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System-Based ProtocolsChapter 18

Hematology & Oncology

Neonatal Indirect Hyperbilirubinemia

Transcutaneous bilirubin (TCB)

Timing

qAM first 10 days of life
Clinically indicated

Threshold for follow-up blood test

Gestational Age	TCB threshold	Notify MD if:
< 28 weeks CGA	≥2 mg/dl	≥5 mg/dl
28-29 weeks CGA	≥3 mg/dl	≥6 mg/dl
30-31 weeks CGA	≥5 mg/dl	≥8 mg/dl
32-33 weeks CGA	≥7 mg/dl	≥10 mg/dl
34 weeks CGA	≥9 mg/dl	≥12 mg/dl
For ≥35 weeks CGA, use www.bilitool.org (up to 146 hrs) or www.peditool.org (for > 146 hrs): If TCB in high-intermediate risk zone (>75%ile of Bhutani nomogram) or TCB ≥13, draw stat TSB and notify MD if TSB is high-risk zone or ≥13 mg/dl

Additional TCB screening for DAT+

flowchart TD
  A["DAT+ and GA ≥ 32wks"] --> B["Check TCB at 6 hrs"]
  B --> C["If TCB <4, continue regular screening"]
  B --> D["If TCB 4-5, repeat TCB at 12 hrs"]
  B --> E["If TCB ≥ 5, draw TSB. Notify MD if TSB ≥ 5"]
  D --> E

dotPhrase

Phototherapy for preterm infants

	Phototherapy	Exchange transfusion
Gestational age (week)	Total serum bilirubin (mg/dl)	Total serum bilirubin (mg/dl)
< 28 0/7	5-6	11-14
28 0/7 - 29 6/7	6-8	12-14
30 0/7 - 31 6/7	8-10	13-16
32 0/7 - 33 6/7	10-12	15-18
34 0/7 - 34 6/	12-14	17-19

IVIG for ABO incompatibility

Dose: 1g/kg/dose
Administration instruction: 1mg/kg/min for the first 30 min; if tolerated, increase gradually to a maximum of 8mg/kg/min. Total administration time: 6 hrs.

Alpha-fetoprotein (AFP) Reference Range

Term infants (GA ≥ 37wks) without additional risk factors for AFP elevation

Preterm infants (GA < 37wks) without additional risk factors for AFP elevation

Show the values

Age (days)	AFP mean (ng/mL)	AFP 95% confidence interval (ng/mL)
0	158,125	31,261-799,834
1	140,605	27,797-711,214
2	125,026	24,717-632,412
3	111,173	21,979-562,341
4	98,855	19,543-500,035
5	87,902	17,378-444,631
6	77,625	15,346-392,645
7	69,183	12,589-349,945
8-14	43,401	6,039-311,889
15-21	19,230	2,667-151,356
22-28	12,246	1,164-118,850
29-45	5,129	389-79,433
46-60	2,443	91-39,084
61-90	1,047	19-21,878
91-120	398	9-18,620
121-150	193	4-8,318
151-180	108	3-4,365
181-270	47	8-2,630
271-360	18	4-832
361-720	4	0-372

Reference

M. E. G. Blohm, D. Vesterling-Hörner, G. Calaminus & U. Göbel (1998) Alpha1-Fetoprotein (AFP) Reference Values in Infants up to 2 Years of Age, Pediatric Hematology and Oncology, 15:2, 135-142, DOI: https://doi.org/10.3109/08880019809167228

Anemia of Prematurity Management for ELGAN/ELBW

Background

Extremely low gestational age neonates (ELGAN) / extremely low birth weight (ELBW) infants are born with lower hematocrit and hemoglobin levels.

Reference Ranges at Birth

Week of GA	RBC (×10¹²/L)	Hemoglobin (g/dL)	Hematocrit (%)	Mean Corpuscular Volume (fL)
18–21	2.85 ± 0.36	11.7 ± 1.3	37.3 ± 4.3	131.11 ± 10.97
22–25	3.09 ± 0.34	12.2 ± 1.6	38.6 ± 3.9	125.1 ± 7.84
26–29	3.46 ± 0.41	12.9 ± 1.4	40.9 ± 4.4	118.5 ± 7.96
>36	4.70 ± 0.40	16.5 ± 1.5	51.0 ± 4.5	108.0 ± 5.00

Anemia of prematurity is an earlier and more dramatic physiologic anemia that occurs in preterm infants, often around 4–6 weeks of age, with hemoglobin nadirs of 7–10 g/dL (hematocrit 21–30%).

Common symptoms (when present): tachycardia, pallor, poor feeding, reduced weight gain.
Most infants remain asymptomatic.

Key Evidence Notes

Early high-dose EPO is safe in GA ≤ 26 weeks but does not improve short- or long-term outcomes (Juul et al. 2020).
pRBC transfusions may be associated with transfusion-related acute lung injury (TRALI) and transfusion-associated necrotizing enterocolitis (ta-NEC), although evidence remains limited and inconsistent (Maria et al. 2017; Khashu et al. 2022).

Management

General Measures to Optimize Blood Volume and Reduce Iatrogenic Loss

Deferred cord clamping for up to 60 seconds in infants with good tone in the delivery room (NRP 9th edition).
Correlate serum electrolytes with ABG electrolytes (Na, K, iCa) and trend using ABG when frequent monitoring is required.
Attempt daily correlation during the acute phase.
Combine laboratory tests whenever possible to minimize blood draws.

Epogen (EPO) Therapy

May be started earlier than 7 days of life if there is a rapid drop in hematocrit (at the discretion of the neonatologist) or if Hct < 32%.
From the PENUT trial: Safe to administer from birth. No significant benefit in short- or long-term outcomes, but associated with fewer pRBC transfusions (2 [0–5] vs 4 [2–7]).
Dose: 400 U/kg on Monday, Wednesday, and Friday.

Iron Therapy

Begin once the infant tolerates 100 mL/kg/day of enteral feeds.
Dose: 3 mg/kg/day divided twice daily.

Packed Red Blooc Cell (pRBC) Transfusion

For non-urgent transfusions: The outgoing and incoming neonatologists should discuss and agree on the necessity prior to proceeding.

1. Determine if Infant is Acutely Ill

Category	Not Acutely Ill	Acutely Ill
Respiratory	FiO₂ < 30% on invasive ventilation with adequate support FiO₂ < 40% on non-invasive ventilation with adequate support	FiO₂ ≥ 30% on invasive ventilation despite adequate support FiO₂ ≥ 40% on non-invasive ventilation despite adequate support
Metabolic	No acute severe metabolic acidosis	Acute severe metabolic acidosis (pH < 7.2, BE < -6, or HCO₃ < 12)
Clinical Status	Not on NEC watch Not undergoing sepsis evaluation No upcoming surgery No recent major bleeding Asymptomatic	On NEC watch Being evaluated for sepsis Upcoming surgery Major bleeding (e.g., Grade 3 IVH, pulmonary hemorrhage) within 3 days Symptomatic

2. Transfusion Thresholds

Time Period	Hemoglobin (g/dL) – Not Acutely Ill	Hemoglobin (g/dL) – Acutely Ill	Hematocrit (%) – Not Acutely Ill	Hematocrit (%) – Acutely Ill
DOL 0–7	10	11	30	33
DOL 8–14	8.5	10	25	30
DOL ≥ 15	7	9	21	27

3. Transfusion Volume

Standard: 10–15 mL/kg over 4 hours.
If 20 mL/kg is required: Consider splitting into two 10 mL/kg aliquots, each over 4 hours (total 8 hours).

4. NPO Practice

Keep NPO for 1 hour before and 1 hour after transfusion.

5. Transfusion Routes

References

Juul, Sandra E., et al. 2020. “A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.” The New England Journal of Medicine 382 (3): 233–43.
Khashu, Minesh, et al. 2022. “Current Understanding of Transfusion-Associated Necrotizing Enterocolitis: Review of Clinical and Experimental Studies and a Call for More Definitive Evidence.” Newborn 1 (1): 201–8.
Maria, Arti, Sheetal Agarwal, and Anu Sharma. 2017. “Acute Respiratory Distress Syndrome in a Neonate Due to Possible Transfusion-Related Acute Lung Injury.” Asian Journal of Transfusion Science 11 (2): 203–5.

Refer to Blood transfusion for very and extremely preterm infants.

Procedure

Transfuse over 4 hours with 1 hour NPO before and after transfusion.
15 (10-18) ml/kg per aliquot. If needing 20ml/kg, consider splitting into 2 aliquots.

Order Blood for Transfusion

The BPAM BLOOD TRANSFUSION (ML) LESS THAN 20-30 KG BODY WEIGHT Order Set should be used when ordering any blood product and will automatically prompt you to enter all the information needed, so you should not have to write a separate “transfuse” order.

In the case of emergency blood, we are still able to obtain uncross matched O- PRBCs from blood bank WITHOUT an order, within 20 minutes.
Please remember to document “Yes” under the Informed Consent Obtained section (unless it is an emergency transfusion and/or there was a reason that informed consent was not obtained). This is the section that the nurses reference to ensure that this has been done prior to beginning the transfusion and they document acknowledgement of that as well in their Flowsheet.

Click Here to view and download the workflow PDF.
Click Here to view and download the Provider Practice Alert PDF.

Emergency Blood Release

TWO FORMS TO FILL OUT:

Emergency Blood Release/Waiver Form (Download here)
Blodo Order/Release During Hemorrhage Protocol Form (Download here)

Emergency Blood Release/Waiver Form

This needs a patient sticker and is walked down to blood bank by a member of the nursing team. This doesn’t need to be filled out completely or signed initially. There IS an expectation that it is completely filled out when we are able (when baby is more stable).

Blood Order/Release Hemorrhage Protocol Form

This is more of a prompt that the nurse will need to follow when calling blood blank. It gives them all the information they need to initiate preparing blood/blood products.

Procedures

Physician decide baby needs blood/blood products, calculates the amount and tells the nurse.
Nurse collects/fills out Blood Order/Release Hemorrhage Protocol Form. Follow process instructions. (Once blood bank is notified prbc should be at bedside w/n 30 minutes, plt and FFP w/n 40 minutes).
Nurse obtains Emergency Blood Release/Waiver, places patient sticker on form and walks it down to blood blank.
Physician to place orders/fill out appropriate forms after patient stable enough to do so.

Hypercoagulability Work-Up

Blood tests

Protein C/S
Antithrombin III
PT/INR
aPTT
Anti-cardiolipin IgG/IgM
Factor V Leiden
$\beta_{2}$ Glycoprotein IgG/IgM

Vitamin K Administration at Birth

AAP policy statement summary

Click to open the policy statment

Summary and Recommendations

Vitamin K Deficiency Bleeding (VKDB) remains a significant concern in newborn and young infants. Parenteral vitamin K has been shown to be the most effective way to prevent VKDB of the newborn and young infant, and the AAP recommends the following:
Vitamin K should be administered to all newborn infants weighing >1500 g as a single, intramuscular dose of 1 mg within 6 hours of birth.
Preterm infants weighing ≤1500 g should receive a vitamin K dose of 0.3 mg/kg to 0.5 mg/kg as a single, intramuscular dose. A single intravenous dose of vitamin K for preterm infants is not recommended for prophylaxis.
Pediatricians and other health care providers must be aware of the benefits of vitamin K administration as well as the risks of refusal and convey this information to the infant’s caregivers.
VKDB should be considered when evaluating bleeding in the first 6 months of life, even in infants who received prophylaxis, and especially in exclusively breastfed infants.

Dosing table

>1500g	1 mg (0.5 mL)
1000-1500g	0.5 mg (0.25 mL)
600-999g	0.3 mg (0.15 mL)
400-599g	0.2 mg (0.1 mL)
<400g	0.1 mg (0.05 mL)