1. PREVALANCE OF PULMONARY
HYPERTENSION IN CHILDREN WITH
SICKLE CELL DISEASE
Patel Parvez, Sharma Sujata, Shah Nikita, Chatterjee Goutomi,
Sharma Ratna, Manglani Mamta.
Division of Paediatric Haematology-Oncology.
Lokmanya Tilak Municipal Medical College & General Hospital,
Sion, Mumbai
2. Introduction
• Pulmonary hypertension (PHT) is a widely recognized complication of
hereditary hemolytic anemia including sickle cell anemia, thalassemia,
hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria.
• Recent studies have found the prevalence of pulmonary hypertension
in children to be between 16% and 26.2 %.
• Sickle cell disease is one of the disease at risk to develop PHT.
3. Aims and Objectives
• Aims :
To determine the prevalence of elevated pulmonary artery
pressures in children with sickle cell disease.
• Objectives :
• To identify the risk factors that are associated with the
development of elevated pulmonary artery pressures.
• To correlate with various demographic characteristics.
• To study variation in clinical presentation and biochemical
markers
• To study the transfusion requirements and treatment details in
patients of pulmonary hypertension.
4. Materials
• Design: Observational study
• Place of the study: Paediatrics Haematology-Oncology Division,
LTMGH and LTMMC Sion.
• Duration of the Study: March 2013- February 2014 (12 Months)
• Sample size: 50
• Inclusion Criteria: All patients between the ages of 5 to 18 years
diagnosed to have Sickle Cell Syndromes (Hb-SS, Hb-SC, Hb-SD, Hb-
S/β+,Hb-S/β0 ) who were registered at our Centre for regular treatment.
• Exclusion Criteria: Patients with pulmonary stenosis / or any other
structural obstruction to pulmonary blood flow were excluded.
5. • History included the
• Patient’s age at diagnosis
• Age at first transfusion,
• Frequency of transfusion,
• Frequency and types of crisis
• Treatment details.
• A complete physical examination was performed and findings were
noted.
• Special emphasis was laid on the presence of anemia, icterus,
hepatosplenomegaly and stigmata of crisis.
Methodology
6. Investigations
• Complete hemogram with reticulocyte count,
• Liver function tests,
• Renal function tests,
• Chest radiograph,
• Electrocardiogram
• Pulse-oximeter
• 2D Echogram. :- Pulmonary Hypertension
Normal : TRV < 2.5 m/second (PAP <30 mmhg)
Mild : TRV of 2.5 to 2.9 m/second (PAP 30-39 mmhg)
Moderate : TRV ≥ 3 m/second (PAP >40 mmhg)
to Severe ( Reference from ASC )
7. RESULTS
Age and Gender Distribution of Patients
5 to 10 years 11 to 15 years 15 to 18 yrs
Females 9 10 1
Males 11 15 4
11
15
4
9
10
1
0
5
10
15
20
25
30
No.ofpatients
9. First Presenting Symptom (n=50)
35 (70%)
13 (26%)
1 (2%) 1 (2%)
0
5
10
15
20
25
30
35
40
Painful crisis with
pallor
Fever with pallor Lump in abdomen
with pallor
Severe Pallor with
failure
Number of patients
14. Association of various Factors with PHT
Parameters PHT N Mean SD SE of
Mean
T value P value Significance
No of VO crisis No 31 1.3548 0.984 0.17495 2.130 0.046 Yes
Yes 19 1.7368 1.77375 0.40693
No. of PRC
transfusion No 31 3.4516 7.04196 1.26477 2.231 0.043 Yes
Yes 19 6.1579 8.31507 1.90761
15. Correlation of Hb with PHT
7.25
9.58
6.31
9.26
0
2
4
6
8
10
12
Mean Baseline
Hb
Mean Hb on
treatment
Normal PHT
Parameters PHT N=50 Mean P
value
Significance
Hemoglobin
at baseline
No 31 7.2581 0.046 Yes
Yes 19 6.3158
Hemoglobin
on
treatment
No 31 9.5806 0.496 No
Yes 19 9.2632
16. Cont.…
Parameters PH
T
N=50 Mean SD SE of
Mean
T value P value Significance
Indirect
bilirubin No 31 0.8710 1.1472 0.20605 2.303 0.045 Yes
Yes 19 1.7368 1.2841 0.29461
Serum LDH
No 31 885.789 265.21 67.32870 2.127 0.045 Yes
Yes 19 996.774 374.87 60.84433
Retic count
baseline No 31 3.4516 1.1786 0.21169 2.156 0.036 Yes
Yes 19 4.4211 2.0087 0.46084
17. Cont.…
Parameters PH
T
N=50 Mean SD SE of
Mean
T value P value Significance
Age of
starting
Hydroxyurea
(years)
No 31 6.9677 3.84260 0.69015 1.943 0.049 Yes
Yes 19 6.0000 2.90593 0.66667
Mean dose
of
Hydroxyurea
(mg/Kg/day)
No 31 19.7419 4.93266 0.88593 2.108 0.045 Yes
Yes 19 20.5789 5.55093 1.27347
19. Cont.…
• Patients who had raised biochemical markers of hemolysis had
significant association with raised pulmonary hypertension.
• Patients with PHT had more no. of crisis as compared to those with
normal pulmonary pressures. (p=0.046)
• Hydroxyurea had been started at an earlier age in patients with PHT.
maximum no. of the pts between age groups of 11-15 years, males more predominant than females with ratio of 3:2
Maximum belonged to boddha and Adivasi community
Pallor was the common presentation amongst all patients.
Most frequent clinical presentation was bony crisis followed by hemolytic crisis.
Out of 50 pts,12 had mild & 7 had moderate PHT.
Out of 50 pts, 26 pts had sickle cell homozygous, 22 had sickle beta thalassemia, 2 had sickle d disease. Amongst 26 pts of sickle cell homozygous, 8 had mild & 2 had moderate PHT. Amongst 22 pts of sickle beta thalassemia, 3 had mild & 5 had moderate PHT.
Overall, sickle cell homozygous had more frequent PHT than sickle cell heterozygous.
Pts with PHT had most clinical presentation was bony crisis.
Number of packed red cell transfusions required in patients with pulmonary hypertension was 6.1 ± 8.31 times/year as compared to those with normal pulmonary hypertension (3.4 ± 7.04 times/year) which was statistically significant
Pts with PHT had low mean baseline haemoglobin at the time of diagnosis & over the period of time with the treatment had low haemoglobin.
, the markers of hemolysis such as high reticulocyte count (p = 0.036), increased unconjugated serum bilirubin (p = 0.041), raised serum Lactate Dehydrogenase (LDH) (p = 0.045) had significant association with raised pulmonary hypertension.
In sickle cell patients with raised pulmonary hypertension hydroxyurea had been started at an earlier age (mean 6 ± 2.90 years) as compared to those with normal pulmonary hypertension. (6.9 ± 3.84 years) which was statistically significant.
The mean dose required of Hydroxyurea was 20.5 ± 5.55 mg/kg/day which was higher amongst those with raised pulmonary hypertension.
