Transfusion Therapy

1. Transfusion Therapy Bradley J. Phillips, MD Burn-Trauma-ICU Adults & Pediatrics

2. Transfusion Therapy Resuscitation Therapy Anemia Coagulopathy

3. Resuscitation Prompt correction of severe blood-volume deficits Adequate tissue perfusion

4. Adequacy of Resuscitation • Consistent MAP 70-80 mm Hg • HR decreasing to less than 100-110 • Warm extremities with good capillary refill • Adequate CNS function • Urine output at least 0.5 ml/kg/hr • Absence of lactic acidosis • Core Temperature above 35 C • ? Gastric tonometry pH > 7.30 • ? End tidal CO2 • < 22 mortality increased (50-53%) • aCO2 - end tidal CO2 > 10-13 mortality increased

5. Definition • Crystalloid vs. colloid • solute particles that will or will not pass through a semipermeable membrane • distribute throughout extracellular space • isotonic crystalloid (NS/LR) distributes evenly • hypotonic crystalloid (D5W) distributes with entire body water

6. Crystalloid • Equilibrium within 20-30 minutes (normal) • Intravascular volume (1 hr. post-transfusion) • isotonic solutions = 1/3 volume given • hypotonic solutions = 1/15 volume given • Blood loss equivalent • 1 L isotonic solution per 1 unit blood loss (250 cc)

7. Advantages expand intravascular volume no infectious risks Disadvantages dilution effects  red cells =  O2 carrying capacity  proteins =  buffering and osmotic pressure pulmonary edema Crystalloid

8. Crystalloid and Pulmonary Edema • Lung “edema safety factors” (counteract intravascular oncotic pressure • increased lymph flow • diminished pulmonary interstitial oncotic pressure • increased interstitial hydrostatic pressure • “Bottomline” • does not impair pulmonary function unless lung damage or right-sided heart failure • no difference in lung function in patients with shock if controlled to prevent volume overload

9. NS = LR? • Generally, interchangeable • Disadvantages • NS (Na+ 154 meq/ml, Cl - 154 meg/ml) • large volumes produce dilution acidosis or hyperchloremic acidosis • seldom a problem if normal kidney function • LR (Na + 130, Cl + 109, K + 4, Lactate 28, Ca ++ 3) • precipitate a severe lactic acidosis if severe liver disease or dysfunction • hyperkalemia in patients with renal failure

10. Colloid • Normal colloid oncotic pressure (COP) = 28 mmHg • Profound reduction in COP • reduce LV compliance • increased pulmonary extravascular volume • decrease tissue oxygen deliver • impair wound healing • Types • Albumin, Dextran, Hetastarch, Pentastarch

11. Albumin • Characteristics • MW = 65,000 • 12-14 g/d synthesized by the liver • 30-40% intravascular space (serum level 3.5-5 g/dl) • accounts for 80% of COP • half-life = 20-22 days

12. Albumin • Exogenous half-life • normal 12-16 hours ( loss 7-8% per hour ) • severe sepsis or shock ( loss 30% per hour ) • Products • 5% or 25% solution • prepared by fractionating blood from donors and heated to 60 C for 10 hr. (inactivated HIV/hepatitis) • Intravascular volume expansion • 500 ml of 5% = 250-500 ml • 100 ml of 25% = 300-600 ml

13. Advantages volume expander utility in severe hypoproteinemic bind proteolytic enzymes scavenge free radicals Disadvantages expensive ($32 per 5% soln) binds Ca++ and lead to negative inotropic effect excessive amounts may lead to problems with cardiac function pulmonary edema renal dysfunction Albumin

14. Dextran • Glucose polymer • D40 - MW 10,000 to 80,000 • D70 - MW 40,000 to 100,000 • Urine excretion and MW • < 15,000 lost within 15-30 minutes • 15,000-50,000 lost within 24 hours • 80,000 lost > 24 hours

15. Dextran • Ideal volume expansion • 500 ml D40 = 750 to 1000 ml expansion (last up to 8 hours) • long dwell time in circulation • ultimate biodegradability • benefits • improves blood flow • decrease viscosity • prevent RBC sludging

16. Dextran • Major disadvantages • anaphylactoid reactions (usually < 0.1%) • renal dysfunction • osmotic diuresis (MW < 50,000 renal excretion) • precipitate in tubules if oliguric • interferes with cross-matching blood • increased bleeding • decreased platelet adhesiveness

17. Starches • Hydroxyethyl starch (Hetastarch) • synthetic starch 6% solution • expands intravascular volume 100-170% • retention time of 12-48 hours • Disadvantages • coagulopathy (20 ml/kg/d) • enhanced fibrinolysis and direct effect on VIII

18. Hypertonic Saline Solution • 1,000 to 2,500 mOsm/L • Studies have shown • effective resuscitation • less edema • better tissue perfusion • reduce ICP • Disadvantages • vasodilation • hypernatremia ( Na > 160-165)

19. For Crystalloid key loss is extracellular volume fluid overload less likely to occur since equilibrate with ECF colloids lead to pulmonary edema when leaky capillary free of allergic rxn no coagulation problem less expensive For Colloid key loss is blood loss crystalloid equilibrate with ECF, so need 3-4x the losses crystalloids reduce oncotic pressure and lead to pulmonary edema Crystalloid vs Colloid

20. Crystalloid vs Colloid Successful resuscitation is primarily dependent on the adequacy of the fluid replacement and NOT on the composition of the fluid itself

21. Blood Transfusion • Autologous • Non-autologous • uncrossmatched • type-specific • crossmatched

22. Autologous • Cell saver or Chest tube collection • Advantages • available without delays • reduce risks of blood-borne disease • reduce blood bank needs • Disadvantages • absolute contraindication if intestinal contamination • if used in excess, severe coagulopathy (DIC) • needs to be filtered or wash prior to re-infusion • limit to 3,000 ml or less

23. Blood Transfusions • General rule, Hct 20-25% provides adequate O2 delivery if • blood volume normal • cardiac output normal • Hgb saturation at least 90% • In general in critically ill patients, a Hct of 30-35% is preferable

24. Costs of Transfusion • Costs approx $150 per unit (hospital costs) • 25% of costs attributable to inappropriate transfusion

25. PRBC • Average PRBC = 250-300 cc, Hct 60-80% • Frozen at -80 C • Thawed, washed , and centrifuge to remove glycerol • Resuspended in saline-glucose solution • Advantages (frozen RBC) • no citrated added • no incompatible antibodies • risk of hepatitis reduced • stored indefinitely

26. Changes in Blood During Storage • Reduced RBC viability • Increased plasma free hemoglobin • Abnormal K concentration • Reduced ATP (normal until 3 weeks) • Reduced 2,3-DPG (70% 2 wk, 50% 3 wk) • No platelet function (after 24-48 hrs)

27. RISK most least Type and Crossmatch • Uncrossmatched (immediate) • O negative blood (still anti A- or B- antibodies • Type (15 minutes) • ABO compatibility • Crossmatch (30-45 minutes) • no significant antibody/antigen reaction

28. Massive transfusions Reactions nonhemolytic hemolytic Electrolyte problems Infectious bacterial and viral Hypothermia Pulmonary dysfunction Immune compromise Complications - Blood Transfusion

29. Complications - Blood Transfusion • Massive Transfusion • > 10 units within 24 hrs = mortality of 50% • Wayne State study, 339 trauma patients • 10-19 = 28 % mortality • 20-39 = 65% mortality • > 40 = 83 % mortality • ? marker of severe injury vs. independent variable

30. Complications - Reactions • Non-hemolytic (minor) • most frequent 2-10% • fever, hives, uticaria, or bronchospasms • reduced with washed RBC and filtered leukocytes • Hemolytic (risk 1:33,000, fatal 1:500,000) • antibody/antigen incompatibility • 50% clerical error • occur in spite of adequate type and crossmatch • apparent within 50-100 ml of blood infused • if suspected, stop immediately, give IV Benadryl +/- epinephrine/steroids if severe

31. Complications - Electrolytes • Increased • potassium • increase 1 mEq/d and exceed 6.6 mEq per unit • despite this, hypokalemia almost as common • ammonia, lactate, and hemoglobin • Decreased • bicarbonate and pH • Citrate toxicity (hypocalcemia) • > 1 unit per 3-5 minutes • Ca++ < 0.7 mM associated with increased mortality

32. Complications - Hypothermia • Hypothermia (< 32-33 C) • impairs cardiacvascular function • arrhythmias • coagulation defects • Mortality = 85% if maintained core < 32 • Every effort to maintain temperature • warm fluid/blood • warming blanket/avoid exposure • heated ventilator gases

33. Complications - Pulmonary Dysfunction • Assume significant pulmonary dysfunction • > 20 units transfused • shock > 30 minutes

34. Complications - Infectious • Sepsis major complication in massive transfusions in patients who survive 48 hours • probably impaired host defenses • early and consistent independent risk factor to MSOF and infection (Moore, Arch Surgery, 1997) • Bacterial • up to 2.3 % of units contaminated • reaction similar to transfusion reaction

35. Complications - Infectious • Viral • Hepatitis (risk Hep C < 1:5000, Hep B 1:200,000 ) • Non A,Non B hepatitis (Hep C) = 85-98% • 40-50% of fulminate cases • 87-100% mortality in fulminate cases • chronicity up 36% (?) • Hep B = 2-15% • HIV (risk < 1:420,000 - 660,000 ) • 1-2% cases from blood transfusions

36. Blood Alternatives • Stroma-free hemoglobin • problem high oxygen affinity • Perfluorocarbons • problems with short half-life, prolonged tissue retention, and potential toxicity • little benefit unless severe anemia (Hbg < 5) in patients who will not accept blood • Recombinant erythropoietin

37. Recombinant Erythropoietin • Rationale • risks of blood transfusion • low EPO levels in critically ill patients • Multiple studies (prospective, randomized) • von Ashen, N. Critical Care Medicine 1999 • Corwin, HL. Critical Care Medicine 1999 • van Iperen, CE. Critical Care Medicine, 2000 • Hobisch-Hagen, P. Critical Care Medicine, 2001

38. Recombinant Erythropoietin • Effects • reticulocyte counts increased 4x control in 7-10 days • significantly increased Hct • significant fewer PRBC units transfused • no difference in mortality • improved response if iron supplemented IV and iron deficient • Dose • 40,000 units q week (divided if renal failure)

39. Bleeding Most common caused of operative bleeding is poor surgical hemostasis Preventing Coagulopathies 1. meticulous hemostasis 2. rapid and complete correction of hypovolemia 3. maintaining core temperature > 35 C

40. Clotting Factors • Platelets • DDAVP • Fresh Frozen Plasma (FFP) • Cryoprecipitate

41. Changes in Clotting Factors vs. PRBC 10-19 U 20-39 U 40+ U Platelets 72 K 52K 41K PT 18s 21s 27s PTT 62s 89s 132s Wilson, RF. Management of Trauma: Pitfalls and Practice, 1996

42. Prophylactic Administration In general, routine platelets and FFP for massive transfusion not recommended unless clinically or laboratory evident

43. Platelets • Thrombocytopenia most important cause of diffuse microvascular bleeding at massive blood transfusion • General rules • < 10K to 20K give even if not bleeding • <50,000 and on-going bleeding or planned operation and bleeding time > 15 min • PRBC transfusion > normal blood volume (4-5 L) and microvascular bleeding • 1 unit plts = 5000-10000 increase in plasma count at 1 hr • avoid transfusion in TTP and HIT

44. FFP • All clotting factors present • Must be ABO compatible • Requires time • Thaw time = 20-40 minutes • If given with 2 hours of thaw, normal levels of coagulation factors are present • Indicated for multiple coagulation deficiencies

45. FFP • Coagulation usually normal with 24-30% of normal factors • Replacement of entire blood volume leaves patient with 1/3 of original concentration of factors • In general, PT/PTT > 1.5 normal more likely to have abnormal hemostasis • Even if PT/PTT abnormal, studies confirm no abnormal bleeding unless thromobocytopenia • Should NOT be used for volume expansion

46. DDAVP • Indications • uremia • isolated prolonged bleeding time and NO antiplatelet agents on board • cirrhosis and acquired platelet dysfunction • Dose 0.03u/kg SQ, IM, IV • Response within 30 by bleeding time measurement • Side effects (minimal) • flushing, tachycardia, headache

47. Cryoprecipitate • Factor VIII, approx.. 80 units per bag • Primary indication • hemophilia A • von Willebrand’s • hypofibinogenemia • hepatic insufficiency • DIC • * Massive transfusions • bleeding and fibrinogen levels < 80 mg/dl

48. Questions…?