By definition, the antiphospholipid syndrome (APS) is present when a patient has persistently positive serological tests for antiphospholipid antibodies (aPL) and there is a history of at least one thrombotic event (any vessel: arterial, venous, large or small), well described pregnancy morbidity (three or more unexplained losses before 10 weeks gestation, at least one unexplained fetal death with normal morphology after 10 weeks gestation and/or at least one premature birth because of severe preeclampsia or placental insufficiency), or both (Miyakis et al. J Thromb Haemost 2006). The APS can occur as a stand-alone disorder (primary APS) or occur in association with another disease (secondary APS, SAPS). Systemic lupus erythematosus (SLE) is the most frequently associated disease in SAPS and APS influences morbidity and mortality in these patients. Presence of aPL also associates with “non-criteria manifestations” like thrombocytopenia, kidney disease, livedo reticularis, giant skin ulcers, heart valve lesions, chorea, transverse myelitis and cognitive dysfunction. Of these, thrombocytopenia is most prevalent. Patients with immune mediated thrombocytopenia and aPL have an increased risk for thrombosis (Kim et al. Br J Haematol 2013). APS-nephropathy is by histopathology a well-defined entity (Nochy et al. JASN 1999) that not infrequently accompanies lupus nephritis (LN). The combination of APS and LN has worse renal outcome than LN alone (Hill et al. JASN 2007). Thrombotic micro-angiopathy and severe intimal hyperplasia correlate with prost-kidney biopsy bleeding (Jordan et al. Arthritis Care Res 2013).
Three serological tests are universally used for identification of aPL. These are coagulation-assay based (lupus anticoagulants) or use ELISA methods (anti-cardiolipin or anti-beta 2 glycoprotein I antibodies of IgG or IgM class). Recent reports suggests that all three assays should be performed simultaneously as triple positive patients seem to have the highest risk to develop thrombotic and obstetric complications (Pengo et al. Thromb Haemost 2005 and 2010; Pengo et al. Blood 2011; Ruffatti et al. Rheumatology 2011). Presence of lupus anticoagulants apparently is the strongest denominator of triple positivity (Lockshin et al. Arthritis Rheumatism 2012) and triple positivity probably refers to to high levels and high avidity of related aPL.
For secondary prophylaxis of venous thrombotic events, vitamin K antagonists are most frequently used. Whether anticoagulation or antithrombotic drugs are to be preferred after a non-embolic cerebral ischemic event is an unresolved question due to lack of adequate studies. Hydroxychloroquine (HCQ) is widely used for treatment in SLE as it has proven efficacy for articular and skin manifestations of disease (Ruiz-Irastorza ARD 2010). The drug has some antithrombotic effects and has been used for thromboprophylaxis after orthopedic surgery (Hansen et al. J Bone Joint Surg Am 1976). Studies of moderate quality that evaluated whether use of HCQ is antithrombotic in SLE patients (with or without aPL) had contradictory results (Mo et al. Rheumatology 2005, Tektonidou et al. Arthritis Rheum 2009, Jung Arthritis Rheum 2010). An international prospective study in which 1000 aPL positive patients with no prior thrombosis will be randomized for standard care plus HCQ or standard care alone is recruiting patients and will, apart from providing solid data on the thrombotic risk in asymptomatic aPL-positive persons, give solid information on the beneficial effects of HCQ in reducing blood clot formation (www.apsaction.org). Results of that study are also important for the management of patients with SLE.
Disclosure of Interest None declared