Tranexamic Acid During Upper GI Endoscopic Resection Procedures

Endoscopic resection (ER) is an endoscopic technique used for the removal of sessile or flat neoplasms confined to the superficial layers (mucosa and submucosa) of the gastrointestinal (GI) tract.

This technique is not without risk, and clinically significant intraprocedural bleeding and post-ER bleeding remain the most frequently encountered serious adverse event.

The bleeding rate associated with ER varies for the different regions of the GI tract. This is most probably due to differences in the vascularity within the wall of the GI tract in each region.

Intraprocedural bleeding in the stomach and duodenum is more frequent and may be as high as 11.5% and 19.3%, respectively. Delayed bleeding has been reported at about 5% for these sites.

Management of bleeding is often resource intensive and may necessitate hospitalization, blood transfusion, and repeat intervention. Some techniques, such as soft coagulation with the tip of a snare; epinephrine injection; hemoclip placement or proton-pump inhibitor treatment, are used to decrease the risk of bleeding or treat active bleeding.

Diluted epinephrine, which causes vasoconstriction, is often added to the submucosal injection fluid because of the theoretical benefit of decreasing bleeding. However, epinephrine has a short time-of-action and for long procedures it requires multiple doses to be injected. This can result in systemic effects such as severe hypertension, ventricular tachycardia, and intestinal ischemia, and may also increase postprocedural pain and prolong patient observation after the procedure.

Tranexamic acid (TXA) is a synthetic derivative of lysine that exerts antifibrinolytic effects by inhibition of lysine binding sites on plasminogen molecules and therefore stabilizes the fibrin meshwork produced by secondary hemostasis. TXA was patented by Dr. S. Okamoto in 1957, and it was found to be significantly more potent than a precursor molecule known as epsilon-amino-caproic acid.

During the past few years, TXA has been 'rediscovered' and is currently used in many conditions that are associated with either overt or occult hemorrhage. It is one of the most frequently cited drugs in recent surgical publications involving nearly all surgical specialties.

After the CRASH-2 study which showed that administration of TXA to bleeding trauma patients within 3 hours of injury significantly reduced the risk of death due to bleeding and all-cause mortality without increasing the risk of vascular occlusive events, it has become an important part of trauma management.

It is also widely used in gynecological practice. Early treatment with TXA reduces death due to bleeding in women with post-partum hemorrhage, as well as total blood loss and transfusion requirements in hemorrhage after caesarean delivery. Therefore, TXA has been recommended by the WHO as part of postpartum hemorrhage management.

TXA is also commonly used in orthopedic surgery, either systemically or topically, to reduce excessive bleeding and transfusion requirements.

Other hemorrhagic conditions in which TXA has been shown effective are epistaxis, hemoptysis , endoscopic ear surgery , mastectomy, and hereditary hemorrhagic telangiectasia with bleeding.

Topical use of TXA may be more beneficial than systemic use as it may provide a higher drug concentration on the wound surface with negligible systemic concentrations. Most publications concerning topically administered TXA come from orthopedic literature where instilling TXA as a bolus into the joint reduces bleeding. Recently, a study revealed that intradermal injections of TXA in dermatological surgery reduces bleeding, especially in those on anticoagulant medications.

While TXA is an inhibitor of fibrinolysis, and therefore might theoretically increase the risk of thrombotic vascular events, most studies show no increased risk of thromboembolism. This finding has been consistent with all routes of TXA administration including IV, topical/intra-articular, and other routes.

The most frequently described contraindications to TXA administration include patients with histories of allergic reactions to TXA, seizures, and patients with acute renal failure or chronic kidney disease.

The investigators propose that the use of TXA in the injection gel during ER procedures will be as effective as epinephrine usage in reducing intraprocedural and postprocedural bleeding, while also decreasing the incidence of side effects including abdominal pain.