Hemospray in the treatment of upper gastrointestinal hemorrhage in patients on antithrombotic therapy

• Introduction
• Patients and methods
• Patients
• Methods
• Statistical analysis
• Results
• Patient characteristics
• Bleeding characteristics
• Treatment success
• Discussion
• Conclusions
• References

Patients on antithrombotic therapy (ATT) have the highest risk of ongoing bleeding and mortality. Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) is a novel hemostatic agent for the treatment of upper gastrointestinal bleeding (UGIB). Initial reports on its use appear promising in terms of initial hemostasis and rebleeding rates. It is unknown whether this also pertains to patients on ATT. The aim of the current study therefore was to evaluate the efficacy of Hemospray in the treatment of UGIB in patients taking ATTs. A total of 16 unselected consecutive patients with UGIB who were treated with Hemospray were analyzed (eight taking ATT for various indications and eight not on ATT). Initial hemostasis was achieved after Hemospray application in 5 /8 patients on ATT (63 %) and in all eight patients not on therapy (P = 0.20). Rebleeding rates were similar in both groups. These preliminary data on the use of Hemospray in the management of UGIB are promising in both patients with and without ATT; however, caution should be exercised for its use in patients on ATT with spurting arterial bleeding.

Introduction

Antithrombotic therapy (ATT) includes antiplatelet therapy (e. g. aspirin and clopidogrel) and anticoagulants (e. g. warfarin) and potentially can give rise to life-threatening gastrointestinal hemorrhage. Whereas the use of ATT is reported in most major studies on the management of acute upper gastrointestinal bleeding (UGIB), outcome of endoscopic treatment is typically not specified by subgroup [1] [2]. Nevertheless, antithrombotic agents may precipitate and prolong bleeding from pre-existing lesions [3], suggesting impaired clot formation and disrupted coagulation. As a result, patients on antiplatelet agents may have a higher risk of ongoing bleeding and are thus difficult to manage endoscopically. Furthermore, vitamin K antagonist (VKA)-induced elevation of international normalized ratio (INR) > 1.5 significantly predicts mortality [4]. Therefore, UGIB in patients on ATT can be hard to treat with current endoscopic modalities and novel approaches should be evaluated to overcome this.

Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) is a hemostatic agent recently introduced for the management of UGIB. Its efficacy has been shown in peptic ulcer bleeding (PUB) [5], as well as in cancer-related UGIB [6]. When applied to the bleeding site endoscopically, this inorganic hemostatic powder becomes cohesive and adhesive, and forms a stable mechanical barrier that covers the bleeding source ([Fig. 1] and [Fig. 2]). Currently, an ongoing multicenter European initiative on the use of Hemospray for nonvariceal UGIB is prospectively collecting data to assess Hemospray in daily practice [7]. In a small study reporting on the effectiveness of Hemospray in UGIB, patients on ATT were excluded [7]. We describe the first eight cases of Hemospray application for UGIB in patients on ATT.

Patients and methods

Patients

From June 2011 to May 2012, unselected and consecutive patients who were evaluated endoscopically for suspected UGIB were treated with Hemospray for active bleeding of various origins. Data on sex, age, medication use, procedural details, and outcome were collected prospectively, anonymized, and analyzed retrospectively. Approval was obtained by the Institutional Review Board of the Erasmus MC University Medical Centre.

Methods

Endoscopic hemostatic interventions (using an Olympus Q180 – 1 T scope; Olympus, Tokyo, Japan) were performed exclusively by expert endoscopists who were experienced in therapeutic endoscopy for UGIB and were specially trained in Hemospray application. The training consisted of a theoretical part and hands-on training on a model. Hemospray (maximum 20 g) was applied onto the active bleeding site through a 10-Fr catheter (Cook Medical) in short bursts of a CO₂-propelled canister until hemostasis was confirmed. Successful initial hemostasis was defined when Hemospray application led to hemostasis after 5 minutes of visual inspection. Hemospray was used either as monotherapy or as salvage therapy at the discretion of the endoscopist and depending on the origin of UGIB. Salvage therapy was defined as application of Hemospray after failure of one or more other endoscopic modalities. Failed initial hemostasis was defined as the need for a subsequent modality for cessation of bleeding after application of 20 g of Hemospray. No standard scheduled second-look endoscopy was carried out unless clinical signs of rebleeding were present, including tachycardia, hypotension, and a drop in hemoglobin concentration.

Statistical analysis

Fisher’s exact test and Mann – Whitney U test were used to compare patients on ATT (ATT + group) with those not receiving ATT (non-ATT group). All analyses were performed using PASW statistics 17.0 for Windows (SPSS, IBM, Armonk, New York, USA). A two-sided P value of < 0.05 was considered to be statistically significant.

Results

Patient characteristics

A total of 16 patients (median age 69.5 years, range 47 – 88 years; 75 % male) with UGIB were treated with Hemospray during the study period ([Table 1]).

Eight patients were on ATT at the time of bleeding: three on antiplatelet therapy, one on a combination of antiplatelet therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), one with chronic use of NSAIDs, two on VKA (INR 5.1) or heparin (activated partial thromboplastin time 38 seconds at time of the bleed), and one on a combination of NSAIDs and VKA (INR 1.4). In the ATT + group, prophylactic proton pump inhibitor co-therapy was also being used by four patients. Interestingly, none of the patients receiving gastroprotective co-therapy bled from a peptic ulcer.

Bleeding characteristics

The origin of the bleeding was a peptic ulcer in 9 /16 patients (56 %), tumor bleeding in 2 /16 (13 %), and other (e. g. Dieulafoy lesion, variceal bleeding, anastomotic bleeding) in 5 /16 (31 %).

Treatment success

As our centre is a tertiary referral centre, a substantial number of the included patients were referred from other hospitals, where prior endoscopic treatment had failed in 5 /16 patients (31 %) ([Table 2]). In the analysis, this prior endoscopic therapy did not count as the first modality. The first treatment of the bleed at our center, which was a rebleed in these five patients, was considered the first modality. This percentage was slightly higher in the patients on ATT (3 /8 [38 %]) compared with the non-ATT group (2 /8 [25 %]).

Successful initial hemostasis was achieved by Hemospray in 5 /8 ATT + patients (63 %) and in all of the non-ATT group (P = 0.20). In these successful cases, Hemospray was used as monotherapy in three ATT + patients (38 %) and five non-ATT patients (63 %). Hemospray as part of salvage therapy was used in two ATT + patients and three non-ATT patients. In all cases, a maximum of 20 g of Hemospray was used.

Of the three ATT + patients in whom Hemospray failed to achieve hemostasis, two had a spurting arterial bleed, which could be controlled by additional clipping. In the third patient, radiological intervention by means of angiography with coiling of the bleeding vessel was necessary to achieve hemostasis.

Rebleeding within 7 days occurred in five patients in total: 3 /8 patients (38 %) in the ATT + group and in 2 /8 patients (25 %) in the non-ATT group (P = 1.0). In two of the three cases in the ATT + group, Hemospray was applied to arterial spurting bleeding (postampullary adenoma resection and Forrest Ia ulcer in a mucosa-associated lymphoid tissue lymphoma). In both rebleeding cases in the non-ATT group, Hemospray was used for a PUB-related arterial bleed. No deaths occurred within 7 days and 30 days after Hemospray application.

Discussion

In this patient series, the outcomes are presented for 16 consecutive patients with UGIB who were treated with Hemospray in a high-volume tertiary care referral center. In expert hands, Hemospray was very effective in reaching initial hemostasis of UGIB in patients without ATT (non-ATT group). In addition, a majority of patients on ATT also reached initial hemostasis after treatment with Hemospray. However, the reported success rate cannot be compared directly with other series because outcome of endoscopy in patients taking ATT is often not reported [4] [5] [8] [9]. Failed initial hemostasis and rebleeding in the ATT + group was almost exclusively observed when Hemospray was applied to arterial spurting bleeds, suggesting limited effectiveness of Hemospray in a selection of patients on ATT.

This series is the first to describe the successful use of Hemospray in patients on ATT. The use of ATT results in impaired activation and aggregation of thrombocytes or distortion of the direct and indirect coagulation cascade, which might prevent formation of a thrombin-mediated clot on the bleeding site [10]. The current data suggest that endoscopic hemostasis by Hemospray is not hampered by the effects of systemic ATT. As Hemospray was also successfully applied as salvage therapy, this may even suggest beneficial effects on clot formation that cannot be achieved by current endoscopic hemostatic modalities such as clipping. More research is needed to further elucidate the role of Hemospray in clot formation both in vitro and in vivo.

The current case series is limited by the small number of patients and the high proportion of spurting bleeds (50 %). This may be explained by the tertiary care setting and the use of Hemospray as salvage therapy and treatment for high-risk cases. Further studies are required to confirm the efficacy of Hemospray in daily endoscopic practice in less-selected cases.

Conclusions

Effectiveness of Hemospray in the management of UGIB is promising in a small series of patients, both those with and those without ATT but caution is advised in using Hemospray in patients on ATT with a spurting arterial bleed. The inclusion of these patients in future trials is recommended to increase the generalizability of the results.

Competing interests: None.

Acknowledgments

Material support was provided by Cook Medical (Winston-Salem, North Carolina, USA).

• References

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• 4 Shingina A, Barkun AN, Razzaghi A et al. Systematic review: the presenting international normalised ratio (INR) as a predictor of outcome in patients with upper nonvariceal gastrointestinal bleeding. Aliment Pharmacol Ther 2011; 33: 1010-1018
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  Search in Google Scholar
• 6 Chen YI, Barkun AN, Soulellis C et al. Use of the endoscopically applied hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary experience (with video). Gastrointest Endosc 2012; 75: 1278-1281
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Corresponding author

• References

• 1 Hearnshaw SA, Logan RF, Palmer KR et al. Outcomes following early red blood cell transfusion in acute upper gastrointestinal bleeding. Aliment Pharmacol Ther 2010; 32: 215-224
  CrossrefPubMedSearch in Google Scholar
• 2 Theocharis GJ, Thomopoulos KC, Sakellaropoulos G et al. Changing trends in the epidemiology and clinical outcome of acute upper gastrointestinal bleeding in a defined geographical area in Greece. J Clin Gastroenterol 2008; 42: 128-133
  CrossrefPubMedSearch in Google Scholar
• 3 Sung JJ. Chapter 3: Gastrointestinal bleeding: antiplatelets and anticoagulants. In: Sung JJ, Kuipers EJ, Barkun AN, eds. Gastrointestinal bleeding. 2nd. edn. London: Wiley-Blackwell; 2012
  Search in Google Scholar
• 4 Shingina A, Barkun AN, Razzaghi A et al. Systematic review: the presenting international normalised ratio (INR) as a predictor of outcome in patients with upper nonvariceal gastrointestinal bleeding. Aliment Pharmacol Ther 2011; 33: 1010-1018
  CrossrefPubMedSearch in Google Scholar
• 5 Sung JJ, Luo D, Wu JC et al. Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding. Endoscopy 2011; 43: 291-295
  Search in Google Scholar
• 6 Chen YI, Barkun AN, Soulellis C et al. Use of the endoscopically applied hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary experience (with video). Gastrointest Endosc 2012; 75: 1278-1281
  CrossrefPubMedSearch in Google Scholar
• 7 Smith LA, Stanley AJ, Bergman JJ et al. Hemospray for non-variceal upper gastrointestinal bleeding: results of the SEAL dataset (survey to evaluate the application of Hemospray in the luminal tract). Abstract presented at Digestive Disease Week; 2012 May 20–22; San Diego, California. Gastrointest Endosc 2012; 75: AB133-AB134
  PubMedSearch in Google Scholar
• 8 Park CH, Min SW, Sohn YH et al. A prospective, randomized trial of endoscopic band ligation vs. epinephrine injection for actively bleeding Mallory–Weiss syndrome. Gastrointest Endosc 2004; 60: 22-27
  CrossrefPubMedSearch in Google Scholar
• 9 Lo CC, Hsu PI, Lo GH et al. Comparison of hemostatic efficacy for epinephrine injection alone and injection combined with hemoclip therapy in treating high-risk bleeding ulcers. Gastrointest Endosc 2006; 63: 767-773
  CrossrefPubMedSearch in Google Scholar
• 10 Gross PL, Weitz JI. New antithrombotic drugs. Clin Pharmacol Ther 2009; 86: 139-146
  CrossrefPubMedSearch in Google Scholar