Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (706 page)

   One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ. Thrombosis must be confirmed by objective validated criteria (i.e., unequivocal findings of appropriate imaging studies or histopathology). For histopathologic confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wall.

   
Pregnancy morbidity

a.   One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus.

b.   One or more premature births of a morphologically normal neonate before the 34th week of gestation because of (i) eclampsia or severe preeclampsia defined according to standard definitions or (ii) recognized features of placental insufficiency.

c.   Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.

d.   In studies of populations of patients who have more than one type of pregnancy morbidity, investigators are strongly encouraged to stratify groups of subjects according to a, b, or c above.

   
Laboratory criteria.
(Investigators are strongly advised to classify APS patients in studies into one of the following categories: I, more than one laboratory criteria present [any combination]; IIa, LA present alone; IIb, aCL antibody present alone; IIc, anti-β
₂
glycoprotein-I antibody present alone.)

   LAs present in plasma, on two or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Haemostasis (Scientific Subcommittee on LAs/phospholipid-dependent antibodies).

   ACA of IgG and/or IgM isotype in serum or plasma, present in medium or high titer (i.e., >40 GPL or MPL, or greater than the 99th percentile), on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA.

   Anti-β
₂
glycoprotein-I antibody of IgG and/or IgM isotype in serum or plasma (in titer >99th percentile), present on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA, according to recommended procedures.

   Limitations

   The cardiolipin IgA isotype is usually detected with either IgG or IgM isotypes in patients with APS; however, agreement among patients grouped according to cardiolipin titers for IgA seems lower than those for the other types. In patients with collagen disease, IgA associates with thrombocytopenia, skin ulcers, and vasculitis, indicating a patient subgroup at risk for specific clinical manifestations, and it is highly prevalent in African American patients with SLE. Hence, this isotype appears to identify patient subgroups rather than adding diagnostic power.

   A negative result means only that the cardiolipin antibody class tested (IgG, IgM, and/or IgA) is not present at this time. Because cardiolipin antibodies are the most common of the antiphospholipid antibodies, it is not unusual to find them emerging, temporarily due to an infection or drug, or asymptomatically as a person ages. The low to moderate concentrations of antibody seen in these situations are frequently not significant, but they must be examined in conjunction with a patient’s symptoms and other clinical information.

Suggested Reading

Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).
J Thromb Haemost.
2006;4:295–306.

ANTICOAGULANTS, CIRCULATING
*

   Definition