Autologous Transfusion

Why use blood-sparing strategies? World’s Most Precious Liquid

Indications Patient request Difficulty in finding suitable blood Availability/Economic considerations Complications relating to blood transfusion

Complications of blood transfusion Infection Hepatitis B and C, HIV, CMV, vCJD Immunological Early: anaphylaxis, acute lung injury, alloimmunization, urticaria, acute haemolysis Delayed: delayed haemolysis, immunosuppression

Complications of blood transfusion Metabolic Hyperkalaemia, hypocalcaemia, acid– base disturbance, coagulopathy Physical Hypothermia, microemboli, air embolus, circulatory overload

Allogeneic blood-sparing strategies Pharmacological Preoperative - Erythropoietin - Ferrous sulphate, vitamin B12, folate - Discontinue drugs that may impair haemostasis Perioperative - Aprotinin - DDAVP - Tranexamic acid - Topical haemostatic agents

Erythropoietin Daily s/c inj for at least 10 days before surgery. Disadvantages of erythropoietin Expensive Labour intensive Side effects - thrombosis / hypertension. Unsuitable for emergency surgery. Restricted to patients aged less than 70 years Studies support use cardiac/ orthopaedic surgery

Optimization of haemostatic function Discontinue NSAIDs, anticoagulants Haematology advice – cong. coagulopathy Haemophilia - factor VIII conc. Liver-associated coagulopathy - vitamin K CRF - preoperative dialysis improves platelet function

Pharmacological manipulation- Periop. Evidence supporting use from studies in cardiac surgery Aprotinin - non-specific protease inhibitor /inhibits plasmin- reducing fibrinolysis - Reduces blood loss in cardiac surgery - May be associated with graft failure - Use in valve surgery is proven - Hypersensitivity reactions Tranexamic acid - synthetic antifibrinolytic drug - Minimal side effects - Effective in cardiac surgery. Desmopressin acetate (DDAVP) - analogue of vasopressin - Increases conc. of factor VIII/ von Willebrand factor - Indicated in haemophilia or vonWillebrand’s - No evidence to support use in patients without congenital bleeding disorders.

Allogeneic blood-sparing strategies Non-pharmacological Anaesthetic technique - Regional anaesthesia - Careful positioning - Controlled hypotension - Avoidance of hypertension/hypothermia Surgical technique - Planning of procedure - Minimally invasive choices - Dissecting instruments - Use of tourniquets

Surgical techniques Staging of complicated procedures or sequencing a procedure harvesting a vein by one member of a team whilst another member prepares the receiving site. Use of minimally invasive surgical techniques e.g. laparoscopic surgery or interventional radiology for embolization of aneurysms Dissecting instruments – spare blood vessels / provide haemostasis e.g monopolar diathermy knife, laser, harmonic scalpel Topical agents e.g thrombin-based sealants, fibrin- based sealants and calcium alginate - Role in reducing allogeneic transfusion is unclear Tourniquets - clearer surgical field / unlikely to contribute to blood-sparing

Allogeneic blood-sparing strategies Transfusion protocols Autologous transfusion - Preoperative donation - Acute normovolaemic haemodilution - Cell salvage

Preoperative autologous blood donation (PABD) Criteria for autologous donors (American Association of BloodBanks (AABB) Standards for Blood Banks and Transfusion Services) Candidates for preoperative collection - stable patients for surgery in which blood transfusion is likely such as orthopedic, vascular, cardiac, thoracic and radical prostatectomy Hb not less than 11 g/dL or Hct 33% No age or weight limits May donate 10.5 mL/kg Donations may be scheduled more than once a week, but the last should occur no less than 72 hours before surgery Autologous blood with positive viral markers commonly precluded

Contraindications 1. Evidence of infection and risk of bacteremia 2. Scheduled surgery to correct aortic stenosis 3. Unstable angina 4. Active seizure disorder. 5. Myocardial infarction or cerebrovascular accident within 6 months of donation 6. Patients with significant cardiac or pulmonary disease who have not yet been cleared for surgery by their treating physician 7. High-grade left main coronary artery disease 8. Cyanotic heart disease 9. Uncontrolled hypertension

Standards no longer permits allogeneic transfusion of unused autologous units ("crossover") because autologous donors are not volunteer donors

PABD Efficacy of PABD depends on the degree of patient's erythropoiesis Compensatory erythropoiesis suboptimal under "standard" conditions [expansion in RBC volume of 11% (with no oral iron supplementation) to 19% (with oral iron supplementation) ] Not sufficient to prevent anemia PABD results in perioperative anemia and an increased likelihood of any blood transfusion

PABD “Aggressive“ autologous blood phlebotomy (twice weekly for 3 weeks, beginning 25 to 35 days before surgery) endogenous erythropoietin levels increase with RBC volume expansion of 19% to 26% Exogenous erythropoietin therapy stimulates erythropoiesis (Expansion up to 50% RBC volume)

PABD Transfusion Trigger - Hb/Hct level at which autologous blood should be given - Trials indicate that even critical care patients can tolerate substantial anemia ( Hb ranges of 7 to 9 g/dL) with no apparent benefit from more aggressive transfusion

PABD Disadvantages of PABD Labour intensive-identification of suitable patients, organizing appropriately timed blood donation, storing the blood Storage life of blood (5 weeks) limits number of units that can be donated / reduces flexibility in the postponement of surgery Not suitable for emergency surgery. Clerical errors can occur at any stage of the process Not suitable for anaemic patients / ischaemic heart disease

Acute normovolaemic haemodilution (ANH) Principle Removal of whole blood from a patient, while restoring the circulating blood volume with an acellular fluid shortly before an anticipated significant surgical blood loss Blood collected in standard blood bags containing anticoagulant Stored at room temperature Reinfused during surgery after major blood loss has ceased, or sooner Simultaneous inf. of crystalloid (3: 1 ) or colloid (1:1) Blood reinfused in the reverse order of collection Augmented hemodilution (replacement of ANH collected in part by synthetic oxygen carriers)

V = EBV. Hi – Hf / Hav Physiological consequences - Increased cardiac output - Decreased viscosity

Criteria for selection High likelihood of transfusion Hb > 12 No significant ds. Absence of severe hypertension Absence of infection

ANH Advantages of ANH Reduction in the RBC mass lost for a given blood loss Perceived lower relative cost compared with PABD or allogeneic blood transfusion Almost negligible potential for clerical error because blood is kept in the operating theatre until transfusion Infectious and immunological complications associated with allogeneic blood are avoided Platelet function and coagulation factors are preserved Theoretically improved tissue oxygen delivery due to right shift of oxygen dissociation curve and reduced viscosity.

Acute normovolaemic haemodilution (ANH) Disadvantages of ANH Greater haemodynamic instability Hypovolaemia is more likely Potential complications of administration of large volumes ofcrystalloid. Useful only in healthy adults having surgery with substantial anticipated blood loss, who have a high preoperative haemoglobin and who can tolerate low intraoperative haemoglobin

Intraoperative cell salvage Physics of cell saver Technique based on centrifugation, separating red blood cells (RBC) from the lighter components and fluids, including plasma, saline and buffy coat System filled with ml heparinized saline (“priming”) Blood released at the wound site aspirated via a double-lumen suction catheter ( mmHg) Anticoagulated stored in a reservoir with a filter pumped into a rotating separation chamber washed with ml saline and concentrated

Intraoperative cell salvage Optimising red cell return - Suction - Rinsing of sponges - Anticoagulant - Collection reservoir

Intraoperative cell salvage Calculation of blood loss during cell salvage [Hs/Hp]. Vb. Nb / SE

Intraoperative cell salvage Advantages of cell salvage Suitable for elective and emergency surgery. Reduced risk of administration of incorrect blood Reduced use of allogeneic blood Disadvantages of cell salvage No preservation of clotting factors or platelets necessary. Initial financial outlay to buy the machine and train staff (but the cost of the disposables is less than the cost of one unit of blood) Use in malignancy is controversial Blood salvaged from contaminated fields is unsuitable for re- infusion.

Factor VIIa central role in initiating the process of coagulation Active after forming complex with tissue factor Activates factors IX and X Induction of thrombin burst on surface of activated platelets Formation of fibrin clots at the site of vascular injury Fibrin clots are stable / resistant to premature lysis The use of for treatment of intractable life- threatening haemorrhage is

Recombinant factor VIIa (rFVIIa ) FDA-approved – - Hemophiliacs with factor VIII or IX inhibitors - Factor VII deficiency Novel therapy for the treatment of acquired coagulopathies - severe trauma - intractable bleeding after pelvic surgery - life-threatening post-partum haemorrhage - pulmonary haemorrhage - correction of coagulopathy in neurosurgical patients - Jehovah's Witness after cardiac surgery Other uses of rFVIIa - severe thrombocytopenia - platelet function disorders - impaired liver function

rFVIIa Bolus dose - 90–120 mg kg1 used with caution in - patients with known hypercoagulability - DIC or other states of generalized activation of the hemostatic system