VIMS Journal: December 2015

Review Article

Preoperative Blood Transfusion in Paediatric Patients

Dr. Tulsi Nag, Dr. Kasturi Hussain Banerjee

Abstract :
Paediatric patients undergoing surgical procedures commonly require some volume of blood or blood component replacement in perioperative period. Those undergoing major surgery with substantial blood loss should be evaluated preoperatively.

Preoperative Correction of anaemia may be done considering the age, plasma volume status, clinical condition and co morbidities. Maximum allowable blood loss (MABL) for surgery must be calculated and appropriate quantity of blood and blood components should be arranged. Intra operative monitoring of blood loss should be done and volume of transfusion should be assessed considering the volume status and trigger threshold for transfusion.

Early haemostasis should be achieved by judicious administration of red blood cells, blood components and pharmacological agents.

Key Words: :
Paediatric patients, Perioperative transfusion, Blood loss, Anaemia.

Introductions:
Perioperative blood management refers to perioperative blood transfusion and adjuvant therapies. Perioperative blood transfusion addresses the preoperative, intraoperative and postoperative administration of blood and blood components.

Adjuvant therapies refer to drugs and techniques used to reduce or prevent blood loss and need for allogenic blood transfusion.

Guidelines for Blood Transfusion and Adjuvant Therapy.

Preoperative Evaluation:

It identifies the cause for blood transfusion or adjuvant therapy by:

  • - Reviewing previous medical records.
  • - Conducting a patient or family interview.
  • - Reviewing laboratory test results.
  • - Ordering additional laboratory tests when indicated.

Review of previous medical records and interview of patient or family help to elicit: H/O previous blood transfusion, drug induced Coagulopathy, Congenital Coagulopathy, thromoembolic events and risk factors for organ ischaemia.

Review of laboratory tests exhibits haemoglobin level, Haematocrit and coagulation profile.

Additional tests are ordered based on medical condition like anaemia, Coagulopathy. Physical examination is done to detect pallor, petechiae and ecchymosis.

Preoperative evaluation is performed well in advance to allow time for patient preparation.

Preadmission Patient Preparation :
It includes :

  • - Treatment of anaemia
  • - Discontinuation of anticoagulants and anti platelets.
  • - Preadmission autologous blood collection

Anaemia is treated with erythropoietin and/or iron to improve haemoglobin levels. Iron is administered to treat patients with iron deficiency anaemia.

Discontinuation of anticoagulation therapy is done before surgery with transition to a shorter acting drug like low molecular weight heparin. Antiplatelet agent like clopidogrel needs discontinuation well in advance of surgery except for patients having percutaneous Coronary intervention. The risk of thrombosis versus the risk of bleeding should be considered during altering anticoagulation status.

Availability of blood component should be assured when significant blood loss or transfusion is expected.

Preoperative autologous donation (PAD) off sets the risk of allogenic blood transfusion. PAD targets specific surgical procedures where excessive blood loss is expected. Compensatory crythropoiesis occurs during the Course of PAD. RBC production increases with increasing interval from last donation to surgery and this interval should be maximized. Treatment with erythropoietin during PAD increases the amount of blood collected and decreases allogenic blood transfusion. Erythropoietin is used to increase haematocrit preoperatively either alone or as an adjunct to PAD.

Pre-procedural Patient Preparation :
Strategies for reducing intra operative allogenic blood transfusion consists of :

  • - Blood management protocols
  • - Reversal of anticoagulation
  • - Prophylactic anti fibrinolyties for excessive blood loss.
  • - Acute normovolaemic haemodilution(ANH)

Multimodal protocols consist of predetermined "bundle" of interventions to reduce blood loss and transfusion requirements.

Algorithms are intended to identify decision points or pathways during procedure.

Haemoglobin criteria of less than 8g/dL and haematocrit value of less than 25% are typically reported as restrictive transfusion. In restrictive transfusion strategies, fewer blood cell transfusion are required.

Massive transfusions are implemented in cases of life threatening haemorrhage after trauma and/or during a procedure to minimize adverse effects of hypovolaemia and dilutional Coagulopathy. This requires availability of large amount of allogenic blood & blood products. Often transfusion of fresh frozen plasma (FFP) and platelets in a ratio of 1:1 is prescribed with transfusion of red cells. Studies indicate that the ratio of FFP to cells is higher after the implementation of massive transfusion.

For urgent reversal of anticoagulation from warferin preprocedural administration of prothrombin complex concentrates (PCCS) and FFP is indicated and reduces INR.

Vitamin k is administered for non-urgent reversal from warferin. Antifibrinolytics are used as prophylaxis for excessive blood loss. They reduce allogenic blood transfusion during surgical procedures with excessive bleeding. Preoperative and intra operative administration of €-aminocaproic acid is effective in reducing total perioperative blood loss, the number of patients transfused and the volume of blood transfused. There are less blood loss and low RBC transfusion requirement when prophylactic e-aminocaproic acid is administered for excessive bleeding during surgery.

Preoperative and intraoperative administration of tranexamic acid effectively reduces perioperative blood loss, the number of patients transfused and the volume of blood products transfused.

A cute normovolaemic haemodilution (ANH) is effective in reducing the volume of allogenic blood transfusion and number of patients transfused with allogenic blood for major surgeries. Combined ANH with intraoperative RBC recovery is more effective in reducing volume of allogenic blood transfusion than ANH alone in patients with high risk of excessive bleeding.

Interventions for Intraoperative and Postoperative Management of Blood Loss :
These include:

  • - Allogenic RBC transfusion
  • - Reinfusion of recovered RBC
  • - Treatment of excessive bleeding
  • - Intraoperative and postoperative monitoring.

Transfusion of allogenic RBC transfusion should consider the age of stored RBC and leukocyte reduction in it. ASA members disagree regarding the administration of blood without considering the duration of storage. They also strongly agree that to reduce complications associated with allogenic blood transfusion, leukocyte reduced blood should be used.

Intraoperative RBC recovery is effective in reducing the volume of allogenic blood transfused. Postoperative RBC recovery and reinfusion reduces the frequency of allogenic blood transfusion in patients undergoing major surgeries. Treatment of intraoperative and postoperative excessive bleeding is done by transfusion of platelets, FFP, Cryoprecipitate and pharmacological treatment. Coagulation tests are obtained before transfusion of FFP. In patients with excessive bleeding fibrinogen level should be assessed before administration of cryoprecipitate.

Pharmacological treatment of excessive bleeding is done using:

  • - Desmopressin which effectively reduces the amount of postoperative blood loss.
  • - Antifibrinolyties such as €-aminocaproic acid and tranexamic acid.
  • - Topical haemostatics like fibrin glue and thrombin get which effectively reduce blood loss and time to haemostasis.
  • - Uses of PCCs are considered in patients with excessive bleeding and increased INR.
  • - When traditional options for treating excessive bleeding due to Coagulopathy have been exhausted, administration of recombinant activated factor VII is considered.
  • - Fibrinogen concentrate is considered for treatment of excessive bleeding due to hypotibrinogenemia.

Intraoperative and postoperative monitoring is done for :

  • Blood loss
  • Vital organ perfusion
  • Anaemia
  • Coagulopathy
  • Adverse effects of transfusion.

Blood loss is monitored periodically by visual assessment of surgical field including extent of blood present, presence of micro vascular bleeding, surgical sponges, clot size and shape and volume of blood in suction canister.

Perfusion of vital organs is monitored by standard ASA monitorings. Additional monitoring include:

  • - Echocardiography
  • - Renal monitoring
  • - Cerebral monitoring

Anaemia is monitored by estimation of haemoglobin and haematocrit levels based on estimated blood loss and clinical signs.

Monitoring of Coagulopathy involves standard coagulation tests and platelet count. Additional monitoring includes tests of platelet function and viscoelastic assay (Thromboelastogram).

Adverse effects are assessed by periodic checking for-

  1. Signs of ABO incompatibility such as :
    - Hyperthermia
    - Halmoglobinuria
    - Micro vascular bleeding
  2. Signs of transfusion related lung injury such as fever, dyspnea of hypoxia.
  3. Transfusion associated circular overload characterized by:
    - Hypoxia, respiratory distress and increased peak airway pressure.
  4. Signs of bacterial contamination as:
    - Hyperthermia
    - Hypotension
  5. Signs of allergic reactions like urticaria.
  6. Signs of citrate toscicity such as hypocalcaemia.

Before initiating therapy for transfusion reactions, blood transfusion should be stopped and appropriate diagnostic testing should be ordered.

Transfusion in Paediatric Patients :
The current guidelines for paediatric blood transfusion in adults, keeping a higher transfusion threshold for children as haemoglobin levels are usually lower in normal children. Though transfusion guidelines for children and adolescents are similar to adults, neonates have special needs.

Guidelines of Paediatric Haemotherapy Committee of American Association of Blood Bank :
The committee considers that:

  • - Blood components should be the neonates' own ABO and RHD group or an compatible ABO and RHD group.
  • - For all paediatric patients blood donated from first degree relatives should be indicated.
  • - Gamma irradiated cellular products are used for preterm infants in many Countries.
  • - Frozen cellular products such as FFP and antihaemophylic factors do not need irradiation.
  • - All cellular blood products except granulocyte concentrates should be leukocyte depleted by gamma irradiation.

RBC transfusion is primarily indicated to increase oxygen carrying capacity along with control of haemorhage and restoration of tissue perfusion.

Before RBC transfusion the MABL should be estimated to avoid over transfusion.

The MABL is estimated as follows:

[ MABL = {EBV* (HO - H1) / HO}]

EBV = estimated blood volume
HO = initial or starting Haematocrit.
H1 = Lowest acceptable or target Haematocrit.

The MABL indicates the volume of red packed cells to be transfused according to desired haematocrit. Blood volume is estimated according to age.

Estimated Circulatory Volume Based on Age of Children :

AGE BLOOD VOLUME
Preterm newborn 90ml/kg
Term newborn to 3 months of age 80-90ml/kg
Over 3 months of age 70-80ml/kg
Over 2 months of age 70ml/kg

Normal Haemoglobin Concentration and Haematocrit Values Based on Age of Children :

Age Haemoglobin(g/dl) Haematocrit (%)
1-3 days 18.5 56
3-6 months 11.5 35
6 months-2 years 12.0 36
2-6 years 12.5 37
6-12 years 13.5 40

For blood transfusion, paediatric patients are divided between younger and older than 4 months on physiological basis.

Preterm and low birth weight infants along with infants younger than 4 months need special consideration of their immature haemostatic and immune system with limited capacities to tolerate thermal and metabolic alterations from transfusion.
Before ordering RBC transfusion the desired haemoglobin level should be assessed to estimate the required transfusion volume. Special care is taken to minimize the multiple units and maximize the use of each unit.

Transfusion Threshold for Infants Under 4 Months.

Causes Haemoglobin Threshold
Anaemia in first 24 hours of life 12g/dl
Cummulative blood loss in 1 week in neonates requiring ICU. 10% of blood volume
Neonates receiving ICU care 12g/dl
Acute blood loss 10% of blood volume
Chronic O2 dependency 11g/dl
Late anaemia in stable child. 7g/dl

Guidelines for RBC Transfusion in Infants Under 4 Months:

  • - Haematocrit less than 20% with low reticulocyte count.
  • - Haematocrit less than 30% in an infant on:
    a. 30% hood oxygen, oxygen via nasal mask, CPAP or IMV with a mean airway pressure less than 6cm H2O and with
    b. Signs of tachycardia or tachypnoea (Tachycardia-HR more than 180beats/min for 24 hours. Tachypnoea-RP more than 80 breaths/min)
    c. Signs of apnoea or bradycardia. (A pnoea- more than 6 episodes in 12hrs. or 2 episodes in 24hrs. requiring bag-mask ventilation while receiving xanthenes)
    d. Low weight gain (gain of less than 10g/day observed over 4 days while receiving more than 100kcal/kg/day)

  • - Haematocrit less than 35% in an infant on:
    a. More than 35% hood oxygen.
    b. CPAP or IMV with a mean airway pressure between 6-8cmH2O.

  • - Haematocrit less than 45% in an infant :
    a. With congenital heart disease
    b. On ECMO.

Guidelines for RBC Transfusion in Children and Adolescents :

  • - Acute blood loss more than 25% of blood volume.
  • - Haemoglobin level below 8g/dl inperioperative period and below 13g/dl associated with cardiopulmonary disease.
  • - Symptomatic chromic anaemia or bone marrow failure.
  • - Severe chronic anaemia with haemoglobin level less than 7g/dl.
  • - Hypovolaemia not responding to other treatment.
  • - Preparative haemoglobin less than 12g/dl with severe cardiopulmonary disease.
  • - Post operative anaemia with haemoglobin less than 10g/dl

RBC transfusions though life saving is associated with complications like:

  • - Transfusion transmitted infection
  • - Haemodynamic instability
  • - Intravenous volume overload
  • - Acute haemolysis
  • - Transfusion related acute lung injury
  • - Various Immunological consequences.

Therefore RBC transfusion should only be given when true benefits are likely.

Indications for Transfusion :
For over 40 years transfusion was indicated to maintain haemoglobin concentration above 10g/dl and haematocrit level above 30%.
Over past 10 years paediatric physician became more restrictive in use of RBC.
In anaemic children, the only indication for RBC is to prevent or reverse tissue hypoxia due to inadequate circulating RBC mass.
A child's haemoglobin value though important should not be the sole deciding factor when considering RBC transfusion. Decision to transfusion must be based on an assessment of risk of anaemia versus the risk of transfusion. In addition to assessment of child's duration of anaemia must be taken into account.
The extent of trauma and surgery with probability of blood loss and co-existing conditions should also be considered.
Acute anaemia usually needs immediate medical attention. Treatment depends on severity and under lying cause.
As per restrictive criteria, in healthy children a transfusion haemoglobin threshold of 7 g/dl is appropriate. In presence of cardiac disease it may be safe to maintain haemoglobin level above 9 g/dl.

Haemoglobin Threshold for RBC Transfusion in Paediatric Age Group.
In infants less than 4 months :

Haemoglobin threshold for RBC transfusion is less than:

  • a. 7g/dl in a stable infant with late anaemia
  • b. 8g/dl for symptomatic anaemia
  • c. 10g/dl for major surgery
  • d. 10g/dl in infant with moderate cardio- pulmonary disease.
  • e. 13g/dl in infant with severe cardio- pulmonary disease.

In children :
The threshold for RBC transfusion is

  • a. Haemoglobin level less than
    1. 7g/dl for symptomatic anaemia and
    2. 9g/dL in presence of cardio-pulmonary disease

  • b. Acute blood loss more than 30% of blood volume.

In practice diagnosis of presence and degree of blood loss is quite difficult in healthy young children who can sustain a large hemorrhage with few external signs of cardiovascular compromise such as:

  • - Hypotension
  • - Cold extremeties
  • - Weak peripheral pulse
  • - Decreased capillary filling time

During active bleeding transfusion is appropriate to maintain haemoglobin above 7g/dL. In critically ill children with anaemia, transfusion is effective to control symptoms of anaemia if haemoglobin level falls below 7g/dL with an aim to maintain haemoglobin between 7-9 g/dL. A packed RBC product comprises the sedimented or centrifuged RBC from one unit of single donor whole blood and is the component of choice for replacement therapy during RBC loss from surgery or trauma.

As transfusion of allogenic cellular blood products is associated with deleterious effects from presence of residual leukocytes, these should be reduced. Specialized leak filtration or pheresis collection devices achieve a reduction of leukocyte count more than 104 fold, in final blood products.

Routine leukoreduction of RBC to less than 5*106 leukocytes/unit reduces the incidence of febrile, non-hemolytic reactions and alloimmunization to human histocompatibility antigens in transfusion dependent children. It is also effective in preventing CMV transfusion in neonates.

The long term use of leukoreduced RBCs in children and neonates' undergoing surgery for malignancy is evidence supported. The use of CMV seronegative leukoreduced products is recommended in:

  • - Children undergoing haemopoietic stem cell transplants.
  • - Infants of CMV-seronegative mothers
  • - Children with immune-deficiencies.

Washing of RBC is indicated only in the event of allergic or anaphylactic transfusion reactions to allogenic plasma proteins. Washing a unit of RBC with sterile normal saline removes all plasma proteins, electrolytes and antibodies.

As the extracellular Kt concentration increases with duration of RBC storage, small infants may require saline washed RBC if fresh RBCs are not available for rapid or large transfusion (more than 20ml/kg) such as during exchange transfusion or ECMO procedures. Transfusion over 25ml/kg or more than one volume of RBC in 24 hours need careful attention for :

  • - Cardiovascular instability
  • - Dilutional Coagulopathy
  • - Metabolic and thermal disturbances.
  • - In massive transfusion citrate binds to ionized ca++ causing hypocalcaemia.

Rapid RBC transfusion containing high concentration of extracellular K+, results cardiac disturbances in small children.

Hypothermia is a concern when rapid transfusion is needed.

Varieties of additive solution have evolved with well developed storage systems improving safety and effectiveness of RBC transfusion. Small stored in an extended storage preservative solution with haematocrit of 55-60%. RBC components centrifuged before transfusion have improved volume and RBC mass attaining a uniformly packed RBC concentrates with haematocrit of 80-90%.

Considerations in Neonates :
Anaemia in infants may be physiological or non- physiological.
A physiological drop in haemoglobin occurs during the first several weeks or mouths of life. In healthy term infants the lowest value rarely falls below 9g/dL. This occurs at the age of 10- 12 weeks, remains stable for several weeks and then increases progressively. It is asymptomatic and does not require transfusion. The decline in haemoglobin is more pronounced and occur earlier in premature infants.

In sick preterm infants anaemia of prematurity can be exacerbated by non-physiological anaemia, the most common of which is blood loss related to repeat laboratory testing. The optimum haemoglobin for neonates facing major surgery is not established but it seems reasonable to maintain haemoglobin above 10g/dL, because of limited ability of neonate’s heart, lungs and vasculature to compensate for anaemia.

Anaemia is defined as the reduction in RBC mass or haemoglobin concentration that results in decreased oxygen carrying capacity. Infants with chronic anaemia are well compensated having only tachycardia.

In acute anaemia the heart responses to tissue hypoxia by increasing cardiac output which is matched by decreased systemic vascular resistance and decreased blood viscosity without increase in blood pressure.

In neonates cardiac output depends on heart rate rather than stoke volume. Hence tachycardia if prolonged may compromise cardiac output.

Increased oxygen extraction from anaemic blood by tissues produces increased concentration of deoxyhaemoglobin in RBC, stimulating production of 2, 3, DPG which shifts oxygen dissociation curve to right decreasing affinity of oxygen for haemoglobin resulting better oxygen delivery to tissues. In case of more gradual onset, the blood volume, size of vascular bed and rate of production of RBC increase, resulting mild to moderate anaemia, without significant symptoms. Severe anaemia is detrimental to sick children causing shock and haemodynamic compromise.

Need for Intraoperative Transfusion Depends on :

  • - Rapidity and amount of blood loss
  • - Assessment of blood volume
  • - Preoperative Haematocrit
  • - Medical conditions like cardiopulmonary disease.
  • - Nature of surgery
  • - Risk benefit ratio of transfusion.

Intraoperative Monitoring Based on Expected Blood Loss :

Expected Blood Loss Monitoring / Action Required
Less than 30% of circulating blood volume. Routine monitoring.
30-50% of circulating blood volume. Additional urine output monitoring, two venous line done.
50-100% of circulating blood volume. Additional Central venous lines, Arterial line, rapid transfusion equipments.
Massive blood transfusion expected. Arterial blood gases, Metabolic and Coagulation monitoring, Hypothermia prevented, in addition to above monitoring.

Conclusion :
The current guidelines for paediatric blood transfusion are mainly based on available information regarding transfusion in adults, except that the transfusion thresholds are kept higher in children.

Though guidelines are similar to adults in children and adolescents, neonates have special needs. Additional information are needed to better define the guidelines for children.

Transfusion decision in children should be based on child's physical status, associated co- morbidities, presence of bleeding, risks of anaemia versus transfusion and not only on haemoglobin level.

Before RBC transfusion MABL should be estimated to know the volume of red packed cells to be transfused, avoiding over transfusion.

During active bleeding transfusion is appropriate to maintain haemoglobin above 7g/dL. Restrictive strategy For RBC transfusion with haemoglobin less that 7g/dL is equally effective as liberal transfusion strategy with haemoglobin less than 10g/dL.

A symptomatic transfusion strategy is as effective as or superior to haemoglobin based transfusion strategy.

Despite significant improvement in blood testing and handling, there remains infections or non- infections risks associated with allogenic blood transfusion. Incidence of adverse effects is greater in children specially infants with long term repercussion.

Antifibrinolyties are used as prophylaxis for excessive blood loss and to reduce allogenic blood transfusion in children undergoing procedures with excessive blood loss.
Acute normovolaemic haemodilution is effective in reducing the volume of allogenic blood transfusion and member of children transfused with allogenic blood during procedures associated with excessive bleeding.
Blood conservation modalities can be used safely in paediatric patients.
Paediatric transfusion medicine is evolving and intense research into manufacture of red cells are ongoing of promissing.

References
  1. Bharadwaj A. Khadelwal M and Bhargava sk. Preoperative neonatal and Paediatric blood transfusion. Ind J Anaesth. 2014; 58(5) : 652-657.

  2. Roganovic J. Transfusion in the critically ill Pediatric Patient. Pediatric Health, 2010; 4(2): 201-208.

  3. Lavoie J. Blood transfusion risks and alternative strategies in Pediatric patients. Pediatric Anesthesia, 2010, 21:14-24.

  4. Updated report by ASATF. Practice guidelines for preoperative blood management. Anesthesiology. 2015;122(2):1-35.

  5. Krishnan BS, Vinodh MP and Sriram N. Guidelines for Blood and Blood product Transfusion in Paediatrics in: Rebecca Jacob ed. Understanding Paediatric Anaesthesia, 2nded, Bl Publications Pvt. Ltd. New Delhi 2008;81-86.

  6. Ronald D. Miller. Transfusion Therapy. In: Miller's Anaesthesia, 7th Ed, Churchil Livingstone Pheladelphia, 2010; 1739-1766.

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