Keywords endoscopic treatment - Haemoseal Spray - upper GI bleeding
Introduction
Upper gastrointestinal bleeding (UGIB) is commonly associated with morbidity and mortality
with a worldwide annual incidence of ~40 to 150 per 100,000 and mortality rate of
10%.[1 ] Common causes of UGIB include peptic ulcers, erosive gastritis, portal hypertension,
malignancies, vascular malformations, and Mallory-Weiss syndrome. Endoscopic management
of UGIB includes conventional methods like injection, mechanical and thermal modalities.
European Society of Gastroenterology guidelines recommend a combination of two modalities
for the management of peptic ulcer bleeding. With a combination of modalities, hemostasis
can be achieved in 85 to 95% patients but rebleeding occurs in 5 to 10%.[2 ] Endoscopic therapy of difficult, diffuse, multiple or large lesions, however, remains
a challenge. We report our single-center experience with Haemoseal Spray (HS) in patients
with UGIB over a 5-year period.
Patients and Methods
Records of patients who received HS for endoscopic hemostasis for UGIB at our tertiary
center in North India from January 2013 to June 2018 were studied retrospectively.
Patients with UGIB not controlled with conventional therapy and patients not amenable
to conventional therapy due to diffuse/multiple lesions were included. Conventional
therapy was defined as use of intravenous proton pump inhibitor, and endotherapy with
the use of 1; 10,000 epinephrine or saline injection, application of clip, or Argon
Plasma Coagulation (APC) singly or in combination. Patients with known allergy to
egg (as collagen powder used in the study was prepared from egg cell membrane) or
multiple allergies were excluded from this study. This study was approved by the local
institutional review board.
Primary end-point was clinical success, defined as control of bleeding over 24 hours.
Secondary end-points studied were recurrent bleeding within 7 days, in-hospital mortality,
and complications secondary to HS.
The criteria for recurrent bleeding included recurrence of hematemesis or melena,
development of hemodynamic instability, drop in hemoglobin by 2 g/dL or more, transfusion
requirement of 4 or more units, or presence of bleeding from the treated site at follow-up
endoscopy.
UGI endoscopy was performed with Olympus gastroduodenoscope (GIFH180) within 12 hours
of presentation. Nasogastric tube insertion with gastric lavage and administration
of 20 mg of Metoclopramide or 25 mg of levosulpiride were routinely performed. All
procedures were performed under sedation by using midazolam/fentanyl/propofol administered
by anesthesiologist. During endoscopy, all attempts were made to identify the exact
source of bleeding with flushing and removal of clots where feasible.
In patients with focal lesions, HS was used as salvage therapy when bleeding could
not be controlled with conventional methods outlined above. In patients with multiple
or diffuse lesions, HS was used as primary treatment modality. The HS kit consisted
of an air pump, Haemoseal probe, a 7.5 Fr spray catheter, 230 cm in length (Shaili
Endoscopy, India), and a preloaded collagen cartridge containing 5 g of powder ([Fig. 1 ]). The spray catheter was passed through the working channel of the endoscope. Collagen
powder was applied in short bursts through the spray catheter with an air pump. To
prevent clogging of the HS catheter, care was taken to first dry the channel of the
endoscope by flushing with 100 cc of air and avoiding the contact of catheter tip
with the mucosa.
Fig. 1 Components of Haemoseal Spray (pump with connecting tubes, Haemoseal probe, Fibro
protein in preloaded syringe).
Result
Thirty-eight patients received HS in this study. The median age was 57 (range: 5–87)
years with 27 males and 11 females. In 24 patients, HS was used as monotherapy (patients
not amenable to conventional therapy due to diffuse/multiple lesions), while it was
combined with APC/injection/clip application in 14 (patients not controlled with conventional
therapy, that is, salvage therapy) ([Figs. 2A ]
[B ]). All patients were kept nil by mouth following the procedure and received intravenous
pantoprazole at a dose of 8 mg per hour for 24 hours.
Fig. 2 (A ) Endoscopic image showing diffuse upper gastrointestinal
bleeding. (B ) Endoscopic image of hemostasis after Haemoseal Spray
in diffuse upper gastrointestinal bleeding.
Eighteen patients (47.4%) had underlying gastrointestinal malignancy, 8 patients (21%)
had history of coronary artery disease, 6 patients (15.8%) had history of chronic
liver diseases, 3 patients (7.9%) had chronic kidney disease, and 2 patients (5.2%)
had cerebrovascular disease. Seven patients (18.4%) had history of antiplatelets drug
ingestion either aspirin 75 mg and or clopidogrel 75 mg, two (5.2%) had history of
ingestion of oral anticoagulant warfarin 2 mg, and 4 mg daily and in two patients
(5.2%) there was history of nonsteroidal anti-inflammatory drug intake ([Table 1 ]).
Table 1
Associated comorbidities and use of drugs in patients with upper gastrointestinal
bleeding
Co-morbidities and drug use
n (%)
Coronary artery disease
8 (21)
Chronic liver disease
6 (15.8)
Chronic kidney disease
3 (7.9)
Cerebrovascular disease
2 (5.2)
Antiplatelet drugs
7 (18.4)
Oral anticoagulants
2 (5.2)
Nonsteroidal anti-inflammatory drugs
2 (5.2)
Indications were ulcers or erosions in 22, malignancy in 10, portal hypertensive gastropathy/gastric
antral vascular ectasia in 4, and radiation gastropathy in 2. There were 32 (84%)
inpatients, 5 of whom were admitted to intensive care unit. Among ulcers, 11 patients
had esophageal ulcers, 8 patients had gastric ulcers, and 3 patients had duodenal
ulcers ([Table 2 ]).
Table 2
Causes of upper gastrointestinal bleeding
Etiology of bleeding
No. of patients (%)
Abbreviations: GAVE, gastric antral vascular ectasia; PHG, portal hypertensive gastropathy.
Ulcers
22 (57.9)
Esophagus
Gastroesophageal reflux disease
5 (13.2)
Infective ulcers
3 (7.9)
Post-chemotherapy ulcers
Cameron
1 (2.6)
1 (2.6)
Mallory-Weiss syndrome
1 (2.6)
Stomach
Peptic ulcers
5 (13.2)
Anastomotic ulcers
2 (5.3)
Corrosive poisoning
1 (2.6)
Duodenal
Peptic ulcers
3 (7.9)
Malignancy
10 (26.3)
Gastric carcinoma
4 (10.5)
Gastric lymphoma
2 (5.3)
Local duodenal infiltration
4 (10.5)
Carcinoma gall bladder
2 (5.3)
Hepatocellular carcinoma
1 (2.6)
Periampullary
1 (2.6)
Portal hypertensive gastropathy/GAVE
4 (10.5)
GAVE
3 (7.9)
PHG
1 (2.6)
Radiation gastropathy
2 (5.3)
Clinical success was achieved in 32/38 (84%). All six nonresponders had coagulopathy
related to chemotherapy/bone marrow transplant. Follow-up endoscopy was done within
24 hours in 4 patients and after 24 hours in 2 patients.
Follow-up UGI endoscopy was not routinely performed. Repeat UGI endoscopy for recurrent
bleeding within 7 days was observed in 4 patients (gastric malignancy 2, radiation
gastropathy 2). In-hospital mortality was seen in 8/38 (21%) patients, of whom 2/38
(4.8%) were related to active ongoing GI bleeding ([Table 3 ]). There was no therapy-related complication
Table 3
Causes of mortality
Cause of mortality
No. of patients (%)
Sepsis
2 (5.2)
Bleeding related
2 (5.2)
Acute coronary syndrome
1 (2.6)
Cardiac arrhythmia
1 (2.6)
Aspiration
1 (2.6)
End-stage liver disease
1 (2.6)
Discussion
United States Food and Drug Administration recently approved the use of Hemospray
for the management of GI bleeding. Various hemostatic powders are available for use
during endoscopy, that is, Ankaferd Blood Stopper, Hemospray (TC-325), Endoclot Polysaccharide
Hemostatic System, and HS.[3 ]
[4 ]
[5 ]
[6 ] Hemospray (Cook Medical, Winston-Salem, North Carolina, United States) consists
of an inorganic powder that becomes cohesive and adhesive on coming in contact with
moisture, thus forming a stable mechanical barrier and sealing the site of bleeding.
Due to its composition, it is neither absorbed nor metabolized within the mucosa,
hence minimizing the risk of systemic toxicity.[4 ] HS consists of collagen that is the major protein of the extracellular matrix. It
activates intrinsic coagulation pathway as well as platelet activation. Collagen acts
as a scaffold in tissues because of its stiff, triple-stranded helical structure.[7 ] Collagen binds with platelets via the glycoprotein IV/IX/V receptors, exposing procoagulant
phospholipids and leading to thrombosis.[8 ] Collagen also accelerates reparative processes and initiates wound healing through
activation of inflammatory cells and tissue vascularisation.[9 ] Collagen has also been shown to stimulate angiogenic growth factors and epithelial
cell migration and proliferation, leading to re-epithelialization.[10 ]
[11 ]
[12 ]
Efficacy of Hemospray has been demonstrated in bleeding from peptic ulcers, cancer,
and postbanding variceal ulcers.[5 ]
[13 ]
[14 ] The first multicenter prospective nonrandomized survey analyzing the effectiveness
of Hemospray in acute nonvariceal upper GI bleed from Europe (SEAL study) demonstrated
successful immediate hemostasis in 85% and a rebleeding rate of 15% in nonpeptic-ulcer
bleeding.[15 ] Prasad et al who pioneered use of HS in India reported initial hemostasis in 90%
of patients with peptic ulcer and rebleeding rate of 20%.[7 ] In another study from India, initial hemostasis was seen in 90% of cases with rebleeding
in 20%.[16 ] A recent study from Canada on 86 applications of Hemospray could achieve immediate
hemostasis in 88.4%, but the rebleeding rate was high at 33.7%.[17 ] This may be attributed to higher prevalence of Forrest 1A and 1B ulcers in their
series. A randomized control trial compared use of Hemospray and endoscopic clip application
in patients with nonvariceal UGIB, majority of whom had bleeding from peptic ulcer.[18 ] Hemostasis was achieved in 100% patients with Hemospray as compared with 90% with
hemoclip (p = 0.487). However, during second-look endoscopy, 5/20 (25%) patients required an
additional hemostatic procedure.
In our study, clinical success was achieved in 84% patients with rebleeding rate of
10%. The lower clinical success in our study is possibly due to use in a wide variety
of causes of UGIB including difficult to treat patients with gastric malignancies.
Recent guidelines from International Consensus Group recommend use of hemostatic powder
like TC-325 as a temporizing therapy to stop bleeding when conventional endoscopic
therapies are not available or fail, in patients with actively bleeding ulcers.[19 ] However, monotherapy with TC-325 in patients with actively bleeding ulcers is not
advisable.
Generally, all the homeostatic powders are considered safe. Transient abdominal discomfort
due to rapid air insufflation and gastric distension, reported by others, was not
seen by us. Allergic reaction to egg protein used for synthesis of HS, though unreported,
remains a possibility with HS.[7 ]
All hemostatic powders are simple to use. Moreover, they can be used for control of
bleeding from areas difficult to access with endoscopic injection, clip, or other
direct methods. Availability and cost are the two major concerns, especially in our
country. HS is available for about Rs 15,000/- while other hemostatic powders are
not available.
Our study has few limitations. This is a retrospective analysis and a single-center
experience with small number of subjects.
Conclusions
HS is an effective, safe, and cost-effective tool in the endoscopic management of
UGIB. Well-designed prospective multicenter studies are required to ascertain the
efficacy and safety of HS to establish its role as hemostatic agent and acceptance
in every endoscopy unit.
