Prevalence and risk factors for pulmonary hypertension in patients with hemoglobin E/β‐thalassemia disease

Atichartakarn, Vichai; Chuncharunee, Suporn; Archararit, Napaporn; Udomsubpayakul, Umaporn; Lee, Ratchanee; Tunhasiriwet, Anusith; Aryurachai, Katcharin

doi:10.1111/ejh.12242

Cited by 20 publications

(13 citation statements)

References 34 publications

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“…A recent multicenter Italian study reported TRV>3.0 m/s in 5.7% and RHC confirmed pulmonary hypertension in 2.1% [31]. However, the prevalence of pulmonary hypertension varies significantly with genotype [32] and [33] and our study cohort was much more ethnically and genetically diverse than the Italian studies. Previous reports from a large American cohort suggested TRV > 2.5 m/s in 33% of patients and TRV > 3 m/s in 5% [17].…”

Section: Discussionmentioning

confidence: 68%

Pulmonary hypertension in well-transfused thalassemia major patients

Meloni¹,

Detterich²,

Pepe³

et al. 2015

Blood Cells, Molecules, and Diseases

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The risk for pulmonary hypertension (PH) in thalassemia major (TM) patients remains controversial. We report echocardiography results from 60 TM patients: we evaluated the association between tricuspid regurgitation velocities (TRV), iron stores, and serologic markers of hemolysis and arginine dysregulation. Patients were enrolled from August 2004 until May 2009. All parameters were inversely weighted by the number of exams. TRV was comparable between sexes and it was uncorrelated with age. At the first exam, TR velocities at the upper limits of normal (2.5–2.7 m/s) were observed in 8 patients. An abnormal TRV (2.9 m/s) was found in 1 patient. Borderline increases in TRV were associated with a reduced global arginine bioavailability (R=−0.399 P=0.005), increased anemia (haemoglobin: R=−0.219 P=0.0461), cardiac index (R=0.223 P=0.0481), and diastolic dysfunction (E/A: R=0.289 P=0.0088; E/E′: R=0.223 P=0.0453), but not hemolysis, iron overload and systolic function evaluated by Magnetic Resonance Imaging, and splenectomy. Well-transfused TM patients have a lower risk for PH than thalassemia intermedia patients. However, they do have vascular stressors that raise their lifetime PH risk to levels higher than for the general population. Consequently, we support recommendations for annual echocardiographic screening and cardiac catheterization for persistent TRV above 3 m/s.

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Section: Discussionmentioning

confidence: 68%

Pulmonary hypertension in well-transfused thalassemia major patients

Meloni¹,

Detterich²,

Pepe³

et al. 2015

Blood Cells, Molecules, and Diseases

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“…Moreover, cell-free hemoglobin can activate platelets through the action of adenosine diphosphate-bound hemoglobin (79). Chronic platelet activation may, in part, contribute to an increased frequency of vascular complications in thalassemia such as pulmonary hypertension (3,11), pulmonary embolism (173), cerebral thrombosis (209), and peripheral arterial and venous thrombosis (22,30). Prevention of thrombosis, particularly FIG.…”

Section: Fig 2 Hbe Acts As a Bmentioning

confidence: 99%

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

Hirsch

Sibmooh

Fucharoen

et al. 2017

Antioxidants & Redox Signaling

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Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The b E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for b-thalassemia is not serious, it remains unexplained why HbE/b-thalassemia (HbE/b-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/b-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess a-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26,[794][795][796][797][798][799][800][801][802][803][804][805][806][807][808][809][810][811][812][813]

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“…World Health Organization (WHO) group IV pulmonary hypertension and WHO group I pulmonary hypertension (pulmonary arterial hypertension, PAH) have been demonstrated in patients who have undergone splenectomy for pyruvate kinase deficiency, stomatocytosis, hereditary spherocytosis, unstable hemoglobinopathies, paroxysmal nocturnal hemoglobinuria, myeloid metaplasia, thalassemia, Gaucher disease, trauma, and nonhemolytic conditions, as well as in a case of congenital asplenia (13,15,21,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53).…”

Section: Association Of Splenectomy With Pulmonary Hypertensionmentioning

confidence: 99%

Review of the Association between Splenectomy and Chronic Thromboembolic Pulmonary Hypertension

Kimmig

Palevsky

2016

Annals ATS

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Recent evidence suggests that there may be a link between splenectomy and the later development of pulmonary hypertension, in particular World Health Organization group IV pulmonary hypertension (chronic thromboembolic pulmonary hypertension). Epidemiological studies have demonstrated an odds ratio as high as 18 for the development of chronic thromboembolic pulmonary hypertension after splenectomy in comparison with matched control subjects who have not undergone splenectomy. The mechanisms governing the association between removal of the spleen and the subsequent development of chronic thromboembolic pulmonary hypertension remain incompletely understood; however, recent advances in understanding of coagulation homeostasis have shed some light on this association. Splenectomy increases the risk of venous thromboembolic disease, a necessary precursor of chronic thromboembolic pulmonary hypertension, by generating a prothrombotic state. This prothrombotic state likely results from a reduction in the removal of circulating procoagulant factors from the bloodstream after splenectomy. Although much is to be learned, circulating microparticles have emerged as the most likely mediator for the development of thrombosis after splenectomy. Apparently because of a reduction in reticuloendothelial cell clearance, microparticle levels are elevated in patients after splenectomy. Elevated circulating microparticle levels have been linked to thromboembolism and pulmonary hypertension in a dose-dependent fashion. It is important for health care providers to be aware of the link between splenectomy and chronic thromboembolic pulmonary hypertension. We are optimistic that clarification of the exact mechanisms that govern this association will yield clinical guidelines and potential treatments.

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Prevalence and risk factors for pulmonary hypertension in patients with hemoglobin E/β‐thalassemia disease

Abstract: Prevalence of PHT in E/β-Thal patients was 37.3% without gender preponderance. Those with severe hemolysis and asplenia invariably had severer PHT. Strong risk factors were asplenia and associated markedly elevated values of sVCAM-1, cell-free Hb, and NRBCs in blood.

Cited by 20 publications

References 34 publications

Pulmonary hypertension in well-transfused thalassemia major patients

Pulmonary hypertension in well-transfused thalassemia major patients

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

Review of the Association between Splenectomy and Chronic Thromboembolic Pulmonary Hypertension

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