Venous thromboembolism (VTE) risk was associated with the plasma level of complement C5, in a recent analysis published in the journal Blood.

“During the past decades, inflammation and coagulation have been shown to be overlapping processes involving many humoral and cellular components of the vasculature,” the study’s investigators explained in their report. The complement system is involved in innate immune activity, and prior research has implicated C5 in venous thrombus formation. However, the importance of C5 to coagulation in the general population, as well as factors influencing C5 levels, have not been well established.

The analysis was based on data from the Tromsø Study, which is a population-based cohort study involving residents of Tromsø, Norway. Information used in this analysis came from 27,158 participants who entered the study in 1994 and 1995 and who were observed until incident VTE, migration, death, or the end of the follow-up period, which was September 1, 2007.

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A total of 415 individuals who developed VTE were compared with 848 age- and sex-matched control individuals in this analysis with a nested case-control study design. Plasma samples had been obtained at inclusion, and they were evaluated for any association between plasma C5 level and future VTE risk. Other plasma parameters were also examined, and whole-exome sequencing and protein quantitative trait loci analyses were also performed. Plasma C5 levels were analyzed both as a continuous variable and as a categorical variable with tertiles of 27 to 52 mg/mL, 52 to 60 mg/mL, and 60 to 118 mg/mL.

Gene variants did not appear to impact plasma C5 levels, but plasma C5 levels appeared correlated with plasma C-reactive protein levels; a linear regression analysis showed an increase in plasma C5 of 2.1 mg/mL for every 1 mg/L increase in plasma C-reactive protein.

Plasma C5 levels appeared linked to VTE risk. Levels of C5 above the lowest tertile were associated with increased VTE risk in an analysis adjusted for age and sex. In this analysis, participants with plasma C5 levels in the highest tertile showed an adjusted odds ratio (OR) for VTE of 1.45 (95% CI, 1.07-1.96), compared with the lowest tertile of plasma C5. For unprovoked VTE, patients in the highest tertile of plasma C5 showed an OR of 1.70 (95% CI, 1.11-2.60), compared with the lowest tertile. Models that were adjusted for body mass index and C-reactive protein showed slightly reduced impacts of plasma C5 on VTE risk estimates.

“In summary, the results of our nested case-control study show 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 study investigators concluded in their report.


Skjeflo EW, Brækkan SK, Ludviksen JK, et al. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. 2021;138(21):2129-2137. doi:10.1182/blood.2021010822