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Neonates often develop thrombocytopenia at some time during hospital stay. Platelet transfusion are frequently given to them and are likely to result in unnecessary transfusion.
Thus, we analyzed thrombocytopenia in neonates, its prevalence, and relationship if any, between clinical condition and platelet transfusion in neonates, which would have been helpful in developing guidelines and/or protocols for platelet transfusion (and reducing the donor exposure) in neonates.
A total of 870 neonates who were admitted in Neonatal Intensive Care Unit (NICU) with various morbidities had platelets count done; of these, 146 (16.7%) neonate revealed thrombocytopenia.
Low birth weight babies (P 0.009) and babies born with mother having hypertension (P 0.04) showed significant thrombocytopenia. Neonates with intrauterine growth retardation (IUGR) diagnosed during antenatal screening showed lower platelet count (P 0.022). Neonates having associated illness, such as sepsis, gastrointestinal, and respiratory problems, and on vasopressor drugs were found to be associated with low platelet count.
In our study, 16.40% of thrombocytopenic neonates required platelet transfusion either alone or with other blood component during their stay in NICU.
Thrombocytopenia is defined as platelet count less than 150 × 109/l, and is not uncommon among neonates. Up to 30% of NICU patients develop thrombocytopenia at some time during hospital admission.[3–6] Platelet transfusion is frequently given to NICU patients and are likely to result in unnecessary transfusion. Improved guidelines are required for safe lower limit for platelet transfusion in stable and sick neonates, effective platelet transfusion protocols in sick neonates, and improved therapy for conditions which precipitate thrombocytopenia. While most neonates with thrombocytopenia have a moderate reduction in platelet count and resolve with appropriate treatment of underlying cause, about 25% receive one or more transfusion. There is paucity of data on the prevalence and causes of thrombocytopenia in neonates from India. Present study was undertaken to investigate the prevalence of thrombocytopenia and to ascertain its relationship if any, between clinical condition and platelet transfusion in neonates, which would have been helpful in developing guidelines and/or protocols for appropriate platelet transfusion (and reducing the donor exposure) in neonates.
Data included were neonatal demographic information (age, sex, gestational age, and birth weight). Information regarding the clinical data of neonate, e.g., sepsis, renal failure, ventilator assistance, use of ionotropes, birth asphyxia (delayed cry), gastrointestinal problems, and medications were noted prospectively on "epi-info" during NICU stay. The maternal data included age, parity, pregnancy related complications, antenatal findings in ultrasound, and any other associated illness. The data related to transfusion consisted of frequency and volume of transfused platelets or other components. All admissions in NICU between Jan. 2001 and Sept. 2004 were included in this study. Whenever required, neonates were investigated for platelet counts and were the subject of this study. Neonates with platelet count <100 × 109/l were further subdivided into three groups depending on platelets count [Table 1]; group I (51–100 × 109/l, mild thrombocytopenia), group II (30–50 × 109/l, moderate thrombocytopenia), and group III (<30 × 109/l, severe thrombocytopenia).
Means were calculated for variables. Statistical analysis was done and P value was derived from Fisher's test. P value less than or equal to 0.05 was considered statistically significant.
A total of 870 neonates who were admitted in Neonatal Intensive Care Unit (NICU) with various morbidities had platelets count done. Of these, 146 (16.7%) neonates showed platelet count less than 100 × 109/l and consisted of 70, 40, and 36 in group I, II, and III, respectively [Table 1].
Thrombocytopenia in neonates was analyzed in relation to birth weight and gestational age of neonates [Tables [Tables22 and and3].3]. Platelet count was significantly lower in low birth weight (LBW) babies having birth weight < 1500 g than babies with birth weight > 2500 g (169400 ± 87200 vs. 200100 ± 88300). About, 44.4% babies in LBW group experienced thrombocytopenia. Gestational age showed no effect on neonatal thrombocytopenia. Although 45% and 36% premature neonates in geastational age of <30 weeks and 31–35 weeks, respectively, showed decrease in platelet count, but statistical analysis showed no significance (P 0.054).
Of maternal factors, platelet count was significantly lower in neonates born with mother with hypertensive disorders of pregnancy (HDP) [Table 4]. Maternal hypertension was present in 220 cases and a significant cause for lower platelet count (180400 ± 84100 vs. 190600 ± 85500, P 0.04). Mean platelet count decreased with the severity of HDP. HDP noted in 64 cases of thrombocytopenia; of these 15 had platelets count < 30 × 109/l. 135 neonates with intrauterine growth retardation (IUGR) diagnosed during antenatal screening showed lower platelet count (172900 ± 79400 vs. 191000 ± 73600, P 0.022). Details of antenatal screening were not available in five cases. No association was noted for fetal distress, antepartum hemorrhage, maternal diabetes, parity, prolonged leaking, and type of delivery.
Among 146 thrombocytopenic neonates, sepsis was observed in 81.5% (119), GI problems in 57.7% (80), respiratory problem (delayed cry, meconium) in 43.1% (63), and intracranial hemorrhage in 13.6% (20) either alone or in combination [Table 5]. In addition, 41.7% (61) neonates received inotropic support. Clinical sepsis lowered the platelet count (21819 ± 21268 vs. 49256 ± 21894), 41 had positive blood culture; 35 showed infection with gram-negative bacteria, 2 had shown growth of gram-positive bacteria, and 4 showed growth of Candida. Neonatal respiratory problems, ventilation, and neurological problems had an association with low platelet counts but showed no significance statistically. Neonatal gastrointestinal problems were significantly higher among thrombocytopenic babies (P 0.03); the later may be due to association with sepsis.
With regard to platelet transfusions, 16.4% (24) neonates were transfused with platelet, number being 13, 3, 5, 2, and 1 for 1, 2, 3, 4, and ≥5 units of platelet transfusion, respectively [Table 6]. It was given for babies with evident and anticipated bleeding tendency with severe thrombocytopenia. In addition, whole blood and fresh frozen Plasma (FFP) was transfused in 75.3% (110) and 53.4% (78) neonates, respectively, either alone or in association with platelet. Platelet transfusion was more in group III (70.8%) as compared to groups I and II.
Thrombocytopenia is one of the most common hematological condition in neonates, affecting about 25% of NICU admission, and about one third of preterm neonates in NICU. In the present study, lower platelet count was found in 16.7% (146/870) neonates, of which 70 (8.0%) showed platelet count between 51-100 × 109/l, 40 (4.5%) showed 31-50 × 109/l, and 36 (4.2%) showed count less than 30 × 109/l. The prevalence of thrombocytopenia in NICU is comparable with studies from other places.[3–6]
One important factor responsible for neonatal thrombocytopenia is birth weight. Neonates in all thrombocytopenic group showed no significant differences in birth weight; however, LBW babies showed statistically significant (P 0.009) thrombocytopenia due to their limited ability to compensate for accelerated destruction of platelets. Similarly, neonates with IUGR diagnosed during antenatal screening showed lower platelet count (P 0.022).
Numerous maternal and fetal conditions are associated with low platelet count. Newborn of mothers with maternal hypertension are prone for thrombocytopenia due to disorders associated with placental insufficiency[10,11] leading to hypoxia. Newborn with respiratory problems during birth (delayed cry, meconeum) often develop thrombocytopenia. The hypoxic injury to baby during birth drives the progenitor cells to produce erythroid cells at the expense of leucocytes and thrombocytes.
Clinical sepsis was found in association with thrombocytpenia in 81.5% (119) neonates in present study, 41 had positive blood culture. Bacterial infection causes damage to vascular endothelial lining, thus accelerating adhesion, destruction, and removal of platelets. Sepsis also causes DIC, immune-mediated destruction, and decreased production of platelets from infected marrow. In our setup, organisms isolated in order of frequency were Klebsiella sp. (16), E. coli (11), Pseudomonas sp. (8), gram-positive cocci (2), and Candida in 4 patients. Viral infection increases platelet destruction due to loss of sialic acid from platelet membrane, increases platelet aggregation, and decreases production from infected marrow.[10,13]
A total of 870 neonates investigated for platelet count, 146 were found thrombocytopenic. 24 neonates were transfused with platelets; out of these, 45.8% (11) neonates received multiple platelet transfusion. In addition, other blood component (red cells in 110 and FFP in 78 neonates) were also transfused. 20% (27) neonates did not receive any transfusion. Each transfusion consisted of 10–15 ml of product per kg of body weight. Demographic features and clinical diagnosis who received single unit of platelet were contrasted with those who received more than one unit. It has been shown that about 70.8% patients in group III received platelet transfusion in comparison who are mildly thrombocytopenic.
In present study, we aimed to identify thrombocytopenic neonates prospectively who would require platelet transfusion during their stay in NICU. Our results suggest that gestational age and sex do not predict the thrombocytopenia among NICU neonates. LBW, IUGR, and maternal hypertension were associated with neonatal thrombocytopenia; however, not to conclude that these factors alone are responsible for thrombocytopenia in neonates independently. These conditions in association with sepsis, GI problems, and hypoxia, rather necessitate more transfusion of platelet and blood components in NICU. The need of platelet transfusion in neonates could be a marker of severity of clinical illness in NICU patients.
Guidelines for platelets transfusion in neonates were available, but were not strictly followed while administering platelet in NICU and is a limitation for the present study. There is practice amongst neonatologist towards more liberal use of platelet transfusion. The frequent need of repeated platelet transfusion may require use of recombinant thrombopoeitin (rTPO) as an alternative for platelet transfusion, as megakaryocyte progenitors are sensitive and responds even with lower concentration[16,17] of rTPO; however, not all thrombocytopenic neonates respond well. Further studies are needed for a definite role in neonates, as anti-TPO antibody develop in patients receiving rTPO.
Our study documents the incidence of thrombocytopenia in NICU and the conditions necessitate the need for platelets transfusion in neonates. Statistical analysis showed that neonates who are more likely to develop thrombocytopenia are LBW (P 0.009) and born with mother having maternal hypertension (P 0.04). IUGR is another predisposing factor for thrombocytopenia (P 0.022). Neonates with sepsis having GI problems and on vasopressure drugs are more likely to develop thrombocytopenia, thus received more transfusion. In our study, 16.40% of thrombocytopenic neonates received platelet transfusion either alone or with other blood component during their stay in NICU. However, further studies from other centers are required to establish prevalence, pattern, and predisposing factors of thrombocytopenia and transfusion of platelet in neonates in Indian population.
Source of Support: Nil
Conflict of Interest: None declared.