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Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 667

Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide

1 Department of Pediatric Oncology, Gulhane Military Medical Academy, Ankara, Turkey
2 Department of Hematology, Gulhane Military Medical Academy, Ankara, Turkey

Date of Web Publication9-Oct-2015

Correspondence Address:
Erman Atas
Department of Pediatric Oncology, Gülhane Military Medical Academy, 06018 Etlik, Ankara
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.138106

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 > Abstract 

After hematopoietic stem cell transplantation (HSCT), patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI) which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa) and octreotide infusion.

Keywords: Gastrointestinal bleeding, octreotide, recombinant activated factor VII

How to cite this article:
Atas E, Kesik V, Gursel O. Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide. J Can Res Ther 2015;11:667

How to cite this URL:
Atas E, Kesik V, Gursel O. Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide. J Can Res Ther [serial online] 2015 [cited 2022 Jul 5];11:667. Available from: https://www.cancerjournal.net/text.asp?2015/11/3/667/138106

 > Introduction Top

Massive gastrointestinal (GI) bleeding has serious morbidity and mortality in children. After hematopoietic stem cell transplantation (HSCT), nearly 32% of the patients suffer at least one bleeding episode with a mean duration of 7 days. [1] Any hemostatic event is observed during autologous and allogeneic HSCT in the rate of 73.5 and 85.4%, respectively. The rates of GI bleeding are 20.5% in autologous and 34.9% in allogeneic HSCT. GI bleeding is more often severe (3%) or lethal (32.5%) than bleeding from other locations. [2] Treatment options are limited in massive GI hemorrhage which may be accompanied with portal hypertension and refractory to platelets and fresh frozen plasma (FFP) transfusion. In these cases, octreotide and recombinant activated factor VII (rFVIIa) can be used successfully as new treatment modalities. [3],[4],[5] Herein, we presented a 6-year-old female child, who had life-threatening upper GI bleeding post autologous HSCT controlled successfully by using rFVIIa and octreotide infusion.

 > Case Report Top

A 6-year old girl with yolk sac tumor who was treated with multiple chemotherapy regimens such as BEP (bleomycin, cisplatin, etoposide), BVP (bleomycin, vinblastine, cisplatin), VAC (vincristine, actinomycin-D, cyclophosphamide), VADRAC (vincristine, adriamycin, cyclophosphamide), TCI (pacl,taxel, carboplatin, ifosfamide), surgical resection, and radiotherapy with the dose of 4500 cGy to residual mass, underwent to autologous HSCT with conditioning regimen including cyclophosphamide, carboplatin, and etoposide after two cycles TCI which was given as fifth line treatment owing to relapse after previous treatment. She developed massive GI bleeding with hypotension, melena, and low hemoglobin level as 6.2 g/dl before the completion of engraftment. The coagulation function (active partial thromboplastin time (aPTT) and prothrombin time (PT) in the course of the treatment did not exceed 1.5 times the normal value. There was a severe mucositis which was the source and cause of the bleeding in our patient. Once she was repleted with platelets suspension and FFP, her bleeding could not be stopped. Hemoglobin level continued to fall nearly 2 g/dl during the day and decreased from 6.2 to 4 g/dl. Patient continued to have life-threatening massive GI bleeding. Thus, we decided to administer octreotide with a dose of 1 μg/kg bolus which was followed by 1 μg/kg/h infusion and rFVIIa with a dose of 90 μg/kg intravenous (IV) bolus at hour of 0,2 and 6. The massive GI bleeding subsided completely after three doses of rFVIIa and the blood pressure normalized. But melana continued during the following 5 days. Her low hemoglobin level was supported with erythrocyte suspension. On the 2 nd day of treatment, decrease rate of hemoglobin level was slowed and stabilized on the 5 th day. Octreotide infusion was stopped after 24 h of melena-free interval on the 9 th day of treatment [Table 1]. After myeloid, eritroid, and platelet engraftment; she was discharged from hospital on day + 24 post autologous HSCT.
Table 1: Some important laboratory values, treatments, and follow-up of our patient

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 > Discussion Top

After HSCT, the most important risk factors for the development of bleeding are platelet engraftment time and coagulation abnormalities. In the form of massive GI bleeding and intracranial hemorrhage as a complication, may create very serious conditions. [2] Sometimes we are not able to solve the problem about bleeding with platelets and FFP transfusion. Platelet refractoriness making the situation more complex and difficult, can lead to morbidity and mortality. The most effective way to manage GI bleeding is to identify the source, whether it is due to peptic ulcer, esophageal varices, diffuse hemorrhagic gastritis, severe and acute colitis etc. Also, appropriate management of GI bleeding are gastroprotective treatment with anti-acid drug and nasogastric decompression. The possible causes of GI bleeding in our case were due to persistent thrombocytopenia and severe mucositis. Nasogastric decompretion was not used owing to severe mucositis. We only used lansoprazol, ranitidine as anti-acid drug and glutamine.

In the early stages of transplantation without platelet engraftment, the patient who is considered to remain thrombocytopenic for a long time, should be treated with more careful and aggressive approach. If platelets and FFP are not successful to control severe GI bleeding, rFVIIa and octreotide are effective alternative treatment options. [3],[4] The mechanism of rFVIIa is generation of thrombin, platelet, and factor X activation and formation of hemostatic plug. [6] Octreotide has been shown to reduce splanchnic circulation, to inhibit gastric acid circulation, and to reduce gastroduodenal blood flow. [3] Our patient received rFVIIa and octreotide treatment, after no response to first-line treatment such as platelet and FFP transfusion. The patient's response to treatment was very good. The bleeding stopped after three doses of rFVIIa. Octreotide therapy was continued until fecal occult blood (FOB) was negative. Hemoglobin level reached from 2 to 10 g/dl slowly with erythrocyte suspension support. Despite contribution of octreotide with its mechanism for cessation of bleeding, we thought that rFVIIa was much more effective than octreotide.

In conclusion, if there is no response to the hemostatic agents with classic approach to stop GI bleeding owing to severe thrombocytopenia and platelet refractoriness, we suggest that rFVIIa and octreotide are considered as an additional options of therapy for massive GI bleeding post HSCT. If there is an inability to treat the cause of the GI bleeding, these agents may save some patient's lives.

 > References Top

Bacigalupo A. Haemopoietic stem cell transplants: The impact of haemorrhagic complications. Blood Rev 2003;17:S6-10.  Back to cited text no. 1
Pihusch R, Salat C, Schmidt E, Gohring P, Pihusch M, Hiller E, et al. Hemostatic complications in bone marrow transplantation: A retrospective analysis of 447 patients. Transplantation 2002;74:1303-9.  Back to cited text no. 2
Eroglu Y, Emerick KM, Whitingon PF, Alonso EM. Octreotide therapy for control of acute gastrointestinal bleeding in children. J Pediatr Gastroenterol Nutr 2004;38:41-7.  Back to cited text no. 3
Yadav SP, Sachdeva A, Bhat S, Katewa S. Successful control of massive gastrointestinal bleeding following umbilical cord blood transplantation (UCBT) by use of recombinant activated factor VII (rFVIIa) and octreotide infusion. Pediatr Hematol Oncol 2010;27:24-30.  Back to cited text no. 4
Culligan DJ, Salamat A, Tait J, Westland G, Watson HG. Use of recombinant factor VIIa in life-threatening bleeding following autologous peripheral blood stem cell transplantation complicated by platelet refractoriness. Bone Marrow Transplant 2003;31:1183-4.  Back to cited text no. 5
Jen H, Shew S. Recombinant activated factor VII use in critically ill infants with active hemorrhage. J Pediatr Surg 2008;43:2235-8.  Back to cited text no. 6


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