Neonatal thrombocytopenia is a significant cause of morbidity and mortality particularly in the sick newborns, premature babies and neonates admitted in neonatal intensive care units and usually indicate an underlying pathologic process.

Neonatal thrombocytopenia is defined as a platelet count less than 150×109 /L regardless of gestational age. ^1,2,3 The important causes of thrombocytopenia in neonates are sepsis, birth asphyxia, prematurity, intra-uterine growth retardation, hyperbilirubinemia, respiratory distress syndrome, meconium aspiration syndrome and low birth weight. Apart from platelet count, bleeding manifestations depend on underlying ailments.⁴Multiple disease processes can cause thrombocytopenia in neonates and these can be classified as early onset (<72 hours) and late onset (>72 hours) neonatal thrombocytopenia. Early onset neonatal thrombocytopenia has a benign course and predictable outcome. Whereas late onset is more severe.⁶

Thrombocytopenia (platelet count <1.5lakhs/μl) is one of the most common hematological problems in NICU with 18-35% of neonates developing this problem.⁷

The overall prevalence of thrombocytopenia in neonates ranges from 1 to 5% and is reported to be much higher in neonates admitted to neonatal intensive care units, ranging from 22 to 35%.⁸

The evaluation and management of neonatal thrombocytopenia is a frequent challenge for neonatologists since one out of each four neonates develops thrombocytopenia at some point of hospital stay.⁹

Ethical clearance was obtained from Institutional Ethics Committee. A prospective observational study was done on 100 neonates with thrombocytopenia in the Department of Pathology for over a period of two years i.e August 2022 to July 2024 at Tagore Medical College and Hospital.All newborns admitted in NICU (inborn/outborn) developed neonatal thrombocytopenia were included. Neonates whose parents or guardians who do not agree to be a part of study were excluded.

Methodology  

At admission the parents and/or the guardian were informed about the study and written consent was obtained. A detailed history including of maternal obstetric history, birth history, perinatal history, onset of thrombocytopenia and neonatal risk factors of thrombocytopenia as per the proforma was obtained.

Gestational age of all neonates was determined based on the New Ballard’s scoring system till 14 days of life. Growth assessment at birth or admission by recording birth weight to detect intrauterine growth restriction was based on growth charts.

All the neonates underwent necessary blood investigations as complete blood count, platelet count, peripheral smear study, blood culture and septic screen. Blood was collected in sterile EDTA bulbs by venepuncture after taking all aseptic precautions and transferred to Central Laboratory of our hospital, the time lag between collection and estimation was usually 10 to 15 minutes.

CBC was obtained from a 5 part automated haematology analyser. The automated haematology analyser used in our laboratory was sysmex 5partxp300. Peripheral smear examination and blood cultures were done using standard laboratory methodology. Low platelet counts were cross verified by peripheral smear study. Other investigations such as urine culture, chest X-ray, neurosonogram and CT brain were performed whenever the need arises. Neonatal details such as clinical symptoms, diagnosis, platelet count and other relevant investigations, duration of the stay and outcome were documented. Follow up was kept till neonatal period. Relevant data was entered in a proforma and analyzed.

Statistical analysis:

Descriptive data are presented as numbers or percentages. Comparison of the groups for categorical variables was done by Chi-square test. Continuous variables were analyzed using unpaired two-tailed student t-tests or by one-way analysis of variance (ANOVA). A ‘P’ value below 0.05 was considered significant.

Gender distribution: Males (60%) were more reported compared to females (40%) . M:F Ratio-3:2

Figure-1: Gender distribution in present study

Distribution of maternal age :Age distribution varied from 20 years to 30 years, majority noted among 31-40 years constituting 50% and next common were among 31-40 years accounting 40% .Only 10 cases were noted among 41-50 years ,

Based on distribution of  Gravida : Primigravida constituted 65% and Multigravida 35%

Based on distribution of type of delivery: Majority of the neonates delivered by  preterm delivery(< 37 weeks) in 58% cases where as term delivery(>37 weeks)  noted in 42% cases with a mean (SD) gestational age of 35.2 (4.7) weeks. Full term babies had moderate thrombocytopenia and preterm babies had severe neonatal thrombocytopenia which was statistically significant (P value 0.012).

Based on distribution of mode of delivery: Majority delivered by normal delivery accounting 65%, LSCS in 30% cases and forceps delivery in 5% cases.

Based on distribution of Birth weight :Majority of the neonates were of VLBW(less than 1000gms) constituting 45% followed  by LBW(1001-2500 gms) in 30% cases and   25% neonates showed birth weight  of> 2500 gms and the mean (SD) birth weight was 980 gm.Very  Low birth weight was significantly associated with moderate to severe thrombocytopenia (P value 0.007).

Based on distribution of maternal risk factors - Majority of the mothers noted anemia as the major risk factor in 60% cases, next common was Hypertensive diseases of pregnancy constituting 20%. Eclampsia 10%, PROM and Oligohydramnios 5% .

Table 1: Distribution of etiology of thrombocytopenia

In our study, sepsis was commonest etiological factor contributing 42 %, next common was prematurity accounting for 28 %. Respiratory distress in 10% cases, intrauterine growth retardation 8% cases, meconium aspiration syndrome 3%, birth asphyxia 5% and jaundice 4%

Based on distribution of onset of thrombocytopenia: 55% with Late onset thrombocytopenia(> 72hours) and 45% showed Early onset thrombocytopenia (< 72 hours)

Table-2: Distribution of etiology of thrombocytopenia and thrombocytopenia

In our study Mild, moderate and severe thrombocytopenia noted in 15% , 60% and 25% cases.

Sepsis was associated with severe neonatal thrombocytopenia and it was statistically significant (P value 0.0001).

Figure-2: Bar diagram showing etiology of thrombocytopenia and thrombocytopenia

In our study, males (60%) were more reported compared to females (40%). M:F Ratio-3:2, similar findings were noted in Mohamed Eltawe et al ¹¹,Keerthi et study  ¹⁰with (57, 70.4%) and  112 (56%) .We found a larger proportion of male babies (3:2 male to female ratio). Male gender was associated with moderate and severe thrombocytopenia; however it was statistically not significant (p value 0.24).

In our study, age distribution varied from 20 years to 30 years, majority noted among 31-40 years constituting 50%, next common were among 31-40 years accounting 40% .Only 10 cases were noted among 41-50 years. In Mohamed Eltawe et al study ¹¹  the mean maternal age was 30 (5.5) years, with 46 (54.8%) older than 30 years.

In our study, primigravida constituted 65% and multigravida 35% .In Mohamed Eltawe et al ¹¹ mothers with a gravidity of 3 or less numbered 49 (58.3%), whereas those with a parity of 2 or less numbered 51 (60.7%).

In the present study, majority of the neonates delivered by preterm delivery (< 37 weeks) in 58% cases, term delivery (>37 weeks) noted in 42% cases. Whereas in Mohamed Eltawe et al study ¹¹ almost half of the neonates (n = 42, 51.9%) were full-term, whereas 20 (24.7%) were classed as moderate to late preterm, 14 (17.3%) were very preterm, and 5 (6.1%) were extremely preterm,

In the present study, majority of the neonates were of VLBW (less than 1000gms) constituting 45% followed  by LBW(1001-2500 gms) in 30% cases and 25%  neonates showed birth weight  of > 2500 gms. In Mohamed Eltawe et al study ¹¹neonates with a normal birth weight comprised 39 (48.1%) of the sample, followed by 18 (22.2%) with a low birth weight, 17 (21%) with a very low birth weight, and 7 (8.7%) with an extremely low birth weight. Keerthi et al study, babies with low birth weight (<2.5 kg) constituted 125 (62.5%) of total babies and babies with birth weight ≥2.5 kg constituted 75 (37.5%) of total babies with neonatal thrombocytopenia.

In our study, very low birth weight was significantly associated with moderate to severe thrombocytopenia (P value 0.006).This was in concordance with Keerthi et al study.¹⁰ Aboli daha et al study ¹⁴(62%) subjects were appropriate for gestational age (AGA), and the rest (38, 38%) were small for gestational age (SGA), and there was no large for gestational age (LGA) baby in our group.

In the present study, majority of the mothers noted anemia as the major risk factor in  60% cases, next common was hypertensive diseases of pregnancy constituting 20% . Eclampsia 10%, PROM and oligohydramnios 5%. In Mohamed Eltawe et al ¹¹study, mothers with a history of abortion numbered 24 (28.6%), and those with complicated pregnancies (featuring, for example, oligohydramnios, membrane rupture, hypertension, or gestational diabetes) numbered 17 (21.2%). In Keerthi et al study ¹⁰,among maternal risk factors, PIH (pregnancy induced hypertension) was the commonest cause. 27 (13.5%) babies had PIH as the maternal risk factor followed by PROM in 15 (7.5%) babies, anemia in 11 (5.5%) babies, oligohydramnios in 8 (4%) babies and eclampsia in 6 (3%) babies.

|In our study, sepsis  was commonest etiological factor  contributing 42 %, next common was prematurity accounting 28 % , respiratory distress in 10% cases, intra uterine growth retardation 8% cases, meconium aspiration syndrome 3% ,birth asphyxia 5% , j jaundice 4%. Sepsis along with thrombocytopenia noted with poor outcome in present study. In Purushotam et al study ¹² sepsis (60%), prematurity (13%), birth asphyxia (11%) and respiratory distress (8%) were common causes of death of neonates with thrombocytopenia. Sonam et al¹³ showed prematurity (38.3%) as the most common cause of neonatal thrombocytopenia followed by neonatal sepsis (22.2%). Keerthi et al study¹⁰ among multiple neonatal risk factors, sepsis was the most common cause of neonatal thrombocytopenia and was found in 97(48.5%) babies. Birth asphyxia was present in 40(20%) babies, RDS (respiratory distress syndrome) in 14(7%) babies, NNH (neonatal hyperbilirubinemia) in 39(19.5%) babies and MAS (meconium aspiration syndrome) in 10 (5%) babies. In Aboli daha et al ¹⁴ study, in neonatal sepsis, (95, 95%), early-onset thrombocytopenia was present in 33 neonates (34.74%), and late onset was present in 62 (65.26%) neonates. Late-onset thrombocytopenia (47, 62.67%) was more predominant in preterm neonates as compared to early-onset thrombocytopenia, which was seen in 28 (37.33%) neonates. 

In the present study 55% showed late onset thrombocytopenia (> 72 hours) and 45% with early  onset thrombocytopenia (> 72hours).In keerthi et al study¹⁰ , 88 (44%) babies had early onset neonatal thrombocytopenia and 112 (56%) babies had late onset neonatal thrombocytopenia.

We found that the incidence of  late onset neonatal thrombocytopenia was more common and it was associated with moderate to severe neonatal thrombocytopenia in our study .Similar results were obtained by Lim et al. ¹⁵with LOS compromising the majority (93.7%). While in a study done by Bagale and Bhandari ¹⁶, the majority (27%) of neonates presented with EOS, while LOS was seen in only 2.7%.

In our study, mild, moderate and severe  thrombocytopenia noted in 15% ,60% and 25% cases, where as in  Mohamed Eltawe  et al study  ¹¹the incidences of mild, moderate, and severe thrombocytopenia were 56 (1.3%), 19 (0.4%), and 6 (0.1%), respectively. Aboli daha et al ⁴study majority of neonates had moderate thrombocytopenia (37, 37%), while mild and severe thrombocytopenia was seen in 32 (32%) and 31 (31%) neonates, respectively.

Neonatal thrombocytopenia is a common clinical entity in NICU and a prognostic marker of many disease conditions in neonates. The severity of neonatal thrombocytopenia in our NICU was moderate to severe type. Early onset neonatal thrombocytopenia i.e onset of thrombocytopenia after 72 hours was more common than late onset neonatal thrombocytopenia. Very low birth weight babies were more prone to severe thrombocytopenia. Preterm babies had severe thrombocytopenia whereas term babies had moderate thrombocytopenia. The most common maternal predisposing factors were anemia, pregnancy induced hypertension (PIH), premature rupture of membranes (PROM). Sepsis and prematurity were the commonest neonatal factors associated with thrombocytopenia. Severe thrombocytopenia can be used as a prognostic indicator in sick neonates.  Neonatal thrombocytopenia is a treatable and reversible condition. Hence it is important to identify neonates at risk and initiate appropriate therapy to prevent severe bleeding and potentially significant morbidity. Babies born to mothers with PIH and PROM and those with sepsis, birth asphyxia, and other risk factors should be closely monitored for thrombocytopenia and early intervention should be done to control them.

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