The frequency of anticardiolipin antibodies and genetic mutations associated with hypercoagulability among patients with Wegener's granulomatosis with and without history of a thrombotic event.
ABSTRACT Venous thrombotic events (VTE), including both deep venous thrombosis and pulmonary emboli, are now recognized as an important complication of Wegener's granulomatosis (WG), but the mechanism(s) of this occurrence is unclear. The frequency of anticardiolipin antibodies (aCL), anti-beta2-glycoprotein antibodies (anti-beta2-GP), and several genetic hypercoagulable factors were examined in a large cohort of patients with WG.
One hundred eighty patients with active WG had serum and DNA samples collected upon entry into a clinical trial. Of the 180 patients, 29 patients had VTE -- 13 before trial entry, 16 during trial. aCL (IgG, IgM, and IgA) and anti-beta2-GP (IgG and IgM) were evaluated in 176 patients. Factor V Leiden (FVL), the prothrombin gene mutation (G20210A, PGM), and methylenetetrahydrofolate reductase (MTHFR) gene mutation were tested in the 29 patients with thrombotic events, and 36 patients without.
aCL occurred with increased frequencies in patients with WG when compared to the general population (1%-5%): 12% had aCL and 3% had anti-beta2-GP. There was no difference in the prevalences of aCL or anti-beta2-GP based on clotting status. The prevalence of the genetic hypercoagulable factors examined in patients with WG was comparable to the reported rates in the general population.
Although the incidence of clinically significant VTE is increased in patients with WG, this increased risk is not explained by increased prevalences of aCL, anti-beta2-GP, FVL, or mutations in PGM or MTHFR. These observations suggest a need to search for new genetic or acquired prothrombotic abnormalities to account for the increased thrombotic event rate in patients with active WG.
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ABSTRACT: BACKGROUND: Pulmonary haemorrhage (PH) is a serious manifestation of systemic vasculitis with high mortality rates yet vasculitis is associated with an increased prevalence of venous thromboembolism (VTE). The concurrent presentation of severe PH and VTE poses a challenge in terms of therapeutic management.METHODS: This is a retrospective case review of the clinical manifestations and response to treatment in vasculitis patients presenting with concurrent pulmonary haemorrhage and VTE (pulmonary embolism and/or deep venous thrombosis).RESULTS: Of 35 patients with severe PH due to systemic vasculitis, 7 (20%) had concurrent VTE. The most common cause was anti-neutrophil cytoplasm antibody-associated vasculitis, followed by anti-glomerular basement membrane disease. Vasculitis responded to conventional therapies and VTE treatment with anticoagulation was uncomplicated in five of six cases. In one case, anticoagulation precipitated the PH and another was not anticoagulated and developed recurrent VTE. All patients survived without further complications after a mean follow-up of 46 months (3-98).CONCLUSIONS: Concurrent VTE occurred in one-fifth of cases with severe PH due to vasculitis. Management of VTE with anticoagulation was effective but led to pulmonary haemorrhage in one patient.Nephrology Dialysis Transplantation 05/2012; DOI:10.1093/ndt/gfs099 · 3.49 Impact Factor
Article: Thrombosis in vasculitis.[Show abstract] [Hide abstract]
ABSTRACT: Thrombo-embolic disease is an increasingly recognised complication of several vasculitides. A common observation is that thrombo-embolic complications coincide with periods of increased vasculitis disease activity, but the mechanism through which this happens is still unknown. Thrombo-embolic disease has been recognised for decades as a significant contributor to the morbidity and mortality of Behçet's disease, and the role of anticoagulation in its management is being minimised in favour of immunosuppression, although evidence from randomised controlled trials is lacking. Ancillary data from a randomised clinical trial and retrospective observational studies have confirmed an association between venous thrombo-embolic disease and vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCAs). An increased cardiovascular risk is now also recognised for vasculitides associated with ANCAs. Thrombosis plays a prominent role in the pathogenesis of thromboangiitis obliterans (Buerger's disease). The association of thrombosis with other vasculitides such as giant-cell arteritis and levamisole-induced vasculopathy is under investigation.Best practice & research. Clinical rheumatology 02/2013; 27(1):57-67. DOI:10.1016/j.berh.2012.12.005 · 3.06 Impact Factor
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ABSTRACT: In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients.Thrombosis Journal 04/2015; 13(1):15. DOI:10.1186/s12959-015-0047-z · 1.31 Impact Factor