BLOOD TRANSFUSION THERAPY

1. BLOOD TRANSFUSION THERAPY PRESENTED BY-DR.NITIN SHANKER MODERATOR-DR.B.KAUR www.anaesthesia.co.inanaesthesia.co.in@gmail.com

2. BENEFITS • Enhanced oxygen carrying capacity • Improved homeostasis with blood component therapy • Volume support of Cardiac output

3. BLOOD COMPONENT THERAPY • Whole blood • Packed Red Blood Cell • Leukoreduced Red Blood Cell • Fresh Frozen Plasma • Cryoprecipitate • Platelet concentrate • Prothrombin Complex • Single Donor Plasma

4. PACKED RED BLOOD CELL • Contain same amount of Haemoglobin as whole blood, but much of plasma has been removed. • Haematocrit 70%,whereas whole blood 40% • Reconstituted with 5% Dextrose,0.4% saline,5% Dextrose in 0.9% saline,0.9% saline and Normosol-R with a ph of 7.4.

5. STORAGE OF BLOOD • Citrate phosphate Dextrose Adenine (CPDA-1) anticoagulant preservative in which Blood stored at 1 degree celsius-6 degree celsius • Addition of Adenine to CPD solution allows RBC to synthesize ATP and extend storage time from 21 days to 45 days. • Shelf life can be further extended to 42 days AS-1(Adsol),AS-3(Nutricel) or AS-5(Optisol)

6. INDICATION FOR TRANSFUSION The Practice Guidelines for Blood Component Therapy developed by the American society of Anaesthesiologists (ASA) state that “red blood cell transfusion is rarely indicated when the hemoglobin concentration is greater than 10 g/dl and is almost always indicated when it is less than 6 g/dl”

7. COMPENSATORY MECHANISMS DURING ANEMIA • Increased Cardiac output • Redistribution of Cardiac output • Increased Oxygen extraction • Changes in Oxygen-Hemoglobin affinity

8. COMPARISON OF WHOLE BLOOD AND PACKED RED BLOOD CELL

9. CONDITIONS THAT MAY DECREASE RBC TRANSFUSION THRESHOLD • Impaired oxygenation • Pulmonary disease • High altitude • Increased oxygen demand • Hyperthermia • Hyperthyroidism • Sepsis • Pregnancy

10. Contd….. • Limited ability to increase Cardiac Output • Coronary artery disease • Myocardial dysfunction • β-AdenergicBloackade • Inability to redistribute cardiac output • Low SVR states • Occlusive vascular disease • Left shift of Oxygen-Haemoglobin curve

11. Contd…. • Abnormal Haemoglobins • Presence of recently transfused Hb (decreased 2,3-DPG) • Hb S (sickle cell disease) • Acute Anemia (limited 2,3-DPG compensation) • Ongoing or imminent blood loss • Traumatic/surgical bleeding • Placenta previa or accreta,abruption,uterineatony • Clinical coagulopathy

12. PLATELET CONCENTRATES • Prepared by differential centrifugation of whole blood or by plateletpheresis techniques. • Stored at room temperature;satisfactorily kept for 7 days. • Platelet concentrate transfusion,third leading cause of transfusion-related deaths (following sepsis). • One unit of platelet concentrate will increase platelet count of a 70-kg recepient by 5000-10,000/µL;Oneapheresis unit →30,000-60,000/µL

13. INDICATIONS FOR TRANSFUSION American Society of Anesthesiologists (ASA) Task force recommendations: • Prophylatic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (eg.idiopathicthrombocyticpurpura) • Prophylatic platelet transfusion rarely indicated in surgical patients with thrombocytopenia due to decreased platelet production when platelet count >1,00,000 and usually indicated when platelet count > 50,000

14. INDICATIONS FOR TRANSFUSION contd…. • Surgical and obstretic patients with microvascular bleeding usually require platelet transfusion if platelet count >1,00,000 and usually indicated platelet count <50,000;Therapy to be based upon patients bleeding risk. • Vaginal deliveries or operative procedures ordinarily associated with insignifcant blood loss maybe undertaken in patients with platelet count <50,000. • Platelet transfusion maybe indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding.

15. FRESH FROZEN PLASMA • Contains all plasma proteins particularly factors ν and νιιι • ASA task force recommended the administration of FFP with the following guidelines: • For urgent reversal of Warfarintherapy;dosage 5-8ml/kg • For correction of known coagualation factor deficiencies for which specific correlates are unavailaible

16. FRESH FROZEN PLASMA contd.. • For correction of microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than 1 blood volume and when prothrombin and partial thromboplastin time cannot be obtained in a timely fashion. • Calculated to achieve a minimum of 30% plasma factor;dosage 10-15 ml/kg. • Contraindicated for augmentation of plasma volume or albumin concentration.

17. INDICATIONS FOR FFP ADMINISTRATION • Replacement of isolated factor deficiencies • Reversal of Warfarin effect • Antithrombinιιι deficiency • Treatment of immunodeficiencies • Treatment of thrombotic thrombocytopenic purpura • Massive blood transfusion(when factors ν and νιιι < 25% normal) • Requirements of above points if PT atleast 1.5 times longer than normal

18. CRYOPRECIPITATE • Precipitate that remains when FFP thawed slowly at 4 degree celsius • Primarily contains factor νιιι and fibrinogen;also has Von Willebrand factor and fibronectin • All other plasma proteins in trace • Used in Haemophillia A and fibrinogen deficiency treatment.

19. CRYOPRECIPITATE contd…. • ABO compatibility not must. • Administered within 6 hours after thawing. • One unit increases fibrinogen levels by 5-7 mg/dL

20. COMPLICTIONS OF BLOOD TRANSFUSION • Development of various infections • Transfusion associated reactions(Hemolytic transfusion reaction) • Transfusion related lung injury • Left shift of oxygen dissociation curve • Coagulopathy noticed with massive transfusions

21. COMPLICATIONS OF BLOOD TRANSFUSION contd…. • Dilutional Thrombocytopenia • Low levels of factor ν and νιιι • Disseminated Intravascular Coagulation like syndrome • Citrate Intoxication and Hyperkalemia • Hypothermia • Acidosis • Transfusion associated Graft versus Host Disease • Adverse ocular reaction • Transfusion related immunomodulation

22. RISKS OF BLOOD TRANSFUSION Type Occurrence in Red Blood Cell Units Transfused Infectious • Human immunodeficiency virus 1 in 1.4–2.4×106 • Hepatitis B 1 in 58,000–149,000 • Hepatitis C 1 in 872,000–1.7× 106 • Bacterial infection 1 in 2,000 Immunologic reactions • Febrile nonhemolytic transfusion reactions 1 in 100 • Anaphylactic transfusion reactions 1 in 20,000–50,000 • ABO mismatch • Hemolysis 1 in 60,000 • Death 1 in 600,000 • Leukocyte-related target organ injury 1 in 20 to 1 in 50 • Transfusion-related acute lung injury 1 in 2000 • Post-transfusion purpura Rare Transfusion services error 1 in 14,000

23. HEMOLYTIC TRANSFUSION REACTIONS • Signs and symptoms: • Chills • Fever • Chest and flank pain • Nausea • Hemoglobinuria • Bleeding diasthesis(noticed during surgery) • Hypotension

24. STEPS IN TREATMENT OF A HEMOLYTIC TRANSFUSION REACTION • STOP THE TRANSFUSION • Maintain urine output at a minimum of 75-100 ml/hr(generous fluid administration,mannitol,furosemide) • Alkalinize the urine • Assay urine and plasma hemoglobin concentrations • Determine platelet count,partialthromboplastin time and serum fibrinogen levels • Return unused blood to blood bank for repeat cross match • Send patients blood and urine sample to blood bank for examination • Prevent hypotension to ensure adequate renal blood flow

26. BLOODCONSERVATIONSTRATEGIES

27. BLOOD CONSERVATIONS • Increasing interest in in Blood conservation since last 15 years • Significant risks of allogenic blood transfusion. • Shortage of allogenic blood • Patient choice • Improvement in availaibilty of transfusion alternatives.

28. HIGH RISK PREDICTORS • Advanced age • Low preoperative red blood cell volume (preoperative anemia or small body size) • Preoperative antiplatelet or antithrombotic drug • Reoperative or complex procedures • Emergency operations • Noncardiac patient comorbidities

29. INTERVENTIONS TO LIMIT BLOOD TRANSFUSION Pharmacologic agents: • Hemostatic Drugs with Antifibrinolytic Properties • Erythropoetin • DDAVP • Recombinant factor 7 A Devices to Aid Blood conservation: • Cell Saver • Ventilator-assisted Blood Conservation PEEP • Oxygenator types • Perfusion Blood Pumps • Heparin Bonded Circuits • Leukocyte Filtration

30. INTERVENTIONS TO LIMIT BLOOD TRANSFUSION contd…. Perfusion techniques and OPCAB • Heparin Management • Protamine dosing • Acute NormovolemicHemodilution • Preoperative autologous Blood transfusion • Minimized extracoporeal bypass circuits • Retrograde autologous priming • Hemofiltration • Off-pump procedures for Blood conservation Topical agents/Tissue Glues

31. PHARMACOLO-GICAL AGENTS

32. Antifibrinolytic agents: • Aprotonin • Serine protease inhbhitor • Binds with serine protease inhibhitors: • Trypsin Decreasing • Plasmin Affinity • Plasminkallikrein • Tissue kallikrein • Elastase • Urokinase • Thrombin

33. Aprotonin: Pharmocokinetics: • Inactive via oral route • Rapid distribution into extravascular space • Following redistribution plasma half life aprox.150 mins • Less than 10% excreted as unchanged drug • Slowly degraded as lysosomal enzymes • Terminal elimination phase half life-10 hr

34. Aprotonin: Mechanism of action: • Inhibhits serine proteases that attenuates: • Inflammatory responses • Fibrinolysis • Thrombin generation • Inhibhits pro-inflammatory cytokine release and maintains glycoprotein homeostasis

35. Aprotinin- Mechanism of Action Blood/Surface activation Intrinsic Pathway Plasmin Kallikrein Heparin Non Specific SerineAntiprotease:Aprotinin Complement activation Clotting Fibrinolysis Kinins Cytokines/ Adhesion Molecules Systemic Inflammatory response

36. Aprotonin-dosage: 1-2 million KIU followed by a continous infusion of 100,000-200,000 KIU/hr

37. Aprotonin: Adverse effects: • Hypersenstivity • Graft occlusion • Heart failure • Renal Dysfunction • Stroke

38. Lysine Analogues: • Epsilon Amino Caproic Acid • Tranexemic acid MOA: • They inhibit plasminogen by binding to the lysine binding sites on the plasminogen molecule. • Spare platelet function by inhibiting the deleterious effects of plasmin. • Tranexamic acid is similar in action to Epsilon-aminocaproic acid but it is approximately 10 times more potent.

39. Lysine Analogues: Dose: • Intravenous loading dose of 10 mg/kg for tranexamic acid followed by 1 mg/kg/hr • 100-150 mg/kg of ε-aminocaproic acid followed by infusions of 25 mg/kg/hr

40. Erythropoeitin: • Endogenous glycoprotein-stimulates red cell production in response to hypoxia and anemia. • Recombinant EPO: Reduce preoperative anaemia in patients undergoing autologous blood donation • Safe and effective • Drawbacks • Expensive • Hypertension • Lag period: 4-6 days-less effective post operatively • Beta blockers and cardiopulmonary bypass inhibit effect • Dose • 50-150 U/kg s/c or I/v 3 times a week

41. Desmopressin (DDAVP): • Releases • Endogenous factor VIII precursors • Von Willebrand factor • Tissue type plasminogen activator. • Not helpful prophylactically to reduce bleeding after cardiac procedures. • Helpful in patients with demonstrable and specific platelet dysfunction known to respond to this agent (eg, uremic or CPB-induced platelet dysfunction, type I von Willebrand’s disease). • Dose • 0.3 μg/kg iv, sc or intranasal

42. Recombinant Factor VIIa: • Vitamin K-dependent glycoprotein • Currently FDA approved only for the treatment of severe bleeding episodes in hemophiliacs with factor inhibitors or patients with FVII deficiency • Binds to tissue factor→ Activation of factor X (FXa) on the platelet surface (a phospholipid surface); • FXa + Activated factor V→ prothrombinase complex → Thrombin formation.

43. Recombinant Factor VII a: • Plasma concentrations ~50 nM→ partial Thrombin Generation • Plasma concentrations ~ 100 to 150 nM → Full activation of Thrombin (Thrombin burst) • Recommended dose for bleeding in hemophiliac patients is 90 µg/kg i.v. • Doses for the treatment of uncontrolled hemorrhage varied from 15 to 180 µg/kg i.v • Recommended as rescue therapy for severe intractable bleeding without an identifiable surgical source that is unresponsive to routine approaches after cardiac procedures using CPB.

44. DEVICES

45. Disadvantages Cell Salvage Techniques: Advantages ↓ risk of infection ↓ risk of transfusion reaction Safer in patients with rare blood groups & multiple antibodies No immunosuppression ? Acceptable to Jehovah’s Witnesses ↓ demand for allogenic blood products ↑ cost- setup cost inc. staff training Unused blood wasted ↑ risk of bacterial contamination

46. Ventilator-assisted Blood Conservation: Positive End Expiratory Pressure • Increased end-expiratory airway pressure (PEEP) exerts mechanical pressure on the myocardium and may limit microvascular bleeding after heart surgery. • Use of prophylactic PEEP postoperatively is not effective.

47. Oxygenator Type: Membrane oxygenator systems during cardiopulmonary bypass are preferred for reduction in blood utilization and improved safety. • Advantages • Fewer cerebral emboli • Better biocompatibility • Reduced blood utilization

48. HEPARIN-BONDED CIRCUITS: • Heparin coating of the oxygenator or of the entire bypass circuit • Limits platelet activation • Reduces complement activation • Alters cellular adhesion to the bypass tubing • Diminishes the inflammatory pulmonary injury seen after CPB • Need of Low dose Heparin & consequently reduced protamine dose

49. PERFUSION TECHNIQUE

50. ACUTE NORMOVOLEMIC HEMODILUTION (INTRAOPERATIVE AUTOLOGOUS DONATION): • Removal of one to two units of blood immediately before surgery • To maintain circulating blood volume, the volume is replaced with crystalloid / colloid. • Contraindications: • Evolving acute myocardial infarction • Unstable angina • Cardiogenic shock • Preoperative anemia • Sepsis • known bacteremia. • Relative contraindications • Low EF (< 30%)