Neonatal thrombocytopenia.

Thrombocytopenia (platelets <150 x 10(9)/L) is one of the most common haematological problems in neonates, particularly those who are preterm and sick. In those preterm neonates with early thrombocytopenia who present within 72 h of birth, the most common cause is reduced platelet production secondary to intrauterine growth restriction and/or maternal hypertension. By contrast, the most common causes of thrombocytopenia arising after the first 72 h of life, both in preterm and term infants, are sepsis and necrotizing enterocolitis. The most important cause of severe thrombocytopenia (platelets <50 x 10(9)/L) is neonatal alloimmune thrombocytopenia (NAIT), as diagnosis can be delayed and death or long-term disability due to intracranial haemorrhage may occur. Platelet transfusion is the mainstay of treatment for severe thrombocytopenia. However, the correlation between thrombocytopenia and bleeding is unclear and no studies have yet shown clinical benefit for platelet transfusion in neonates. Studies to identify optimal platelet transfusion practice for neonatal thrombocytopenia are urgently required.

Thrombocytopenia in the neonate.

Thrombocytopenia is one of the commonest haematological problems in neonates, affecting at least 25% of all admissions to neonatal intensive care units (NICUs) [Murray NA, Howarth LJ, McCloy MP et al. Platelet transfusion in the management of severe thrombocytopenia in neonatal intensive care unit patients. Transfus Med 2002;12:35-41; Garcia MG, Duenas E, Sola MC et al. Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit. J Perinatol 2001;21:415-20; Del Vecchio A, Sola MC, Theriaque DW et al. Platelet transfusions in the neonatal intensive care unit: factors predicting which patients will require multiple transfusions. Transfusion 2001;41:803-8]. Although a long list of disorders associated with neonatal thrombocytopenia can be found in many textbooks, newer classifications based on the timing of onset of thrombocytopenia (early vs. late) are more useful for planning diagnostic investigations and day-to-day management. The mainstay of treatment of neonatal thrombocytopenia remains platelet transfusion although it is important to note that no studies have yet shown clinical benefit of platelet transfusion in this setting. Indeed some reports even suggest that there may be significant adverse effects of platelet transfusion in neonates, including increased mortality, and that the effects of transfusion may differ in different groups of neonates with similar degrees of thrombocytopenia [Bonifacio L, Petrova A, Nanjundaswamy S, Mehta R. Thrombocytopenia related neonatal outcome in preterms. Indian J Pediatr 2007;74:269-74; Kenton AB, Hegemier S, Smith EO et al. Platelet transfusions in infants with necrotizing enterocolitis do not lower mortality but may increase morbidity. J Perinatol 2005;25:173-7]. There is also considerable variation in transfusion practice between different countries and between different neonatal units. Here we review recent progress in understanding the prevalence, causes and pathogenesis of thrombocytopenia in the newborn, the clinical consequences of thrombocytopenia and developments in neonatal platelet transfusion.

Neonatal thrombocytopenia.

Neonatal thrombocytopenia is a common clinical problem. The majority of episodes are early-onset thrombocytopenias due to impaired fetal megakaryocytopoiesis associated with placental insufficiency; the commonest causes of severe early-onset thrombocytopenia are immune thrombocytopenias, congenital infections, and asphyxia. By contrast, about 90% of cases of severe thrombocytopenia presenting after the first few days of life are due to late-onset bacterial sepsis, necrotizing enterocolitis, or both. Although clinically stable neonates tolerate relatively low platelet counts without significant risk of hemorrhage, ill or clinically unstable neonates with profound thrombocytopenia often have a poor outcome. Currently, the only therapy is platelet transfusion. Despite many published guidelines for platelet transfusion in the newborn, however, there have been no randomized trials to define the safe lower limit for platelet counts in sick neonates. The platelet threshold at which the benefits of transfusion outweigh the risks in neonates remains unclear. Well-designed trials are urgently needed.

Thrombocytopenia in the newborn.

Thrombocytopenia remains a common problem in sick newborns. A quarter of all neonates admitted to neonatal intensive care units develop thrombocytopenia, and in 20% of episodes the thrombocytopenia is severe (platelets <50 x 10(9)/L). Practical and clinically relevant classifications of neonatal thrombocytopenia have now been developed which, by highlighting the principal conditions precipitating severe thrombocytopenia (eg, sepsis, necrotizing enterocolitis, perinatal asphyxia, and the immune thrombocytopenias), aid the practicing neonatologist. Recent reviews demonstrate that many neonates with severe thrombocytopenia receive repeated platelet transfusions, although evidence of their clinical benefit is lacking, and there exists a significant variation in platelet transfusion practice between centers. These facts support the need for the development of evidence-based protocols for platelet transfusion in the newborn and stimulate continued interest in the potential of hemopoietic growth factors (, thrombopoietin and interleukin-11) to prevent or treat neonatal thrombocytopenia.

Interleukin-11 levels in healthy and thrombocytopenic neonates.

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. Although recombinant human (rh) thrombopoietin remains under therapeutic development, rhIL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, nothing is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis (NEC) with or without thrombocytopenia. At birth IL-11 was undetectable (<10 pg/mL) in healthy term neonates (n = 20) and 27 of 31 (87%) stable preterm neonates. Three stable preterm neonates with detectable IL-11 (mean+/-SD, 11.3 +/- 0.4 pg/mL; median, 11.6 pg/mL) suffered chorioamnionitis, the remaining neonate (IL-11, 14 pg/mL) being one of nine with early onset thrombocytopenia (present by <72 h of age). IL-11 was also measured in 58 preterm neonates with suspected sepsis or NEC. In 25 of 58, sepsis or NEC was unconfirmed and IL-11 was undetectable. By contrast, 14 of 33 with proven sepsis or NEC had elevated IL-11 (median, 14.9 pg/mL; range, 11.2-92.2 pg/mL). Of these 33 neonates, 19 developed thrombocytopenia: nine of 19 (47%) had detectable IL-11 and 10 of 19 (53%) did not (p > 0.05). Although its role in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response.