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Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 102-106

What is the Prevalence of Pulmonary Hypertension in Thalassemic Patients in Guilan? A Retrospective Analytic Study

Department of Cardiology, Cardiovascular Diseases Research Center, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Date of Submission24-Apr-2022
Date of Decision06-Sep-2022
Date of Acceptance27-Sep-2022
Date of Web Publication12-Dec-2022

Correspondence Address:
Dr. Seyyed Aboozar Fakhr-Moosavi
Department of Cardiology, Cardiovascular Diseases Research Center, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, 15 Khordad Street, District 2, Rasht, Guilan Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/rcm.rcm_18_22

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Introduction: Pulmonary hypertension (PH) is quite common among patients with thalassemia, and it can lead to cardiac failure and even death in those patients. Methods: This current cross-sectional study was conducted with 155 patients with β-thalassemia major and thalassemia intermedia referring to Razi Hospital Rasht, Iran in a recent year. All patients underwent echocardiography and the data (including age, sex, thalassemia type, splenectomy history, deferoxamine usage, hydroxyurea usage, hemoglobin, and ferritin level) were collected by a researcher-made checklist. Data analysis was performed using SPSS software. Results: The prevalence of PH was 13.7% in this study. There was a correlation between sex, thalassemia type, deferoxamine usage, and ferritin level with a prevalence of PH. However, there was not a significant relationship between splenectomy history, hydroxyurea usage, and hemoglobin level with PH prevalence (P = 0.187, P = 0.035, and P = 0.178, respectively). Conclusions: The findings of the study represented that the proposed variables can cause and exacerbate cardiac complications and may have a correlation with the disease's side effects. By conducting more studies and designing a more promising interventional study with a higher sample size, using the results of this study and similar studies, a step could be taken to identify patients susceptible to exacerbation of cardiac complications earlier. By treating them, we may be able to increase their chance of survival in the long run.

Keywords: Heart failure, pulmonary hypertension, thalassemia intermedia, thalassemia major

How to cite this article:
Fakhr-Moosavi SA, Salari A, Borghei Y, Hasandokht T, Haghdoost A, Mousavi SM, Ramezani S. What is the Prevalence of Pulmonary Hypertension in Thalassemic Patients in Guilan? A Retrospective Analytic Study. Res Cardiovasc Med 2022;11:102-6

How to cite this URL:
Fakhr-Moosavi SA, Salari A, Borghei Y, Hasandokht T, Haghdoost A, Mousavi SM, Ramezani S. What is the Prevalence of Pulmonary Hypertension in Thalassemic Patients in Guilan? A Retrospective Analytic Study. Res Cardiovasc Med [serial online] 2022 [cited 2023 Apr 1];11:102-6. Available from: https://www.rcvmonline.com/text.asp?2022/11/4/102/363173

  Introduction Top

Globally, thalassemia which is the most common hereditary hemoglobinopathy occurs in 4.410,000 live births.[1] Thalassemia includes a number of disorders which are associated with the defective synthesis of either the α-globulin or β-globulin subunit of hemoglobin A. These are categorized as inherited disorders, causes of hemolytic anemia, and they can most frequently be observed in the Mediterranean and Middle East, the tropical as well as the subtropical regions of Africa and Southeast Asia.[2] Thalassemia intermedia (TI) is milder than thalassemia major (TM), and its symptoms usually do not appear until early childhood. Blood transfusions are not frequently needed among patients suffering from this disorder.[3] The leading cause of mortality in patients who have TM or TI is known to be heart failure.[4]

Thalassemia can lead to various complications, and among them, pulmonary hypertension (PH), which is a cardiac complication, is a great concern.[5] PH is common and is considered a major cause of morbidity and mortality in patients with thalassemia.[6],[7] In PH, it is reported that pulmonary artery pressure (PAP) is 25 mmHg or higher when the patient is resting and 30 mmHg or even higher when the patient is exercising.[8] It was reported that the rate of incidence in symptomatic and asymptomatic forms were 10% and 5%–60%, respectively.[3] Asymptomatic PH is one of the most common causes of heart failure and mortality in thalassemia.[8] PH development in patients with thalassemia may be the result of multiple interacting pathogenic mechanisms, such as chronic iron deposition and the subsequent increased oxidative stress, which is believed to be a central etiological mechanism in TM.[7] Clinical manifestations of PH are represented as a heart murmur, fatigue, lethargia, exertional syncope, pain in the chest, feeling sleepy during the day, headaches frequent in the morning, and, finally, cor pulmonale.[3]

Elevated PAP produces right ventricular strain, which can eventually progress to right ventricular failure and death.[5] Unfortunately, we do not know the exact cause of this condition yet. Nevertheless, anemia and iron overload are reported as the two main risk factors. As a result, to prevent the advanced complications of the disease, blood transfusion on a regular basis as well as chelation therapy must be prescribed as soon as the patient is diagnosed with PH.[3] Splenectomy is a serious risk factor in the development of PH.[9] A number of studies proposed that PH rarely occurs in well-treated TM patients.[10] PH universally portends a poor prognosis.[11] The course of treatment mostly depends on success in controlling the chronic hemolysis that is associated with both symptomatic anemia and organ. The most common methods of treatment include chronic transfusion therapy, iron chelation, hydroxyurea therapy, and splenectomy.[11] Based on the results obtained from one study, PH is common in patients with TI.[3]

One of the most frequent screening methods is known to be echocardiography.[12],[13] However, it is usually employed as a screening tool.[11]

According to the review of research conducted until now, a study of PH has not been performed in Guilan, Iran, yet. The aim of this study was to determine the prevalence of pulmonary artery hypertension and associated factors in thalassemia patients in Rasht, Iran.

  Methods Top


This cross-sectional study was conducted on 155 patients with different types of thalassemia who were referred to Razi Hospital in Rasht, Iran in a recent year.

Data collection

After obtaining necessary permits from the deputy of research and technology and the administrator of the hospital, all patient medical records were included in the study by census method. A total of 155 patient's medical records during this period were referred to the hospital and monitored for blood transfusion, and if they had inclusion criteria, they were included in the study, and data were collected using a researcher-made checklist.

Patients with thalassemia who underwent transfusion and received regular chelator and had the following conditions were included in the study: (1) started regular transfusions before the age of 2, (2) started treatment with chelators before the age of 5, and (3) had subcutaneous administration of deferoxamine, 40–50 mg/kg/d and were infused within 8–12 h at least 5 days a week. Moreover, patients with TI, who did not have regular transfusions and just sometimes received blood due to exacerbation of anemia, were also included in this study. All patients with ejection fraction (EF) <40%, increased PH due to left heart involvement, pulmonary disease and thromboembolism, lack of required clinical and demographic information, and lack of data related to cardiac echocardiography were excluded.

The checklist includes three sections: demographic and hematological information, history of diseases, and echocardiographic information.

Pulmonary artery systolic pressure was obtained by maximal systolic pressure of the right ventricle to the right atrium (tricuspid). If the tricuspid gradient was more than 40 mmHg, it is considered an increased pulmonary artery systolic pressure. All echocardiographs were performed by one cardiologist.

Patients' personal information is not going to be disclosed in the publication of the results of the study and researchers have considered themselves obliged to observe research ethics according to the provisions of Guilan University of Medical Sciences.

Statistical analysis

Data were first entered into SPSS software (version 18, IBM, Corporation, Armonk, NY, USA) and then the statistical analysis was performed using both Chi-square and independent t-test and, if necessary, nonparametric tests. The significance level of data was considered < 0.05.

  Results Top

The retrospective study was performed on the medical records of all thalassemia patients. One hundred and fifty-five patient's medical records were existing. The mean age of 32.78 ± 8.47 years, of which 77 patients were female (49.7%). Ninety-seven (62.6%) cases had TM and 58 (37.4%) cases had TI. The mean value of hemoglobin and ferritin was 8.2 ± 1.5 and 1427 ± 1206, respectively [Table 1].
Table 1: Demographic and clinical characteristics of the thalassemia patients

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Because one of the causes of increased PAP is a decrease in EF, according to the exclusion criteria, nine patients (5.8% of patients) were excluded from the study due to EF <40%. Of these nine cases, seven cases had TM and two had TI. Finally, 146 patients were divided into two groups based on PAP value: the group in which PAP was normal which means <40 mmHg in 126 (86.3%) patients, and the group in which the PAP was high that was ≥40 mmHg in 20 (13.7%) patients.

Based on the severity of PAP, the participants were divided into four groups: 126 (86.3%) cases had normal PAP (<40 mmHg), 15 (10.3%) mild PAP (40–50 mmHg), four (2.7%) moderate PAP (50–60 mmHg), and one case (0.7%) had severe PAP (more than 60 mmHg).

Out of 74 men cases, three (4.1%) of them and from 72 women cases, 17 (23.6%) of them had PH. As a result, using the Chi-square test, it was clear that the frequency of PH in women was significantly higher than in men (P = 0.001).

Out of 90 patients with TM, just nine (8.9%) of them had PH, whereas from 65 cases of TI cases, 12 (21.4%) of them had PH. The Chi-square test showed that the frequency of PH in intermedia cases was significantly higher than in TM cases (P = 0/032).

Based on the findings of our study, no significant difference was noticed in the duration of diagnosis of thalassemia, hemoglobin level, number of pack cell units received, number of blood transfusions per year, time elapsed since splenectomy, and EF in patients with PH and patients without it based on analysis by independent t-test [Table 2].
Table 2: Comparison of variables in patients with pulmonary artery hypertension and those without pulmonary artery hypertension with thalassemia

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A comparison of the frequency of PH based on the history of splenectomy, hydroxyl urea, and deferoxamine usage in patients suffering from thalassemia was shown in [Table 3], which showed a significant relation between PH and hydroxyl urea.
Table 3: Frequency of pulmonary artery hypertension

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  Discussion Top

This study aimed at investigating the prevalence of PH and associated factors in thalassemia patients. In our study, 14.7% of patients did not have normal PAP. This finding was also reported in one study in which PH was observed in 18.5% of the patients, but the clinically significant disease was observed in just 3.7%,[14] whereas in our study, this rate was 0/7%. In a study by Derchi et al. which was conducted on a large group of β-thalassemia patients through using right heart catheterization, in which PH was measured using right heart catheterization, and PH prevalence was reported to be 2.1%.[15] The reason for the difference in the above statistics may be due to the difference in the definition of PH and the difference in sample numbers and different measurement methods.

In our study, the mean estimated age of patients with PH was significantly higher than the mean estimated age of patients without it, which is similar to Derchi et al.'s findings.[15] The frequency of PH in men (4.1%) was significantly lower than in women (23.6%) and using logistic regression analysis, the chance of developing PH was 0.13 times lower in men than in women. According to a study by Mair et al.,[16] female gender is an accepted risk factor for PH and the female-to-male ratio was 4.3:1.

PH in patients suffering from TI (21.4%) was reported to be significantly higher than in patients with TM (8.9%) (2.7 times higher). In a study which was conducted in Egypt, the prevalence of PH in patients with TM was reported to be 40%, which is higher than the current study. This discrepancy may be due to that in the first study systolic PAP (sPAP) >35 mmHg was considered a PH criterion, whereas in the current study sPAP >40 mmHg was considered a PH criterion.[17]

From 98 patients who had a history of splenectomy, PH was seen in 16 patients (16.3%). Although the prevalence of PH was higher in people with a history of splenectomy, no statistically significant difference was observed in the frequency of PH, previous studies showed that splenectomy was one of the most noticeable risk factors.[15]

The frequency of PH in patients who received hydroxyurea was significantly higher than in patients who did not use it. In a study by Gladwin et al. on 188 patients with sickle cell disease, they showed that there was no relationship between hydroxyurea consumption and the frequency of PH. The reason for this significant relationship in the current study can be due to the fact that 63% of patients with TI were treated with hydroxyurea, whereas only 15% of patients with TM took hydroxyurea and this difference caused us to do subgroup analysis for further investigation and as it was guessed, hydroxyurea consumption did not cause a significant difference in the frequency of PH in patients with TM and TI.[18]

Our findings demonstrated that the frequency of PH in patients who were taking deferoxamine was significantly lower than in patients who did not take it. It may be due to the fact that patients with TM consume more deferoxamine than those with TI. Deferoxamine is shown to have positive effects in preventing the effects of iron overload in patients who suffer from TM and prevents cardiomyopathy due to iron accumulation. In addition, deferoxamine may also indirectly reduce iron deposition in the lungs and liver and play an important role in the treatment of PH.[19] The significant difference in the prevalence of PH in deferoxamine users may be due to the fact that patients with TM consume more deferoxamine than those with TI.

The mean hemoglobin in patients with PH was reported not to be significantly different from the mean hemoglobin in patients without PH. Furthermore, a study by Hagar et al. on TM patients achieved the same result.[20] We also found that the prevalence of PH with higher average ferritin levels was lower, which is in line with Rashidi et al.'s and Vlahos et al.'s findings.[7],[14] This may be due to the higher ferritin level in patients with TM compared to the ferritin level in patients suffering from TI.

  Conclusions Top

Our study showed that the type of thalassemia, gender, and deferoxamine usage was effective in increasing PAP. The chances of PH in patients with TI were 2.7 times higher than those with TM, and the chance of PH in men was 0.13 times lower than in women. People who did not take deferoxamine were 5.4 times more likely to have increased PH than those who took deferoxamine. This study indicated that the proposed variables can be also effective in causing and exacerbating cardiac complications in patients who are suffering from thalassemia and may be associated with the complications of this disease. By conducting more studies and by designing a prospective and intervention with a larger sample size and using the results of this study and similar studies, a step can be taken to identify patients more prone to exacerbation of cardiac complications and by treating them, their survival rate can be increased in a long time.

Ethical clearance

All participants gave their informed consent prior to their inclusion in the study. Moreover, the study protocol was approved by scientific vice chancellor for research and the ethics committee of Guilan University of Medical Sciences (IR.GUMS.REC.1395.72) in June/14/2016 and conformed to the ethical guidelines of the 1975 Declaration of Helsinki.


We thank the participants of the present study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Aessopos A, Tsironi M, Andreopoulos A, Farmakis D. Heart disease in thalassemia intermedia. Hemoglobin 2009;33 Suppl 1:S170-6.  Back to cited text no. 4
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Rashidi F, Sate H, Mohammadi A, Koohi A, Nejati B, Naybzadeh A. Echocardiographic evaluation of prevalence of pulmonary hypertension in β-thalassemia major: A cross sectional study. Pediatr Hematol Oncol 2018;35:322-30.  Back to cited text no. 7
Alwataify AS, Alfatlawy SS, Altufaily YA. Pulmonary hypertension in thalassemia patients. Blood: Updates on Hemodynamics and Thalassemia. London: United Kingdom; 2022. p. 115.  Back to cited text no. 8
Phrommintikul A, Sukonthasarn A, Kanjanavanit R, Nawarawong W. Splenectomy: A strong risk factor for pulmonary hypertension in patients with thalassaemia. Heart 2006;92:1467-72.  Back to cited text no. 9
Siri-Angkul N, Chattipakorn SC, Chattipakorn N. Diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients. Expert Rev Hematol 2018;11:471-9.  Back to cited text no. 10
Fraidenburg DR, Machado RF. Pulmonary hypertension associated with thalassemia syndromes. Ann N Y Acad Sci 2016;1368:127-39.  Back to cited text no. 11
Meloni A, Detterich J, Pepe A, Harmatz P, Coates TD, Wood JC. Pulmonary hypertension in well-transfused thalassemia major patients. Blood Cells Mol Dis 2015;54:189-94.  Back to cited text no. 12
Pinto VM, Musallam KM, Derchi G, Graziadei G, Giuditta M, Origa R, et al. Mortality in β-thalassemia patients with confirmed pulmonary arterial hypertension on right heart catheterization. Blood 2022;139:2080-3.  Back to cited text no. 13
Vlahos AP, Koutsouka FP, Papamichael ND, Makis A, Baltogiannis GG, Athanasiou E, et al. Determinants of pulmonary hypertension in patients with Beta-thalassemia major and normal ventricular function. Acta Haematol 2012;128:124-9.  Back to cited text no. 14
Derchi G, Galanello R, Bina P, Cappellini MD, Piga A, Lai ME, et al. Prevalence and risk factors for pulmonary arterial hypertension in a large group of β-thalassemia patients using right heart catheterization: A Webthal study. Circulation 2014;129:338-45.  Back to cited text no. 15
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Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004;350:886-95.  Back to cited text no. 18
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  [Table 1], [Table 2], [Table 3]


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