A diagnostic classification of antiphospholipid syndrome was adopted in 1999 and requires at least one laboratory and one clinical manifestation (Table 34–2). The clinical criteria include a vascular occlusion involving veins, arteries, or capillaries in any organ or pregnancy complications including at least three miscarriages before the tenth gestational week, loss of a normal fetus after 10 weeks, or prematurity of a normal fetus (earlier than 34 weeks). The antiphospholipid syndrome may involve one or more organs including the central nervous system, kidney, endocrine, gastrointestinal tract, lungs, skin, and cerebrovascular and cardiovascular systems. Renal manifestations are protean, and include acute renal failure, progressive chronic kidney disease sometimes culminating in kidney failure, cortical necrosis, mild to malignant hypertension, thrombotic microangiopathy, and thrombosis of renal allografts. The syndrome may occur in a “catastrophic” form, defined by involvement of at least three organ systems simultaneously. The kidney is the most frequently affected organ in the catastrophic form involved in 78% of cases, characterized by hypertension, which is often malignant. Dialysis is required in 25% of those with renal involvement. Other end-organ involvement includes pulmonary (66%), central nervous system such as cerebrovascular accidents (56%), cardiac including premature myocardial infarction (50%), and dermatologic (50%). Disseminated intravascular coagulation is uncommon.
The diagnosis requires the presence of an antiphospholipid antibody, including immunoglobulin (Ig)G and/or IgM, anticardiolipin antibody, or lupus anticoagulant. Antibodies to phospholipid binding proteins frequently are present, but are not yet included in the diagnostic classification. Anticardiolipin antibodies are identified by immunoassays that measure pathologic reactivity to anionic phospholipids including the anticardiolipin antibody, antiphospholipid antibody, or false-positive VDRL test. Lupus anticoagulants are identified by abnormalities in coagulation assays including prolonged prothrombin time or partial thromboplastin time, particularly when the latter is not normalized when diluted with normal serum; abnormalities in the kaolin cephalin clotting time or the thromboplastin inhibition test; or abnormal Russel viper venom test. The anticardiolipin antibody or lupus anticoagulant must be detected twice at least 6 weeks apart according to the diagnostic criteria. Thrombocytopenia is frequent in antiphospholipid syndrome. Up to 5% of healthy individuals have circulating anticardiolipin antibodies, and it is unclear how many of these individuals eventually will develop antiphospholipid syndrome. It has been estimated that 12-30% of patients with SLE have anticardiolipin antibodies and 15–34% have evidence of a lupus anticoagulant. As many as 50–70% of these individuals may have an associated clinical event over the course of 20 years of follow-up.