Repeated episodes of VTE were reported in 10% patients


Repeated episodes of VTE were reported in 10% patients. 2019 (COVID-19) is associated with endothelial injury and NETosis, mechanisms which are in common with AAV. Reports of new-onset AAV following COVID-19 have been described in the literature, and there could be shared mechanisms driving these processes that require further evaluation. strong class=”kwd-title” Keywords: Anti-neutrophil cytoplasmic antibody-associated vasculitis, Antiphospholipid antibodies, Deep vein thrombosis, Embolism and thrombosis, Neutrophil extracellular traps, Vascular endothelium The association of anti-neutrophil cytoplasmic antibody (ANCA) and ANCA-associated vasculitis with thrombosis Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a group of systemic diseases pathogenetically linked by small vessel vasculitis, presenting with myriad clinical features involving the lungs, kidneys, peripheral nerves, and other internal organs [1]. When AAV was first Ntrk2 recognized, they were associated with early mortality in nearly 90% patients [2]. Over the past three decades, the recognition LDC000067 of cyclophosphamide and rituximab as potent therapies for remission induction in AAV has markedly improved the outlook, with long-term survival in nearly 90% patients [2, 3]. Longer survival in patients with AAV has brought into focus the impact of comorbid conditions on these individuals [4, 5]. Increasing attention has focused on the higher risk of venous and arterial thromboses in AAV. The risk of venous thrombotic events [deep venous thrombosis (DVT), pulmonary thromboembolism (PTE)] as well as arterial thrombotic events (ATE) leading on to cardiovascular disease (CVD) or coronary artery disease (CAD) is increased in patients with AAV, summarized in Table ?Table11 [6C11]. These findings have been observed across population-based observational cohorts as well as in patients recruited for participation in clinical trials of AAV. Some studies have reported a greater risk of thrombotic events in those with renal involvement due to AAV [8, 9]. This risk might be driven in part by the loss of anti-thrombotic factors in urine of patients with renal involvement, although this is more common with LDC000067 nephrotic syndrome rather than with the glomerulonephritis usually seen in AAV [12]. While most studies report an increased risk of venous thromboembolism (VTE) during active disease and early on during the course of AAV, studies have reported increased thrombogenic potential in peripheral blood of AAV in remission also [13]. Table 1 Risk of thrombotic events in patients with ANCA vasculitis thead th align=”left” rowspan=”1″ colspan=”1″ Reference number, location /th th align=”left” rowspan=”1″ colspan=”1″ Type of study /th th align=”left” rowspan=”1″ colspan=”1″ n /th th align=”left” rowspan=”1″ colspan=”1″ Key findings /th /thead [6] GermanyRetrospective cohort105- 13 VTE episodes (2 fatal due to PTE)[7] North AmericaPopulation-based cohort58- Over 6.5-year median follow-up, HR (95% CI) for CVD adjusted for age, gender, and time of recruitment to the cohort was 3.15 (1.51C6.57). HR increased when traditional CVD risk factors were adjusted for (HR 4.62, 95% LDC000067 CI 1.87C11.42) – HR for VTE was 3.26 [6.25 for DVT and 1.33 for PTE; increased HR for VTE and PTE not statistically significant]. Highest risk for CVD in the first 2?years following diagnosis [8] USA, NetherlandsClinical trial of rituximab in AAV197- VTE in 8.1% individuals. Occurred early [median 1.5 (range 1C2.75) months following enrollment] – Factors associated with VTE risk on multivariable-adjusted analyses: ? Cardiac involvement (HR 21.84, 95% CI 2.56C185.81) ? Pulmonary hemorrhage (HR 3.91, 95% CI 1.45C10.52) ? Urinary red cell LDC000067 casts (HR 16.46, 95% CI 3.61C75.08) ? Anti-PR3 antibody positive AAV (HR 9.12, 95% CI 1.16C71.84) LDC000067 [9] EuropeClinical trials of AAV by the EUVAS417-VTE in 9.8% – Factors associated with VTE risk on multivariable-adjusted analyses: ? Increasing CRP levels ? Cutaneous or gastrointestinal involvement ? Impaired renal function at baseline [10] UKRetrospective cohort204- Follow-up 1088 person-years – Incidence of ATE of 2.67 [CAD 1.56, stroke 1.1] per 100 person-years and VTE of 1.47 [DVT 0.83, PTE 0.64] per 100 person-years – AAV had 15 times higher risk of CAD, 11 times greater risk of stroke and 20 times greater risk of VTE versus the general population – The risk of vascular thrombotic events was highest in the first year following diagnosis – ATE (but not.