Neonatal

Thrombopoiesis
content

– Introduction
– Platelet function
– Bleeding time
– Platelet Antigen and glycoprotein
Introduction

– The origin of platelets from megakaryocytes was reported in 1906

– The platelet counts in term and preterm infants are between 150 - 400 × 109/L
– Thrombopoiesis-stimulating activity appears lower in cord serum than in adult
serum, and reduced levels of G-CSF, GM-CSF, and IL-3 may play a role in the
impaired response.
– Thrombocytopenia of less than 100 × 109/L may occur in high-risk infants with
respiratory distress or sepsis, SGA infants, and newborns with trisomy
syndromes.
Introduction

– Progenitor cells committed to the megakaryocyte lineage can be identified by

two methods: a culture system, in which they are identified by their ability to
form megakaryocyte colonies, and immunologic staining
– In the human fetus, megakaryocytes are first detected in the circulatory system
at eight weeks of gestation, and the first platelets appear at five weeks.
– 2 different megakaryocyte progenitor cells:
– the burst-forming unit megakaryocyte (BFU-MK), which is a more primitive
megakaryocyte progenitor
– later progenitor known as the colony-forming unit megakaryocyte (CFU-MK)
Introduction
Thrombopoietin (TPO)

– TPO, the main physiologic regulator of platelet production mRNA is expressed

primarily in the liver, in other tissues, including kidney and bone marrow
stromal cells.
– TPO acts as a potent stimulator of all stages megakaryocytopoiesis of
megakaryocyte growth and development, except platelet release
– It also plays roles in platelet activation, mostly by priming the platelets to the
effects of other agonists.
– In vitro, TPO alone stimulates the proliferation and survival of erythroid,
myeloid, and multipotential progenitors.
Thrombopoietin (TPO)

– TPO also enhances erythropoietin-induced erythroid burst formation, an effect

mediated by its ability to inhibit apoptosis of erythroid progenitors
– TPO transcript have been detected early as 6 weeks post conception and the
primary source of TPO in the fetus and neonate is thought to be the liver.
– Serum TPO levels are higher in preterm and term neonates compared to adults.
Platelet function

– A variety of differences in the platelet function of neonates:

– Decreased ADP release
– Decreased platelet factor 3 activity
– Decreased platelet adhesiveness
– Decreased platelet aggregation in response to ADP, epinephrine, collagen,
or thrombin.
– These defects result from intrinsic differences in neonatal compared to
adult platelets.
Bleeding time

– Generally, newborn infants have shorter bleeding times than those of children
and adults.
– Due to:
– Higher haematocrit
– Increased concentration of von Willebrand factor
– Higher proportion of high molecular weight multimers of von Willebrand factor.
– Children have longer bleeding times than either adults or newborns, and may
be as high as 13 min before age 10, compared to an upper limit of 7 min in
adults.
Platelet Antigen and glycoprotein

– The glycoprotein complex GPIIb/IIIa represents about 15 % of platelet surface

protein and exhibits two allelic forms, PlA1 and PlA2.
– The PlA1 antigen:
– Able to be identified on foetal platelets by 16 weeks gestation.
– Higher percentage between 18 and 26 weeks than in adults.
– The complete expression of the PlA1 antigen during early gestation likely permits
early sensitization in women who are PlA1 negative even during their
first pregnancy.
– The membrane glycoprotein GPIb, as well as the GPIIb/IIIa complex, is
expressed by 18 weeks of gestation.
– Prenatal diagnosis of the glycoprotein genotype using DNA from amniocytes
and the PCR can establish the potential for neonatal alloimmune
thrombocytopenia as well as the diagnosis of Glanzmann’s thrombasthenia.