Blood components

Blood component therapy and transfusion releted adverse effects

1. BLOOD COMPONENT THERAPY PRESENTER : Dr. Supriya Jamatia MODERATOR : Prof. Robinson Ningshen

2. Allows optimal use of limited community resource First animal to human transfusion on 1667 by Denis Landsteiner description of blood group on 1901 Direct transfusion by means of arterio -venous anastomosis on 1917 Introduction Transfusing only the portion of the blood needed by the patient is called blood component therapy

3. Red blood cell  Oxygenation of tissues Platelets  Prevention or cessation of bleeding Fresh frozen plasma  Cessation of bleeding Cryoprecipitate  Cessation of bleeding Cryoprecipitate-poor plasma  Plasma exchange Granulocytes  Treatment of infection Frozen blood cells  Storage of rare blood Leukocyte-depleted red cells  Prevention of reaction and certain diseases Component and Medical use

4. BLOOD COMPONENT SEPARATION

5. Maintain viability and function Prevent physical changes Minimize bacterial contamination Goals Of Blood Collection

6. Phlebotomy Hemapheresis ( using differential centrifugation) Methods of collection from donors

7. Anticoagulants prevent blood clotting Preservatives provide nutrients for cells Anticoagulants - Preservative Solutions

8. Anticoagulants CPD CPD-A1 Storage time 21 days 35 days Temperature 1-6 °c 1-6 °c Slows glycolytic activity Adenine None Substrate for ATP synthesis Volume 450 +/- 10% Dextrose Supports ATP generation by glycolytic pathway Citrate Prevents coagulation by binding calcium

9. Add additive solution to RBCs which consists of: Saline Adenine Glucose Mannitol Extends storage to 42 days Final hematocrit approximately 66% Additive Solution

10. Affects oxygen dissociation curve pH drops ↓ 2,3-DPG Once transfused RBCs regenerate ATP , 2,3-DPG Few functional platelets present Viable (living) RBCs decrease Changes in stored blood

11. Plasma hemoglobin Plasma K + Viable cells pH ATP 2,3-DPG Plasma Na + Helps release oxygen from hemoglobin (once transfused, ATP & 2,3-DPG return to normal) K + Na +

12. Modified by Irradiation Leukoreduction (filters) Washing ( saline or saline-anticoagulant sol) Modifications of blood component

13. Blood/ Start infusion Complete infusion blood product Whole blood/ within 30 min. of within 4 hour red cells removing pack ( less in high ambient temperature) Platelet immediately within 20 min concentrates FFP within 30 min within 20 min

14. Plasma derivatives are fractionated from large volumes of plasma in large industrial units Ex: Albumin, intravenous gamma globulin, Factor 8 etc.. Difference between blood component and plasma derivatives?

15. Types Whole blood Packed red blood cells RED CELL TRANSFUSIONS Used to increase the haemoglobin level in patients with anemia or to replace losses after acute bleeding episodes

16. Comparison between Whole blood and PRBC Parameter Whole blood Packed red cells Volume 350 – 450 ml 250 – 300 ml Increment in Hb 1 -1.5 gm/dl 1 -1.5 gm/dl Red cell mass /ml Same as PRBC Same as WB Viable platelets No No Labile factors No No Plasma citrate ++++ + Allergic reactions ++++ + FNHTR ++++ + Waste of components Yes No

17. Volume – 225 to 350 ml Anticoagulant used – citrate phosphate dextrose adenine Shell life ( with additive solutions)- 35 to 42 days Stored at 4°c Must be ABO compatible, ↑Hb One unit by 1 g/dl or ↑ Hct 3% Adverse reactions can be prevented by leukoreduction and irradiation PACKED RED BLOOD CELLS

18. Whole blood : Acute and massive loss of blood where volume replacement is required Packed RBC : Anemia with Hb ≤7.0 gm /dl To increase the oxygen carrying capacity Indications Exceptions to this rule are Symptomatic myocardial ischemia with Hb <10gm/dl. Trauma or on-going blood loss where strict cut-off may not be possible

19. Loss of Total blood volume (TBV) : TBV - 30-40% Rapid volume replacement RBC transfusion likely needed TBV - >40% Life-threatening bleeding Requires rapid volume replacement Requires RBC transfusion Indication in Acute Blood Loss

20. Treat the underlying cause (e.g. iron,folate,B12 ) Try EPO trial if the patient can be observed rather than treated immediately Indication in Chronic Blood Loss Hb >10g/dl , rarely needed Hb <6g/dl, usually needed Hb 6-10g/dl and Co-morbid Conditions

21. 20 % blood volume loss can do well without transfusion Change in vitals signs not due to anaesthesia Decreased Urine Output Estimated blood loss > 1000 ml Indication in Intraoperative Usage Whether patient requires transfusion or not should be decided based upon clinical condition, not solely by the haemoglobin level

22. FFP – plasma is separated and stored at -18 to -30°c within 8 hours of collection PF24 - separated within 24 hours of collection. (Both of above products can be stored upto one year) PLASMA COMPONENTS Thawed plasma – after plasma is thawed it can be kept in refrigerator(1-6 ̊C) for 4 days . Liquid plasma - plasma that has never been frozen. Expire in 5 days. Solvent/detergent plasma - treatment with viral inactivating agents prior to freezing .

23. Method of collection: whole blood or plasma by apheresis technique Standard unit : 200-250 ml. Dosage and infusion rate Infused in 1-2 hour, in neonate 15ml/kg/ hr in volume overload patients- 1ml/kg/hr Due to the short half-life of coagulation factors, frozen as FFP within 8 hours of collection of blood FRESH FROZEN PLASMA (FFP)

24. INR 1.6 with bleeding INR 1.6 and patients about to go to undergo an invasive procedure, Therapeutic exchange Major bleeding associated with warfarin anticoagulation or vitamin K deficiency Deficiency of multiple coagulation factors , Ex: L iver disease, DIC Factor replacement for rare inherited coagulation factor disorders Indications

25. FFP is thawed at 4°c & resulting precipitate is separated from plasma by centrifugation Contains factor 8(100 units), factor 9, fibrinogen(200mg), fibronectin and von willebrand factor in each unit Storage in freezer for one year. CRYOPRECIPITATE ( cryoprecipitated antihaemophilic factor)

26. Deficiencies of factor 8 and fibrinogen Fibrinogen 100 and the patient is bleeding or about to undergo an invasive procedure Massive bleeding Can be used in uremic bleeding, which is not responding to other measures. Indications

27. Types Random donor platelets (pooled platelets) Single donor platelet (apheresis platelets ) PLATELET TRANSFUSION

28. One unit of platelet is isolated from every unit of donated blood by centrifuging 4 to 6 units of pooled platelets are required in single setting to raise the platelet level Advantages : Low cost, easy collection and processing Disadvantages : Exposure to multiple donors in single transfusion and risk of infection Random donor platelets (Pooled platelets )

29. Platelets are collected from a single donor in blood bank over two hour P heresis procedure Platelets and some white cells are removed while red cells and plasma are returned back to donor One unit of SDP is equivalent to six units of RDP Advantage : Here recipient is exposed to only single donor Single donor platelet (Apheresis platelets )

30. Storage : A t 20 ̊C- 24 ̊C with continuous gentle agitation Shell life : o nly 5 days, longer storage increases risk of bacterial contamination Platelet – cont.

31. [To treat active bleeding] Count must be kept above 50,000/mm 3 in most bleeding situations In DIC and central nervous system bleeding , cut off is 1,00,000/mm 3 Bleeding on anti platelet medication Indications (Therapeutic )

32. Preparation for an invasive procedure : Neurosurgery or Ocular surgery : 1,00,000/mm 3 Major surgery : 50,000/mm 3 Endoscopic procedures : 50,000/mm 3 for therapeutic : 20,000/mm 3 for diagnostic Central line placement : 20,000/mm 3 Lumbar puncture : 40,000/mm 3 to 50,000/mm 3 Epidural anaesthesia : 80,000/mm 3 Bone marrow aspiration : 20,000/mm 3 (Can be done with lower counts with applying pressure at site of procedure) Indications (Prophylactic ) [To prevent spontaneous bleeding]

33. Prevention of spontaneous bleeding Afebrile patients (Bone marrow suppression) : 10,000/mm 3 Febrile or septic patients : 30,000/mm 3 ITP, TTP or HIT : Transfusion is indicated only if they bleed Haematological malignancies and chemotherapy : 10,000 – 20,000/mm 3 Indications – cont..

34. Dosage of platelets One unit of SDP or 4-6 units of RDP over a period of 20-30 minutes Increases platelet count by approximately 30,000/mm 3 Platelet – cont. Platelets express ABO and HLA type 1 class antigens , usually compatible transfusions appear to cause a greater count increment in patients

35. Method of collection : by apheresis technology , after granulocytes are stimulated by dexamethasone and G-CSF To be transfused within few hours of collection Shell life – 24 hours at room temperature Indications : Neutropenia from chemotherapy or transplantation Aplastic anaemia Neonatal sepsis Chronic granulomatous disease GRANULOCYTE TRANSFUSION

36. Features of PBM Evidence based guidelines for transfusion indication and dose Physician education and monitoring Patient B lood M anagement (PBM) PBM is a multidisciplinary approach to improve patient outcome using evidence based strategies in patients who may need transfusion

37. Preoperative anemia evaluation and management Intraoperative and postoperative autologous salvage Intraoperative normovolemic hemodilution Point of care hemostasis testing Use of hemostatic agents Limiting phlebotomy blood loss for laboratory testing Features of PBM – cont..

38. Types Immune mediated Non-immune mediate I nfectious complication ADVERSE REACTION TO BLOOD TRANSFUSION

39. 1. Acute hemolytic transfusion reaction : Recipient has preformed antibodies that lyse donor erythrocytes ABO isoagglutinins are responsible for the majority of these reactions Clinical Features : Hypotension, tachypnoea , tachycardia, fever chills, hemoglobinemia , hemoglobinuria , chest or flank pain, discomfort at the infusion site, renal dysfunction Work up : S erum haptogloblin , Serum LDH, Indirect bilirubin Transfusion Reaction – Immune mediated

40. Management : STOP blood transfusion immediately Diuresis- Furosemide or Mannitol Subject post transfusion blood to coomb’s test Transfusion Reaction – Immune mediated Cont.. Delayed hemolytic transfusion reactions: - Occurs in patients previously sensitized to donor allo -antigens .

41. Immunohematology and other testing in DSHTR DSHTR (Delayed serologic/hemolytic transfusion reactions) DAT (Direct Anti-globulin Test) Negative Positive Ongoing hemolysis not suspected No further testing recommended Ongoing hemolysis suspected Perform eluate Positive eluate : Antigen type units transfused – if unit segment available Repeat immunohematology on previous specimen – if available Other markers of hemolysis LDH Total Bilirubin Direct Bilirubin Haptoglobin Negative eluate : No further testing recommended

42. Febrile Non-hemolytic Transfusion Reaction Most frequent reaction Chills and rigors and a rise in temperature >1°c Diagnosis of exclusion Antibodies directed against donor leukocyte and HLA antigens mediates these reactions Leukoreduction of blood products reduces the risk Transfusion Reaction – Immune mediated Cont..

43. Anaphylactic Reaction: Symptoms and signs : Shortness of breath, coughing, nausea, vomiting, hypotension, bronchospasm, loss of consciousness, respiratory arrest and shock Treatment : Stop the transfusion and maintain vascular access Epinephrine (0.5- 1 mL of 1 : 1000 dilution subcutaneously) Steroids in severe cases Transfusion Reaction – Immune mediated Cont..

44. 5. Transfusion Associated Lung Injury (TRALI) New ALI/ARDS occurring during or within six hours after blood product administration Anti HLA or anti granulocyte Ab in donor plasma Recipient WBC Complement activation Pulmonary sequestration and activation of neutrophils Endothelial damage Capillary leak in Lungs TRALI Transfusion Reaction – Immune mediated Cont..

45. Symptoms and signs : Dyspnoea, hypotension, fever Bilateral non-cardiogenic pulmonary edema, Pao2/FIo2 <300mmHg Management : Supportive Avoid plasma transfusion from multiparous women and screening for anti-HLA antibodies TRALI Transfusion Reaction – Immune mediated Cont.. 5. TRALI – cont..

46. 6. Transfusion Associated GVHD (TA-GVHD) : Mediated by donor T lymphocytes that recognize host HLA antigens as foreign and mount an immune response Clinical features : Fever with characteristic Cutaneous eruption, Diarrhoea and liver function abnormalities Treatment : GVHD highly resistant to treatment with immunosuppressive therapies Irradiation of cellular components reduces the risk Transfusion Reaction – Immune mediated Cont..

47. 7. Post-transfusion Purpura : Thrombocytopenia 7-10 days after platelet transfusion C ommon in women Antibody react with both donor and recipient platelets Antigen HPA-1a found on platelet glycoprotein receptor ш a receptor Avoid further transfusion IV immunoglobulin or plasmapheresis can be tried Transfusion Reaction – Immune mediated Cont..

48. 8. Allergic reaction: Urticarial reaction are related to plasma protein found in transfused components Treatment : Stop transfusion and A dminister antihistamines (diphenhydramine 50 mg orally or IM) C ontinue transfusion after symptom resolved Premedication with antihistamines can be tried when history of transfusion reaction present Transfusion Reaction – Immune mediated Cont..

49. 1. Fluid over load (TACO) : Clinical Features : S evere hypoxemia, Raised BP, Jugular venous distension, Raised central venous pressure Diagnosis : CXR- pulmonary edema, cardiomegaly, distended pulmonary artery, BNP – elevated >1.5 Treatment : Upright posture, Supplemental oxygen, Diuresis Prevention : S low transfusion rate, Transfuse in small volumes Transfusion Reaction – Non-Immune mediated

50. 2. Hypothermia : - Because of rapid transfusion of refrigerated (4 ̊c) or frozen (18 ̊c) components can cause cardiac dysrhythmia by exposing SA node to cold fluid - can use in line warmer 3. Electrolyte toxicity : Hyperkalemia - Neonate and renal failure patient at risk. Use fresh or washed RBC Hypocalcemia - In multiple transfusion Inj. C alcium IV in separate line Transfusion Reaction – Non-Immune mediated

51. 4. Iron overload : Common after 100 units of RBC transfusion Deferoxamine or Deferasirox can be used 5. Hypotensive reactions : Noted in patient on ACE inhibitors because of increased B radykinin. BP returns to normal without intervention 6. Immunomodulation : Transfusion of allogenic blood is immunosuppressive Mediated by transfused leukocytes L eukocyte depleted cellular products cause less immunosuppression Transfusion Reaction – Non-Immune mediated

52. The transmittable risks include : Hepatitis B , C, D Human T-cell lymphotropic viruses (HTLV-1 & HTLV-2) HIV-1 & HIV-2 Cytomegalovirus West Nile Virus Epstein-Barr virus Transfusion Reaction (Infectious complications) Malaria Syphilis Parvovirus B19 Prions including Creutzfeldt-Jakob and variant Lyme Disease

53. Pre-transfusion: Informed consent, Temp, Pulse, BP, O 2 saturation During transfusion: Vitals after 15 min Only 0.9% NS is compatible Avoid RL and hypo/hypertonic solution Avoid medication in same line, if possible avoid al-together Post transfusion: Check sign for any reaction Vitals 4-6 hr after BT Clinical aspect of BT No transfusion is zero risk event

54. THANK YOU

55. Harrison’s internal medicine 20 th edition Rossis principle of transfusion medicine 5 th edition REFERENCES