European Journal of Cardiovascular Medicine

Pneumonia is defined as inflammation of the parenchyma of the lungs. From the pathological view point, it results from invasion of lungs by infectious agent which may start an inflammatory response and ensuing damage may involve airways, alveoli, connective tissue, visceral pleura and vascular structures ^[1]. According to the revised World Health Organization (WHO), pneumonia is defined as the presence of cough with fast breathing (≥60 breaths/ min in <2 months of age, ≥50 breaths/ min in 2–12 months of age, and ≥40 breaths/min in 1–5 years of age) and/or lower chest in drawing, which requires home therapy with oral amoxicillin and severe pneumonia is defined as pneumonia with any general danger sign like presence of refusal to feed, persistent vomiting, convulsions, lethargy or unconsciousness, cyanosis, and stridor in a calm child with chest indrawing, which requires a referral and injectable therapy ^[2]. Pneumonia is the single largest infectious cause of death in children worldwide. Pneumonia killed 740180 children under the age of 5 in 2019, accounting for 14% of all deaths of children under 5 years old but 22% of all deaths in children aged 1 to 5 years ^[2].               

Community-acquired acute pneumonia refers to lung infection in otherwise healthy individuals that is acquired from the normal environment ^[3]. Pneumonia prognosis in children is based on complications associated with it like pleural effusion, empyema, lung abscess, respiratory failure, sepsis among which Respiratory failure and sepsis are the important cause of death in children having pneumonia ^[4].

Platelets are important part of host defence, induction of inflammation and repair of tissue. Activation of platelets causes activation of complement system, cell mediated and humoral immunity. Inflammatory thrombocytosis is associated with increased levels of cytokines like thrombopoietin, interleukin-6, interleukin-1alpha, interleukin-8 and TNF alpha.  Severe community acquired pneumonia is associated with significant rise of inflammatory cytokines TNF-α, IL-1b, IL-6, IL-8. The TNF-α, IL-1b and IL-6 also seen in the bronchoalveolar lavage fluid of patients with community acquired pneumonia, interactions with complement proteins and humoral immune components, as well as leukocytes and endothelial cells. Normal platelet counts 150000/mm³ and 450000/mm³ in neonates, infants, children and adolescents. The rise in the peripheral blood platelet count values to >500000/mm³ is common in infancy and childhood, occurring in 3 to 13% of children. Bacterial, viral infections (acute or chronic) are commonest cause for reactive thrombocytosis (37-78%) in children. Within this group, infections of the respiratory system will have 60-80% of reactive thrombocytosis ^[5].

Only few studies have been done on platelet count and its association with pneumonia depicting various controversial results. Therefore, the aim of the present study is to establish relationship between abnormal platelet counts as a prognostic indicator in community acquired pneumonia. This study will help us identify the prognosis or risk based on abnormal platelet counts in CAP and helps us to plan appropriate early interventions to prevent complications and to reduce Infant mortality & Under 5 mortality rates.

After obtaining ethical clearance from the institutional ethical committee, a retrospective observational study was conducted in the Department of Paediatrics in a tertiary care teaching hospital in Karwar from April 2021 to April 2023 for a duration of 24 months.

Objectives: To observe the association between

1. Abnormal platelet count (high and low) and complications of CAP in children.
2. To study the relationship among Platelet count and total leukocyte count (TLC) and CRP in the same patients.
3. Platelet count and the time taken for recovery of pneumonia.

Inclusion criteria:

1. All the children aged between 2 months to 5 years.
2. Fulfilling the clinical criteria of “Pneumonia” and “Severe Pneumonia” according to the revised WHO classification and admitted to the Paediatric ward/ Paediatric intensive care unit (PICU).
3. Children of the parents who have given the informed consent.

Exclusion criteria: Children suffering from

1. Congenital heart disease (CHD)
2. Respiratory diseases like tuberculosis, cystic fibrosis, bronchial asthma, foreign body inhalation, laryngomalacia, aspiration and chemical pneumonitis, trauma causing pneumothorax.
3. Leukaemia and other malignancies.
4. Any known cases of idiopathic thrombocytopenic purpura
5. Known cases of HIV
6. Children of the parents who are not willing to give consent.

The necessary clinical and laboratory data was retrieved from case sheets in medical records department. All the consecutive pneumonia and severe pneumonia diagnosed cases presented to the paediatrics department fulfilling the inclusion and exclusion criteria during the study period were considered in the present study. A total of 150 cases including both pneumonia and severe pneumonia were added into the study after getting written informed consent from their parents or guardians.

Epidemiological data like name, age, gender, socioeconomic status along with date and type of admission which includes paediatric ward and PICU, date of discharge and number of days of hospital stay were recorded. The presenting clinical complaints such as fever, cough, coryza, fast and noisy breathing, refusal to feeds including other complaints like vomiting, lethargy, loose stools, convulsions, headache, chest pain, throat pain etc., along with their duration were considered. Documented vitals, general and respiratory system examination findings like temperature, pulse rate, blood pressure, Spo₂, glasgow coma scale (GCS) and respiratory rate along with various clinical signs such as grunting, chest indrawing, cyanosis, crepitations, rhonchi and conducted sounds at the time of admission, discharge and on daily basis were noted.

Values of various laboratory investigations performed at the time of admission, discharge and at regular intervals were taken into account. These include haemoglobin (Hb), TLC and platelet count estimated using Sysmex XN500 automated haematology analyser and CRP through turbidimetric immunoassay in automated analyser. Haematological values from Dacie-Lewis practical haematology were taken as reference for Hb, TLC and platelet count. Complications like pleural effusion, empyema, sepsis and lung abscess were taken into consideration. Treatment given was in noted as type and duration of antibiotics, need, mode and duration of oxygen requirement. Final clinical outcome in terms of treated, referred, discharge against medical advice, discharge at request and death were noted. Data analysis was done using Microsoft excel, spss software.

A total of 150 children were included in this study, of which 113 (75.3%) children were diagnosed to have pneumonia and 37 (24.7%) severe pneumonia at the time of admission. Most of the children were in the age group of 3 to 5 years accounting for 58%. Male children were 87 (58%) and female children being 63 in number accounts for 42% with male to female ratio being 1.38. Duration of hospital stay was observed to be less than 7 days predominantly consisting of 111 children, forming 74%, followed by 8 to 14 days 21.3% and least number of children 7 (4.7%), of which 10.8% form severe pneumonia were admitted for more than 14 days. The most common complication observed was septicemia seen in 18 (12%), followed by respiratory failure in 3 (2%), seizures in 2 (1.3%) and 1 child was on ventilatory support which were significantly associated with severe pneumonia having p value of less than 0.001. Age, gender, duration of hospital stay and complications concerning pneumonia and severe pneumonia were mentioned in table 2.

Fever and cough were the most common presenting complaints followed by coryza, fast breathing and refusal to feeds seen in few children and showed significant association with severity of pneumonia in our study which is shown in table 3. Among various vital signs normal pulse rate observed in 61.4% and tachycardia in 37.3%. Tachypnea noted as major respiratory rate (RR) manifestation in 53.3% followed by normal RR in 43.4% of children. Out of 150 cases 2 severe pneumonia shown to have hypoxemia and rest 148 children have normal Spo_2. Hypothermia was observed as predominant temperature variation in 121 (80.7%), followed by normal temperature in 13.3% and 6% children observed to be febrile. Only 2% children shown to have GCS of 13/15 and majority (98%) were with normal GCS of 15/15. Association of various vital signs with respect to severity of pneumonia is shown in table 4.

Table 2: Complications and Duration of hospital stay showed significant association with severity of pneumonia

Table 3: Clinical complaints and their association with severity of pneumonia

Table 4: Association between vital signs and severity of pneumonia

Abnormal platelet count was observed in 29 cases, of which 12 (8.0%) showed thrombocytopenia and 17 (11.3%) showed thrombocytosis. High CRP values were noted in 130 (86.7%) of children. Low and high TLC were seen in 9.3% and 24% respectively. Various haematological parameters with respect to pneumonia and severe pneumonia is shown in table 5. Platelet count abnormality is significantly associated with complications in 51.7% cases having p value of less than 0.001 and TLC variation didn’t show any such association which is depicted in table 6. A significantly greater proportion of children with severe pneumonia had thrombocytopenia (16.2%) and thrombocytosis (24.3%) compared to children with non-severe pneumonia, as depicted in table 7. Significant weak positive pearson’s correlation between platelet count and TLC is shown in image1.

Table 5: Association of haematological parameters with severity of pneumonia

Table 6: Platelet count and TLC association with complications

Majority of the children were admitted to ward and account for 76% and the major outcome noted was successfully treated children comprising of 79.3% followed by 12% of DAMA, 4.7% of discharge at request, 4 cases were referred and 2 children have succumbed to death. The relation between type of hospital stay and the outcome concerning the severity of pneumonia is shown in table 8.

Table 7: *Significant, p-value for significance calculated using z-test for difference in proportions

Table 8: Association of outcome and type of stay with severity of pneumonia

Chest indrawing observed in 20.7% children, around 36% of children required O2 which was most commonly through nasal prongs in 17.3%, followed by face mask in 10.7%, hfnc in 5.3%, hfnc with np in 2.7% and 1 child was given hfnc with fm.

Image 1: Scatter diagram showing weak positive correlation between platelet count and TLC

Weak positive association identified between platelet count and TLC (Pearson's Correlation coefficient, r = 0.217 with p = 0.008*) [Image 1]. No significant association noted between platelet count and CRP (Pearson's Correlation coefficient, r = 0.094 with p = 0.255) [Image 2]. No significant association noted between platelet count and duration of hospital stay (Pearson's Correlation coefficient, r = 0.007 with p = 0.933) [Image 3]. 

Image 2: Scatter diagram showing no correlation between platelet count and CRP

Image 3: Scatter diagram showing no correlation between platelet count and duration of hospital stay

Platelets are important part of host defence, induction of inflammation and repair of tissue. Inflammatory thrombocytosis is associated with increased levels of cytokines like thrombopoietin, interleukin-6, interleukin-1alpha, interleukin-8 and TNF alpha. Pneumonia is most common cause of death in children of under 5 years of age as we most of the time use total validate abnormal platelet count as a prognostic indicator in community acquired pneumonia ^[5].

In our study, most children were in the age group of 3-5 years (58%). In a study by Chandrakala P et al., 55% of children were aged between 1-5 years which was concordant with our study ^[7]. In contrast to our study, Baruah A et al., found the majority of children in the age group of 2-12 months (85.9%) ^[4]. Males (58%) were predominant in our study compared to females (42%) with M:F ratio of 1.38:1 which is in concordance with the studies conducted by Atwa Z TH et al., (1.26:1) ^[8] and Chandrakala P et al., (1.25:1) ^[7]. In the current study severe pneumonia consisted 37% and whereas it was 20% in the study of Chandrakala P et al., ^[7] 50% in a study conducted by Sreenivasa B et al., ^[5] and 49% according to the study of Ansari MD E et al., ^[9].

In our study, the majority of children aged <1 year were admitted with severe pneumonia (21.6%) and 3-5 years age group children with non-severe pneumonia (62.8%). Similarly, in the study of Sreenivasa B et al., 51.9% of 2-12 months age group children were admitted with severe pneumonia, and children of 13-60 months of age were admitted with severe pneumonia (45.4%) followed by pneumonia (31.8%) indicating that, the severity of pneumonia is frequent during infancy ^[5]. Our study found systemic complications including septicemia in 14%, and respiratory complications in 2% of the cases. Baruah A et al., found 7.38% of children with pulmonary complications and 26.2% developed systemic complications ^[4]. In contrast, Atwa Z TH et al., documented most of the children to have pulmonary (27.3%) compared to systemic (17.4%) complications.

Our study found that most children with pneumonia have stayed in hospital for <7 days (74%) and 4.7% stayed for > 14 days. Similarly, in the study of Atwa Z TH et al., 66.5% have stayed for <2 weeks and 33.5% for >2 weeks. Baruah A et al., also observed that length of hospital stay for <5 days in 50% and >10 days in 3.4% of children ^[4]. 

In our study among 28 children with abnormal platelet count, 53.6% developed complications and 50% of the thrombocytopenia children developed systemic complications (sepsis). Similarly, Baruah A et al., found 76.84% children developing complications among 95 with abnormal platelet count and thrombocytopenia having a significant association with the development of systemic complications ^[4]. Atwa Z TH et al., also stated that acquiring sepsis is associated with thrombocytopaenia (p, 0.019, OR, 1.28, CI, 1.002-1.503).

In our study, among cases with thrombocytosis, 55.5% developed sepsis and 22.2% pulmonary complications. Significant association was observed between thrombocytosis and systemic complications. Where as Baruah A et al., found significant association between thrombocytosis and pulmonary complications but not with systemic complications ^[4]. Similarly, even Atwa Z TH et al., also found thrombocytosis (P, 0.000, OR 1. 56 CI, 225–2.390) is associated with the risk of developing pulmonary complications ^[8]. This discrepancy could be due to less number of children with pulmonary complications in our study. In our study significantly greater proportion of children with severe pneumonia had thrombocytosis (24.3%) (p=0.002). Chandrakala P et al., study also showed thrombocytosis was significantly associated with severity of pneumonia (p<0.0000001) ^[7].

In our study, Pearson's Correlation coefficient, r = 0.217 with p=0.008 showed a significant weak positive correlation between platelet count and TLC. In contrast, Baruah A et al., documented no association between platelet count and TLC ^[4]. In our study, abnormal leukocyte count did not show any association with the complications (p=0.697). In our study, Leukopenia noted in 13 cases, of which 3 (23.1%) showed complications, 1 child had Respiratory failure & 2 had Septicaemia.  Baruah A et al., found leukopenia was significantly associated with sepsis but not with pulmonary complications ^[4]. According to Atwa Z TH et al., leukopenia is associated with death (p=0.01) ^[8]. Our study identified leukocytosis in 36 cases, among which, 6 (16.7%) children developed complications, 1 child had Respiratory failure & 5 had sepsis. Baruah A et al., stated that leukocytosis had a significant association with pulmonary complications majorly ^[4]. In the study of Atwa Z TH et al., leucocytosis was not indicative of mortality (P = 0.787) or poor outcome of pneumonia ^[8].

In our study, we found no correlation between platelet count and CRP with Pearson's Correlation coefficient, r =0.094 with p = 0.255. Baruah A et al., derived a significant negative correlation with CRP (r=−0.119, p=0.04) ^[4]. We also found no significant association between platelet count and duration of hospital stay in our study with Pearson's Correlation coefficient, r = 0.007 with p = 0.933. In contrast to this, Baruah A et al., derived a weak but significant positive correlation between platelet count and the time taken for recovery (r=0.13, p=0.029) ^[4].

Platelet count plays an important role in children with CAP. Abnormal platelet count helps as a prognostic indicator and valuable marker to detect the complications and severity of outcome in CAP children. Thrombocytopenia and thrombocytosis are associated with systemic complications. There is no significant association between abnormal TLC and complications. There is a weak, but significant association between platelet count and TLC. No significant association noted between platelet count with CRP and duration of hospital stay.

CONFLICTS OF INTEREST

No conflicts of interest in our study.

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