Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (411 page)

   Who Should Be Tested for APS?

Medical patients
: APS occurs either as a primary condition or in the setting of an underlying disease, most commonly systemic lupus erythematosus (SLE), or other connective tissue disorders, infections, or drugs. The deep veins of the lower limbs and the cerebral arterial circulation are the most common thrombotic sites.
Catastrophic APS
develops in a small group of patients and leads to multiorgan failure with a high mortality.

Obstetrical patients
: unexplained fetal death of morphologically normal fetus at or after 10 weeks of gestation; pregnancy loss at or before the 34th week of gestation due to severe preeclampsia, eclampsia, or placental insufficiency; early onset (second or early third trimester) of severe intrauterine growth retardation and premature birth.

LABORATORY EVALUATION

   Laboratory Findings

There is no pathognomonic single test for APS. A panel of tests should be ordered. Typically, one screens for APL with coagulation-based tests to detect the presence of a LA. Anticardiolipin antibodies (ACA) and anti-β2 GP 1 should be done in parallel.

LA
are identified by coagulation-based tests in which the antibodies prolong the clotting time of a PT or PTT. The PT is commonly prolonged, but it may be only borderline prolonged, or even normal. Not all reagents for the PTT assay will demonstrate a prolongation, because many are insensitive to the LA.

Coagulation-based tests for LA:

  1.  PT is used mostly to rule out the effect of oral or other anticoagulants. This is followed by two screening tests.

  2.  PTT using a LA-sensitive PTT reagent.

  3.  PT using a dilute reagent confirms the suspicion of a LA if elongated. If either is prolonged, proceed with a confirmatory test.

  4.  Staclot LA test, this reagent inhibits the LA antibodies by hexagonal phase phospholipid. If a LA is present, the prolonged clotting time in the PT or PTT assay is corrected, and the diagnosis of LA is confirmed.

  5.  A second test, the dilute Russell’s viper venom time (dRVVT) is recommended. This reagent activates clotting factor X. If the dRVVT is prolonged, a LA is suspected. A confirmatory test confirms the presence of LA if the clotting time shortens. 6.
Factor II
level determination is indicated in patients with greatly prolonged PT and/or bleeding manifestations. In these patients, antibodies to factor II may be present.

Immunoassays

   ELISA tests are used for the detection of IgG or IgA ACA. Their usefulness is now being debated.

   Anti-β2 GP 1 ELISA.

   ANA assay may be positive in low titers (1:40 to 1:160) in half the patients with the APS.

   Biologically false-positive serologic test for syphilis.

   
CBC
to assess possible anemia, leukopenia, and especially
thrombocytopenia.

   
Serology for SLE.

   
Renal function
investigation.

   Limitations

The detection of the LA is more difficult (but not impossible) in the presence of heparin or oral anticoagulant therapy.
The laboratory should be notified of anticoagulant therapy
when the assays are ordered.

Suggested Readings

Giannakopoulos B, Krilis SA. Mechanism of disease: the pathogenesis of the antiphospholipid syndrome.
N Engl J Med.
2013;368:1033–1044.

Giannakopoulos B, Passam F, Ioannou Y, et al. How we diagnose the antiphospholipid antibody syndrome.
Blood.
2009;113:985–994.

Rand JH, Wolgast LR. Dos and don’ts in diagnosing antiphospholipid syndrome.
Hematology Am Soc Hematol Educ Program.
2012;2012:455–459.