POLICITEMIA

DEFINITIE: SE CONSIDERA POLICITEMIE LA NN CAND HT ESTE PESTE 65%HT ESTE PESTE 65% SI

CONCENTRATIA HB DEPASESTE 22 G/DLHB DEPASESTE 22 G/DL.

CAUZELE POLICITEMIEI

• A. HIPERTRANSFUZIE PLACENTARA

• Intarzierea in pensarea CO

cand se penseaza imediat volumul sg al nn este de 83,4 mg/kg.

Tinerea nn pe un plan mai jos decat mama imediat dupa nastere.

Transfuzia materno-fetala sau feto-fetala in cazul unei sarcini gemelare.

• B. insuficienta placentara (eritropoieza fetala crescuta)

nn cu distrofie intrauterina

nn. Rezultat din mama cu toxemie gravidica

nn postmatur

C. Alte cauze

Nn din mama diabetica

Hiperplazie congenitala de suprarenala, sindromul Beckwith, boala Down, tireotoxicoza neonatala.

• In conditiile unui Ht mai mare de 65% se produce o crestere considerabila a vascozitatii sanguine, urmata de scaderea irigarii si oxigenarii tesuturilor si de tendinta la microtromboze. La randul lor hipoxia si acidoza cresc vascozitatea sanguina.

• Simptomatologie clinica- maj cazurilor sunt asimptomatice. In functie de teritoriul afectat de hipoxie si trombozele secundare hipervascozitatii sanguine, se pot intalni urmatoarele semne clinice: SDR, ICC, cianoza prin nesaturarea completa a Hb, semne de suferinta din partea SNC(convulsii, letargie, iritabilitate), tromboza venei renale, hipoglicemie, icter prin cantitate crescuta de bilirubina secundara hemolizei (pericol de icter nuclear).

• Modificari paraclinice –hiperbilirubinemie, hipocalcemie, hipoglicemie, trombocitopenie, acidoza, hipoxie.

• Tratamentul – combaterea prin metode nespecifice a hipoglicemiei, hipocalcemie, hiperbilirubinemiei. Tratamentul specific se face atunci cand simptomele clinice mai apar (in general la un Ht de 70%). Acest tratament consta in efectuarea unei exanguinotransfuzii cu plasma proaspata (de acelasi grup cu nn), sau cu albumina umana 5%. Scopul acestui tratament este de a scadea Ht la 60%.

• Cantitate de plasma in ml folosita=vol.sanguin x (Ht actual – Ht dorit)/ Ht actual.

• volumul sanguin al nn este de 85-100 ml/kg.• Normalizarea Ht si a vascozitatii sg determina

regresiunea simptomelor intr-un interval de 8 ore la 3 zile. Administrarea de lichide perfuzate nu are nici un efect, atat clinic, cat si asupra vascozitatii sanguine.

• Maiorescu M.

• R=VZ• Viscosity (V) is a flow property defined as resistance (R) to the movement of

blood: R = VZ, where Z is the resistance resulting from the vessel geometry.• Blood viscosity decreases with increasing shear forces due to red blood cell

(RBC) aggregation at low shear rates and ellipsoidal deformation of• RBCs at high shear.

• Without this so called Fahraus-Lindqvist effect, blood with a hematocrit of 50% and higher could probably not pass through arterioles and capillaries with diameters below 50 μm.

• The model takes into account the dependence of apparent viscosity of blood on vessel diameter and hematocrit (the Fahraeus-Lindqvist effect), the reduction of intravascular hematocrit relative to the inflow hematocrit of a vessel (the Fahraeus effect), and the disproportionate distribution of red blood cells and plasma at arteriolar bifurcations (phase separation).

• Hyperviscosity is frequently used synonymously with polycythemia (i.e., high hematocrit). However, blood viscosity increasesincreases with increasing hematocrit, plasma viscosity and RBC aggregation and with decreasing red decreasing red blood cell deformabilityblood cell deformability.

• Neonatal blood has several favorable propertiesfavorable properties including lower plasma viscositylower plasma viscosity and RBC RBC aggregationaggregation (due to lower concentrations of high molecular weight proteins) and increased increased RBC deformability.RBC deformability.

• neonatal RBCs due to their large volume.

• However, neonatal RBCs appear to be more sensitive than adult cells to agents that can impair RBC deformability such as acidosis, hypoxemiaacidosis, hypoxemia and bacterial toxinsbacterial toxins

• Moreover, neonatal blood contains more neonatal blood contains more RBCs with irregular shapeRBCs with irregular shape and impaired impaired deformability than adult blooddeformability than adult blood

• In the majority of newborn infants, the hematocrit shows marked changes from cord blood levels through the first 24 hours of birth. The changes in the hematocrit depend on the blood volume at birth.

• In neonates with low blood volume (e.g., due to early cord-clamping), the hematocrit changes little, whereas in neonates with high blood volume (e.g., after late cord-clamping), the hematocrit rises considerably after birth, reaches the highest values at two hours of postnatal age,

• and decreases slowly over the next 24 hours

The most commonly used definition for neonatal polycythemia

is a venous hematocrit of 0.65 L/L or more• In unselected neonates, the umbilical hematocrit

is on• average 0.10 L/L higher than that of venous or

arterial blood in the infant at 2 hours of birth.• The definition of polycythemia as a venous

hematocrit of 0.65 L/L or more is based on clinical observations in adults who are at high risk of cardio-circulatory disorders such as stroke and heart attack if their hematocrit exceeds this critical value .

• However, as outlined in the Introduction, neonatal blood neonatal blood demonstrates several beneficial flow properties such demonstrates several beneficial flow properties such as decreased plasma viscosity and increased RBC as decreased plasma viscosity and increased RBC deformability when compared with adult blooddeformability when compared with adult blood.

• Moreover, otherwise healthy neonates with hematocrit values of 0.65–0.69 L/L may show some clinical manifestations of polycythemia, but long-term sequelae are rare . For clinical practice the following definitions of polycythemia may be used: 1) a hematocrit of 0.70 L/L 1) a hematocrit of 0.70 L/L or more independent of clinical signsor more independent of clinical signs, and 2) a 2) a hematocrit of 0.60–0.69 L/L with clinical signs of hematocrit of 0.60–0.69 L/L with clinical signs of polycythemia.polycythemia.

• Hyperviscosity is usually defined as a blood viscosity (measured by means of a Wells Brookfield Microviscometer) that is two standard deviations greater than the mean of a normal population. Blood viscosity techniques are not generally available. However, blood viscosity in narrow tubes that have diameters of 50 or 100 μm can be calculated from published formulas .

• Blood transfusion from the placenta to the neonate occurs when the umbilical cord is clamped at some time after 5 seconds of birth. Before birth, the fetal blood volume is approximately 70 mL/kg of blood

• Late cord-clamping may increase the neonatal blood volume by 35 mL/kg if the newly born infant is kept at or below the level of the placenta.

• A recent• meta-analysis on effects of late cord-clamping revealed little• evidence of harmful effects of late-clamping, but an increased• risk for anemia after early cord-clamping . Moreover,• neonatal polycythemia resulting from late-cord clamping did• not cause developmental or neurologic sequelae during 20• months follow-up . In preterm infants, late cord-clamping• appears to result in smaller hematocrit rises than in full-term• infants, whereas infants with intrauterine growth restriction• or diabetic mothers are at higher risk of developing severe• polycythemia after late cord-clamping due to increased intrauterine• erythropoiesis

• In some disorders such as maternal diabetesmaternal diabetes and asphyxiaasphyxia, increased plasma viscosityincreased plasma viscosity, decreased RBC deformabilitydecreased RBC deformability and increased increased RBC aggregationRBC aggregation may contribute to increased blood viscosity in addition to polycythemia .

• In septicemia,septicemia, impaired RBC deformabilityRBC deformability, increased RBC aggregation and a large number of rigid neutrophils may contribute to impaired micro- and macro-circulation .

• Transfusion of blood componentsTransfusion of blood components may cause symptomatic• hyperviscosity if the hematocrit rises above a critical limit or• the plasma viscosity and RBC aggregation increase as a result• of treatment with high doses of immunoglobulinstreatment with high doses of immunoglobulins .

• Because of the higher plasma viscosity of adult plasma, fresh frozen plasma should not be used for hemodilution in polycythemic neonates.

• RBCs from adult donors are less deformable than neonatal RBCs. Transfusion of adult RBC should, therefore, not result in a hematocrit of more than 0.55 L/L (see Fig. 79.1).

• Uncontrolled erythropoietin treatment can cause polycythemia if the infant responds particularly well to erythropoietin. However, erythropoietin treatment improves RBC deformability, due to the increased formation of young well-deformable RBC.

• Symptoms and Signs of Polycythemia• and Hyperviscosity• Increased blood viscosity can increase the flow resistance in• various organs, thereby impeding their blood and oxygen supply.• Polycythemia in the neonate decreases cardiac outputdecreases cardiac output,• and blood flow to the brainblood flow to the brain, the gastrointestinal tractgastrointestinal tract, the kidneyskidneys,• the lungslungs, the limbs limbs and the skinskin .

• There is concern that this may increase the risk of pulmonary increase the risk of pulmonary hypertension, renal failure, necrotizing enterocolitis, cerebral hypertension, renal failure, necrotizing enterocolitis, cerebral ischemia, intracranial hemorrhage, and developmental retardationischemia, intracranial hemorrhage, and developmental retardation.

• However, systemic RBC transport (calculated as product of cardiac output times hematocrit) and RBC transport to the brain (blood flow velocity times hematocrit) remain stable in the neonate over a hematocrit range of 0.40 to 0.70 L/L. Moreover, cerebral oxygenation does not decrease in the neonate up to a hematocrit of 0.70 L/L . At hematocrit of 0.70 L/L and greater, systemic and cerebral RBC transport decrease markedly.

• Clinical consequences of a high blood viscosity are principally a result of impaired circulation and oxygen supply in affected organs (Table 79.3).

• Central nervous system symptoms such as hypotonia or irritability are of particular concern, since they may indicate increased risk for long-term neurological and developmental sequelae

• Peripheral or systemic cyanosisPeripheral or systemic cyanosis and plethoraplethora are merely signssigns of a high hematocrit, but not of compromised circulation. A decrease in

• platelet count has been suggested as an indicator of polycythemia, but is also observed in infants with growth retardation and in infants of mothers with gestosis or smoking during pregnancy.

• Reported frequencies of clinical manifestations in polycythemic neonates vary widely. This may be explained by inclusion of neonates who have a high risk of perinatal complications independent of the occurrence of polycythemia (e.g, asphyxia, intrauterine growth restriction, diabetic mother, malformations), and by inclusion of different numbers of neonates who have venous hematocrits of 0.70 L/L or greater. Wiswell et al. observed clinical signs and symptoms in 50% of neonates who had hematocrits of 0.65 L/L or greater. Van der Elst et al. found most polycythemic infants healthy and unaffected. Moreover, most clinical signs and symptoms of polycythemia are of minor importance and can be observed in neonates who do not have polycythemia. Moreover, some complications such as Moreover, some complications such as thromboses or necrotizing enterocolitis may be caused thromboses or necrotizing enterocolitis may be caused by the exchange transfusion procedure rather than by by the exchange transfusion procedure rather than by the polycythemia.the polycythemia.

• Prevention and Treatment• of Polycythemia and Hyperviscosity• Prevention of polycythemia includes prevention of risk factors such as poor control of

maternal diabetes and intrauterine asphyxia. If the risk of polycythemia is increased, the umbilical cord should be clamped immediately after birth to avoid placental transfusion]. However, late cord-clamping in otherwise healthy neonates should not be avoided for concern of polycythemia, since overall late cord-clamping is more beneficial for the normal neonate than early cordclamping

• Since the hematocrit decreases spontaneously subsequent to the peak value at 2 hours of birth, it appears reasonable to accelerate this natural hemodilution by infusion of normal saline. Although several text books recommend “liberal fluid intake” for polycythemic infants, no study using the efficacy of this approach has been found in the literature. According to our own experience, the infusion of 10 mL/kg of normal saline over 1 hour decreases the hematocrit below the critical level in approximately 50% of infants.

• The general recommendation for the treatment of polycythemia is partial exchange transfusion (isovolemic hemodilution) via an umbilical vein catheter or using a radial artery for blood withdrawal and a scalp or peripheral vein for blood replacement [42]. Isovolemic hemodilution in neonates is performed via an umbilical venous catheter using 5% human serum albumin, serum (free of activated clotting factors), or crystalloids (normal saline or Ringer solution). Adult plasma increases the plasma viscosity and the RBC aggregation and, therefore, should not be used for hemodilution [26]. De Waal et al [43] conducted a systematic review to determine the efficacy of crystalloid (normal saline or Ringer solution) versus colloid (plasma or 5% albumin) for hemodilution. No meaningful differences in effectiveness (decrease in hematocrit, relief of symptoms) between plasma, 5% albumin and crystalloid solutions were observed in six studies.

• Plasma expanders such as hydroxyethyl starch and Hemaccel have been used for hemodilution in neonates , but little is known about their distribution and metabolism in the neonate.

• The use of umbilical vein catheterization for partial exchange transfusion may cause severe complications including septicemia, vasospasm, vessel perforation with hemoperitoneum or intrahepatic hematoma, air embolism, arrhythmia, thrombosis, portal hypertension and necrotizing enterocolitis.

• The exchange transfusion itself may cause blood volume and pressure fluctuations, electrolyte abnormalities, hypoglycemia, thrombocytopenia and hemolysis. The stress resulting from the procedure may explain that the heart rate and energy expenditure may rise after hemodilution for neonatal polycythemia. Exchange transfusion with plasma via the umbilical vein increases the risk of necrotizing enterocolitis.

• Since the central hematocrit is 0.65 L/L or greater in about 3% of all neonates, several thousand otherwise healthy neonates may be exposed to this potentially harmful invasive procedure of partial exchange transfusion if this threshold is used as indication, although long-term studies of children who had neonatal polycythemia failed to show the benefits of exchange transfusion for hemodilution.

• Hemodilution, therefore, is presently recommended if the hematocrit is 0.70 L/L or higher or if symptoms of compromised circulation are present at hematocrits of 0.60 to 0.69 L/L.

The following recommendations for the treatment of neonatal polycythemia are widely used.

• Screening for polycythemia may be done in small and large for gestational age infants, infants of diabetic mothers and some of the rarer risk factors listed in Table 79.1.

• It can be performed in umbilical blood, in skin prick (“capillary”) blood, venous blood taken without prolonged tourniquet or excessive squeezing, and in arterial blood.

• • If symptoms of polycythemia are observed, other explanations should be explored before an exchange transfusion is performed. The laboratory work-up includes measurements of hematocrit, blood gases, leukocyte and platelet count, CRP, serum glucose and calcium (Table

• 79.2)• . Pulse oximetry and echocardiography may be indicated.• Hypoxia, acidosis, hypoglycemia and electrolyte abnormalities should be corrected.• • If the venous or arterial hematocrit is 0.65–0.69 L/L and signs of impaired circulation are

present or if the hematocrit is 0.70 L/L or greater with or without signs, an infusion with 10 mL/kg of normal saline is given in 1 hour, and the venous hematocrit is determined again.

• • If the hematocrit remains above the critical level, exchange transfusion is performed with normal saline or

• Ringer solution. Cristalloids are as efficacious as colloids (plasma, 5% albumin and plasma expanders) for hemodilution.

• • In infants with high risk of impaired RBC deformability (e.g., diabetic mother), hemodilution may be indicated

• in some symptomatic infants with a hematocrit of 0.60–0.64 L/L.• • Informed consent of the parents must be obtained as efficacy and safety of exchange

transfusions for polycythemia are uncertain.• • The exchange transfusion can be performed via an umbilical vein catheter or a radial artery for

blood withdrawal• and a routine venous infusion for blood replacement.• • The volume of serum exchanged is:• Volume = 100 mL/kg × (observed – desired hematocrit)• where 100 mL/kg is the total blood volume in polycythemic infants and the desired hematocrit is

usually• 0.55 L/L. Usually an exchange volume of 20–30 mL is satisfactory. In each single withdrawal 1–

1.5 mL/kg of• blood is removed over 2–3 minutes and replaced over another 2–3 minutes.• • Infants should be monitored during the procedure and for• several hours thereafter.

• Hyperviscosity-Polycythemia Syndrome

• The plasma volume immediately after birth of infants who are SGA averages 52 mL/kg compared with 43 mL/kg in infants who are AGA. When equilibrated at 12 hours of life, the plasma volume becomes equivalent in the two groups.

• In addition to an enhanced plasma space, the circulating red blood cell mass is expanded. Fetal hypoxia and subsequent erythropoietin synthesis induce excessive red blood cell production. Alternatively, a placental-fetal transfusion during labor or periods of fetal asphyxia may result in a shift of

• placental blood to the fetus. Nonetheless, the elevation of the hematocrit level potentially increases blood viscosity, which interferes with vital tissue perfusion.

• The altered viscosity adversely affects neonatal hemodynamics and results in an abnormal cardiopulmonary and metabolic postnatal adaptation, producing hypoxia and hypoglycemia.

• Polycythemic infants are at increased risk of developing necrotizing enterocolitis. In the event that polycythemia is present (central hematocrit level greater than 65%) with symptoms, appropriate therapy is directed at correcting hypoxia and hypoglycemia, and a partial exchange transfusion to reduce blood viscosity and to improve tissue perfusion should be considered.

• POLYCYTHEMIA• Polycythemia is defined as an increase in RBC mass more• than 2 standard deviations above mean for age and gestation.• For a term infant, polycythemia occurs when a peripheral• venous blood sample has an Hb greater than 22 g/dL or a• hematocrit greater than 65%. Capillary blood samples are• generally higher than those drawn from peripheral blood,• and central venous values are lower still. The real issue is• viscosity, which has a linear relationship to the hematocrit up• to about 60%. Blood viscosity increases more rapidly above• 60% hematocrit, but less predictably.• Laboratory testing for hyperviscosity is not generally available, so

decisions are made using the hematocrit or hemoglobin and clinical symptoms.

• Symptoms include listlessness, irritability, plethora, acrocyanosis, poor feeding, hypoglycemia, respiratory distress, and systemic thromboses.

• Persistent pulmonary• hypertension of the newborn can be caused by increased• pulmonary vascular resistance. The increased load of RBCs• also contributes to hyperbilirubinemia. Symptoms often appear• at or after 2 hours of life, when the hematocrit is highest• due to fluid shifts. Some patients with excessive extracellular• fluid losses may become symptomatic on day 2 or 3 of life.• Conditions that result in transfusion to the fetus, such as• twin-twin or maternal-fetal transfusion or delayed clamping• of the umbilical cord, can cause polycythemia. Exacerbations• in the degree of intrauterine hypoxia, such as may be seen• with placental insufficiency, maternal toxemia, and postmaturity,• trigger increased production of EPO, which causes an• increase in RBC mass. Maternal smoking has been associated• with symptomatic polycythemia in infants. Several endocrine• conditions are associated with increased RBC production and• polycythemia, including maternal diabetes, hyperthyroidism• or hypothyroidism, and congenital adrenal hyperplasia.• Excessive EPO production and polycythemia also are seen in• infants with Down syndrome and some other trisomies and

• Beckwith-Wiedemann syndrome. Less commonly, an alteration• in hemoglobin can greatly increase the affinity of the• hemoglobin for oxygen, but most of the cases described have• involved b-chain defects that would be expected to manifest• later in infancy. Hereditary defects in the EPO receptor associated• with polycythemia also have been reported.• Management remains controversial for most infants because• exchange transfusion is associated with the usual• transfusion risks as well as increased risk for necrotizing• enterocolitis. Asymptomatic infants with a hematocrit of 60%• to 70% should be monitored closely with adequate hydration• and glucose levels. Symptomatic patients and those with a• central hematocrit greater than 70% more often undergo• partial volume exchange transfusion with normal saline to• reduce the RBC mass (see Part 2 of this chapter), but some• are still managed with supportive care.

• Polycythemia• Chronic fetal hypoxia results in increased

erythropoietin production and release by the fetal kidney, causing excessive blood red cell production.

• In addition, a shift of blood from the placental compartment to the fetus during labor or fetal hypoxic ischemia constitute important causes of polycythemia in FGR fetuses.

• Polycythemia adds to the risk of IUGR infants developing hypoglycaemia, hyperbilirubinaemia and necrotizing enterocolitis (NEC) .