Is there any type of #bloodsubstitute on the market or coming soon?

Tranexamic acid is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken either orally or by injection into a vein. Side effects are rare.

Prothrombin complex concentrate, also known as factor IX complex, is a medication made up of blood clotting factors II, IX, and X. Some versions also contain factor VII. It is used to treat and prevent bleeding in hemophilia B if pure factor IX is not available.

The drug aprotinin, is a small protein bovine pancreatic trypsin inhibitor, or basic trypsin inhibitor of bovine pancreas, which is an antifibrinolytic molecule that inhibits trypsin and related proteolytic enzymes.

Aprotinin reduces the blood loss and transfusion of blood products in children undergoing major surgery. Aprotinin has been associated with severe side effects in adults, and tranexamic acid and aminocaproic acid have been found to be safer alternatives in adults.

The Journal of Arthroplasty recently published a paper entitled “The Efficacy of Combined Use of Intraarticular and Intravenous Tranexamic Acid on Reducing Blood Loss and Transfusion Rate in Total Knee Arthroplasty”. Tranexamic acid (TXA) is an antifibrinolytic drug whose administration during the perioperative period either by intravenous route or topically applied to the surgical field has been shown to reliably reduce blood loss and need for transfusion in patients undergoing total knee arthroplasty (TKA). Although randomized trials and meta-analyses did not show an increase in thromboembolic events, concerns remain about its repeated systemic application. The authors of the study introduced a novel regimen of TXA administration combining a preoperative intravenous bolus followed by local infiltration at the end of surgery with the idea of maximizing drug concentration at the surgical site while minimizing systemic antifibrinolytic effects. The combined dosage regimen appears to be more effective than single dose local application in reducing blood loss and transfusion rate without any complications noted.

Tranexamic acid for the reduction of blood loss in total knee arthroplasty

TKA may be associated with considerable blood loss, and transfusion carries substantial risk of immunologic reaction and disease transmission. Blood transfusion also involves additional cost, therefore a reduction in its use is important. Several methods reportedly reduce postoperative blood loss and avoid homologous blood transfusion with traditional TKA approaches, but it is unclear these reductions apply to a minimally invasive technique.

Tranexamic Acid Reduces Blood Loss and Blood Transfusion after TKA: A Prospective Randomized Controlled Trial

Although prothrombin complex concentrate (PCC) is increasingly used for the treatment of trauma-induced coagulopathy, few studies have investigated the impact and safety of PCC for this indication. The present study was performed to assess PCC for treatment of coagulopathy after blunt liver injury under severe hypothermia. Coagulopathy in 14 anaesthetised pigs was induced by haemodilution. Subsequently, standardised blunt liver injury was induced under severe hypothermia (32.8-33.2°C). Animals were randomised to receive either PCC (35 IU kg⁻¹) or saline (control). Coagulation was assessed over the following 2 hours by thromboelastometry and thrombin generation. Internal organs were examined to determine presence of emboli. The administration of PCC showed a significant reduction in blood loss (p=0.002 vs. controls) and a significant increase in the rate of survival (p=0.022 vs. controls). Plasma thrombin generation in the PCC group increased considerably above baseline levels, with significant increases in peak thrombin levels and endogenous thrombin potential versus controls throughout the follow-up period. In addition, PT decreased significantly in the PCC group versus the control group. However, only slight improvements in thromboelastometry variables were observed. Histology showed an equal degree of liver injury in both groups, and no thromboembolism. In severely hypothermic pigs, the application of PCC corrected trauma-induced coagulopathy and reduced blood loss. Thus, the infusion of PCC might be a reasonable approach to reduce the need for blood cell transfusion in trauma. Furthermore, the impact and safety of PCC application can be monitored through thrombin generation and thromboelastometry under hypothermia.

Prothrombin complex concentrate reduces blood loss and enhances thrombin generation in a pig model with blunt liver injury under severe hypothermia

Prothrombin complex concentrates (PCCs) contain vitamin K-dependent clotting factors (II, VII, IX, and X) and are marketed as 3 or 4 factor-PCC formulations depending on the concentrations of factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but like with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and the individual patient prothrombotic predisposition. PCCs are approved by the US Food and Drug Administration for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and, therefore, can be administered when urgent surgery is required in patients taking warfarin. However, there is growing experience with the off-label use of PCCs to treat patients with surgical coagulopathic bleeding. Despite their increasing use, there are limited prospective data related to the safety, efficacy, and dosing of PCCs for this indication. PCC administration in the perioperative setting may be tailored to the individual patient based on the laboratory and clinical variables, including point-of-care coagulation testing, to balance hemostatic benefits while minimizing the prothrombotic risk. Importantly, in patients with perioperative bleeding, other considerations should include treating additional sources of coagulopathy such as hypofibrinogenemia, thrombocytopenia, and platelet disorders or surgical sources of bleeding. Thromboembolic risk from excessive PCC dosing may be present well into the postoperative period after hemostasis is achieved owing to the relatively long half-life of prothrombin (factor II, 60-72 hours). The integration of PCCs into comprehensive perioperative coagulation treatment algorithms for refractory bleeding is increasingly reported, but further studies are needed to better evaluate the safe and effective administration of these factor concentrates.

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

Prothrombin complex concentrate (PCC) comes from the process of ion-exchange chromatography from the cryoprecipitate supernatant of large plasma pools and after removal of antithrombin and factor XI. This agent’s initial development was for hemophilia; however, with the availability of recombinant replacement factors, it no longer has a use in this setting. It is now used to replace congenital or acquired vitamin-K deficiency warfarin-induced anticoagulant effect, particularly in the emergent setting. The FDA-approved indication is for urgent reversal of acquired coagulation factor deficiency induced by warfarin-induced anticoagulation in patients presenting with major acute bleeding (intracerebral hemorrhage-ICH) or needing urgent invasive surgery or procedure. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of prothrombin complex concentrate, so providers can direct patient therapy in treating conditions for which it is indicated, as part of the interprofessional team.

Prothrombin Complex Concentrate