Figure.

Antiphospholipid Syndrome (APS) Diagnostic Algorithm

1,11-13
Vascular Thrombosis and/or
Pregnancy Morbidity
Clinical
Criteria
Laboratory

Criteria
Pregnancy morbidity defined as at least 1 of the following:
1) 1 unexplained deaths of morphologically normal fetus 10 weeks gestation
2)

1 premature births of morphologically normal fetus <34 weeks gestation, because
of eclampsia, pre-eclampsia, or placental insufficiency
3) 3 consecutive spontaneous abortions before 10
th

week of gestation
Cardiolipin
antibody
negative

2

-GPI
antibody
negative
APS identified
Cardiolipin
antibody
positive

2

-GPI
antibody
positive
IgG and/or
IgM >40
GPL/MPL on
2 tests, 12
wks apart
IgG and/or
IgM >99
th

percentile of
controls on
2 tests, 12
wks apart
IgG and/or
IgM 40
GPL/MPL on
2 tests, 12
wks apart
IgG and/or
IgM 99
th

percentile of
controls on
2 tests, 12
wks apart
Abnormal
LA positive LA negative
Correction No correction
Both PTT-LA and
dRVVT normal
LA negative
LA negative LA negative
Negative
Positive Negative Positive
Abnormal
Lupus anticoagulant (LA) test
(both PTT-LA and dRVVT)
Cardiolipin Antibody
2

-GPI Antibody
PTT-LA dRVVT
Hexagonal
phase confirmation
dRVVT
confirm
dRVVT 1:1
Mixing Study
Repeat LA testing and
confirmation after 12 wks
APS-associated clinical features such as thrombocytopenia, livedo reticularis, and stroke are excluded from the 2006 international
consensus classification criteria to maintain diagnostic specificity.
1

Only one positive test (PTT-LA or dRVVT) is required for LA positivity.
1

The presence of LA is confirmed when the PTT-LA is abnormal and neutralization by hexagonal phase phospholipids is demonstrated.
13

The hexagonal phase confirm test also incorporates a heparin neutralizer and a source of normal plasma (for patients on anticoagulant
therapy such as warfarin), which further improves the specificity for LA. At Quest Diagnostics, a positive dRVVT screen reflexes

to dRVVT
confirm (phospholipid neutralization) which reflexes to a dRVVT mixing study. Repeat testing recommended in the figure is in accordance
with the classification criteria in the 2006 international consensus statement.
1

Positive cardiolipin IgG or 2-GPI IgG tests are associated
with a high risk of APS, while positive cardiolipin IgM or 2-GPI IgM tests are associated with a low APS risk.
4,7

Cardiolipin or 2-GPI IgM
antibodies very rarely occur without IgG antibodies in APS patients.
4,7

If LA, cardiolipin, and 2-GPI antibodies are all negative, APS is
unlikely.
1

Nonfirst-line antiphospholipid antibodies may help identify risk of developing clinical symptoms in symptomatic patients with
negative test results. See text.

PTT-LA indicates the activated partial thromboplastin time assay that is sensitive for lupus anticoagulant
antibodies; and dRVVT, dilute Russells viper venom time assay. References
LA negative
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