Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS or), often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membranephospholipids that provokes blood clots (thrombosis) in both arteries andveins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, or severe preeclampsia. The syndrome occurs due to the autoimmune production of antibodies against phospholipid (aPL), a cell membrane substance. In particular, the disease is characterised by antibodies against cardiolipin (anti-cardiolipin antibodies) and β2 glycoprotein I. The term "primary antiphospholipid syndrome" is used when APS occurs in the absence of any other related disease. APS however also occurs in the context of other autoimmune diseases, such as systemic lupus erythematosus (SLE), in which case the term "secondary antiphospholipid syndrome" is used.
Antiphospholipid syndrome can cause (arterial/venous) blood clots (in any organ system) or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities (blood clot of the deep veins of the legs) and the most common arterial event is stroke. In pregnant women affected by APS, miscarriage can occur prior to 20 week of gestation, while pre-eclampsia is reported to occur after that time. Placental infarctions, early deliveries and stillbirth are also reported in women with APS. In some cases, APS seems to be the leading cause of mental and/or development retardation in the newborn, due to an aPL-induced inhibition of trophoblastdifferentiation. The antiphospholipid syndrome responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.
Other common findings, although not part of the APS classification criteria, are thrombocytopenia (low platelet count), heart valve disease, and livedo reticularis (a skin condition). Some patients report headaches, migraines, and oscillopsia (Oscillopsia is a visual disturbance in which objects in the visual field appear to oscillate). Very few patients with primary APS go on to develop SLE.
Antiphospholipid syndrome is tested for in the laboratory using both liquid phase coagulation assays (lupus anticoagulant) and solid phase ELISA assays (anti-cardiolipin antibodies).
Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus genetic thrombophilia screening can consist of: Further studies for Factor V Leiden variant and the prothrombin mutation, Factor VIII levels, MTHFR mutation. Levels of protein C, free and total protein S, Factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1)
The testing of antibodies to the possible individual targets of aPL such as β2 glycoprotein 1 and antiphosphatidyl serine is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though cardiolipin is not considered an in vivo target for antiphospholipid antibodies. Lupus anticoagulant: This is tested for by using a minimum of two coagulation tests that are phospholipid sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged APTT. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion demonstrating persistent positivity to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc.) being diagnosed as positive.
Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: Factor VIII). This is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact activation pathway factors (Factor VIII, Factor IX, Factor XI and Factor XII). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) where as a specific factor antibody will rarely give a result higher than 10 iu/dl (10%). Monitoring IV anticoagulant therapy by the APTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of Factor Xa by antithrombin in the presence of heparin.
Classification with APS requires evidence of both one or more specific, documented clinical events (either a vascular thrombosis and/or adverse obstetric event) and the confirmed presence of a repeated aPL. The Sapporo APS classification criteria (1998, published in 1999) were replaced by the Sydney criteria in 2006.
1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or direct examination of the fetus) at or beyond the 10th week of gestation and/or 3 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 or at least 1 premature birth of a morphologically normal neonate before the 34th week of gestation due to eclampsia or severe pre-eclampsia according to standard definitions, or recognized features of placental insufficiency plus
Anti-β2 glycoprotein I IgG and/or IgM measured by standardized ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (> the 99th percentile) and/or
Lupus anticoagulant detected on 2 occasions not less than 12 weeks apart according to the guidelines of the International Society of Thrombosis and Hemostasis.
Often, this disease is treated by giving aspirin to inhibit platelet activation, and/or warfarin as an anticoagulant. The goal of the prophylactic treatment is to maintain the patient's INR between 2.0 - 3.0. In refractory cases plasmapheresis may be used.