ORs for association of FVL with thrombosis in individual studies range from 1


ORs for association of FVL with thrombosis in individual studies range from 1.5 to 20 with one study obtaining an SB-334867 free base OR of 0.4 (Sasso et. C.I. 1.98-4.20). In the secondary analysis with our individual patient dataset (n=1447 European-derived individuals), SLE subjects with the FVL polymorphism still had more than two times the odds of thrombosis compared to subjects without this polymorphism, even when adjusting for covariates such as gender, age, and aPL status. SLE and/or aPL positive patients with the FVL variant have more than two times the odds of thrombosis compared to those without this polymorphism. strong class=”kwd-title” Keywords: Systemic lupus erythematosus, factor V Leiden polymorphism, thrombosis, risk factors, antiphospholipid antibodies INTRODUCTION Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with diverse clinical manifestations. Some SLE patients develop a malar rash, arthralgias, and characteristic autoantibodies while others experience life-threatening manifestations such as nephritis or thrombosis. A thrombotic event can manifest as a cerebral vascular accident (CVA), deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), retinal vein thrombosis, or recurrent miscarriages. Because a thrombotic event can be devastating, and because treatment is life-long anticoagulation (which itself carries significant bleeding risks), identifying risk factors for thrombosis in SLE patients is crucial to preventing undesirable outcomes. In a large European study, thrombosis was responsible for 27% of SLE mortality1 and significant morbidity. In another ten-year prospective study of SLE patients, thrombosis was the second most frequent cause of death.1 One established risk factor for thrombosis is production of anti-phospholipid antibodies (aPL). These antibodies are a heterogeneous group of immunoglobulins directed against epitopes that result from the interaction of phospholipids and proteins such as annexin V, prothrombin, cardiolipin and ?2glycoprotein. APL are associated with an increased risk of venous and arterial thrombosis but the mechanism of increased risk is not well understood.2 Thirty to forty percent of SLE patients produce these autoantibodies but only 10% of those patients experience HAS3 a thrombotic event.3 This risk factor does not fully explain the increased thrombosis risk in SLE because 40% of SLE thrombosis cases are aPL negative. 4 Other established risk factors for thrombosis include smoking 5, longer disease duration, and older age at SLE diagnosis. 6 A polymorphism in a gene involved in the coagulation cascade – Factor V – may explain part of this increased thrombosis risk in SLE patients. Normally, a balance exists between the factors SB-334867 free base in the clotting cascade which lead to the formation of thrombin and the natural anticoagulants such as activated protein C which help maintain a balance between bleeding and clot formation. Once the clotting cascade is activated, Factor V is one SB-334867 free base in a series of factors whose sequential activation leads to the formation of a cross-linked fibrin clot. The Factor V Leiden (FVL) polymorphism (the risk variant) is a single point mutation resulting in a guanine to adenine substitution at nucleotide position 1691. The presence of this true point mutation confers level of resistance to triggered proteins C, and shifts the total amount towards thrombosis in the clotting cascade as a result. All people with FVL talk about the same FV haplotype, recommending a founder impact.7 FVL includes a five to seven percent prevalence in Europeans and is particularly common (up to 15%) in southern Sweden, Germany, and Cyprus.7 FVL may be the most common inherited risk element for venous thrombosis in the overall population. The FVL variant is situated in 20-60% of (non-SLE) individuals with idiopathic DVT.8 The relative risk for topics heterozygous for DVT and FVL occurrence was 8.1 in the Leiden Thrombophilia Research and 80 for topics homozygous for the polymorphism.9 Many reports have analyzed the association of FVL with thrombosis in SLE, however, most have already been underpowered. Because SLE individuals have an increased occurrence of thrombosis compared to the general human population, actually in the lack of aPL (probably the most founded risk element for thrombosis with SB-334867 free base this human population), the result of the polymorphism in SLE may be unique of in the overall population. Indeed, just 22% of topics with aPL without SLE develop thrombosis, but 70% of individuals with both aPL and SLE develop thrombosis 10, recommending that different systems and.