Recombinant factor VIIa for severe gastrointestinal hemorrhage associated with Crohn disease.

Crohn disease (CD) may be responsible for life-threatening gastrointestinal (GI) bleeding, and the management of severe GI bleeding in CD is a therapeutic challenge.

The report by Girona et al, in the current issue of the Southern Medical Journal, provides a novel therapeutic approach to a patient with GI bleeding associated with Crohn disease. (1) It is important to note that this patient was diagnosed with CD three months before admission with gastrointestinal hemorrhage. While this is unusual, there are cases in the literature of patients with CD who developed major gastrointestinal hemorrhage as the initial presentation or at very early stages of their disease. (2)

Although surgical intervention generally provides good results with respect to postoperative mortality, hemorrhage relapse and relapse of the disorder itself are not uncommon. Also, preoperative and intraoperative identification of the bleeding site is difficult, as multiple segments of gross disease may obscure the precise source of bleeding at surgery. In such cases, highly selective angiography and methylene blue injection may aid in the preoperative and intraoperative localization of occult bleeding sites in patients with CD. (3,4) A multidisciplinary approach incorporating the gastroenterologist, radiologist, and surgeon is extremely helpful in managing these cases.

Although conservative therapeutic methods have improved considerably, bleeding relapse rates remain high. These approaches include specific medical therapy for Crohn disease, vasopressin infusion, infliximab, endoscopic sclerotherapy, or angiographic intervention and surgery. (5-7)

In the aforementioned case, bleeding and hypovolemic shock continued following red blood cell and plasma infusion. As angiography was not available, the decision was made to start rFVIIa in an attempt to stabilize the patient. Faced with a potentially catastrophic event, I believe the authors made the correct decision by starting rFVIIa, due to the persistent massive bleeding, the unknown location of the bleed, hypovolemic shock, high surgical risk and life-threatening situation.

Although the use of rFVIIa in this patient was critical, there are limitations for future use of this medication, due to the well-known correlation between CD and thromboembolic events. Thrombophilia in Crohn disease is probably due to inappropriate hemostasis with a hypercoagulable state, thrombocytosis, hyperfibrinogenemia, hyperhomocysteinemia and increased levels of lipoproteins, which probably play a role in local microcirculatory alterations leading to CD itself. (8,9) However, despite the above limitations, the favorable response of this patient to rFVIIa is promising. As the authors point out, well-designed prospective studies should be performed to attain a better understanding of the effect and dose of rFVIIa. If the efficacy and safety is confirmed with future studies, rFVIIa may be one of the first-line treatment strategies in gastrointestinal bleeding in Crohn disease.

References

1. Girona E, Borras-Blasco J, Conesa-Garcia V, et al. Successful treatment of severe gastrointestinal bleeding secondary to Crohn disease with recombinant factor VIIa. South Med J 2007;100:601-604.

2. Kostka R. [Acute bleeding in the Crohn's disease] Rozhl Chir 2005;84:124-127.

3. Remzi FH, Dietz DW, Unal E, et al. Combined use of preoperative provocative angiography and highly selective methylene blue injection to localize an occult small-bowel bleeding site in a patient with Crohn's disease: report of a case. Dis Colon Rectum 2003;46:260-263.

4. Kazama Y, Watanabe T, Akahane M, et al. Crohn's disease with life-threatening hemorrhage from terminal ileum: successful control by superselective arterial embolization. J Gastroenterol 2005;40:1155-1157.

5. Belaiche J, Louis E, D'haens G, et al. Acute lower gastrointestinal bleeding in Crohn's disease: characteristics of a unique series of 34 patients. Belgian IBD Research Group. Am J Gastroenterol 1999;94:2177-2181.

6. Papi C, Gili L, Tarquini M, et al. Infliximab for severe recurrent Crohn's disease presenting with massive gastrointestinal hemorrhage. J Clin Gastroenterol 2003;36:238-241.

7. Sans M, Llach J, Bordas JM, et al. Life-threatening hemorrhage: an unusual form of presentation of Crohn's disease treated with endoscopic injection sclerotherapy. Endoscopy 1998;30:S83-S84.

8. Wakefield AJ, Sawyerr AM, Dhillon AP, et al. Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction. Lancet 1989;2:1057-1062.

9. Heneghan MA, Cleary B, Murray M, et al. Activated protein C resistance, thrombophilia, and inflammatory bowel disease. Dig Dis Sci 1998;43:1356-1361.

Levent Filik, MD

From Division of Gastroenterology, Ankara Teaching and Research Hospital, Anakara, Turkey.

Reprint requests to Levent Filik, MD, Ankara Teaching and Research Hospital, Division of Gastroenterology, Anakara, Turkey, 06600. Email: [e-mail]