blood seminar by anaesthesia contains blood transfusion

blood and its rationale use

1. Moderator : Dr. Nitin BLOOD & BLOOD PRODUCTS : RATIONALE OF THEIR USE

2. History Of Blood Transfusion 1628- Sir William Harvey described Venous circuilation . 1665- First blood transfusion was done in animal-to-animal (dog) blood transfusion by Richard Lower. 1818 – James Blundell, a British obstetrician, performed the first successful transfusion of human blood for treating PPH. Father of Auto transfusion and devised various instruments for performing blood transfusions. 1828 – First successful transfusion in humans.

3. Further Developments 1900 – Karl Landsteiner , an Austrian physician documented the first three human blood groups A,B and O 1914 - Long term anticoagulants, among them sodium citrate, were developed allowing longer preservation of blood. 1916 – First use of blood storage 1939 – Levine described the Rh factor 1972- Apheresis was used to extract one cellular component

4. Definitions BLOOD PRODUCTS Any therapeutic substance prepared from human blood. Whole blood : Unseparated blood collected into an approved container containing an anticoagulant-preservative solution. Blood component : a constituent separated from whole blood, by differential centrifugation of one donor unit or by apheresis : Red cell concentrate, fresh frozen plasma, cryoprecipitate , platelet concentrates etc. Plasma derivative : Human plasma proteins prepared under pharmaceutical manufacturing conditions, such as: Albumin, Immunoglobulin.

5. Blood Components Type Description Preparation Storage and Transportation Indication Dose

6. Components of Blood

7. Principle of Separation Blood component preparation – essential part of blood transfusion services. Increasing demands can only be met by separating it into various components. Helps in rationalizing use of blood. Most commonly prepared using physical properties of blood e.g. centrifugation. Primary Goal – to provide right component to the right patient in the right quality and quantity at the right time. DIFFERENTIAL- CENTRIFUGATION : Sediment of blood cells depend on their size as well as the difference of their density from that of surrounding fluid, viscosity of medium and temperature dependent flexibility of cells.

8. Methods of Preparation : Various methods to separate : Gravity separation – crude but cheaper method. Low speed refrigerated centrifugation - for preparing PRP (platelet rich plasma). High speed refrigerated centrifugation – for PC (platelet concentrate) , FFP and CP (cryoprecipitate). 4. Apheresis by cell seperator .

9. Blood Bank Centrifuge

10. Whole Blood : Whole blood is obtained from a suitable human blood donor by venesection. collected into a sterile, disposable, plastic pack which contains a pyrogen free anticoagulant-preservative solution. variations exist in the volume of blood collected and in the type of anticoagulant-preservative solution used in different regions of the world. Major use – Blood component separation.

11. 450 ml of blood 63 ml of anticoagulant solution Hb approx. 12 g/dl, Hct - 36-45% No components have been removed. Storage Store at 1 -6 °C in an approved blood bank refrigerator, ideally fitted with temperature chart and alarm Shelf life CPD : 21 days CPDA-1 : 35 days AS-1 , AS-2 , AS-5 : 42 days Start within 30 min and COMPLETE infusion within 4 hours of commencement.

12. Anticoagulants and Preservatives CPDA : shelf life-35 days citrate –anticoagulant, phosphate acts as buffer, dextrose act as RBC energy source and adenine act as substrate for ATP synthesis. Adsol ( AS-1 ) : extends shelf life to 42 days . Contain adenine, sodium chloride, glucose & mannitol . Nutricel (AS-3 ) : adenine, Sodium chloride, glucose, Citrate & phosphate. Optisol ( AS-5 ) : adenine, sodium chloride, dextrose & mannitol .

13. Effects of Storage : During storage changes in composition occur resulting, from ongoing RBC metabolism. Reduction in the pH - lactate & pyruvate . Rise in plasma potassium concentration. Progressive reduction in the red cell (2,3 DPG) which may reduce the release of oxygen at tissue level. Loss of platelet function and WBC in whole blood after >24 hours of storage. Reduction in Factor V and VIII (labile factors) to 10–20% of normal within 48 hours of donation. factors such as VII and IX are relatively stable in storage.

14. Parameter 35d(whole blood ) 35 d(packed cell ) Ph 7.55 6.73 6.71 Plasma Hb (mg/dl) 0.50 46.00 246.00 Potassium ( meq /l) 4.20 17.20 76.00 Plasma sodium ( meq /l) 169.00 153.0 122.0 Dextrose (mg/dl) 440.00 282 84.00 2,3 DPG (µm/ml ) 13.20 1.00 1.00 Percent survival - 79 % 71%

15. Indications Increase oxygen carrying capacity – is the only real indication. Acute blood loss >20% TBV. Exchange transfusion Patients needing red cell transfusions where red cell concentrates are not available Contraindications : Risk of volume overload in patients with - chronic anemia Incipient cardiac failure Administration : Must be ABO and Rh compatible with the recipient Never add medication to a unit of blood Use a blood administration set, standard blood filter (150-280 microns). Start slowly 1 Unit : Increases Hct by 3% or Hb 1g/dl.

16. ABO- Rh Typing most serious and tragic reactions are usually caused by accidental transfusion of ABO-incompatible blood. naturally occurring antibodies (i.e., anti-A and anti-B), which activate complement and lead to rapid intravenous hemolysis . Rh (D antigen)- Rh (D) positive – around 85% population; Rh(D ) negative- remaining 15%, anti-D not usually expressed constitutively.

17. Compatibility Testing ABO- Rh typing. Cross matching : a. immediate phase b. incubation phase c. anti globulin phase. 3. Antibody screening.

18. Cross- Matching Trial transfusion , donor RBC mixed with recipient serum complete process take around 45-60 minutes. Immediate phase (1 to 5 minutes ) – at room temp, check against errors in ABO typing & incompatibilities due to naturally occurring antibodies in the M,N, P, and Lewis systems . Incubation phase ( 37˚ C ) – in albumin (30-45 mins) or low ionic strength salt solution (10-20 mins). aids in detection of incomplete antibodies or those antibodies that are able to attach to a specific antigen (i.e., sensitization) but are unable to cause agglutination in saline.

19. Antiglobulin phase ( A ntiglobulin test) : anti globulin sera to incubated tt . detects most incomplete antibodies in the blood group systems, including the Rh, Kell , Kidd, and Duffy blood group systems . In order of significance : anti-Rh(D) , Kell , C, E and Kidd. ANTIBODY SCREENING: Done in both recipient as well as donor for detection of unexpected antibodies trial transfusion between the recipient's serum and commercially supplied RBCs ( screen cells ) that will react with antibodies that are commonly implicated in hemolytic transfusion reactions.

20. Is the Crossmatch Really Needed? ABO-Rh typing - 99.8% chance of a compatible transfusion Antibody screen - increases the safety to 99.94% Cross-match - increases safety to 99.95%. EMERGENCY TRANSFUSION : In severely injured or hemmorhaging patients : Lethal triad of hypothermia, acidosis and a coagulopathy. Approach of damage control resuscitation including permissive hypotension, damage control surgeries or urgent need of blood transfusion - Type-Specific, Partially Cross-matched Blood. Type-Specific, Uncross-matched Blood. Type O Rh-Negative (Universal Donor), Uncross-matched Blood.

21. Selection of donor Blood donors must be selected with care. Donor’s blood be accurately typed & he/she must be free from diseases. Mandatory Screening Tests : HBsAg Anti HCV Anti HIV 1 and 2 VDRL/TPPA Malarial parasite

22. Other tests carried out depending on local need : Prion diseases – Creutzfeldt Jacob Disease. Cytomegalovirus. Also mandatory that the donor should be free from fever a fortnight before donating blood , free from parasitic diseases like Malaria and Filariasis

23. Component production : Whole blood donations & subjecting to centrifugation. Apheresis : It is a sterile process in which a donor is connected to a specialized device by which blood is withdrawn and a specific component , usually plasma or platelets, is mechanically separated and collected. The remaining components not required are then re-infused back into the donor. Advantages : Relatively large amounts of plasma or platelets can be collected from one donor. RBC’s are returned- donor not rendered anemic .

24. Red Cell Components : Packed red blood cells/ red cell concentrates : By removing 150-200ml of supernatant citrated plasma from centifuged whole blood. A unit of packed red cells has a Hct of between 75-80% . increase Hct by 3%-5% and Hb by 1 g/dl. Advantage : oxygen carrying capacity equals that of whole blood in half the volume. significant decreased levels of isoagglutinins , metabolites and electrolytes. 2. Washed RBC/ micro-aggregate free blood : Saline washing removes residual plasma (98%), and reduces the concentration of leucocytes, platelets and cellular debris. prevent reactions to leucocytes and platelet antigens. Hct of 70-80% , volume of about 180ml .

25. 3. Irradiated Red cells: Gamma radiated to destroy the lymphocytes Lack of T cells prevent graft- vs - host disease . used in severely immunocompromised patients, lymphoma patients, Stem cell / marrow transplants 4 . Leukocyte depleted RBC : Leukocyte depleted red cells have 99.9% of WBC removed by freezing or microfiltration. Little loss of RBC volume. Minimises white cell immunisation in patients. This reduces, but does not eliminate the risk of CMV, Epstein-Barr, HTLV infections, Creutzfeld Jacob disease and FNHTR.

26. ASA Guidelines Transfusion of PRBC : These recommendations are proposed by, the American Society of Anesthesiologists Practice Guidelines 2015 . Recommendations : Monitoring for blood loss : visual inspection of surgical field, suction bottles, soaked gauze pieces. Monitoring for inadequate perfusion and oxygenation of vital organs : monitoring e.g. NIBP, heart rate,SpO 2 ,urine output, ECG or special monitoring like : ABG analysis, mixed venous saturation

27. 3 . T ransfusion indications . The use of a single hemoglobin ‘ trigger’ for all patients that fail to consider all important physiologic and surgical factors affecting oxygenation is not recommended. Estimation of Hb concentration perioperatively should guide red cell transfusion : Hemocue at bedside or OR in 5-15 mins / SpHb technique. 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 , especially when the anemia is acute.    The determination of whether intermediate hemoglobin concentrations (6 to 10 g/dl) justify or require RBC transfusion should be based on the patient's risk for complications of inadequate oxygenation. a transfusion trigger of 8.0 g/ dL or less can be tolerated by patients who are not critically ill or do not have severe cardiorespiratory disease. Symptomatic patients should be transfused.

28. Recommendations continued : acute blood loss >1500 ml or 20% of blood volume or active ongoing blood loss. clinical indication of tissue hypoxia . Hemoglobin level less than 8  g/ dL Hemoglobin level less than 9-10 g/ dL with major disease (e.g., emphysema, ischemic heart disease ) Hemoglobin level of less than 10 g/ dL with autologous blood Hemoglobin level less than 11-12   g/ dL with ventilator dependent

29. Conditions That May Decrease Tolerance for Anemia and Influence the RBC Transfusion Threshold Increased oxygen demand : hyperthermia, pregnancy , sepsis etc. Limited ability to increase Cardiac output : CAD, cardiomyopathy, b-blockade. Occlusive vascular disease : cerebral or coronary Left shift of oxy- Hb dissociation curve : alkalosis, hypothermia. Abnormal hemoglobin : sickle cell disease Impaired oxygenation : high altitude, pulmonary disease Ongoing or imminent blood loss : traumatic bleeding, placenta previa or accreta .

30. Platelets concentrates Collection of platelets : Pooled platelets / RDP : platelets prepared from 4 to 6 donor units ‘pooled’ into one pack to be given to a thrombocytopenic patient. Disadvantage : Increase the risk of transmission of infection Apheresis platelets / SDP : These are collected from a single donor (to reduce the risk of disease transmission). Special requirement : selected donor Advantage : The amount of platelets collected with this procedure represents the equivalent of 6-8 units of random donor platelets .

31. Volume : 30-50 ml Storage : 20°C–24°C (with agitation) and pH of 6.2-7.8 Shelf life : 3 days in platelet incubator and agitator. 24 hours if no storage cabinet. Longer storage increases the risk of bacterial proliferation and septicemia in the recipient. Administration : After thawing , platelet concentrates should be infused as soon as possible, generally within 30 mins , because of the risk of bacterial proliferation. Must not be refrigerated before infusion as this reduces platelet function.

32. Platelet concentrates prepared from Rh D positive donors should not be given to a Rh D negative potential child-bearing female. Whenever possible ABO compatible platelets preferable. Dosage : 1 unit of RDP - increases platelet count by ~ 5000- 10,000/cu.mm. 1 unit of SDP - increases platelet count by ~ 30,000 – 60,000/cu.mm Increase may be less in cases of septicemia, splenomegaly or DIC etc.

33. Platelet incubator

34. Indications – by ASA 2015 1. Prophylactic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction e.g . ITP , Heparin induced thrombocytopenia etc. 2. Prophylactic platelet transfusion is rarely indicated in surgical patients with thrombocytopenia due to decreased platelet production when the platelet count is greater than 100 × 10 9 /L and is usually indicated when the platelet count is less than 50 × 10 9 /L .

35. 3. Surgical and obstetric patients with microvascular bleeding usually require platelet transfusion if the platelet count is less than 50 × 10 9 /L and rarely require therapy if it is greater than 100 × 10 9 /L. 4. Vaginal deliveries or operative procedures ordinarily associated with insignificant blood loss may be undertaken in patients with platelet counts less than 50 × 10 9 /L . 5. Platelet transfusion may be indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding . Eg : patient receiving clopidogrel .

36. Platelet thresholds - British Committee for Standards in Hematology, ASA & French safety agency for health products

37. Fresh frozen plasma collected as the supernatant after centrifuging a donation of whole blood . Contains normal plasma levels of labile and non labile clotting factors, Protein C and S, complement, albumin and immunoglobulin It is frozen within 6-8 hours and may be stored for up to 1 year at -20 °C or below . (-65 °C for 7 yrs ) Before use , thawed using a dry oven (10 mins ), microwave (2-3 mins ) or a water bath at 30-37 ˚C (20 mins ). Thawed FFP is best used immediately but may be stored at 4°C and infused within 24 hours. Labile coagulation factors (V & VIII) rapidly degrade; use within 6 hours of thawing.

38. Water bath

39. Dosage & administration : Volume – 200-250 ml For effective coagulation to occur: clotting factors of ~ 20-30% of normal levels suffice. This level is achieved by ~ 10-15 ml/kg of FFP. 1 U/kg raises factor VIII by 2% and factor IX by 1% in plasma. Must normally be ABO compatible to avoid risk of hemolysis in recipient. No cross-matching however needed .

40. Indications for FFP For urgent reversal of warfarin therapy- 5-8 ml/kg suffice when PCCs are not available For correction of inherited coagulation factor deficiencies for which specific concentrates not available. Correction of a quired multifactor deficiencies with clinical evidence of bleeding or in anticipation of a major surgery or an invasive procedure. Microvascular bleeding associated with massive transfusion and estimated blood loss > one blood volume approx 70ml/kg (when PT or aPTT >1.5 times the control or can’t be obtained or INR greater than 2.0, in the absence of heparin) Liver dysfunction or DIC with clinical signs of bleeding. Heparin resistance ( antithrombin III deficiency) in a patient requiring heparin.

41. FFP is not indicated : If PT or INR and aPTT are normal. Solely for augmentation of plasma volume ( hypovolemia ) or albumin concentration. Immunoglobulin replacement. Nutritional support. Wound Healing. Precautions: Acute allergic reactions are common. Anaphylactic reaction may occur.

42. Cryoprecipitate Cold- insoluble portion of plasma that precipitates when FFP is thawed between 1-6◦C very rich in high molecular weight proteins, including factor VIII, vWF and fibrinogen, factor XIII, fibronectin . Usually supplied as a single donor pack or a pre pooled pack of 6 or more single donor units 1 unit of whole blood provides about 15ml of cryoprecipitate. Factor VIII: 80–150 i.u /pack Factor XIII : 20-30% of whole blood.

43. Administration : If possible, use ABO-compatible product After thawing, infuse as soon as possible through a standard blood administration set. Must be infused within preferably 30 mins of thawing . Dose- 1 bag – 350 mg fibrinogen ( r ecovery rate approx 75%) In a 70 kg patient : 6 bags of cryo raises fibrinogen by 45 mg/dl.

44. Indications : Microvascular bleeding with hypofibrinogenemia DIC with fibrinogen < 80-100 mg/ dL Hemorrhage or massive transfusion with fibrinogen < 100-150 mg/ dL For patients with vWD if no availability or response to vWF /VIII concentrate. Congenital fibrinogen deficiencies. Factor XIII deficiency. When a test of fibrinogen activity indicates a fibrinolysis As an adjunct in massively transfused patients when fibrinogen concentrations cannot be measured in a timely fashion

45. Granulocytes concentrate They are collected either by apheresis from family members or derived from whole blood. Infused within 24 hours of collection Stored at 20-24 °C. Contain 1.0 × 10 10 granulocytes Pretreatment with recombinant G-CSF and dexamethasone can yield 4-8 × 10 10 granulocytes Indicated for life- threatening infections in neutropenic cancer patients unresponsive to antibiotics. Nowadays, G-CSF ( filgastrim ) are being used instead of granulocytes.

46. Criteria ANC < 500 Documented infection (bacterial or fungal) for 24-48 hours Unresponsive to appropriate antibiotics Marrow recovery

47. Prothrombin Complex Concentrates (PCC) Factor IX recovered from plasma/plasma fractions by absorption with ion exchanges or inorganic chemicals. These products are all complexes of factor II, VII, IX and X Indication : treatment of factor IX deficiency or hemophilia B. For treatment of aquired hypoprothrombinemic bleeding disorders, warfarin overdose .

48. Albumin and Plasma Protein Preparations Albumin as 5% or a 25% solution in isotonic saline. Plasma protein fractions containing Albumin and globulins. Prepared from large pools of plasma reconstituted in isotonic electrolyte solutions. Can be given without ABO typing and crossmatching . Primarily as Volume expanders , documented hypoproteinemia or burns/peritonitis . Very expensive and short in supply. Bacterial Sepsis associated.

49. Blood Transfusion WHO RECOMMENDATIONS : Well organized, nationally coordinated blood transfusion service National blood policy and plan incorporating the clinical use of blood. Provide training for all clinicians, nurses, blood bank staff involved in the transfusion process. Establish transfusion committees in each hospital. Establish a national haemovigilance system to monitor, report and investigate adverse events associated with transfusion .

50. Strategies to minimize transfusions : Pre-operative Considerations • A planned surgical transfusion checklist may be helpful in guiding transfusion and avoiding inappropriate red cell transfusion. • Patients should have a full blood count and group and antibody screen performed when placed on the waiting list for an elective surgical procedure that is likely to require red cell transfusion. The use of surgical blood ordering schedules can help decide. Prevention and early diagnosis and treatment of anemia (2-4 weeks prior) preoperatively as a vehicle for decreasing the need for intraoperatively transfusions is widely accepted. The use of recombinant erythropoietin in the peri -operative setting is still under investigation . • Use of crystalloids and colloids in acute blood loss.

51. Meticulous surgical technique ( diathermy, hemostatic packs, fibrin glue). Use of posture ( 2.5 cm vertical height from heart decrease 2mm Hg in BP). Use of torniquets . Blood Conservation Strategies : preoperative autologous blood donation, Acute Normovolemic hemodilution ( ANH) perioperative blood salvage and measures to decrease blood loss ex: deliberate hypotension by SNP, NTG Using alternative approaches to minimize surgical bleeding such as use of desmopressin , antifibrinolytics . Desmopressin (0.3 µ/kg IV) may be used to reduce bleeding times in patients with mild forms of Haemophilia A or vWD . It promotes the endothelial cell release of ( vWF ). Improves platelet function in uraemic patients.

52. Maximum Surgery Blood Ordering Schedule Reference used to guide clinicians in ordering blood before surgery. Aim to maintain a C/T ratio :: crossmatch /transfusion ratio of 2.1 to 2.7 Limits the outdating of blood and blood products and excess use of personnel time. Is a table of elective surgical procedures which lists the number of units of blood routinely requested and cross matched for them pre-operatively.

53. COMPLICATIONS OF BLOOD TRANSFUSION

54. Transfusion reactions may be : Immune mediated and Non immune mediated.

55. ACUTE HEMOLYTIC TRANSFUSION

56. Signs & symptoms Fever with chills Nausea, headache, flushing Burning sensation along the vein Oppressive feeling in chest Under GA Haemoglobinuria (presenting sign) Bleeding Tachycardia , hypotension Consequences – mainly affects Renal - ARF ( acid hematin formation ) Coagulation – DIC Hypotension - Kallikreins

57. Lab tests: Serum hemoglobin and haptoglobin . Plasma & urine haemoglobin (plasma Hb 150 mg/dl) Serum bilirubin . PC, PT and aPTT . Compatibility testing. Direct antiglobulin tests (direct coombs tests).

58. TREATMENT 1. STOP THE TRANSFUSION. 2. Maintain the urine output min of 75 to 100mL/hr by the following methods: Generously administer IV fluids and possibly mannitol (12.5 to 50 g, given over 5 to 15 minutes). If ineffective, administer furosemide (20 to 40 mg) intravenously. 3. Alkalinize the urine (just 40-70 mEq per 70 kg required to raise the urine pH to 8).

59. 5. Return unused blood to blood bank for repeat cross-match . 6. Send patient's blood and urine sample to blood bank for examination. (immediate and post 24 hr) 4ml in plain tube for antibody identification. 2ml in EDTA tube for FDP. >10 ml urine sample – Hb 7. Prevent hypotension to ensure adequate renal blood flow. 8. “ Report of reaction to blood or plasma transfusion’’ form must be completed.

60. Delayed Hemolytic Tranfusion Reactions Occur in patients previously sensitized to RBC allo -antigens. Hemolysis occurs in 2 to 21 days. IgG antibodies to minor RBC antigens most commonly involved are the Rh and Kidd . Manifested by a decrease in the post-transfusion hematocrit value . Patient can also have fever, anemia and jaundice. No specific therapy is usually required . Self limited .

61. Febrile non-hemolytic Transfusion Most frequent reaction. Characterized by chills, rigors, headache and myalgia and a ≥ 1°C rise in temperature. Mediated by antibodies directed against donor leukocyte and HLA antigens. Anti-HLA antibodies may be demonstrated in the recipient's serum. Also, storage generated leucocyte derived pro-inflammatory cytokines. It is a diagnosis of exclusion, DAT readily differentiates. Prevention : use of leukocyte-reduced blood products : Prevent or delay sensitization to leukocyte Ag Therapy : stop transfusion, antipyretics, supportive care.

62. Transfusion Related Acute Lung Injury TRALI presents as acute respiratory distress, either during or within 6 h of transfusing the patient. Leading cause of transfusion-associated fatalites . It is caused by donor antibodies in plasma-containing blood components (usually FFP or platelets, and occasionally red blood cells) interacting with antigens on the patient’s granulocytes (human leukocyte antigen or granulocyte specific). resulting in granulocytes aggregation and complement activation in the pulmonary vasculature and increase capillary permeability.

63. Develops signs and symptoms of respiratory compromise (fever , acute onset dyspnea, fluid in the endotracheal tube, severe hypoxia, ↑ peak airway P ) and non cardiogenic pulmonary edema within 6 h after the transfusion . (without any left atrial hypertension) Chest X ray - bilateral interstitial infiltrates Treatment Stop transfusion Supportive measures P atients usually recover within 96 hrs .

64. Allergic Reactions Urticarial reactions are related to soluble antigens in donor plasma . Response to plasma proteins in the blood component – type 1 hypersensitivity response Mild reactions may be treated symptomatically by : - temporarily stopping the transfusion (not actually allergic to blood components but antibodies) - administering antihistamines (Inj. Avil 0.1mg/kg ) Pt. with a past history of allergic reaction should be premedicated with an antihistamine. Cellular components can be washed to remove residual plasma for the extremely sensitized patient.

65. Anaphylactic Reactions presents after transfusion of only a few ml of the blood component . Generally an I gG anti IgA in an IgA deficient recipient transfused with IgA containing blood products Formation of IgA/ IgG immune complexes activation of complement release of C3a and C5a anaphylatoxins Symptoms and signs Apprehension and impending doom Generalised flushing Nausea and vomiting Diarrhea abdominal cramps Larngeal edema Bronchospasm Dyspnea Profound hypotension shock and arrest

66. Treatment Remove trigger ( Stop the transfusion ). Assess circulation, airway, breathing, mental status and skin. High flow supplemental O 2. Establish large bore IV access. Inject Epinephrine (0.01 mg/kg of 1:1,000 dilution intramuscularly to a max of 0.5 mg adult and 0.3 mg child). Position of comfort in case of respiratory distress or vomiting. Glucocorticoids may be required in severe cases. Patients who have anaphylactic or repeated allergic reactions to blood components should be tested for IgA deficiency.

67. GRAFT vs HOST DISEASE Transfusion-related GVHD is mediated by donor T lymphocytes engraft in receipients and attack host HLA antigens as foreign. Immunocompromised host Manifested clinically by : Fever Cutaneous eruption Diarrhea Liver function abnormalities. Marrow aplasia & pancytopenia .

68. Highly resistant to treatment with immunosuppressive therapies, Clinical manifestations appear at 8–10 days, and death may occur at 3–4 weeks post transfusion. Prevented by gamma irradiation of cellular components.

69. Post Transfusion Purpura Presents as thrombocytopenia 7–10 days after platelet transfusion. Recipient antibodies attack donor platelet antigen. Occurs predominantly in women. Delayed thrombocytopenia is due to the production of antibodies that react to both donor and recipient platelets. Treatment intravenous immunoglobulin. plasmapheresis can be used to remove the antibodies.

70. Non Immunological Reactions Transfusion Associated Cardiac Overload Blood components are volume expanders, and hence quickly lead to volume overload. Features : Dyspnoea , hypertension , crepitations and low O 2 saturation Pt. with cardiac or renal disease, infants or the critically ill are at increased risk Monitoring the rate and volume of the transfusion and using a diuretic can minimize this problem.

71. Hypothermia Refrigerated (2 - 4°C) or frozen (–18°C or below) blood components can result in hypothermia when rapidly infused. One unit at 4°C decreases the body temperature by 0.25 °C Cardiac dysrhythmias can result from exposing the SA node to cold fluid. Prevented by warming the blood to body temperature before transfusion The safest method of warming blood is to pass it through plastic coils or plastic cassettes in a warm water (37° to 38°C) bath or warming plates.

72. Dyselectrolytemia Hyperkalemia RBC leakage and cell hemolysis during storage increases the concentration of potassium in the unit. Neonates and patients in renal failure are at risk Prevention - using fresh or washed RBCs

73. Citrate Toxicity Citrate used to anticoagulate blood components, chelates calcium and thereby inhibits the coagulation cascade. Hypocalcemia , may result from multiple rapid transfusions leading to muscle weakness, tetany , arrhythmias, myocardia l dysfunction and acquired coagulopathy. Calcium infusion is not always required If calcium or any other intravenous infusion is necessary, it must be given through a separate line.

74. Iron Overload Each unit of RBCs contains 200–250 mg of iron. Symptoms and signs of iron overload include dysfunction of endocrine, hepatic, and cardiovascular systems Prevention - using alternative therapies (e.g., erythropoietin) and judicious transfusion is preferable and cost effective. Treatment - Chelating agents ( deferoxamine & deferasirox )

75. Hypotensive Reactions Blood products contain bradykinin that is normally degraded by ACE. Also, coagulation pathway activation as well activates bradykinin pathway. The blood pressure typically returns to normal without intervention. Therapy : Stop transfusion Large bore IV access Continuous monitoring.

76. Transfusion related Immunomodulation (TRIM) Homologous ( allogenic ) blood transfusion exerts a nonspecific immunosuppressive action on the recipient. Mediated by transfused leukocytes. Leukocyte-depleted cellular products may cause less immunosuppression . Recurrence of resected cancers postoperative infections and virus activation.

77. Infections : Blood donors may carry infectious agents in their blood. : Hepatitis B and C HIV-1 and HIV-2 HTLV-I and HTLV-II Cytomegalovirus (CMV ) Syphilis ( Treponema pallidum ) Chagas disease ( Trypanosoma cruzi ) Malaria

78. Hepatitis C Majority of post-transfusion hepatitis is caused by the hepatitis C virus. Infection with HCV may be asymptomatic ( < 1/3 rd develop jaundice ) or can lead to chronic active hepatitis, cirrhosis, liver failure. Hepatitis B Donated blood is screened for HBV using assays for HbsAg . Vaccination of individuals who require long-term transfusion therapy can prevent this complication .

79. HIV I and II Several measures have been recommended to decrease the transmission of HIV Routine screening of the donor is being done for HIV I and II (ELISA). Blood banks discourage members of high-risk groups from donating blood. HTLV I and II Human T-cell lymphotropic virus type 1 (HTLV-1) associated with adult T-cell leukemia and progressive myelopathy can be transmitted by blood transfusions.

80. Cytomegalovirus Asymptomatic chronic infection with CMV is so common in healthy adults. CMV survives within cells and exist in latent form in the monocytes of people with antibodies indicative of earlier infection. The evidence for transmission of CMV is when the recipient changes from a seronegative to a seropositive state accompanied by the mononucleosis-like illness several weeks after transfusion. Components such as fresh frozen plasma and cryoprecipitate, components from seronegative donors, and leukoreduced components are safe. Syphilis Post-transfusion syphilis is unlikely because the infective agent cannot survive during storage at 1°C to 6°C. Platelet concentrates are most likely to transmit because they are commonly stored at room temperature .

81. Other rare transfusion-transmissible infections include: Human parvovirus B19 Brucellosis Epstein-Barr virus Toxoplasmosis Infectious mononucleosis Lymes disease Creutzfelt Jakob Disease

82. Changes in Oxygen Transport RBCs are transfused primarily to increase transport of oxygen to tissues. ↑ in circulating red cell mass leads to ↑ O 2 uptake in lungs and probable ↑ in O 2 delivery to tissues . The respiratory function is impaired during preservation owing to ↓ in 2,3 DPG levels, making it difficult for them to release O 2 to the tissues immediately after transfusion.

83. Acid-Base Abnormalities The pH of most storage media is very acidotic. Accumulation of lactic and pyruvic acids by RBC metabolism and glycolysis, the pH of blood continues to decrease to about 6.9 after 21 days of storage. P co 2 is high mainly because the plastic container of blood does not provide an escape mechanism for CO 2 . Citrate present in large quantities, endogenous generation o f bicarbonate → metabolic alkalosis after blood transfusion. Empirical administration of sodium bicarbonate not indicated.

84. Coagulation Major trauma and/or blood loss itself will initiate a cascade of coagulation abnormalities, consumptive coagulopathy from tissue hypoperfusion The addition of a large amount of blood (e.g., 6 to 10 units of packed RBCs) augments this coagulopathy. Coagulopathy is caused by the volume of blood given and the duration of hypotension or hypoperfusion .

85. Dilutional thrombocytopenia Dilutional thrombocytopenia is a cause of a hemorrhagic diathesis in a patient who has received multiple units of blood. Platelets in stored whole blood at 4 ⁰C are damaged sufficiently to be readily trapped and absorbed by the RES soon after infusion. After storage for 24 hrs - 10% of normal activity only 48 hrs - 5% of normal activity only Infusion of blood stored for longer than 24 hours dilutes the available platelet pool.

86. Decreased factor V and VIII Factors V and VIII gradually decrease to 15% and 50% of normal in whole blood after 21 days of storage The following criteria should be used: 1. Generalized bleeding that cannot be controlled with surgical sutures or cautery. 2. Partial thromboplastin time at least 1.5 times normal. 3. Platelet count greater than 70,000/mm3.

87. The traditional definition of massive transfusion is 20 units RBCs in 24 hours, approximately 1 blood volume in a 70 kg pt.

88. Activation of Massive transfusion protocol (1:1:1) Hemodynamically unstable SBP < 90 mm Hg Anticipated ongoing blood loss in a pt. undergoing major surgery Lab values : pH < 7.1 Base deficit > 6 meq /L Temperature < 34  C INR >2.0 Platelet count< 50,000/mm3 Aim for 1:1:1 ( PRBC:FFP:Platelets )

89. Blood bank sends 4 or 6 units of un- crossmatched O negative PRBC if status not known 4 units of thawed plasma 6 units of RD platelets or 1 unit of SDP Monitoring Protocol : Hct , PT, PTT, fibrinogen, Platelets, TEG, ROTEM . After this, if the patient remains bleeding, 6 more units of PRBC and FFP is prepared along with 20 units of cryoprecipitate. Latter given in order to elevate the fibrinogen level before the next step i.e is to transfuse recombinant activated factor VII At any point if hemorrhage stops, the protocol is terminated after notifying blood bank

90. Thank you

91. Gauze pieces blood? Tbv ? Dic ? Pt aptt ?