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The antiphospholipid syndrome is defined as a clinical disorder with recurrent arterial and venous thrombotic events, pregnancy wastage and/or thrombocytopenia in the presence of the lupus anticoagulant and/or moderate to high positive anticardiolipin test. Both a primary form, in patients without clinically or serologically evident autoimune disorders, and a secondary form, usually in patients with systemic lupus erythematosus, are recognized. This separation is solely for academical purposes.
B)Pregnancy Loss
Some patients may present with recurrent pregnancy losses often, but not always, in late second or third trimester of gestation. Both preeclampsia and intrauterine growth retardation have been observed concomitantly. Patients who present a history of previous pregnancy loss are subject to a new event more frequently.
C) Nervous System Disorders
Most neurologic abnormalities are consequent to cerebrovascular thrombosis which result in reversible or fixed focal deficit. The neurological manifestations of the patient with antiphospholipid antibody syndrome are much wider transient ischemic attacks, cerebral infarcts and cerebral venous thrombosis. Other neuralgic presentations include epilepsy, transverse myelopathy, Guillain-Barré syndrome and chorea.
D)Other Features
Association of antiphospholipid antibodies with renal vein thrombosis, Addison’s disease, gut ischemia, Budd-Chiari syndrome, thrombocytopenia, autoimune hemolytic anemia, idiopathic thrombocytopenic purpura, cardiac valve abnormalities (insufficiency mitral and aortic) and Libman-Sacks endocarditis have all been described. Dermatologic manifestations are extremely frequent. The most common of them is livedo reticularis while others such as leg ulceration, distal cutaneous ischemia or necrosis, superficial thrombophlebitis, blue-toe syndrome, splinter hemorrhage and porcelain-white scars are also seen.
B)Lupus Anticoagulant (LA) :
The lupus anticoagulant is an immunoglobulin, either IgG or IgM, that prolongs clotting time in vitro because they agglutinate phospholipids present in the plasma thereby preventing their participation as cofactors in coagulation steps. Its in vitro action appears to be the inhibition of the conversion of prothrombin to thrombin.
Since phospholipids are not very antigenic, the true antigen for the lupus anticoagulant antibody probably includes a plasma protein. The heterogeneity of the lupus anticoagulant can therefore be explained by the concept that the lupus anticoagulants are a family of antiphospholipid-plasma antibodies, with subgroups defined by both the phospholipids and plasma protein involved. Accordingly, no lupus anticoagulant test is 100% sensitive. Therefore, the following criteria are required for a positive lupus anticoagulant test: 1-prolonged partial thromboplastin time, Russel Viper Venom time, or Kaolin clotting time; 2-failure to correct the test by mixing patient plasma with normal plasma (suggesting a clotting inhibitor is present); 3-normalization of the test with freeze-thawed platelets, or phospholipids.
C)Anticardiolipin Test (Acl) :
Realizing that cardiolipin was the major antigenic component of the false-positive test for syphilis, a radioimmunoassay was created directed against this phospholipid. Over time, an enzyme-linked assay (ELISA) replaced the radioimmunoassay. Cardiolipin, which is found in the mitocondria is unlikely the antigen against which the antibody reacts in vivo. Nevertheless, because antiphospholipid antibodies cross-react with other negatively charged phospholipids, cardiolipin can serve as a representative antigen in the system.
Anticardiolipin antibody is one of the few autoantibodies that have assays which allows the identification and quantification of specific isotypes (IgG, IgM and IgA).The IgG isotype was the major predictor of thrombosis and pregnancy loss while the IgM class was associated especially with hemolytic anemia in addition to thrombosis. Besides the identification of different isotypes, the antibody titer seems an useful predictor of pathogenicity (even though it is still not clear that quantity of antibody is the best or the only one). The higher-titer of IgG anticardiolipin antibody (>40GPL) correlates strongly with thrombosis and fetal loss. Most patients with antiphospholipid syndrome have medium to high IgG anticardiolipin antibody levels with or without other isotypes.
D)Relationship of the LA and aCL :
Both lupus anticoagulant and anticardiolipin antibody are associated with each of the clinical manifestations of the antiphospholipid syndrome. There are controversy between the relation of aCL and LA, thus the test may be positive for one, negative for other, or positive for all.
The differential diagnosis will vary depending on the clinical manifestations. In cases in which thrombosis is the main presentation, other procoagulation states - such as protein C, protein S or antithrombin III deficiency, malignancy, oral contraceptives, nephrotic syndrome, polycytemia, thrombocitosis, dysfibrinogemia, paroxysmal nocturnal hemoglobinuria, homocystinuria - should be in mind and excluded. In the case of pregnancy loss, other mechanisms may be responsible for the fetal loss. These include fetal chromossomal abnormalities, anatomic anomalies of the maternal reproductive tract and others such as endocrine, infectious, autoimmune, drug induced disorders.
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