Ukrainian Public Health Ministry
Dnepropetrovsk State Medical Academy
“Сonfirmed;”
at methodical meeting
of hospital pediatrics №1 department
Сhief of department
professor _____________V. A. Kondratyev
“______” _________________ 2013 y.
METHODICAL INSTRUCTIONS
FOR STUDENTS` SELF-WORK
WHILE PREPARING FOR PRACTICAL LESSONS
Educational discipline
module №
Substantial module №
Theme of the lesson
Course
Faculty
pediatrics
2
8
HAEMOLYTIC DISEASE OF THE NEWBORN
HEMORRAGIC DISEASE OF THE NEWBORN
5
medical
Dnepropetrovsk, 2013.
1
1. Theme urgency:
Coagulopathy takes first place among hemostatic disorders of the newborn. Hemorragic disease of
the newborn (HrDN) is caused by severe depression of vitamin-K-dependent cofactors
(ІІ,VІІ,X,ІХ). So newborns become at risk for developing severe life-threatening hemorrhages.
Hemolytic disease of the newborn (HDN) often has severe course and in some cases unfavorable
prognosis (through the complications). Therefore prophylaxis, timely diagnostics and appropriate
treatment of HDN has importance in neonatology and pediatrics in the whole.
2. Specific purposes
А. Student has to know:
1. Features of hemostasis at term and preterm infants.
2. Etiology of HrDN.
3. Clinical findings consistent with HrDN.
4. Auxiliary diagnostic criteria of HrDN.
5. Complications of HrDN.
6. Principles of rendering treatment at urgent states at umbilical bleeding, gastrointestinal
haemorrhages.
7. Form plan of treatment of HrDN.
8. Carry out prophylaxis of HrDN..
9. Definition of term «hemolytic disease of the newborn».
10. Settings, in which HDN most likely to occur.
11. Essential pathogenetic mechanisms of developing various variants of HDN.
12. Clinical findings consistent with various variants of HDN.
13 Additional methods of examination for confirmation the diagnosis of HDN.
14. Basic complications of HDN
15. Causes and developmental phases of bilirubin encephalopathy.
16. Principles of treatment of HDN depending upon clinical form.
17. Indications and technique of exchange transfusions.
18. Principles of prophylaxis of HDN.
B. Student has to be able to:
1. Determine clinical symptoms of HrDN.
2. Carry out auxiliary investigations and evaluate its results.
3. Carry out differential diagnosis among other hemorrhagic disorders of infants.
4. Make the diagnosis of HrDN.
5. Form plan of treatment of chidren having HrDN.
6. Give emergency medical care to newborns having haemorrhage.
7. Determine clinical symptoms of HDN.
8. Reveal and и analyse anamnestic factors, which could contribute to the development of HDN.
9. Carry out differential diagnosis among HDN and other diseases, which is accompanied by
jaundice.
10. Carry out differential diagnosis among various forms of HDN.
11. Make the diagnosis of HDN.
12. Make plan of investigation of chidren having HDN.
13. Make plan of treatment of chidren having HDN
14. Reveal signs of complications of chidren having HDN.
15. Determine indications and make the plan of performing exchange transfusions.
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3. Tasks for students` self-dependent work during preparation for the
classes.
3.1 List of main terms, parameters, characteristics, which students has to
master preparing for the classes.
Term
1.Hemolytic disease of the newborn (HDN)
2.Icteric form of HDN
3.Anemic form of HDN
4.Edematous form of HDN
5. Bilirubin encephalopathy
6. Syndrome of bile clotting
7. Coombs` test
8. Phototherapy
9. Hemorragic disease of the newborn (HrDN).
10. Vitamin-K-dependent cofactors
11. Melena
12. Hematemesis
13. The Apt test
definition
Disease, which is caused by Rh D alloimmunisation or by maternal and fetus ABO
incompatibility, or by other erythrocyte
antigens.
Accompanied by significant increase of indirect
bilirubin and first of all manifested by yellowish
colouring of skin and mucous membranes.
Manifested predominantly by low hemoglobin
(<120 g/l) and hematocrit (< 40%) level since
birth. Characterized by signs of anemic
syndrome.
Almost always caused by \ maternal and infant
Rh-incompatibility. Manifested in generalized
edema and anemia since birth. Has high
percentage of lethality.
Complication of HDN HDN related to toxic
effect of bilirubin to nerve cells.
Complication of HDN related to intense
production of direct bilirubin and change of bile
biophysical features.
Serologic method for revealing antibodies.
Indirect hyperbilirubinemia`s method of
treatment with usage of light energy with
wavelength according to spectrum of visible
light.
Primary hemorrhagic syndrome, caused by
deficiency of plasmatic clotting factors in the
neonate, predominantly vitamin-K-dependent.
Plasmatic clotting factors, synthesis of which in
liver requires the presense of vitamin K (ІІ, VІІ,
ІХ, Х).
Presense of blood in stool.
Presense of blood in vomiting
Can determine if it is swallowed maternal blood
or fetal hemorrhage. This test relies on the
increased sensitivity of adult hemoglobin to
alkali (NaOH) compared with fetal hemoglobin.
3.2. Theoretical questions for classes:
1. Kinds of hemorrhagic disorders at children.
2. Hemostasis features at infants.
3. Causes of hemorrhagic disorders of the newborn.
4. Causes of HrDN development.
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5. Clinical characteristics of HrDN.
6. Bleeding types among HrDN.
7. Principles of rendering treatment at urgent states at newborn hemorrhages.
8. Auxiliary diagnostic methods of HrDN.
9. Complications of HrDN.
10. Treatment of HrDN.
11.Nutrition of children having HrDN.
12. HrDN profilaxis.
13. Definition of term ” HDN ".
14. Freguency of HDN among other infant diseases.
15. Causes of HDN development.
16. Conditions causing HDN.
18. Features of developing various forms of HDN.
19. General clinical symptoms consistent with HDN .
20. Clinical characteristics of particular HDN forms.
- edematous
- icteric
- anemic
- mixed
21. Significance of auxiliary research procedures in HDN diagnostics.
22. Classification of HDN.
23. Complications of HDN.
24 Settings, in which bilirubin encephalopathy most likely to occur.
25. Bilirubin encephalopathy prophylaxis.
26. Syndrome of bile clotting
27. Principles of HDS treatment.
28. Prophylaxis of HDS and its complications.
4.3 . Practical works (tasks) which are performed on occupation:
1 To collect complaints, case history and personal (life) history
2. To inspect the child
3. To reveal early symptoms of hemolytic, hemorrhagic disease of the newborn
4. To reveal the signs of hemolytic, hemorrhagic disease of the newborn
5. To evaluate the condition of the child and available clinical symptoms.
6. To evaluate the results of the additional methods of investigation
7. To make the clinical diagnosis according to classification.
8. To make the plan of urgent therapeutic measures.
9. To make recommendations of dispensary supervision.
.
4. Maintenance of the subject:
Haemolytic disease of the newborn (HDN). MKB code - X - P55
- Rezus-isoimmunisation P55.0
- Autoo-isoimmunisation P55.1
- Other forms
P55.8
- Not specified
P55.9
Definition
The haemolytic disease of the fetus and newborn (GBN) is the isoimmune haemolytic anemia
caused by the immune conflict through incompatibility of blood of mother and the fetus by
erithrocite anti-genes.
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Etiology and pathogenesis
The reason of haemolytic disease of newborns most often is incompatibility on a Rh-factor or ABO
(group) blood of mother and the child, or on other anti-genes of erythrocytes.
At the heart of development of HDN such sequence of processes lies:
1. Inheritance from the father of an anti-gene factor, alien is relative to erythrocyte anti-genes of
mother.
2. Penetration of an foreign erythrocyte anti-gene from fetal blood in blood of mother, i.e. a
fetomaternal transfusion (FMT). The last increases in a case of violation of an integrity of chorion
(gestosis, extragenital pathology, premature birth, fetal hypoxia, threat of interruption of
pregnancy).
3. Depending on immune reactivity of an organism of mother production of specific antibodies (i.e.,
isoimmunization of a maternal organism), especially after decrease in suppressive T-lymphocytic
system begins. In this case anti-genes of the fetus serve as the reason of the increased formation of
Rhesus-antibodies or immune group anti-A-and anti-B-antibodies (agglutinins and haemolysines).
4. Penetration of immune antibodies from a blood of mother in blood of the fetus and their further
pathological influence on erythrocytes of the fetus and the newborn child.
As a rule, all immune antibodies belong to the class Ig G and can get through a placenta to the fetus.
If antibodies (especially it concerns Rh-antibodies) affects the fetus throughout the most part of
pregnancy, pre-natal maceration of the fetus, edematous or the HDN severe congenital icteric and
anemic form develops. In case of penetration of antibodies at the time of delivery (ABO-HDN, less
severe Rh-HDN forms), develops a postnatal icteric or anemic form.
Further in patogenesis of HDN define two main links: pathological immune hemolysis of
erythrocytes of the fetus and insufficiency of the enzimatic function of a liver with development
(GB) of unconjugated type. Leading link is pathological hemolysis of erythrocytes which is carried
out in macrophages of a liver, spleens, lymph nodes, marrow as a result of action of incomplete
antierithrocite antibodies and membranes of erythrocytes. The second link of pathogenesis of HDN
is pathology of bilirubine exchange which arises not only in connection with pathological hemolisis,
and against insufficient enzimatic function of a liver of the sick child. It is known that conjugation
processes worsen, concentration of transport proteins in cytoplasm of hepatocites decreases,
bilirubin excreting function of a liver is affected. Besides, increase of level of undirect bilirubin can
be supported through increase in enterohepatic circulation of bilirubin owing to bigger activity of
beta glucoronidase in intestine and through an insufficient enteral nutrition or a delay of mekonium.
Thus, at the majority of children in the first 4-5 days of an illness in blood contents of undirect
bilirubin dominate, but about 5-6 days at some children level and the conjugated bilirubin that is
connected with a syndrome of a condensation of bile and insufficiency of bilirubin excriting
function of a liver can raise.
Patogenesis of bilirubine encephalopathy.
Bilirubine encephalopathy (or nuclear jaundice) correlates with a severe course of HDN or severe
unconjugated HD of other genesis and further neurologic pathology at children if they remain live.
Unconjugated HD leads to defeat of the most different organs, nevertheless leading clinical value
has damage of bazal ganglia, hippocampus, cerebellum almonds, arises at concentration of UB in
blood plasma about 340 µmol/l. at the full-term. Prematurely born children such dangerous level
have 256-270 µmol/l, nevertheless occasionally defeat of a brain can be at much smaller
concentration of NB.
It is proved that risk factors of bilirubine encephalopathy most often is: prematurity and low birth
weight, a hypoxia, acidosis, hyper osmolarity, an infection, a hypothermia, a hypoglycemia, a
hypoalbuminemia, severe anemia, the intra cranial hemorrhages, some medicines.
With such risk factors pathology of a brain can develop at concentration of UB about 155-170
µmol/l. Toxic action of UB on neurons is in activity reduction of adenilatecyclase, ATPase that lifts
functions of membranes. Besides, defeat of mechanisms of oxidizing phosphorylation is noted, the
energy potential of cages with their subsequent necrosis decreases. Thus, UB is a metabolite which
5
slows down processes of fabric breath owing to what the bilirubine anoxia develops. The bilirubin
anoxia at the severe course of haemolytic process becomes complicated a hemic hypoxia.
HDN classification.
Type of the conflict: incompatibility of erithrocites of mother and the fetus by a Rh-factor, by ABO
system, by the rare erithrocite anti-genes.
Clinical forms:
1) pre-natal death with maceration;
2) edematous (congenital general edema of the fetus);
3) icteric (haemolytic jaundice of newborns);
4) anemic (anemia of newborns).
Severity at icteric and anemic forms: light, moderate, severe.
Complication: without complications, with complications (bilirubin encephalopathy, toxic hepatitis,
a hemorrhagic syndrome, defeat of kidneys, hearts, a syndrome of a condensation of bile and etc. )
GDN clinical forms:
The icteric form isseen most often. It is shown by icteric coloring of skin and mucous.
The anemic form is seen in 10-20% of newborns and is manifested by pallor, low level of
hemoglobin (<120 g/l) and гематокрита (<40%) at the birth.
The edematous form (hydrops foetalis) is the heaviest manifestation of a disease and has high
percent of a lethality. Practically always connected with incompatibility of blood of mother and the
child behind a Rh-factor. It is shown by generalized hypostases and anemia at the birth.
At the mixed form symptoms of 2 or 3 forms described above unite.
Light course of GDN diagnose in the presence for the child of expressed clinical-laboratory or only
laboratory data. Hemoglobin level in umbilical blood during the first hours lives - is more than 140
g/l, UB in umbilical blood - is less than 60 µmol/l. In the absence of serious background conditions
and accompanying diseases it is enough to carry out only conservative therapy.
Moderate severity course of GDN - hemoglobin less than 140 g/l, existence at the child with
jaundice of three and more risk factors of bilirubin intoxication of a brain concentration of bilirubin
in umbilical blood to 85 µmol/l, hemoglobin during the first hours. The course of average weight is
characterized by HD at which there can be a requirement (EBT) or haemosorptions but which isn't
accompanied by bilirubin intoxication or development of complications.
Severe course of GDN - bilirubin level at the birth over 85 µmol/l, hemoglobin to 100 g/l,
existence of symptoms of bilirubin intoxication (defeat of a brain, disorder of breath and heart
activity which aren't connected with accompanying diseases), need of performance more than two
EBT.
• Obligatory investigationds:
o Definition of a blood type of the child and his Rhesus factor (if it wasn't defined earlier)
o Definition of level of the total bilirubin in blood serum
o Definition of an hourly gain of level of bilirubin
o Definition of direct test of Koombs
o the General analysis of blood with calculation of erythrocytes, hemoglobin, hematocrit,
reticulocytes
• Criteria of the diagnosis
o the birth of the child with generalized edema and anemia (hemoglobin <120 g/l and
гематокрит <40%)
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o Emergence of icteric coloring of skin of the child in 1 day after the birth and Koombs's
positive test. Level of the general bilirubin of serum answers level of carrying out exchange blood
transfusion
o Emergence of pale coloring of skin in 1 day, laboratory confirmation of anemia (hemoglobin
<135 g/l and гематокрит <40%), and also increase in reticulocytes
• Treatment
o
At least 50% of newborns from group of risk on development of a haemolytic illness have
no clinical manifestations of this pathology after the birth and don't need therapy.
o
At children with clinical manifestations of a haemolytic illness of newborns by main
objectives of therapy are the following:
- The prevention of development of defeat of the central nervous system owing to toxic influence of
bilirubin
- Prevention of development of heavy haemolytic anemia
o
the most frequent manifestation of a haemolytic illness of newborns is an icteric form at
which a starting method of treatment is the phototherapy. At a phototherapy inefficiency taking
into account dynamics of indicators of an hourly gain of level of bilirubin it is necessary to
consider a question of carrying out a replaceable transfusion.
o
Phototherapy
- To begin phototherapy immediately at emergence of icteric coloring of skin with a simultaneous
blood sampling for definition of the general bilirubin of serum.
- To solve a question of the termination or continuation of phototherapy after receiving results of
the general bilirubin of serum according to standards.
- In case of unsuccessful phototherapy for 4-6 hours at definition of level of the general bilirubin of
serum of blood which answers levels for exchange blood transfusion, it is necessary to carry out
exchange blood transfusion.
o
Exchange blood transfusion:
2 . The indications to exchange blood transfusion at full-term newborns with HDN:
- Level of the general bilirubin in umbilical blood >80 µmol/l
- Hourly gain of bilirubin (on condition of phototherapy which is carried out):
- incompatibility behind a Rh-factor of 7 µmol/l
- incompatibility behind ABO system 10 µmol/l
- Anemia in the first days (irrespective of bilirubin level) Hb (100 g/l, Ht <35%
- Ratio of levels of the general bilirubin of serum (µmol/l) and albumine (g/l) depending on the
weight of the child: <1250.0 gram 6,8
1250,0-1499,0 grams 8,8
1500,0-1999,0 grams 10,2
2000,0-2500,0 grams 11,6
>2500,0 grams 12,2
If level of the general bilirubin of serum is at the level of carrying out replaceable blood
transfusion in figure 1, it is necessary to direct immediately blood of the child to laboratory for
repeated definition of a blood type and a Rh-factor and carrying out tests on compatibility.
At definition of an hourly gain to use indicators only the general bilirubin of serum of blood
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Fig. 1. The indication to phototherapy and exchange blood transfusion at the newborn child
with symptoms of a hemolytic illness or at the prematurely born newborn
Carrying out operation of exchange blood transfusion (EBT)
EBT is carried out in establishment 3 levels of providing medical aid or in establishments of the
lowest level at obligatory existence to them departments (chambers) of intensive therapy of
newborns. EBT is sterile procedure and is carried out with accurate observance of all relevant
requirements.
• Blood and plasma preparation for carrying out EBN
o Use the blood prepared not later than 3 last days. In exceptional cases it is possible to use
the blood prepared not later than 5 days.
o Blood has to be surveyed on existence of causative agents of hepatitis B and C, HIV,
syphilis (Wasserman's reaction)
o in the presence of HDN behind Rh-incompatibility to use the same group blood with the
child of Rh-negative or Rh-negative erythrocytes of the group ABO (I) in blood type AB (IV)
plasma.
o in the presence of HDN for ABO-incompatibility use identical with the child behind a
Rh-factor erythrocytes group ABO (I) in group AB (IV) plasma. In urgent cases at unknown Rh- of
the child to use Rh-negative erythrocytes group ABO (I) in group AB (IV) plasma.
o At simultaneous existence of incompatibility behind a Rh-factor and AVO-system to use
Rh-negative erythrocytes group ABO (I) in group AB (IV) plasma
o to carry out test on compatibility of donor blood with blood of the child and mother
• Types of EBT
o At full-term newborns the volume of circulating blood (VCB) makes 80 ml/kg, in
prematurely born newborns - 90-95 ml/kg
o At transfusion of integral blood blood volume for transfusion pays off at the rate of 160
ml/kg for full-term newborns and 180-190 ml/kg for prematurely born newborns.
- Carrying out simple exchange blood transfusions in volume of two EBT or isovolemic
EBT also in volume of two EBT with a simultaneous conclusion of blood with umbilical (or
another) is recommended to an artery and introduction of donor blood in umbilical (or another) a
vein (such type of EBT is better transferred by prematurely born newborns or newborns with the
HDN edematous form)
o At transfusion of the restored blood calculation of the used eruthrocites and plasma of blood is
carried out on one of below given formulas:
Formula 1
Total amount for EBT x 0,5 (desirable Ht)
Quantity of erythrocites (ml) = ---------------------------------------------------------------------0.7 (Ht эритромассы)
Formula 2
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Amount of plasma = Total amount for EBT - volume of erythrocites
Formula 3
If it is impossible to define hematocrit, the ratio between plasma and erythrocytes approximately
makes 2,5:1
- Hematocrit blood for transfusion has to make 45-50%
- Blood temperature for transfusion has to be 370 C
• Preparation for carrying out EBT
o Before carrying out EBT need to define group and Rh-factor of donor blood, it hematocrit,
and also to carry out tests on group, individual and biological compatibility.
o to weigh the child
• Practical aspects of carrying out EBT
o to enter a catheter into an umbilical vein on depth to receiving the return current of blood.
To record a catheter.
o before exchange transfusion follows aspiration of stomach content
-In the first and last portion of the removed blood to determine by level of the general
bilirubin of serum
o during carrying out EBT is desirable to continue phototherapy
o during carrying out EBT need to take the body temperature of the child of at least 1 times
at an o'clock
o during carrying out EBT to carry out control of frequency of breath, heart rate, blood
presuure and a saturation (at opportunity), diuresis isn't more rare than 1 time at an o'clock
Blood to remove and enter o equal volumes:
On 5 ml at children weighing up to 1500,0 grams
On 10 ml at children weighing 1500,0-2500,0
On 15 ml at children weighing 2500,0 - 3500,0
On 20 ml at children weighing more than 3500,0
o Speed of introduction of blood of 3-4 ml/min.
o After introduction of each 100 ml of blood need to enter 2 ml of 10% of solution of calcium of a
gluconate.
o Considering high risk of infection of the child during carrying out EBT, with the preventive purpose
after carrying out transfusion the antibiotic is entered.
o In case the child after EBT won't need infusion therapy, it is necessary to extend a catheter and to apply
pressing bandage the umbilical rest.
o In case the child after EBT will need carrying out infusion therapy, it is necessary to fix a catheter in a
vein.
o After the carried-out exchange blood transfusion is recommended to carry out definition of level of
bilirubin, гематокрита, glucose of blood and the general analysis of urine each 4-6 hours.
• Documentation registration
o Is recommended filling of the protocol of exchange blood transfusion
Hemorrhagic disease of the newborns. MKX-X CODE - P53.
The hemorrhagic illness of newborns develops in 0,25-0,5% of newborns owing to insufficient
synthesis vitamin of K-dependent clotting factors.
Etiology and patogenesis
In norm at newborns, especially prematurely born, the reduced concentration of plasma clotting
factors, especially vitamin K-dependent (11, V11, 1X, X) and also the reduced quantity of
platelets. Physiological decrease in activity of clotting system prevents DIC-syndrome
development in childbirth. At a chronic hypoxia of the fetus, acidosis, birth trauma, intoxications,
at prematurely born deficiency vitamin of K-dependent factors is expressed more which can be
manifested for 3-5 days of life of the child hemorrhagic frustration.
9
After parenteral introduction of vitamin K right after the birth became usual practice, the frequency
of a hemorrhagic illness essentially decreased. At a classical clinical picture of a disease between
the second and fifth days of life newborns have a bleeding from an umbilical wound, places of a
puncture, GI. There can be intracranial hemorrhages.
Clinical picture
Typical emergence of hemorrhages in the first 3 days after the birth in the form of
bleedings from the rest of an umbilical cord, bloody vomiting (haematemesis),
melena(emergence of blood in excrements at intestinal bleeding), hematuria, availability of
blood in the sputum, hemorrhage on skin, mucous membranes, is more rare - hemorrhages in
an internal and a brain.
The most frequent manifestation of a hemorrhagic illness of newborns is real melena that
3-4 times on the date of dark red color or black are characterized by dense bloody excrements
that sometimes also is accompanied by bloody vomiting
. Primary defeat of intestines is connected with formation of ulcers on a mucous membrane
of GIT in which genesis plays a role surplus of glucocorticoids as result of a patrimonial stress
with ischemia mucous a stomach and intestines.
Diseases is manifested for the 3rd day after the birth, are more rare right after the birth and
1-3 days last. At big bleedings severe anemia develops. The child becomes sluggish, grows
thin, transient fever can develop. From real melena (melene vera) it is necessary to distinguish
wrong (melena spuria) that arises when swallowing blood from patrimonial ways of mother at
the time of delivery.
The diagnosis of a hemorragic illness of newborns establish in the presence of
hemorrhagic frustration which unite with lengthening fibrillation time, decrease in a
protrombinovy index (it is lower than 60%), increase in protrombinovy time (norm – 13-16 c),
partsialny tromboplastinovy time (norm 45-65 c) at normal parameters of quantity of platelets,
fibrinogen, duration of bleeding, trombinovy time, a retraktion of a blood clot.
Differential diagnosis
The hemorrhagic illness of newborns should be differentiated with other diseases which are
shown by a hemorrhagic syndrome. For hemophilia the recessive inheritance linked to the Xchromosome (boys are ill) is characteristic, the disease is seldom shown in the newborn period
(possibly bleeding from the umbilicus, massive cephalogematoma). For hemophilia the
characteristic hematic type of bleeding, hemorrhage in joints, laboratory - find considerable
lengthening of clotting time and partsial tromboplastin time, and also decrease in the V111
level of clotting factor at A or 1X hemophilia - at hemophilia of B.
For 11 - 111 stages of the DIC-syndrome development of a hemorrhagic syndrome against
infectious diseases, patrimonial traumas, asphyxia in childbirth is characteristic, a syndrome of
respiratory frustration, etc. Laboratory - signs of hypocoagulation, activation of fibrinolysis
find, thrombocytopenia.
For trombocitopenia the petehial-purple type of bleeding, normal indicators of a coagulative
hemostasis is characteristic at decrease in quantity of platelets, lengthening of time of bleeding
and decrease in a retraction of a blood clot. Infections, immune violations, anomalies of
marrow, medical influences, excessive peripheral utilization (at huge hemsngioma KazabakhaMerritt, etc.), hereditary thrombocytopenia (Viskotta-Aldrich's syndrome, etc.) and etc. can be
the reasons of trombocitopenia. To the immune belong transimmune trombocitopenic purple
which develops at children who were born from mothers with idiopathic trombocitopenic
purpure owing to transplacental transition of maternal antitrombocite antibodies; isoimmune result of an izoimmunnization of mother trombocite anti-genes of the fetus, and also idiopathic
trombocitopenic purple - Verlgof's illness which very seldom meets at newborns.
Newborns from group of the increased risk have additional reasons for emergence of
deficiency of vitamin K. So, in cases when the disease of newborns interferes with the
enteroalimentation beginning, or demands its termination, vitamin K production is oppressed
by bacteria of intestines.
10
Vitamin K synthesis by bacteria decreases and as a result of their oppression by antibiotics of a
wide range of action. Therefore to children who are deprived of an enteroalimentation and/or
receive antibacterial therapy, weekly introduction of vitamin K is shown. Newborns with cystic
fibrosis, biliary atresia, other diseases which are accompanied by a malabsorbtion syndrome,
represent group of risk concerning development of "late" deficiency of vitamin K in weeks and
months after parenteral vitamin K introduction.
Treatment
Vitamin K in a dose of 2-5 mg 2-3 times per day intramuscularly in the form of 1% of solution
vikasol 0,3-0,5 ml of full-term, 0,2-0,3 ml to prematurely born children. At gastric bleeding deep
into appoint on 2 ml of solution of thrombin and adroxon in aminokapronic acid (an ampulle of dry
thrombin + 1мл 0,025% of solution of adroxon + 50 ml of 5% of solution of aminokapronic acid).
In hard cases immediate transfusion is fresher than blood of the group of the same name from
calculation of 10-15 ml/kg. At melena it is possible to appoint in the middle thrombin solution in
aminokapronic acid on 1 teaspoon 3 times to day (an ampoule of dry thrombin dissolve in 50 ml 5%
of solution of aminokapronic acid and add 1 ml of 0,025% of solution of adroxon)
Additional materials for the self-control
А. Clinical cases
Case 1
You are examining a neonate who is jaundiced at 10 hours of life. The baby was born at 39–
5/7 weeks’ gestation to a 30-year-old G1P0 mother by vacuum-assisted vaginal delivery. Labor was
complicated by thick meconium staining of the amniotic fluid, but on intubation, no meconium was
found below the cords. Apgar scores were 8 and 9 at 1 and 5 minutes of life, respectively. The baby
had transient nasal flaring and mild retractions.
The baby’s weight is 3,724 g, temperature is 98.1°F (36.8°C), heart rate is 142 beats/min,
and respiratory rate is 48 breaths/min. Jaundice is noted down to the abdomen. There is scalp
swelling and bruising, and a scabbed vesicle is present over the occiput, with two similar lesions
noted on the abdomen and one on the left thigh. All other findings on physical examination are
normal.
The mother is rubella-immune, hepatitis B surface antigen-negative, and rapid plasma
reagin-nonreactive. She declined human immunodeficiency virus testing, and her group B
Streptococcus status is unknown. The mother’s blood group is O+, the baby’s is A+, and the direct
antigen (Coombs) test is negative. The baby’s bilirubin level is 7.9 mg/dL (135 mcmol/L) total, 0.4
mg/dL (6.8 mcmol/L) direct; white blood cell count is 23.9 x 103/mcL (23.9 x 109/L) (with 72%
neutrophils, 16% lymphocytes, 9% monocytes, and 3% immature granulocytes); hemoglobin is 10.2
g/dL (102 g/L); hematocrit is 30.3% (0.3); and platelet count is 238 x 103/mcL (238 x 109/L).
After a lumbar puncture was performed, the baby was started on ampicillin, gentamicin, and
acyclovir. In the meantime, additional questioning revealed that the mother had experienced
varicella-zoster (VZV) infection late in the second trimester. A reticulocyte count on the baby was
13.9% (0.139) (corrected, 9.8% [0.098]), and the peripheral smear revealed numerous spherocytes,
reticulocytes, and nucleated cells. A red blood cell (RBC) elution test on the neonate’s blood
showed anti-A antibodies.
Questions
1. What is the definitive diagnosis?
2. Write down confirmation of the diagnosis.
3. What is the differential diagnosis of early jaundice (in the first 24 hours of life)?
4. How to treat this condition?
11
Case 2
A 23-year-old primiparous mother delivered a 36 weeks’ gestation male infant following an
uncomplicated pregnancy. The infant initially had some difficulty latching on for breastfeeding, but
subsequently appeared to nurse adequately, although his nursing quality was considered “fair.” At
age 25 hours, he appeared slightly jaundiced, and his bilirubin concentration was 7.5 mg/dL (128.3
mcmol/L). He was discharged at age 30 hours, with a follow-up visit scheduled for 1 week after
discharge. On postnatal day 5, at about 4:30 PM, the mother called the pediatrician’s office because
her infant was not nursing well and was becoming increasingly sleepy. On questioning, she also
reported that he had become more jaundiced over the previous 2 days. The mother was given an
appointment to see the pediatrician the following morning. Examination in the office revealed a
markedly jaundiced infant who had a high-pitched cry and intermittently arched his back. His total
serum bilirubin (TSB) concentration was 36.5 mg/dL (624.2 mcmol/L). He was admitted to the
hospital, and an immediate exchange transfusion was performed. Neurologic evaluation at age 18
months showed profound neuromotor delay, choreoathetoid movements, an upward gaze paresis,
and a sensorineural hearing loss.
Questions
1. What is the definitive diagnosis?
2. What is the complication, manifested by neurological disorders?
3. How this complication could be prevented?
4. What is the prognosis for this child?
Case 3
A 3-day-old boy is brought to the emergency department after having hematemesis and melena
for 24 hours. He was born at home by spontaneous vaginal delivery. The parents are not related, and
the family history is unremarkable for bleeding diathesis and drug intake.
Physical examination reveals a mildly hypoactive, pale infant whose axillary temperature is
97.7°F (36.5°C), heart rate is 140 beats/min, and respiratory rate is 50 breaths/min. His weight is 3.1
kg, length is 51 cm, and head circumference is 35 cm. Cardiac examination reveals a grade 1/6 early
systolic murmur over the left sternal border. His abdomen is soft, and no hepatosplenomegaly is
noted. Gross melena is noted on his diaper. All other physical findings are normal.
Laboratory results are as follows: white blood cell count, 9.0x103/mcL (9.0x109/L) with a normal
differential count; hemoglobin, 9.2 g/dL (92 g/L); hematocrit, 29% (0.29); platelet count,
250x103/mcL (250x109/L); direct antiglobulin test (Coombs), negative; reticulocyte count, 4%
(0.04); C-reactive protein, normal; fibrinogen, 265 mg/dL (2.65 g/L) (normal, 200 to 400 mg/dL [2
to 4 g/L]); prothrombin time (PT), 68 sec (normal, 10 to 15 sec); and activated partial
thromboplastin time (APTT), 105 sec (normal, 25 to 34 sec). Cultures of the blood and urine are
negative. The condition of the patient improves following intravenous therapy with specific agents.
Questions
1. What is the presumptive diagnosis?
2. Which disorders do you include in the differential diagnosis?
3. How this disorder could be prevented?
4. How to stop the bleeding in the child?
B. Tests
Question 1.High risk factors for neonatal jaundice include all of the following except:
A. Neonatal polycythemia
B. A sibling with jaundice
C. Poor enteral intake
D. Asian heritage
E. Post dates
Answer E. Explanation: Postmature infants have a lower incidence of jaundice unless polycythemia
is present. Other risk factors for jaundice include hemolysis, Gilbert disease, breast-feeding,
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prematurity, diabetic mother, bruising, intestinal obstruction, hypothyroidism, and diseases
producing cholestatic disorders.
Question 2. A 3-wk-old breast-fed infant has deepening jaundice. On physical examination, the
liver is 3 cm below the right costal margin. The most important laboratory test in this child at this
time is:
A. Serum ceruloplasmin determination
B. Direct and total bilirubin level
C. Hepatic ultrasonography
D. Complete blood count
E. Urine urobilinogen determination
Answer B. Explanation: Until this test is done, it is unknown whether the infant has cholestatic or
indirect hyperbilirubinemia. In this child, the total bilirubin was 20 mg/dL and the direct was 10
mg/dL. She had biliary atresia.
Question 3. A term infant at 12 hours of age is normal except for jaundice. Initial laboratory values
reveal a total bilirubin of 12 mg/dL and several spherocytes on the peripheral blood smear.
Among the following, which is the most likely diagnosis?
A. hereditary elliptocytosis
B. hereditary spherocytosis
C. glucose-6-phosphate dehydrogenase deficiency
D. disseminated intravascular coagulopathy
E. ABO isoimmune hemolytic disease
Answer E. Jaundice in the first day of life nearly always is a pathologic process in term infants.
Hereditary spherocytosis has an incidence of approximately 1/5000 in populations of Northern
European origin, less in most other ethnic groups. ABO isoimmune hemolytic anemia occurs much
more frequently, in about 3% of pregnancies, and is associated with earlyonset jaundice and
spherocytes on the blood smear. The spherocytes are generated as splenic disruption of the red cell
membrane occurs. Glucose-6-phosphate dehydrogenase deficiency (the most frequently inherited
RBC enzyme defect) is associated with normal RBC shape. Patients with disseminated intravascular
coagulopathy have bleeding, abnormal coagulation studies, and thrombocytopenia.
Question 4. All of the following are true about breast milk jaundice except:
A. It is associated with a risk of kernicterus
B. It peaks on the 3rd day of life
C. It resolves within 24 hr of temporarily stopping breast-feeding
D. It is most common in the second week of life
E. The cause is unknown
Answer B. Explanation: Breast-feeding jaundice (poor intake, dehydration) may be present this
early, but breast milk jaundice traditionally appears during the second week of life (and of nursing).
Kernicterus has been reported with breast-feeding and bilirubin levels between 21 and 50 mg/dL.
Question 5. A term female infant is born with Apgar scores of 9 and 9. At 15 hr of age, she is noted
to be pale. The vital signs reveal tachycardia; there is no hepatosplenomegaly or jaundice. The
family history is not contributory, and the review of the labor and delivery do not reveal any sources
of blood loss. Her hematocrit at 16 hr of age is 30%. The reticulocyte count is 15%, whereas the
platelet and WBC counts are normal, as is the blood smear. The bilirubin is 2 mg/dL.
The next important step in her evaluation is to do:
A. Red blood cell fragility test
B. Coombs test
C. Kleihauer-Betke test
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D. Apt test
E. Serum ferritin determination
Answer C. Explanation: The Kleihauer-Betke test is performed on maternal blood and tests for the
presence of fetal hemoglobin containing erythrocytes from a fetal-to-maternal transfusion. A low
bilirubin suggests that there is no hemolysis, and a normal examination, except for tachycardia,
suggests no internal blood loss. Fetal-to-maternal bleeding can be chronic or acute.
Question 6. Which of the following is most appropriate for treating hyperbilirubinemia (11.2
mg/dL) in a 3-wk-old, breast-fed infant with normal growth and development?
A. Phototherapy
B. Exchange transfusion
C. Phenobarbital
D. None of the above
Answer D. Explanation: No treatment is necessary for the infant described in the question,
assuming normal growth and development.
Question 7. A 4-wk-old, A-positive, African-American infant (former 40-wkgestationalage) was born to an O-positive mother and experienced hyperbilirubinemia, which required 2 days
of phototherapy in the newborn nursery after birth. The infant appears apathetic and demonstrates
pallor, a grade 2/6 systolic ejection murmur, and a heart rate of 175 beats/min. The most likely
diagnosis is:
A. Anemia of chronic disease
B. Cholestasis secondary to neonatal hepatitis
C. Hereditary spherocytosis
D. Sickle cell anemia hemolytic crisis
E. ABO incompatibility with continued hemolysis
Answer E. Explanation: Jaundice usually resolves in all infants with hyperbilirubinemia due to
ABO incompatibility in the first week of life. Nonetheless, the hemolysis continues without
evidence of jaundice because the liver can now excrete the bilirubin load. Late-onset anemia must
be watched for and treated with a packed red blood cell transfusion if the infant is symptomatic.
Hereditary spherocytosis is a possibility but is relatively rare. A thorough family history and
examination of the child's and parents' blood smear are helpful (because most cases of spherocytosis
are inherited as an autosomal dominant trait). Sickle cell anemia hemolytic crisis is not encountered
this early in life because a considerable amount of fetal hemoglobin remains; thus, there are few chains to sickle.
Question 8. All of the following are advantages of breast-feeding except:
A. Reduced incidence of allergy
B. Reduced incidence of otitis media
C. Reduced incidence of colic
D. Increased psychologic comfort
E. Vitamin K content
Answer E. Explanation: Vitamin K must be given (intramuscularly at birth) to all infants. Breast-fed
infants whose diet is not supplemented with vitamin K are at risk for bleeding. 6. Utility for preterm
infants weighing less than 2000 g
Question 9. A 2-day-old infant has significant nasal and rectal bleeding. He was delivered by a
midwife at home; the pregnancy was without complications. His Apgar scores were 9 at 1 minute
and 9 at 5 minutes. He has breast-fed well and has not required a health-care professional visit since
birth. Which of the following vitamin deficiencies might explain his condition?
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A. Vitamin A
B. Vitamin B1
C. Vitamin C
D. Vitamin D
E. Vitamin K
Answer E. Newborn infants have a relative vitamin K deficiency, especially if they are breast-fed;
most infants are given vitamin K at birth to prevent deficiency-related bleeding complications.
Question 10. A term infant weighing 4530 g is born without complication to a mother with class A
pregestational diabetes (non-insulin requiring). His initial glucose level is 30 mg/dL, but the level
after he consumes 30 cc of infant formula is 50 mg/dL, and another level obtained 30 minutes
later is 55 mg/dL. His physical examination is unremarkable except for his large size.
Approximately 48 hours later he appears mildly jaundiced. Vital signs are stable, and he is eating
well. Which of the following serum laboratory tests are most likely to help you evaluate this
infant’s
jaundice?
A. Total protein, serum albumin, and liver transaminases
B. Total and direct bilirubin, liver transaminases, and a hepatitis panel
C. Total bilirubin and a hematocrit
D. Total bilirubin and a complete blood count
E. Total and direct bilirubin and a complete blood count with differential and platelets
Answer C.
Question 11. A neonate was born from the 1st gestation on term. The jaundice was revealed on
the 2nd day of life, then it became more acute. The adynamia, vomiting and hepatomegaly were
observed. Indirect bilirubin level was $275 \mu$mol/L, direct bilirubin level - $5\mu$ mol/L,
Hb - 150 g/l. Mother’s blood group - 0[I], Rh+, child’s blood group- A[II], Rh+. What is the
most probable diagnosis?
A Hemolytic disease of the neonate [АВО incompatibility], icteric type
B Jaundice due to conjugation disorder
C Hepatitis
D Physiological jaundice
E Hemolytic disease of the neonate [Rh - incompatibility]
Question 12. A woman delivered a child. It was her fifth pregnancy but the first delivery. Mother's
blood group is A(II)Rh-, newborn's - A(II)Rh+. The level of indirect bilirubin in umbilical
blood was 58 micromole/l, haemoglobin - 140 g/l, RBC- 3,8\10^12/l. In 2 hours the
level of indirect bilirubin turned 82 micromole/l. The hemolytic disease of newborn
(icteric-anemic type, Rh-incompatibility) was diagnosed. Choose the therapeutic tactics:
A Replacement blood transfusion (conservative therapy)
B Conservative therapy
C Blood transfusion (conservative therapy)
D Symptomatic therapy
E Antibiotics
Question 13. A baby was born at 36 weeks of gestation. Delivery was normal, by natural way.
The baby has a large cephalohematoma. The results of blood count are: Hb- 120g/l, Er- 3,5\10^12/l,
total serum bilirubin - 123 mmol/l, direct bilirubin - 11 mmol/l, indirect 112 mmol/l. What are causes of hyperbilirubinemia in this case?
A Erythrocyte hemolysis
B Intravascular hemolysis
C Disturbance of the conjugative function of liver
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D Bile condensing
E Mechanical obstruction of the bile outflow
Question 14. Full term newborn has developed jaundice at 10 hours of age. Hemolytic disease of
newborn due to Rh-incompatibility was diagnosed. 2 hours later the infant has indirect
serum bilirubin level increasing up to 14 mmol/L. What is most appropriate for treatment of
hyperbilirubinemia in this infant?
A Exchange blood transfusion
B Phototherapy
C Phenobarbital
D Intestinal sorbents
E Infusion therapy
Question 15. A newborn aged 3 days with hyperbilirubinemia (428 mkmol/L) developed
following disorders. From beginning there were severe jaundice with poor suckling, hypotomia and
hypodynamia. Little bit later periodical excitation, neonatal convulsions and neonatal
primitive reflexes loss are noted. Now physical examination reveals convergent squint,
rotatory nystagmus and setting sun eye sign. How to explain this condition?
A Encephalopathy due to hyperbilirubinemia
B Skull injury
C Brain tumour
D Hydrocephalus
E Spastic cerebral palsy
Question 16. On the 3rd day of life a baby presented with haemorrhagic rash, bloody vomit, black
stool. Examination revealed anaemia, extended coagulation time, hypoprothrombinemia, normal
thrombocyte rate. What is the optimal therapeutic tactics?
A Vitamin K
B Sodium ethamsylate
C Epsilon-aminocapronic acid
D Fibrinogen
E Calcium gluconate
Question 17. On the 1st day of life a full-term girl (2nd labour) weighing 3500g, with Apgar score
of 8 points, presented with jaundice. Indirect bilirubin of blood - was 80 micromole/l, 6 hours
later - 160 micromole/l. What is the optimal method of treatment?
A Exchange blood transfusion
B Phototherapy
C Infusion therapy
D Phenobarbital treatment
E Enterosorbents
Question 18. Term infant, born from 1st not complicated pregnancy, complicated delivery, has
cephalogematoma. Since 2 day jaundice was observed, since 3 – neurological disorders: nistagmus,
Grefe symptom. Urine is yellow, feces is of golden-yellow color. Mother has blood A (II) Rhnegative, child – A (II) Rh-positive. Since 3 day child has Hb of 200g/l, erhythrocytes 6,1x10*12/l, bilirubin - 58 mcmol/l caused by increase in undirect fraction, Ht - 0,57. How this
joundice be explained?
A Cranial birth trauma
B Physiological jaundice
C Hemolitic disease of the newborn
D Biliary atresia
E Fetal hepatitis
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Question 19. Childbirth has come to the end with a birth live, term girl, without asphyxia.
Objectively: the child is weakened, the skin is pale, slightly yellowish. Edema is absent. Abdoman
is soft, liver and spleen are enlarged. Mother has blood type - A [II], Rh-negative, child - A [II],
Rh-positive. What disorder of the newborn should be suspected?
A Hemolytic disease of the newborn
B Disorders of brain circulation
C Anomalies of parenchymatous organs development
D Physiological jaundice
E Intracranial brain trauma
Question 20. 26-year-old pregnant woman has arrived in maternity home in labors. This is the
second pregnancy, the first has ended with a premature birth of the deadborn. In 30 minutes from
the beginning of labors the live girl gave birth, having weight 3600. She cried at once, the skin is
pale, with an icteric shade, hepatosplenomegaly. The placenta has separated in 15 minutes, weight
of the placenta is 800 g. The mother is a Rhesus-negative, blood of 0 (1) group, the child has 0 (1)
group, Rhesus-positive. Bilirubin is 64 mcmol \l, hemoglobin is 160 g\l at infant serum. What is the
most probable diagnoses of the listed?
A Haemolytic illness of the newborn, icterous-anemic form
B Intracranial birth trauma
C Severe asphyxia of the newborn
D Birth tumor
E Intrauterine infection
4. LITERATURE FOR STUDENTS
1. Nelson Textbook of Pediatrics. - 18th ed. / Ed. by R. Kliegman et al.-Philadelphia: Saunders Co,
2007.- 3146 p.
2. Pediatry. Guidance Aid / За ред. О.В. Тяжка; О.П. Вінницька, Т.І. Лутай – К. : Медицина, 2007 . – 158
с.
3. Current Pediatric Diagnosis & Treatment (CPDT). - 18th ed./ Ed. By W.W.Hay et al. - The
McGraw-Hill Companies. – 2006.
4. Current pediatric therapy -18th ed. / Ed. by F.D.Burg et al. - Elsevier Inc. – 2007.
5. Nelson Essentials of Pediatrics -5th ed. / Ed. by B.S.Siegel, J.J.Siegel. - Elsevier Inc. – 2007.
6. Examination of the Newborn. A Practical Guide / Ed. by Helen Baston and Heather Durward. the Taylor & Francis e-Library. - 2005.
7. Fetal and neonatal secrets. - second edition . / Ed. by R.A.Polin, A.R.Spitzer. - Elsevier.- 2006.
8. Key Topics in Neonatology / Ed. by R.H. Mupanemunda, M. Watkinson. - Oxford Washington
DC. -1999.
Performed by ass. Shiricina M.V, ass. Tkachenko N.P.
Approved “_____”____________20____y.
Сhief of the department, professor
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V. A. Kondratyev
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Сhief of the department, professor
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Сhief of the department, professor
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V. A. Kondratyev
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Protocol №_____
V. A. Kondratyev
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