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

Abstract

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.

Dynamics of the blood plasma proteome during hyperacute HIV-1 infection

“…For example, vWF and FN1 were the most significantly elevated proteins during hAHI (at peak viremia) and were both persistently elevated after hAHI. vWF reflects persistent endothelial cell activation due to activation of the inflammation/coagulation pathway, whereas FN1 is involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape 40 . FN1 also binds to HIV-1 gp120, which has been shown to enhance complement interaction and infection of primary CD4+ T-cells 41 .…”

Pregnancy Related Venous Thromboembolism-Associated with HIV Infection and Antiretroviral Therapy

“…38,39 Endothelial signaling pathways are also activated with downstream reduction in nitric oxide synthesis. Other biochemical markers of endothelial injury in HIV, which have 20,40,41 In particular, the release of increased ultra-large VWF multimers, which results in the formation of platelet-VWF thrombi in the microcirculation, has been proposed as one of the possible mechanisms for the increased risk of thrombotic thrombocytopenic purpura like syndrome in HIV. 42,43 The increased large multimers, nonetheless, have not been associated with a significant deficiency in, and/or antibodies directed against, ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) to cause overt pathology.…”