ANEMIA OF PREMATURITY Dr - PowerPoint Presentation

Slide1

ANEMIA OF PREMATURITY

Dr

Mohammmad

Torkaman

Neonatologist

Associate professor

Slide2

Physiologic anemia

The postnatal changes in

tissue oxygenation

and erythropoietin production result in a physiologic anemia of infancy with a mean minimal hemoglobin concentration in healthy term infants of about 11g/dL at 8 to 12 weeks of life

Slide3

Anemia of prematurity (AOP) is an exaggerated, pathologic response of the preterm infant to this transition. AOP is a normocytic, normochromic,

hyporegenerative

anemia characterized by a low serum EPO level, often despite a remarkably reduced hemoglobin concentration.

Slide4

Because of the shorter

life

span of RBCs in preterm infants with low EPO levels,

the nadir is noted by 6 weeks of age and ranges from 7 to 10g/dL. In ELBW infants whose nadir falls below 7g/dL, this so-called physiologic anemia of prematurity can be associated with

pallor

, tachypnea, tachycardia, poor feeding, and poor

weight

gain

Slide5

Slide6

This

exaggerated

physiologic anemia of prematurity

is related to a combination ofDecreased RBC mass at birthIncreased iatrogenic losses from laboratory blood samplingShorter RBC life span(40-60 days)Inadequate

erythropoietin

production

R

apid

body growth

Slide7

dietary factors

F

olic

acid deficiencyUnless there has been significant blood loss, iron stores should be sufficient to maintain erythropoiesis early on. Vitamin E deficiency does not play a role in anemia of prematurity

Slide8

Erythropoietin (EPO)

B

inds

to erythropoietin receptors on early erythroid progenitor cells and via the JAK2 signaling pathway regulates RBC production by protecting them from apoptosis. Erythropoietin is produced primarily in the fetal liver and later in the cortical

peritubular

cells

of the kidney, so that in adults renal production of

EPO

is the most

important.

Slide9

Erythropoiesis is highly responsive to blood oxygenation. Hypoxia inducible factors (HIFs), constitutively expressed EPO transcription factors, are destroyed in the presence of oxygen.

Under hypoxic conditions, EPO production increases.

Levels of EPO in cord blood are higher than in adult blood samples. but there is a dramatic decrease after birth in response to higher levels of tissue oxygenation.

By 1 month of age, serum levels in healthy term infants reach their nadir. This is followed by a rise to maximal levels at 2 months of age and then a slow drift down to adult value

Slide10

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The reason for diminished EPO levels is not fully

understood. During fetal life, EPO synthesis is handled primarily by

the liver, whose oxygen sensor

is relatively insensitive to hypoxia when compared to the oxygen sensor of the kidney. The developmental switch from liver to kidney EPO production is not accelerated by early birth, and thus the preterm infant must rely on the liver as the primary site for synthesis, leading to diminished responsiveness to anemia. An additional mechanism thought to contribute to diminished EPO levels may be accelerated EPO metabolism.

Slide12

Although

preterm infants

will

respond to hypoxia with a rise in EPO levels, the increase is lower than that expected for term infants. The suboptimal EPO response may be due to developmental changes in transcription factors or to the site of fetal EPO production.

Slide13

F

requent blood sampling

The

physiologic anemia of infancy can be exaggerated in the sick or premature infant by frequent blood sampling: the smaller the infant, the proportionally greater the volume of blood that is withdrawn for laboratory testing

Slide14

Blood transfusion

Most RBC transfusions in neonates occur within

the first 3 to 4 weeks of life, with the majority being in

the first 2 weeks. Physiologically lower levels of EPO in neonates provided the rationale for the pharmacologic use of erythropoietin to reduce the volume and risks of blood transfusions.

Slide15

Blood transfusion

A

restrictive

strategy does not increase infant morbidity or mortality. In addition, long-term neurodevelopmental outcomes have been found to be poorer in liberally transfused neonates. Late exposure to packed RBC may be related to the development of necrotizing

enterocolitis

,

and

early

transfusions may be associated

with the

risk of

intraventricular

hemorrhage

.

Slide16

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Increased risks in adult patients

D

eath

Myocardial infarctionStrokeVenous thrombosisCancer progression.

Slide18

Erythropoietin (EPO)

Early

Starting on day 1 or 2,

1200–1400 U/kg/wk. r-HuEPO is added to the total parenteral nutrition solution, and 1 mg/kg/d of iron is added.Late(after 8 days)500–700 U/kg/wk given 3–5 times per week subcutaneously. Supple-

mental oral iron needs to be provided at

3 mg/kg/d

in 3 divided doses. The

iron dose is increased to 6 mg/kg/d as soon as the infant is tolerating full

enteral feeds

Slide19

Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

Aher

SM

1, Ohlsson A.Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant but not the total volume of RBCs transfused per infant. [Cochrane Database

Syst

Rev. 2006]

Slide20

Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

Ohlsson

A

1, Aher SM.Early administration of EPO reduces the use of RBC transfusions, the volume of RBCs transfused, and donor exposureIn this update there was no significant increase in the rate of ROP (stage ≥ 3) for studies that initiated EPO treatment at less than eight days of age.

The rates for mortality and morbidities including

intraventricular

haemorrhage

and necrotizing

enterocolitis

were not significantly changed by early EPO treatment

[Cochrane Database

Syst

Rev. 2012]

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Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

Aher

SM

1, Ohlsson A.Cochrane Database Syst Rev. 2012 Oct

A non-significant reduction in the 'Use of one or more RBC transfusions' [two studies 262 infants; typical RR 0.91 (95% CI 0.78 to 1.06); typical RD -0.07 (95% CI -0.18 to 0.04; I(2) = 0% for both RR and RD]

favouring

early EPO was noted

.

Early EPO administration resulted in a non-significant reduction in the "number of transfusions per infant" compared with late

EPO

There

was no significant reduction in total volume of blood transfused per infant or in the number of donors to whom the infant was exposed. Early EPO led to a significant increase in the risk of retinopathy of prematurity (ROP) (all stages

)

No other important

favourable

or adverse neonatal outcomes or side effects were reported.

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Stable and larger preterm infants have a better response

to EPO therapy when compared with ELBW infants.

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Recombinant human erythropoietin improves neurological outcomes in very preterm infants.

Song J

1

, Sun H2, Xu F1,3, Kang W2, Gao L1, Guo J1

,

Zhang Y

1

,

Xia L

1

,

Wang X

1,4

,

Zhu C

1,2,3,5

.

Repeated low-dose

rhEPO

treatment reduced the risk of long-term neurological disability in very preterm infants with no obvious adverse effects.

Ann

Neurol

2016;80:24-34.

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When transfusions are necessary, an RBC volume of

10-15

mL/kg

is recommended It is good practice to split units derived from a single donor so that sequential transfusions can be given as required and donor exposure can be minimized.

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Delayed cord clamping or umbilical cord milking at birth results in fewer transfusions and a reduction in both

intraventricular

hemorrhage and necrotizing

enterocolitis in preterm infants. Given the impact of phlebotomy losses during monitoring in the neonatal ICU, attention to reducing unnecessary blood draws also has been advocated.

Slide26

Spontaneous recovery of mild anemia of prematurity (AOP) may occur 3-6 months after birth. In more severe, symptomatic cases, medical intervention may be required.