Blood Transfusion Presented by: Dr. Dhritiman Chakrabarti
An adult human has about 4–6 liters of blood circulating in the body. Among other things, the primary function of blood is to transport oxygen to various parts of the body. Blood consists of several types of cells floating around in a fluid called Plasma.
The Red Blood Cells contain Hemoglobin, aprotein that binds oxygen. Red blood cellstransport oxygen to, and remove carbondioxide from, the body tissues.The White Blood Cells are the cells primarilyresponsible for immunity.The Platelets help in hemostasis.The Plasma contains ions and various kindsof proteins serving diverse functions.
DefinitionsA Blood Transfusion is the infusion of wholeblood or a blood component such asplasma, red blood cells, or platelets into thepatient’s venous circulation.A blood transfusion is given because of redblood cell loss, such as with hemorrage orwhen the body is not adequately producingcells such as platelets. The person receivingthe blood is the Recipient. The person givingthe blood is the Donor.
Blood GroupsAn Individual’s blood is commonly classifiedinto one of the four main groups(A, B, AB, and O). The surface of anindividual’s red blood cells contains a numberof proteins known as Antigens that are uniquefor each person. Many blood antigens havebeen identified, but the antigens A, B, and Rhare the most important in determining bloodgroup or type. Because antigens promoteagglutination or clumping of blood cells, theyalso known as Agglutinogens.
The A antigen or agglutinogen is present on theRBCs of people with blood group A , the Bantigen is present in people with blood groupB, and both A and B antigens are found on theRBC surface in people with group AB blood.Neither antigen is present in people with groupO blood .
Preformed antibodies to RBC antigens arepresent in the plasma; these antibodies areoften called Agglutinins. People with bloodgroup A have B antibodies (Agglutinins ), Aantibodies are present in people with bloodgroup B , and people with blood group O haveantibodies to both A and B antigens . Peoplewith group AB blood do not have antibodiesto either A or B antigens .
If a person with type O blood is transfusedwith blood from a person with either group Aor group B blood, there would be destructionof the recipient’s red blood cells because hisor her anti-A or anti-B agglutinins would reactwith the A or B antigens in the donor’s redblood cells.
This example shows why individuals with typeAB blood are often called UniversalRecipients (because people in this bloodgroup have no agglutinins for either A or Bantigens) and group O people are often calledUniversal Donors (because they have neitherA nor B antigens).
Rhesus (RH) FactorThe Rh factor is an inherited antigen in humanblood.Blood that contains the Rh factor is known asRh-positive, when it is not present the blood issaid to be Rh-negative. Rh blood does notnaturally contain Rh antibodies. If Rh-positiveblood is injected into an Rh-negativeperson, the recipient develops Rh antibodies.Subsequent transfusion with Rh-positive bloodmay cause serious reactions with clumping andhemolysis of red blood cells.
Other Blood Groups In addition to the ABO antigens and Rh antigens, many other antigens are expressed on the RBC surface membrane. The International Society of Blood Transfusion currently recognizes 30 blood-group systems (including the ABO and Rh systems). For Eg. MNS, Kell, Kidd, Duffy, Lewis etc. These are mostly involved in Delayed Hemolytic Transfusion reactions.
Typing and Cross MatchingBefore any blood can be given to a patient, itmust be determined that the blood of the donoris compatible with the patient. The laboratoryexamination to determine a person’s bloodgroup and Rh factor is called Blood Typing.
The process of determining compatibilitybetween blood specimens is Crossmatching.RBCs from the donor blood are mixed withserum from the recipient, a reagent (Coombs’serum) is added, and the mixture is examinedfor visible agglutination. If no antibodies tothe donated RBCs are present in therecipient’s serum, agglutination does not occurand the risk of transfusion reaction is small.
Selection of Blood Donors Blood donors must be selected with care. Not only must the donor’s blood be accurately typed, but it is also important to determine that the donor is free from diseases. The primary tests recommended by WHO are the following:1. Surface antigen for hepatitis B( HbsAg)2. Antibody to Hepatitis C3. HIV antibody (Subtypes 1 & 2)4. Serology tests for Syphilis
Other tests carried out depending on local need :1. Prion diseases – Creutzfeldt Jacob Disease2. Cytomegalovirus3. HIV Nucleic acid test (p24) Also mandatory that the donor should be free from fever a fortnight before donating blood. Also should be free from parasitic diseases like Malaria and Filariasis.
Blood Conservative Strategies Preoperative Autologous Donation – Effectiveness is limited because of less vigorous erythropoietic response and the process simply results in anemia at time of surgery. – Benefits are the elimination of disease transmission, allergic and incompatible reactions. – But, more expensive, sometimes wasted. – Usage has declined.
Acute Normovolemic Hemodilution – Patient is bled immediately before surgery. – Down to haematocrit 25-30% with CVP monitoring – Strategy is that intraoperatively the patient will lose blood of low hematocrit value and reduce total red blood cell loss. – Collected blood is transfused back after surgery. – Less frequently used.
Intraoperative blood salvage – Blood is salvaged intraoperatively from sites where fresh blood has collected before the surgery – Only applicable to clean operative sites without bacterial, bowel or tumor cell contamination. – Contemporary cell salvage devices anticoagulate the blood, separate the RBCs from the blood, wash the RBCs extensively in saline and reinfused to the patient in aliquots of 125 – 225ml with Hematocrit of 45 – 65%.
Transfusion of Whole blood has been largely replaced by FFP and specific component therapy depending on nature of deficiency.
Whole blood – Haematocrit of 35%-45% – 300 ml of 4:1 mixture of donor plasma and a nutrient citrate anticoagulant solution – Stored at 2-6 deg C (maximum for 35 days) – Deterioration is rapid when kept out of refrigerator or transport box – Transfusion should be completed within 4 hrs – Warmer is used if large volume has to be transfused in a short time – Not suitable for symptomatic or critical anemia
Packed Red Blood Cells – Obtained from single donor – Contains Red cells in CPDA solution (citrate, phosphate, dextrose and adenine) with Hct of 70- 75% and a total volume of 250-275ml. – Has a shelf life of 35 days at storage temp. of 1-6 deg C. – In case Additive solution solution is added, the infusate is of Hct 60%, Total volume 250-350ml., less citrate, longer shelf life of 42 days at storage temp. of 1-6 deg C. – Improves tissue oxygenation after hemorrhage and in anemic patient – One unit of PRBCs typically will raise the hematocrit by 3- 4% and the blood hemoglobin concentration by 1 g/dl.
Red Blood Cell Transfusion GuidelinesAcute and Perioperative Blood Loss1. Estimate blood loss If > 30-40% of rapid blood loss: transfuse RBCs and use volume expanders If < 30-40% of rapid blood loss: RBCs not usually needed in otherwise healthy person2. Monitor vital signs; Tachycardia and hypotension not corrected with volume expanders: RBCs needed3. Measure haemoglobin If Hb > 10 g/dL: RBCs rarely needed If Hb < 7 g/dL: RBCs usually needed If Hb 7-10 g/dL: RBCs may be needed, determined by additional clinical conditions4. Hematocrit trigger point for transfusion is <21%.5. For cardiac disease patients, threshold goes up to Hb <10gm% and hematocrit <30%.
Chronic Anaemia1. Transfuse only to decrease symptoms and to minimize risk (generally at Hb of less than 7 g /dL). Do not transfuse above 7g/dL Hb unless patient is symptomatic.2. Treat nutritional and mild blood loss anemia with specific therapeutic agents as indicated (iron, folic acid, B12).
Guidelines for Paediatric Transfusion If Hb is < 4 g/dL, transfuse. If Hb is > 4 g/dL and < 5 g/dL, transfuse when signs of respiratory distress or cardiac failure are present. If patient is clinically stable, monitor closely and treat the cause of the anaemia. If Hb is > 5 g/dL, transfusion is usually not necessary. Consider transfusion in cases of shock or severe burns. Otherwise, treat the cause of the underlying anaemia. Transfuse with 10 to 15 ml/kg of PRBCs or 20 ml/kg of whole blood. In the presence of profound anaemia or very high malaria parasitaemia, a higher amount may be needed.
Platelets – Available as concentrates from single or multiple donors – Manual Thrombapheresis is done either by ‘soft spin’ centrifugation or re-centrifugation of buffy coat layer. – Can also be prepared from single donor by an Automated Apheresis machine – Platelets have very short shelf life, typically five days & are stored under constant agitation at 20-24 deg C. – No effective preservative solutions, lose potency very quickly, best when fresh, thus very short turnover time. – One unit has about 3 10^11 platelets
Indications for platelet transfusion Indicated when platelets count fall 50,000/cumm1. Chemotherapy, Radiotherapy for leukemia, multiple myeloma2. Aplastic anemia3. AIDS4. Hypersplenism5. ITP6. Sepsis7. Bone marrow transplant, organ transplant or surgeries such as cardiopulmonary bypass. Avoided in those with heparin-induced thrombocytopenia (HIT) or disseminated intravascular coagulation (DIC) or Thrombotic thrombocytopenic purpura(TTP).
Expected Platelet Counts After Infusion Platelet count increase as well as platelet survival after transfusion is related to the dose of platelets infused and to the patients body surface area (BSA). Usually these values are less than what would be expected. Expected platelet increase (per μL) = # platelets infused x CCI / BSA (m2) The theoretical value of the CCI is 20,000/μL but clinically, the value is closer to 10,000/μL. If the CCI is less than 5,000/μL, patients are said to have "refractoriness" to platelet transfusion.(Corrected platelet count increment (CCI) = platelet increment at one hr x BSA (m2) / # platelets infused x 10^11 )
Fresh-frozen plasma – Produced from a Single donation – 200-300 ml of plasma with 40-60 ml of citrate anticoagulant nutrient mixture – Stored at -30 deg C (shelf life of 12 months) – Thawed rapidly at 37 deg C – Infused intravenously through a standard blood set with on- line filter – ABO group must be compatible – Infusion of 1 unit should be complete within 4 hr of thawing
Indication for FFP transfusion – To correct isolated plasma protein deficiencies – To reverse oral warfarin anticoagulation – In patient with liver disease, major hepatic resection and severe liver injuries – DIC – Bleeding diathesis after large volume blood transfusion – TTP
Cryoprecipitate – Concentrate of factor VIII, VonWillebrand’s factor, fibrinogen and factor XIII – Each 15 mL unit typically contains 100 IU of factor VIII, and 250 mg of fibrinogen. – The product is manufactured by slowly thawing a unit of FFP at temperatures just above freezing (1- 6 C) and then centrifuged to remove the majority of the plasma, and the precipitate is resuspended in the remaining plasma or in sterile saline – Stored at -30 deg C (shelf life 12 month). – Also thawed at 37 deg C. – Transfusion should be completed within 4 hrs.
Indication of Cryoprecipitate transfusion – Fibrinogen deficiency and dysfibrinogenaemia – Uraemic bleeding – VonWillebrand’s disease
Special blood components – Irradiated components:- It is the only effective means of preventing Graft vs. Host Disease while transfusing blood components to immuno-compromised patients. – Leuco-reduced cellular component:- Benefits are 1. Decreased alloimmunization/platelet refractoriness in multiply transfused leukemics. 2. Prevention of febrile reactions to RBC/platelet transfusions in multiply transfused patients. 3. Reduction of CMV transmission. 4. Reduction in inflammatory mediator accumulation during storage – preventive strategy for TRALI.
Adverse effect of transfusion ofblood and blood products Acute – Allergic – Anaphylaxis – Hemolytic – Metabolic – Transfusion related acute lung injury – Circulatory overload – Non-hemolytic febrile transfusion reactions – Haemostatic: dilution of clotting factors and thrombocytopenia – Infective Risks
Late – Delayed hemolytic transfusion reactions – Sensitization/Alloimunization – Transfusion Related Immune Modulation – Graft-vs-Host disease – Transfusion iron overload (haemosiderosis)
Non hemolytic Febrile Transfusion Reactions – Result of alloimmunization to leucocyte and platelet antigens ( HLA antigens) – Symptoms: Rigor followed by Fever usually within the start of 30-60 min of transfusion – Managed by cessation or slowing of the transfusion and administration of an antipyretic – Pretreated with antipyretic in repeated transfusions and patient who has history – If above measure fail, leucocyte-depleted cell components are given.
Allergic reaction – Symptoms: Urticarial rash and itch within minutes – Treatment: Antihistamines and reduction of transfusion rate
Anaphylaxis – Rare, fatal, caused by antibodies to IgA in patients who have extremely low levels of this immunoglobulin in plasma (Hereditary IgA Deficiency), who have been sensitized to IgA in previous transfusions. – Treatment: Termination of blood transfusion, IV crystalloids, Maintenance of airway, Oxygen, Adrenalin, IV antihistamine and salbutamol
Acute haemolytic reaction – Result of ABO incompatibility – Serious complication – Mortality is high when more than 200 ml has been transfused – Clinical feature Pain at the infusion site and along the vein Facial burning Chest and back pain Fever, rigor and vomiting Restlessness, breathlessness, flushing and hypotension Bleeding from vascular access sites and wound
Management Immediate recognition Cessation of transfusion Replacement of the blood transfusion set Adequate hydration Forced diuresis Vasopressor/ Inotrope support might be required Further investigations – Re-cross matching and serological testing – Blood unit for culture – Blood sample for clinical chemistry – Coagulation screen
Transfusion Related Acute Lung Injury – Occurs when mediators (anti HLA antibodies and anti- granulocyte antibodies) present in the donor plasma activate leucocytes in the host. – Pulmonary microvascular occlusion by platelets, leucocytes and fibrin – Clinical feature (within 6 hrs of transfusion) Fever Breathlessness Non-productive cough Hypoxia – Chest X-ray shows typical features of ARDS – Transfusion related circulatory overload should be ruled out. – Multiparous female donors have been identified as most common source in TRALI fatalities.
Treatment of TRALI1. Treatment is largely supportive.2. Monitor Oxygen saturation, Provide supplemental oxygen to maintain saturation above 92%3. Hypoxemia severe enough to require Endotracheal Intubation and PPV occurs in 70-75% of patients.4. No evidence supports the routine use of Corticosteroids.
Metabolic complications – In patients with massive blood transfusion( 1 ml/kg/min or 1 unit of blood per 5 minutes). – Metabolic consequences include 1. Hypothermia (prevented by transfusing blood through blood warmer) 2. Acidosis 3. Increased affinity of oxyhaemoglobin for oxygen( due to transfusion of 2,3 DPG depleted blood) 4. Citrate intoxication( causes temporary reductions in ionised calcium levels – If symptomatic treated by administering calcium gluconate) 5. Hyperkalemia
Haemostatic complications1. Dilutional Coagulopathy– Stored blood is deficient in platelets and labile clotting factor (factor V and VIII)– Massive transfusion induces dilution of Fibrinogen, Clotting factor – II, V and VIII in addition to moderate Thrombocytopenia.– Treated by administering FFP or platelets as decided on basis of laboratory evidence of coagulopathy or by clinical suspicion due to rapid ongoing blood loss.2. Post Transfusion Purpura– Platelet-specific alloantibodies may cause post-transfusion purpura– It is initially treated with high dose corticosteroids and intravenous immunoglobulin– If platelets needed , have to be compatible with patient alloantibodies
Circulatory overload1. Encountered when blood is administered too rapidly or in large volumes2. Pulmonary edema is common3. Must be differentiated from ARDS4. Diuretics may be used – Furosemide administered at incremental dosage of 20-40 mg depending on response 6-8 hrly until desired diuresis occurs.
Transfusion haemosiderosis – Iron overload in monocyte-macrophage system – Especially a problem in childhood anemias (e.g. thalassemia) and in patients with chronic refractory anemia – Iron chelation therapy with desferrioxamine
Graft-versus-host disease – Rare, but fatal complication – Occurs mainly in immunodeficient patients – Caused by the T-lymphocytes from donor blood get engrafted into the immunodeficient host’s marrow and launch an immune response against the host. – Starts 3-30 days after the transfusion – Patient develops high fever, diffuse erythematous skin rash, desquamation, GI symptoms, severe hepatic dysfunction and pancytopenia – Prevented by administering gamma-irradiated cellular components
Delayed Hemolytic Transfusion Reactions1. Result of Anamnestic Response to Donor RBC antigen to which a recipient has been previously exposed.2. Commonly involve antibodies against Kell, Kidd and Rhesus antigens.3. Occur within first or second week following transfusion4. Symptoms include low grade fever, increased indirect bilirubin or unexpected reduction in Hb concentrations.5. It is typically mild and self limiting.6. Treatment is supportive including Hb monitoring, hydration and provision of compatible blood if necessary.
Transfusion Related Immunomodulation1. There are changes in immunity related processes such as T-lymphocyte Helper/Suppressor ratio, function of T Killer cells, Lymphocyte responsiveness and Delayed Hypersensitivity.2. Adverse effects on immunocompetence such as accelerated reccurences of malignancy, increased rates of infection and more rapid progression of HIV/AIDS.3. Cause Unknown.
Infective risks1. Hepatitis B, C and G2. HIV 1 and 23. HTLV 1 and 24. Cytomegalovirus5. Parasitic diseases – Malaria, Filariasis and Chaga’s disease.6. Prion related Diseases ( CJD)
7. Bacterial Contamination: More common with platelet transfusions. Risk is less in single donor apheresis derived units. Gram negative Yersinia enterocolitica is the most common cause of fatal sepsis. Symptoms – Fever, Chills, Tachycardia, Dyspnea, Shock, DIC and Acute Renal Failure. Needs to be distinguished from other common transfusion reactions. Treatment:1. Transfusion stopped immediately2. Blood cultures obtained3. Broad spectrum Antibiotics4. Supportive care as required.5. Notification of blood bank.