Tiny Patients, Big Questions: Rethinking Pediatric and Neonatal Transfusion Thresholds

When we talk about blood transfusions, most people picture adults — trauma victims, surgical patients, the critically ill. But what about the smallest, most vulnerable patients: children and newborns?

Pediatric and neonatal transfusion medicine is a field riddled with tough questions, thin evidence, and sometimes, uncomfortable extrapolations from adult data. Despite heroic efforts by clinicians and researchers, there remains a striking lack of robust, large-scale evidence to guide transfusion decisions in these populations. Why? Because no one wants to experiment on fragile babies. But without strong data, we’re often left making decisions in the dark.

In this post, I’m summarizing two comprehensive reviews of current transfusion practices — one focused on pediatric patients1 and one on neonates2 — highlighting key studies, existing guidelines, and open questions in the field. These reviews help illuminate both where we’ve made progress and where major evidence gaps remain.

Let’s break down what we know, where we’re guessing, and what the latest research is telling us.

Pediatric Patients: Blood, Platelets, and Plasma

For pediatric red blood cell (RBC) transfusions, guidelines like those from the AABB and TAXI (Pediatric Critical Care and Anemia Expertise Initiative)3 recommend a restrictive approach — usually transfusing when hemoglobin drops below 7 g/dL in stable, non-cardiac intensive care patients. This approach stems largely from the TRIPICU study, 4 which showed no difference in outcomes (like mortality, infections, or multi-organ failure) between children transfused at 7 g/dL versus 9.5 g/dL. In fact, multiple analyses now suggest no clear benefit to “liberal” transfusion strategies.

When it comes to pediatric platelets, things get trickier. Adult guidelines offer thresholds (e.g., 10,000/μL for prophylaxis, 50,000/μL for most surgeries), but evidence in children is sparse — and what we do have suggests that platelet count alone is a poor predictor of bleeding risk. The PLADO trial5 found that lower platelet doses worked just as well to prevent bleeding, but importantly, children were at higher bleeding risk than adults, regardless of pre-transfusion count. This raises provocative questions: Do kids’ platelets behave differently? Do their vascular systems react in ways we don’t fully understand?

For plasma transfusions, the story is sobering. Many plasma transfusions in both children and adults are given to “correct” lab abnormalities (like a high INR) before procedures when no bleeding is present — but randomized trials consistently show no benefit in such situations. It’s a potent reminder: abnormal numbers don’t always mean intervention is needed.

Neonatal Patients: A World Apart

Newborns, especially preemies, bring their own unique challenges.

Neonatal red cell transfusion practices are influenced by the fascinating physiology of perinatal hematopoiesis. Term infants start with high hemoglobin levels (16–17 g/dL), but experience a “physiologic anemia” around 8 weeks as levels naturally drop before rising again. Premature infants, however, face even steeper drops due to shorter red cell lifespans and immature erythropoiesis.

Two recent landmark trials, ETTNO6 and TOP7, compared liberal and restrictive hematocrit thresholds for RBC transfusions in premature neonates. Both found no difference in survival or neurodevelopmental outcomes, supporting a move toward more restrictive strategies — though the nuances (like how early or prolonged anemia affects development) are still being debated.

Platelet transfusion in neonates is another evolving area. Thrombocytopenia is common in preemies, but high thresholds (like 50,000/μL) may actually increase the risk of death and bleeding, as shown in the PlaNet-2 study.8 A lower threshold of 25,000/μL appears safer, especially in the most fragile babies.

In neonates, plasma transfusions are typically used for active bleeding, disseminated intravascular coagulation (DIC), severe liver disease, or as replacement fluid during procedures like ECMO or plasma exchange. While abnormal lab values (like elevated INR or aPTT) often trigger plasma use, studies show little benefit in correcting mild or moderate abnormalities in non-bleeding infants. This is partly because neonatal coagulation is naturally different: most clotting factors are around 50% of adult levels, but factors like fibrinogen, Factor V, Factor XIII, Factor VIII, and vWF are at or above adult levels at birth.

Cryoprecipitate is mainly used to replace fibrinogen in cases of hypofibrinogenemia or dysfibrinogenemia, especially when bleeding or before surgery. Some centers are exploring human fibrinogen concentrate as an alternative, but thresholds for when to treat (often <100–150 mg/dL) remain debated. Importantly, routine prophylactic use of plasma or cryo in non-bleeding neonates is not well supported by evidence.

What’s Next?

If there’s a unifying theme across pediatric and neonatal transfusion medicine, it’s this: We need more and better evidence, and we need to stop reflexively applying adult rules to tiny bodies.

Future research must tackle not just laboratory thresholds, but meaningful clinical outcomes — survival, development, quality of life. We also need smarter tools to assess bleeding risk beyond raw platelet counts or clotting times, especially in neonates whose physiology is fundamentally different.

Until then, clinicians must walk a delicate line: applying the best available evidence, challenging outdated practices, and recognizing when “normalizing the numbers” may do more harm than good.

Final Thoughts

Pediatric and neonatal transfusion medicine asks us to confront some of the hardest questions in healthcare: How do we protect our most vulnerable patients without overreacting to imperfect data? How do we balance caution with evidence? And how do we, as stewards of limited and precious blood products, make sure we’re giving — or holding back — for the right reasons?

In the end, perhaps the most powerful transfusion decision is the one not made lightly.

1. Mo YD, Delaney M. Transfusion in Pediatric Patients. Clin Lab Med. 2021;41(1):1-14. doi:10.1016/j.cll.2020.10.001

2. Zerra PE, Josephson CD. Transfusion in Neonatal Patients. Clin Lab Med. 2021;41(1):15-34. doi:10.1016/j.cll.2020.10.002

3. Valentine SL, Bembea MM, Muszynski JA, et al. Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Pediatric Critical Care Medicine. 2018;19(9):884-898. doi:10.1097/PCC.0000000000001613

4. Lacroix J, Hébert PC, Hutchison JS, et al. Transfusion Strategies for Patients in Pediatric Intensive Care Units. New England Journal of Medicine. 2007;356(16):1609-1619. doi:10.1056/NEJMoa066240

5. Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage. New England Journal of Medicine. 2010;362(7):600-613. doi:10.1056/NEJMoa0904084

6. Franz AR, Engel C, Bassler D, et al. Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants. JAMA. 2020;324(6):560. doi:10.1001/jama.2020.10690

7. Kirpalani H, Bell EF, Hintz SR, et al. Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants. New England Journal of Medicine. 2020;383(27):2639-2651. doi:10.1056/NEJMoa2020248

8. Curley A, Stanworth SJ, Willoughby K, et al. Randomized Trial of Platelet-Transfusion Thresholds in Neonates. New England Journal of Medicine. 2019;380(3):242-251. doi:10.1056/NEJMoa1807320