Long-term treatment with oral sildenafil in a thalassemic patient with pulmonary hypertension

Littera, Roberto; Nasa, Giorgio La; Derchi, Giorgio; Cappellini, Maria Domenica; Chang, Christy; Contu, L.

doi:10.1182/blood-2002-04-1171

Cited by 50 publications

(39 citation statements)

References 12 publications

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“…Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5) that promotes selective smooth muscle relaxation in lung vessels. It has so far demonstrated beneficial effects in the treatment of PH 4,5 even in patients with hemoglobinopathies, as described previously by our group, 6,7 and as recently reported by Morris and colleagues in this Journal.…”

supporting

confidence: 53%

Efficacy and safety of sildenafil for the treatment of severe pulmonary hypertension in patients with hemoglobinopathies: results from a long-term follow up

et al. 2014

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supporting

confidence: 53%

Efficacy and safety of sildenafil for the treatment of severe pulmonary hypertension in patients with hemoglobinopathies: results from a long-term follow up

et al. 2014

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Section: Discussionmentioning

confidence: 99%

“…6,14,15,19,25 Even with the high mortality rate generally associated with PH regardless of its underlying etiology, few patients with thalassemia are on therapies approved by the Food and Drug Administration (FDA) for PH, and there is a paucity of intervention studies to date. Much of what is being done clinically is empiric, extrapolating from the PH literature, 5 case reports, 58,59 and small pilot studies, 53 although a sildenafil trial was recently completed through the TCRN.Improved longevity in patients with thalassemia is because of advances in medical management during the last decade. Ongoing assessments in the TLC and prospective longitudinal studies of PH, including evaluation of high-risk patients by cardiac catheterization, are needed to understand the natural history and pathophysiology in thalassemia to determine the optimal therapy for this neglected complication.…”

mentioning

confidence: 99%

Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report

Morris¹,

Kim

Trachtenberg

et al. 2011

Blood

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IntroductionPulmonary hypertension (PH) is emerging as a significant cause of mortality and morbidity in patients with hemolytic anemias. 1,2 Mortality rates associated with PH are universally high in conditions in which the natural history has been established, including sickle cell disease (SCD), 3,4 scleroderma and other connective tissue diseases, chronic obstructive lung disease, thromboembolic disorders, and idiopathic pulmonary artery hypertension. 5 Although the frequent occurrence of PH has been recognized in both thalassemia intermedia (TI) and major (TM) for some time, 1,6-14 the natural history and mortality risk of this comorbidity in the thalassemia syndromes has yet to be established, and prospective longitudinal studies are limited. Prevalence rates vary by study design with an elevated tricuspid regurgitant jet velocity (TRV) noninvasively measured by Doppler echocardiography (echo), suggesting risk for PH detected in up to 75% in some cohorts. 15,16 Although the high prevalence of PH in nontransfused TI patients has now been well documented, 14,16,17 PH risk was established in Ͼ 50% of patients with ␤-thalassemia major despite transfusion. 6,17,18 In another study of TM, pulmonary systolic pressure Ͼ 30 mm/Hg was found in all patients Ͼ 22 years of age. 6 However, recent studies in more uniformly treated patients have shown a lower frequency of PH risk in TM patients who undergo transfusion regularly. 7,12 The etiology of PH in thalassemia is multifactorial, involving a complex interaction of platelets, the coagulation system, erythrocytes, and endothelial cells along with inflammatory and vascular mediators. 13,19 Contributing mechanisms include oxidative stress, 20 hemolysis, 21,22 thrombosis, 23-25 splenectomy, 17,22,26 abnormal arginine-nitric oxide bioavailability, 13,21 red cell membrane pathology, 27 and iron overload. 28 Although overlap in pathways contributing to vasculopathy and PH is expected in all forms of thalassemia, 13 the pathophysiology of PH is fundamentally different in patients with TI compared with TM. Hemolysis is likely a driving force toward PH in nontransfused TI patients, whereas the consequences of iron overload and oxidative stress may play a more significant role in TM patients receiving transfusion therapy. 19 Autopsy studies in patients with thalassemia revealed histopathologic findings that are common to all forms of PH, including plexiform and concentric medial hyperplastic pulmonary vascular lesions, and in situ pulmonary artery thrombosis. 29 However, despite multiple similarities with pulmonary artery hypertension of various etiologies, PH in hemolytic disease is a unique disorder that differs from other forms Submitted November 29, 2010; accepted July 1, 2011. Prepublished online as Blood First Edition paper, July 19, 2011; DOI 10.1182 DOI 10. /blood-2010 An Inside Blood analysis of this article appears at the front of this issue.The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by pa...

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“…15,17 The ability of sildenafil to inhibit platelet activation 30 and treat chronic thromboembolic PH 31 may provide additional benefits for thalassemia given the hypercoagulable state present in this condition. 32,33 Small case reports suggest that treatment with oral sildenafil improved exercise tolerance and lowered the risk of PH in patients with thalassemia. 32,33 Given the high mortality rate associated with PH in other disorders, the Thalassemia Clinical Research Network (TCRN) developed a proof-of-principal, pilot trial to evaluate the safety and efficacy of sildenafil in patients with thalassemia and increased risk of PH.…”

Section: Introductionmentioning

confidence: 99%

“…32,33 Small case reports suggest that treatment with oral sildenafil improved exercise tolerance and lowered the risk of PH in patients with thalassemia. 32,33 Given the high mortality rate associated with PH in other disorders, the Thalassemia Clinical Research Network (TCRN) developed a proof-of-principal, pilot trial to evaluate the safety and efficacy of sildenafil in patients with thalassemia and increased risk of PH.…”

Section: Introductionmentioning

confidence: 99%

Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension

et al. 2013

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Long-term treatment with oral sildenafil in a thalassemic patient with pulmonary hypertension

Cited by 50 publications

References 12 publications

Efficacy and safety of sildenafil for the treatment of severe pulmonary hypertension in patients with hemoglobinopathies: results from a long-term follow up

Efficacy and safety of sildenafil for the treatment of severe pulmonary hypertension in patients with hemoglobinopathies: results from a long-term follow up

Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report

Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension

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