TXA in UGIB

Dr. Farrah Nasrollahi

Editor: Omar Lopez, MS3

Background

GI bleeding is often an intimidating topic for residents especially since the spectrum of stable to unstable can present widely and ambiguously. There are multiple possible sites in the GI tract to bleed from and all present in their own nuanced ways. Knowing how they present and knowing how to manage each individually can reduce the time to diagnosis and initiation of correct treatment of each condition.
Evaluating the practices we utilize in differentiating GI bleeds:
1. Do the diagnostic steps we take change our management?
2. What decisions do we make that change patient centered outcomes the most?
3. What decisions do we make that don’t change outcomes but are done anyway?

Digital Rectal Exam (DRE) Shretha et al.
Retrospective cohort study 2 Arizona ED hospitals
EMR ID GI bleed, looked for documentation of Rectal Exam by ED provider
Examination of the stool color may provide a clue to the location of the bleeding

“TXA for Upper GI bleeding” Raymond Beyda, MD and Davood Johari, MD published in SAEM
Systematic review identified 8 RCT of TXA in 1701 patients with acute upper GI bleeding among pts admitted to the hospital
2 comparisons: TXA VS PLACEBO, TXA VS ANTIULCER THERAPY (cimetidine or lansoprazole)
Compared to placebo, TXA reduced mortality (RR=.6, 95% CI=.42 to .87, ARR=3.5%, NNT=30, moderate quality evidence)
TXA vs antiulcer therapy (cimetidine or lansoprazole) only 2 trials were included and only a small trend toward mortality benefit was found (RR= 0.91, 95% CI 0.50-1.64).
Administration of TXA did not reduce the risk of rebleeding (RR=.72, 95% CI=.5 to 1.03, low quality evidence) or blood transfusion (RR=1.02, 95%, CI=.94 to 1.11, very low quality evidence).

Factors that are predictive of an upper GI source include:
1. 1. 1. A patient-reported history of melena (likelihood ratio [+LR] 5.1-5.9)
    2. Melenic stool on examination (+LR 25), blood or coffee grounds detected during nasogastric lavage (+LR 9.6)
    3. A ratio of blood urea nitrogen to serum creatinine greater than 30 (+LR 7.5) [5].
On the other hand, the presence of blood clots in the stool made an upper GI source less likely (-LR 0.05).
Factors associated with severe bleeding included:
1. red blood detected during nasogastric lavage (+LR 3.1)
2. Tachycardia (+LR 4.9)
3. Hemoglobin level of less than 8 g/dL (+LR 4.5-6.2).
The presence of frankly bloody emesis suggests moderate to severe bleeding that may be ongoing, whereas coffee-ground emesis suggests more limited bleeding.

Acute lower gastrointestinal (GI) bleeding refers to blood loss of recent onset originating from the colon. The causes of acute lower GI bleeding may be grouped into several categories:
1. 1. 1. Anatomic (Diverticulosis),
    2. Vascular (Angiodysplasia)
    3. Ischemic
    4. Radiation-induced
    5. Inflammatory (infectious, inflammatory bowel disease),
    6. Neoplastic.
    7. Therapeutic interventions (polypectomy)
Patients with acute lower gastrointestinal (GI) bleeding typically present with hematochezia, although hematochezia may also be seen in patients with massive upper GI or small bowel bleeding, consider in severe cases. Rarely, patients with right-sided colonic bleeding will present with melena. The bleeding will stop spontaneously in 80 to 85 percent of patients, and the mortality rate is 2 to 4 percent.

Tranexamic acid reduces bleeding by inhibiting fibrinolysis. Based on this mechanism of action, we do not expect any substantial reduction in non-bleeding deaths.
For UGIB patients there is moderate evidence for improved survival with TXA based on a 2014 Cochrane systematic review. However, the review showed no significant difference in bleeding, surgery, or transfusion requirements which is somewhat puzzling given the decrease in mortality that was shown. Currently this Cochrane review showing is the most robust evidence we have and it is only of moderate quality. HALT-IT is a large multi-center prospective randomized-controlled trial in progress looking to assess the impact of TXA on UGIB morbidity and mortality. For LGIB there is no evidence for benefit or harm.
TBD if we will use TXA in the future for GI bleed
1. 1. 1. Current controlled trial: Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial
    2. HALT-IT trial TBD...

Tranexamic acid has a half-life of 2–3 h so 99% will be eliminated within about 2 days of randomisation. Primary outcome will consider early deaths due to bleeding only, defined as those that occur within 5 days of randomisation.
While the trial was underway, accumulating evidence from other large trials of TXA showed no apparent effect on non-bleeding causes of death. This may be because a considerable proportion of deaths are due to non-bleeding causes. This hypothesis is supported by evidence from trials of TXA in trauma and postpartum haemorrhage. Patients with a clear indication (e.g. traumatic haemorrhage) or contraindication (e.g. history of convulsions, thromboembolic disease) for TXA are excluded in the HALT- IT trial

Do a rectal exam to:
1. Figure out the undifferentiated pt
2. Quantify bleeding
3. Characterize bleeding (to help differentiate source of bleeding and subsequent management)
There is mounting evidence regarding TXA and its potential superiority to standard therapy in massive GI bleed and thus far it has not demonstrated harm. If you see a massive unstable GI bleed you can include it safely. However, there are no robust RCTs presently to definitively confirm benefit. Hopefully the HALT-IT trial will further elucidate this issue.