Introduction

In Neonates (term and preterm) and children (infants toddlers, and old paediatric patients) Thrombocytopenia is defined as a platelet count below 150 X 109/L (1). The incidence of platelet transfusion and thrombocytopenia are both inversely related to the gestational age at birth. Almost 1% of term and 35 to 40% of preterm neonates will have thrombocytopenia and among these preterm babies will have platelet count <50 × 109/L.(2-7) In neonates born with a weight of <1000g thrombocytopenia may be estimated as to even 70%.(8) The causes of thrombocytopenia in neonates could be categorized based on the time of onset (early onset ≤72 h after birth and late-onset ≥72 h after birth) and whether it occurs in a sick or in a well-appearing new-born.(9)  Important considerations in platelet transfusion in paediatric or neonate population is  1) Choice of transfusion threshold and dose 2) Use of ABO-mismatched platelets; 3) Transfusion of Platelet product 4) Adverse effects associated with platelet transfusion in this population.

Indications & Thresholds

Recent randomized trials have established that a restrictive prophylactic trigger shows a lower composite rate of death or major bleeding compared with a liberal approach.

Neonates

Table 1: Causes of Neonatal Thrombocytopenia (10)

Causes of thrombocytopenia

Indication and Threshold for platelet transfusion

Early (≤72 h)

Late (≥72 h)

 

 

Non bleeding Pre‑term neonates, a prophylactic threshold of 25 × 109/L is now recommended. (11,12)

 

Term neonates: Healthy stable 25 × 109/L

 

Higher thresholds are used for specific risks:

 ECMO : 50–100 × 109/L,

Hypoxic ischemic encephalopathy:

up to 130 × 109/L to prevent haemorrhage.(1)

FNAIT: 50–100 × 109/L (first week of life)

*HPA-1a or 5b antigen negative platelets may be needed

Ill-appearing:

Ill-appearing:

Sepsis (bacterial, viral)

Sepsis (bacterial, viral, fungal)

TORCH infections

Toxoplasma, rubella, cytomegalovirus, herpes simplex virus

Necrotizing enterocolitis (NEC)

Birth asphyxia

Inborn error of metabolism

Well-appearing:

Well-appearing:

Placental insufficiency

Drug-induced thrombocytopenia

Genetic disorders

Thrombosis

Autoimmune

Fanconi anemia

Neonatal alloimmune thrombocytopenia (NAIT)

Paediatric Population

Table 2: Thresholds for prophylactic platelet transfusion in children (1, 10)

Causes of thrombocytopenia

Indication

Platelet transfusion threshold

 

Myelodysplasia,

Marrow infiltrative processes

Bone marrow failure syndromes

Congenital platelet disorders

Aplastic Anemia

Chemotherapy

Radiation

Hypo proliferative thrombocytopenia

10 × 109/L (15–20 × 109/L for HSCT)(AABB)

Line placement

20 × 109/L

Lumbar puncture

30–50 × 109/L (higher threshold considered when circulating blasts present)

CNS bleeding in children with sickle cell disease undergoing transplantation

30–50 × 109/L

Major surgery

50 × 109/L

CNS surgery

<100 × 109/L

Platelet dysfunction with bleeding and/or in need of an invasive procedure

Not applicable

 

 

Cause and severity of bleeding will guide platelet transfusion. For instance, bleeding

during surgery or extracorporeal membrane oxygenation (ECMO) should trigger platelet

transfusion when platelet count is 50–100 × 109/L.

Platelet Dose and Increments

For neonates and infants, a platelet dose of 5–10 mL/kg should increase the platelet count by 50–100 × 109/L (11). The desired platelet increment is achieved by transfusing 10 mL/kg of platelets providing around 10X 109 platelets from either a whole blood-derived random donor platelet or apheresis-derived platelet product. (4) By body weight, one unit of platelet transfusion per 10 kg should increase platelet count by 35–50 × 109/L and by 7–11 × 109/L/m2. (12) The response to platelet transfusion is measured by platelet increment, platelet count increase within 1 h post-transfusion. With adequate platelet dose transfusion, the platelet CI should be above 20% of the pre-transfusion platelet count if measured within 10– 60 min and higher than 10% if measured with 24 h post transfusion. (12) This dose is generally recommended to be transfused over 30 min, is now being advocated to be transfused over a period of 2–3 h to avoid the risk of IVH and existing evidence of no difference in platelet recovery between these time frames. American Association of Blood Banks (AABB) recommends a dose of 5–10 mL/kg at a rate of 5 mL/kg/h while some guidelines recommend a dose of 10–20 mL/kg. (11,13-16)

Platelet products used in neonates and children

In neonatal platelet transfusion choice of platelets affect platelet recovery and survival in vivo. International practices different between countries. Platelets used in neonatal transfusion are typically collected by apheresis from a single donor, instead of pooled platelets from multiple donors.(15) Single‑donor apheresis platelets (SDAP) adult apheresis units collected from one donor can be administered whole or split into paediatric aliquots(17,18,19). Random donor platelets (RDP) a whole blood derived platelet concentrates are most common product in low‑ and middle‑income settings (20). In the UK, since 2020, NHS Blood and Transplant has manufactured neonatal platelet packs of approximately 50 mL containing 20 percent platelet additive solution for neonatal and infant transfusion (16). In these packs, the platelet content per unit volume was reduced by about 20 percent to limit plasma exposure and associated risks. (16, 21) Leukoreduced platelet products – RDP or SDAP processed to remove white cells, decreases inflammatory and allo‑immune risk . ABO identical or non-identical compatible platelets are preferred to reduce the risk of haemolyses from passive transfer of donor iso hemagglutinins and to avoid reduced platelet survival due to ABO incompatibility. Rare but fatal haemolytic reactions have been reported with high titres ranging from 1:128 to 1:8000. (22).Volume‑reduced/split apheresis platelets (NeoVRs‑SDAP) for neonates delivering a higher platelet yield per mL and lowering donor exposure is a new approach being evaluated. (23)

Safety Considerations

Platelet transfusions in neonates are associated with intraventricular haemorrhage (IVH) and increased mortality through several inter‑related mechanisms. First, adult platelets carry a larger load of proangiogenic and vasoactive mediators which when transfused to neonates can deliver inappropriate angiogenic signals to a brain that is still undergoing vascular development, potentially destabilising the fragile germinal‑matrix vessels and precipitating IVH. Second, neonatal platelets are intrinsically hypofunctional, and the abrupt introduction of fully active adult platelets can create a pro‑thrombotic milieu, promoting microvascular thrombosis and further endothelial injury. Third, the transfusion volume itself (often 15 mL/kg) represents a rapid expansion of the circulating blood volume, which can alter cerebral perfusion pressures and exacerbate bleeding risk . Fourth, adult platelets may elicit heightened inflammatory responses in neonates with underlying infection or endothelial activation, amplifying systemic inflammation and contributing to organ dysfunction and death.(24,25,26)Together, these biological effects excess angiogenic signalling, pro‑thrombotic and pro‑inflammatory actions, and abrupt volume shifts—provide a plausible explanation for the paradoxical increase in IVH and mortality observed in randomized neonatal trials of liberal platelet‑transfusion thresholds. Additionally, adverse effects associated with transfusions in pediatric cases constitute approximately 8% of all reports submitted annually to SHOT, 50% of which are transfusion errors while febrile, allergic, and hypotensive reactions account for one-quarter of these reports.(24)

 

References

  1. Patel RM, Josephson C. Neonatal and pediatric platelet transfusions: current concepts and controversies. Curr Opin Hematol. 2019.
  2. Ferrer-Marin F, Liu ZJ, Gutti R, Sola-Visner M. Neonatal thrombocytopenia and megakaryocytopoiesis. Semin Hematol. 2010.
  3. Josephson CD, Su LL, Christensen RD, Hillyer CD, Castillejo MI,Emory MR. Platelet transfusion practices among neonatologists in the United States and Canada: results of a survey. Paediatrics. 2009.
  4. Strauss RG. How I transfuse red blood cells and platelets to infants with the anemia and thrombocytopenia of prematurity. Transfusion. 2008.
  5. Christensen RD, Henry E, Wiedmeier SE, et al. Thrombocytopenia among extremely low birth weight neonates: data from a multihospi tal healthcare system. J Perinatol. 2006.
  6. Dreyfus M, Kaplan C, Verdy E, Schlegel N, Durand-Zaleski I, Tchernia G. Frequency of immune thrombocytopenia in newborns: a prospective study. Blood. 1997.
  7. Strauss RG. Platelet transfusions in neonates: questions and answers Expert Rev Hematol. 2010.
  8. Elmoneim AA, Zolaly M, El-Moneim EA, Sultan E. Prognostic significance of early platelet count decline in preterm newborns. Indian J Crit Care Med. 2015.
  9. Sillers L, Van Slambrouck C, Lapping-Carr G. Neonatal thrombocytopenia: etiology and diagnosis. Pediatr Ann. 2015.
  10. Khillan K, Bandeira FM, Sato T, Pavenski K. Platelet transfusion. In: Smit Sibinga CT, Abdella YE, editors. Clinical Use of Blood: A Different Approach. Cham: Springer Nature Switzerland AG; 2024.
  11. Standards for Blood Banks and Transfusion Services. 28th ed. Bethesda, MD:AABB (2012).
  12. Kahn S, Chegondi M, Nellis ME, Karam O. Overview of plasma and platelet transfusions in critically ill children. Front Pediatr. 2020.
  13. Moore CM, Curley A. Platelet transfusion thresholds in neonatal medicine. Early Hum Dev. 2019.
  14. Mokhtar G, Adly A, Abdel Baky A, et al. Transfusion of blood components in pediatric age groups: an evidence-based clinical practice guideline adapted for the use in Egypt using “adapted ADAPTE”. Ann Hematol. 2024.
  15. Ferrer-Marín F, Sola-Visner M. Neonatal platelet physiology an implications for transfusion. Platelets. 2022.
  16. New HV, Stanworth SJ, Gottstein R, et al. British Society for Haematology guidelines on transfusion for fetuses, neonates and older children (Br J Haematol. 2016; 175: 784–828). Addendum august 2020. Br J Haematol. 2020.
  17. Coletti K, Hershey JA, Devine M, et al. An improvement project standardizing low prophylactic platelet transfusion dosing for infants. Perinatol. 2025. 
  18. Carr R, Kelly AM, Williamson LM. Neonatal thrombocytopenia and platelet transfusion-a UK perspective. Neonatology. 2014.
  19. New York State Council on Human Blood and Transfusion Services. Guidelines for transfusion of pediatric patients. New York State Department of Health, Wadsworth Center; 2016;64.
  20. Strauss RG. Platelet transfusions in neonates: questions and answers.Expert Rev Hematol. 2010.
  21. Pagano MB, Katchatag BL, Khoobyari S, Van Gerwen M, Sen N, Rebecca Haley N, et al. Evaluating safety and cost-effectiveness of platelets stored in additive solution (PAS-F) as a hemolysis risk mitigation strategy. Transfusion. 2019;59(4):1246–51. (PubMed: 30592057
  22. Angiolillo A, Luban NL. Hemolysis following an out-of-group platelet transfusion in an 8-month old with Langerhans cell histiocytosis. Journal of pediatric hematology/oncology. 2004.
  23. Dhiman Y, Patra S, Chetan C, et al. Improvising neonatal thrombocytopenia management: Insights from split, volume-reduced, single-donor apheresis platelets (NeoVRs-SDAP). Transfus Med. 2025.
  24. 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.
  25. 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.
  26. Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010.

The authors

Yashaswi Dhiman

Yashaswi Dhiman

Associate Professor, Clinical Transfusion Working Party Secretary, Department of Immunohematology and Blood Transfusion, HIMS, SRHU, Dehradun, Uttarakhand, India

Richard R. Gammon

Richard R. Gammon

Clinical Transfusion Working Party Chair, Medical Director, Moffitt Cancer Center and Research Institute, Tampa, Florida USA

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