Coagulation factor VII (EC 3.4.21.21, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene F7. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa (or blood-coagulation factor VIIa, activated blood coagulation factor VII), which in turn activates factor IX and factor X. Using genetic recombination a recombinant factor VIIa (eptacog alfa) (trade names include NovoSeven) has been approved by the FDA for the control of bleeding in hemophilia. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market. In April 2020, the US FDA approved a new rFVIIa product, eptacog beta (SEVENFACT), the first bypassing agent (BPA) approved in more than 2 decades. As an rFVIIa product, eptacog beta works in a complex with tissue factor to activate factor X to Xa, thereby bypassing FVIII and FIX. The activation of Factor X to Xa initiates the coagulation cascade’s common pathway, leading to clot formation at the site of hemorrhage.
Ongoing trials
There are several ongoing studies testing the feasibility and efficacy of stem cell therapies for single ventricle diseases such as HLHS. These trials focus on what are the most effective stem cells, what is the best timing in the 3-stage repair, and what is the optimal delivery method. Phase IIb trial testing the efficacy of intramyocardial injections umbilical cord blood cells during Stage II (Glenn) repair. Phase I trial testing the efficacy of autologous cord blood cell infusion during Stage 1 (Norwood) repair within two-to-three days of birth. The ELPIS trial is a phase I/IIb open pilot testing the efficacy and safety of intramyocardial donor human mesenchymal stem cell injections in patients during Stage 2 (Glenn) and Stage 3 (Fontan) repairs. Phase I trial testing the efficacy of umbilical cord blood intramyocardial injections during Stage 2 (Glenn) repair. The PERSEUS study is a phase II trial testing the efficacy of intracoronary infusions of cardiac progenitor cells and evaluating function 3-months post-treatment. APOLLON study is a phase III clinical trial testing the efficacy and safety of intracoronary injections of autologous cardiac stem cells during Stage 2 (Glenn) or Stage 3 (Fontan) repair. CHILD Study is a phase I clinical trial testing the feasibility and safety of intramyocardial injections of c-kit+ cells during Stage 2 (Glenn) repair.It is important to keep in mind that patients with HLHS are at increased risk of developing heart failure as adults. It remains unknown if these potential therapies would reduce the future risk of heart failure in these patients.