Trial Information

Role of Tranexamic Acid for Reducing Blood Loss in Patients Undergoing Major Gastro-intestinal Surgery

Background:

Surgery is one of the major causes of blood loss. Though major blood loss is associated with
cardiovascular procedures, liver transplantation etc, transfusions are frequently required
in major gastrointestinal surgeries such as Whipples Procedure; Liver resections etc.1
Transfusion is associated with numerous risks such as mismatched transfusion, allergic
reactions, transmission of infections, and acute lung injury etc.2 Though transfusion can be
life saving, it is essential to rationalize transfusion whenever possible.

A number of agents have been tried in the past that stabilizes the coagulation system in the
body minimizing blood loss; an ideal agent is yet to be found. Tranexamic acid,
{trans-4-(aminomethyl) cyclohexanecarboxylic acid} is a competitive inhibitor of plasminogen
activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin.3
Tranexamic acid was first approved by the FDA in 1986 as an injection, under the brand name
Cyklokapron®. This agent has been in use for last 40 years in many traumatic conditions with
various successes with waxing and waning of its use. There has been a resurgence of interest
in its use lately as more is known of this molecule. Tranexamic acid has been found to be
very effective in orthopedic surgeries.4,5,6 A Cochrane review on 'antifibrinolytic use for
minimizing perioperative blood transfusion' involving 21 trails of tranexamic acid vs.
control in patients undergoing orthopedic surgery showed significant reduction in blood
transfusion and perioperative blood loss.7 Randomized trial of tranexamic acid done on
cardiac surgery patients as early as 1996 had shown significant reduction of red-cell
transfusion and other blood products.8 CRASH 2 Trial (Clinical Randomization of an
Antifibrinolytic in Significant Haemorrhage) is a large placebo-controlled trial studying
the effects of early administration of a short course of tranexamic acid on death, vascular
occlusive events and blood transfusion in adult trauma patients with significant hemorrhage.
It involved 274 hospitals across 40 countries and started in 2005 and concluded that
tranexamic acid could safely reduce the risk of death in bleeding trauma patients.9
Intraoperative use of low dose tranexamic acid has been observed to be safe and effective in
reducing the rate of perioperative blood transfusions in patients undergoing radical
retropubic prostatectomy.10 It has also been approved by FDA for use in menorrhagia.

Though it is being used in gastrointestinal bleeding and abdominal trauma, it is not
routinely used in major gastrointestinal surgeries. In this context, this study is
undertaken to evaluate the efficacy of tranexamic acid in major gastrointestinal surgeries.

Investigators hypothesize that addition of Tranexamic acid, an antifibrinolytic agent, to
conventional therapy will lead to an improved outcome characterized by lower transfusion
requirements.

Detailed Description:

After informed consent is obtained patients will be randomized to receive either Tranexamic
acid along with the conventional therapy or conventional therapy only. All patients
undergoing major gastrointestinal surgery (involving resection of stomach, pancreas,
esophagus, colon, liver) will be included for the surgery and this will be decided by the
surgeon prior to the surgery. Randomization will be done prior to surgery by the closed
envelope method. Tranexamic acid will be administered in a loading dose of 1 gm
intravenously over 10 minutes, 30minutes before surgery followed by 10mg / kg body weight, 8
hourly for 5 days. Post operative blood requirements and the fluids in the drain will be
monitored along with the HB/PCV level every day for 7 days or until the drains are removed.

Tranexamic acid is an antifibrinolytic agent that has been shown to be associated with
reduced bleeding and transfusion requirement in surgical patients. We would like to
randomize patients to receive either Tranexamic acid in addition to conventional therapy or
the conventional therapy only and monitor outcome. Intraoperative blood requirements are
usually governed by the intraoperative blood loss hence, only post operative blood
transfusions will be taken as the 'Post operative blood requirements' for these patients.
Post operative complications will be assessed according to the Clavien-Dindo Classification
system for surgical complications.11,12,13 Patients will be monitored until discharge and
after 30 days to assess for any complication. Duration of ICU stay, duration of admission
and Mortality will be monitored for both groups of patients.

Requirement for Transfusion will be assessed by the operating surgeon. Patients will be
monitored post operatively with the hemoglobin and PCV level and the drain fluid amount and
nature. Transfusion will be given for ongoing blood loss at the discretion of the operating
surgeon or when hemoglobin level is <8milligram per deciliter hemoglobin or hematocrit value
of less than 24 percent in healthy individual or < 10mg/dl in high risk patients.14
Transfusion of Fresh Frozen Plasma (FFP) and Platelet Rich Plasma (PRP) will be done as
required.

This study should provide us with information about the efficacy of this medicine in
patients undergoing major GI surgery. Data from this trial will provide us information about
utility of pursuing this modality of therapy.