Letter to the Editor
The Journal of Clinical Pharmacology
An Old Drug for a New Application:
Carbazochrome-Sodium-Sulfonate in HHT
Giulio Cesare Passali, MD, PhD1, Eugenio De Corso, MD, PhD1,
Giovanni Bastanza, MD1, Leonardo Di Gennaro, MD2, and
the HHT Gemelli Study Group
To the Editor,
Hereditary hemorrhagic teleangiectasia (HHT, Rendu-
Osler-Weber Syndrome) is a dominantly inherited genetic
vascular disorder in which epistaxis is the most frequent
manifestation, responsible for high morbidity and very
poor quality of life.1 Unfortunately, management of
epistaxis in this disorder has no standard care and local
treatments such as laser procedures, septodermoplasty
intervention, or surgical closure of the nostrils are often
aggressive.2 Therefore, the efforts in the approach to
management are typically directed to minimize bleeding,
as well as administration of blood transfusions avoiding
invasive procedures as much possible. In this setting,
blood transfusions bound with hormone therapy and
antifibrinolytic treatment are used with unclear efficacy.3
Recently, experimental studies utilizing antiangiogenic
drugs are reported as ongoing, but their efficacy has also
not been proven.4,5
We report a collection of HHT patients showing a
good response during treatment with an old hemostatic
drug with capillary stabilizing action, carbazochrome-
sodium-sulfonate, never tested before in such patients.
Carbazochrome-sodium-sulfonate is used clinically for
the treatment of hemorrhage due to capillary fragility. Its
mechanism of action is unknown, but it may modulate
fibrinolysis through alteration of endothelial cell function.
Carbazochrome had various applications in bleeding
disorders.6
With ethics committee approval and after written
informed consents, we treated, orally, 10 HHT patients
(3 male, 7 female; median range age of 42.8) who had
carbazochrome-sodium-sulfonate 50 mg twice per day
for 2 months. Patients were administered the epistaxis
severity score (ESS) questionnaire pre- and post-
treatment.7
We observed a reduction in the ESS score in all
subjects and, in particular, the pretreatment mean score
(6.4  2.1) vs. post-treatment score at 1 month (4.9  1.8)
and at 2 months (3.4  1.3) showed a statistically,
2015, 55(5) 601–602
© 2015, The American College of
Clinical Pharmacology
DOI: 10.1002/jcph.452
significant difference (P < .05) compared to baseline
(9.0  1.6) at both time points. Furthermore, the mean
hemoglobin level increased at 1 month (9.9 gr/dL  1.3)
compared to baseline (9.0 gr/dL  1.6) and at 2 months
(10.9 gr/dL  1.15) statistical analyses showed signifi-
cance (P < .05) at both time points (Table 1).
To our knowledge, this is the first report on the
potential beneficial effect of carbazochrome-sodium-
sulfonate in treating HHT. Moreover, this observation
may relate to an effect on endothelial barrier dysfunction
through inhibition of agonist-induced phosphoinositide
hydrolysis that may be involved in the pathogenesis
of HHT-related epistaxis and these results may lead
to further research that may determine safety and
1
Department of Head and Neck Surgery, Catholic University of
Sacred Heart School of Medicine, Rome, Italy
2
Department of Medical Sciences, Hemostasis and Thrombosis
Centre Catholic, University of Sacred Heart School of Medicine,
Rome, Italy
Submitted for publication 17 October 2014; accepted 18 December
2014.
Corresponding Author:
Giulio Cesare Passali, MD, PhD, Department of Head and Neck
Surgery, Catholic University of Sacred Heart School of Medicine, L.go
F. Vito n8, 00168 Rome, Italy
Email: giulio.passali@rm.unicatt.it
HHT Gemelli Study Group (Bastanza G.1 MD; Bonadia N.2 MD;
Costamagna G.3 MD, PhD; De Corso E.1 MD, PhD; De Cristoforo R.2
MD, PhD; Di Gennaro L.2 MD; Galli J.1 MD, PhD; Landolfi R.2 MD, PhD;
Marmo C.3 MD; Morretti T.2 MD; Paludetti G.1 MD, PhD; Pandolfini M.1
MD; Passali G.C.1 MD, PhD; Riccioni M.E.3 MD, PhD).
1
Department of Head and Neck Surgery, Catholic University of Sacred
Heart School of Medicine, Rome, Italy.
2
Department of Medical Sciences, Haemostasis and Thrombosis Centre
Catholic, University of Sacred Heart School of Medicine, Rome, Italy.
3
Digestive Endoscopy Unit, Catholic University of Sacred Heart School
of Medicine, Rome, Italy.
602 The Journal of Clinical Pharmacology / Vol 55 No 5 (2015)

Table 1. Hemoglobin (Hb) and Epistaxis Severity Score (EES) Values Before, 1 Month, and 2 Months During Therapy

Hb Hb Hb
Age of (Baseline) (After 1 Month) (After 2 Months) ESS ESS ESS
Patients Age Sex Onset Genotype gr/dL gr/dL gr/dL (Baseline) (Post-ADONA 1 Month) (Post-ADONA 2 Months)

Pat.1 51 M 7 HHT1 9.6 10.1 10.3 6 5 4

Pat.2 28 F 9 HHT1 11.8 11.9 12 1 1 1
Pat.3 53 M 11 HHT1 8.1 9.6 10.3 7 6 4
Pat.4 48 F 13 HHT2 7.9 8.6 10.9 7 5 3
Pat.5 60 M 6 HHT1 5.8 7.4 9.2 8 6 4
Pat.6 71 F 5 HHT2 9.1 9.5 10.1 7 5 5
Pat.7 30 F 14 Unknown 10.2 10.3 10.3 6 5 5
Pat.8 18 F 5 HHT1 10.4 11.2 12.2 6 4 2
Pat.9 28 F 6 HHT1 8.9 9.5 11.8 9 8 4
Pat.10 41 F 7 Unknown 8.6 11.1 12.2 7 4 2

Hb, hemoglobin; EES, epistaxis severity score; HHT, hereditary hemorrhagic teleangiectasia; Pat, patient; M: male; F: female.

efficacy for a new approach to management of epistaxis in
HHT.
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