Systematic Literature Review and Meta-analysis of Venous Thromboembolism Events in Systemic Lupus Erythematosus

Abstract

The objective of this work was to conduct a systematic literature review (SLR) and metaanalysis (MA) to evaluate the relative risk (RR) of venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients with systemic lupus erythematosus (SLE) compared with patients without SLE, as well as the absolute risk (AR) (measured by incidence proportion) and incidence rate (IR) of VTE events in patients with SLE. The SLR was conducted using Embase, MEDLINE, and MEDLINE In-Process to identify observational studies evaluating the risk of VTE, DVT, and PE events in adult patients with SLE compared with the general population, published January 2000 to September 2020. Random-effects models were used as the primary approach in the MA. Heterogeneity was assessed on the basis of the I 2 value. Sensitivity analyses were performed to assess the robustness of results to various conditions, and subgroup analysis was performed for the AR of VTE by antiphospholipid status (aPLs) and antiphospholipid syndrome (APS). Of the 50 publications included for data extraction, 44 contained data for consideration in the MA of any one of the measures of interest (RR, AR, or IR) for VTE, DVT, or PE. The pooled RR indicates statistically significantly higher risk of VTE (RR 4.38, 95% confidence interval 2.63-7.29) in patients with SLE compared with the general population. Considerable heterogeneity was present in nearly all MA (I 2 = 75-100%). Moreover, a higher pooled AR of VTE was estimated in patients with SLE with aPLs (n/N = 0.13) and APS (n/N = 0.63) compared with patients with SLE without aPLs/APS (n/N = 0.07). Overall, there was evidence of an increased risk of VTE, DVT, and PE in patients with SLE compared with the general population.

Risiko venöser Thromboembolien bei Autoimmunerkrankungen: Eine umfassende Übersicht

“…Beim sekundären APS erhöht das Vorhandensein von aPL das VTE-Risiko, wie eine große Metaanalyse von 45 Studien bei SLE-Patienten zeigt. Die Untergruppe der aPL-positiven Patienten hatte im Vergleich zu den aPL-negativen Patienten ein erhöhtes absolutes VTE-Risiko [18].…”

“…Zu den klinischen Manifestationen gehören Arthralgien, nicht erosive Polyarthritis, Schmetterlingserythem, hämatologische Anomalien (Anämie, Leukopenie, Thrombozytopenie), neurologische Störungen, Serositis, renale und kardiovaskuläre Beteiligung [57]. Im Hinblick auf Letztere haben SLE-Patienten ein erhöhtes Risiko für kardiovaskuläre Komplikationen, einschließlich VTE [18, 58, 59]. Es sollte auch beachtet werden, dass etwa 40% der Patienten mit SLE aPL haben, aber < 40% von ihnen thrombotische Ereignisse entwickeln [60].…”

“…In einer großen Metaanalyse von 25 Studien wurde eine kumulative VTE-Inzidenz von 7,29% berichtet [27]. Eine kürzlich durchgeführte Metaanalyse zeigte, dass Patienten mit SLE im Vergleich zur Allgemeinbevölkerung ein statistisch signifikant erhöhtes VTE-Risiko haben (RR 4,38), wobei das VTE-Risiko bei jüngeren (< 40 Jahre) SLE-Patienten im Vergleich zu 41- bis 64-Jährigen besonders hoch ist [18]. Darüber hinaus ergab die Subgruppenanalyse ein höheres absolutes Risiko für VTE bei Patienten mit SLE mit aPL und APS im Vergleich zu Patienten mit SLE ohne aPL/APS [18].…”

NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease

“…95 Reduced activity of these DNases, for example, in patients with systemic lupus erythematosus leads to reduced NET degradation and, therefore, contributes towards a higher susceptibility in these patients to form thrombi. [96][97][98] Different studies support the idea that NETs also promote coagulation by preventing fibrin degradation (fibrinolysis). Elastase bound to NETs-DNA backbone degrades plasminogen needed for fibrinolysis and results in a high amount of NE-derived plasminogen fragments in the plasma of septic shock patients.…”

A hypothesis - generating Swedish extended national cross-sectional family study of multimorbidity severity and venous thromboembolism

“…Although the frequency of multimorbidity increases with age, the burden of multimorbidity may be more common in those aged 65 years or younger, and this is especially common in socially deprived neighbourhoods 19. Several NCDs, but not all, included in the multimorbidity study by Barnett et al 14 have been associated with VTE 20–39. For some associations between NCDs and VTE, the associations are bidirectional,36–38 for example, atherosclerotic disease and atrial fibrillation, but for most NCDs, the association with VTE is unidirectional 20–35.…”