test may occur.

As previously mentioned, clinical evidence of glomerulonephritis is found in more than 50% of cases of SLE. Histologically, the following 6 classes of lupus glomerulonephritis have been recognized by the World Health Organization (WHO):

• Class I - Normal glomeruli observed with light microscopy; may show deposits with immunofluorescence or electron microscopy

• Class II - Mesangial lesions

• Class III - Focal proliferative glomerulonephritis

• Class IV - Diffuse proliferative glomerulonephritis

• Class V - Membranous glomerulonephritis

• Class VI - Diffuse glomerular sclerosis