Persistent lupus anticoagulant (LAC) positivity in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is associated with higher Vasculitis Damage Index (VDI) scores, according to a restrospective study published in Arthritis Care & Research.
To investigate if the presence of antiphospholipid (aPL) antibodies or a concurrent antiphospholipid syndrome (APS) diagnosis was associated with increased long-term damage in AAV, researchers at Guy’s and St. Thomas’ National Health Service Foundation Trust, London, UK, retrospectively analyzed data from a cohort of patients at a vasculitis clinic who fulfilled the Chapel Hill Consensus Conference definitions for AAV.
“Damage accrual is an important outcome measure in AAV, given the associated morbidity and impact on long-term prognosis and patient quality of life,” the authors stated. ” Although previously reported in AAV patients, the prognostic impact of aPL on long-term damage accrual had not been extensively examined.”
Patients seen at the clinic over a 4-year period were categorized by researchers into two groups: those who carried an AAV diagnosis alone or those who had both an AAV diagnosis and persistently positive aCL or LAC titers, or a diagnosis of APS. Patients classified into the AAV-alone group were permitted to have a history of one positive test for aPL as long as subsequent tests were negative. Patients classified into the AAV diagnosis with aCL/LAC/APS tested positive for aPL on at least 2 separate occasions. APS diagnosis was defined by the Sydney classification criteria.
LAC positivity screening was done according to the dilute Russell’s viper venom time assay, with mixing studies done thereafter as confirmatory tests. Immunoglobulin(Ig)-G and IgM anticardiolipin (aCL) antibodies were quantified using standardized enzyme-linked immunosorbent assays.
The Vasculitis Damage Index (VDI), a validated measurement tool, was used to quantify long-term accumulation of damage. The VDI utilized 64 items categorized by organ system into 11 separate groups. A total of 5 composite VDI scores were assessed, including total VDI score, extent of vasculitis disease based on the number of separate involved systems (system score), number of items consistent with organ failure (critical damage score), items attributable to treatment toxicity (treatment-related damage score), and items relating to major blood vessel damage secondary to disease and/or complications (major vascular damage score).
A total of 122 patients with AAV were analyzed, of which 54% were female (n = 66), 90% were of European ancestry (n = 110), 7% were South Asian (n = 8), 3% were African (n = 4), 29% had eosinophilic granulomatosis with polyangiitis (EGPA,n = 35), 5% had undifferentiated AAV (n = 6), and 1% had microscopic polyangiitis (MPA, n = 1). A total of 42% of study participants were anti-proteinase 3 (PR3)-ANCA positive (n = 51) and 14% were myeloperoxidase(MPO)-ANCA positive (n = 17).
Seventy six patients (66% of those evaluated) were subsequently classified into the AAV-alone group. Mean VDI scores were significantly higher in the combined AAV/aPL group as compared to the AAV-alone group (P < .0001). LAC positivity was present in a higher proportion of AAV/aPL positive patients than those in the AAV-alone group (P < .0001).
Critical damage scores, associated with organ failure, were also higher in AAV/aPL study participants compared to AAV-alone participants (P = .0002). Major vascular damage scores were also significantly higher in AAV/aPL study participants compared to AAV-alone participants (P = .007). Positivity for aCL was not associated with higher VDI score in this group of AAV patients.
Summary and Clinical Applicability
“Given the frequency of aPL positivity noted in our study and the association with long-term damage accrual, particularly with LAC, [performing aPL screening may be worthwhile] in this patient group,” the study authors recommended.
Limitations and Disclosures
While this data suggests that screening for aPL in patients with AAV may have clinical utility, there is currently no recommended course of action as to what to do with a positive screening result. Not every patient with AAV and a single positive aPL or LAC test would benefit from systemic anticoagulation.
This study was also retrospectively designed, and the single center where it was conducted was a tertiary vasculitis referral center.
“A patient with persistently positive aPL, particularly LAC, may merit further consideration, especially if there is evidence of damage accrual, but this decision will depend on the attribution of the damage,” the study authors note.
Jordan N, D’cruz DP. Association of Lupus Anticoagulant With Long-Term Damage Accrual in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken). 2016;68(5):711-5.