Antiphospholipid syndrome (APS) is an autoantibody-mediated acquired thrombophilia characterized by recurrent arterial or venous thrombosis and/or pregnancy morbidity. It affects primarily females. APS may occur alone (primary) or in association with other autoimmune diseases, mainly systemic lupus erythematosus (SLE) (secondary). Catastrophic APS (CAPS) is a life-threatening rapidly progressive thromboembolic disease involving simultaneously three or more organs.
The major autoantibodies detected in patients’ sera are directed against phospholipids and/or phospholipid (PL)-binding plasma proteins such as prothrombin and β2 glycoprotein I (β2GPI). PLs are components of the cytoplasmic membrane of all living cells. The antibodies are directed against negatively charged PLs including among others cardiolipin, phosphocholine, and phosphatidylserine. The plasma protein β2GPI is a 43-kDa plasma apolipoprotein, which consists of 326 amino acids arranged in five domains (I through V). Domain V forms a positively charged patch, suitable to interact with negatively charged PLs. In plasma, β2GPI has a circular conformation with domain V binding to and concealing the B cell epitopes lying on domain I. Another group of antibodies termed lupus anticoagulant (LA) prolongs clotting times in vitro, which are not corrected by adding normal plasma (Table 350-1). Patients with APS often possess antibodies recognizing Treponema pallidum PL/cholesterol complexes, detected by Venereal Disease Research Laboratory (VDRL) tests and characterized as biologic false-positive serologic tests for syphilis (BFP-STS).
TABLE 350-1Classification and Nomenclature of Antiphospholipid Antibodies |Favorite Table|Download (.pdf) TABLE 350-1 Classification and Nomenclature of Antiphospholipid Antibodies
|Name ||Assay for Their Detection ||Comments |
|Antibodies against cardiolipin (aCL) ||Enzyme-linked immunosorbent assay (ELISA) using as antigen cardiolipin (CL), a negatively charged phospholipid ||aCL from patients with APS recognize β2GPI existing in the human serum as well as in bovine serum, which is used to block the nonspecific binding sites on the ELISA plate. CL simply stabilizes β2GPI at high concentration on the polystyrene surface. |
|Antibodies against β2GPI (anti-β2GPI) ||ELISA using as antigen affinity purified or recombinant β2GPI in the absence of PL ||Antibodies recognize β2GPI bound in the absence of CL to an oxidized polystyrene surface, where oxygen atoms in the moieties C–O or C=O were introduced by γ-irradiation. |
|Lupus anticoagulant (LA) || |
Activated partial thromboplastin time (aPTT)
Kaolin clotting time (KCT)
Dilute Russel viper venom test (DRVVT)
|Antibodies recognize β2GPI or prothrombin (PT) and elongate aPTT, implying that they interfere with the generation of thrombin by prothrombin. Prolongation of the clotting times is an in vitro phenomenon, and LA induces thromboses in vivo. |
The incidence of APS is estimated to be around 5 cases per 100,000 persons per year. Anti-PL antibodies occur in 1–5% of the general population. Their prevalence increases with age; however, it is questionable whether they are able to induce thrombotic events in elderly individuals. Moreover, one-third of patients with SLE and other autoimmune diseases (Chap. 349) possess these antibodies, ...