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

Morris, Claudia R.; Kim, Hae-Young; Wood, John C.; Porter, John B.; Klings, Elizabeth S.; Trachtenberg, Felicia; Sweeters, Nancy; Olivieri, Nancy F.; Kwiatkowski, Janet L.; Virzi, Lisa; Singer, Sylvia T.; Taher, Alì; Neufeld, Ellis J.; Thompson, Alexis A.; Sachdev, Vandana; Larkin, Sandra; Suh, Jung Hee; Kuypers, Frans A.; Vichinsky, Elliott

doi:10.3324/haematol.2012.082065

Cited by 40 publications

(25 citation statements)

References 61 publications

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“…NO destruction by hemoglobin can also cause further impairment in vascular endothelial function via activation of adhesion molecules and potent vasoconstrictors such as endothelin 1 60 . This phenomenon, foreshadowed by evidence of NO scavenging and oxidant stress with early generation blood substitutes, 80 has now been implicated as a mechanism of NO depletion in the RBC storage lesion 70 and other hemolytic conditions such as thalassemia, malaria, and paroxysmal nocturnal hemoglobinuria 67 , 81 – 83 …”

Section: Physiology Of Conditionally Essential Amino Acidsmentioning

confidence: 99%

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

et al. 2017

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Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others. Catabolism of arginine by arginase enzymes is the most common cause of an acquired arginine deficiency syndrome, frequently contributing to endothelial dysfunction and/or T-cell dysfunction, depending on the clinical scenario and disease state. Glutamine, an arginine precursor, is one of the most abundant amino acids in the body and, like arginine, becomes deficient in several conditions of stress, including critical illness, trauma, infection, cancer, and gastrointestinal disorders. At-risk populations are discussed together with therapeutic options that target these specific acquired amino acid deficiencies.

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Section: Physiology Of Conditionally Essential Amino Acidsmentioning

confidence: 99%

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

et al. 2017

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“…In a recent open-label study of 10 patients with β-thalassemia and an TRV greater than 2.5 m/s on Doppler echocardiography (none of the patients underwent confirmatory RHC), treatment with sildenafil resulted in a significant decrease in tricuspid regurgitant jet velocity and improved left ventricular end systolic/diastolic volume but did not change the 6-minute walk distance. 88 There are also case reports of favorable response to bosentan 89 and epoprostenol 90 in patients with RHC-confirmed precapillary PH. Given the lack of data, an RCT of pulmonary vasodilators in these patients should be considered.…”

Section: Hemoglobinopathiesmentioning

confidence: 99%

Pulmonary Hypertension Associated with Chronic Hemolytic Anemia and Other Blood Disorders

Machado

Farber

2013

Clinics in Chest Medicine

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“…We read with interest the article by Morris et al 1 evaluating the role of sildenafil therapy for thalassemia patients with Doppler-defined risk for pulmonary hypertension (PH). Here we reflect on the Authors' findings and highlight our experience with sildenafil therapy in a similar patient group, although on long-term therapy.…”

mentioning

confidence: 94%

“…In our study, 7 we noted a significant improvement in the New York Heart Association (NYHA) functional classification and the 6 Minute Walking Test (6MWT) functional capacity following therapy in patients who had severe PH with high tricuspid regurgitant velocity (TRV) and low 6MWT at baseline. However, Morris et al 1 only noted improvement in TRV in patients with Doppler-echocardiography defined increased risk for PH (TRV >2.5 m/s) without improvement in 6MWT. We believe the lack of improvement in 6MWT may be due to the fact that the base-line values in this group of patients were almost normal.…”

mentioning

confidence: 99%