European Journal of Cardiovascular Medicine

Congenital structural hemoglobinopathy sickle cell disease is inherited as autosomal recessive. The most prevalent kind of sickle cell disease (SCD), sickle cell anemia (SCA), is caused by a homozygous situation involving two S genes. This is an autosomal recessive genetic condition caused by an aberrant substitution of valine for glutamic acid at the beta globin chain's sixth position [1]. It is a disorder where there are not as many healthy red blood cells to provide enough oxygen throughout the body. RBCs are typically spherical, flexible, and readily pass through blood arteries. RBCs with sickle cell anemia have a sickle or crescent moon shape and become sticky and stiff. With a prevalence rate of 20–25 million people globally, it is one of the most prevalent illnesses. Geographically, sickle cell anemia is found in Odisha, Maharashtra, Madhya Pradesh, and Jharkhand, with a prevalence of heterozygotes ranging from 1 to 40% [2]. Acute chest syndrome, nephropathy, anemia, infection, stroke, and pulmonary hypertension may all contribute to SCD morbidity5. Infection, stroke, splenic sequestration, renal failure, pulmonary hypertension, and left ventricular failure are among the common causes of mortality [3].

The pathophysiology of pulmonary hypertension seems to include many factors, such as hemolysis-induced endothelial dysfunction, iron overload, chronic hypoxemia, chronic thrombosis, and sickle cell sequestration inside the blood vessel. One of the main pathogenic mechanisms for pulmonary hypertension in sickle cell anemia and other hemolytic illnesses is intravascular hemolysis that results in nitric oxide deficit. It is linked to a notable several-fold increase in death rates from simple sickle cell anemia. [4].

Regardless of age, with the exception of infancy, pulmonary arterial hypertension (PAH) is defined as a mean pulmonary artery pressure (MPAP) during activity that is more than or equal to 30 mmHg as assessed by cardiac catheterization. The diagnosis of pulmonary hypertension is delayed until the disease is far progressed since the early symptoms of the condition are comparable to those of many other conditions that cause dyspnea when exerted. [5]. Right-sided cardiac catheterization is the gold standard for measuring mean pulmonary artery pressure (MPAP), however it is a very invasive procedure that is not appropriate for screening. By assessing pulmonary artery pressure, two-dimensional echocardiography is utilized to screen for pulmonary hypertension.

Place of study: The study was conducted in Veer Surendra Sai Institute of Medical Sciences and Research, Burla. It is a tertiary care teaching hospital with about 1100 beds and 20 departments.

Setting of study: The study settings were at the IPD and OPD of Department of Paediatrics and the Sickle Cell Institute of VIMSAR, Burla.

Study design: Observational-Cross-sectional study.

Study population: All clinically suspected subjects of sickle cell anaemia with age group between 5 to 14 years attending paediatric OPD, IPD & sickle cell institute of VIMSAR during study period were included as the study population.

Sample size

Sample size estimation was done by Master version 2.0, BRTC, Vellore applying method one sample proportion –confidence interval estimating single proportion –absolute precision of 5 % method. Adding 10% as dropout final minimal sample size was calculated to be 502+50=552.

Inclusion criteria

1. Hb electrophoresis / HPLC confirmed subjects of sickle cell homozygous children of either gender aged between 5 to 14 years.

Exclusion criteria

1. Congenital heart disease (ECHO screened).
2. Pulmonary stenosis (ECHO screened).
3. Rheumatic heart disease (ECHO screened).
4. Patients with splenectomy. (confirmed from history and documentation)
5. Critically ill patients. (patients in ICU care

Table 1: Comparison of Clinical abnormalities of subjects and laboratory parameters of SCA with and without PHT

Table 2: Independent variables associated with PHT

Table 3: Severity of pulmonary hypertension in subjects

The clinical results of SCA patients who were either PHT-positive or not. There were notable differences between SCA participants with and without PHT in terms of the prevalence of jaundice, parasternal heave, splenomegaly, and a loud component of the second heart sound. splenomegaly, heaving in the para-sternum, and a loud second heart. A higher frequency of sound was seen in SCA participants who had PHT. The features of SCA participants in the lab, both with and without pulmonary hypertension. At the time of admission, the average hemoglobin level was 7.2 ± 4.3 g/dl. The mean reticulocyte count, hemoglobin F levels without PHT were 5.0±(0.8) %  and 18.6±(6.2)% respectively. SCA subjects with PHT have lower mean values of hemoglobin and fetal hemoglobin and these values were statistically significant.

Physical findings including jaundice, parasternal heave, hepatomegaly, and the presence of a loud component of the second heart sound were substantially different between SCA participants with and without PHT. Multivariate analysis using logistic regression was performed on these factors to find independent relationships of PHT in SCA individuals, controlling for confounders. The odds ratios of the factors that are independently related. The presence of a loud second heart sound is a statistically significant association of PHT in children with SCA and subjects with this clinical finding were 5.5 times more likely to have PHT. PHT is statistically significantly 8.6 times more common in individuals with parasternal heave who also have SCA.In our study, 552 sickle cell disease patients (311 men and 241 women) with a male to female sex ratio of 1.29: 1 were included. In our study, the overall prevalence of pulmonary hypertension was 20.4% (113/552). Of them, 439/552 (79.5%) have normal pulmonary pressure, 77 (14%) have moderate pulmonary hypertension, and 36/113 (6.5%) have mild pulmonary hypertension.

Over a two-year period, a total of 2952 youngsters were screened to form the research population. Strict inclusion and exclusion criteria were used to enroll 552 instances of sickle cell anemia as research participants, leaving out 55 dropouts. With a male to female ratio of 1.29:1, there were 311 (56.3%) male children and 241 (43.7%) female children among them.

Prevalence of pulmonary hypertension among sickle cell anemia in our study was 20.4% which was similar to figures reported by Ambrusko et al [6] and Colombati et al [7].

In our study the prevalence of PHT is increased with age in children with SCA in steady state. This is consistent with the findings of Minniti et al. [8] and Colombatti et al. [7] in the USA, Italy and Nigeria respectively in which the prevalence of PAH also increased with rising age. The results, however, are at odds with those of another Nigerian research by Aliyu et al. [9] on children and adults, in which it was shown that the prevalence of pulmonary hypertension decreased with age. In a research including adults and children, Pashankar et al. 7 in the USA found no association between advancing age and rising pulmonary hypertension. Therefore, additional research is needed to confirm the prevalence of PHT in children with SCA, as it is currently impossible to explain the difference in the age-related trend of prevalence of PHT between the current study and the previously mentioned studies.

Males were more frequently affected by PHT than females in the current study which was statistically significance (p = 0.010). There are similar studies which showed a significant association with male sex in children 10 years aged or older66 , while other studies failed to document an association with gender [10].

Our study was incongruent with the findings of Sokunbi et al. [11] in Lagos and Al-Alawi et al. [12] in Iraq. It was also noted that SCA children without PHT had higher HbF levels than those with PHT, and it is therefore likely that HbF offers some protection. This difference was statistically significant (0.021). Even though HbF is the primary genetic regulator of sickle cell disease's hematologic and clinical aspects, it seems that children with SCA who have high levels of HbF may not be fully protected from PHT. More research will be necessary because this is uncertain.

Our study shows a significant, positive correlation between SCA children with PHT and reticulocyte count. Therapies aimed at decreasing hemolysis have been postulated as measures to prevent occurrence of and delay progression of PHT in children with SCD [13].

In our study demographically 330 (59.7%) were of age group between 5 to 10 years and 222 (40.1%) were of age group more than 10 years. Out of all sickle cell children with pulmonary hypertension, 42 (37.2%) were of age group less than 10 years and 71 (62.8%) were of age group of more than 10 years. Association between these age groups and occurrence of pulmonary hypertension were statistically significant. Previous study by Patel et al had observed 36.8% of pulmonary hypertension in children with sickle cell anemia were between 5 to 10 years of age and 63.2% of pulmonary hypertension were more than 10years of age [14].

Twelve (24%) of the children with SCA in the same research by Patel et al. [14] had mild pulmonary hypertension, and seven (14%) had significant pulmonary hypertension. In contrast, 36/113 (6.5%) of the kids in our study had mild pulmonary hypertension, and 77 (13.9%) have moderate pulmonary hypertension. Therefore, more extensive research is required to link the grading of pulmonary hypertension in children with SCA across various age groups.

Providing fresh perspective on the prevalence of pulmonary arterial hypertension in children with sickle cell anemia in Western Odisha was the goal of this dissertation. Additionally, a comparison between our study location and the national average for the prevalence of pulmonary arterial hypertension among children with sickle cell anemia was sought. The findings of this study show that children with sickle cell anemia in the age range of 5 to 14 years had a prevalence of 20.4% pulmonary arterial hypertension. In older male sickle cell anemia children, pulmonary arterial hypertension is more prevalent. Depending on the demographic and diagnostic method, children with sickle cell anemia have varying rates of pulmonary hypertension.  More thorough community-based studies that evaluate children with sickle cell anemia and involve echocardiography are required in order to estimate prevalence more accurately.

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