Childhood hematopoiesis and hematological features

Yongmin TangDept. Hematology-oncology

Chidlren’s HospitalZhejiang University School of medicine

• Hematopoietic Stem Cells (HSC), CD34 is the marker of HSCs.

5 um

• All the daughter blood cells are derived from the HSCs.

Early development of the fertilized egg.

Embryo development and tissue (cell) commitment

Development of hematopoietic stem cells

PLURIPOTENT STEM CELL CD34+CD38- HPP-CFU, LTC-IC,CFU-BL

MYELOID STEM CELLCD34+CD38-CD33+CD13+

LYMPHOIDSTEM CELLTdT+CD34+

BFU-MKCD34+CD61+/-

BFU-ECD71+CD36+/-

CFU-GMCD34+CD33+

CFU-M CFU-G

CD19+T PROGENITOR CD7+

TOTIPOTENT STEM CELL

T4T8

CFU-ECD71+CD36+

CFU-MKCD61+

SELF-RENEWAL

B CELL

B PROGENITOR

HEMATOPOIESIS

The features of hematopoiesis in children

HEMATOPOIESIS DURING FETAL DEVELOPMENT

HEMATOPOIESIS AFTER BIRTH

3. Medullary hematopoiesis: 4th-5th months

2. Hepatic hematpoiesis: 2nd - 6th months

1. Mesoblastic hematopoiesis: 3rd – 6th wks

Hematopoiesis during fetal development

Islet of York Sac In liver In BM

Migration of HSCs

liver BM

HSC

Mesoblastic Hepatic Madullary

0

2

4

6

8

10

12

yal k sac l i ver BM

(Wks ）

Kinetics of hematopoiesis

during fetal development

hepatosplenomegaly with circulating nucleated erythrocytes in the blood stream

HEMAYOPOIESIS AFTER BIRTH

1. Medullary hematopoiesis:

“ red marrow”

“yellow marrow”

When needed: Yellow marrow red marrow hematopoiesis compensation

2. Extramedullary hematopoiesis:

Comparisons of hematopoietic locations between preschool children

and adults

Blood pictures in children (1)

Juxtaglomerular apparatus

A. RBC

----->EPO------> RBC

Fetal stage: RBC 5 ~ 7 x 1012/L

Hb 150 ~ 220g/L

Afferent arteriole of glomerulus Efferent arteriole

of glomerulus

Dynamic changes of RBC during infancy

Age

RB

C c

oun

ts (

x 1

012/L

)

Blood pictures in children (2)

Physiological hemolysis:

circulating nucleated RBC with elevated reticulocytes

(stopping lysing within 1wk)Physiological anemia:

infant 2-3 months

RBC 3 x1012/L

Hb 100 g/L

(self-limited, recovers within 6 months)

Low limits of Hb in different age groups

Newborns 145 g/L

1 ～ 4m 90 g/L

4～ 6m 100 g/L

6m ～ 6y 110 g/L

6y ～ 14y 120 g/L

• 4% of increase per 1000 meter above sea level.

0 － 3d 4~7d 4~6wk after 5mon

4 ~ 6% 0.5~1.5% 2~8% 0.5~1.5%

Reticulocytes ：

Molecular structure of hemoglobin

Types and proportions of hemoglobin during embryo, fetus and infancy stages

Different proportions of Hb during infancy and early young children

Blood pictures in children (2)

fetal 6 M at birth 1yr 2 yr adults

HbF (22) 90% 70% < 5% < 2% < 2%

HbA (22) 5~10% 30% 93% 95% 95%

HbA2 (22) < 1% 2~3%

Dynamic changes of WBC during childhood period

(x 109/L) at birth 6~12h day7 infant > 8yrs

15~20 21~28 12 10 4~8

B. White blood cell count and differential count:

DC (%) at birth 4~6d d7~ 4yrs 4 ~ 6 yrs 7 yrsN L N L N L N L N L65 35 50 50 35 65 50 50 as adult

(%)80

605040

20

0

Neutrophils

Lymphocytes

Age

Blood pictures in children (3)

4 ~ 6yrs4 ~ 6 d

Blood picture in children (4)

• Platelets: normal 100 ~ 300 x109/L

• Total blood volume:

Newborn: 10% of body weight

Childhood: 8 ~ 10% of BW

Adults: 6 ~ 8% of BW

Important nutritional components for erythropoiesis

• Iron

• Vitamin 12

• Folic acid

Features of iron metabolism in children

• Iron store:

• Factors affecting fetal iron store:

• Mechanism of iron supply in fetus: restricted

premature, severe maternal iron deficiency, intra-uterus transfusion etc.

Anemic pale

RBCs of IDA

Blood smear(2):

Metabolism of Vit B12 and Folic acid

• Folic acid:

food: rich in green vegetable, lack in sheep milk ;

Absorptive site: at upper portion of jejunum;

• Vitamin B12:

Food: rich in animal derived food;

Absorptive site: terminus of ileum;

Absorption helping factor: internal factor.

Pathogenesis of nutritional megaloblastic anemia

5-MythotetrahydroxylFolic acid Vit B12 + Vit C

DNA synthesis

Megaloblasts

Fragile

Invalid hematopoiesis

Uridine

dThymidine4H-FA2H-FA

Lipid Metabolites: Methyl Malonic acid Succinic Acid Citric Cycle Vit B12

Pathogenesis of Vit B12 induced nervous system manifestation

Vit B12: associated with the formation of nerve sheath lipoprotein to maintain the integrated function of CNS and peripheral nerve fibers.

Vit B12 deficiency ： degeneration of peripheral nerve, combined subacute degeneration of spinal cord and damage to the brain.

Hyperfragmented neutrophil

Clinical relevant cytokines or hormones associated with hematopoiesis

• EPO

• G-CSF

• GM-CSF

• IL-11

• TPO

Clinical Application of CD34+ cells

• CD34 as marker of HSC or HPC for quantitation

• Selection of the stem cell sources for transplantation (BM, PBSC, Cord blood)

• Positive selection of the CD34+ cells for tumor purging

• Gene therapy

Clinical Application of CD34+ cells

Thank you for attention !