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  • Persistent antiphospholipid antibodies (lupus anticoagulant test, anticardiolipin [aCL] antibodies, and anti–β2-glycoprotein-I antibodies [aβ2GPI]) measureable in the peripheral blood.

  • Arterial and venous thrombosis affecting the micro- and/or macro-vasculature.

  • Pregnancy morbidity, including pregnancy losses beyond the first trimester.

  • Nonthrombotic manifestations such as thrombocytopenia or cardiac valve disease.

  • Wide spectrum of manifestations including multiple organ thromboses (catastrophic antiphospholipid syndrome).

  • Traditional thrombosis and cardiovascular disease risk factors also contribute to clinical events.

General Considerations

Antiphospholipid syndrome (APS) is defined as thrombosis (venous, arterial, or microvascular) or pregnancy morbidity occurring in individuals with antibodies against phospholipid-binding plasma proteins (antiphospholipid antibodies [aPL]). The most common aPL are anticardiolipin antibodies (aCL), anti–β2 glycoprotein-I antibodies (aβ2GPI), and lupus anticoagulants (LA). APS may be seen in patients with other autoimmune diseases, such as systemic lupus erythematosus (SLE), or in otherwise healthy persons (primary APS).

Livedo racemosa, cardiac valve disease, thrombocytopenia, hemolytic anemia, aPL-associated nephropathy, cognitive dysfunction, and subcortical white-matter changes are recognized as clinically relevant manifestations in aPL-positive patients. Because these manifestations are not currently part of the APS classification criteria, however, they are now generally termed as “noncriteria” manifestations.

The clinical manifestations of aPL-positive patients comprise a spectrum of features (Figure 21–1). aPL-related vascular events range from superficial venous thrombosis to multiple simultaneous organ thromboses (catastrophic APS). In addition, patients may present solely with obstetric morbidity or nonthrombotic manifestations, for example, thrombocytopenia. The presence of aPL positivity in the absence of clinical manifestations characteristic of APS does not equate to an APS diagnosis.

Figure 21–1.

Spectrum of clinical manifestations in persistently antiphospholipid antibody (aPL)–positive individuals.

Suspicion for APS should be raised when individuals of young age develop thromboses that are recurrent or at unusual sites, especially when unprovoked. Unexplained pregnancy morbidity, such as late pregnancy losses, severe preeclampsia, or the HELLP syndrome (Hemolysis, Elevated Liver enzyme levels and Low Platelet count) may also be indicative of APS. Livedo racemosa (Figure 21–2), particularly in young patients with history of vascular or pregnancy events, should alert physicians to the possibility of aPL positivity. Patients with prolonged activated partial thromboplastin time (aPTT) and false-positive screening tests for syphilis (rapid plasma reagin [RPR]; Venereal Disease Research Laboratory [VDRL]) should be screened for aPL in the appropriate clinical setting.

Figure 21–2.

Livedo racemosa in a patient with persistent antiphospholipid antibodies.

The prevalence of aPL in the general population is not well known due to lack of large-scale, population-based studies. In healthy blood donors, positive aCL have been noted in 10% of the samples. At 1 year of follow-up, however, less than 1% of these donors remained positive, and LA assays were negative in all tested donors at ...

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