Thromboembolic disease in vasculitis

Tómasson, Gunnar; Monach, Paul A.; Merkel, Peter A.

doi:10.1097/bor.0b013e32831de4e7

Cited by 81 publications

(68 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies in four distinct AAV patient cohorts have identified an increased incidence of venous thromboembolic events (VTE), which does not seem to be attributable to conventional prothrombotic risk factors. 16,17 Meanwhile, anti-plasminogen antibodies correlated with VTE episodes in PR3-ANCA patients. 3 Although one of the Dutch patients with particularly high titers of anti-plasminogen antibodies had a history of deep venous thrombosis, we do not have comprehensive data on VTE episodes in the cohorts.…”

Section: Discussionmentioning

confidence: 99%

Anti-Plasminogen Antibodies Compromise Fibrinolysis and Associate with Renal Histology in ANCA-Associated Vasculitis

Berden

Nolan

Morris

et al. 2010

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Antibodies recognizing plasminogen, a key component of the fibrinolytic system, associate with venous thrombotic events in PR3-ANCA vasculitis. Here, we investigated the prevalence and function of anti-plasminogen antibodies in independent UK and Dutch cohorts of patients with ANCA-associated vasculitis (AAV). We screened Ig isolated from patients (AAV-IgG) and healthy controls by ELISA. Eighteen of 74 (24%) UK and 10/38 (26%) Dutch patients with AAV had anti-plasminogen antibodies compared with 0/50 and 1/61 (2%) of controls. We detected anti-plasminogen antibodies in both PR3-ANCA-and MPO-ANCA-positive patients. In addition, we identified anti-tissue plasminogen activator (tPA) antibodies in 13/74 (18%) patients, and these antibodies were more common among patients with anti-plasminogen antibodies (P ϭ 0.011). Eighteen of 74 AAV-IgG (but no control IgG) retarded fibrinolysis in vitro, and this associated with anti-plasminogen and/or anti-tPA antibody positivity. Only 4/18 AAV-IgG retarded fibrinolysis without harboring these antibodies; dual-positive samples retarded fibrinolysis to the greatest extent. Patients with anti-plasminogen antibodies had significantly higher percentages of glomeruli with fibrinoid necrosis (P Ͻ 0.05) and cellular crescents (P Ͻ 0.001) and had more severely reduced renal function than patients without these antibodies. In conclusion, anti-plasminogen and anti-tPA antibodies occur in AAV and associate with functional inhibition of fibrinolysis in vitro. Seropositivity for anti-plasminogen antibodies correlates with hallmark renal histologic lesions and reduced renal function. Conceivably, therapies that enhance fibrinolysis might benefit a subset of AAV patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-Plasminogen Antibodies Compromise Fibrinolysis and Associate with Renal Histology in ANCA-Associated Vasculitis

Berden

Nolan

Morris

et al. 2010

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…In fact, several studies have suggested a link between inflammation and thrombosis and were recently reviewed (43). For example, active vasculitis in ANCAassociated vasculitides as well as Behçet's disease is associated with deep venous thrombosis (43). It is believed that disruption of the endothelial layer due to the vasculitic process exposes active tissue factor, which in turn leads to activation of coagulation factors.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, a link between active vascular inflammation and thrombosis in lupus is self-intuitive, and we believe that our patient's lupus flare was probably the trigger for his LAC-mediated thrombosis. In fact, several studies have suggested a link between inflammation and thrombosis and were recently reviewed (43). For example, active vasculitis in ANCAassociated vasculitides as well as Behçet's disease is associated with deep venous thrombosis (43).…”

Section: Discussionmentioning

confidence: 99%

A 26‐year‐old white man with a systemic lupus erythematosus flare and acute multiorgan ischemia: Vasculitis or thrombosis?

Cherian¹,

Duculan²,

Amigues³

et al. 2011

Arthritis Care & Research

View full text Add to dashboard Cite

A 26-year-old white man with a systemic lupus erythematosus (SLE) flare and acute multiorgan ischemia. History of the present illnessThe patient was in his usual state of health until 2 months before admission, when he developed pain and stiffness in his right shoulder, neck, and back after playing softball. His symptoms progressively worsened despite manipulation by a chiropractor, and he developed new pain in his soles. This was diagnosed as plantar fasciitis and he was given a topical steroid injection and a short course of methylprednisolone. This treatment improved his pain, but at its completion, he developed disabling diffuse arthralgias in his shoulders, elbows, knees, and feet, along with fevers, anorexia, and weight loss. Worsening symptoms prompted hospitalization in another institution 3 weeks before admission, where he was febrile up to 103°F and hypertensive (144/100 mm Hg). An extensive evaluation revealed elevated inflammatory markers, including erythrocyte sedimentation rate (ESR; 102 mm/hour), C-reactive protein level (56 mg/liter), positive antinuclear antibodies (ANAs; Ͼ1:640), strongly positive anti-doublestranded DNA (anti-dsDNA) titers, low levels of C4 (9 mg/dl, normal range 16 -38), prolonged prothrombin time (16.2 seconds, normal range 10 -13), prolonged activated partial thromboplastin time (60 seconds, normal range 27-38), and positive lupus anticoagulant (LAC) by dilute Russell's viper venom time. His urine analysis showed proteinuria (0.440 gm protein/gm creatinine), hematuria (11-25 red blood cells [RBCs]/high-power field [hpf]), and pyuria (3-10 white blood cells [WBCs]/hpf). Antibodies to Sm/RNP, Ro/SSA, and La/SSB; anticardiolipin antibodies; antineutrophil cytoplasmic antibodies (ANCAs); and anticyclic citrullinated peptide antibodies were negative, and creatine phosphokinase was normal. An infectious disease evaluation was performed and was negative for all pathogens, including Lyme disease, human immunodeficiency virus, and viral hepatitis. Renal ultrasound and Doppler were performed and were negative for renal pathology and venous thrombosis. He was placed on prednisone 10 mg orally twice daily, losartan 50 mg daily, and aspirin 81 mg daily, and his fevers resolved with some improvement in joint pains. Two weeks before admission, he was evaluated by a rheumatologist who discontinued aspirin in anticipation of a kidney biopsy to rule out lupus nephritis. Laboratory evaluation again revealed persistent proteinuria (2ϩ), hematuria (10 -20 RBCs/hpf), C4 hypocomplementemia (C3 111 mg/dl, C4 9 mg/dl), and strongly positive anti-dsDNA. The patient could not tolerate tapering of prednisone to 15 mg and he stayed at 17.5 mg daily.He presented to our clinic 3 days before admission and his scheduled kidney biopsy. Over the course of the previous week he had developed a few small tender erythematous skin lesions and some skin excoriation on his fingers and palms. He also experienced numbness of his fingertips and bilateral soles for 2 or 3 days. Weight loss of 30 -33 pounds over the cou...

show abstract

“…Endothelial activation and injury are central to the pathogenesis of vasculitides with increased endothelial cell adhesion molecule expression, and a switch to a prothrombotic endothelial phenotype, both contributing to the vascular pathology (Tomasson et al, 2009;Blake et al, 1985). In systemic vasculitis impaired endothelial repair capacity of EPC was addressed and the significant inflammatory milieu could adversely affect EPC function, resulting in defective colony formation, adhesion and ability to integrate into vascular networks.…”

Section: Epcs In Vasculitismentioning

confidence: 99%

Endothelial progenitor cells: Are they displaying a function in autoimmune disorders?

Ferrante

Guggino

Liberto

et al. 2016

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

a b s t r a c tEndothelial Progenitor Cells (EPCs) are bone marrow derived cells able to differentiate in mature endothelial cells (EC) contributing to the generation of new vessels, connecting to fibronectin, and forming colonies and/or colony forming units.Since circulating EPCs can be actively considered part of endothelial damage in several cardiovascular diseases and autoimmune disorders the possibility to have a measure for endothelium damage should be considered of interest to predict the patient out-come. At the same time the EPCs proliferative and regenerative role could be considered for therapeutic applications.

show abstract

Thromboembolic disease in vasculitis

Cited by 81 publications

References 56 publications

Anti-Plasminogen Antibodies Compromise Fibrinolysis and Associate with Renal Histology in ANCA-Associated Vasculitis

Anti-Plasminogen Antibodies Compromise Fibrinolysis and Associate with Renal Histology in ANCA-Associated Vasculitis

A 26‐year‐old white man with a systemic lupus erythematosus flare and acute multiorgan ischemia: Vasculitis or thrombosis?

Endothelial progenitor cells: Are they displaying a function in autoimmune disorders?

Contact Info

Product

Resources

About