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

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.

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.

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.

• 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

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 )

RESULTS Age and Gender Distribution of Patients

5 to 10 years 11 to 15 years 15 to 18 yrs

Males 11 15 4

Females 9 10 1

2.5

7.5

12.5

17.5

22.5

27.5

1115

4

9

10

1

No.

of p

atien

ts

Community Distribution of Patients

Boudha, 27

Adivasi,8

Bairagi, 1

Mahar, 1

Oriya, 1

Banjara, 1

Patel, 1

Suryavanshi, 1

Konkani, 2

Muslim, 2

Dhobi, 2Mang, 1 Prajapati, 1 Katkari, 1

Boudha Adivasi Bairagi Oriya Banjara Patel Suryavanshi Konkani Muslim Dhobi Mang Prajapati

Katkari

First Presenting Symptom (n=50)

Painful crisis with pallor

Fever with pallor Lump in abdomen with pallor

Severe Pallor with failure

05

10152025303540

35 (70%)

13 (26%)

1 (2%) 1 (2%)

Number of patients

Frequency of Clinical Presentation

Bony Crisis

No Crisis

VO+Hemolytic

Acute Chest

Syndrome

Sickle Hepato

pathy

Hemolytic

Splenic Sequestr

ation0

5

10

15

20

25

30

35

4036

4 42 2 1 1

Grades of PHT

62%, (31)

24%, (12)

14%, (7)

No PHT

Mild PHT

Moderate PHT

Correlation of PHT with Types of Sickle Cell Disease

Types of Sickle Cell Disease

PHTTotal

(N=50)Mild Moderate Normal

Sickle cell homozygous

8 (16%) 2 (4%) 16 (32%) 26

HbS/ β+ thalassemia

3 (6%) 5 (10%) 14 (28%) 22

Hb S/ D disease 1 (2%) 0 (0%) 1 (2%) 2

Total12 7 31 50

Correlation of PHT with Clinical Presentation

0

5

10

15

20

25

30

12

2 2 2 1 0 0

24

2 20 0

2 1

PHT NO PHT

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      

Correlation of Hb with PHT

Mea

n Bas

eline H

b

Mea

n Hb on

trea

tmen

t0

2

4

6

8

10

12

7.25

9.58

6.31

9.26

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    

Cont.…Parameters PH

TN=50 Mean SD SE of

MeanT 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      

Cont.…Parameters PH

TN=50 Mean SD SE of

MeanT 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 doseof

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      

conclusion

• Out of 50 patients, 19 (38%) PHT • 10 (52.63%)- Sickle cell homozygous, • 8 (42.11%) -HbS/β+ Thalassemia,• 1 (5.26%) - Sickle HbS/D disease.

• Severity Of PHT• 12 (24%) Mild PHT, • 7 (14%) Moderate PHT.

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.

Thank You