Heart disease in thalassemia intermedia: a review of the underlying pathophysiology

Aessopos, Athanasios; Kati, Maria; Farmakis, Dimitrios

doi:10.3324/haematol.10915

Cited by 99 publications

(126 citation statements)

References 40 publications

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“…10 They also has a similarly high rate of functional limitation (New York Heart Association Functional Classification) and considerable decrease in the 6-minute walk distance. 10 This parallels studies confirming that PAH in β-thalassemia is a serious morbidity associated with subsequent right ventricular dysfunction, 28,30,38,49,[55][56][57] and warranting prompt diagnosis and treatment. The higher prevalence of PAH in β-thalassemia intermedia compared with β-thalassemia major patients suggests a protective role for transfusion therapy in this setting.…”

Section: Discussionsupporting

confidence: 55%

Prevalence and Risk Factors for Pulmonary Arterial Hypertension in a Large Group of β-Thalassemia Patients Using Right Heart Catheterization

et al. 2014

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Distinction of the various forms of β-thalassemia relies on clinical grounds. Patients with β-thalassemia major present to medical attention in early childhood with severe anemia requiring life-long transfusion and iron chelation therapy for survival.2 Conversely, patients with β-thalassemia intermedia present later in childhood with milder anemia and remain largely transfusion-independent.3 Such variation in phenotype has been attributed to several environmental and genetic factors that alter the α/β-chain imbalance and subsequent ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process in β-thalassemia. 4 Clinical Perspective on p 345Among the sequelae associated with a diagnosis of β-thalassemia, pulmonary arterial hypertension (PAH) has received great attention in recent years.5 PrevalenceBackground-Pulmonary arterial hypertension (PAH) remains a concern in patients with β-thalassemia major (TM) and intermedia (TI); however, studies evaluating its prevalence and risk factors using systematic confirmation on right heart catheterization are lacking. Methods and Results-This was a multicenter cross-sectional study of 1309 Italian β-thalassemia patients (mean age 36.4±9.3 years; 46% men; 74.6% TM, 25.4% TI). Patients with a tricuspid-valve regurgitant jet velocity ≥3.2 m/s (3.6%) on transthoracic echocardiography further underwent right heart catheterization to confirm the diagnosis of PAH (mean pulmonary arterial pressure ≥25 mm Hg and pulmonary capillary wedge pressure ≤15mm Hg). The confirmed PAH prevalence on right heart catheterization was 2.1% (95% confidence interval [CI], 1.4-3.0) and was higher in TI (4.8%; 95% CI, 3.0-7.7) than TM (1.1%; 95% CI, 0.6-2.0). The positive predictive value for the tricuspid-valve regurgitant jet velocity ≥3.2 m/s threshold for the diagnosis of pulmonary hypertension was 93.9%. Considerable functional limitation and decrease in the 6-minute walk distance were noted in patients with confirmed PAH. On multivariate logistic regression analysis, independent risk factors for confirmed PAH were age (odds ratio, 1.102 per 1-year increase; 95% CI, 1.06-1.15) and splenectomy (odds ratio, 9.31; 95% CI, 2.57-33.7). Conclusions-The prevalence of PAH in β-thalassemia patients as confirmed on right heart catheterization was 2.1%, with an ≈5-fold higher prevalence in TI than TM. Advanced age and splenectomy are risk factors for PAH in this patient population. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01496963.(Circulation. 2014;129:338-345.)

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Section: Discussionsupporting

confidence: 55%

Prevalence and Risk Factors for Pulmonary Arterial Hypertension in a Large Group of β-Thalassemia Patients Using Right Heart Catheterization

et al. 2014

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“…29 Hypercoagulability results from a spectrum of abnormalities, including the native erythrocyte precoagulant surface, the frequently performed splenectomy, some coexistent genetic coagulation defects, and the previously mentioned endothelial dysfunction and vasculopathy. 30 More recent clinical and experimental studies suggest an interaction between hemolysis, platelet or coagulation activation, and decreased nitric oxide bioavailability both in sickle cell disease 31,32 and in other hemolytic conditions such as paroxysmal nocturnal hemoglobinuria. 20 Several thromboembolic complications have been reported in hemoglobinopathy patients, especially in those with thalassemia intermedia and splenectomy or sickle cell disease, including pulmonary embolism and in situ thrombosis.…”

Section: Pathophysiologymentioning

confidence: 99%

Pulmonary Hypertension Associated With Hemoglobinopathies

Farmakis

Aessopos

2011

Circulation

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“…Consequently, patients with Hb E β 0 thalassemia may also develop severe transfusional iron overload and, like other patients with β thalassemia major, eventually succumb to cardiac failure. 26 A β 0 thalassemia mutation coinherited with alpha gene triplication may also result in a thalassemia intermedia phenotype from globin chain imbalance. In many cases, the β thalassemia genotype may not explain the observed clinical phenotype, reflecting the complex genetic interactions between β-globin genes, β-globin gene production controlling regions, and a growing list of other potential genetic modifiers.…”

Section: Clinical Significance Of Non-sickling Hemoglobinopathiesmentioning

confidence: 99%

Newborn screening for non-sickling hemoglobinopathies

Hoppe¹

2009

Hematology

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The hemoglobinopathies encompass a heterogeneous group of disorders associated with mutations in both the alpha-globin and beta-globin genes. Non-sickling disorders are found primarily in individuals of Mediterranean, Asian and Southeast Asian ancestry. With rapid growth in the Asian and Hispanic segments of the US population, the geographic distribution of hemoglobinopathies is expected to become significantly different from what it is today. The epidemiologic changes in the prevalence of non-sickling hemoglobin disorders have important implications for future public health programs, including newborn screening. The purpose of newborn screening for hemoglobinopathies is to identify clinically significant disorders and provide early education and specialized care prior to the onset of clinical symptoms. Although newborn screening for sickle cell disease is mandated in all states, screening for non-sickling hemoglobinopathies is directed in only one state and limited to reporting of a presumptive diagnosis in most other states. Early delivery of comprehensive care, as well as new and potentially curative therapies, has significantly improved the prognosis for affected patients. This review will consider the increasing prevalence of once uncommon hemoglobinopathies in the US, highlighting the rationale for expanding newborn screening beyond sickle cell disorders.

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Heart disease in thalassemia intermedia: a review of the underlying pathophysiology

Cited by 99 publications

References 40 publications

Prevalence and Risk Factors for Pulmonary Arterial Hypertension in a Large Group of β-Thalassemia Patients Using Right Heart Catheterization

Prevalence and Risk Factors for Pulmonary Arterial Hypertension in a Large Group of β-Thalassemia Patients Using Right Heart Catheterization

Pulmonary Hypertension Associated With Hemoglobinopathies

Newborn screening for non-sickling hemoglobinopathies

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