Blood Product Transfusions for Children in the Perioperative Period and for Critically Ill Children

Abstract

Background

Approximately 1% to 2% of all hospitalized children receive a transfusion of blood products, in Germany as in other countries. High-quality scientific evidence on transfusions in children is scarce. The available evidence is discussed in this review.

Methods

This review is based on publications on blood product transfusions in children that were retrieved by a literature search, including clinical studies, international guideline recommendations, the recommendations of the German cross-sectional guideline, and results of other recent, relevant publications.

Results

A restrictive transfusion strategy is recommended for all children, including those who are critically ill. Randomized controlled trials have shown that a restrictive strategy for erythrocyte concentrate transfusion in the intensive care unit is safe for children, including neonates. No robust data are available to enable the definition of a suitable threshold for the intraoperative administration of red blood cell concentrates in children undergoing extracardiac surgery. On the basis of studies from pediatric intensive care units, transfusions for hemodynamically stable children with a hemoglobin concentration of more than 7 g/dL are recommended only in exceptional cases. Therapeutic plasma is not recommended as volume replacement, except in massive transfusion. Platelet concentrate transfusions are indicated in case of active hemorrhage, and only rarely for prophylaxis.

Conclusion

There is a broad lack of evidence from randomized controlled trials concerning the indications for transfusions in children. A restrictive transfusion strategy, which has been found safe in the intensive-care setting, is favored by the guidelines in the perioperative setting as well. Further studies are needed to evaluate transfusion triggers and indications for all types of blood products, especially therapeutic plasma. Until more evidence is available, physicians should be aware of what the current evidence supports, and blood products should be given restrictively, and not prophylactically.

CME plus⁺

This article has been certified by the North Rhine Academy for Continuing Medical Education. The questions on this article may be found at http://daebl.de/RY95. The closing date for entries is January 25, 2025.

Participation is possible at cme.aerztebatt.de

In the field of medicine, “blood” is an indispensable resource, yet it is becoming increasingly scarce. At the same time the transfusion of foreign blood is associated with risks for recipients if there is inadequate indication for its use (1). For this reason, a rational approach to the use of allogeneic blood transfusions is recommended in all areas of medicine and encouraged by the World Health Organization (WHO) (2). This recommendation also applies to pediatric patients before, during and after surgery. This is because transfusions in these patients are also associated, amongst other things, with increased 30-day mortality, more postoperative infections, and longer hospital stays (3, 4).

Approximately 1% to 2% of all hospitalized children in Germany receive a transfusion of blood products (5), while internationally this rate is reported to be 2% (6) or 9% (7). Apart from those undergoing oncology treatment, these numbers primarily include children who receive transfusions before, during, and after surgery. The transfusion rate for surgical patients in the European region is 7% of neonates and infants. The rate of perioperative transfusions for injured children in the USA is 18% (8, 9).

Methods

We conducted a selective literature review in the PubMed database on March 01, 2023. We analyzed relevant trials covering the indication for perioperative transfusion and international guidelines and recommendations for blood product transfusions in neonates and children.

Red cell concentrates

Transfusion thresholds in the cross-sectional guidelines for red cell concentrate transfusions

The evidence for the right time and the correct hemoglobin (Hb) transfusion threshold, or trigger, is significantly weaker for neonates and children than for adults (10). A groundbreaking randomized multicenter study (TRIPICU) involving stable, critically ill children under intensive care demonstrated the safe use of restrictive Hb transfusion thresholds (11) (Table 1). As a result, this study and an empirical lowering of the threshold values led to a reduction of the threshold for transfusions in children. A subsequent meta-analysis of premature infants involving four randomized studies showed no rise in mortality after applying a low threshold (12). However, when the cross-sectional guidelines (CSGs) were published, these results were still conflicting with regard to the neurological and intellectual development of premature infants when restrictive Hb transfusion thresholds were applied (10, 13–16).

Table 1. Selected studies on perioperative transfusion thresholds for red cell concentrate and platelet concentrate*.

Study	Design/setting	Intervention	Outcome primary endpoint	Comments
Red blood cell concentrates
ETTNO (17)	Multicenter RCT Neonatal ICUs Neonatals <1000 g	Difference between liberal and restrictive transfusion strategy (see text), based on infants’ postnatal age and current health state	1013 pats./36 centers, no difference between liberal versus restrictive regarding death or neuro-disability (cognitive deficit, cerebral palsy, or severe visual or hearing impairment) at age of 24 months (44.4% vs. 42.9%, p = 0.72)	The actual restrictive and liberal Hb thresholds applied differed by 0.5 to 1.2 g/dL per week
TOP-Trial (18)	Multicenter RCT Neonatal ICUs Preterm infants <1000 g	Difference between liberal and restrictive transfusion strategy (see text), based on infants’ postnatal age and current health state	1824 pats./41 centers, no difference between liberal versus restrictive regarding death or neuro-disability (cognitive deficit, cerebral palsy, or severe visual or hearing impairment) at age of 22 to 26 months (50.1% vs. 49.8%, p = 0.93)	The actual restrictive and liberal Hb thresholds applied differed by 1.9 g/dL
Cochrane Review (12)	Meta-analysis 4 RCTs involving premature infants using mortality and major morbidity as outcomes	Transfusion based on restrictive versus liberal Hb levels	No difference regarding death or major morbidity at hospital discharge	The need for studies with a longer follow-up was met with the ETTNO and TOP trials.
TRIPICU (11)	Multicenter RCT Pediatric ICUs Stable children >3 days and <14 years	Transfusion 7 g/dL vs. 9.5 g/dL	The restrictive transfusion strategy is not superior to liberal transfusion with regard to multiple-organ dysfunction 28 days after randomization (12% vs. 12%)
Cholette et al. (29)	Single-center randomized postoperative on ICU Children <10 kg cyanotic/acyanotic with biventricular or palliative surgery	Transfusion biventricular: 7.0 g/dL vs. 9.5 g/dL palliative: 9.0 g/dL vs. 12 g/dL	162 pats. (105 biventricular, 57 palliative) significantly lower Hb levels/transfusion rates/volumes in restrictive group despite same oxygen supply parameters and same clinical outcome
Platelet concentrates
Nellis et al. (40)	Prospective cohort study involving 82 pediatric ICUs in 16 countries Children >3 days <16 years	Observation of platelet transfusion prevalence, platelet transfusion indication, outcome, mortality Various age groups, various pre-existing conditions, different standards on the PICUs	559/16 934 pats. received at least 1 platelet transfusion (prevalence 3.3%). Indications were prophylaxis (67 %, of which 34% had platelets over 50 000/µL), minor bleeding (21%), and major bleeding (12%).	Upon adjusted analysis, the PC dose was independently associated with ICU mortality.
PlaNeT-2 trial (e9) Moore et al. (e10)	Multicenter RCT Neonatal ICUs Preterm infants born <34th WoG with severe thrombocytopenia 2-year follow-up	Platelet transfusion at a threshold of 50 000/µL vs. 25 000/µL	660 preterm infants; rate of major bleeding or death significantly higher in transfused children over 50 000/µl (26% vs. 19% in transfused children over 25 000/µL, p = 0.02) Rate of death or neuro-disability after 2 years was higher in the transfused children at 50 000/µl (50%/39%, p = 0.017)	No difference with regard to serious adverse events in both groups

* No relevant studies could be identified for plasma

Hb, hemoglobin; ICU, intensive care unit; OP, operation; pats., patients; PICU, pediatric intensive care unit; Plt, platelet level; RCT, randomized controlled trial; WoG, week of gestation; PC, platelet concentrate

Two important neonatology trials which address this unresolved question were published shortly after the current CSGs and confirm the safety of the restrictive transfusion strategy recommended in the CSGs for this vulnerable group of patients (Table 1) (17, 18). Different transfusion thresholds are recommended in the Table of the CSGs for premature infants and neonates (Table 2), depending on their age and clinical condition. The Table is taken from the very extensive and detailed “Guidelines on transfusion for fetuses, neonates and older children” drawn up by the British Committee for Standards in Haematology (BCSH) (19). The hemoglobin concentrations for premature neonates on room air provided in the Table are also recommended in the original guidelines as thresholds for perioperative transfusion in neonates, as there is no evidence for higher thresholds in this group. Furthermore, the CSGs also recommend that red cell concentrates (RCCs) be administered to premature and full-term infants as acute treatment of volume depletion secondary to blood loss (Level 1 C+ recommendation).

Table 2. Indications for the administration of red blood cell concentrates in premature infants and neonates according to the CSGs*.

Age	Transfusion thresholds
	Invasive ventilation	O2 therapy or non-invasive ventilation	Room air
0–24 hrs	<12.0 g/dl	<12.0 g/dl	<10.0 g/dl
1–7 days	<12.0 g/dl	<10.0 g/dl	<10.0 g/dl
8–14 days	<10.0 g/dl	<9.5 g/dl	<7.5 g/dl
>14 days	<10.0 g/dl	<8.5 g/dl	<7.5 g/dl

* Cross-sectional guidelines on therapy with blood components and plasma derivatives issued by the German Medical Association (10)

hrs, hours

The age limit from which transfusions may be carried out even more restrictively has been reduced from four months to four weeks. A hemoglobin concentration (Hb) of less than 6–7 g/dL and a hematocrit level (Hct) below 20% are regarded as transfusion thresholds for acute hemorrhage in hemodynamically stable children over four weeks of age. Hb levels must not fall below 10 g/dL and Hct not below 30% in hemodynamically unstable children older than four weeks. The guideline recommends an Hb threshold of 7 to 8 g/dL in the presence of chronic anemia in children beyond the neonatal period who are not hypoxemic, not hemodynamically unstable, nor have a cyanotic heart disease.

Thresholds for red blood cell concentrate transfusions in children as stated in worldwide guidelines

The guideline from the “European Society of Anaesthesiology and Intensive Care” (ESAIC) for “severe perioperative bleeding” (20) (Box), revised in 2022, is opposed to transfusion if the child is hemodynamically stable and the Hb concentration is at least 7 g/dL. The decision to transfuse RBC concentrates should not only be based on laboratory results but should also depend on the child’s clinical condition and take risks and advantages of transfusion into account. Please refer to the guideline of the “Pediatric Critical Care Transfusion and Anemia Expertise Initiative” (TAXI) for further details (21). TAXI clearly recommends transfusion for critically ill full-term neonates, children up to the age of 18 years, and children with a risk for critical illness if the Hb concentration is below 5 g/dL. In critically ill children who are hemodynamically stable and have an Hb concentration of 7 g/dL or more, it is recommended not to administer a transfusion unless the children are suffering from acute brain injury, have specific oncological diagnoses or heart disease. A transfusion may possibly be considered or recommended for the latter group of children (more information available in the Figure). It is recommended to consider transfusion based on clinical judgment in critically ill children with an Hb concentration between 5 and 7 g/dL. No transfusion threshold values are provided for critically ill children with unstable, non-hemorrhagic shock. In this situation, transfusion should be adapted to the clinical situation.

Box. International guidelines together with hemoglobin (Hb) threshold values, modified from (31).

British guidelines 2016 “British Committee for Standards in Haematology” (BSCH) (19)

• Premature infant

  Initial 24 hrs:

  • without oxygen <10 g/dl

  • with oxygen/non-invasive ventilation <12 g/dl

  • ventilated <12 g/dl

  1–7 days:

  • without oxygen <10 g/dl

  • with oxygen/non-invasive ventilation <10 g/dl

  • ventilated <12 g/dl

  8–14 days:

  • without oxygen <7.5 g/dl

  • with oxygen/non-invasive ventilation <9.5 g/dl

  • ventilated <10 g/dl

  ≥ 15 days

  • without oxygen <7.5 g/dl

  • with oxygen/non-invasive ventilation <8.5 g/dl

  • ventilated <10 g/dl

• Neonates

  • transfusion of small amounts not related to heart surgery:

    0–7 days: <10 g/dl

    ≥ 8 days: <7.5 g/dl

  • transfusion of large quantities or major blood loss:

    therapeutic goal 8 g/dL, ratio of red blood cells/therapeutic plasma 1:1

  • heart surgery using heart-lung machine:

    no transfusion threshold

  • heart surgery after using heart-lung machine:

    non-cyanotic and cyanotic cardiac diseases:

    threshold >7 g/dL may be adequate

• Infants and children

  • pediatric intensive care: hemodynamically stable children without cyanosis: 7 g/dL,

    unstable children or with symptomatic anemia: higher

  • non-cardiac surgical procedures and without major bleeding: perioperative threshold of 7 g/dL

  • major blood loss: therapeutic goal 8 g/dL, ratio of red blood cells/therapeutic plasma 1:1

  • heart surgery using heart-lung machine:

    no evidence for appropriate transfusion thresholds

  • heart surgery after heart-lung machine use:

    hemodynamically stable children with non-cyanotic cardiac diseases: 7 g/dL

  • cyanotic cardiac diseases: inadequate level of evidence

Guideline Australia 2016 (22)

under revision

Guideline Europe 2023 “European Society of Anesthesiology and Intensive Care” (ESAIC) (20)

• Neonates and children

  • no transfusion if hemodynamically stable and Hb ≥ 7 g/dL

  • take into account the clinical condition of the child

  • weigh up the risks and benefits of transfusion

  • apply TAXI guideline (21)

Guideline Canada 2017 (23)

• Premature infant without ventilation

  • 0–7 days: 10 g/dL

  • 8–14 days: 8.5 g/dL

  • >14 days: 7.5 g/dL

• Full-term neonate

  • <8 g/dL for stable neonates with symptoms of anemia

  • <12 g/dL for severe respiratory disease or congenital heart disease

  • acute blood loss >10% of blood volume

• Children >4 months

  • <7 g/dL with symptoms of anemia

  • acute blood loss >15% of blood volume

Guideline USA 2018 “Pediatric Critical Care Transfusion and Anemia Expertise Initiative” (TAXI) (21)

• full-term infants and children (Figure)

Guideline network 2019 “Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis” (NATA) (24)

• Cardiac surgery for neonates and children

  • while using heart-lung machine: target hematocrit level at 24%

  • postoperative

    • hemodynamically stable children with acyanotic heart disease with symptomatic anemia: 7 g/dL

    • hemodynamically stable children with non-cyanotic heart disease with symptomatic anemia: 8 g/dL

    • hemodynamically stable children with cyanotic heart disease with symptomatic anemia: 9 g/dL

Guideline of American blood banks 2023 “American Association of Blood Banks” (AABB) (25)

• hemodynamically stable, critically ill children or children with the risk for critical illness, who are hemodynamically stable: <7 g/dL (not when associated with hemoglobinopathy, cyanotic heart disease, or severe hypoxemia)

• hemodynamically stable children with congenital heart disease:

  7 g/dL (biventricular repair),

  9 g/dL (single-ventricle palliation),

  7–9 g/dL (uncorrected congenital heart disease)

Figure.

Transfusion and Anemia Expertise Initiative(TAXI) RBC transfusion decision tree for critically ill children (21). Recommendations apply to full-term infants and older children with critical illnesses who are being treated in intensive care. The TAXI guideline differs from the cross sectional guideline in several aspects: no information is given on premature babies, Hb thresholds of 5–7 g/dL are tolerated depending on the patient cohort and clinical condition.

No information is given on Hb measurements in unstable children or children in hemorrhagic shock. However, greater detail is given on Hb thresholds in relation to different operations in stable children.

* converted to the German product units: 8:4:1 or 4:4:1

Flow chart adapted from Valentine et al. (21); printed with the kind permission of Wolters Kluwer Health Inc.;

ACS, acute chest syndrome; ECMO, extracorporeal membrane oxygenation; Hb, hemoglobin; PARDS, pediatric acute respiratory distress syndrome; VAD, ventricular assist device.

In children with hemorrhagic shock, it is recommended to transfuse RBCs, plasma, and platelets empirically in ratios between 2 : 1 : 1 and 1 : 1 : 1 until the bleeding is no longer life-threatening. Converted to the German product units (in bags) RBCs, fresh frozen plasma, and platelet concentrate (PC), this means ratios between 8 : 4 : 1 and 4 : 4 : 1. The Figure is based on the TAXI guideline and presented as a flow diagram to facilitate the decision-making process (21).

The very detailed and practice-orientated “National Blood Authority, Australia: Patient Blood Management Guidelines: Module 6 – Neonatal and Paediatrics”, from the year 2016 (22), is currently being updated. The guideline from the Canadian Blood Service of 2017 (23) stresses that there is no single value of Hb concentration that indicates that a transfusion is required. Clinical judgement is critically important. The major indication for transfusion is the prevention or alleviation of symptoms or signs of inadequate oxygen delivery to the tissue (see Box for details).

In 2019, the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA) published guidelines on “Patient Blood Management for Neonates and Children Undergoing Cardiac Surgery” (24) (Box).

For the first time, the currently revised guidelines of the American Association of Blood Banks (AABB) for critically ill children (25) also provide recommendations for children (Box).

The Box shows that Hb threshold values tend to be lower with progressively more recent publication dates of the guidelines. The lower threshold value of 5 g/dL from the TAXI guideline is here the lowest of the lower threshold values. The threshold value of 10 g/dL from the cross-sectional guideline of the German Medical Association (BÄK) for unstable children with acute blood loss older than four weeks is the highest Hb threshold value stated for this age group.

Current studies on the evidence regarding red blood cell transfusions

A randomized controlled trial from the year 2020 (ETTNO) examined the effects of liberal versus restrictive transfusion strategies on survival and neurodevelopment in 1013 extremely premature children with birth weights between 400 and 999 g in 36 level III/IV neonatal intensive care units in Europe (17). They were randomly assigned to liberal or restrictive transfusion strategies. The primary outcome was death or neuro-disability (cognitive deficit, cerebral palsy, or severe visual or hearing impairment) at 24 months. The restrictive transfusion threshold for stable children aged between three and seven days was an Hb concentration below 9.5 g/dL and below 11.9 g/dL for the liberal strategy. The Hb concentration was below 8.2 g/dL for the restrictive strategy and below 10.5 g/dL for the liberal strategy for ages between eight and 21 days. The Hb concentration was below 7.1 g/dL for the restrictive strategy and below 9.5 g/dL for the liberal strategy for ages older than 21 days. In each case, the values were two to 2.1 g/dL higher for unstable children. After 24 months there was no difference with regard to death or neuro-disability between the liberal and the restrictive group (44.4% versus 42.9%, p = 0.72), thus demonstrating the safe application of the restrictive transfusion strategy. The restrictive and liberal Hb thresholds ultimately used in practice in the study differed significantly on average by 0.5 to 1.2 g/dL.

Using a similar study design, yet with more restrictive Hb values, in unstable premature infants, the multicenter randomized controlled trial “TOP Trial” (18) examined the Hb threshold values in neonates while taking their clinical condition into consideration. These results also show that liberal in comparison with restrictive Hb thresholds in extremely premature neonates did not produce any difference after 22 to 26 months as regards neurodevelopment and survival (50.1% versus 49.8 %, p = 0.93).

The two studies TOP Trial and ETTNO Trial show that a restrictive transfusion strategy is safe for this vulnerable age group of premature infants in the intensive care unit. The results support and substantiate the transfusion recommendations of the CSGs for premature infants and the BCSH for stable premature infants on room air and for premature infants on non-invasive ventilation/O2 therapy. The recommendations of the CSGs for invasively ventilated children, however, tend to be higher than the restrictive thresholds validated in both studies.

There is a lack of studies in the perioperative pediatric field on the applied transfusion thresholds. Few studies are available on Hb transfusion thresholds in children undergoing cardiac surgery applied before, during, and after surgery which suggest that a restrictive transfusion strategy generally appears to be safe (26–29). A meta-analysis of these studies concludes that these data are not yet adequate for a recommendation with robust evidence (30). The present authors know of no studies with Hb transfusion thresholds for non-cardiac surgical children. The pathophysiology and requirements of children bleeding during surgery differ from children in intensive care units. However, the recommendations of the guidelines reported here for non-cardiac surgical children transfused during surgery had to be derived from the results of the studies in intensive care units due to the lack of other data (Table 1). They must be assessed against this background by the users (31, 32).

Even though the identification of “safe” hemoglobin thresholds for children is extremely important in practical anesthesia and perioperative medicine, it is also, and especially, true for pediatric patients that a transfusion decision should never be made solely on the basis of the Hb value. Oxygen supply and demand, lactate levels, regional oxygen saturation as well as the hemodynamic and respiratory status should, together with other parameters, be considered for the decision-making process. Downey and Goobie have proposed a model that includes these factors (32). Studies on such a complex transfusion model in children are still pending.

Therapeutic plasma

Therapeutic plasma stored in quarantine (formerly known as fresh frozen plasma, FFP, quarantine-stored therapeutic plasma, quarantine or Q plasma) comprises 200 to 300 mL coagulation-active plasma with a concentration of factor VIII of more than 70%. It is cell-free, has a shelf-life of one, two or three years, depending on its marketing authorization, and is frozen at minus 30 °C or below. The special indication for transfusing therapeutic plasma in children is cited in the cross-sectional guideline of the German Medical Council (10, 33) (eTable 1).

eTable 1. Recommendations for the administration of therapeutic plasma to premature infants and neonates, infants, and children, modified according to the cross-sectional guideline (10).

Recommendations	Level of evidence
Plasma combined with red blood cell concentrates could be used as priming fluid in neonates and infants undergoing cardiopulmonary bypass surgery or extracorporeal membrane oxygenation.	2C
Exchange transfusion in neonates shall be performed using red blood cell concentrates and plasma.	1C+
Plasma shall not be transfused prophylactically in premature infants with the objective of preventing intracerebral bleeding.	1A
Plasma shall not be transfused in children with hemolytic uremic syndrome without coagulopathy.	1B
Partial exchange transfusion in neonates with polycythemia and hyperviscosity syndrome shall not be performed using plasma.	1B

Level of evidence:

1A: strong recommendation valid for most patients

1B: strong recommendation probably valid for most patients

1C+: strong recommendation valid for most patients.

Depending on the individual case, a different course of action may be indicated. The most important recommendation is not to transfuse therapeutic plasma prophylactically in preterm infants with the objective of preventing intracerebral hemorrhage.

2C: very weak recommendation. Depending on the individual case, a different course of action may be indicated.

Administration of therapeutic plasma is indicated for active bleeding with coagulopathy (22), abnormal viscoelastic point-of-care testing, perioperative or peri-procedural 1.5-fold increase in activated partial thromboplastin time (aPTT), and is an essential component of massive transfusion (34–37). Regardless of age and laboratory parameters, therapeutic plasma should not be administered as protection against bleeding – with the following exceptions: before major surgery and for severe coagulation imbalance. Its prophylactic administration, for example, to correct laboratory abnormalities, is contraindicated. Therapeutic plasma should not be used for volume replacement, unless for massive transfusion.

Platelet concentrates

A PC comprises 200 to 400 mL and contains a minimum of two times 10¹¹ platelets and less than 1 000 000 white blood cells per unit. PCs are resuspended in plasma or additive solution and have a shelf life after donation of more than four days, provided they are stored at 22 plus or minus two degrees Celsius under agitation. A PC of 200 to 300 mL is obtained from a donor by apheresis. One pool of PC contains platelets from four to six donors. In Germany, around 60% of PCs are obtained by apheresis and around 40% from pool preparations.

The threshold values in eTable 2, based on the German Medical Council cross-sectional guideline of 2020 (10), should be applied.

eTable 2. Recommendations for the administration of platelets to neonates with Level of evidence 2 C+ (see Figure 2 for an explanation of the levels of evidence), modified according to the cross-sectional guideline (10)*.

Indication	Threshold value
No signs of bleeding	<25 000/μl
NAIT* with no family history of cerebral hemorrhage	<30 000/μl
Signs of bleeding, coagulopathy, NAIT with cerebral hemorrhage in one sibling	<50 000/μl
Major hemorrhage or impending major surgery	<100 000/μl

* Depending on the clinical situation, neonates are transfused at platelet counts of less than 25 000/µL if there are no signs of bleeding, before major surgery, or in the event of a major hemorrhage.

NAIT, neonatal alloimmune thrombocytopenia

Studies on the administration and evidence of PCs in neonates and children

Studies involving critically ill children show that more than 50% of PC administrations are provided for prophylaxis to non-bleeding children (38–40; e1–e3). A prospective, multicenter cohort study made a detailed assessment of PC transfusions in 82 pediatric intensive care units (PICUs) in 16 countries. Of these, 67% of the PCs were given prophylactically and only 33% for bleeding. The platelet count was above the indication level of 50 000/µL in 34% of the PC transfusions. This study showed that the total administered platelet dose was independently associated with increased ICU mortality (Table 1) (40). There was also a high incidence of neonatal thrombocytopenia in premature infants, occurring in 1.8/1000 live births, often developing in neonates with sepsis or asphyxia. Platelet transfusion was administered in 21% of cases. The mortality rate was not related to the severity of neonatal thrombocytopenia but did correlate with the number of PCs (e4).

In their review article, Goel et al. were unable to demonstrate any clear relationship between low platelet counts and clinical bleeding situation in neonates (e5). However, thrombocytopenia was associated with retinopathy in preterm infants (e6). Two studies compared restrictive with prophylactic PC transfusions in neonates without major bleeding. They showed that restrictive transfusion management is superior to a prophylactic approach: In a randomized controlled trial, Kumar et al. examined the effect of platelet transfusions on closure of patent ductus arteriosus. Transfusions were given to maintain platelet counts to either above 100 000 per µL or to different platelet counts below 100 000/µL. There was no difference with regard to ductus closure, although 41% of infants in the liberal platelet transfusion group demonstrated intraventricular hemorrhage in comparison with only 4.5% in the restrictive group (e7). In the multicenter “Randomized Trial of Platelet-Transfusion Thresholds in Neonates“ (PlaNeT-2), neonates born at less than 34 weeks of gestation received a platelet transfusion at a platelet-count threshold of either 25 000/µL or 50 000/µL (Table 1) (e8, e9). Major bleeding events and mortality were higher in the platelet transfusion group with the liberal strategy (26%/19%, p = 0.02).

The two-year follow-up was published in 2023 and presented data for 92% (601/653 neonates) of the children. Half (50%) of the neonates included in the liberal group died or demonstrated neurodevelopmental impairment, while 39% died in the restrictive group (p = 0.017). These data indicate that prophylactic or liberal PC transfusions are harmful (e10). The reasons for this are unknown, but the authors of the study consider that the immunological and inflammatory effects of thrombocytes and transfusion-related changes in organ and brain perfusion could be responsible for the negative effects.

One limitation which is already clear from this presentation is that the studies were each conducted for a specific cohort and that different definitions were used with regard to restrictive and liberal PC administration, making generalization difficult at the present time.

Summary

In summary, it may be said: Multicenter randomized studies have shown that a restrictive transfusion strategy is safe for premature infants in the intensive-care setting when it comes to the transfusion of ECs. For children of other age groups, however, there is a lack of evidence from randomized studies, particularly with regard to the transfusion of ECs in the intraoperative context and to therapeutic plasma in general.

Guidelines advocate a restrictive transfusion strategy in the intensive-care setting and, based on the results of the studies conducted in intensive care units, also in the perioperative setting. There are very few trials involving the administration of plasma. As far as platelet administration is concerned, data to date speak against prophylactic administration and in favor of a transfusion threshold of less than 25 000/µL in premature neonates.

Questions on the article in issue 2/2024:

Blood Product Transfusions for Children in the Perioperative Period and for Critically Ill Children

CME credit for this unit can be obtained via cme.aerzteblatt.de until January 25, 2025.

Only one answer is possible per question. Please select the answer that is most appropriate.

Question 1

Approximately what percentage of children hospitalized in Germany receive a transfusion?

1.  1–2%

2.  3–5%

3.  7–11%

4. 13–15%

5. 15–20%

Question 2

According to the cross-sectional guidelines of the German Medical Association on therapy with blood components and plasma derivatives, which hematocrit value is considered a threshold for transfusion in premature and neonate infants within the first 24 hours of life in children requiring invasive ventilation or oxygen therapy or non-invasive ventilation?

1. Hb: <10 g/dL

2. Hb: <7.5 g/dL

3. Hb: <12 g/dL

4. Hb: <15 g/dL

5. Hb: <18 g/dL

Question 3

According to the TAXI guidelines, which components should a transfusion contain for pediatric hemorrhagic shock?

1. Fresh frozen plasma and red cell concentrate in a ratio of 3:1 (German product units)

2. Red cell concentrate, fresh frozen plasma, and platelet concentrate in a ratio of 8:4:1 or 4:4:1 (German product units)

3. Platelet concentrate and red cell concentrate in a ratio of 1:3 (German product units)

4. Fresh frozen plasma and platelet concentrate in a ratio of 1:1 (German product units)

5. Red cell concentrate, fresh frozen plasma, and platelet concentrate in a ratio of 1:2:4 (German product units)

Question 4

For which patients was the NATA guideline, published in 2019, created?

1. For premature infants with cerebral edema

2. For full-term infants with jaundice

3. For premature infants with iron deficiency anemia

4. For premature infants with poor lung maturity

5. For cardiac surgical neonates and children

Question 5

What is the composition of therapeutic plasma?

1. 100–200 mL coagulation-active, cell-free plasma with a factor V concentration >70%

2. 200–300 mL coagulation-active, cell-free plasma with a factor VIII concentration >70%

3. 300–500 mL coagulation-active, cell-free plasma with a factor VIII concentration <30%

4. 500–700 mL coagulation-active, cell-free plasma with a factor V concentration >50%

5. 400–600 mL coagulation-active, cell-free plasma with a factor VIII concentration <50%

Question 6

What details are mentioned in the text regarding temperature and storage time for therapeutic plasma?

1. Storage at ≤ -30 °C for at least 4 months (quarantine)

2. Storage in liquid nitrogen for at least 3 months (quarantine)

3. Storage at -20 °C for no more than 6 months (limited shelf life)

4. Storage in liquid nitrogen for no more than 9 months (limited shelf life)

5. Storage at a maximum of +4 °C for at least 4 months (quarantine)

Question 7

The randomized controlled ETTNO study compared restrictive with liberal transfusion thresholds in extremely premature infants with birth weights between 400 g and 999 g. Which statement about the comparison of the groups (restrictive versus liberal transfusion thresholds) is correct?

1. The group with restrictive transfusion thresholds developed significantly more neuro-disabilities.

2. Significantly more deaths occurred in the group with the liberal transfusion thresholds.

3. Death and neuro-disabilities did not differ significantly between the groups.

4. There were significantly more deaths in the group with restrictive transfusion thresholds.

5. The study had to be terminated prematurely due to the enormous disadvantage of the group with restrictive transfusion thresholds.

Question 8

How are platelet concentrates resuspended and stored until use (within 4 days)?

1. Resuspension in distilled water with agitation during storage at 22 ± 2 °C

2. Resuspension in isotonic saline solution with agitation during storage at 6 ± 4 °C

3. Resuspension in isotonic saline solution with agitation during storage at 4 ± 2 °C

4. Resuspension in plasma or additive solution with agitation during storage at 22 ± 2 °C

5. Resuspension in plasma or additive solution with agitation during storage at 2 ± 2 °C

Question 9

Which statement about the use of platelet concentrates in neonates and children is true according to the statements in the article?

1. Prophylactic or liberal administration of PC is more likely to be harmful

2. Prophylactic administration of PC has proven to be very safe

3. The liberal regime for PC is favored in premature infants <34 weeks of gestation

4. Mortality in premature infants with thrombocytopenia is unrelated to the number of transfused PCs

5. The liberal administration of PCs in particular accelerates closure of the ductus arteriosus

Question 10

Which of the following statements on hemoglobin thresholds is correct?

1. The recommended threshold tends to be lower for premature infants as compared with full-term infants.

2. The recommended threshold tends to fall with increasing age of the neonates.

3. The ventilation mode is irrelevant for the recommended threshold value.

4. The recommended threshold rises with increasing weight of the children.

5. The recommended threshold is oriented in the first year of life primarily according to the birth weight of the children.