Venous thrombosis was first reported as a possible manifestation in AAV in 2003 [1
] and there is now evidence from four distinct cohorts of patients from North America and Europe that AAV is associated with an increased incidence of venous thrombosis () [2
] compared with the rates of VTE in the general population [5
] or among individuals with chronic inflammatory diseases [2
Clinical studies on thrombosis in antineutrophil cytoplasmic antibodies-associated vasculitis
In 2005, Merkel et al.
] reported an increased incidence of VTEs in AAV among 180 people with Wegener’s granulomatosis enrolled in the Wegener’s Granulomatosis Etanercept Trial (WGET) in the United States [6
]. All subjects were enrolled during a period of active disease and were assigned to either etanercept or placebo in addition to treatment with glucocorticoids and either cyclophosphamide or methotrexate. Subjects were evaluated every three months, which included determination of disease activity as measured by the Birmingham Vasculitis Activity Score for WG (BVAS/WG) [6
] and full interim medical history. Information on VTEs prior to the study onset was obtained, and there was continuous surveillance for VTEs during the trial [7
]. All VTEs were clinically apparent and confirmed with diagnostic studies. Thirteen individuals had had VTEs prior to enrollment in the trial. Among the 167 individuals without a history of VTE, 16 experienced events during 228 person-years of observation, an incidence of 7.0 VTEs per 100 person-years. The VTEs were either deep venous thrombosis (DVT) of lower extremities or pulmonary embolism. Most VTEs occurred during or closely following periods of active disease. No difference was found in use of acetylsalicylic acid (ASA) or hospitalization length among those who suffered from VTE versus those who did not.
In 2006, Weidner et al.
] retrospectively reviewed all patients who were treated for AAV at a single nephrology clinic (University of Erlangen-Nürnberg, Germany) during a 16-year period. This patient population is different from the WGET cohort as it included patients with microscopic polyangiitis and renal-limited vasculitis; moreover, all patients had kidney involvement. Thirteen of 105 patients had VTEs during the 367.5 person-years of observation, yielding an incidence of 4.3 events per 100 person-years. Twelve of the 13 events occurred during periods of active vasculitis. No patients with VTEs in this cohort were found to have protein C, protein S, or antithrombin deficiencies, antiphospholipid antibodies, the factor V Leiden mutation, or the nephrotic syndrome.
In a report from the Netherlands in 2008, Stassen et al.
] looked at VTE in a cohort of 198 patients with AAV, including Wegener’s granulomatosisG, microscopic polyangiitis, and renal-limited vasculitis. During a median follow-up period of 6.1 years, 25 VTEs occurred in 25 patients, an incidence of 1.8 events per 100 person years. Similar to what was found in the two above-outlined studies, a much higher incidence of VTE (6.7 per 100 person years) was observed during periods of active disease. VTEs were more common among the subset of patients with microscopic polyangiitis and renal-limited vasculitis than among patients with Wegener’s granulomaotsis (24 vs. 7.0%, P
A recent study from France [8
] (so far only published as an abstract) also addressed thrombosis in AAV (Churg Strauss syndrome, Wegener’s granulomatosis and microscopic polyangiitis). These investigators found that 7.6% of 845 patients with AAV had VTEs during a mean follow up of 58 months. Most of the VTEs occurred in close temporal proximity to the time of diagnosis of vasculitis.
The importance of established hypercoagulable risk factors in the development of VTE in AAV remains to be fully determined. The prevalences of antiphospholipid antibodies and common genetic mutations associated with hypercoagulability were recently determined among individuals in the WGET study [9•
]. Although there was a slightly increased prevalence of antiphospholipid antibodies among persons with Wegener’s granulomatosis compared with the general population (confirming prior reports), there was no association found between the presence of anticardiolipin antibodies and VTE. Additionally, the same study reported that the prevalences of mutations in factor V Leiden, prothrombin G20210A, and methylentetrahydrofolate reductase were not different among patients with Wegener’s granulomatosis and VTE compared with rates in the general population [9•
In summary, recent studies from four different cohorts of patients with AAV strongly suggest an increased occurrence of VTE associated with these types of vasculitis and that this increase in thrombosis is tightly associated with vasculitis disease activity.