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Von Willebrand’ s disease (vWD) is the most common inherited bleeding disorder and is caused by quantitative deficiency or qualitative abnormalities of von Willebrand factor (vWF). Until recently, treatment of bleeding from the gastrointestinal tract in patients with vWD included administration of tranexamic acid or clotting factor products such as fresh frozen plasma, cryoprecipitate, purified vWF concentrates, or preparations that contain vWF and factor VIII. Desmopressin, beta blocking drugs, and hormonal therapy with oestrogen with or without progesterone have also been used.1,2
We report a patient with vWD who had suffered recurrent and life threatening bleeding from the gastrointestinal tract in whom, despite an extensive investigation, no apparent cause of haemorrhage was identified. He was successfully treated with combined administration of octreotide LAR (long active released) and propranolol. This is the first report on the use of octreotide LAR in a patient with vWD.
A 55 year old man presented to our department because of recurring episodes of melaena, which first appeared five years previously. He had a history of epistaxis during his childhood. During investigation of his bleeding diathesis, he was found to have type I vWD. His niece was also diagnosed with type I vWD whereas his father, brother, and grandmother suffered from bleeding diathesis but no specific investigation had been undertaken. Laboratory investigation was compatible with the diagnosis of vWD, with prolonged bleeding time (15 minutes), moderate prolongation of activated partial thromboplastin time (41 seconds), mild deficiency of factor VIII (42%; normal range 50–150%), complete absence of ristocetin induced platelet aggregation, moderate decrease in vWF (29%; normal range 50–160%), and a moderate decrease in vWF antigen (33%; normal range 50–160%). Platelet count and prothrombin time were within normal limits and the extensive laboratory investigation excluded the presence of concomitant disorders.
Over a period of 17 months, the patient had been admitted 14 times for recurrent episodes of melaena with an overall hospitalisation time of 98 days and consequent sick leave from his job. On two occasions, haemoglobin concentration on admission was 6 g/dl. He required 40 red cell transfusions and 22 000 IU of purified vWF. During this period, upper endoscopy was performed five times, small bowel series radiography twice, and colonoscopy three times; computed tomography of the abdomen, radionuclide scanning with 99mTc pertechnate labelled autologous red blood cells, angiography of the superior mesenteric artery, and exploratory surgery with intraoperative enteroscopy were also performed, but the source of bleeding could not be localised. He had received intranasal desmopressin for three months with no effect on the frequency of bleeding. He was subsequently treated with octreotide LAR 20 mg (Sandostatin LAR; Novartis, Athens, Greece) intramuscularly once a month, along with propranolol 20 mg orally three times a day. With this therapeutic regimen the bleeding stopped completely, haemoglobin values stabilised at normal levels (13.2 g/dl), and no treatment related side effects were observed. During a follow up period of eight months, bleeding did not recur and the patient has returned to his work. Repeated evaluation of vWD revealed that vWF levels did not rise (28%), ristocetin induced platelet aggregation remained absent, and activated partial thromboplastin time and bleeding time prolongations remained unchanged.
Octreotide is mainly used in acromegaly and in gastrointestinal and pancreatic tumours.3,4 Nevertheless, it has also been proved to be effective in controlling bleeding from the gastrointestinal tract due to angiodysplasia and variceal bleeding.3–8 It is postulated that it exerts its actions through a reduction in splanchnic and portal blood flow.3 Octreotide LAR, compared with conventional octreotide, has the advantages that it is administered once monthly, does not require hospitalisation, and has a similar efficacy and safety profile.9
Only one report on the effectiveness of octreotide therapy in two patients with vWD was found in the literature.10 In one of these patients, vWF was increased after administration of octreotide. In our patient, octreotide did not cause any increase in the synthesis or release of vWF. We can therefore assume that the combined administration of octreotide LAR and propranolol was effective in preventing bleeding in our patient through a direct effect on the splanchnic circulation. Undoubtedly, more trials are required to clarify the mechanism of action of octreotide in this setting.
In conclusion, combined administration of octreotide and propranolol appears to be an attractive alternative treatment in patients with vWD and recurrent bleeding from the gastrointestinal tract, particularly when other therapeutic modalities have failed.
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