Platelet Transfusion and Death or Neurodevelopmental Impairment in Children Born Extremely Preterm.

Importance: Infants born extremely preterm receive transfusions at higher platelet count thresholds than older children and adults due to concerns for intracranial hemorrhage. A recent randomized trial comparing 2 platelet transfusion thresholds showed the higher threshold was associated with increased risk of long-term adverse neurodevelopmental outcomes. Objective: To evaluate the association of platelet transfusion exposure with death and severe neurodevelopmental impairment (NDI) at 2 years' corrected age in a cohort of infants born extremely preterm. Design, Setting, and Participants: An observational cohort study and secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, a randomized, placebo-controlled clinical trial of erythropoietin neuroprotection in neonates born extremely preterm, was conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 819 infants born extremely preterm at 24 to 27 completed weeks of gestation who had a documented outcome (death or neurodevelopmental assessment). Analysis was performed in April 2023. Exposures: Any platelet transfusion during neonatal intensive care unit hospitalization. Main Outcomes and Measures: The primary composite outcome was death or severe NDI evaluated at 2 years' corrected age using the Bayley Scales of Infant Development-Third Edition (BSID-III) and the Gross Motor Function Classification System and was defined as the presence of severe cerebral palsy or a BSID-III composite motor or cognitive score 2 SDs below the mean. Confounding by indication for platelet transfusion was addressed with covariate adjustment and propensity score methods. Results: Of the 819 infants included in the analysis (429 [52.4%] male; mean [SD] gestational age, 25.5 [1.1] weeks), 245 (30.0%) received at least 1 platelet transfusion during their initial hospitalization. The primary outcome occurred in 46.5% (114 of 245) of infants exposed to a platelet transfusion and 13.9% (80 of 574) of nonexposed infants with a corresponding odds ratio of 2.43 (95% CI, 1.24-4.76), adjusted for propensity score, gestational age at birth, and trial treatment group. The individual components of death and severe NDI were directionally consistent with the overall composite outcome. Conclusions and Relevance: The findings of this study suggest that platelet transfusion in infants born extremely preterm may be associated with an increased risk of death or severe NDI at 2 years' corrected age, although the possibility of residual confounding by indication cannot be excluded.

Can Red Blood Cell and Platelet Transfusions Have a Pathogenic Role in Bronchopulmonary Dysplasia?

OBJECTIVE: To evaluate whether transfusions in infants born preterm contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We conducted a multihospital, retrospective study seeking associations between red blood cell or platelet transfusions and BPD. We tabulated all transfusions administered from January 2018 through December 2022 to infants born ≤29 weeks or <1000 g until 36 weeks postmenstrual age and compared those with BPD grade. We performed a sensitivity analysis to assess the possibility of a causal relationship. We then determined whether each transfusion was compliant with restrictive guidelines, and we estimated effects fewer transfusions might have on future BPD incidence. RESULTS: Eighty-four infants did not develop BPD and 595 did; 352 developed grade 1 (mild), 193 grade 2 (moderate), and 50 grade 3 (severe). Transfusions were given at <36 weeks to 7% of those who did not develop BPD, 46% who did, and 98% who developed severe BPD. For every transfusion the odds of developing BPD increased by a factor of 2.27 (95% CI, 1.59-3.68; P < .001). Sensitivity analyses suggested that transfusions might contribute to BPD. Fifty-seven percent of red blood cell transfusions and 68% of platelet transfusions were noncompliant with new restrictive guidelines. Modeling predicted that complying with restrictive guidelines could reduce the transfusion rate by 20%-30% and the moderate to severe BPD rate by ∼4%-6%. CONCLUSIONS: Transfusions were associated with BPD incidence and severity. Lowering transfusion rates to comply with current restrictive guidelines might result in a small but meaningful reduction in BPD rates.

Neonatal Thrombocytopenia: Factors Associated With the Platelet Count Increment Following Platelet Transfusion.

OBJECTIVE: To understand better those factors relevant to the increment of rise in platelet count following a platelet transfusion among thrombocytopenic neonates. STUDY DESIGN: We reviewed all platelet transfusions over 6 years in our multi-neonatal intensive care unit system. For every platelet transfusion in 8 neonatal centers we recorded: (1) platelet count before and after transfusion; (2) time between completing the transfusion and follow-up count; (3) transfusion volume (mL/kg); (4) platelet storage time; (5) sex and age of platelet donor; (6) gestational age at birth and postnatal age at transfusion; and magnitude of rise as related to (7) pre-transfusion platelet count, (8) method of enhancing transfusion safety (irradiation vs pathogen reduction), (9) cause of thrombocytopenia, and (10) donor/recipient ABO group. RESULTS: We evaluated 1797 platelet transfusions administered to 605 neonates (median one/recipient, mean 3, and range 1-52). The increment was not associated with gestational age at birth, postnatal age at transfusion, or donor sex or age. The rise was marginally lower: (1) with consumptive vs hypoproductive thrombocytopenia (P < .001); (2) after pathogen reduction (P < .01); (3) after transfusing platelets with a longer storage time (P < .001); and (4) among group O neonates receiving platelets from non-group O donors (P < .001). Eighty-seven neonates had severe thrombocytopenia (<20 000/µL). Among these infants, poor increments and death were associated with the cause of the thrombocytopenia. CONCLUSION: The magnitude of post-transfusion rise was unaffected by most variables we studied. However, the increment was lower in neonates with consumptive thrombocytopenia, after pathogen reduction, with longer platelet storage times, and when not ABO matched.

Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.

Dnm2fl/fl Pf4-Cre (Dnm2Plt-/- ) mice lacking the endocytic GTPase dynamin 2 (DNM2) in platelets and megakaryocytes (MKs) develop hallmarks of myelofibrosis. At the cellular level, the tyrosine kinase JAK2 is constitutively active but decreased in expression in Dnm2Plt-/- platelets. Additionally, Dnm2Plt-/- platelets cannot endocytose the thrombopoietin (TPO) receptor Mpl, leading to elevated circulating TPO levels. Here, we assessed whether the hyperproliferative phenotype of Dnm2Plt-/- mice was due to JAK2 constitutive activation or to elevated circulating TPO levels. In unstimulated Dnm2Plt-/- platelets, STAT3 and, to a lower extent, STAT5 were phosphorylated, but their phosphorylation was slowed and diminished upon TPO stimulation. We further crossed Dnm2Plt-/- mice in the Mpl-/- background to generate Mpl-/-Dnm2Plt-/- mice lacking Mpl ubiquitously and DNM2 in platelets and MKs. Mpl-/- Dnm2Plt-/- platelets had severely reduced JAK2 and STAT3 but normal STAT5 expression. Mpl-/- Dnm2Plt-/- mice had severely reduced bone marrow MK and hematopoietic stem and progenitor cell numbers. Additionally, Mpl-/- Dnm2Plt-/- mice had severe erythroblast (EB) maturation defects, decreased expression of hemoglobin and heme homeostasis genes and increased expression of ribosome biogenesis and protein translation genes in spleen EBs, and developed anemia with grossly elevated plasma erythropoietin (EPO) levels, leading to early fatality by postnatal day 25. Mpl-/- Dnm2Plt+/+ mice had impaired EB development at three weeks of age, which normalized with adulthood. Together, the data shows that DNM2-dependent Mpl-mediated endocytosis in platelets and MKs is required for steady-state hematopoiesis and provides novel insights into a developmentally controlled role for Mpl in normal erythropoiesis, regulating hemoglobin and heme production.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III).

BACKGROUND: To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. STUDY DESIGN AND METHODS: This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. RESULTS: A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5 g/dl (10-90th percentile: 6.4-8.8 g/dl), with 45.7% of transfusions being given at 7 to <8 g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. DISCUSSION: Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Implementation of a neonatal platelet transfusion guideline to reduce non-indicated transfusions using a quality improvement framework.

OBJECTIVE: Variation exists in neonatal platelet transfusion practices. Recent studies found potential harm in liberal platelet transfusion practices, supporting the use of lower transfusion thresholds. Our aim was to reduce non-indicated platelet transfusions through implementation of a restrictive platelet transfusion guideline. STUDY DESIGN: Platelet transfusions from January 2017 to December 2019 were classified as indicated or non-indicated using the new guideline. Interventions included guideline implementation and staff education. Outcomes were evaluated using statistical process control charts. Major bleeding was the balancing measure. RESULT: During study, 438 platelet transfusions were administered to 105 neonates. The mean number of non-indicated platelet transfusions/month decreased from 7.3 to 1.6. The rate of non-indicated platelet transfusions per 100 patient admissions decreased from 12.5 to 2.9. Rates of major bleeding remained stable. CONCLUSIONS: Implementation of a restrictive neonatal platelet transfusion guideline significantly reduced potentially harmful platelet transfusions in our NICU without a change in major bleeding.

Screening With Reticulocyte Hemoglobin Increased Iron Sufficiency Among NICU Patients.

INTRODUCTION: To increase the rate of iron sufficiency among neonatal intensive care unit (NICU) patients from 16% to >35% within 12 months of implementing standardized assessment of reticulocyte hemoglobin (retHE). METHODS: We implemented a quality improvement (QI) study to improve iron sufficiency in our out-born level III/IV NICU. We screened 2,062 admissions, of which 622 were eligible based on feeding status at discharge. QI interventions included educational efforts and guideline implementation. Our primary outcome measure was the percentage of patients with their discharge retHE measure within the normal range. We also tracked the process measure of the number of retHE tests performed and a balancing measure of the incidence of elevated retHE among patients receiving iron supplementation. Statistical process control (SPC) charts assessed for special cause variation. RESULTS: The percentage of patients with a retHe within the normal range was significantly increased from a mean of 20% to 39% on SPC chart analysis. We measured significantly more retHE values after guideline implementation (11/mo to 24/mo) and found no cases of elevated retHE among patients receiving iron supplementation. CONCLUSIONS: After the implementation of a standardized guideline, a higher rate of iron sufficiency was found in NICU patients at discharge. This work is generalizable to neonatal populations with the potential for a significant impact on clinical practice.

Pooling, room temperature, and extended storage time increase the release of adult-specific biologic response modifiers in platelet concentrates: a hidden transfusion risk for neonates?

BACKGROUND: Adult donor platelets (PLTs) are frequently transfused to prevent or stop bleeding in neonates with thrombocytopenia. There is evidence for PLT transfusion-related morbidity and mortality, leading to the hypothesis on immunomodulatory effects of transfusing adult PLTs into neonates. Candidate factors are biologic response modifiers (BRMs) that are expressed at higher rates in adult than in neonatal PLTs. This study investigated whether storage conditions or preparation methods impact on the release of those differentially expressed BRMs. STUDY DESIGN AND METHODS: Pooled PLT concentrates (PCs) and apheresis PCs (APCs) were stored under agitation for up to 7 days at room temperature (RT) or at 2 to 8°C. The BRMs CCL5/RANTES, TGFß1, TSP1, and DKK1 were measured in PCs' supernatant, lysate, and corresponding plasma. PLT function was assessed by light transmission aggregometry. RESULTS: Concerning the preparation method, higher concentrations of DKK1 were found in pooled PCs compared to APCs. In supernatants, the concentrations of CCL5, TGFß1, TSP1, and DKK1 significantly increased, both over standard (≤4 days) and over extended storage times (7 days). Each of the four BRMs showed an up to twofold increase in concentration after storage at RT compared to cold storage (CS). There was no difference in the aggregation capacity. CONCLUSION: This analysis shows that the release of adult-specific BRMs during storage is lowest in short- and CS APCs. Our study points to strategies for reducing the exposure of sick neonates to BRMs that can be specifically associated to PLT transfusion-related morbidity.

Thrombocytopenia is associated with severe retinopathy of prematurity.

Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (<100 × 109/l) at ≥30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.

Developmental differences between newborn and adult mice in response to romiplostim.

Thrombocytopenia is frequent among sick neonates. While most cases are transient, some neonates experience prolonged and severe thrombocytopenia. These infants often pose diagnostic and therapeutic challenges, and may receive large numbers of platelet transfusions. Romiplostim (ROM) is a thrombopoietin (TPO)-receptor-agonist approved for treatment of adults with chronic immune thrombocytopenia (ITP). The immature platelet fraction (IPF) is a novel measure of newly produced platelets, which could aid with the diagnostic evaluation of thrombocytopenic neonates. This study had the following two objectives: (1) compare the response of newborn and adult mice to escalating doses of ROM in vivo and (2) assess the correlation between IPF and megakaryocyte (MK) mass in newborn and adult treated and untreated mice. In the first set of studies, newborn (day 1) and adult mice received a single subcutaneous (SC) dose of ROM ranging from 0 to 300 ng/g, and platelet counts were followed every other day for 14 days. Both sets of mice responded with dose-dependent platelet and IPF increases, peaking on days 5-7 post-treatment, but neonates had a blunted response (2.1-fold compared to 4.2-fold maximal increase in platelet counts, respectively). On day 5 post-treatment with 300 ng/g ROM, MKs in the bone marrow (BM) and spleen of adult mice were significantly increased in numbers and size (p < 0.0001 for both) compared to controls. MKs in the spleen and BM (but not liver) of treated neonates also increased in number, but not in size. The immature platelet count (IPC, calculated as IPF x platelet count) was highly correlated with the MK number and size in neonatal and adult BM and spleen, but not neonatal liver. The lack of response of neonatal liver MKs was not due to a cell-intrinsic reduced responsiveness to TPO, since neonatal liver progenitors were more sensitive to murine TPO (mTPO) in vitro than adult BM progenitor. In vivo treatment of newborn mice with high mTPO doses or with higher doses of ROM (900 ng/g) resulted in peak platelet counts approaching 3-fold of controls. Taken together, our data indicate that newborn mice are less responsive to ROM than adult mice in vivo, due to a combination of likely pharmacokinetic differences and developmental differences in the response of MKs to thrombopoietic stimulation, evidenced by neonatal MKs increasing in numbers but not in size. PK/PD studies in human infants treated with ROM are warranted.

Assessing Initial Response to High-Frequency Jet Ventilation in Premature Infants With Hypercapnic Respiratory Failure.

BACKGROUND: High-frequency jet ventilation (HFJV) has been used in conjunction with conventional ventilation for infants with respiratory failure. We sought to identify parameters that were associated with successful application of HFJV in patients with hypercapnic respiratory failure. METHODS: A single-center, retrospective review of infants who received HFJV was conducted. Subjects were enrolled if birthweight was ≤2,000 g and capillary PCO2 was ≥55 mm Hg. Ventilator parameters and physiologic data were recorded at 1 h before HFJV initiation and at hours 1, 4, and 6 following conversion. Subjects were classified as responders if capillary PCO2 was reduced by ≥10% after 1 h of HFJV. Data included peak inspiratory pressure, PEEP, capillary PCO2 , and oxygen saturation index (equal to mean airway pressure × FIO2 × 100/SpO2 ). Because the data were not normally distributed, they are reported as median (interquartile range), and the Mann-Whitney test was used to assess differences in continuous data between groups. Categorical data were analyzed using a chi-square and Fisher exact test. RESULTS: Thirty-four premature infants (n = 24 male) were studied. Twenty-five subjects were classified as responders and demonstrated a significant reduction of capillary PCO2 and FIO2 and increased pH within the first hour. The non-responders demonstrated a higher conventional ventilation peak inspiratory pressure (25 cm H2O vs 19 cm H2O, P = .005) and had a greater postmenstrual age (30 weeks vs 26.5 weeks, P = .01). This group had a higher oxygen saturation index (7.25 vs 3.36, P = .03) and FIO2 requirements (0.6 vs 0.35, P = .038) at 4 h. CONCLUSIONS: We identified that lower postmenstrual age, improvements in capillary PCO2 and pH at 1 h, and a reduction of FIO2 were associated with good response to HFJV. These data may help to identify patients who are likely to benefit from HFJV in the neonatal intensive care unit.

Thrombocytopenia in Small-for-Gestational-Age Infants.

BACKGROUND: Thrombocytopenia is common among small-for-gestational-age (SGA) neonates (birth weight <10th percentile reference range), but several aspects of this thrombocytopenia are unclear, including the incidence, typical nadir, duration, association with preeclampsia, mechanism, and risk of death. METHODS: Using 9 years of multihospital records, we studied SGA neonates with ≥2 platelet counts <150,000/µL in their first week. RESULTS: We found first-week thrombocytopenia in 31% (905 of 2891) of SGA neonates versus 10% of non-SGA matched controls (P < .0001). Of the 905, 102 had a recognized cause of thrombocytopenia (disseminated intravascular coagulation, early-onset sepsis, or extracorporeal membrane oxygenation). This group had a 65% mortality rate. The remaining 803 did not have an obvious cause for their thrombocytopenia, and we called this "thrombocytopenia of SGA." They had a mortality rate of 2% (P < .0001) and a mean nadir count on day 4 of 93,000/µL (SD 51,580/µL, 10th percentile 50,000/µL, 90th percentile 175,000/µL). By day 14, platelet counts were ≥150,000/µL in more than half of the patients. Severely SGA neonates (<1st percentile) had lower counts and longer thrombocytopenia duration (P < .001). High nucleated red cell counts at birth correlated with low platelets (P < .0001). Platelet transfusions were given to 23%, and counts typically more than tripled. Thrombocytopenia was more associated with SGA status than with the diagnosis of maternal preeclampsia. CONCLUSIONS: SGA neonates with clearly recognized varieties of thrombocytopenia have a high mortality rate. In contrast, thrombocytopenia of SGA is a hyporegenerative condition of moderate severity and 2 weeks' duration and is associated with evidence of intrauterine hypoxia and a low mortality rate.

A de novo T73I mutation in PTPN11 in a neonate with severe and prolonged congenital thrombocytopenia and Noonan syndrome.

We observed a neonate with severe congenital thrombocytopenia and features of Noonan syndrome where evaluations were negative for immune-mediated thrombocytopenia, congenital infections, and Fanconi anemia. The marrow findings and a significantly elevated plasma thrombopoietin (Tpo) level were consistent with congenital amegakaryocytic thrombocytopenia; we sought a genetic mutation that could explain this phenotype. No mutations were identified in c-MPL (the Tpo receptor gene). Microarray analysis of peripheral blood did not reveal an abnormality. DNA sequencing of the PTPN11 gene showed a heterozygous C>T nucleotide substitution in exon 3 (c.218C>T) predicted to result in a threonine-to-isoleucine change at residue 73 (T73I). A 6-week trial of eltrombopag (an agonist of the Tpo receptor) failed to increase the platelet count. We propose this specific PTPN11 mutation results in abnormalities of the protein product SHP-2, which, because of its role in signal transduction, results in severe congenital thrombocytopenia refractory to c-MPL agonists.

Developmental differences in megakaryocyte size in infants and children.

Developmental differences in megakaryocytes between neonates and adults have been described. However, the age at which megakaryocytes make a transition to an adult phenotype is unknown. Small megakaryocytes are often described as "dysplastic" in the pathology literature. Thus, recognizing the normal features of megakaryocytes at different ages has diagnostic implications. We identified 72 samples from 61 patients, aged 3 days to 80 years, who had negative staging based on bone marrow examination. Megakaryocyte diameters, as highlighted with anti-CD61, were measured. A scatter plot of megakaryocyte size by age revealed a normal distribution of sizes at the youngest ages, with a shift to multiple peaks starting at 24 months indicating that neonates have megakaryocytes of uniform sizes, which diverge into separate clusters of smaller and larger cells beginning at 2 years; this is followed by an overall shift toward larger megakaryocytes at age 4 years. These observations have direct implications for the evaluation of bone marrow megakaryocytes in young children.

The hibernating 13-lined ground squirrel as a model organism for potential cold storage of platelets.

Hibernating mammals have developed many physiological adaptations to extreme environments. During hibernation, 13-lined ground squirrels (Ictidomys tridecemlineatus) must suppress hemostasis to survive prolonged body temperatures of 4-8°C and 3-5 heartbeats per minute without forming lethal clots. Upon arousal in the spring, these ground squirrels must be able to quickly restore normal clotting activity to avoid bleeding. Here we show that ground squirrel platelets stored in vivo at 4-8°C were released back into the blood within 2 h of arousal in the spring with a body temperature of 37°C but were not rapidly cleared from circulation. These released platelets were capable of forming stable clots and remained in circulation for at least 2 days before newly synthesized platelets were detected. Transfusion of autologous platelets stored at 4°C or 37°C showed the same clearance rates in ground squirrels, whereas rat platelets stored in the cold had a 140-fold increase in clearance rate. Our results demonstrate that ground squirrel platelets appear to be resistant to the platelet cold storage lesions observed in other mammals, allowing prolonged storage in cold stasis and preventing rapid clearance upon spring arousal. Elucidating these adaptations could lead to the development of methods to store human platelets in the cold, extending their shelf life.

Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants?

OBJECTIVE: To test the hypothesis that red blood cell (RBC) transfusions increase the risk of necrotizing enterocolitis (NEC) in premature infants, we investigated whether the risk of "transfusion-associated" NEC is higher in infants with lower hematocrits and advanced postnatal age. STUDY DESIGN: Retrospective comparison of NEC patients and control patients born at < 34 weeks gestation. RESULTS: The frequency of RBC transfusions was similar in NEC patients (47/93, 51%) and control patients (52/91, 58%). Late-onset NEC (> 4 weeks of age) was more frequently associated with a history of transfusion(s) than early-onset NEC (adjusted OR, 6.7; 95% CI, 1.5 to 31.2; P = .02). Compared with nontransfused patients, RBC-transfused patients were born at earlier gestational ages, had greater intensive care needs (including at the time of onset of NEC), and longer hospital stay. A history of RBC transfusions within 48-hours before NEC onset was noted in 38% of patients, most of whom were extremely low birth weight infants. CONCLUSIONS: In most patients, RBC transfusions were temporally unrelated to NEC and may be merely a marker of overall severity of illness. However, the relationship between RBC transfusions and NEC requires further evaluation in extremely low birth weight infants using a prospective cohort design.

Differences between newborn and adult mice in their response to immune thrombocytopenia.

BACKGROUND: Sick neonates frequently develop severe thrombocytopenia. OBJECTIVE AND METHODS: In order to test the ability of fetal mice to increase their megakaryocyte size and ploidy in response to thrombocytopenia, we injected an antiplatelet antibody (MWReg30) into pregnant mice daily for 7 days, and into nonpregnant adult mice to serve as controls. After that time, platelet counts were obtained and megakaryocytes in the bone marrow, liver, and spleen were stained with anti-von Willebrand factor antibody, individually measured, and quantified. RESULTS: Our study demonstrated that megakaryocytopoiesis in newborn mice shares many features of human fetal/neonatal megakaryocytopoiesis, including the small size of megakaryocytes. In response to thrombocytopenia, adult mice increased megakaryocyte volume and concentration, primarily in the spleen. Newborn mice, in contrast, increased the megakaryocyte concentration in the spleen, but exhibited no increase in megakaryocyte volume in any of the organs studied. In fact, the megakaryocyte mass was significantly lower in the bone marrow of thrombocytopenic neonates than in age-matched controls. CONCLUSIONS: We concluded that fetuses have a limited ability to increase their megakaryocyte mass in response to consumptive thrombocytopenia, compared to adult mice. These observations provide further evidence for the existence of biological differences between fetal/neonatal and adult megakaryocytopoiesis.

Testing platelet mass versus platelet count to guide platelet transfusions in the neonatal intensive care unit.

BACKGROUND: Platelet (PLT) transfusions can bestow significant benefits but they also carry risks. This study sought a safe means of reducing PLT transfusions to neonatal intensive care unit (NICU) patients with thrombocytopenia by comparing two transfusion guidelines, one based on PLT count and the other on PLT mass (PLT count times mean PLT volume). STUDY DESIGN AND METHODS: Using a prospective, two-centered, before versus after design, PLT transfusion usage and hemorrhagic events were contrasted during a period when PLT count-based transfusion guidelines were in use (Period 1) versus a period when PLT mass-based guidelines were in use (Period 2). RESULTS: No differences were observed between Periods 1 and 2 in NICU admissions, sex, race/ethnicity, percentage of inborn patients, or percentage of patients with a PLT count less than 50 x 10(9) or 51 x 10(9) to 99 x 10(9)/L. In the first period 3.6% of NICU admissions received one or more PLT transfusions. This fell to 1.9% during the second period (p < 0.002). The number of PLT transfusions administered per transfused patient was the same in both periods: 2.0 (1-23) (median [range]) in Period 1 and 2.0 (1-17) in Period 2 (p > 0.40). Significantly fewer PLT transfusions were given in Period 2 for prophylaxis (patient not bleeding; p < 0.001 vs. Period 1). The number given for bleeding did not change between the two periods. In Period 2 no increases were seen in rate of intraventricular hemorrhage (IVH); Grade 3 or 4 IVH; or pulmonary, gastrointestinal, or cutaneous bleeding. CONCLUSIONS: The use of PLT mass-based NICU transfusion guidelines was associated with fewer PLT transfusions and no recognized increase in hemorrhagic problems.