von Willebrand factor propeptide-to-antigen ratio in HIV-infected pregnancy: Evidence of endothelial activation

Background: Endothelial activation has been proposed as a potential mechanism for the increased risk of venous thromboembolism (VTE) in human immunodeficiency virus (HIV)–infected pregnancy. Objectives: To assess the state of endothelial activation in HIV-infected pregnancy by measuring the von Willebrand factor (VWF) propeptide-to-antigen ratio, as an index of acute endothelial activation. Methods: VWF antigen and VWF propeptide were measured in HIV-negative participants (n = 85), HIV-infected virologically suppressed participants, (n = 89) and HIV-infected participants with HIV viral load (VL) of >50 copies/ml (n = 63) in each trimester. Results were correlated with multimer patterns and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) antigen, activity, and antibody levels. Results: VWF propeptide-to-antigen ratio was increased, in the first, second, and third trimester, in the HIV-infected virologically suppressed group (1.7 ± 0.7, 1.7 ± 0.4, 1.6 ± 0.5) and the HIV-infected group with VL > 50 copies/ml (1.9 ± 0.9, 1.7 ± 0.9, 1.6 ± 1.1) compared to the HIV-negative group (1.4 ± 0.6, 1.3 ± 0.4, 1.2 ± 0.3, P <.05). Increased high molecular weight multimers were observed in the HIV-infected groups, despite only a mild reduction in ADAMTS-13 activity compared to the HIV-negative group (P <.001). No correlation was observed between VWF antigen or VWF propeptide and ADAMTS-13 activity. Conclusion: HIV-infected virologically suppressed pregnant participants showed persistent endothelial activation. Future research should focus on whether endothelial activation contributes to the excess risk of pregnancy-related VTE.