71: Polycythemia

The hematocrit (Hct) is 68% in a newborn. Polycythemia is defined as a venous hematocrit above 65% or a hemoglobin >22 g/dL. Polycythemia occurs in 2–4% of newborns and is rare in premature infants <34 weeks' gestation. The current definition and management of neonatal polycythemia is empirical and not evidence based. Polycythemia may result in an increase in blood viscosity, which causes a reduction in blood flow, acidosis, hypoglycemia, tissue hypoxia, and an increase in microthrombi formation. Hyperviscosity is defined as a viscosity value >14 centipoise (shear rate of 11.5 seconds) and is also defined as 2 standard deviations greater than the norm. Polycythemia hyperviscosity syndrome (PHS) is the symptom complex that involves polycythemia, hyperviscosity, and the symptoms that accompany it. Forty seven percent of polycythemic infants have hyperviscosity. Twenty-four percent of infants with hyperviscosity have polycythemia.

1. What is the central hematocrit (Hct)? In blood obtained by heelstick, the Hct may be falsely elevated by up to 5–20%. Treatment should never be initiated based on heelstick Hct values alone; a central (peripheral venous phlebotomy) Hct is needed. If the sample is from the umbilical vein or radial artery, the upper limit of normal is 63%. The hematocrit in a newborn peaks at 2 hours of age and then decreases to a baseline by 24 hours of age. A micro-centrifuge hematocrit can be 2% higher than hematocrit by a hematology analyzer.

2. Does the infant have symptoms of polycythemia? Many infants with polycythemia are asymptomatic. Symptoms of hypoperfusion correlate more with viscosity than the hematocrit. One study found that feeding problems and lethargy were the most common symptoms. There are many signs of polycythemia, most of them nonspecific, which can include the following:

   1. Central nervous system. Lethargy, hypotonia, irritability, jitteriness, weak sucking reflex, vomiting, seizures, tremulousness, apnea, sleepiness, exaggerated startle, tremors, and cerebrovascular accidents.

   2. Cardiovascular. Heart murmurs, congestive heart failure, cyanosis, plethora, tachycardia, cardiomegaly, and prominent vascular markings on chest radiograph.

   3. Respiratory. Respiratory distress, tachypnea, and cyanosis.

   4. Gastrointestinal. Poor feeding, poor sucking, vomiting, and necrotizing enterocolitis (NEC).

   5. Renal. Proteinuria, oliguria, hematuria, renal vein thrombosis and decreased glomerular filtration rates, and transient hypertension.

   6. Hematologic. Thrombocytopenia, hepatosplenomegaly, thrombosis, disseminated intravascular coagulation (rare), and elevated reticulocyte count.

   7. Metabolic. Hypoglycemia (most common; 12–40%), hypocalcemia (1–11%), and increased jaundice (hyperbilirubinemia).

   8. Skin. Plethora or ruddiness.

   9. Genitourinary (GU). Testicular infarcts or priapism (majority are idiopathic).

3. Is the mother diabetic? Poor maternal control of diabetes during pregnancy leads to chronic fetal hypoxia, which may result in increased neonatal erythropoiesis. Infants of diabetic mothers have a 25 to >40% incidence of polycythemia. Infants of mothers with gestational diabetes also have an increased incidence (30%) of polycythemia.

4. What is the infant's age? The Hct normally rises after birth and reaches a peak at 2 hours of age, and then slowly decreases and stabilizes by 12 to 24 hours of age.

5. Is the infant dehydrated? Dehydration may cause hemoconcentration, resulting in a high Hct. It usually occurs in infants >48 hours old.

6. Does the mother live at a high altitude? Infants born to mothers at high altitudes have a higher incidence of polycythemia.

7. Is the infant at high risk for polycythemia? Infants that are small for gestational age, post-term infants, infants of diabetic mothers, infants with twin to twin transfusion, and infants with chromosomal abnormalities (Down syndrome, trisomy 13 and 18) have an increased risk for polycythemia.

See also Chapter 122.

1. Falsely elevated Hct. Most often occurs when blood is obtained by heelstick.

2. Dehydration. Also called “relative polycythemia,” it is associated with weight loss and decreased urine output (sensitive indicators of dehydration). Hemoconcentration secondary to dehydration is suspected if >8–10% of the birthweight has been lost. It usually occurs on the second or third day of life.

3. Primary polycythemia (very rare in newborns). Occurs when there is a problem with the production of red blood cells (excess production) in the bone marrow and occurs from inherited and acquired mutations. Polycythemia vera, idiopathic erythrocytosis, and primary familial and congenital polycythemia are examples.

4. Secondary polycythemia. Caused by an increase in the production of erythrocytes secondary to either fetal transfusions or placental insufficiency.

   1. Fetal transfusions. Placental transfusion (hypertransfusion) occurs with delayed cord clamping (the most common cause in term infants). Clamping the cord >3 minutes after delivery can increase the blood volume by 30%, as can twin-twin transfusion, maternal–fetal blood transfusion, stripping the cord, and holding the infant with an intact cord 15–20 cm below the mother at delivery. Intrapartum asphyxia can cause blood volume to shift from the placenta to the fetus and cause polycythemia. Oxytocin administration can increase the volume of placental transfusion.

   2. Iatrogenic polycythemia. Caused by overtransfusion of red cells.

   3. Intrauterine hypoxia. Increased red blood cells (RBCs) are produced as a compensatory mechanism for intrauterine hypoxia. It may be caused by placental insufficiency.

      1. Infant. Intrauterine hypoxia may be seen in postmature, intrauterine growth restricted, or small for gestational age infants; preeclampsia/eclampsia; and infants with perinatal asphyxia.

      2. Mother. Maternal smoking, chronic or recurrent abruptio placentae, maternal hypertension, and severe maternal heart, pulmonary, or primary renovascular disease may also cause intrauterine hypoxia. Heavy maternal alcohol intake can be a cause. Severe maternal diabetes can cause reduced placental blood flow or pregnancy at high altitudes.

   4. Other causes/associations

      1. Infant of a diabetic mother has a 22–29% incidence of polycythemia. This occurs with gestational and insulin-dependent diabetes and is due to increased erythropoiesis.

      2. Chromosomal or congenital abnormalities. Down syndrome (trisomy 21; 15–33%), trisomy 13 (8%), trisomy 18 (17%), fumarate hydratase deficiency, and Beckwith-Wiedemann syndrome.

      3. Thyroid disorders. Neonatal thyrotoxicosis and congenital hypothyroidism.

      4. Congenital adrenal hyperplasia.

      5. Large for gestational age infants.

      6. Maternal use of propranolol.

      7. Sepsis.

   5. Idiopathic. No specific cause found.

1. Physical examination. Evaluate for possible dehydration. The mucous membranes will be dry. Increased skin turgor is usually not seen. True polycythemia is often, but not always, associated with visible skin changes. Ruddiness, plethora, or “pink-on-blue” or “blue-on-pink” coloration may be evident. In males, priapism may be seen secondary to sludging of red blood cells. Clinical signs are listed in Section II.B. Hypothermia is a sign of polycythemia.

2. Laboratory studies. The American Academy of Pediatrics (AAP) does not recommend universal screening for polycythemia, but it does recommend it for high-risk infants (infant of diabetic mother [IDM], infants with placental insufficiency).

   1. Hct in cord blood >56% can predict polycythemia at 2 hours of age (controversial).

   2. Central Hct (venous or arterial) is essential. Typically recommended at 2, 12, and 24 hours of age.

   3. Serum glucose. Hypoglycemia is commonly seen with polycythemia.

   4. Complete blood count (CBC) with differential and platelets. Thrombocytopenia can accompany polycythemia. Disseminated intravascular coagulation (DIC) is rare.

   5. Serum bilirubin. Infants with polycythemia can have problems with hyperbilirubinemia because of the increased turnover of red blood cells.

   6. Sodium and blood urea nitrogen. If dehydration is being considered. They are usually high, or higher than baseline values, with dehydration present.

   7. Urine specific gravity >1.015 is usually seen with dehydration.

   8. Blood gas should be obtained to rule out inadequate oxygenation.

   9. Calcium. Hypocalcemia can also be seen but is uncommon.

3. Imaging and other studies. These studies are usually not needed acutely.

   1. Chest radiograph. Cardiomegaly, increased pulmonary vascular markings, and pleural effusions may be seen on chest radiography.

   2. Electrocardiogram (ECG) and electroencephalogram (EEG). An abnormal ECG and EEG can be seen, but these tests are not routinely indicated. An ECG can show right ventricular hypertrophy and right and left atrial hypertrophy.

   3. Echocardiogram. Shows increased pulmonary resistance and decreased cardiac output.

(See also Chapter 122.) Treatment is controversial. Routine use of partial exchange transfusion (PET) is not recommended or supported. It is important to rule out other causes such as sepsis.

1. Preventive measures. Early cord clamping (clamping within 10 seconds vs clamping later) in high-risk infants caused fewer manifestations of polycythemia. This may be an effective way to prevent polycythemia in at-risk infants. Holding the infant at the level of the introitus at the time of delivery may also help minimize the maternal-to-fetal transfusion. Late cord clamping up to 2 minutes can be beneficial (improved Hct, improved iron levels and iron stores, and a decrease in anemia) in term infants, but there is a risk of polycythemia and jaundice, with a need for phototherapy. Cochrane review stated that delayed cord clamping (30–120 seconds) resulted in fewer transfusions and a decrease in intraventricular hemorrhage (IVH) in preterm infants.

2. Falsely elevated Hct (>65%). If the confirmatory central Hct is normal, no further evaluation is needed. If the central Hct is high, either dehydration or polycythemia is present.

3. Hemoconcentration secondary to dehydration. If the infant is dehydrated but does not have symptoms or signs of polycythemia, a trial of rehydration over 6–8 hours can be attempted. The type of fluid used depends on the infant's age and serum electrolyte status and is discussed in Chapter 9. Usually, 130–150 mL/kg/d is given. The Hct is checked every 6 hours and usually decreases with adequate rehydration.

4. True polycythemia. Treatment is usually based on whether or not the infant is symptomatic. The AAP states that there is no evidence that partial exchange transfusion affects the long-term outcome of the infant.

   1. Asymptomatic infants

      1. Central Hct of 65–70% and the infant is asymptomatic, only close observation and hydration (enteral or intravenous) may be needed. Many of these patients respond to increased fluid therapy; increased fluids of 20–40 mL/kg/d can be attempted. The central Hct must be checked every 4–6 hours. About 25% of infants with an Hct of 60–64% have hyperviscosity.

      2. Central Hct >70%. Treatment is controversial. Evaluate each case individually and follow your institutional guidelines. Some recommendations in the literature include

         1. Central Hct of >70–75% and the infant is asymptomatic, controversy exists as to whether a PET should be done. Hydration can be considered. Some advocate IV fluids be given and feedings withheld until Hct is <70%. Liberal IV fluid therapy can be associated with problems in preterm infants.

         2. Central Hct >75%. Traditionally, neonatologists would do a partial exchange transfusion with the Hct >75%. PET should be considered if repeated Hct remains >75%.

   2. Symptomatic infants. Some authorities recommend that any infant with polycythemia and symptoms should be treated. The goal of PET is to decrease blood viscosity and improve end-organ perfusion. Controversy exists but some recommendations are

      1. Central Hct >65% in the symptomatic infant. Partial exchange transfusion should be performed (controversial). To calculate the volume that must be exchanged, use the following formula (blood volume = 80 mL/kg):

         

         Desired Hct is usually <60%, with a goal of decreasing it to 50–55%. PET may be administered via an umbilical venous catheter (UVC). Care must be taken not to place the catheter in the liver (see Chapter 44). A high umbilical artery catheter (UAC) or a peripheral intravenous catheter can also be used. Normal saline is preferred in most institutions, as crystalloids are as effective as colloids in PET. Crystalloids do not carry the risk of infection or anaphylaxis and are cheaper and more readily available. Plasmanate, 5% albumin, and fresh frozen plasma (FFP) can be used but are not recommended. Colloid products have also been associated with NEC. Serial Hct levels should be obtained after transfusion. The PET procedure is discussed in detail in Chapter 30. Use these guidelines when performing PET:

         1. Aliquots should not exceed 5 mL/kg and should be removed or delivered over 2–3 minutes.

         2. Removal of blood can be from any arterial or venous line. Arterial lines are not recommended for infusion.

         3. If there is both a UAC and a UVC, withdraw blood from the UAC while giving the replacement fluid through the UVC.

         4. If only a UVC is in place, use the push-pull method: pull out the blood, and then push in the replacement fluid. Never remove >5 mL/kg. Isovolumetric method through 2 vessels is preferred.

         5. If you have a UVC, UAC, and peripheral venous catheter in, you can use either the UAC or UVC for blood withdrawal and then use the peripheral line for replacement fluid. Removal from the UVC and infusion in the peripheral venous catheter did not result in NEC in one study.

   3. Symptomatic infant with a central Hct of 60–65%. If all other disease entities are ruled out, these infants may indeed be polycythemic and hyperviscous. Management is controversial. Use clinical judgment and institutional guidelines to decide whether or not these infants should have a partial exchange transfusion.

   4. Restrictive management of neonatal polycythemia follows a more conservative approach. Hct of 65–69%: no treatment. Hct of 70–75%: IV fluids and no feedings until Hct is <70%. Hct ≥76% or in symptomatic neonates: use PET. A review demonstrated that the groups did not differ in morbidities or hospital stay, nor was there an increase in risk of short-term complications.

5. Observe for complications of polycythemia and disorders that are more common in polycythemic infants.

   1. Apnea.

   2. Hypocalcemia, hypoglycemia, electrolyte abnormalities.

   3. Thrombocytopenia.

   4. Hyperbilirubinemia.

   5. Neurologic. Seizures, stroke, cerebral vein thrombosis.

   6. Vascular. Vasospasms, peripheral gangrene.

   7. Cardiac. Arrhythmia, congestive heart failure.

   8. GI

      1. Necrotizing enterocolitis (NEC) risk is increased in neonates with hyperviscosity who received a partial exchange transfusion via a UVC with colloid (FFP, albumin, or Plasmanate). The development of NEC in these infants may be related to PET with colloid, not the polycythemia.

      2. Ileus, spontaneous intestinal perforations, intestinal atresia.

   9. Genitourinary. Renal failure, renal vein thrombosis, testicular infarcts, priapism.

   10. Air embolism.

6. Follow-up data. Polycythemia and hyperviscosity syndrome treated by PET can be associated with significant complications (increased risk of NEC) and may be associated with an earlier improvement in symptoms. Further research is needed to assess the impact on newborns, as there is conflicting (controversial) literature.

   1. PET decreases viscosity and ameliorates most symptoms but does not significantly improve long-term neurologic outcomes. However, decreased IQ scores and lower achievement were reported in infants with hyperviscosity syndrome who were not treated with PET.

   2. PET improves microcirculation in polycythemic neonates. Near infrared spectroscopy showed increased cerebral oxygenation and decreased fractional tissue oxygen extraction.

   3. PET has been shown to improve cerebral blood flow velocity and decrease pulmonary vascular resistance, and may normalize cerebral hemodynamics.

   4. There is no evidence of improvement in long-term neurologic outcome or early neurobehavioral assessment scores following PET in symptomatic or asymptomatic infants.

   5. Polycythemic infants are at risk for speech abnormalities and for fine/gross motor delays.

   6. Umbilical vein partial exchange transfusion with colloid increases the risk of NEC.

   7. Intrauterine fetal hypoxia is related to polycythemia and the impaired long-term outcome.

   8. Coexisting hypoglycemia may worsen the long-term outcome.

   9. Cochrane review states no proven benefit to PET in infants with polycythemia who are well or who have minor symptoms. PET may increase the risk of NEC. It notes that the risk and benefits of PET are not clear at this time.