Hereditary hemorrhagic telangiectasia treated with low dose intravenous bevacizumab

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that leads to mucocutaneous telangiectasias, epistaxis, and gastrointestinal bleeding. Depending on the severity and manifestation of the disease, various therapeutic modalities have been used, from local bleeding control to surgery or concomitant drug therapy. Several articles under review have presented guidelines for treatment of HHT with bevacizumab as a direct anti-angiogenesis strategy. Still, neither the exact optimal dose nor the minimum effective dose of intravenous bevacizumab in patients with severe HHT has been reported. A 55-year-old man presented with long-standing epistaxis, recent melena, dizziness, and a three-generation family history of chronic epistaxis, anemia, and regular blood transfusions. Treatment with argon plasma coagulation (APC) for the gastrointestinal bleeding failed to raise hemoglobin levels, we considered using the bevacizumab. We report a patient with severe HHT, who was treated with low-dose bevacizumab (2 mg/kg) and improved substantially.

Bevacizumab and gastrointestinal bleeding in hereditary hemorrhagic telangiectasia

“…Since the discovery of elevated vascular endothelial growth factor (VEGF) expression in patients with HHT[1], reports of bevacizumab, a monoclonal antibody against VEGF, in managing complications of HHT have emerged[2-16], with most of the reported experience in recurrent epistaxis. We present a case of HHT with massive, refractory transfusion requirements secondary to severe GI bleeding that did not respond to conventional therapy, but subsequently achieved transfusion-independence with anti-VEGF mono-therapy.…”

Nintedanib as a novel treatment option in hereditary haemorrhagic telangiectasia

“…While non-selective beta-blockers also have an antiangiogenic effect, comprehensive studies in HHT are still lacking 2. Bevacizumab is a direct VEGF inhibitor4 and has been shown in multiple small series studies to have a positive impact on iron-deficiency anaemia, epistaxis and other systemic symptoms in HHT 4 5. However, once again, the potential side effects of bevacizumab should not be understated and include thromboembolic events, nasal septal perforation, gastrointestinal perforations and arterial hypertension 2 4…”

Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

“…This recombinant humanized monoclonal antibody is directed against the vascular endothelial growth factor, a protein which plays a critical role in the pathophysiology of ROW [17]. In addition to having been successfully applied in the management of epistaxis and in the reduction of high cardiac output in patients with severe hepatic involvement [18], bevacizumab was shown to be effective controlling gastrointestinal bleeding in a few case reports [19][20][21][22][23]. In fact, patients who were refractory to several other medical and endoscopic approaches, and whose transfusion requirements ranged from 1 unit of PRBC every week to about 300 units in a year, all were reported to have developed a significant decrease in bleeding episodes and transfusion needs [19][20][21][22][23].…”

“…In addition to having been successfully applied in the management of epistaxis and in the reduction of high cardiac output in patients with severe hepatic involvement [18], bevacizumab was shown to be effective controlling gastrointestinal bleeding in a few case reports [19][20][21][22][23]. In fact, patients who were refractory to several other medical and endoscopic approaches, and whose transfusion requirements ranged from 1 unit of PRBC every week to about 300 units in a year, all were reported to have developed a significant decrease in bleeding episodes and transfusion needs [19][20][21][22][23]. Furthermore, as in our case, authors described an extremely quick and long-term response, as well as the occurrence of early relapse following drug discontinuation [19][20][21].…”

“…The optimal dose and regimen for this agent are not fully established yet. Although the majority of authors used 5 or 7.5 mg/kg every 2 or 3 weeks, successful use of low-dose bevacizumab (1 or 2 mg/kg, every 3 weeks) was already reported, which could potentially decrease drug-related costs and adverse events [22,23]. In our patient, in whom hormonal therapy did not achieve clinical remission and who did not tolerate octreotide, intravenous bevazicumab at a dose of 5 mg/kg every 3 weeks was able to attain a dramatic and sustained response, without any complication.…”