Blood Transfusion: What are the Expected Complications?

1. Blood Transfusion: What are the Expected Complications? Ahmad Sh. Silmi Msc , FIBMS Staff Specialist in Hematology Head of Medical Laboratory sciences Dept Islamic University of Gaza

2. “Blood is the most dangerous medication that a physician ever prescribes”

3. Blood Transfusion Reactions (BTR’s) • may be life-threatening and even fatal • require immediate recognition and management • must be treated if indicated and prevented in transfusion practice

4. Transfusion Reaction any unfavorable transfusion-related event occurring in a patient during or after transfusion of blood components

5. Blood Transfusion Reactions HaemovigilanceSerious Hazards of Transfusion ( SHOT ) 65% Incorrect Blood Component10% Acute Transfusion Reaction10% Delayed Transfusion Reaction5% Transfusion Lung Injury3% Post-transfusion purpura3% Transfusion Transmitted Infection1% Transfusion-GVHD

8. Blood Transfusion: ImmediateReactions • Acute Haemolytic Transfusion Reactions • Febrile Non-Haemolytic Transfusion Reactions • Allergic Reactions: • Anaphylaxis • Skin Reaction • Transfusion-related Acute Lung Injury • Bacterial Contamination • Circulatory Overload • Physically or Chemically Induced Transfusion Reactions (PCITR’s)

9. Blood Transfusion: Delayed Reactions • Delayed Haemolytic Transfusion Reactions • Post- transfusion Purpura • Infection Transmission • Transfusion-related Graft-versus-Host Disease • Immune Modulation • Iron Overload

10. Immediate Blood Transfusion Reactions: Acute Haemolytic Transfusion Reactions • Intra-vascular • Extra-vascular

11. Immediate Blood Transfusion Reactions: Acute Intra-vascular Haemolytic Transfusion Reactions • Trigger: ABO antigens on transfused red cells Not shared by the Recipient • Reactor: Anti-A or Anti-B of Ig M type

12. Immediate Blood Transfusion Reactions: Acute Intra-vascular Haemolytic Transfusion Reactions Pathophysiology Full Complement Cascade Activation • Complement Components C3a,C5a • Cytokines: IL-1, IL-6,IL-8, TNF • Free Haemoglobin. • DIC

14. Immediate Blood Transfusion Reactions: Acute Intra-vascular Haemolytic Transfusion Reactions Clinical Picture • Fever, Flushing, Rigors • Headache • Heat or pain at cannulated vein • Restlessness • Bronchospasm • Hypotension • Back or loin pain • Oozing in the surgical field • Red urine ( haemoglobinuria ) • Oliguria or anuria

15. Immediate Blood Transfusion Reactions: Acute Intra-vascular Haemolytic Transfusion Reactions Diagnosis • Clinical picture • Transfusion Mistake • Red urine • Red plasma • Lab Confirmation

16. Immediate Blood Transfusion Reactions: Acute Intra-vascular Haemolytic Transfusion Reactions Laboratory Workup • Obtain Blood and urine samples, inspect color • Check paper work • Repeat cross Match • CBC • Direct Coombs’ test • DIC screen: PT,PTT, Fibrinogen • BUN, Cr, electrolytes • Haemolysis screen: LDH, Haptoglobin • Blood culture if sepsis is suspected

17. Immediate Blood Transfusion Reactions: Acute Intra-vascular Haemolytic Transfusion Reactions Management • Stop transfusion Immediately • Replace giving set, keep IV line with Normal saline • Check patient ID against donor unit • Cardio-pulmonary support • Insert urine cath. And start Forced Diuresis ( ensure 100 ml/h for 24 h to get rid of free Hb)

18. Immediate Blood Transfusion Reactions: Acute Intra-vascular Haemolytic Transfusion Reactions Outcome Mortality ~ 10 %

19. Immediate Blood Transfusion Reactions: Acute Extra-vascular Haemolytic Transfusion Reactions Trigger: Rh antigens not shared by the patient Reactor: Anti-Rh antibodies of Ig G type

20. Immediate Blood Transfusion Reactions: Acute Extra-vascular Haemolytic Transfusion Reactions Response: Pathophysiology • Incomplete complement activation Coating of transfused red cells with C3b • Extravascular phagocytosis by RES • Cytokines from activated RES

21. Immediate Blood Transfusion Reactions: Acute Extra-vascular Haemolytic Transfusion Reactions Clinical Features • Less severe, may be no signs • Onset > I hour • Fever • + Jaundice • Rarely Haemoglobinuria or renal dysfunction

22. Immediate Blood Transfusion Reactions: Acute Extra-vascular Haemolytic Transfusion Reactions Laboratory • Anti-complementary Coombs positive

23. Immediate Blood Transfusion Reactions: Acute Extra-vascular Haemolytic Transfusion Reactions Managment • Stop Transfusion • Supportive • Mortality very rare

24. Immediate Blood Transfusion Reactions: Febrile Non-Haemolytic Transfusion Reaction ( FNHTR) Trigger: Leucocyte antigens on infused blood not shared by the patient Reactors: Leuco-agglutinins in the patient from previous exposure

25. Immediate Blood Transfusion Reactions: Febrile Non-Haemolytic Transfusion Reaction ( FNHTR) Pathophysiology • Cytokine released from the transfused activated leucocytes

26. Immediate Blood Transfusion Reactions: Febrile Non-Haemolytic Transfusion Reaction ( FNHTR) Clinical Features • Fever after 30-90 min • + Rigors • + Headache • No Hypotension • No Bronchospasm • No flank pain • No haemoglobinaemia • No Haemoglobinuria

27. Immediate Blood Transfusion Reactions: Febrile Non-Haemolytic Transfusion Reaction ( FNHTR) Management • If Temp < 40 + Stable patient: • Stop transfusion • Antipyretics ( No rule of Anti-histamines ) • Check the bag and cross match • Exclude red urine or red plasma • Resume transfusion at a slower rate • If recurrent: Leucodepleted transfusion in the future

28. Immediate Blood Transfusion Reactions: Febrile Non-Haemolytic Transfusion Reaction ( FNHTR) Management • If Temp 40 or more + Unstable patient: • Stop transfusion • Manage as possible acute haemolytic reaction till lab. Confirmation or exclusion.

29. Immediate Blood Transfusion Reactions: Febrile Non-Haemolytic Transfusion Reaction ( FNHTR) • Prevention/ Recurrence of FNHTR’s: • pre-transfusion administration of antidotes • documented BTR, warrants pre-transfusion medications 30 minutes before blood transfusion • use leukocyte-depleted blood • removal of buffy coat • sedimentation • red cell washing • use of micro-aggregate filtration (leukoreduction)

30. Immediate Blood Transfusion Reactions: Transfusion- Related Acute Lung Injury ( TRALI) Sudden onset of acute respiratory distress within 6 hours( u. 1-2h) of transfusion

31. Immediate Blood Transfusion Reactions: Transfusion- Related Acute Lung Injury (TRALI) Rare: 1/5000 transfusions

32. Immediate Blood Transfusion Reactions: Transfusion- Related Acute Lung Injury ( TRALI) Pathophysiology • Trigger: Leucoagglutinins in the bag against patient’s leucocytes • Reactors: Patient leucocytes • Result: massive Leucocyte activation  Cytokine storm  Pulmonary Endothelial and Epithelial Injury  ARDS

33. Pathophysiology of (TRALI) Leukocyte Ab in donor react with pt. leukocytes Activate complements Adherence of granulocytes to pulmonary endothelium with release of proteolytic enz.& toxic O2 metabolites Endothelial damage Interstitial edema and fluid in alveoli

34. Immediate Blood Transfusion Reactions:Transfusion- Related Acute Lung Injury ( TRALI) Clinical Features • Fever, chills • Acute Respiratory Distress • Normal CVP (Central Venous Pressure) • CXR: Pulmonary Infiltrate

35. Immediate Blood Transfusion Reactions:Transfusion- Related Acute Lung Injury ( TRALI) Management • Cardio-Pulmonary Support • Steroids • Diuretics of No value Mortality High

36. Immediate Blood Transfusion Reactions: Allergic Acute Transfusion Reactions Pathophysiology • Trigger: Plasma proteins in the transfused blood • Reactors: Patient antibodies of IgE type • Response: • Mast cell degranulation • + Complement Activation • + Cytokines

37. Immediate Blood Transfusion Reactions: Allergic Acute Transfusion Reactions Clinical Features • Mild / Skin-restricted ( common: 1%): • Pruritus, Uerticaria, No fever or Hypotension • Severe / Systemic ( Anaphylaxis): • As above + • Fever • Hypotension • Bronchospasm, Angio-edema

38. Immediate Blood Transfusion Reactions: Allergic Acute Transfusion Reactions Management • Mild / Skin-restricted : • Stop transfusion temporary • Anti-histamines • Resume Transfusion

39. Immediate Blood Transfusion Reactions: Allergic Acute Transfusion Reactions Management • Severe / Systemic ( Anaphylaxis): • Stop transfusion • Anti-histamines ( H1+H2 blockers) • Epinephrine: 1 ml of 1/1000 IM • Hydrocortisone 100 mg IV • Cardio-pulmonary support

40. Immediate Blood Transfusion Reactions: Acute Pyrogenic Transfusion Reactions Pathophysiology • Trigger:Bacterial Pyrogens/Endotoxins in the transfused blood contaminated with cold-growing organisms as: • Pseudomonas • Yersinia • Some Staph • Reactors:Patient Mono-nuclear cells • Response: • Cytokine Storm

41. Immediate Blood Transfusion Reactions: Acute Pyrogenic Transfusion Reactions Clinical Features Like : • Acute Haemolytic reaction BUT: • No Hemoglobinuria • No Hemoglobinaemia • FNHTR BUT More Severe

42. Immediate Blood Transfusion Reactions: Acute Pyrogenic Transfusion Reactions Management • As Acute Haemolytic reaction BUT Add Broad- spectrum Antibiotics

43. Immediate Blood Transfusion Reactions: Acute Circulatory Overload • Acute cardiogenic pulmonary edema • In rapidly transfused, non-bleeding (euovolemic) patients • More in infants, elderly or cardiac patients

44. Immediate Blood Transfusion Reactions: Acute Circulatory Overload D.D. from other Acute transfusion reactions: • No Fever ( DD from TRALI, FNHTR) • No red urine or plasma and Negative Coombs ( DD from Acute haemolytic reaction)

45. Immediate Blood Transfusion Reactions: Acute Circulatory Overload Prevention • Never exceed 2-3 ml/kg/hour Unless Bleeding • Pre-medicate with Diuretics in Cardiac or severely anemic patients Management • Diuretics • Consider Haemodialysis • Supportive

46. Immediate Blood Transfusion Reactions: Physically or Chemically Induced Transfusion Reactions (PCITR’s) heterogenous group of conditions including: physical RBC damage depletion and dilution of coagulation factors and platelets hypothermia citrate toxicity hypokalemia / hyperkalemia

47. Immediate Blood Transfusion Reactions: Physically or Chemically Induced Transfusion Reactions (PCITR’s) Physical Damage to RBC’s intravascular lysis due to hypertonic or hypotonic solutions heat damage from blood warmers, during shipping, in hot rooms freeze damage in absence of cryoprotective agent during shipping

48. Immediate Blood Transfusion Reactions:Physically or Chemically Induced Transfusion Reactions (PCITR’s) Mechanical Damage blood pumps, roller pumps infusion under pressure through small bore needles

49. Immediate Blood Transfusion Reactions: Physically or Chemically Induced Transfusion Reactions (PCITR’s) Citrate toxicity ACD/ CPD has 1.4-1.6 g of citrate - no toxicity citrate > 100 mg/ dl - citrate toxicity Causes ADULTS rate of BT > 1 liter/ 10 min or BT volume exceeds 6 L administered in < 2 hours CHILDREN exchange transfusion - hypocalcemia

50. Immediate Blood Transfusion Reactions:Physically or Chemically Induced Transfusion Reactions (PCITR’s) Potassium toxicity: Mechanism: high potassium load with prolonged blood storage - hyperkalemia Clinical manifestations: cardiac excitability ECG findings: peak T waves Laboratory findings: hyperkalemia Management: calcium gluconate