Hematologic Conditions of the Newborn Flashcards
When does early hematopoiesis begin?
one of the earliest systems to achieve some fx capactity
- begins in the yolk sac at 12-15d
When does circulation begin?
by 22days with primitive cells arising intravascularly from vessel walls
* circulation is vital for the well-being of the fetus for transport of nutrients, O2 and removal of waste products
From where do blood cells arise?
all blood cells come from the pluripotent hematopoietic stem cell that divides into a myeloid or lymphoid stem cell
When is the pluripotent hematopoietic stem cell present in the yolk sac?
at 16 days
What happens to the pluripotent hematopoietic stem cell?
becomes unipotent stem cells (colony forming cells) which develop into specific cells. When they divide, they are committed to making only one kind of cell; structural differentiation occurs
following yolk sac hematopoiesis, when and where does this activity take place?
migration of pluripotent stem cells from yolk sac to the liver where hepatic hematopoiesis is established by 9 weeks; peak fx at 4-5mo GA
As hepatic hematopoiesis regresses, where is the primary site of this function?
medullary (bone marrow) hematopoiesis becomes dominant at 22 wk GA
Why is extra-medullary hematopoiesis necessary?
as the long bones mature, extra-medullary hematopoiesis aids the process
What are the extra-medullary sites for hematopoiesis?
spleen, lymph nodes, thymus and kidneys
What are the formed elements present in a CBC in order from greatest to least?
erythrocytes, plt and leukocytes
What is included in the differential of a CBC?
- Granulocytes: Neutrophils (40-70%); Eosinophils (1-4%) and Basophils (0-1%)
- Agranulocytes: Lymphocytes (20-45%) and Monocytes (4-8%)
What is the process of erythropoiesis?
production of erythrocytes
1) pluripotent stem cell
2) myeloid stem cell
3) proerythroblasts cells
4) erythroblasts
5) reticulocytes
6) RBCs
What does erythropoietin regulate?
erythropoiesis and the synthesis of hemoglobin
Where is erythropoietin produced?
in the kidneys post natally, however, it is produced in the liver and submandibular glands during fetal life
What stimulates erythropoietin production?
anemia and decreased O2 availability to the tissues
What are the 2 major components of a RBC?
heme and globin (95%)
Describe an erythrocyte.
- biconcave discs and flexible
- plasma membrane but no nuclei or organelles
- packed with hemoglobin molecules
What is a hemoglobin molecule?
- O2 carrying CO2 is carried a well (carries from lungs to tissues)
- a conjugated protein consisting of an Fe containing pigment called heme and a simple protein, globin
- composed of 4 chains of AA, each with Fe which is a binding site for O2
What are young erythrocytes carrying ribosomes called?
reticulocytes
What is the life span of a RBC?
adult: 100-120d
FT: 60-70d
PT: 35-50d
what do fetal RBCs contain relative to adult RBCs?
more fetal hgb; newborns have more fetal hgb. the more mature the baby the less fetal hgb
At 10 weeks GA, what is the major component of RBC?
HbF
When does production shift from HbF to HbA?
at the end of fetal life; 70-90% HbF in RBC at birth
What is the importance of 2,3 diphophglycerate?
binds with hgb and causes a release of O2 to the tissues as a result
What is the composition of HbA?
the globin, or protein portion of each HbA molecule consists of 2 identical alpha chains and 2 identical beta chains
What is the composition of HbF?
normal HbF has 2 alpha chains and 2 gamma chains; these gamma chains increase hgb’s attraction to O2 and facilitates transfer of maternal O2 across the placenta, but reduces release to the tissues; net result hgF more readily holds onto O2
Where is HbF primarily produces and at what GA?
- liver
- predominant from 10-12 weeks and increases rapidly to 90-95% by 30-32 wk
- slow decrease to 84% by 34 weeks and to 60-80% by FT
Where is HbA2 primarily produces and at what GA?
- bone marrow
- appear after6-8 weeks and increase rapidly after 16-20
- levels simultaneously rise as HbF decreases along with total body hgb mass
Where is HbA primarily produces and at what GA?
- bone marrow
- by 6 mos of age, the switch from HbF to HbA synthesis is r/t postconceptual age, not post birth age
- not significantly affected by intrauterine transfusions or exchange transfusions after birth
What is acid elution?
process of extracting one material from another, by washing with a solvent
How does HbF differ from HbA?
- resistant to acid elution
- can be oxidized to methemoglobin more readily, increasing susceptibility of newborn to methemoglobinemia
When is the Kleihauer- Betke test indicated?
in the event of fetal/maternal hemorrhage
- blood smear of MOB is washed with acid removing hbA from maternal RBCs, leaving HbF
What is HCT/PCV?
the volume of erythrocytes packed by centrifugation in a given volume of blood
- expressed as the % of total blood vol that consists of erythrocytes
What is the normal range of HCT/PCV?
45-58% from 28wks GA to FT and up to 14 dol
What is the normal pattern of HCT/PCV rise and fall with birth?
- increases in the first few hours or days r/t the movement of fluid from intravascular to interstititial spaces.
- falls again to levels near cord blood values by the end of the first week.
What is the avg HCT/PCV value in male and female pts?
male: 47
female: 42
What is plasma?
found at the top of a sample after centerfuged (spun)
- composed of H2O, many ions, molecules and 3 types of proteins
What are the 3 important types of proteins found in plasma?
1) albumin
2) globulins
3) fibrinogen
What is oxyhemoglobin?
when 1g of hemoglobin can combine with 1.36cc of O2
What is an important chemical in the process of releasing O2 to tissue?
2,3 DPG
What is the normal range of Hgb in a neonate?
14.5-18.4 from 28 weeks GA to FT and up to 14 dol
What is the normal range for hgb and HCT in a 28 weeks infant?
hgb: 14.5
hct: 45
What is the normal range for hgb and HCT in a FT infant?
hgb: 16.8
hct: 53
What are platelets?
fragments of cells
What is process of thrombopoiesis?
1) pluripotent hematopoietic stem cell
2) myeloid stem cell
3) megakaryoblast
4) promegakaryocyte
5) megakaryocyte
6) thrombocyte
Describe a normal platelet.
- round, or oval shaped disc
- fragments of megakaryocytes (lg cells found in bone marrow)
What is the fx of a plt?
aid in blood coagulation, hemostasis and blood thrombus formation
What is the typical trajectory of plt production?
- first appear in fetus at 5 weeks
- reaches 150 by end of first trimester
- adult range reached by 22 weeks
what is the normal range for plt?
150-400k
What is unique about neonatal plt?
decreased functional reserve capacity and reactivity to stimuli in the first few days
- plt reactivity corresponds to GA
What are undesirable clots?
- thrombus
- embolus
What is bilirubin?
the end product of hemoglobin catabolism
- the Fe is released and stored, heme is further degraded by macrophages to CO and biliverdin under the influence of heme oxygenase
- biliverdin is catabolized to indirect (unconjugated) bilirubin
What amount of albumin is required to bind to bilirubin?
1g albumin binds to 8.5-10mg of bilirubin
Describe indirect (unconjugated) bilirubin.
- orange/yellow
- fat soluble
- not readily excreted in bile or urine
- transported in plasma bound to albumin ro rhw liver for metabolism and excretion
What mechanism of hyperbili are PT babies most susceptible to?
hyperbili as it r/t immature processing
What is direct hyperbili?
level > 2 mg/dL or > 10-15% of total bili level
Describe direct (conjugated) bilirubin.
- water soluble
- has been metabolized by the liver to form bilirubin monoglucuronides or diglucuronides
- direct bili is excreted through the biliary tree into the intestines and forms a major component of bile and feces; small amts may be excreted through the kidneys
What are hepatocellular causes for direct hyperbili?
- hepatitis
- metabolic disorders
- intestinal obstruction
What are ductal causes for direct hyperbili?
- biliary atresia
- choledochal cyst
- bile plug syndrome
How are ductal causes for direct hyperbili tx?
- tx with ursidol and vitamin ADEK supp
- ∆ formula to portagen or progestimil
- tx underlying cause (most likely TPN cholestatiss in NICU –> advancement of enteral feeds if possible)
Describe physiologic jaundice in the neonate.
- onset >36h
- usual time of peak is 3-4 days
- peak serum level is 5-12mg/dL
- incidence in FT: 50-60%
Describe breast-feeding associated jaundice in the neonate.
- onset 2-4d
- usual time of peak is 3-6 days
- peak serum level is > 12mg/dL
- incidence in FT: 12-13%
Describe breast milk jaundice in the neonate.
- onset 4-7d
- usual time of peak is 5-15 days
- peak serum level is > 10mg/dL
- incidence in FT: 2-4%
What is kernicterus?
permanent brain damage secondary to deposition of bilirubin in brain cells, with yellow staining and neuronal necrosis
What areas of the brain are most affected by kernicterus?
- basal ganglia
- brain stem auditory pathways
- oculomotor nuclei
What is the critical level of bili beyond which brain damage occurs?
unknown
What population is at greatest risk for kernicterus?
PT babies d/t immaturity of blood-brain barrier, in addition to the individual ∆ that occur to the BBB given their clinical status
- may require prophylactic tx, anticipate the rise based on clinical picture
What is essential to the prevention of kernicterus?
prudent recognition of infants at risk and aggressive tx
Why is phototx effective?
light reduces bilirubin by photoisomerization and photooxidation
- usually provided by fluorescent, halogen, halide or fiber optic lights and blankets
How does photoisomerization work?
involves conversion of poorly soluble indirect bilirubin into H2O soluble photoisomers. The photoisomers, they can be excreted into bile w/o conjugation
What is a reticulocyte?
last immature stage of a RBC
What is the normal range of a reticulocyte?
- normally constitute about 1% of circulating blood cells
- count is elevated at birth ranging from 3-7% in FT infants and up to 8-10% in PT
- decreases markedly to 0-1% by 1 week of age
What is the Coomb’s test?
a postnatal test of neonatal blood for presence of maternal antibodies against fetal blood type
What does a direct Coomb’s test reveal?
(direct antiglobulin test or DAT): used to detect these antibodies or compliment proteins that are bound to the surface of RBCs
What does an indirect Coomb’s test reveal?
(indirect antiglobulin test or IAT): used in prenatal testing of pregnant women and in testing blood prior to transfusion. it detects antibodies against RBCs that are present unbound in the pt’s serum
Why is the Coomb’s test important?
reveals evidence of Rho (D) isoimmunization or ABO incompatability causing isoimmune hemolytic dz, hemolytic dz of the newborn or erythroblastosis fetalis
- all of these are terms for a disorder caused by transplacental passage of maternal IgG antibody that reacts with antigens on the fetal RBC and leads to cell lysis
What is the normal circulating blood vol of a FT baby?
80-100mL/kg
What is the normal circulating blood vol of a PT baby?
90-105mL/kg
Why is there variation in circulating blood vol?
variations at birth are due primarily to placental trnasfusion and GA; the high blood vol of the PT infant is r/t increased plasma vol which decreases with GA
What is the etiology of an acute neonatal hemorrhage?
acute OB blood loss including:
- abruptio placentae
- placenta previa
- incision of placenta at CSX
- rupture of anomalous vessels
- hematoma of cord
- pulmonary hemorrhage
- subglaeal hemorrhage
- organ rupture
What is the etiology of a chronic or occult neonatal hemorrhage?
- feto-maternal bleeding
- feto-placental bleeding
- twin to twin transfusion
- massive cephalohematoma
- hemolytic disorders
- iatrogenic losses from sampling w/o adequate replacement
What is the etiology of a vitamin K deficiency related neonatal hemorrhage?
- characterized by low plasma vitamin K1, low liver K1 and near absence of K2 (the major vit K component in the liver)
- newborn has reduced levels of all the vit k dependent clotting factors (II, VII, IX, X) at birth, leading to physiologic hypothrombinemia
Why is vitamin K necessary?
not required for the synthesis of clotting factors per se, but rather for the conversion of precursor proteins, synthesized in the liver to activated proteins with coagulant properties
What is the etiology of inherited anomalies leading to neonatal hemorrhage?
- hemophilia A&B: sex- linked recessive disorders of clotting factors XIII and IX respectively
- Von Willebrand’s dz: the most common inherited coagulation defect: decreased levels of von Willebrand factor, which is responsible for plt adhesive-ness
As it relates to neonatal hemorrhage, what are high-risk infants most suseptible to?
- thromboembolism
- consumptive coagulopathies (ex: DIC)
Why are PT infants most at risk for hemostatic problems?
as a result of significant decreases in clotting factors, plt fx and factors protecting against excessive clot formation
What is the most common cause of bleeding due to impaired hemostasis in the neonate?
DIC
What are the risk factors for the development of DIC?
1) those with vulnerability to pathologic problems known to initiate DIC, including trauma
2) severe RDS
3) sepsis
4) NEC
5) indwelling lines (thrombosis)
6) severe perinatal asphyxia
7) CNS hemorrhage
8) endothelial injury (viral infx)
In the evaluation of neonatal hemorrhage, what might the Ob history reveal?
an assoc anomaly and provide clues to the origin of blood loss
How does neonatal hemorrhage present clinically?
- cyanosis
- poor perfusion
- acidosis
- pallor
- jaundice
- hepatosplenomegaly (can differentiate bw acute, chronic and hemolytic blood loss)
How is neonatal anemia evaluated?
- CBC
- retic count
- coombs test
- bilirubin
- apt test (used to differentiate maternal blood from GI bleeding of the neonate)
- Kleihauer- Betke test
- G6PD level (inherited disorder of RBC, sex linked affecting mostly males)
- BCX and TORCH w/u
How is neonatal hemorrhage managed?
- transfusion of blood products
- PRBC generally in vol of 15-20mL/kg
- exchange transfusion with PRBC for severely anemic
babes if vol of RBC would cause vol overload - FFP vol 10mL/kg replaces clotting factors immediately
- Plt in vol of 10mL/kg
- Vitamin K1 oxide (aquamephyton) IV or IM
What is physiologic anemia of infancy?
describes the developmental changes that occur in the RBC blood mass in the neonatal period and ensuing months
What is the mechanism of action for c
- as Hgb levels fall, the ration of HgA to HgF increases, and levels of 2,3 DPG increase as a result of O2 delivery to the tissues is actually increased
- this anemia is not a functional anemia in that O2 delivery to the tissues is adequate
- read nadir at 8-12 weeks, erythropoeitin production is stimulated, RBC production increases
What increases an infant’s risk for physiologic anemia of infancy?
an exaggeration of normal physiologic anemia (short life span of the RBC, decreased erythropoietin production, dilutional, also complicated by additonal lab needs)
What is the result of physiologic anemia of infancy?
- RBC mass is decreased at birth
- nadir is reached earlier
- nadir is lower
- FE administration before 10-14 weeks is stored to support later hematopoiesis and therefore does not increase the nadir or diminish the rate of reduction
- once nadir is reached, rapid depletion of Fe stores
What is the indicated management of neonatal anemia?
- limiting iatrogenic losses
- Fe supps (2-4mg/kg/d; 6 mg/kg/d if on EPO)
- erythropoietin supp
- PRBC correction
