ereditary 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, 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 significance (P < .05) at both time points (Table 1). Table 1. Hemoglobin (Hb) and Epistaxis Severity Score (EES) Values Before, 1 Month, and 2 Months During TherapyPatients Age Sex Age of Onset Genotype Hb (Baseline) gr/dL Hb (After 1 Month) gr/dL Hb (After 2 Months) gr/dL ESS (Baseline) ESS (Post-ADONA 1 Month) ESS (Post-ADONA 2 Months) Hb, hemoglobin; EES, epistaxis severity score; HHT, hereditary hemorrhagic teleangiectasia; Pat, patient; M: male; F: female. 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 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 efficacy for a new approach to management of epistaxis in HHT.

Passali, G. C., De Corso, E., Bastanza, G., Di Gennaro, L., An old drug for a new application: carbazochrome-sodium-sulfonate in HHT., <<THE JOURNAL OF CLINICAL PHARMACOLOGY>>, 2015; 55 (5): 601-602. [doi:10.1002/jcph.452] [http://hdl.handle.net/10807/71693]

An old drug for a new application: carbazochrome-sodium-sulfonate in HHT.

Passali, Giulio Cesare;De Corso, Eugenio;Bastanza, Giovanni;Di Gennaro, Leonardo
2015

Abstract

ereditary 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, 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 significance (P < .05) at both time points (Table 1). Table 1. Hemoglobin (Hb) and Epistaxis Severity Score (EES) Values Before, 1 Month, and 2 Months During TherapyPatients Age Sex Age of Onset Genotype Hb (Baseline) gr/dL Hb (After 1 Month) gr/dL Hb (After 2 Months) gr/dL ESS (Baseline) ESS (Post-ADONA 1 Month) ESS (Post-ADONA 2 Months) Hb, hemoglobin; EES, epistaxis severity score; HHT, hereditary hemorrhagic teleangiectasia; Pat, patient; M: male; F: female. 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 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 efficacy for a new approach to management of epistaxis in HHT.
Inglese
Passali, G. C., De Corso, E., Bastanza, G., Di Gennaro, L., An old drug for a new application: carbazochrome-sodium-sulfonate in HHT., <>, 2015; 55 (5): 601-602. [doi:10.1002/jcph.452] [http://hdl.handle.net/10807/71693]
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