A Disintegrin and Metalloprotease with Thrombospondin Motif, Member 13 and Von Willebrand Factor in Relation to the Duality of Pre-eclampsia and HIV- Infection

Normal pregnancy is associated with multiple changes of the coagulation and the fibrinolytic system. In contrast to a non-pregnant state, pregnancy is a hypercoagulable state where the level of vWF increases by 200–375% affecting coagulation activity. Moreover, in this hypercoagulable state of pregnancy, preeclampsia is exacerbated. ADAMTS13 cleaves the bond between Tyr1605 and Met1606 in the A2 domain of vWF, thereby reducing its molecular weight. A deficiency of ADAMTS13 originates from mutations in gene or autoantibodies formed against the protease, leading to defective enzyme production. Von Willebrand protein is critical for hemostasis and thrombosis, promoting thrombus formation by mediating adhesion of platelets and aggregation at high shear stress conditions within the vessel wall. Mutations in vWF disrupts multimer assembly, secretion and/or catabolism thereby influencing bleeding. The release of even small amounts of active ADAMTS13 protease has a profound inhibitory effect on thrombosis and inflammation, making vWF the major regulator of plasma ADAMTS13 concentration. Endothelial activation caused by HIV infection leads to the release of vWF. The SARS-CoV-2 infection promotes circulating proinflammatory cytokines, in-creasing endothelial secretion of ultra large vWF that causes an imbalance in vWF/ADAMTS13. Raised vWF levels corresponds with greater platelet adhesiveness, promoting a thrombotic tendency in stenotic vessels, leading to increased shear stress conditions. Keywords: HIV; Preeclampsia; ADAMTS13; vWF; Pregnancy.