Researchers have identified an association between plasma complement component C5 level and the risk of developing venous thromboembolism (VTE), based on the results of a new study published in the journal Blood.

“The complement system is an important part of the innate immune system, and several points of intersection between the complement and coagulation systems may potentially contribute to a prothrombotic phenotype upon complement activation,” the researchers explained in their report. They also noted that C5 plays a role in hemostatic processes, and potential downstream effects of C5 cleavage range from erythrocyte lysis to expression of tissue factor in endothelial cells, and others.

The researchers set out to determine whether C5 levels in the plasma are influenced by genetic variation or chronic inflammation. They also aimed to determine whether plasma C5 levels are associated with a risk of future VTE.


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The study was a nested case-control study that included patients with VTE and age- and sex-matched control individuals who were participants of the Tromsø Study based in Tromsø, Norway. Participants’ plasma C5 levels were measured upon inclusion in the study, and C5 levels were grouped into 3 categories for analysis. C-reactive protein (CRP) was also evaluated as an indicator of general inflammation. Whole exome sequencing and protein quantitative trait loci analyses were performed to evaluate any connections between genetic variation and C5 levels.

There were 415 patients with VTE and 848 control individuals evaluated in this study. The researchers found no links between genome-wide or C5-specific gene variants and participants’ C5 levels. A significant linear relationship was seen between plasma CRP levels and C5 levels.

Plasma C5 concentration was associated with VTE risk. In patients with C5 levels above that of the lowest of the 3 tertiles, VTE risk was heightened. For patients with C5 levels in the highest tertile, the sex- and age-adjusted odds ratio for overall VTE risk was 1.45 (95% CI, 1.07-1.96) in comparison with the lowest tertile. For unprovoked VTE, the highest tertile of C5 levels displayed a sex- and age-adjusted odds ratio of 1.70 (95% CI, 1.11-2.60) in comparison with the lowest tertile.

“In conclusion, the results from our nested case‐controls study showed that C5 levels were slightly affected by chronic inflammation, and that medium and high C5 levels were associated with increased risk of future VTE, and unprovoked events in particular,” the researchers wrote in their report. They considered this study to support a connection between complement system components and development of VTE.

Reference

Skjeflo E, Braekkan S, Ludviksen J, et al. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. Published online August 2, 2021. doi:10.1182/blood.2021010822