Consultant in Haematology and Transfusion Medicine Massive Transfusion Dr. Dupe Elebute MRCP, MRCPath, MD Consultant in Haematology and Transfusion Medicine

Massive Blood Loss Definitions: Loss of one blood volume within 24 hour period 50% blood volume loss within 3 hours Rate of blood loss  150ml/min Any blood loss >2L (SGH)

Presentation Medical emergency Usually occurs in A&E, operating theatre or obstetric department High morbidity & mortality from: Underlying cause of haemorrhage Pre-existing disease (liver, renal) Complications of massive blood transfusion

SGH: Massive Transfusion by specialty TRAUMA CARDIO THORACIC 9.5% 26% OBSTETRIC 24% ANEURYSM 7.1% SURGICAL GI BLEED 9.5% 24%

Complications of Massive Tx Circulatory overload/ARDS Hypothermia  Acidosis Hyperkalaemia Rare Exacerbated by keeping blood at RT for long periods Increased risk with -irradiated blood

Complications of Massive Tx (2) Citrate toxicity  hypocalcaemia Massive transfusion with whole blood or FFP Massive transfusion in newborn infants Depletion of platelets, coagulation factors Other transfusion reactions (infections!)

Haemostatic complications Replacement of TBV in short period of time Thrombocytopenia Dilution effect Increased consumption Results in microvascular bleeding when <50x109/L Coagulation Factors Deficient in red cell concentrates

Massive Blood Loss:A Vicious Cycle Haemorrhage Dilution of clotting factors/DIC; thrombocytopenia Massive Blood Transfusion

Management Resuscitation rapid infusion of crystalloid; maintain blood volume Optimise oxygen carrying capacity maintain PCV>0.20 Maintain haemostasis platelet count (>50 x 109/l), coagulation factors Correct or avoid metabolic disturbances

Management (2) Monitor Blood component therapy FBC, clotting screen U & Es including Calcium, arterial pH ECG, CXR Blood component therapy effective communication between clinicians, lab staff urgent review of results

Red Cells ‘Flying squad’ – O RhNeg CMV neg If >30-40% of blood volume lost In extreme situations: Group O un-crossmatched red cells ORh (D) Neg for pre-menopausal women ORh (D) Pos for men, post menopausal women ‘Flying squad’ – O RhNeg CMV neg

Platelets Essential to keep platelets >50x109/l Higher target of 100x109/l for: Multiple high-energy trauma Central nervous system injury Prophylactic use in platelet dysfunction e.g. CABG

Coagulation Factors FFP Cryoprecipitate Provides replacement for most coagulation factors Essential to give adequate volume Dose: 12-15ml/kg Cryoprecipitate For treatment of DIC Required if Fibrinogen <1.0 g/L

Code Red Procedure Inform blood bank: ‘Code Red!!!’ If ‘flying squad’ blood used Send 2 group & X-match samples Transfusion Nurse/SpR informed

Code Red: blood components First stage: 6 units blood 1 litre FFP 2 pools platelets Second Stage: 10 units cryo if fibrinogen <0.8g/l 2 pools platelets if count <100 x 109/L Send blood for repeat FBC, coag, chemistry

Adjunctive therapy Tranexamic acid, Aprotinin have been shown to reduce transfusion requirements in CABG Desmopressin (DDAVP) and aprotinin can reduce antiplatelet effect of Aspirin Coagulation factors: Prothrombin Complex Concentrate (Beriplex) Fibrinogen concentrate Factor VIIa (NovoSeven)

Recombinant FVIIa : NovoSeven® Mode of Action Tissue factor (TF)/FVIIa, is necessary to initiate haemostasis rFVIIa directly activates FX on the surface of activated platelets This activation initiates the ”thrombin burst” independently of FVIII and FIX This step is independent of TF The “thrombin burst” leads to formation of a stable clot

Novoseven Recombinant human factor VIIa Activates extrinsic pathway Licensed for: Congenital/acquired haemophilia Factor VII deficiency Glanzmann’s thrombasthenia

Role in non-haemophilia patients? Anecdotal reports: Control of haemorrhage in traumatic and post-surgical bleeding Controlled trials Prophylaxis prior to elective surgery (prostatectomy) Treatment of intracranial haemorrhage

NovoSeven Audit 18 ‘non-haemophilia’ patients on database 12/16 under surgical speciality Increasing use over 12 months by cardiothoracic and vascular surgery 67 vials used in total 2 patients given novoseven twice – neither survived!

NovoSeven audit: outcome 7/16 patients survived to discharge Survival unrelated to age or sex Trend of improved survival when used in patients with haemorrhage complicating a procedure Marked reduction in blood product support BUT at a cost…

NovoSeven Audit:Cost Analysis Dose: 90g/kg 1.2 units = £820 (inc VAT) Total units of Novoseven : 147 Average units per patient: 9 Total cost of Novoseven: £119,326 Average cost per patient: £7458

SGH Blood components Projected spend £3.5 million Platelets £198.76 Red cells £120.22   Cryoprecipitate £35.62 FFP £30.89

Alternatives to allogeneic blood transfusion

Autologous pre-deposit Useful in elective surgery for fit patients Maximum of 4 units Requires sufficient time prior to surgery for collection (done by NBS) begins 3-5 weeks pre-op; last unit >72hours pre-op Does not remove all potential hazards infections: no different from allogeneic blood getting the wrong blood!

Acute Normovolaemic Haemodilution Elective or emergency surgery where blood loss is > 1L Whole blood removed by anaesthetist 1.0-1.5 litres (up to 3 units) can be collected Replaced with crystalloid/colloid Clearly labelled pack with anticoagulant “UNTESTED BLOOD: FOR AUTOLOGOUS USE ONLY” Blood must remain with the patient until re-infused Re-infused during procedure or immediately post-op

Intra-operative Blood Salvage Shed blood from operative field is collected Blood is anticoagulated with citrate or heparin Filtered to remove debris/clots Suitable for cardiac surgery and trauma C/I in contaminated operative fields and malignancy

Postoperative Blood Salvage Blood from wound drains collected and re-infused using special equipment Proven to reduce blood transfusion post hip, knee replacement surgery Cheap, managed by nurses

Erythropoietin Genetically engineered Synthetic form; s/c or iv Suitable for: Renal patients Patients with multiple red cell abs JW patients Can be used to boost pre-deposit

Intravenous iron Improves bioavailability Rapidly increases stores Avoids potential gastric irritation and malabsorption May improve response to EpO