Polycythemia and Hyperviscosity Kirsten E. Crowley, MD June, 2005

Definitions  Polycythemia is increased total RBC mass Central venous hematocrit > 65% Central venous hematocrit > 65% Above 65% blood viscosity rises exponentiallyAbove 65% blood viscosity rises exponentially  Polycythemic hyperviscosity is increased viscosity of the blood resulting from increased numbers of RBCs Not all polycythemic infants have symptoms of hyperviscosity Not all polycythemic infants have symptoms of hyperviscosity

Incidence  Polycythemia occurs in 2-4% of newborns Half of these are symptomatic Half of these are symptomatic  Hyperviscosity occurs in 25% of infants with hematocrit 60-64% Hyperviscosity without polycythmia occurs in 1% (nonpolycythemic hyperviscosity) Hyperviscosity without polycythmia occurs in 1% (nonpolycythemic hyperviscosity)

Pathophysiology  Clinical signs result from regional effects of hyperviscosity and from the formation of microthrombi Tissue hypoxia Tissue hypoxia Acidosis Acidosis Hypoglycemia Hypoglycemia  Organs affected: CNS, kidneys, adrenals, cardiopulmonary system, GI tract

What affects hyperviscosity?  Hematocrit Increased hct is the most important single factor Increased hct is the most important single factor Results from increase in circulating RBCs or decreased plasma volume (dehydration) Results from increase in circulating RBCs or decreased plasma volume (dehydration)  Plasma viscosity Higher plasma proteins = increased viscosity Higher plasma proteins = increased viscosity Especially fibrinogen (typically low in neonates)Especially fibrinogen (typically low in neonates) Not usually an issue in neonates Not usually an issue in neonates  RBC aggregation Occurs in areas of low blood flow = venous microcirculation Occurs in areas of low blood flow = venous microcirculation Not a large factor in neonates Not a large factor in neonates  Deformability of RBC membrane: usually normal

Conditions that alter incidence  Altitude: increased RBC mass  Neonatal age Physiologic increase in hematocrit due to fluid shifts away from intravascular compartment with maximum at 2-4 hours of age Physiologic increase in hematocrit due to fluid shifts away from intravascular compartment with maximum at 2-4 hours of age  Obstetric factors: delayed cord clamping or “stripping” of the umbilical cord  High-risk delivery, especially if precipitous

Perinatal processes  Enhanced fetal erythropoiesis usually related to fetal hypoxia Placental insufficiency Placental insufficiency Maternal hypertension, abruption, post-dates, IUGR, maternal smokingMaternal hypertension, abruption, post-dates, IUGR, maternal smoking Endocrine disorders: due to increased oxygen consumption Endocrine disorders: due to increased oxygen consumption IDM (>40% incidence), congenital thyrotoxicosis, CAH, Beckwith-Wiedemann syndrome (hyperinsulinism)IDM (>40% incidence), congenital thyrotoxicosis, CAH, Beckwith-Wiedemann syndrome (hyperinsulinism)

Hypertransfusion  Delayed cord clamping Placental vessels contain 1/3 of the fetal blood volume, half of which will be returned within 1 minutePlacental vessels contain 1/3 of the fetal blood volume, half of which will be returned within 1 minute  Gravity: positioning below the placenta will increase placental transfusion  Meds: oxytocin can increase contractions and thus transfusion Decreased in c-section b/c no contractionsDecreased in c-section b/c no contractions  Twin-twin transfusion  Maternal-fetal transfusion  Intrapartum asphyxia Enhances net umbilical flow toward the infant, while acidosis increases capillary leak leading to reduced plasma volumeEnhances net umbilical flow toward the infant, while acidosis increases capillary leak leading to reduced plasma volume

Clinical presentation  Symptoms are non-specific!  CNS: lethargy, hyperirritability, proximal muscle hypotonia, vasomotor instability, vomiting, seizures, cerebral infarction (rare)  Cardiopulmonary: respiratory distress, tachycardia, CHF, pulmonary hypertension  GI: feeding intolerance, sometimes NEC  GU: oliguria, ARF, renal vein thrombosis, priapism  Metabolic: hypo-glycemia/-calcemia/- magnesemia  Heme: hyperbili, thrombocytopenia  Skin: ruddiness

Diagnosis  Central venous hematocrit > 65%  ALWAYS draw a central venous sample if the capillary hematocrit is > 65% Warmed capillary hematrocrit > 65% only suggestive of polycythemia Warmed capillary hematrocrit > 65% only suggestive of polycythemia

Management  Asymptomatic infants Expectant observation unless central venous hematocrit >75% (consider partial exchange transfusion) Expectant observation unless central venous hematocrit >75% (consider partial exchange transfusion) Can do a trial of rehydration over 6-8 hr if dehydrated Can do a trial of rehydration over 6-8 hr if dehydrated Usually at > 48 hours of age and weight loss > 8-10%Usually at > 48 hours of age and weight loss > 8-10% Give ml/kg/dGive ml/kg/d Check central hematocrit q6 hours Check central hematocrit q6 hours Normal peak is at 2-4 hours of age for acute polycythemiaNormal peak is at 2-4 hours of age for acute polycythemia

Management  Symptomatic infants with central hct > 65% Partial exchange transfusion is advisable but debatable Partial exchange transfusion is advisable but debatable For exchange can use normal saline, Plasmanate, 5% albumin, or FFP For exchange can use normal saline, Plasmanate, 5% albumin, or FFP Volume exchanged = Volume exchanged = (Weight (kg) x blood volume) x (hct - desired hct) / hct(Weight (kg) x blood volume) x (hct - desired hct) / hct Blood volume is 80 ml/kg Blood volume is 80 ml/kg Exchange can be done via UVC that is not in the liver, low UAC, or PIV Exchange can be done via UVC that is not in the liver, low UAC, or PIV

Other labs to check  Serum glucose Hypoglycemia is common with polycythemia Hypoglycemia is common with polycythemia  Serum bilirubin Increased bili due to increased RBC turnover Increased bili due to increased RBC turnover  Serum sodium, BUN, urine specific gravity Usually high if baby is deyhdrated Usually high if baby is deyhdrated  Blood gas to rule-out inadequate oxygenation as cause of symptoms  Platelets, as thyrombocytopenia can be present  Serum calcium b/c hypocalcemia can be seen

Prognosis  Increased risk of GI disorders and NEC with partial exchange transfusion (PET)  Older trials show decreased neurologic complications from hyperviscosity with PET, but newer trials show no real benefit PET is controversial! PET is controversial!  Infants with asymptomatic polycythemia have an increased risk for neurologic sequelae Normocythemic controls with the same perinatal history have a similarly increased risk Normocythemic controls with the same perinatal history have a similarly increased risk