Successful Control of Massive Gastrointestinal Bleeding Following Umbilical Cord Blood Transplantation (UCBT) by Use of Recombinant Activated Factor VII (rFVIIa) and Octreotide Infusion

Abstract

Post stem cell transplantation (SCT) bleeding is a dreaded complication especially gastrointestinal (GI). Platelet refractoriness is another but rare cause of bleeding post SCT. Use of rFVIIa for bleeding in setting of SCT was tested by Pihusch et al in 100 patients. Despite no overall effect of rFVIIa treatment on primary endpoint, post hoc analysis showed an improvement in the control of bleeding for 80 ug kg rFVIIa vs. standard haemostatic treatment. There were 38 patients with GI bleeding but none with massive bleeding. There are only 8 other case reports of use of rFVIIa for massive lower GI bleeding post allogeneic SCT with only one patient showing partial response and none of the patients surviving. The role of octreotide is less clear in gastrointestinal bleeding unrelated to portal hypertension. Y. Eroglu reported that, the response rate of gastrointestinal bleeding to octreotide in patients without portal hypertension was 50%. We present a 10 month-old female child, who had three episodes of life threatening lower GI bleeding post unrelated UCBT controlled successfully each time by use of rFVIIa and octerotide infusion. Patient underwent an unrelated UCBT for Thalassemia Major with a 4/6 matched cord unit and was conditioned with Busulfan 14 mg/kg, Cyclophosphamide120 mg/kg and Anti- Thymocyte Globulin. Cyclosporine and Methotrexate was given for Graft vs. host Disease prophylaxis. Cell dose infused was 7 × 107 nucleated cell/kg. She failed to engraft and also developed refractory thrombocytopenia. On Day + 48 post UCBT she developed massive lower GI bleed (passing big clots per rectum) with hypotension. Her platelets were 8,000/mm3, Hb of 4.5 gm/dl. Her coagulation parameters were normal. She was given packed cells, platelets (random donor and apheresis), Fresh Frozen Plasma (FFP) and tranexamic acid (250 mg IV 8 hrly). She was also started on injection octreotide infusion (1μg/kg bolus followed by 1μg/kg/hr infusion). Patient continued to have life threatening lower GI bleed (bleeding score-4) with no rise in platelets so a decision was made to administer rFVIIa (once she was repleted with packed cells, platelets and fresh frozen plasma) using the bolus dose of 90 μg/kg IV 3 doses 2 hrly. Autologous marrow was infused with CD34 cell dose 7 million/kg in view of non-engraftment. The bleeding subsided completely (within 6 hrs) after three doses of rFVIIa and the blood pressure normalized. Octreotide infusion was stopped after 12 hrs of bleeding free interval. After a 24 hr bleeding free period on Day +50 post UCBT, patient again bled with hypotension and again required factor VIIa (two doses) along with blood products and octreotide infusion and again showed excellent response. Again on Day+59 post UCBT she had another episode of massive lower GI bleed with hypotension and again required activated factor VIIa (two doses only) along with blood products and octreotide infusion) and bleeding stopped in next 8 hr. There was no further episode of lower GI bleed. No adverse effects due to rFVIIa were observed. She was discharged after 2 weeks with recovery of neutrophills and platelets and continues to be well Day +100 post transplant. Following this case we suggest that rVIIa with octerotide be considered as a mode of additional therapy for life-threatening GI bleeding in the face of severe thrombocytopenia and platelet refractoriness, where platelet transfusions and other haemostatic agents have failed.