In this study, out of 55 FT infants who developed NT during the study period, about half of them had severe NT at diagnosis, and about two-thirds of cases appeared after 72 hours of life. The most common causes of NT were neonatal sepsis and a postoperative state. Furthermore, when compared to mild/moderate NT, severe NT was associated with higher morbidity (pulmonary or IVH), needed more platelet transfusions, and had increased mortality.
In our study, severe NT was found in 52.73% of total thrombocytopenic cases. This result was higher than other studies. Gupta et al. (15) found that severe NT accounted for 34.4% of cases. In another study, 20% of cases were classified as severe NT (6). However, in a large cohort study including 11,281 NICU admissions of term or preterm infants over 5 years, Roberts et al. (4) found that severe NT was only identified in 2.4% of cases. The reason for a higher incidence of NT in our study was probably because the incidence of sepsis in our group was high. The relationship between the increased severity of thrombocytopenia and rates of neonatal sepsis also shown in Charoo et al. (16). In contrast to FT infants, in preterm babies, Christensen et al. (17) found that about 73% of extremely low birth weight infants, had at least a one-time platelet count <150 x 109/L at some time during their NICU stay, and this incidence increased up to 85% among neonates with a birth weight ≤ 800 g. Furthermore, in our study, most about two-thirds of NT cases in FT infants were late onset (after 72 hours of life). This may also be due to the increased late onset sepsis in our study group. In contrast, in the Resch et al. (9) study, in which 76% of cases were born preterm, early onset NT occurred in the majority of cases (84.1%).
NT occurs more frequently in association with certain factors, such as sepsis, birth asphyxia, babies born to mothers with pre-eclampsia, and low birth weight. This was also seen in our study, where the most common cause of NT was neonatal sepsis, which occurred in about one-third of cases. Furthermore, the most commonly isolated organisms in septic neonates were gram negative (E. coli and Klebsiella) in 55% of cases. These results are in good agreement with Ree et al. (18), who found that severe NT occurred in 20% of septic neonates and the most commonly isolated organisms were gram negative. The pathogenesis of NT in neonatal sepsis is not completely understood. It has been suggested that endothelial damage activates reticuloendothelial removal of platelets in neonatal sepsis, and thrombocytopenia occurs as, ultimately, the rate of platelet production falls behind platelet consumption (2). The second most common cause of NT in our study was a postoperative state. Although the definite causes of postoperative thrombocytopenia have not been established in the literature, many factors have been proposed, including post-transfusion dilution, infection-induced, drug-induced, heparin-induced, immune mediated, and others (19).
In NAT was an analogue of hemolytic disease of the newborn, thrombocytopenia results from transplacental passage of maternal antibodies to fetal platelets. Sensitization may occurs in the first pregnancy in about 50% of cases (4). NAT is often associated with severe NT and may result in major bleeding, particularly IVH, which even occur intrauterine, as thrombocytopenia may occur early in pregnancy particularly in untreated women (20). In this study, neonates suspected of having NAT were assigned as having an idiopathic thrombocytopenia as the diagnostic test for NAT is not available in our laboratory. We found no difference between NT severity and suspected NAT cases. This may be explained with the wide varieties of presentation of NAT (21).
In this study, most cases (58.18%) were asymptomatic. The most common presentations, occurring mostly with severe NT, were cutaneous bleeding from previous puncture sites and gastrointestinal bleeding. These results agree with a study by Baer et al. (6) and also agree with Park et al. (22), who found that gastrointestinal hemorrhage in patients with aplastic anemia and severe thrombocytopenia was recorded in 5% of those for whom the lowest platelet count was 20 x 109/L, compared with 1% of those for whom the lowest count was 20 x 109–50 x 109/L.
We found that pulmonary and IVH occurred exclusively with severe NT. This agrees with studies by Setzer et al. (23), and Bolat et al. (11) as they found that lower platelet counts correlated with a higher prevalence of IVH. Until now, it was unclear whether NT caused the IVH or whether it occurred afterwards, as a result of consumptive mechanisms. In contrast to our results, Baer et al. (6) found no relationship between the lowest platelet count recorded and the presence of pulmonary hemorrhage or IVH in patients with severe NT. They speculated that factors other than NT are prominent in the pathogenesis of those varieties of neonatal bleeding, such as coagulation disorders. Duppre et al. (24) found that a cellular and humoral coagulation disorder had more of a role in the occurrence of IVH in neonates than thrombocytopenia.
In our study, there were no statistically significant differences between duration of hospital stay and severity of NT. This may be explained by the increased mortality rate in severe NT group as the babies died early in the course of illness. These results did not agree with Resch et al. (25), who found the duration of stay to be positively related to the severity of NT and the number of subsequent platelet transfusions. Furthermore, in this study, half of the neonates with severe NT required mechanical ventilation, which may explain the bad general condition of these patients, and the actual morbidity and mortality may not only be related to severe NT but also to the original disease, such as sepsis, respiratory failure, shock, postoperative state, or disseminated intravascular coagulopathy.
The outcomes of NT in our study showed that mortality increased to 10.90% with severe NT. In a study by Resch et al. (9), a mortality rate of 10.8% was significantly associated with signs of bleeding (P<0.05) and correlated with an increasing number of platelet transfusions (P<0.05), but not with the severity of NT (P=0.4). Furthermore, results from studies by Baer et al. (6) and Resch et al. (25) found no relationship between the lowest platelet count recorded and the mortality rate; however, a direct relationship was observed between the number of platelet transfusions received and the mortality rate. In our study, two-thirds of cases with severe NT received at least once platelet transfusion, which may be explained by the fact that ill patients receive more platelet transfusions, or as adverse effects of platelet transfusions (26).
Our study has some limitations, mainly due to the single-center and short study time period. Nevertheless, during this one year study, 55 FT infants with NT were carefully analyzed, and cases were followed up until discharge or death; however, long term follow up may be needed in further researches. Moreover, it should be noted that diagnostic tests for NAT are not available in our lab; therefore, suspected cases were classed as idiopathic.