Polycythemia of the Newborn

Updated: Dec 22, 2017

Author: Jegen Kandasamy, MD; Chief Editor: Ted Rosenkrantz, MD

Overview

Background

The term polycythemia means an increased cell number. However, it is mostly used to refer specifically to increased circulating red blood cell (RBC) mass. RBC mass is estimated using the hematocrit (Hct) measurement, which is defined as the percentage of RBCs in a given volume of blood. Term newborns usually have a higher Hct (51 ± 7%) compared to older children and adults. This increased Hct is a normal compensatory mechanism in these infants for the relative tissue-level hypoxia that is prevalent in the intrauterine environment, and it is exacerbated by the high affinity of fetal hemoglobin for oxygen.[1, 2] Polycythemia in the newborn is defined as a central venous Hct over 65% or a hemoglobin value above 22 g/dL.

Pathophysiology

Most of the clinical significance of polycythemia is related to the associated increase in blood viscosity.[3] Blood viscosity increases linearly with increased hematocrit (Hct), but it can increase exponentially when Hct is greater than 42%. In addition to RBC mass several other factors also determine blood viscosity.[4] These include blood pH, red blood cell (RBC) deformability, plasma protein concentration, platelet and white blood cell (WBC) volume as well as endothelial factors. Most of these factors are not significantly different between infants who are otherwise well. Therefore, RBC mass (or Hct) is the primary determinant of neonatal blood viscosity, and up to 50% of infants with polycythemia have hyperviscosity, although only 24% of infants with hyperviscosity have a diagnosis of polycythemia.[5]

Because the increased viscosity of a fluid and a smaller radius of the conduit through which it flows can increase the internal resistance of the fluid according to Poiseuille's law, polycythemia-induced hyperviscosity increases the resistance of blood to flow, especially in the microcirculation. The resultant decreased microcirculatory perfusion and increased risk for thrombosis and ischemia of end organs are the factors responsible for most of the complications associated with polycythemia. Increased blood viscosity can cause hypoperfusion directly by decreasing blood flow (as is seen in the lungs and the renal system), whereas other organs can become hypoperfused due to changes in arterial oxygen content (as noted in the brain).[6]

Etiology

Increased circulating red blood cell (RBC) mass in the newborn could be secondary to actively increased RBC production by the fetus or the newborn, or due to passive transfusion of RBCs into the fetal or neonatal circulation.

Increased fetal erythropoiesis

Increased fetal erythropoiesis is usually a fetal response to intrauterine stress and fetal hypoxia associated with increased fetal oxygen consumption resulting in fetal hypoxia that could be related to several primary etiologic factors. Most of these conditions are also associated with intrauterine growth restriction (IUGR). Underlying causes include the factors outlined below.

Placental insufficiency

Placental insufficiency could be secondary to the following:

Preeclampsia
Primary renovascular disease
Chronic or recurrent abruptio placenta
Maternal cyanotic congenital heart disease
Postdate pregnancy
Maternal smoking

Endocrine abnormalities

These include congenital thyrotoxicosis and maternal diabetes with poor glycemic control.

Genetics disorders

Genetic conditions that increase fetal erythropoiesis include the following:

Trisomy 13
Trisomy 18
Trisomy 21
Beckwith-Wiedemann syndrome

Hypertransfusion

Polycythemia-hyperviscosity could also be secondary to increased blood volume secondary to transfusion of blood either from maternal or sibling fetal sources.

Placental-fetal transfusion

Animal studies have suggested that acute fetal hypoxia can lead to increased fetal blood volume before birth, but this is unlikely to lead to significant polycythemia.[7] Delayed cord clamping (DCC) allows for an increased blood volume to be delivered to the infant. When cord clamping is delayed more than 3 minutes after birth, blood volume increases 30%. However, potential complications of DCC include polycythemia and hyperbilirubinemia.[8] Gravity, because of the position of the delivered infant in relation to the maternal introitus, and oxytocin release could also be causative factors that increase the voulme of blood that is transfused into the newborn infant's circulation during DCC.

Several studies have examined the incidence of polycythemia as a potential complication when DCC is practiced. A study of 242 newborns whose cords were clamped at less than 60 seconds, between 1 minute and just under 2 minutes, or between 2 and 3 minutes following birth found that their hematocrit (Hct) values at 48 hours after birth were 53%, 58% and 59% respectively.[9] Ferritin and hemoglobin levels also increased in association with later cord clamping. In addition, the number of infants with polycythemia was significantly higher in the group that was clamped at 2-3 minutes, but none of the infants from any of these groups required treatment for symptoms related to polycythemia-hyperviscosity.[9]

A more recent study of 73 infants showed that DCC at 5 minutes after birth did not lead to an increased incidence of polycthemia when compared to early cord clamping.[10] Another study that compared early cord clamping before 10 seconds after delivery with DCC at 3 minutes or later found no differences in the incidence of polycthemia at age 4 months in these infants.[11] Thus, although DCC increases Hct levels, currently available evidence indicates that there is minimal risk for symptomatic polycythemia that requires management.

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) due to a vascular communication occurs in approximately 10% of monozygotic twin pregnancies. In intrapartum asphyxia, blood volume is shifted from the placenta to the fetus.

Monochorionic diamniotic (MCDA) twin pregnancies with amniotic fluid discordance appear to increase the risk of development of twin anemia-polycythemia sequence (TAPS), a form of TTTS, by nearly two-fold.[12]

Epidemiology

Polycythemia is a relatively common disorder, occurring in 1-5%% of neonates.[13] It is more common in infants who are small for their gestational age (SGA) and in infants who are large for their gestational age (LGA). Infants born at higher elevations also have a higher incidence. However, most infants with polycythemia are of appropriate size or weight for their gestational age (AGA). Infants of mothers with diabetes have a polycythemia incidence of 10-30%.

Age-related demographics

The central venous hematocrit (Hct) level peaks 6-12 hours after birth and then declines until the infant is aged 24 hours, at which time it equals the Hct level in cord blood. Fewer than 40% of infants with a Hct level above 64% at 2 hours still have a high value at 12 hours or later.

Presentation

History

Neonates with polycythemia may have the following signs/symptoms:

Lethargy
Irritability
Jitteriness
Tremors
Seizures
Cerebrovascular accidents
Oliguria and/or hematuria
Respiratory distress
Cyanosis
Apnea

Physical Examination

General findings

The most obvious finding is plethora or ruddiness.

Nervous system

Neurologic manifestations include lethargy, irritability, jitteriness, tremors, seizures, and cerebrovascular accidents. These symptoms/signs are most often due to the reduced blood flow and hypoxia associated with polycythemia, but they could also be secondary to polycythemia-induced hypoglycemia and hypocalcemia.

Cardiopulmonary

Manifestations include respiratory distress, tachypnea, cyanosis, apnea, and congestive heart failure. Increases in hematocrit (Hct) are associated with a decrease in pulmonary blood flow in all newborns. In those with a Hct level of 65% or more, the decrease in pulmonary blood flow may be associated with respiratory distress, cyanosis, and pulmonary hypertension. Decreased perfusion to the lungs can lead to hypoxia, and decreased glomerular perfusion can decrease the glomerular filtration rate and lead to oliguria.

Gastrointestinal

Poor feeding is reported in infants with polycythemia and hyperviscosity.

Necrotizing enterocolitis (NEC) is a rare but devastating complication of polycythemia or hyperviscosity. Historically, about 44% of term infants with NEC have polycythemia. More recent data suggest that polycythemia may not have a large role in the development of NEC in the term infant but may be related to partial exchange transfusion (PET) with colloid to reduce the Hct.[14]

Genitourinary

Manifestations include decreased glomerular filtration rates, oliguria, hematuria, proteinuria, and renal vein thrombosis.

Priapism may be observed in male patients.

Metabolic

Hypoglycemia is the most common metabolic derangement and is observed in 12-40% of infants with polycythemia.

Hypocalcemia is the next most common metabolic derangement and is found in 1-11% of neonates with polycythemia.

Coagulation

Polycythemia can affect coagulation. Thrombocytopenia may be noted. In a retrospective study (2006-2013) from the Netherlands, thrombocytopenia occurred in 51% and severe thrombocytopenia affected 91% of 140 neonates with polycythemia.[13]

Disseminated intravascular coagulation (DIC) is rare.

DDx

Differential Diagnoses

Workup

Approach Considerations

Although hyperviscosity is the proximate cause of the complications associated with polycythemia, there are no reliable viscometers in current clinical use. Hence, the venous hematocrit (Hct) value is used as a surrogate marker for viscosity. Hct measured from capillary blood (most often obtained through "heelsticks" in newborn infants) is usually the first-line laboratory measure with which polycythemia is identified. However, simultaneous capillary and venous Hct determinations have shown that these two values are often discordant with capillary values, consistently exceeding venous values by as much as 10%.[15] Therefore, in most situations, a high capillary Hct result should be confirmed with a venous Hct measurement before decisions regarding clinical management are made for newborn infants.

Laboratory Studies

A diagnosis of polycythemia can be made using venous hemoglobin or hematocrit (Hct) values. The following laboratory tests may also need to be obtained in infants diagnosed with polycythemia who have clinical symptoms/signs that are associated with polycythemia-hyperviscosity syndrome as described earlier.

Serum glucose and calcium levels: Measure these to determine if the patient has hypoglycemia or hypocalcemia that requires treatment.
Bilirubin: Measurement of serum bilirubin level is important, as many infants with polycythemia will have an increased red blood cell (RBC) mass which leads to an increased load of bilirubin precursors that can result in hyperbilirubinemia.
Arterial blood gases (ABG): Consider measuring ABG values to assess oxygenation in the polycythemic infant with respiratory distress and cyanosis.
Platelet count: Because the same progenitor cell differentiates to produce RBCs and platelets in the bone marrow, the increased production of RBCs in infants with polycythemia can lead to reduced platelet production and contribute to thrombocytopenia. Reduced platelet number in these infants could also be secondary to thrombosis or when disseminated intravascular coagulation (DIC) is present.[13]
Serum electrolyte, blood urea nitrogen (BUN), and creatinine levels: In infants with oliguria/anuria these laboratory studies are required to assess the presence and severity of the renal dysfunction that can be a complication of polycthemia.

Some authors recommend routine complete blood cell counts in all complicated monochorionic twins, as these infants have a higher risk of severe complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS).[16]

Imaging Studies

The following imaging studies may be required in infants to exclude the presence of conditions other than polycythemia-hyperviscosity that can often lead to similar symptoms and to identify possible complications associated with symptomatic polycythemia.

Cranial ultrasound or computed tomography (CT) scanning or magnetic resonance imaging (MRI) imaging of the brain to rule out neurologic disorders such as intracranial hemorrhage
Echocardiography to evaluate cardiovascular disorders such as persistent pulmonary hypertension and cyanotic congenital heart disease
Chest x-ray to diagnose respiratory diseases such as transient tachypnea of the newborn, respiratory distress syndrome, or pneumonia
Doppler imaging of the renal veins and renal ultrasonography to identify renal vein thrombosis in infants with renal dysfunction
X-rays of the abdomen to look for signs associated with necrotizing enterocolitis

Treatment

Medical Care

Therapy in newborns with polycythemia is based on both the measured central venous hematocrit (Hct) level and the presence or absence of symptoms.[17] Careful monitoring of vital signs, respiratory function, and levels of bilirubin, glucose, electrolytes, and urine output is needed in newborns with polycythemia, and it is very often the only required intervention in these infants.

Treatment for asymptomatic patients

In asymptomatic patients with a Hct level of 65-75%, perform cardiorespiratory monitoring and monitoring of Hct and glucose levels every 6-12 hours, and observe the patient for symptoms. Continue this monitoring for at least 24 hours or until the Hct level declines.

Fluid boluses of crystalloids such as normal saline (NS) are often administed to polycythemic newborns with a Hct value between 65% to 75% with the goal of peventing the Hct from increasing to levels that require treatment with partial exchange transfusion (PET). However, this practice is not usually successful. A study comprising 55 asymptomatic infants with Hct levels between 65% and 75% showed that treating them with NS boluses did not reduce either their subsequent Hct values or their need for a PET.[18]

In asymptomatic patients with a Hct level of more than 75% on repeated measurements, consider adminstering PET although evidence is lacking as to its efficacy.

Treatment for symptomatic patients

In symptomatic patients with a Hct level of 60-65%, consider alternative explanations for the symptoms/signs. Although polycythemia and hyperviscosity may be the etiology, other causes for the manifestations must be excluded.

In symptomatic patients with a Hct level more than 65% with symptoms attributable to polycythemia and hyperviscosity, consider PET to resolve the organ dysfunction. Treatment of polycythemia with PET remains controversial in terms of changing neurologic outcome. The Committee of the Fetus and Newborn of the American Academy of Pediatrics states, "The accepted treatment of polycythemia is partial exchange transfusion (PET)." However, the group also acknowledges that no evidence suggests that exchange transfusion affects the long-term outcome.[19, 20]

PET

Informed consent must be obtained as exchange transfusions have multiple risks. Use of a blood product (eg, albumin) in an exchange transfusion may result in the transmission of infection. Infections related to blood products can be avoided by using NS, which is sterile and which has been shown to be as effective as albumin. Note that umbilical PET increases the risk of necrotizing enterocolitis (NEC), especially if colloid is used.

Perform PET using an umbilical venous catheter to reduce the central Hct level to 50-55%. Sterile technique is required.

The total blood volume to be exchanged is determined as follows:

[blood volume (patient's Hct – desired Hct)]/(patient's Hct), where blood volume = the patient's weight in kilograms multiplied by 90 mL/kg.

NS is the replacement fluid of choice for exchange transfusions because it is effective and inexpensive. As alternatives, plasma protein fraction (Plasmanate), 5% albumin, or fresh frozen plasma can be used. However, none of these products is more effective than NS. In addition, both 5% albumin and fresh frozen plasma are blood products, and certain religious beliefs prohibit their use. Lastly, these colloid products have been associated with complications such as NEC.

An exchange transfusion can be performed in three ways, depending on the type of vascular access that is available. Regardless of the method used, aliquots should not exceed approximately 5 mL/kg delivered or be removed over 2-3 minutes.

With the umbilical venous catheter in place, use a push-pull technique. With this technique, the withdrawal of blood is alternated with the administration of replacement fluid through the single catheter. Do not remove more than 5 mL/kg in any single withdrawal.

Feedings may cautiously be introduced hours after completing the PET.

Outpatient care

After the infant is discharged, clinicians should perform routine newborn follow-up care.

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