Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 29;12(23):7410.
doi: 10.3390/jcm12237410.

Tacrolimus as a Promising Drug for Epistaxis and Gastrointestinal Bleeding in HHT

Paloma Álvarez-Hernández  1 , José Luis Patier  2   3 , Sol Marcos  1 , Vicente Gómez Del Olmo  2 , Laura Lorente-Herraiz  4 , Lucía Recio-Poveda  4 , Luisa María Botella  4 , Adrián Viteri-Noël  2   3 , Virginia Albiñana  4
Affiliations

Tacrolimus as a Promising Drug for Epistaxis and Gastrointestinal Bleeding in HHT

Paloma Álvarez-Hernández et al. J Clin Med. .

Abstract

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting the patient's quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and the need for blood transfusions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT.

Methods: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5-2 mg/day) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. The epistaxis severity score (ESS) and hemoglobin levels were the parameters used to evaluate the impact of tacrolimus. The occurrence of side effects was also recorded.

Results: Tacrolimus was well tolerated in all of the patients except 2 (who stopped the treatment). The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced when comparing the ESS before and after the treatment. Hemoglobin levels significantly increased, overcoming the anemia, during the course of the treatment.

Conclusion: Tacrolimus at low doses should be considered as a promising treatment for epistaxis and gastrointestinal bleeding in HHT.

Keywords: ESS; GI bleeding; HHT; bleeding; epistaxis; hemoglobin; tacrolimus.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hypothetic signalling pathway triggered by FK506. If the cell does not receive TGF-β/BMP9 angiogenic signals, the TRβ-I is inhibited by FKBP12, and the pathway is not initiated. In the presence of TGF-β/BMP9, the pathway will be activated with consequent phosphorylation of SMAD and expression of the target genes. After treatment with the immunosuppressant FK506, the same activation of the pathway is observed, as it sequesters the inhibitor of the TRβ-I, FKBP12, which can phosphorylate SMAD (modified from Albiñana et al., 2013 [20]. Created with BioRender.com, accessed on 2 October 2023).
Figure 2
Figure 2
(A) Evolution of the Epistaxis severity score in all 11 patients before and after tracrolimus treatment. (B) Hemoglobin levels of each patient before and after tacrolimus treatment. (C) Mean values of ESS and Hemoglobin levels. * p < 0.05, *** p < 0.001.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Hereditary haemorrhagic telangiectasia.
    Hermann R, Shovlin CL, Kasthuri RS, Serra M, Eker OF, Bailly S, Buscarini E, Dupuis-Girod S. Hermann R, et al. Nat Rev Dis Primers. 2025 Jan 9;11(1):1. doi: 10.1038/s41572-024-00585-z. Nat Rev Dis Primers. 2025. PMID: 39788978 Review.
  • Potential and emerging therapeutics for HHT.
    Eswaran H, Kasthuri RS. Eswaran H, et al. Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):724-727. doi: 10.1182/hematology.2024000675. Hematology Am Soc Hematol Educ Program. 2024. PMID: 39644056 Free PMC article. Review.

References

    1. Shovlin C.L., Guttmacher A.E., Buscarini E., Faughnan M.E., Hyland R.H., Westermann C.J.J., Kjeldsen A.D., Plauchu H. Diagnostic criteria for Hereditary Hemorrhagic Telangiectasia (RenduOsler-Weber Syndrome) Am. J. Med. Genet. 2000;91:66–67. doi: 10.1002/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P. - DOI - PubMed
    1. Shovlin C.L. Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment. Blood Rev. 2010;24:203–219. doi: 10.1016/j.blre.2010.07.001. - DOI - PubMed
    1. Shovlin C.L. Pulmonary arteriovenous malformations. Am. J. Respir. Crit. Care Med. 2014;190:1217–1228. doi: 10.1164/rccm.201407-1254CI. - DOI - PMC - PubMed
    1. Kjeldsen A.D., Vase P., Green A. Hereditary haemorrhagic telangiectasia: A population-based study of prevalence and mortality in Danish patients. J. Intern. Med. 1999;245:31–39. doi: 10.1046/j.1365-2796.1999.00398.x. - DOI - PubMed
    1. Jessurun G.A.J., Kamphuis D.J., Van der Zande F.H.R., Nossent J.C. Cerebral arteriovenous malformations in the Netherlands Antilles. High prevalence of hereditary hemorrhagic telangiectasia-related single and multiple cerebral arteriovenous malformations. Clin. Neurol. Neurosurg. 1993;95:193–198. doi: 10.1016/0303-8467(93)90123-X. - DOI - PubMed

LinkOut - more resources