HEMOLYTIC DISEASE FOLLOW-UP
Category: Child Health
Abstract : hemolytic disease follow-up - Further Inpatient Care: • The stabilization
of a hydropic newborn requires a high level of intensive coordinated management
by a neonatal team well prepared for the possibly affected infant. In general,
immediate intubation followed by draining of pleural effusions and ascites
results in immediate improvement in respiratory gas exchange. A cautious
hemolytic disease follow-up - Further Inpatient Care:
• The stabilization
of a hydropic newborn requires a high level of intensive coordinated management
by a neonatal team well prepared for the possibly affected infant. In general,
immediate intubation followed by draining of pleural effusions and ascites
results in immediate improvement in respiratory gas exchange.
A cautious
correction of anemia with packed RBCs or by exchange transfusion is necessary to
prevent circulatory overload. These neonates have normal blood volume but
elevated central venous pressure. A close monitoring of metabolic status (eg,
watching for hypoglycemia, hypocalcemia, hyperkalemia, acidosis, hyponatremia,
renal failure) is absolutely essential to achieve a successful outcome.
•
In spite of the first use of phototherapy by Cremer and associates more than 40
years ago, no standard method for delivering phototherapy yet exists.
o
Phototherapy units differ widely with respect to the type and size of lamps
used. The efficacy of phototherapy depends on the spectrum of light delivered,
the blue-green region of visible light being the most effective; irradiance
(μW/cm2/nm); and surface area of the infant exposed. High-intensity phototherapy
first described by Tan in 1977 uses irradiance greater than 25 μW/cm2/nm up to
40 μW/cm2/nm when a dose-response relationship to bilirubin degradation reaches
a plateau. Nonpolar bilirubin is converted into 2 types of water-soluble
photoisomers as a result of phototherapy. The initial and most rapidly formed
configurational isomer 4z, 15e bilirubin accounts for 20% of total serum
bilirubin level in newborns undergoing phototherapy and is produced maximally at
conventional levels of irradiance (6-9 μW/cm2/nm).
o The structural isomer
lumirubin is formed slowly, and its formation is irreversible and is directly
proportional to the irradiance of phototherapy on skin. Lumirubin is the
predominant isomer formed during high-intensity phototherapy. Decrease in
bilirubin is mainly the result of excretion of these photoproducts in bile and
removal via stool. In the absence of conjugation, these photoisomers can be
reabsorbed by way of the enterohepatic circulation and diminish the
effectiveness of phototherapy.
• Exchange transfusion removes circulating
bilirubin and antibody-coated RBCs, replacing them with RBCs compatible with
maternal serum and providing albumin with new bilirubin binding sites.
o The
process is time consuming and labor intensive, but it remains the ultimate
treatment to prevent kernicterus. The process involves the placement of a
catheter via the umbilical vein into the inferior vena cava and removal and
replacement of 5- to 10-mL aliquots of blood sequentially, until about twice the
volume of the neonate's circulating blood volume is reached (ie, double-volume
exchange).
o This process removes approximately 70-90% of fetal RBCs. The
amount of bilirubin removed varies directly with the pretransfusion bilirubin
level and amount of blood exchanged. Because most of the bilirubin is in the
extravascular space, only about 25% of the total bilirubin is removed by an
exchange transfusion. A rapid rebound of serum bilirubin level is common after
equilibration and frequently requires additional exchange transfusions.
o The
indications for exchange transfusion are controversial, except for the fact that
severe anemia and the presence of a rapidly worsening jaundice despite optimal
phototherapy in the first 12 hours of life indicate the need for exchange
transfusion. In addition, the presence of conditions that increase the risk of
bilirubin encephalopathy lowers the threshold of safe bilirubin levels.
o The
following are requirements for exchange transfusion 1. Severe anemia (Hb <10
g/dL) 2. Rate of bilirubin rises more than 0.5 mg/dL despite optimal
phototherapy 3. Hyperbilirubinemia o Exchange transfusion is not free of risk,
with the estimated morbidity rate at 5% and the mortality rate as high as 0.5%
from the procedure. Apnea, bradycardia, cyanosis, vasospasm, and hypothermia
with metabolic abnormalities (eg, hypoglycemia, hypocalcemia) are the most
common adverse effects.
hemolytic disease follow-up
- Deterrence/Prevention:
• Prevention of Rh hemolytic disease
o Rh
immunoglobulin (RhIG) was licensed in 1968 in North America after several
studies demonstrated its effectiveness in preventing Rh alloimmunization when
administered to the mother within 72 hours of delivery. The current standard is
to administer RhIG to all unsensitized Rh-negative women at 28 weeks' gestation
with an additional dose administered soon after birth if the infant is
Rh-positive, irrespective of the ABO status of the baby.
o The standard dose
of RhIG is 300 mcg and is increased (300 mcg for every 25 mL of fetal blood in
maternal circulation) based on the amount of fetomaternal hemorrhage, which can
be quantified using the Kleihauer-Betke technique. Because the time required for
the Kleihauer-Betke test usually is longer, most physicians resort to the
indirect Coombs test in the mother to assess the adequacy of RhIG dose in a
woman with significant fetomaternal hemorrhage. The indirect Coombs test result
should become positive in a woman with a prior negative test result, suggesting
the presence of excess antibody in circulation. Also administer RhIG to
unsensitized Rh-negative women after any event known to be associated with
transplacental hemorrhage. The current incidence of Rh immunization stands at
0.1% with the above recommendations.
Complications:
• The 2 major
complications of HDN are bilirubin encephalopathy (kernicterus) and late anemia
of infancy.
o Bilirubin encephalopathy
Before the advent of exchange
transfusion, kernicterus affected 15% of infants born with erythroblastosis.
Approximately 75% of these neonates died within 1 week of life, and a small
remainder died during the first year of life. Survivors had permanent neurologic
sequelae and were thought to have accounted for 10% of all patients with
cerebral palsy (CP) .
The mechanism by which unconjugated bilirubin enters
the brain and damages it is unclear. Bilirubin enters the brain as lipophilic
free bilirubin unbound to albumin, as supersaturated bilirubin acid that
precipitates on lipid membrane in low pH, or as a bilirubin-albumin complex that
transfers bilirubin to tissue by direct contact with cellular surface. A damaged
blood-brain barrier enhances the entry of all forms of bilirubin into the brain,
which is especially important in preterm neonates with respiratory acidosis and
vascular injury.
Bilirubin has been postulated to cause neurotoxicity via
4 distinct mechanisms: (1) interruption of normal neurotransmission (inhibits
phosphorylation of enzymes critical in release of neurotransmitters), (2)
mitochondrial dysfunction, (3) cellular and intracellular membrane impairment
(bilirubin acid affects membrane ion channels and precipitates on phospholipid
membranes of mitochondria), and (4) interference with enzyme activity (binds to
specific bilirubin receptor sites on enzymes).
The pathologic findings
include characteristic staining and neuronal necrosis in basal ganglia,
hippocampal cortex, subthalamic nuclei, and cerebellum. The cerebral cortex is s
generally pared. About half of these neonates also have extraneuronal lesions,
such as necrosis of renal tubular, intestinal mucosal, and pancreatic
cells.
Clinical signs of bilirubin encephalopathy typically evolve in 3
phases. Phase 1 is marked by poor suck, hypotonia, and depressed sensorium.
Fever and hypertonia are observed in phase 2, and at times, the condition
progresses to opisthotonus. Phase 3 is characterized by high-pitched cry,
hearing and visual abnormalities, poor feeding, and athetosis. The long-term
sequelae include choreoathetoid CP, upward gaze palsy, sensorineural hearing
loss, and, less often, mental retardation.
Currently, the mortality rate
stands at 50% in term newborns, but mortality is nearly universal in the preterm
population who may simply appear ill without signs specific for kernicterus.
Lately, research has indicated that bilirubin production rates may be the
critical piece of information identifying jaundiced infants at risk of
neurotoxicity. A high bilirubin production rate is thought to result in rapid
transfer of bilirubin to tissue, causing high tissue load, in which case any
small further increase has great potential to enter the brain. Because the total
serum bilirubin represents not only bilirubin production but also distribution
and elimination, it is not an absolute indicator of risk of kernicterus.
Techniques have been developed to measure the bilirubin production rates
accurately and noninvasively using end-tidal carbon monoxide measurement and
percutaneous measurement of carboxyhemoglobin.
o Late anemia of
infancy
Infants with significant hemolytic disease often develop anemia in
the first few months of life and frequently require packed RBC transfusion. The
etiology of anemia appears to be diminished hypoxic stimulus from transfusion of
adult Hb during intrauterine or exchange transfusion, resulting in low
erythropoietin levels and reticulocyte count.
Continued destruction of
neonatal RBCs by high titers of circulating maternal antibodies often
contributes to low reticulocyte count and anemia. Administration of recombinant
human erythropoietin (rh-EPO) has been shown to minimize the need for
transfusion in these newborns.
• Potential complications of exchange
transfusion include the following:
o Cardiac - Arrhythmia, volume overload,
congestive failure, and arrest
o Hematologic - Overheparinization,
neutropenia, thrombocytopenia, and graft versus host disease
o Infectious -
Bacterial, viral (CMV, HIV, hepatitis), and malarial o Metabolic - Acidosis,
hypocalcemia, hypoglycemia, hyperkalemia, and hypernatremia
o Vascular -
Embolization, thrombosis, necrotizing enterocolitis, and perforation of
umbilical vessel
o Systemic - Hypothermia
Prognosis:
• Most
survivors of alloimmunized gestation are intact neurologically. However,
Janssens and colleagues have reported neurologic abnormality to be closely
associated with severity of anemia and perinatal asphyxia.
Medical/Legal
Pitfalls:
• Failure to provide RhIG therapy to an Rh-negative woman resulting
in maternal alloimmunization and affecting the outcome of her future offspring
has a very high potential for medicolegal litigation. This warrants that
significant attention should be paid to blood type and Rh status of every
pregnant woman beginning at the first prenatal visit.
• Explain in detail to
every parent the risk of adverse outcome of an alloimmunized gestation
irrespective of its severity, including fetal loss, prematurity, brain injury,
risk of bilirubin encephalopathy, and subsequent CP.
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