Transfusion in massive haemorrhage in Neonates & Paediatrics (birth - 16years)

NB: Page 11 should be printed and displayed in relevant clinical areas.

• Summary
• Aims
• Background
• Diagnosis
• Investigation
• Treatment/Management
• De-briefing
• Appendix 1 - Tranexamic Acid^5,6
• Appendix 2 - Risks of massive transfusion

Summary

In line with recent evidence on the benefits of using a higher plasma to red cell transfusion ratio in adults with massive haemorrhage, these guidelines extend this concept to neonatal and paediatric patients.

NB: It is not appropriate to use this guideline for the treatment of meningococcal sepsis or for treatment of controlled bleeding or correction of anaemia.

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Aims

To improve outcome in neonatal and paediatric patients with massive haemorrhage through the use of appropriate and timely blood component transfusion.

To optimise blood component use and minimise wastage of blood components.

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Background

This document must be used in conjunction with the:
LTHT Policy on Safer Transfusion and the Policy for the use of written informed consent for transfusion of blood and blood components

Complications of major blood loss and massive transfusion may jeopardise the survival of patients from many different specialities, and challenge haematological and blood transfusion resources.

An accumulating body of evidence and expert opinion supports earlier use of blood components in the resuscitation of patients with massive haemorrhage. Red blood cells and fresh frozen plasma (FFP) should be given in a ratio of 1:1(1 dose:1 dose)^1,2,3,4 Platelets and cryoprecipitate are also necessary following large volume blood component resuscitation. It is vital that scarce blood component resources are used appropriately.

To improve confidence and maintain best practice when managing massive haemorrhage and to comply with NPSA SPN RRR017 which stipulates teams hold regular (at least annually) ‘dry-runs’ / ‘drills’ to practice individual team member roles in a massive haemorrhage scenario and to ensure a cohesive team approach in managing patient care.

A member of the clinical team should be nominated to act as co-ordinator responsible for overall organisation, liaison, communication and documentation during a massive haemorrhage episode. This is a critical role for a designated member of the permanent clinical staff.

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Diagnosis

The massive haemorrhage guideline for neonatal & paediatric patients (birth -16 years) should be activated when:

There is active massive haemorrhage as defined by any of:

• a loss of one blood volume (80ml/kg) within a 24-hr period or,
• 50% blood volume loss (40ml/kg) within 3 hrs or,
• a rate of blood loss of 2 – 3ml / kg per minute

Or, signs of continuing shock following 40ml/kg crystalloid and/or colloid resuscitation for acute haemorrhage

A consultant with experience in the management of massive haemorrhage authorises activation of the guideline – usually a surgeon, anaesthetist, intensivist, neonatologist or A&E consultant.

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Investigation

This guideline does not cover the investigation of the source of the bleeding but assumes that all appropriate measures to identify and stop the bleeding are ongoing.

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Treatment / Management

This guideline does not cover the management of bleeding in neonates or paediatrics per se but rather the appropriate use of blood components for the resuscitation of patients experiencing massive haemorrhage. The guideline assumes that all necessary measures to identify and control bleeding sites are on-going. Furthermore, effort must be directed at preventing hypothermia by the use of fluid warmers and external warming devices (e.g. Bair hugger or overhead warmer).

In event of massive haemorrhage:

Red cells: FFP (Fresh Frozen Plasma) should be administered on a 1:1 ratio i.e. 1 dose:1 dose
(20 ml/kg Red Cells to 20 ml/kg FFP
Requests should be the total volume in mls required rather than units.

1. Call blood bank LGI: x23398. SJUH: x65559
   • State that the request is to initiate the “neonatal / paediatric massive haemorrhage”, urgency of request
   • Provide the patients full name, ID (NHS) number and Date of birth of patient & location
   • Request blood components by volume. The initial request will be for red cells 20ml / kg & Fresh Frozen Plasma 20ml / kg - you will need to calculate the volume to request e.g. for a 10kg child “I need 200ml red cells and 200ml FFP Blood bank will not calculate blood volumes.
   • Avoid any further calls to blood bank unless the situation changes.
2. Ensure that the patient is wearing a CORRECTLY LABELLED patient ID wristband.
   • Inpatient wristbands must have NHS number, first name, surname and date of birth
   • Accident and emergency wristbands must be labelled according to the unknown patient labelling system which consists of 3 identifiers for the unknown patient.
   • If the patient does not have a wristband, they cannot receive a transfusion
3. Ensure that the laboratory receive a correctly labelled transfusion sample
   • Samples must be labelled with the core identifiers that match with those on the patient’s wristband.
   • Children >4months old a minimum of 2mls of blood in a 6ml EDTA sample tube
   • Children less than 4months old, a 1-2 ml EDTA sample
     • Initially check with the blood bank laboratory staff if a maternal sample is required. Please provide the laboratory staff with the maternal core identifiers to enable the laboratory staff to check the details on the laboratory system
     • If a maternal sample is required, please send a correctly labelled sample to the appropriate blood bank immediately
     • If a maternal sample cannot be obtained or there is not enough time to wait for the laboratory to process the maternal sample please ensure that at least 2ml EDTA sample of baby’s blood is taken.

   Samples should be taken to Blood Bank on A-Floor of Jubilee Wing or, Blood Bank on Level Zero of Bexley Wing by hand as this is the fastest route and allows immediate confirmation that the sample is acceptable.

4. Samples for FBC, clotting screen and U&E and should be obtained from the patient and taken to LGI Blood Sciences Lab School or SJUH main Pathology laboratory. Send by Airtube or hand deliver.
5. On receipt of a correctly labelled transfusion sample, group-specific red cells can be available within 20 minutes.
6. If immediate red cell transfusion is essential, use Emergency O D-negative blood (20ml/kg) from the Blood Bank, delivery suite and C floor theatres Clarendon Wing.
   Please note if emergency O D negative blood is transfused: the total number of mls/kg of O D-negative red cells must count towards the total number of mls/kg red cells given in the first instance to maintain the 1 dose:1 dose ratio.
   Once the decision to activate the massive transfusion in neonates / paediatrics protocol has been taken, aim to avoid using additional crystalloid or colloid unless the patient is in shock
   
   NB: SJUH: Remember to call for porters at the beginning of the emergency if you require them to collect / deliver samples or blood components, OR you may need to consider nominating a departmental member of staff to act as ‘runner’ who is trained and competent to collect blood.
   LGI: Blood Bank will automatically arrange for porters to collect / deliver urgent blood components
   
   
7. Give red cells and FFP in a 1:1 ratio i.e. 1 dose:1 dose1. Administer red cells 20 ml / kg & FFP 20ml / kg. In a controlled situation, the rate of transfusion can be over minutes, depending on clinical picture. Administer FFP alongside red cells using separate IV access.
8. Intravenous Tranexamic acid must be administered following completion of initial resuscitation with red cells and fresh frozen plasma. The Tranexamic acid must be administered within 3 hours of the start of haemorrhage5. then further doses every 8 hours as necessary. The infusion is given over 10 minutes. The dose depends on age & weight of the child. Intravenous phytomenadione (vitamin K) should be administered to help prevent coagulopathy, dose depends on age/weight of the child. Please refer to appendix 1 for further guidance
9. After each transfusion of 20ml / kg of red cells, ionised hypocalcaemia may occur, especially if there is liver synthetic dysfunction due to the large citrate load from anticoagulated blood components. This may interfere with coagulation and have other adverse metabolic consequences. Ionised calcium can be reliably measured on a blood gas machine. This must be corrected by intravenous infusion of calcium gluconate. See appendix 1 for recommended dose of calcium gluconate, this dose should be followed by repeat of the assay. (See appendix 2 for further risks of transfusion).
10. After one 80ml / kg total volume (crystalloid/ colloid/ red cells/ FFP/ or, 20 ml / kg red cells has been given AND there is still evidence of continuing haemorrhage, the senior clinician must decide whether further transfusion is required. Contact blood bank as soon as this decision is made and request components outlined below in point 11.
11. After initial resuscitation, platelets and cryoprecipitate must be considered if active bleeding persists. Appropriate aliquots to be transfused are as follows1:
    • RBCs 20 ml/kg aliquots (maximum 4 adult units), O D-negative or ABO and D-specific (ideally, cross-matched)
    • FFP in 20 ml/kg aliquots (maximum 4 adult units)
    • Platelets in 15 ml/kg aliquots (maximum 1 adult therapeutic dose) to be considered after every 40 mL/kg RBCs
    • Cryoprecipitate 10 ml/kg (maximum 1 adult therapeutic dose)
    
    These aliquots should be repeated in recommended 1:1(i.e. 20 ml/kg Red Cells to 20 ml/kg FFP to 15ml/kg Platelets to 10ml/kg Cryoprecipitate) ratio as necessary until bleeding is controlled. Once laboratory parameters are available ratios should be modified accordingly.

The therapeutic aims should be:

• Hb 80 g/L
• Fibrinogen >1.5 g/L
• PT ratio <1.5
• Platelets >75 x 10⁹/L.

Careful monitoring for adequacy of resuscitation and for circulatory overload is essential.

In order to prevent over-transfusion of blood components all prescriptions should be ordered and prescribed in millilitres rather than units. The maximum prescribed volume should not be greater than the volume for equivalent adult transfusions.

12. Details of the patients receiving any emergency O D-negative Red Blood Cells (RBC) used must be communicated to Blood Bank as soon as possible to ensure that the O D-negative units are replaced.
13. Any unused blood components MUST be returned to blood bank immediately
14. All red cells received in areas with a satellite blood fridge must be scanned into the blood fridge. If blood arrives in a cool box it should be kept in the cool box in which it arrives for up to the maximum length of time stated on the transport slip. Each blood unit should be removed and used one at a time, between each removal ensure the lid is securely positioned on the cool box at all times. Platelets, FFP, cryoprecipitate MUST NOT be stored in a cool box or fridge. Please note one exception to this rule is that FFP can be stored in A+E fridge at the LGI site due to being the Trauma centre. See Safer Transfusion Policy.
15. All blood components must be recorded on a transfusion authorisation chart and fated (for “traceability”) using the BloodTrack system or by signing and sending the manila tag attached to each blood component to the issuing blood bank. See Safer Transfusion Policy
16. Patients on warfarin with significant bleeding should be given 25 international units / kg of intravenous Octaplex (requested on the Octaplex request form:
    http://lthweb/sites/hospital-transfusion-team/how-to-order-blood-and-blood-products/how-to-order-blood-and-blood-products) - see appendix 1 and assuming they do not have an absolute contraindication to reversal. Do not wait for an INR result before giving the Octaplex. Remember that Octaplex has a short half life (4-6 hours)
17. Successful patient outcome requires prompt action and good communication between clinical specialties, diagnostic laboratories and blood bank staff
18. All activations of the massive transfusion protocol in neonates and paediatrics must be reviewed as part of the departmental clinical governance procedure. See below re: de-briefing.
19. In a life-threatening massive haemorrhage do not wait to obtain written consent for use of blood components. Good practice is to gain verbal consent at the earliest opportunity. If the parents/guardians have specifically objected to use of blood components (e.g. on religious grounds) then you must act in what you consider to be the best interests of the patient. See Written Informed Consent for Transfusion Policy
20. OctaplasLG ® is a solvent detergent treated virally inactivated blood group specific pooled plasma product. OctaplasLG® is administered in the same way as FFP - clearly state OctaplasLG® on the blood authorisation chart.
    • The decision to transfuse OctaplasLG® rather than FFP is made by the clinical team treating the patient. The decision must be communicated to the laboratory staff.

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De-briefing

It is recommended that the clinical areas involved hold a joint ‘de-brief’/audit after each massive haemorrhage case to establish any learning points and/or if any changes in practice are required to improve the outcome in future massive haemorrhage situations. The de-brief should be initiated by the Consultant in charge and/or the Hospital Transfusion Team. Feedback on any lessons learned will be circulated to relevant stakeholders by the Consultant in charge and/or the Hospital Transfusion Team.

The de-brief group should consist of all key stakeholders including representation from the Hospital Transfusion Team and Transfusion lab to enable a full and
robust analysis of the approach to the massive haemorrhage case.

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Appendix 1 - Tranexamic Acid^5,6

Loading Dose – 15mg/kg (max 1g) diluted in a convenient volume of Sodium Chloride 0.9% or Glucose 5% and given over 10 minutes

Maintenance infusion: 2mg/kg/hour. Suggested dilution 500mg in 500ml of sodium chloride 0.9% or glucose 5% given at a rate of 2mls/kg/hour for at least 8 hours. The infusion should be stopped if investigations show that no significant bleeding has occurred.

MAXIMUM infusion dose of 1g

Contraindications:

Relative (assess risk vs benefit on an individual patient basis). If there is a realistic suspicion of significant bleeding the benefits will most likely outweigh the risks.

• Patients with previous deep vein thrombosis (DVT), pulmonary embolism (PE) or arterial thrombosis
• History of convulsions
• Patients with indwelling cardiac stent
• Severe renal impairment due to risk of accumulation -the risk of accumulation even in severe renal impairment is very slight (see National Poisons Information Service Toxbase).

Absolute

• Hypersensitivity to tranexamic acid or any of the ingredients
• Greater than 3 hours between time of injury and initial bolus dose

Tranexamic acid is associated with an increased risk of thrombosis. However in the CRASH 2 study the treatment group had a lower incidence of thrombotic events. The risks are felt to be very small.

Calcium Gluconate: by slow intravenous injection over 5-10 minutes.

Neonate (less than 1 month): 0.11 mmol / kg (0.5mL/kg of calcium gluconate 10%)

Aged 1 month – 16 years: 0.11 mmol / kg (0.5mL/kg of calcium gluconate 10%) - - maximum dose of 4.5 mmols (20mL of 10% calcium gluconate)

Phytomenadione (Vitamin K): by slow intravenous injection

Neonate (less than 1 month): 1mg as a single dose

1month - 18 years 250-300 micrograms/kg (max 10mg) as a single dose

Octaplex (Prothrombin Complex Concentrate): by slow intravenous injection.

Dose: 25 international units / kg (requested from blood bank on an Octaplex request form).

N.B.: The only indication to use Fresh Frozen Plasma (10-20 ml/kg) to reverse warfarin is if octaplexLG® is not available.

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Appendix 2 - Risks of massive transfusion

Clinicians should be aware that there are risks associated with massive transfusion and blood component therapy; including:

• Incorrect Blood Component Transfused (IBCT)
• Transfusion Associated Circulatory Overload (TACO)
• Transfusion Related Acute Lung Injury (TRALI)
• Immune complications and acute reactions
• Hyperkalaemia due to high extracellular potassium in stored red cell units and ionised hypocalcaemia due to citrate toxicity especially if there is liver synthetic dysfunction. This may interfere with coagulation and have other adverse metabolic consequences. It cannot be diagnosed from a routine plasma calcium measurement but many modern blood gas analysers accurately measure ionised calcium, or send a blood sample to the Clinical Biochemistry laboratory for analysis. This may be corrected by slow intravenous bolus of calcium gluconate.

All suspected transfusion reactions MUST be reported to the Hospital Transfusion Team immediately to comply with MHRA investigation & reporting requirements.

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Glossary

Activated Partial Thromboplastin Time (APTT) - a laboratory test that measures the activity of clotting factors in the intrinsic pathway of coagulation. It is commonly prolonged in DIC and following dilution of normal clotting factors by massive red cell transfusion.

Disseminated intravascular coagulation (DIC) occurs when there is generalised activation of the coagulation and fibrinolytic pathways with consumption of multiple clotting factors and platelets. Common causes include sepsis and traumatic tissue injury. The laboratory profile typically includes prolongation of both the Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT), reduced plasma fibrinogen level and elevation of D-dimer (a breakdown product of fibrin clots). There is often thrombocytopenia due to consumption of platelets and evidence of red cell fragmentation on the blood film. Decompensated DIC may be associated with clinical signs of both bleeding and thrombosis in the same patient.

FFP - Fresh Frozen Plasma - obtained from normal blood donors and used as a therapeutic source of clotting factors.

Prothrombin Time (PT) - a laboratory test that measures the activity of clotting factors in the extrinsic pathway of coagulation. It is commonly used to monitor warfarin therapy and is often prolonged in liver disease and DIC and following dilution of normal clotting factors by massive red cell transfusion.

Prothrombin Time Ratio (PT Ratio) - the ratio of the patient's PT to the PT of normal plasma. It provides a measure of the degree of clotting abnormality.

Thrombocytopenia - a reduction in the peripheral blood platelet count (normally 150-400x10(9)/l). A level of 75x10(9)/l is adequate for most surgery and is the minimum target for patients requiring massive transfusion or bleeding from DIC. Requests for platelet transfusion therapy are initiated at 100x10(9)/l in patients with massive bleeding (predictable when 2 blood volumes have been replaced by red cells and plasma transfusion) as platelets have to be ordered from the Regional Blood Transfusion Centre.