NEONATAL BLOOD TRANSFUSION AND EXCHANGE TRANSFUSION
Thabet M El Masri
NICU, Shifa Hospital GAZA , Palestine
Address for Correspondence
Thabet M, Head of NICU, Shifa Hospital GAZA , Palestine.
Email
thmasri205@hotmail.com
Introduction

  • Transfusion practices vary widely among neonatal intensive care units.
  • The risks and benefits of transfusion as well as the disease being treated and the condition of the patient must be considered before determining whether to give blood products.
  • Premature infants, especially those below 1500 grams, often receive multiple blood products transfusions.
  • The more preterm an infant the more likely blood transfusions will be required.

Storage

  • Whole blood transfusion was replaced over time with component therapy in which whole blood is separated into plasma, platelets, and RBCs.
  • A single unit of blood consists of approximately 450 ml collected from one donor, and then stored in bags with an anticoagulant preservative.
  • One unit of whole blood produces one unit of RBCs, one unit of platelets, a unit of cryoprecipitate, and a unit of platelet and cryoprecipitate poor plasma.
  • Infant blood volume is approximately 80 ml/Kg.
  • Stored RBCs have a shelf life of 35 - 42 days.
  • Many neonatology groups prefer to use fresh blood (< 5 - 7 days) because of the concern regarding storage and hyperkalemia, shortened RBCs life, hyperglycemia, hypernatremia, acidosis, renal toxicity (adenine, mannitol), and increase oxyhemoglobin affinity (decreased 2, 3 - DPG levels).
  • RBCs component, used for small volume transfusions (10 - 15 ml/Kg) in neonates, are usually stored in citrate - phosphate - dextrose - adenine solution (CPD, or CPDA1), saline - adenine - glucose - mannitol (SAGM), or extended - storage preservative solution.
  • One unit of whole blood is centrifuged to allow the separation of plasma from RBCs and then suspended to a hematocrit of 70 %, or 55 - 60 %.
  • Heparinized blood doesn't maintain RBCs function and viability thus the blood must be used within 24 -48 hours of collection.

Blood Components

They consist of RBCs, Granulocytes, Fresh frozen plasma, Albumin, Platelets, and cryoprecipitate.

Cellular Components
RBCs:

  • Indications for RBCs transfusion: to improve tissue oxygenation, and correct anemia.
  • Anemia is defined as hemoglobin or hematocrit value less than two standard deviations below the mean for the gestational or chronological age. Anemia may be physiological, or pathological.
  • Signs and symptoms of anemia: tachypnea, tachycardia, lethargy, pallor, apnea, bradycardia, poor feeding, poor growth, and elevated lactic acid.
  • Studies have shown that there is no proven benefit from transfusion of asymptomatic infants with anemia.
  • Often HCT is maintained above 40% in infants with severe cardiopulmonary disease, greater than 30% for those with moderate cardiopulmonary disease or major surgery and above 25% in infants with apnea or poor growth.
  • Methods to decrease WBCs in RBCs transfusion: Washed RBCs: Washing RBCs with 0.9% sodium chloride to remove > 95% of nonviable RBCs and 85 - 90% of WBCs and extracellular potassium, this reduces the risk of graft versus host disease (GVHD), and has 24 hours shelf life only.
  • Leukocyte- poor RBCs: techniques that remove approximately 70% of WBCs, but these result in significant loss of RBCs mass.
  • Irradiation of RBCs: this prohibits T-lymphocytes proliferation.


Transfusion Guidelines
I. Determination of Hematocrit (Hct)

  • Capillary Hct will generally be higher (up to 10 points) than central Hct.
  • Prior to transfusion, therefore, if infant is asymptomatic and Hct is <30, check a central Hct.
  • Consider checking reticulocyte count weekly after 1-2 months of age in growing premature.


II. Hypovolemic shock, acute blood loss, or sick, septic neonate In this situation, the determined Hct may be of little value, therefore use clinical judgment and transfuse PRBC's rapidly until infant is normovolemic.

III. Infants with cardiopulmonary disease
CategoryDescriptionTransfusion Criteria
SevereRDS and/or MAP > 8 cm H2O, and FiO2 > 50%Hct < 40%
ModerateMAP 6-8 cm H2O and/or FiO2 > 35%, NCPAP, nasal cannulaHct < 35%
MildMAP < 6 cm H2O and/or FiO2 25-35%, NCPAP, nasal cannulaHct < 30%


IV. Stable growing premature

A. Transfuse if Hct < 20% and reticulocyte count < 100,000 or < 2% and totally asymptomatic
B. Transfuse if Hct < 25% and any of the following symptoms are present:

  • Requiring < 24% O2 or < 1/4 liters/min O2
  • Onset or increased severity of A&B episodes - 10-12 episodes in 12 hour period or 2 episodes in 24 hrs requiring positive pressure ventilation (PPV), and unrelated to other causes and unresponsive to methylxanthines
  • Tachycardia (>170-180/min) or tachypnea (>70-80/min) persisting for 24 hours, not preexisting or related to other causes
  • Cessation of weight gain (< 10 gms/day) for 4 days while receiving optimal caloric intake (approx. 120 cal/kg/day) Note: If Hct <25% in otherwise asymptomatic infant ready for discharge, consult with PMD to determine if transfusion is wanted prior to discharge.

C. Transfuse if Hct < 30% if having surgery or post-op.

D. Congenital heart disease

  • Hct < 40% or as determined by cardiologist
  • In VSD with L>R shunt, Hct < 55%


E. Iron prophylaxis

  • At 1-2 months of age, Hct < 30%, retic. count < 4%
  • Dose 2 mg/kg/day

V. Dose of PRBC transfusion

A. Hct < 30%

  • Give 10 cc/kg PRBC over 4 hours X 2 aliquots 12 hrs apart
  • Check Hct after 2nd aliquot

B. Hct > 30%

  • Give 10 cc/kg PRBC over 4 hours
  • Check Hct after first transfusion
  • Give 2nd aliquot of 10 cc/kg PRBC if Hct < 40%


VI. Transfusion Risks

  • HIV 1:250,000-400,000
  • Hepatitis B 1:100,000
  • Hepatitis C 1:3000


Exchange transfusion:

Indications: hyperbilirubinemia, Polycythemia, severe anemia to avoid fluid overload and heart failure.

  • The need for exchange transfusion has been reduced due to improved bilirubin surveillance, phototherapy, immunoprophylaxis with anti- Rh IG, and intrauterine transfusion of non-maternal RBCs.
  • Exchange transfusion is done when other methods to reduce bilirubin have failed, and rate of rise of bilirubin is approaching dangerous levels (risk of Kernicterus).

Types of exchange transfusion:

  1. Partial exchange transfusion: is typically performed for Polycythemia (HCT>65%) that may be due to : delayed clamping of the cord , twin - twin transfusion, maternal - fetal transfusion , iatrogenic transfusion , and increased RBCs production in utero due to hypoxia. It consists of removing whole blood and replacing it with albumin, plasma, or normal saline to lower the HCT to approximately 55%.
  2. Single blood volume exchange :using (80 - 100 ml/Kg ) and usually performed for anemia with heart failure (i.e. hydrops fetalis)
  3. Double volume exchange: (160 - 200 ml/ Kg of blood). Usually performed for severe hemolytic disease of newborn. Exchange transfusion is usually done through umbilical venous catheter taking 5 - 10 ml/ Kg of blood out at a time and replacing it ml for ml.


Granulocytes:

Generally WBCs are responsible for protecting against infection.

  • Neutrophils serve as the primary defense system against bacterial infection through phagocytosis.
  • Eosinophils are involved in antigen - antibody reaction, rise in allergic / asthmatic diseases, drug reaction, and parasitic infection.
  • Basophils provide histamine and platelet - activating factors to inflamed tissues.
  • Monocytes are phagocytic cells responsible for injured and dead cells.
  • Causes of neutropenia in neonates: infection, intrauterine growth restriction, neonatal alloimmune neutropenia, and, less commonly, due to intrinsic diseases of the bone marrow.
  • Granulocyte transfusion may be considered in neonates with severe sepsis together with antibiotics .Neutropenia (<3.0 X 109/L in first week of life, or < 1.0 x 109 /L thereafter), or severe bone marrow depletion.
  • Granulocytes are collected from a unit of fresh (<24 hours from collection) whole blood by automated leukopheresis or apheresis.
  • Granulocytes should be irradiated and matched to the recipient blood type before transfusion which should take place within few hours of collection to avoid rapid deterioration in function.
  • Daily granulocyte doses (up to 1x109 granulocyte / Kg / day) for a minimum of 4 days are recommended.


Plasma:

  • Plasma is a component of blood, composed of 91-92% solids including proteins involved with coagulation cascade, albumin, electrolyte, and enzymes.
  • Fresh frozen plasma (FFP) contains adequate levels of all soluble coagulation factors as well as albumin, immunoglobulins, and naturally occurring anticoagulants.
  • Indications for FFP transfusion: - DIC, prevention of thrombocytopenia, liver failure, congenital clotting deficiencies, and sepsis (for opsonins).
  • Dose of FFP is 10-15 ml / Kg every 12 - 24 hours as clinically indicated.

Albumin:

Albumin is a plasma protein that maintains colloid osmotic pressure, contributes to Ph and electrolyte balance, and serves as a carrier protein for many substances including bilirubin. It contributes to approximately 80% of intravascular colloid oncotic pressure normally.

Indications for albumin transfusion:

  1. Volume expansion during resuscitation of an infant in shock (5% albumin). Studies have shown no benefit of using albumin versus crystalloid in resuscitation and there may be increased mortality when using albumin.
  2. 25% albumin (0.5 - 1 gram/ Kg I.V) is used sometimes in case of hypoalbuminemic infants.


Platelets:

Causes of neonatal thrombocytopenia (platelets <150 x 109/L):- infection, DIC, immune thrombocytopenia (due to moderate ITP), neonatal alloimmune thrombocytopenia.

Guidelines for platelets transfusion:-

  1. Platelets below 30 x 109/L, unless infant is unstable, or at increased risk for hemorrhage (ELBW < 1 week of age).
  2. Platelets < 50 x 109/L in actively bleeding infant.
  3. Infants with ECMO to maintain platelets > 100x 109/L.


  1. Dose of platelets is generally 10 - 15 ml / Kg.
  2. Platelets can be irradiated and washed to avoid GVHD and to remove incompatible plasma.


Cryoprecipitate

  • It is the cold-insoluble fraction prepared from FFP by slow thawing and refreezing at 2-4 degree Celsius.
  • Cryoprecipitate is rich in factor VIII and fibrinogen, and also contains, to a lesser degree, factor XIII, and Von Willebrand factor.
  • Factor concentrate are utilized for DIC, liver disease, and specific factor deficiencies.

Donors

  • Multipack RBCs collection system with additive preservative from one donor are preferred to decrease the number of donors and can be used for approximately 4 weeks.
  • Preferred donors are individuals with blood type O -ve who frequently donate such that a record of safety can be established.
  • Family blood donation is generally discouraged.
  • Mothers may have antibodies that react against RBCs, leukocytes, platelets, or HLA antigens expressed on neonatal cells. These antibodies may escape detection when blood components are screened.
  • Paternal transfusion carry a theoretical risk of exposing the infant to RBCs, leukocytes, and platelets' antigens that the neonate might have been passively immunized to by the placental transfer of maternal anti-paternal antibodies to the fetus.
  • Donated blood from first, or second -degree relative should be irradiated to inactivate the donor T- lymphocytes and avoid the risk of GVHD.

Potential adverse reactions to blood components therapy:
  • Infectious complications :


    • Include HIV, CMV, and hepatitis B and C. These complications increase proportionally to the number of donors to whom the infant is exposed.
    • Donor screening and serological testing have significantly reduced the risk of HIV, hepatitis B and C in recipients.
    • Transfusion-induced CMV infection has been estimated to be greater than 10%.
    • Signs and symptoms of CMV infection in transfused infants: respiratory distress, hepatosplenomegaly, thrombocytopenia, hemolytic anemia, jaundice, grey pallor, and atypical lymphocytosis, with potential long-term sequelae including microcephaly, motor disorders, and mental retardation.
    • Leukocytes are believed to be the site of CMV latency and thus mediate CMV transmission.
    • Risk of CMV transmission is reduced through selection of CMV sero-negative cellular blood components, or the use of leukocyte filters to remove 93 - 99% of leukocytes in the blood transfused.

  • Noninfectious complications:

  • They include coagulation abnormalities, GVHD, cardiovascular abnormalities, electrolyte abnormalities, hypothermia, and air embolism.

    • Thrombocytopenia and coagulation factor deficiency may occur due to lack of viable platelets, and clotting factors V and VIII in stored RBCs.
    • Catheterization for transfusion may cause damage to the vessel wall with the risk of thrombosis.
    • Post transfusion GVHD may occur in immunodeficient infants following transfusion of platelets, whole blood, packed RBCs, washed erythrocytes, fresh frozen plasma, and leukocytes. It is due to transfused donor lymphocytes which attack the recipient cells. Symptoms of GVHD occur within 100 days of the transfusion and can include; dermatitis, wasting, diarrhea, hepatitis, bone marrow suppression and death. Post transfusion GVHD can be prevented by irradiation of blood products before transfusion to prevent the transmission of viable lymphocytes.
    • Cardiovascular complications:


    • - Volume overload.

      - Congestive heart failure.

      - Arrhythmias.

      - Metabolic abnormalities; hyperkalemia, hypoglycemia and hypocalcaemia.

    • Transfusion through venous line may lead to damage to the vessel wall and thrombosis.
    • Transfusion through umbilical artery should be avoided as this can lead to spasm of the artery and ischemia of the spinal cord with resultant paralysis.
    Funding
    None
    Conflict of Interest
    None
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    Masri E M T. NEONATAL BLOOD TRANSFUSION AND EXCHANGE TRANSFUSION. Pediatric Oncall [serial online] 2006[cited 2006 January 1];3. Art #3. Available From : http://www.pediatriconcall.com/Journal/Article/FullText.aspx?artid=253&type=J&tid=&imgid=&reportid=338&tbltype=
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