Skip to main content
NCBI home page
Blood Transfusion logoLink to Blood Transfusion
. 2025 Nov 4;24(1):35–46. doi: 10.2450/BloodTransfus.1120

Optimizing platelet transfusion thresholds in preterm infants: a systematic review and narrative synthesis of impacts on survival and neurodevelopment

Dengjun Liu 1,2, Qian Gao 1,2, Jogender Kumar 3, Yan Yue 1,2, Jing Shi 1,2, Jun Tang 1,2,*, Tao Xiong 1,2,*
PMCID: PMC12860587  PMID: 41325580

Abstract

Background

The aim of this analysis was to evaluate the impact of different platelet transfusion thresholds on short-term and long-term outcomes in preterm infants, and to inform evidence-based, individualized transfusion strategies.

Materials and methods

PubMed, Embase, and the Cochrane Library (database initiation until December 2024) were searched. Comparative studies of restrictive transfusion strategies vs liberal transfusion strategies in thrombocytopenic neonates were included. The review protocol was prospectively registered (CRD42020169262).

Results

Of 4,102 reports screened, three randomized controlled trials and two cohort studies were included (1,851 patients). Restrictive transfusion strategies did not increase short-term adverse events and may potentially reduce the incidence of mortality and severe neurodevelopmental impairment at 2 years corrected age.

Discussion

Restrictive platelet transfusion thresholds (25×109/L, or even 20×109/L) appear to be safe and may improve long-term prognosis. These findings support a shift toward more individualized, evidence-based transfusion practices in neonatal care.

Keywords: long-term outcomes, thrombocytopenia, platelet transfusion, preterm neonates, systematic review

INTRODUCTION

Thrombocytopenia (platelet count ≤150×109/L) is one of the commonest hemostatic abnormalities among neonates1,2. It affects approximately 9.4% to 35% of neonates admitted to neonatal intensive care units (NICU)3–7. Neonatal thrombocytopenia has diverse etiologies. It may present as an isolated laboratory finding or in association with systemic conditions such as sepsis and necrotizing enterocolitis, or coexist with complications of prematurity including bronchopulmonary dysplasia, patent ductus arteriosus (PDA), and retinopathy of prematurity5,8–15. As severe thrombocytopenia can lead to significant clinical bleeding and increase the risk of mortality, it is of great concern for clinicians. Platelet transfusions (PT) are widely used to prevent and treat bleeding episodes in thrombocytopenic neonates. As an invasive therapy, PT has acknowledged adverse events, including infections, febrile reactions, and circulatory overload8,16–18. So far, whether a low platelet count is a marker of bleeding episodes and mortality is not clear, and the role of PT in preventing bleeding remains controversial19–24.

Many guidelines recommend a prophylactic PT for thrombocytopenic neonates, depending upon gestation, postnatal age, platelet count, and sickness level25–29. The recommended pre-transfusion thresholds vary from 20 to 30×109/L21,25,26,29–35 for non-bleeding stable neonates and 30 to 50×109/L21,29,31,34–36 for non-bleeding unstable neonates. Although these guidelines are widely followed, they are more expert consensus than evidence-based28,37. Moreover, there is a marked diversity in PT thresholds among different NICU38,39.

Theoretically, thrombocytopenic neonates could benefit from PT, which could reduce the risks of severe bleeding episodes and mortality. However, several cohort studies have reported that restrictive implementation may reduce the need for transfusions without imparting additional risks of bleeding and mortality21,40. Surprisingly, a randomized controlled trial (RCT) published in 2019, reported that PT at a high threshold (50×109/L) increased mortality or major bleeding episodes compared with PT at a low threshold (25×109/L) in preterm infants with severe thrombocytopenia (Platelets for Neonatal Transfusion-2/Management of Thrombocytopenia in Special Subgroup, PlaNeT-2/MATISSE study)20. The robust evidence provided by the PlaNeT-2/MATISSE study has significantly transformed clinical practice. Subsequent observational studies have consistently demonstrated that restrictive PT strategies do not increase bleeding risk, and may potentially reduce the incidence of hemorrhagic complications41–45.

With the emergence of an increasing number of clinical studies, reviews and systematic reviews have proliferated to synthesize this evidence. Multiple reviews have demonstrated correlations between PT strategies and short-term clinical outcomes in NICU populations38,46–48. Nevertheless, critical knowledge gaps persist regarding: (i) direct comparisons of specific platelet count thresholds to inform clinical decision-making, and (ii) longitudinal assessments of mortality and neurodevelopmental outcomes at 2 years corrected gestational age. Focusing on thrombocytopenic preterm neonates, this systematic review addresses these gaps by contrasting restrictive and liberal PT thresholds, assessing their respective impacts on survival rates, bleeding risk, and long-term morbidity outcomes.

MATERIALS AND METHODS

This systematic review, including the study selection and data collection, was conducted according to the Cochrane Handbook for Systematic Review of Interventions49 and the checklist presented as a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement50. The review protocol was registered in the PROSPERO database (CRD42020169262, July 2020)51.

Data sources and search strategy

Two researchers independently searched in PubMed, the Cochrane Library, and Embase databases until December 1st, 2024, using the following keywords: (“infant” or “newborn” or “neonatal” or “neonate” or “preterm” or “premature” or “neonatology”) and (“thrombocytopenia” or “thrombocytopenic” or “NT”) and (“platelet transfusion” or “platelet infusion therapy” or “platelet administration” or “PT” or “thrombocyte transfusion” or “thrombocyte infusion therapy” or “thrombocyte administration”). The detailed search strategy is shown in the Online Supplementary Content, Tables SI-SIII. No restriction for language was applied to the search. Additionally, we hand-checked the reference lists of all identified trials, relevant systematic reviews, and current treatment guidelines to avoid missing important studies.

Study eligibility

We included (Study Design) RCT and cohort studies enrolling (Participants) neonates (less than 28 postnatal days) with thrombocytopenia (platelet counts <150 ×109/L) admitted to NICU, (Interventions and Comparators) which compared the effects of different platelet count thresholds for PT according to predefined outcomes. We excluded studies for infants with congenital malformations.

(Outcomes) The primary outcome was a composite of in-hospital mortality and bleeding episodes. Bleeding episodes included any grade of intracranial hemorrhage, any grade of intraventricular hemorrhage (IVH) as described by J. Volpe52,53, pulmonary hemorrhage, digestive hemorrhage, and other bleeding. The secondary outcomes were the following: morbidity (including PDA, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, death or neurodevelopmental impairment at 2 years of corrected age), abnormal prothrombin time, abnormal activated partial thromboplastin time, abnormal fibrinogen concentration, discharge by 38 weeks of corrected gestational age, and length of stay.

Study selection

The selection process was performed by two researchers independently using EndNoteX9 software to organize and track the process. Full texts of potential eligible references were obtained and assessed, following title and abstract screening. Studies approved by both investigators were included in this study. Discrepancies in inclusion and exclusion decisions were resolved with a third senior researcher.

Data extraction

A structured extraction sheet as well as Review Manager V.5.3 (Cochrane Collaboration, Oxford, UK) software were used for data extraction by two investigators independently and disagreement was resolved by a third senior researcher. The extracted data items included first author, year of publication, study design, site, study period, number of participants, patients’ eligibility criteria containing gestational age, birth weight and platelet count, platelet count thresholds, predefined outcomes, primary results, number of participants receiving PT, and cumulative volume of platelet concentrate received.

Data analysis

We intended to pool and meta-analyze study results, but there was such evident heterogeneity that quantitative synthesis (meta-analysis) could not be performed. Thus, we have conducted a narrative systematic review including structured tables and a flow chart to present the results from the studies included, describing potential gaps in evidence, and providing suggestions for future study design. If there are statistical effect quantities in the original research, we also present them.

RESULTS

Study selection

Initially, 4,102 records were retrieved. Among them, 626 duplicates were removed and 3,476 articles were excluded after screening titles and abstracts. Thirty-seven full texts were reviewed, of which 31 were excluded because they compared irrelevant interventions, did not have different thresholds, or were not a RCT or cohort study, leaving six records for inclusion in our study. The PRISMA flow diagram demonstrating the selection process is presented in Figure 1.

Figure 1.

Figure 1

Open in a new tab

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram for study inclusion

Study description

The final analysis included three RCT plus a 2-year outcome study and two cohort studies with 1,851 neonates overall; an overview of the included studies is shown in Table I. Among these, Curley et al. (2019)20 reported the short-term outcomes of the PlaNeT-2/MATISSE study, and Moore et al. (2023)54 reported the long-term follow-up neurodevelopmental outcomes at 2 years of corrected age. The study by Moore et al54. is a follow-up study and serves as a supplement to the 2-year outcome results of the study by Curley et al20.

Table I.

Overview of included studies

First authorref, year, design, country Study period No. of participants Patients’ eligibility Postnatal age, median (IQR) GA, weeks BW, g Liberal transfusion criteria, PLT count ×109/L Restrictive transfusion criteria, PLT count ×109/L
Andrew19, 1993, Multicenter RCT, Canada 7 days after randomization 152 (L=78, R=74)

  1. GA: <33 weeks

  2. PLT count: 50–150×109/L

  3. BW: 500–1,500 g

  4. Without: PVL

 <72 hoursa L:

  1. 27.4±2.2b

R:

  1. 27.7±2.5b

 L:

  1. 915±235b

R:

  1. 931±266b

 <150

  1. <50

  2. Bleeding
Curley20, 2019, Multicenter RCT, Europe (PlaNeT-2 / MATISSE study) 28 days after randomization 660 (L=331, R=329)

  1. GA: <34 weeks

  2. PLT count: <50×109/L

  3. Without: major IVH

 L:

  1. 8.4

  2. (4–21) days

R:

  1. 7.0

  2. (3.7–18.9) days

 L:

  1. 26.6

  2. (24.9–28.9)c

R:

  1. 26.7

  2. (24.9–28.7)c

 L:

  1. 728

  2. (600–940)c

R:

  1. 743

  2. (605–990)c

 <50 <25
Moore54, 2023 Multicenter RCT, a 2-year outcome study Europe (PlaNeT-2 / MATISSE study) At 2 years of corrected age 601 (L=296, R=305) Same as in study Curley, 2019 NA NA NA <50 <25
Kumar Kuma39, 2019, Single-center RCT, India 120 hours after randomization 44 (L=22, R=22)

  1. GA: <35 weeks

  2. PLT count: <100×109/L

  3. With: hs-PDA

  4. Without: CHD

 L:

  1. 3 (2–4.2) days

R:

  1. 3 (2–4.2) days

 L:

  1. 29.3±2.4b

R:

  1. 30.01±2.0b

 L:

  1. 1,075±307b

R:

  1. 1,149±303b

 <100

  1. <20

  2. Bleeding

  3. <50 and requiring a nonneurosurgical intervention

  4. <100 and requiring a neurosurgical procedure
Von Lindern40, 2012, Retrospective cohort study, The Netherlands 7 days of life 288 (L=141, R=147)

  1. GA: <32 weeks

  2. PLT count: <150×109/L

 NA NA Not provided

  1. <100 and active bleeding/ET

  2. <50 and unstable or before planned surgery

  3. <30 and clinically stable

 No routine transfusion (irrespective of platelet count) in absence of clinical bleeding.
<50 and any of the following:

  1. major bleeding

  2. massive petechiae

  3. bruising

  4. need for surgery/ invasive procedures

  5. requiring indomethacin for PDA closure
Billion41, 2024, Before-after retrospective cohort study, Europe Neonatal stay and 28 days after the diagnosis of severe thrombocytopenia 707 (R=347, L=360)

  1. GA: <37 weeks

  2. PLT count: <150×109/L

 NA L:

  1. 29.0±3.8b

R:

  1. 29.4±3.8b

 L:

  1. 1,121±577b

R:

  1. 1,166±577b

  1. <80–100 and active bleeding/ surgery

  2. <50

  1. <50, in cases of active hemorrhage or serious hemorrhaged in the previous 72 h, GA < 26 weeks in the first 72 h of life, lumbar puncture, or hemodynamic instability

  2. <25
Open in a new tab
a

The original study did not show the postnatal age of participants, but the infants were randomized during the first 72 hours of life.

b

Values are given as mean ± standard deviation.

c

Values are given as median (interquartile range).

d

Serious hemorrhage was defined as high-grade intraventricular hemorrhage or pulmonary or digestive hemorrhage.

IQR: interquartile range; GA: gestational age; BW: birth weight; PLT: platelet; RCT: randomized controlled trial; L: liberal transfusion group; R: restrictive transfusion group; PVL: periventricular leukomalacia; IVH: intraventricular hemorrhage; NA: not available in the original study; hs-PDA: hemodynamically significant patent ductus arteriosus; CHD: congenital heart disease; ET: exchange transfusion.

According to our inclusion criteria, enrolled neonates had platelet counts below the normal range. Specifically, Andrew et al19. included neonates with mild and moderate thrombocytopenia, Kumar et al39. included those with moderate and severe thrombocytopenia, and the PlaNeT-2/MATISSE study20,54 included neonates with severe thrombocytopenia. Both cohort studies (by Von Lindern et al40. and Billion et al41.) investigated thrombocytopenia of any degree. Besides the inclusion criteria, the population in these studies was limited to preterm neonates. The study by Andrew et al19. was restricted to neonates with a birth weight of 500–1,500 g and without periventricular leukomalacia at initial assessment. In the PlaNeT-2/MATISSE study20,54, enrolled infants were required to be without initial IVH, major bleeding within the previous 72 hours, fetal intracranial hemorrhage, immune thrombocytopenia, a low probability of survival beyond several hours or no administration of parenteral vitamin K and neonates with major bleeding became eligible for randomization 72 hours later if there was no further major bleeding. In the study by Kumar et al39., the infants had hemodynamically significant PDA but met the following exclusion criteria: (i) syndromes associated with PDA, (ii) echocardiographically confirmed structural congenital heart diseases, and (iii) administration of platelet concentrates between the last platelet count measurement and randomization.

The liberal groups in these three RCT plus a 2-year outcome study used prophylactic platelet count thresholds of 150×109/L, 50×109/L, 50×109/L and 100×109/L respectively, while the restrictive groups used 50×109/L, 25×109/L, 25×109/L, 20×109/L. The liberal group in the study by Von Lindern et al40. used the threshold of 30×109/L, while the restrictive group did not routinely receive prophylactic PT. Billion et al41. used 50×109/L and 25×109/L as the liberal and restrictive threshold, which is based on the study by Curley et al20. as a reference. The liberal thresholds in the RCT plus a 2-year outcome study were the same platelet level as the upper limits in eligibility criteria for enrollment. Additionally, in the study by Andrew et al19., the restrictive group used exactly the platelet level as the lower limit.

In the previously published protocol51, we defined the primary outcome as a composite of in-hospital mortality and bleeding episodes and planned to include only studies reporting this outcome. However, due to sparse data, we made post hoc changes to also include studies reporting any component of the predefined primary and secondary outcomes. The common predefined outcomes in these RCT plus a 2-year outcome study were mortality and major bleeding which were assessed up to different study days. The study periods in these RCT plus a 2-year outcome study were 7 days, 28 days, 2 years of corrected age, and 120 hours after randomization. In Andrew et al19., intracranial hemorrhage, bleeding time, and coagulation parameters (prothrombin time, activated partial thromboplastin time, and fibrinogen concentration) were measured. In the PlaNeT-2/MATISSE study20,54 bleeding events were assessed according to severity (minor, moderate, and major bleeding episodes) and time of occurrence (up to day 14 or day 28, and after red-cell transfusion). In addition, chronic lung disease, sepsis, necrotizing enterocolitis, platelet transfusion-related adverse events, retinopathy of prematurity, discharge by 38 weeks of corrected gestational age, and the neurodevelopmental outcome at 2 years of corrected age were considered as outcome measures. In the study by Kumar et al39. the outcome measure included mortality during the study period or during the hospital stay, clinical bleeds, new-onset IVH of any grade, new-onset IVH of grades III and IV, and hemodynamically significant PDA after pharmacological treatment within 120 hours after randomization. In the cohort studies, Von Lindern et al40. reported the occurrence of IVH of different grades, and Billion et al41. recorded in-hospital mortality, grades III and IV IVH, and digestive hemorrhage. All included studies except the one by Kumar et al39. recorded the number of infants who received at least one transfusion, and Kumar et al39. showed the cumulative volume of platelet concentrate received by both groups. Descriptions of mortality and bleeding events from included studies are shown in Table II. Summaries of other outcomes are shown in Table III.

Table II.

Overview of mortality and bleeding events

Outcomes Andrew, 199319 Curley, 201920 Kumar, 201939 Von Lindern, 201240 Billion, 202441
Liberal Restrictive Liberal Restrictive Liberal Restrictive Liberal Restrictive Liberal Restrictive
Mortality or major bleeding a NA NA 85/324 61/329 (OR=1.57; 95% CI: 1.06–2.32; p=0.02) 11/22 11/22 NA NA NA NA
In-hospital mortality 16/78 11/74 48/326 33/330 (OR=1.56; 95% CI: 0.95–2.55) 8/22 9/22 NA NA 33/98b 23/90b (p=0.22)
Major bleeding a NA NA 45/328 35/330 (HR=1.32; 95% CI: 1.00–1.74) NA NA NA NA NA NA
Severe (grade III/IV) intraventricular hemorrhage NA NA NA NA 4/22 2/22 (p=0.60) 16/141 12/145 (p=0.38) 3/90b 1/89b (p=0.32)
Any grade intraventricular hemorrhage NA NA NA NA 9/22 2/22 (p=0.03) 41/141 44/145 NA NA
Intracranial hemorrhage 22/78c 19/78c (p=0.73) NA NA NA NA NA NA NA NA
Pulmonary hemorrhage NA NA NA NA 7/22 8/22 NA NA NA NA
Digestive hemorrhage NA NA NA NA NA NA NA NA 1/90b 1/89b (p=0.99)
Any bleeding NA NA 225/324d 232/328d (HR=0.96; 95% CI: 0.84–1.09) 10/22e 10/22e (p=0.90) NA NA NA NA
Open in a new tab

Results are shown as number/total. If the p-values, odds ratios, hazard ratios, and 95% confidence intervals are reported in the original study, they are displayed here.

a

Definition of major bleed: rectal hemorrhage, frank rectal macroscopic bleeds; pulmonary hemorrhage, acute fresh bleed through the endotracheal tube (or mouth, when not intubated) associated with increased ventilatory requirements or the need for intubation and ventilation; intracranial hemorrhage, (a) neurosurgical intervention is required, or (b) radiological imaging show a midline shift, or (c) in the presence of clinical signs and symptoms of neurological impairment with significant derangement of laboratory investigations; intraventricular hemorrhage, (a) H2 or H3 with ventricular dilatation (V1), or (b) H1, H2, H3 with parenchymal involvement (P3), or (c) any evolution of intracranial hemorrhage to H2V1, H3V1, or (H1, H2, H3) with parenchymal involvement (P3).

b

Outcomes of neonates with severe thrombocytopenia < 50×109/L.

c

Overall increased number of cases during the study period.

d

At least one bleeding episode through trial day 14.

e

Any visible fresh oral, nasal, endotracheal, gastrointestinal, or skin bleed within 120 hours after randomization.

NA: data not available in the original study; OR: odds ratio; CI: confidence interval; HR: hazard ratio.

Table III.

Overview of other outcomes

Outcomes Andrew, 199319 Curley, 201920 Moore, 202354 Kumar, 201939 Von Lindern, 201240 Billion, 202441
Liberal Restrictive Liberal Restrictive Liberal Restrictive Liberal Restrictive Liberal Restrictive Liberal Restrictive
Patent ductus arteriosus 34/78 34/74 NA NA NA NA 15/22a 14/22a (p=0.90) NA NA NA NA
Bronchopulmonary dysplasia NA NA 169/269b 153/281b (OR=1.54; 95% CI: 1.03–2.30) NA NA NA NA NA NA 32/54c 34/50c (p=0.36)
Retinopathy of prematurity NA NA 82/279d 71/297d (OR=1.37; 95% CI:0.91–2.08) NA NA NA NA NA NA NA NA
Necrotizing enterocolitis 3/78 1/74 42/324e 54/326e (HR=0.72; 95% CI: 0.37–1.41) NA NA NA NA NA NA NA NA
Sepsis NA NA 181/324e 175/326e (HR=1.10; 95% CI: 0.92–1.33) NA NA 8/22 2/22 (p=0.07) NA NA NA
Periventricular leukomalacia 0/78 3/74 NA NA NA NA NA NA NA NA NA NA
Death or neurodevelopmental impairment at 2 years of corrected age NA NA NA NA 147/296f 120/305f (OR 1.54; 95% CI: 1.09–2.17, p=0.02) NA NA NA NA NA NA
Abnormal prothrombin time 8/55 11/52 NA NA NA NA NA NA NA NA NA NA
Abnormal activated partial thromboplastin time 2/55 5/52 NA NA NA NA NA NA NA NA NA NA
Fibrinogen levels <1.5 g/L 21/55 14/52 NA NA NA NA NA NA NA NA NA NA
Discharge by 38 weeks of corrected gestational age NA NA 29/326 41/328 (HR=0.68; 95% CI: 0.46–1.00) NA NA NA NA NA NA NA NA
Length of stay among survivors, days, median (IQR) NA NA NA NA NA NA 50 (23–72) 29 (15.5–6.5, p=0.10) NA NA NA NA
At least one platelet transfusion 70/78 24/74 296/328 177/331 (HR=2.75; 95% CI: 2.36–3.21) NA NA NA NA 44/141 21/145 (p<0.001) 99/360 56/347 (p<0.001)
Cumulative volume of platelet concentrate received, mL/kg, median (IQR) NA NA NA NA NA NA 30 (15–55) 0 (0–15, p<0.001) NA NA NA NA
Open in a new tab

Results are shown as number/total. If the p-values, odds ratios, hazard ratios, and 95% confidence intervals are reported in the original study, they are displayed here.

a

Hemodynamically significant patent ductus arteriosus after pharmacological treatment within 120 hours after randomization.

b

Survival with bronchopulmonary dysplasia at 36 weeks of corrected gestational age.

c

Outcomes of neonates with severe thrombocytopenia <50×109/L. dSurvival with unilateral or bilateral retinopathy of prematurity of stage ≥2 at 38 weeks of corrected gestational age.

e

New cases after randomization.

F

Neurodevelopmental impairment included developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss.

NA: data not available in the original study; OR: odds ratio; CI: confidence interval; HR: hazard ratio; IQR: interquartile range.

The short-term outcomes

Results in the included studies revealed that lower platelet count thresholds did not carry higher risks and were, in most of them, beneficial with respect to mortality and major bleed events. Andrew et al19. reported that there was no difference in extension of intracranial hemorrhage between groups (p=0.73). Curley et al20. revealed that a restrictive threshold for prophylactic PT resulted in a significantly lower rate of death or major bleeding than a liberal threshold (p=0.02) and there was no difference between groups considering other outcomes.

Kumar et al39. reported that the restrictive transfusion group had significantly lower rates of any grade of IVH (p=0.034) and sepsis (p=0.07), while grade III or IV IVH, mortality during the first 120 hours post-randomization as well as during the hospital stay, or PDA closure rates were similar in both groups (p>0.05). The cohort studies40,41 found the rates of mortality, IVH, and digestive hemorrhage were similar in both groups (p>0.05). Compared with the liberal group, the restrictive group had fewer participants who received at least one PT19,20,40,41 and had a lower cumulative volume of platelet concentrate (p<0.001)39. PT complications (e.g., infections, allergic reactions) are too rare for meaningful group comparisons.

The long-term outcomes

In the PlaNeT-2/MATISSE study54, thrombocytopenic neonates randomized to a restrictive PT threshold of 25×109/L had a lower rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. Several articles also reported the long-term ending. In the study by Bahr et al45. the restrictive guideline did not increase the rate of moderate to severe neurodevelopmental impairment at 24±6 months in infants admitted into a NICU. Davenport et al44. reported less death and severe neurodevelopmental impairment at 2 years corrected age in extremely preterm infants without PT than in those with PT. Although the possibility of residual confounding by indication cannot be excluded, restrictive use of PT may have a protective effect against death or severe neurodevelopmental impairment at 2 years corrected age.

DISCUSSION

Through systematic retrieval and meticulous screening, we ultimately included three RCT plus a 2-year outcome study and two cohort studies. It is difficult to determine the optimal platelet count thresholds for PT to reduce mortality, bleeding, and major morbidity among neonates with thrombocytopenia because of the sparse data. However, we can pay attention to the trend that restrictive transfusion strategy does not increase but even decreases the risks of poor outcomes: in the included RCT plus a 2-year outcome study19,20,39,54, despite the heterogeneity of the thresholds compared separately, the higher thresholds were exactly the upper limits in enrollment criteria, which meant that neonates with different platelet levels have both PT and non-PT, and there was no inferiority in the restrictive groups compared to the liberal groups. Von Lindern et al40. found that limiting PT in therapeutic use in the restrictive-transfusion NICU did not affect the incidence and severity of IVH compared to the liberal transfusion NICU. The before-after retrospective cohort study by Billion et al41. changed the prophylactic platelet-count threshold from 50×109/L to 25×109/L according to Curley et al20. and concluded that this restrictive strategy did not increase deaths or severe hemorrhages. All these studies reported the transfusion consumption and we found that lower transfusion platelet thresholds significantly reduced the applications of PT and consequent financial costs without leading to more adverse outcomes. This provides some support for restrictive use of PT (such as limiting PT to treatment rather than prevention of bleeding).

Furthermore, evidence from research involving the broader NICU population also supports the use of restrictive transfusion strategies. Studies similarly influenced by Curley et al.20 include those by Davenport et al.43, Bahr et al.45, and Heeger et al.42. These cohort studies compared clinical outcomes before and after guideline changes, that is, between liberal and restrictive strategies. All found that implementing restrictive PT guidelines did not increase the risks of unfavorable outcomes including major bleeding, mortality, severe IVH, severe retinopathy of prematurity (stage ≥3), and moderate to severe bronchopulmonary dysplasia.

This review addresses a critical gap in the literature by synthesizing current evidence on long-term neurodevelopmental outcomes following PT in neonates. The findings suggests that a restrictive PT strategy may confer neuroprotective benefits, potentially reducing mortality and severe neurodevelopmental impairment in thrombocytopenic neonates and extremely preterm infants at 2 years corrected age44,54. However, the available data are limited to preliminary findings from studies with 2-year follow-up periods. Further research with extended longitudinal assessments is needed to validate these observations and characterize developmental trajectories beyond early childhood.

Restrictive PT thresholds reduced the proportion of neonates receiving platelet transfusions and decreased donor exposure in treated infants19,20,29,39–43. However, Bahr et al45. noted that the restrictive strategy did not reduce the number of neonates requiring platelet transfusions, but due to rigorous monitoring, it allowed safe administration at lower thresholds.

All the studies included in this study excluded term infants, which is reasonable as is known that preterm infants have a significantly higher risk of neonatal thrombocytopenia8. Given the complicated and multifactorial etiology and complications of thrombocytopenia, it is hard to explain the direct effects of PT on neonatal thrombocytopenia. It may be practical to explore the effects of PT on thrombocytopenic neonates by dealing with more specific clinical characteristics, such as the severity of the thrombocytopenia, postnatal age, gestational age, and birth weight, and highly recommended to do so through RCT instead of observational studies. Through our systematic search, we also discovered an ongoing multicenter double-blind RCT (Neonatal Platelet Transfusion Threshold Trial, (NeoPlaTT), NIH RePORTER #1UG3HL173303-01). In this RCT, the liberal transfusion threshold will be 50×109/L up to 7 days of life, and then 35×109/L at 7 or more days of life, while the restrictive transfusion threshold will be 25×109/L up to 7 days of life, and 20×109/L at 7 or more days of life. This study is expected to provide new high-quality evidence-based recommendations for PT practices.

Besides a limited number of studies that directly compared specific thresholds, some observational studies have focused on PT administration in comparison to non-PT. Several studies pointed out that a lower platelet count did not act as a causal factor of IVH, and raised doubts on the benefits of PT22,55–58. Multiple mechanisms may mediate the adverse effects of transfusion of adult-derived platelets to neonates, including rapid volume expansion, inappropriate angiogenic signaling during vulnerable periods of brain development, potential prothrombotic effects, and possible pro-inflammatory consequences59–63. Additionally, there are studies demonstrating that PT did not result in a reduction in mortality64 and was even associated with a greater risk of death65. Neonates receiving multiple PT had higher rates of death in a step-wise manner according to the number of PT55,66–68.

However, that PT or the number of PT seem to be markers of high risk of death is not equivalent to PT having a causal relationship with death. It is because some unmeasured factors such as the severity of illness and clinical factors related to bleeding also contribute to the association of PT and outcomes56,68. Josephson et al23. conducted prophylactic PT when morning platelet counts were ≤10×109/L, and compared with adults, pediatric patients overall were at higher risk of bleeding over a wide range of platelet counts, suggesting that their excess bleeding risk may be because of factors other than thrombocytopenia. Coexisting clinical factors, including mechanical ventilation, extracorporeal membrane oxygenation, surgery, necrotizing enterocolitis, sepsis, platelet dysfunction, volemic resuscitation, and therapeutic hypothermia8,21,29,34, influence the PT decisions as well as the outcomes. We, therefore, suggest readers be prudent when interpreting the findings due to heterogeneity in patients’ characteristics.

The PlaNeT-2/MATISSE study–a landmark trial in neonatal hematology–demonstrated that restrictive PT strategies were superior to liberal approaches, reshaping guidelines worldwide. Heeger et al42. and Houben et al69. evaluated the implementation of the restrictive threshold of 25×109/L as used in the PlaNeT2/MATISSE trial in Europe. Over two-thirds (66.9%) of the transfusions primarily based on platelet count were administered when the count was below 25×109/L69 in 22 European countries. This suggests that the restrictive threshold found beneficial in the PlaNeT2/MATISSE trial was being integrated into European neonatal intensive care. However, clinical hesitancy remains regarding its application in complex cases in which balancing bleeding risks against potential complications of PT proves challenging.

The included RCT plus a 2-year outcome study examined distinct infant populations with specific clinical characteristics, providing robust evidence for personalized transfusion guidelines. Thresholds as low as 25×109/L, and potentially even 20×109/L, appear safe for preterm thrombocytopenic neonates. Yet, more RCT remain necessary to comprehensively evaluate the risks and benefits of PT for thrombocytopenic neonates with particular clinical profiles and to establish evidence-based optimal thresholds. It also highlights the need for targeted education and monitoring systems to safely further reduce PT, especially among high-risk neonatal populations.

Strengths and limitations

The strengths of this review are the systematic search, which effectively minimized omissions while maximizing the presentation of available data on PT thresholds, and the fact that we included both RCT and observational studies. Additionally, this study summarized longitudinal outcome measures to provide an evidence base for developing restrictive transfusion protocols.

We recognize that our study had limitations. First, after a post-hoc change was made to use a liberal criterion on the outcome measures, only a limited number of studies were included in this systematic review. Second, the heterogeneity of participants, outcome measures, study period, and PT thresholds in different studies was so evident that we could not make a quantitative analysis. Nevertheless, we performed a comprehensive systematic search and endeavored to present and interpret the current findings with full transparency, clarity, and reproducibility. This was achieved through detailed documentation of the methodologies employed and the study process, including the use of structured tables and an appropriate figure.

Supplementary Information

Footnotes

AUTHORS’ CONTRIBUTIONS: TX contributed to the conception of the study. All Authors developed the framework of the systematic review. TX designed the search strategy. QG and DL ran the search. YY and DL independently screened and selected the relevant records. QG and DL extracted data from included studies. YY and DL assessed the risk of bias. JK and DL performed the data synthesis. TX, JK, JS, and JT arbitrated in cases of any disagreement and ensured no errors occurred during the study. The manuscript for this systematic review was drafted by DL and revised by TX, JS, and JK. All Authors have approved the publication of this manuscript.

The Authors declare no conflicts of interest.

FUNDING INFORMATION: This work was supported by the National Natural Science Foundation of China (82171710, 82371723), Natural Science Foundation of Sichuan Province (General Program: 2025ZNSFSC0639), the Science and Technology Bureau of Sichuan Province (2024YFFK0273), the National Key R&D Program of China (2021YFC2701700, 2021YFC2701704), and Innovative Research Project from 0 to 1 of Sichuan University (2023SCUH0021).

REFERENCES

  • 1.von Lindern JS, van den Bruele T, Lopriore E, Walther FJ. Thrombocytopenia in neonates and the risk of intraventricular hemorrhage: a retrospective cohort study. BMC Pediatr. 2011;11:16. doi: 10.1186/1471-2431-11-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Roberts I, Stanworth S, Murray NA. Thrombocytopenia in the neonate. Blood Rev. 2008;22(4):173–186. doi: 10.1016/j.blre.2008.03.004. [DOI] [PubMed] [Google Scholar]
  • 3.Bolat F, Kılıç SÇ, Oflaz MB, Gülhan E, Kaya A, Güven AS, et al. The prevalence and outcomes of thrombocytopenia in a neonatal intensive care unit: a three-year report. Pediatr Hematol Oncol. 2012;29(8):710–720. doi: 10.3109/08880018.2012.725454. [DOI] [PubMed] [Google Scholar]
  • 4.Castle V, Andrew M, Kelton J, Giron D, Johnston M, Carter C. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr. 1986;108(5 Pt 1):749–755. doi: 10.1016/s0022-3476(86)81059-9. [DOI] [PubMed] [Google Scholar]
  • 5.Dahmane Ayadi I, Ben Hamida E, Youssef A, Sdiri Y, Marrakchi Z. Prevalence and outcomes of thrombocytopenia in a neonatal intensive care unit. Tunis Med. 2016;94:305–308. [PubMed] [Google Scholar]
  • 6.Mehta P, Vasa R, Neumann L, Karpatkin M. Thrombocytopenia in the high-risk infant. J Pediatr. 1980;97(5):791–794. doi: 10.1016/s0022-3476(80)80272-1. [DOI] [PubMed] [Google Scholar]
  • 7.Ulusoy E, Tufekci O, Duman N, Kumral A, Irken G, Oren H. Thrombocytopenia in neonates: causes and outcomes. Ann Hematol. 2013;92(7):961–967. doi: 10.1007/s00277-013-1726-0. [DOI] [PubMed] [Google Scholar]
  • 8.Resch E, Hinkas O, Urlesberger B, Resch B. Neonatal thrombocytopeniacauses and outcomes following platelet transfusions. Eur J Pediatr. 2018;177(7):1045–1052. doi: 10.1007/s00431-018-3153-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Ree IMC, Fustolo-Gunnink SF, Bekker V, Fijnvandraat KJ, Steggerda SJ, Lopriore E. Thrombocytopenia in neonatal sepsis: incidence, severity and risk factors. PLoS One. 2017;12(10):e0185581. doi: 10.1371/journal.pone.0185581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Winkelhorst D, Oepkes D. Foetal and neonatal alloimmune thrombocytopenia. Best Pract Res Clin Obstet Gynaecol. 2019;58:15–27. doi: 10.1016/j.bpobgyn.2019.01.017. [DOI] [PubMed] [Google Scholar]
  • 11.Kamphuis MM, Paridaans NP, Porcelijn L, Lopriore E, Oepkes D. Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics. 2014;133(4):715–721. doi: 10.1542/peds.2013-3320. [DOI] [PubMed] [Google Scholar]
  • 12.Chore¸ziak A, Szpecht D, Chmielarz-Czarnocińska A, Pawłowska I, Gotz-Wie¸ckowska A. The association of platelet counts with development and treatment for retinopathy of prematurity - is thrombocytopenia a risk factor? Arch Med Sci. 2019;18(2):400–405. doi: 10.5114/aoms.2019.85386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Seliniotaki AK, Lithoxopoulou M, Moutzouri S, Bouras E, Diamanti E, Ziakas N, et al. Is thrombocytopenia and postnatal weight gain associated with treatment-requiring retinopathy of prematurity? A matched case-control study. Acta Ophthalmol. 2023;101(4):433–442. doi: 10.1111/aos.15302. [DOI] [PubMed] [Google Scholar]
  • 14.Ribeiro C, Rocha G, Flôr-DE-Lima F, Ferreras C, Moita R, Silva R, et al. Thrombocytopenia requiring platelet transfusions is predictive of retinopathy of prematurity in preterm infants. Minerva Pediatr (Torino) 2023 doi: 10.23736/S2724-5276.23.07336-6. [DOI] [PubMed] [Google Scholar]
  • 15.Liao QW, Zhang WH, Guang XF, Lu YB. [Retrospective analysis of patients with thrombocytopenia after patent ductus arteriosus interventional occlusion]. Zhonghua Xin Xue Guan Bing Za Zhi. 2013;41(3):229–232. Chinese. [PubMed] [Google Scholar]
  • 16.Haass KA, Sapiano MRP, Savinkina A, Kuehnert MJ, Basavaraju SV. Transfusion-Transmitted infections reported to the National Healthcare Safety Network Hemovigilance Module. Transfus Med Rev. 2019;33(2):84–91. doi: 10.1016/j.tmrv.2019.01.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Stolla M, Refaai MA, Heal JM, Spinelli SL, Garraud O, Phipps RP, et al. Platelet transfusion - the new immunology of an old therapy. Front Immunol. 2015;6:28. doi: 10.3389/fimmu.2015.00028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Stainsby D, Jones H, Asher D, Atterbury C, Boncinelli A, Brant L, et al. Serious hazards of transfusion: a decade of hemovigilance in the UK. Transfus Med Rev. 2006;20(4):273–282. doi: 10.1016/j.tmrv.2006.05.002. [DOI] [PubMed] [Google Scholar]
  • 19.Andrew M, Vegh P, Caco C, Kirpalani H, Jefferies A, Ohlsson A, et al. A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. J Pediatr. 1993;123(2):285–291. doi: 10.1016/s0022-3476(05)81705-6. [DOI] [PubMed] [Google Scholar]
  • 20.Curley A, Stanworth SJ, Willoughby K, Fustolo-Gunnink SF, Venkatesh V, Hudson C, et al. Randomized trial of platelet-transfusion thresholds in neonates. N Engl J Med. 2019;380(3):242–251. doi: 10.1056/NEJMoa1807320. [DOI] [PubMed] [Google Scholar]
  • 21.Borges JP, dos Santos AM, da Cunha DH, Mimica AF, Guinsburg R, Kopelman BI. Restrictive guideline reduces platelet count thresholds for transfusions in very low birth weight preterm infants. Vox Sang. 2013;104(3):207–213. doi: 10.1111/j.1423-0410.2012.01658.x. [DOI] [PubMed] [Google Scholar]
  • 22.Muthukumar P, Venkatesh V, Curley A, Kahan BC, Choo L, Ballard S, et al. Severe thrombocytopenia and patterns of bleeding in neonates: results from a prospective observational study and implications for use of platelet transfusions. Transfus Med. 2012;22(5):338–343. doi: 10.1111/j.1365-3148.2012.01171.x. [DOI] [PubMed] [Google Scholar]
  • 23.Josephson CD, Granger S, Assmann SF, Castillejo MI, Strauss RG, Slichter SJ, et al. Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia. Blood. 2012;120(4):748–760. doi: 10.1182/blood-2011-11-389569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.van der Staaij H, Hooiveld NMA, Caram-Deelder C, Fustolo-Gunnink SF, Fijnvandraat K, Steggerda SJ, et al. Most major bleeds in preterm infants occur in the absence of severe thrombocytopenia: an observational cohort study. Arch Dis Child Fetal Neonatal Ed. 2025;110(2):122–127. doi: 10.1136/archdischild-2024-326959. [DOI] [PubMed] [Google Scholar]
  • 25.Girelli G, Antoncecchi S, Casadei AM, Del Vecchio A, Isernia P, Motta M, et al. Recommendations for transfusion therapy in neonatology. Blood Transfus. 2015;13(3):484–497. doi: 10.2450/2015.0113-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.New HV, Berryman J, Bolton-Maggs PH, Cantwell C, Chalmers EA, Davies T, et al. Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol. 2016;175(5):784–828. doi: 10.1111/bjh.14233. [DOI] [PubMed] [Google Scholar]
  • 27.Lopriore E. Updates in red blood cell and platelet transfusions in preterm neonates. Am J Perinatol. 2019;36(S 02):S37–S40. doi: 10.1055/s-0039-1691775. [DOI] [PubMed] [Google Scholar]
  • 28.Del Vecchio A, Franco C, Petrillo F, D’Amato G. Neonatal transfusion practice: when do neonates need red blood cells or platelets? Am J Perinatol. 2016;33(11):1079–1084. doi: 10.1055/s-0036-1586106. [DOI] [PubMed] [Google Scholar]
  • 29.Zabeida A, Chartrand L, Lacroix J, Villeneuve A. Platelet transfusion practice pattern before and after implementation of a local restrictive transfusion protocol in a neonatal intensive care unit. Transfusion. 2023;63(1):134–142. doi: 10.1111/trf.17184. [DOI] [PubMed] [Google Scholar]
  • 30.Carr R, Kelly AM, Williamson LM. Neonatal thrombocytopenia and platelet transfusion - a UK perspective. Neonatology. 2015;107(1):1–7. doi: 10.1159/000365163. [DOI] [PubMed] [Google Scholar]
  • 31.Calhoun DA, Christensen RD, Edstrom CS, Juul SE, Ohls RK, Schibler KR, et al. Consistent approaches to procedures and practices in neonatal hematology. Clin Perinatol. 2000;27(3):733–753. doi: 10.1016/s0095-5108(05)70048-8. [DOI] [PubMed] [Google Scholar]
  • 32.Sparger K, Deschmann E, Sola-Visner M. Platelet transfusions in the neonatal intensive care unit. Clin Perinatol. 2015;42(3):613–623. doi: 10.1016/j.clp.2015.04.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Christensen RD, Carroll PD, Josephson CD. Evidence-based advances in transfusion practice in neonatal intensive care units. Neonatology. 2014;106(3):245–253. doi: 10.1159/000365135. [DOI] [PubMed] [Google Scholar]
  • 34.Baer VL, Lambert DK, Schmutz N, Henry E, Stoddard RA, Miner C, et al. Adherence to NICU transfusion guidelines: data from a multihospital healthcare system. J Perinatol. 2008;28(7):492–497. doi: 10.1038/jp.2008.23. [DOI] [PubMed] [Google Scholar]
  • 35.Christensen RD, Paul DA, Sola-Visner MC, Baer VL. Improving platelet transfusion practices in the neonatal intensive care unit. Transfusion. 2008;48(11):2281–2284. doi: 10.1111/j.1537-2995.2008.01928.x. [DOI] [PubMed] [Google Scholar]
  • 36.Gibson BE, Todd A, Roberts I, Pamphilon D, Rodeck C, Bolton-Maggs P, et al. Transfusion guidelines for neonates and older children. Br J Haematol. 2004;124(4):433–453. doi: 10.1111/j.1365-2141.2004.04815.x. [DOI] [PubMed] [Google Scholar]
  • 37.Cremer M, Sallmon H, Kling PJ, Bührer C, Dame C. Thrombocytopenia and platelet transfusion in the neonate. Semin Fetal Neonatal Med. 2016;21(1):10–18. doi: 10.1016/j.siny.2015.11.001. [DOI] [PubMed] [Google Scholar]
  • 38.Fustolo-Gunnink SF, Huisman EJ, van der Bom JG, van Hout FMA, Makineli S, Lopriore E, et al. Are thrombocytopenia and platelet transfusions associated with major bleeding in preterm neonates? A systematic review. Blood Rev. 2019;36:1–9. doi: 10.1016/j.blre.2018.10.001. [DOI] [PubMed] [Google Scholar]
  • 39.Kumar J, Dutta S, Sundaram V, Saini SS, Sharma RR, Varma N. Platelet transfusion for PDA closure in preterm infants: a randomized controlled trial. Pediatrics. 2019;143(5):e20182565. doi: 10.1542/peds.2018-2565. [DOI] [PubMed] [Google Scholar]
  • 40.von Lindern JS, Hulzebos CV, Bos AF, Brand A, Walther FJ, Lopriore E. Thrombocytopaenia and intraventricular haemorrhage in very premature infants: a tale of two cities. Arch Dis Child Fetal Neonatal Ed. 2012;97(5):F348–352. doi: 10.1136/fetalneonatal-2011-300763. [DOI] [PubMed] [Google Scholar]
  • 41.Billion E, Ghattas S, Jarreau PH, Irmesi R, Ndoudi Likoho B, Patkai J, et al. Lowering platelet-count threshold for transfusion in preterm neonates decreases the number of transfusions without increasing severe hemorrhage events. Eur J Pediatr. 2024;183(10):4417–4424. doi: 10.1007/s00431-024-05709-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Heeger LE, Houben NAM, Caram-Deelder C, Fustolo-Gunnink SF, van der Bom JG, Lopriore E. Impact of restrictive platelet transfusion strategies on transfusion rates: A cohort study in very preterm infants. Transfusion. 2024;64(8):1421–1427. doi: 10.1111/trf.17844. [DOI] [PubMed] [Google Scholar]
  • 43.Davenport PE, Chan Yuen J, Briere J, Feldman HA, Sola-Visner MC, Leeman KT. Implementation of a neonatal platelet transfusion guideline to reduce non-indicated transfusions using a quality improvement framework. J Perinatol. 2021;41(6):1487–1494. doi: 10.1038/s41372-021-01033-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Davenport PE, Wood TR, Heagerty PJ, Sola-Visner MC, Juul SE, Patel RM. Platelet transfusion and death or neurodevelopmental impairment in children born extremely preterm. JAMA Netw Open. 2024;7(1):e2352394. doi: 10.1001/jamanetworkopen.2023.52394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Bahr TM, Christensen TR, Henry E, Astin M, Ilstrup SJ, Ohls RK, et al. Platelet transfusions in a multi-neonatal intensive Care Unit Health Care Organization before and after publication of the PlaNeT-2 Clinical Trial. J Pediatr. 2023;257:113388. doi: 10.1016/j.jpeds.2023.03.003. [DOI] [PubMed] [Google Scholar]
  • 46.Ribeiro HS, Assunção A, Vieira RJ, Soares P, Guimarães H, Flor-de-Lima F. Platelet transfusions in preterm infants: current concepts and controversies-a systematic review and meta-analysis. Eur J Pediatr. 2023;182(8):3433–3443. doi: 10.1007/s00431-023-05031-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Sola-Visner M, Leeman KT, Stanworth SJ. Neonatal platelet transfusions: New evidence and the challenges of translating evidence-based recommendations into clinical practice. J Thromb Haemost. 2022;20(3):556–564. doi: 10.1111/jth.15664. [DOI] [PubMed] [Google Scholar]
  • 48.Christensen RD, Bahr TM, Davenport P, Sola-Visner MC, Ohls RK, Ilstrup SJ, et al. Implementing evidence-based restrictive neonatal intensive care unit platelet transfusion guidelines. J Perinatol. 2024;44(10):1394–1401. doi: 10.1038/s41372-024-02050-x. [DOI] [PubMed] [Google Scholar]
  • 49.Higgins J, Thomas J. Cochrane Handbook for Systematic Reviews of Interventions. 2nd Ed. Chichester (UK): John Wiley & Sons; 2019. [Google Scholar]
  • 50.Moher D, Liberati A, Tetzlaff J, Altman DG PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Surg. 2010;8(5):336–341. doi: 10.1016/j.ijsu.2010.02.007. Erratum in: Int J Surg 2010; 8(8)658. [DOI] [PubMed] [Google Scholar]
  • 51.Liu D, Wu J, Xiong T, Yue Y, Tang J. Platelet transfusion for neonates with thrombocytopaenia: protocol for a systematic review. BMJ Open. 2020;10(10):e039132. doi: 10.1136/bmjopen-2020-039132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Volpe JJ. Volpe’s neurology of the newborn. 6th ed. Philadelphia: Elsevier; 2008. [Google Scholar]
  • 53.You SK. Neuroimaging of germinal matrix and intraventricular hemorrhage in premature infants. J Korean Neurosurg Soc. 2023;66(3):239–246. doi: 10.3340/jkns.2022.0277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Moore CM, D’Amore A, Fustolo-Gunnink S, Hudson C, Newton A, Santamaria BL, et al. Two-year outcomes following a randomised platelet transfusion trial in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2023;108(5):452–457. doi: 10.1136/archdischild-2022-324915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Baer VL, Lambert DK, Henry E, Christensen RD. Severe Thrombocytopenia in the NICU. Pediatrics. 2009;124(6):e1095–100. doi: 10.1542/peds.2009-0582. [DOI] [PubMed] [Google Scholar]
  • 56.Sparger KA, Assmann SF, Granger S, Winston A, Christensen RD, Widness JA, et al. Platelet Transfusion Practices Among Very-Low-Birth-Weight Infants. JAMA Pediatr. 2016;170(7):687–694. doi: 10.1001/jamapediatrics.2016.0507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.von Lindern JS, van den Bruele T, Lopriore E, Walther FJ. Thrombocytopenia in neonates and the risk of intraventricular hemorrhage: a retrospective cohort study. BMC Pediatr. 2011;11:16. doi: 10.1186/1471-2431-11-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Stanworth SJ, Clarke P, Watts T, Ballard S, Choo L, Morris T, et al. Prospective, observational study of outcomes in neonates with severe thrombocytopenia. Pediatrics. 2009;124(5):e826–834. doi: 10.1542/peds.2009-0332. [DOI] [PubMed] [Google Scholar]
  • 59.Yang Z, Luo TT, Dai YL, Duan HX, Chong CM, Tang J. Pharmacological Strategies and Surgical Management of Posthemorrhagic Hydrocephalus Following Germinal Matrix-Intraventricular Hemorrhage in Preterm Infants. Curr Neuropharmacol. 2025;23(3):241–255. doi: 10.2174/1570159X23666240906115817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Hardy AT, Palma-Barqueros V, Watson SK, Malcor JD, Eble JA, Gardiner EE, et al. Significant hypo-responsiveness to GPVI and CLEC-2 agonists in pre-term and full-term neonatal platelets and following Immune thrombocytopenia. Thromb Haemost. 2018;118(6):1009–1020. doi: 10.1055/s-0038-1646924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Ferrer-Marin F, Chavda C, Lampa M, Michelson AD, Frelinger AL, 3rd, Sola-Visner M. Effects of in vitro adult platelet transfusions on neonatal hemostasis. J Thromb Haemost. 2011;9(5):1020–1028. doi: 10.1111/j.1538-7836.2011.04233.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Caparrós-Pérez E, Teruel-Montoya R, Palma-Barquero V, Torregrosa JM, Blanco JE, Delgado JL, et al. Down Regulation of the Munc18bsyntaxin- 11 Complex and β1-tubulin impairs secretion and spreading in neonatal platelets. Thromb Haemost. 2017;117(11):2079–2091. doi: 10.1160/TH17-04-0241. [DOI] [PubMed] [Google Scholar]
  • 63.Stolla MC, Catherman SC, Kingsley PD, Rowe RG, Koniski AD, Fegan K, et al. Lin28b regulates age-dependent differences in murine platelet function. Blood Adv. 2019;3(1):72–82. doi: 10.1182/bloodadvances.2018020859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Bonifacio L, Petrova A, Nanjundaswamy S, Mehta R. Thrombocytopenia related neonatal outcome in preterms. Indian J Pediatr. 2007;74(3):269–274. doi: 10.1007/s12098-007-0042-x. [DOI] [PubMed] [Google Scholar]
  • 65.Bolat F, Kılıç SÇ, Oflaz MB, Gülhan E, Kaya A, Güven AS, et al. The prevalence and outcomes of thrombocytopenia in a neonatal intensive care unit: a three-year report. Pediatr Hematol Oncol. 2012;29(8):710–720. doi: 10.3109/08880018.2012.725454. [DOI] [PubMed] [Google Scholar]
  • 66.Del Vecchio A, Sola MC, Theriaque DW, Hutson AD, Kao KJ, Wright D, et al. Platelet transfusions in the neonatal intensive care unit: factors predicting which patients will require multiple transfusions. Transfusion. 2001;41(6):803–808. doi: 10.1046/j.1537-2995.2001.41060803.x. [DOI] [PubMed] [Google Scholar]
  • 67.Garcia MG, Duenas E, Sola MC, Hutson AD, Theriaque D, Christensen RD. Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit. J Perinatol. 2001;21(7):415–420. doi: 10.1038/sj.jp.7210566. [DOI] [PubMed] [Google Scholar]
  • 68.Baer VL, Lambert DK, Henry E, Snow GL, Sola-Visner MC, Christensen RD. Do platelet transfusions in the NICU adversely affect survival? Analysis of 1600 thrombocytopenic neonates in a multihospital healthcare system. J Perinatol. 2007;27(12):790–796. doi: 10.1038/sj.jp.7211833. [DOI] [PubMed] [Google Scholar]
  • 69.Houben NAM, Lopriore E, Fijnvandraat K, Caram-Deelder C, Carrascosa MA, Beuchée A, et al. Platelet transfusion in neonatal intensive care units of 22 European countries: a prospective observational study. Lancet Reg Health Eur. 2024;47:101086. doi: 10.1016/j.lanepe.2024.101086. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

BLT-24-035_OnlineSupplementaryContent.pdf (776.2KB, pdf)

Articles from Blood Transfusion are provided here courtesy of SIMTI Servizi

RESOURCES