Neonatal Transfusion

1. Neonatal Transfusion

2. Transfusion in the newborn requires selection of appropriate donor, measures to minimize donor exposure and prevent graft versus host disease and transmission of Cytomegalovirus. • Component therapy rather than whole blood transfusion, is appropriate in most situations. • A clear cut policy of cut-offs for transfusions in different situations helps reduce unnecessary exposure to blood products. • Transfusion triggers should be based on underlying disease, age and general condition of the neonate.

3. Neonatal Blood Transfusion Ahmad Sh. Silmi Msc, FIBMS Medical laboratory sciences IUG

4. Introduction • Neonatal period – birth to 4 months. • Indications for transfusion DIFFERENT • Weight • Gestational age • Circumstances of delivery • Maturation

5. Introduction • Ill Infants most transfused patients in hospital. • Iatrogenic blood loss carefully monitored. • Once significant, transfuse • Transfusion service must provide specialized service • Minimize donor exposure if possible. • Use one unit with satellite bags • Use sterile docking device

6. Introduction • Double volume exchange transfusion is mainly used for the management of hyperbilirubinaemia and haemolytic disease of the newborn, when other methods of treatment such as early and intensive use of phototherapy have been ineffective

7. The aim of an exchange transfusion is: • To lower the serum bilirubin level and reduce the risk of brain damage (kernicterus); • To remove the infants' affected red blood cells and circulating maternal antibodies to reduce red cell destruction; • To correct anaemia and treat any potential for heart failure whilst maintaining euvolaemia.

8. Fetal and Neonatal Erythropoiesis • Appropriate transfusion practice requires knowledge of neonatal physiology and careful clinical observation. • As embryo develops predominant sites of hematopoiesis change: • at about the 9th week of gestation shifts from wall of yolk sac to liver. • at about the 24th week from liver to bone marrow. • Hematopoiesis regulated by gradually increasing erythropoietin levels stimulated by low oxygen tensions during intrauterine life. • At 40 weeks (full term), normal infants have cord blood hemoglobin of 19 +/- 2.2 g/dL. • Neonates of lower birth weight have lower normal hemoglobin levels.

9. Fetal and Neonatal Erythropoiesis • Fetal red cells have life span of 45-70 days,53-95% hemoglobin F • Physiologically adapted to low intrauterine oxygen tensions • High oxygen affinity allow red cells to acquire oxygen from maternal RBC throughout pregnancy and release tissues. • High oxygen affinity results in poor tissue oxygenation after birth. • Hemoglobin A replaces hemoglobin F after birth • Oxygen delivery to tissues remains satisfactory despite a physiologic fall in hemoglobin concentration. • Oxygen dissociation curve shifts to the right, reflecting improving oxygen delivery to the tissues. • Premature infants have lower hematocrits and greater percentage of hemoglobin F in their RBC than term newborns.

10. Fetal and Neonatal Erythropoiesis • As tissue oxygenation improves, erythropoietin decline and erythropoiesis diminishes. • Decline in RBC produces a "physiologic anemia of infancy“. • Normally developing infant maintains adequate tissue oxygenation despite lower hemoglobin levels.

11. Haemolytic disease: Indications for exchange transfusion • Cord Hb <12 mg/dl and/or cord SBR >5mg/dl : immediate exchange transfusion • Exchange transfusion if rate of rise in SBR is such that SBR is likely to reach 17mg/dl. • ( aim to keep SBR below 20 mg/dl).

12. Unique Aspects of Neonatal Physiology • Differences between newborns and adults dictate differences in transfusion practice. • Newborns are small and physiologically immature. • Those requiring transfusion are often premature, sick and unable to tolerate minimal stresses.

13. Unique Aspects of Neonatal Physiology • Infant size • Full-term newborns blood volume approximately 85 ml/kg • Premature infants average blood volume of 100 ml/kg. • Survival rates continue to improve for infants weighing 1000 g (2.2 lbs) or less at birth • Transfusion service must provide blood components for patients whose total blood volume is less than 100 mLs. • Small blood volumes and need for frequent laboratory test makes replacement of iatrogenic blood loss most common indication for transfusion.

14. Unique Aspects of Neonatal Physiology • Infants do not compensate for hypovolemia well. • Results in diminished cardiac output, resulting in • poor tissue perfusion, • low tissue oxygenation and • metabolic acidosis. • Bone marrow responds more slowly to anemia. • If hemolysis occurring due to maternal antibody may be no increased erythropoiesis for 2-3 weeks.

15. Unique Aspects of Neonatal Physiology • Cold stress (hypothermia) causes exaggerated effects: • increased metabolic rate • hypoglycemia • metabolic acidosis • tendency to apneic episodes that may lead to hypoxia, hypotension and cardiac arrest. • Blood for transfusion should be warmed if given in large amounts, small amounts reach RT in about 20 minutes and does not need to be warmed.

16. Unique Aspects of Neonatal Physiology • Immunologically immature, antibodies present in plasma originate almost entirely from maternal circulation. • IgG only immunoglobulin class that crosses the placenta. • Passively acquired antibody conserved during the neonatal period due to slow catabolism by the fetus. • Infants exposed to an infectious process in utero or shortly after birth may produce small amounts of IgM detectable by sensitive techniques, but rarely form RBC antibodies of either class during the neonatal period.

17. Unique Aspects of Neonatal Physiology – Metabolic Problems • Immature kidneys have reduced glomerular filtration rate and concentrating ability, the newborn may have difficulty excreting potassium, acid and/or calcium loads. • Acidosis or hypocalcemia may also occur postransfusion because immature liver metabolizes citrate in banked blood inefficiently. • Studies have shown older units do not affect the infant for routine transfusion purposes.

18. Unique Aspects of Neonatal Physiology – 2,3-DPG • Tissue oxygenation poor due to high percentage of hemoglobin F. • Hemoglobin F does not release oxygen to the tissues like adult hemoglobin. • Respiratory distress syndrome (RDS) or septic shock have decreased levels of 2,3-DPG, alkalosis and hypothermia can further increase the oxygen affinity of hemoglobin. • 2,3-DPG levels decrease in stored blood, newborns should be given freshest blood available, less than 5 days old if possible. • Controversy in the field about the practice of using fresh blood. • Greater importance to decrease donor exposures rather than give fresh blood. • Allow CPD donor units to be put on hold for infant for 21 days. • Exception is for massive transfusion

19. Informed Consent • Before the commencement of any blood or blood product infusion the medical officer or registered nurse administering the blood product must ensure that parents have given an informed consent for the procedure. • Benefit versus risk - In otherwise well babies the risk of exchange transfusion are usually small but in preterm babies who are unwell the risks of exchange transfusion are increased and the procedure must be balanced the high morbidity associated with bilirubin encephalopathy.

20. Collection of blood samples and ordering of Red Blood Cells and FFP: • Liaise with the obstetric team and notify blood bank of a possible exchange transfusion before the delivery of an Rh- affected fetus. • Stored red blood cells (RBCs) have a predictable packed cell volume of 60% (+/- 2%) so measurement of haematocrit levels is no longer necessary. In order to dilute the RBCs by 10% you will also need to order Fresh Frozen Plasma (FFP) of suitable type. • A request for RBCs for exchange transfusions is normally considered an urgent request. The RBCs should be ready within 2 hours of request provided antibody testing has been completed.

21. Types of Red Blood Cells • Rh haemolytic disease of the newborn: RBCs less than 5 days old are used. • O Rh negative RBCs do not have major blood group antigens so they are not haemolysed by maternal antibodies that may still be present in the infant's circulation. • If the RBCs are made available before delivery of the sensitised infant the RBCs must be O Rh negative and cross matched against the mother. If the RBCs are sourced after delivery the RBCs must be cross matched against the infant.

22. ABO incompatibility: • Use group O, Rh specific RBCs. These RBCs contain low levels of antibodies and lack antigen that could trigger any circulating maternal antibodies in the newborn. Subsequent transfusions should be done with RBCs that are compatible with that of the mother and infant.

23. Volume of RBCs and FFP to be ordered • The volume required is dependent on the reason for exchange and is determined by the formula next page.

24. SINGLE VOLUME EXCHANGE (anaemia with normovolaemia) • Estimated blood volume depends gestational age and timing of cord clamping ranging from 53 -105 ml/kg/min. Mean blood volume was 70 ml/kg (early cord clamping) versus 90ml/kg (delayed cord clamping for infants weighing 480-2060g.

25. DOUBLE VOLUME EXCHANGE (for established hyperbilirubinaemia or to prevent hyperbilirubinaemia) • Double volume exchange removes about 85% of the infant's red blood cells. At the end of the exchange blood transfusion the bilirubin should be about 50% of pre exchange level. It will rebound at about 4 hours to 2/3rds the pre-exchange level.

26. Ordering blood • A cross match request form must be hand written and collection witnessed and signed by a second MO / RN. Specimen must be labelled by hand • When ordering red cells for an exchange transfusion, remember the priming volume of the exchange circuit is approx 50ml so additional RBCs should be ordered. • Always communicate with blood bank.

27. Collection of blood and plasma from Blood Bank • Blood Bank will notify the nursery when the RBCs and FFP are ready to be collected. • The Ward Assistant will need both the Intravenous Infusion Order Form and the RPA Blood Product Issue Form to collect the blood products form Blood Bank.

28. Possible Complications • These are unusual if the exchange is performed slowly and often the best • management is to slow down or pause the exchange. Any of the following can happen

32. Transfusion Associated Graft versus Host Disease(TA-GVHD) • TA-GVHD reported in newborns receiving intrauterine transfusion followed by postnatal exchange transfusion. • Lymphocytes given during intrauterine transfusion may have induced host tolerance, so that lymphocytes given in subsequent exchange transfusion were not rejected in the normal way. • GVHD not felt to be significant clinical problem for immunologically normal newborns who receive multiple exchange transfusions.

33. Transfusion Associated Graft versus Host Disease(TA-GVHD) • Irradiation of blood kills immunologically competent lymphocytes. • Irradiated blood given to low birth weight, low gestational age or septic premature neonates such infants are immunologically more vulnerable to TA-GVHD. • Blood for intrauterine transfusion should be irradiated. • Any directed donor blood from a relative should be irradiated.

34. Cause of Hemolytic Disease • Maternal IgG antibodies directed against an antigen of paternal origin present on the fetal red blood cells. • IgG antibodies cross the placenta to coat fetal antigens, cause decreased red blood cell survival which can result in anemia. • Produced in response to previous pregnancy with antigen positive fetus OR exposure to red blood cells, ie transfusion.

35. Cytomegalovirus (CMV) Infection • Infection by CMV may occur in the perinatal period, either in-utero or during birth, by breast feeding or by close contact with mothers or nursery personnel. • CMV mays also be transmitted by transfusion, virus seems to be associated with leukocytes in blood and components. • Infection in newborns is extremely variable in its manifestations, ranging from asymptomatic seroconversion to death. • Symptomatic infection may produce pulmonary, hepatic, renal, hematologic and/or neurologic dysfunction.

36. Cytomegalovirus (CMV) Infection • This neonate was found to have respiratory distress, an extensive rash and hepatomegaly. • Results of CMV IgM and IgG tests and both serum and plasma DNA polymerase-chain-reaction assays were positive.

37. Cytomegalovirus (CMV) Infection • Epidemiology and prevention of post transfusion CMV in neonatal patients have been under intense investigation. • The following observations have been noted: • Where CMV rate is high, symptomatic infection is low. • Babies of seropositive moms unlikely to develop CMV. • Premature infants born of seronegative mothers, weigh less than 1200 grams and require multiple transfusions at risk for symptomatic postransfusion infections. • The risk of CMV increases with number of donor exposures. • Risk of transmission decreases by using seronegative donors or components depleted of leukocytes.

38. Cytomegalovirus (CMV) Infection • Standards states that in geographic areas where postransfusion CMV transmission is a problem, blood with minimal risk of transmitting CMV be used for: • newborns weighing less than 1200 g, • born to mothers who lack CMV antibodies or • whose antibody status is unknown. • Most blood banks make it standard practice to transfuse all infants with CMV negative blood.

39. Hemolytic Disease of the Fetus and Newborn - HDFN • HDFN, red cells of fetus coated with IgG alloantibody of maternal origin, directed against antigen of paternal origin present on fetal cells. • IgG coated cells undergo accelerated destruction, both before and after birth. • Clinical severity of the disease is extremely variable, ranging from intrauterine death to a condition that can be detected only by serologic tests on blood from an apparently healthy baby.

40. HDFN - Pathophysiology • Shortened RBC survival causes fetal hematopoietic tissue increase production of RBCs, causes increase in nucleated red cells (NRBCs). • Organs containing hematopoietic tissue increase in size, particularly liver and spleen (hepatosplenomegaly). • If increased hematopoiesis cannot compensate for the immune destruction, anemia becomes progressively more severe.

41. HDFN - Pathophysiology • Severely affected fetus may develop high output cardiac failure with generalized edema, a condition called hydrops fetalis, death may occur in utero. • If live-born, severely affected infants exhibit heart failure and profound anemia. • Less severely affected infants continue to experience accelerated red cell destruction, which generates large quantities of bilirubin.

42. HDFN - Pathophysiology • In-utero fetal bilirubin processed by maternal liver. • After birth neonatal immature liver takes over. • Deficient in uridine diphosphoglucoronyl transferase, bilirubin rises. • Bilirubin 20mg/dL> results in mental retardation or death, condition known as kernicterus.

43. Kernicterus • Kernicterus (bilirubin encephalopathy) results from high levels of indirect bilirubin (>20 mg/dL in a term infant with HDN). • Kernicterus occurs at lower levels of bilirubin in the presence of acidosis, prematurity, hypoalbuminemia and certain drugs (e.g., sulfonamides).

44. Kernicturus • Affected structures have bright yellow color. • Unbound unconjugated bilirubincrosses blood-brain barrier and, because it is lipid soluble, penetrates neuronal and glial membranes. • Bilirubin is thought to be toxic to nerve cells • Mechanism of neurotoxicity and reason for topography of lesions are not known. • Patients surviving kernicterus have severe permanent neurologic symptoms (choreoathetosis, spasticity, muscular rigidity, ataxia, deafness, mental retardation).

45. Three Classifications of HDN • ABO • “Other” – unexpected immune antibodies other than anti-D – Jk, K, Fy, S, etc. • Rh • Immune anti-D alone • Immune anti-D along with other Rh antibodies – anti-C, -c, -E or –e.

46. Maternal Immunization • Fetal cells possessing paternal antigen mother does not possess enter her circulation and stimulate antibody production. • D antigen most immunogenic but other blood group antigens may also immunize. • Fetal cells enter maternal circulation during pregnancy. • Biggest exposure during birth.

47. Maternal Immunization • Can occur with exposure to <0.1mL • Immunization to D correlates with  volume of RBCs entering D neg mom’s circulation.

48. Maternal Immunizing Events • Other than birth can be due to: • Amniocentesis • Miscarriage • Abortion • Chorionic villus sampling • Cordocentesis • Blunt trauma to the abdomen • Rupture of an ectopic pregnancy

49. Maternal Immunization - Transfusion • Severe HDFN in D neg women transfused with D pos RBCs and develop anti-D • Must give D neg RBC and platelet products to females. • If D pos platelets or granulocytes given must give Rh prophylaxis, i.e., RhIg • Avoid directed donation from husband to wife

50. ABO Hemolytic Disease • Mother group O, baby A or B • Group O individuals have anti-A, -B and –A,B in their plasma, fetal RBCs attacked by 2 antibodies • Can occur in any ABO incompatible pregnancy • Occurs in only 3%, is severe in only 1%, and <1:1,000 require exchange transfusion. • The disease is more common and more severe in African-American infants.