Blood transfusion in OMFS

A seminar on blood transfusion in OMFS

1. B LOOD T RANSFUSION By Dr Rayan M Moderator Dr (Col) Suresh Menon

2. Contents Introduction Components of blood Functions of blood History of blood transfusion ABO blood groups Rh blood group Other common significant blood groups General indications for blood transfusion Pre-transfusion testing Principles of blood transfusion Precautions to be taken while blood transfusion Blood products Autotransfusion Complications of blood transfusion Newer modalities

3. INTRODUCTION Blood is a connective tissue in liquid form . It is considered to be the fluid of life as it supplies oxygen to various parts of the body . Blood transfusion can be defined as the transfusion of the whole blood or its components from one person to the other. (Or) Transfusion is simply the transplantation of a tissue consisting of a suspension of cells in a serum It involves the collection of blood from the donor and administration of the blood to the patient

4. BLOOD Plasma (55%) Cells (45%) RBC WBC 90% Water 10% Solids Platelets Organic Inorganic Plasma protein Ions Clotting factors

5. F UNCTIONS OF BLOOD

6. HISTORY OF BLOOD TRANSFUSION As early as the 17 th century, blood has been used as a therapy for a variety of ailments . 1665 – First recorded blood transfusion in England , R ichard Lower revived a dog by transfusing blood from another dog via a tied artery 1818 James Blundell performs the first successful blood transfusion of human blood to treat postpartum hemorrhage. 18 7 The first whole blood transfusion to treat hemophilia is successfully completed. 190 1 Karl Landsteiner discovers the first three human blood groups, A, B and O. 1902 Landsteiner’s colleagues, Alfred Decastello and Adriano Sturli, add a fourth blood type, AB.

7. 1907 Blood typing and cross matching between donors and patients is attempted to improve the safety of transfusions. The universality of the O blood group is identified . 1914 Adolf Hustin discovers that sodium citrate can anticoagulate blood for transfusion . 1940 The Rh blood group is discovered when RBCs of monkeys were injected into rabbits . 1961 Platelet concentrates are recognized to reduce mortality from hemorrhaging in cancer patients . 1972 The process of apheresis is discovered . 1985 The first HIV blood-screening test is licensed and implemented by blood banks.

8. ABO BLOOD GROUPS The ABO antigens (agglutinogen) are carbohydrate structures carried on large oligosaccharide molecules, which are attached to glycoproteins and glycolipids in the RBC membrane The RBC membranes have over 2 million ABO antigens Surface of RBC when viewed under Electron microscope

9. L ANDSTEINER ' S LAW Based on his observations Karl Landsteiner in 190 1 framed a law called Landsteiner's Law It has 2 major components , they are : If an agglutinogen is present in the RBCs of an individual , the corresponding agglutinin must be absent from the plasma If the agglutinogen is absent in the individual RBCs , the corresponding agglutinin must be present in the plasma The agglutinins are gamma globulins as are other antibodies . Most of them are IgM molecules

10. RHESUS BLOOD GROUP The Rh system, which includes the C D E & c d e antigens , differs from the ABO system in several ways It is second only to the ABO system in importance in transfusion medicine. The Rh antigens are highly immunogenic, especially the D antigen since these antigens are membrane-spanning proteins, in contrast to polysaccharide moieties. In the Rh system the antibodies are of IgG type and antigen –antibody reaction occurs best at body temperature .[warm antibodies] In Rh negative individuals , anti – D antibodies are not naturally present in the plasma

11. In Rh negative individuals the anti – D antibodies might be evoked by : Transfusion with Rh positive blood i.e. D positive RBCs Entrance of the D positive RBCs from the Rh positive fetus into the maternal circulation of Rh negative mother

12. HEMOLYTIC DISEASE OR ERYTHROBLASTOSIS FETALIS Erythroblastosis fetalis is a disease of the fetus and new born infant characterised by the progressive agglutination and subsequent phagocytosis of the RBCs If the mother is Rh negative and fetus is Rh positive serious complications may occur . RBCs containing D antigen may cross the placenta from the fetus to the mother, either during pregnancy or a small amount of fetal blood leaks into the maternal circulation at the time of the delivery . The mother reacts by forming anti D which returns to the fetal circulation and tends to destroy the fetal RBCs

13. CLINICAL PICTURE OF ERYTHROBLASTOSIS FETALIS

14. Treatment of erythroblastosis fetalis Transfusion of Rh –ve blood is done i.e. 400ml for 1.5 hrs or more It is repeated several times for the first few weeks of life This is done so as to keep the blirubin levels low Prevention of the Rh hemolytic disease Destruction of Rh positive fetal cells in the maternal blood can be brought about by administering a single dose of anti Rh antibodies in the form of Rh immunoglobulins soon after child birth This prevents the formation of active antibodies by the mother

15. OTHER COMMON SIGNIFICANT BLOOD GROUPS T here are 27 other known blood groups systems with more than 300 known antigens . These are all classified by the antigens found on the surface of our red blood cells. The “ MN blood group antigens ” were discovered in the 1920s by Karl Landsteiner . In this there are 3 groups, M N & MN. It hold importance in paternity testing.

16. Another blood group, the “ S/s variants ”, are named after Sydney, where the blood group was discovered. This blood group is signified by a particular type of molecule on the red blood cells that is a target of the malaria parasite . A blood group known as Duffy is also associated with infection by malaria .When this protein is absent from the red blood cells, the cells are resistant to infection by the malaria parasite . This protein is absent from the blood cells of 90% of sub-Saharan Africans, conferring malaria resistance on this population. Antibodies to the Duffy antigens are commonly found in a patient’s plasma and are a cause of transfusion reactions if carefully matched antigen negative blood is not given.

17. The K antigen was first detected in the 1940s as a result of a woman without the K antigen on her red blood cells being pregnant with a baby with the K antigen on the red blood cells. While almost all women post-partum have antibodies to some antigens found on the baby’s white blood cells, red cell antibodies are less common. Another blood group, Kidd ( Jk) was named after the patient in whom it was discovered. The Kidd proteins are related to proteins in the kidney that help get rid of waste from the body. For the Kid blood group it’s very important to avoid damaging reactions, and therefore carefully matched antigen negative blood is given.

18. BOMBAY BLOOD GROUP [ OH GROUP] o Rare individuals also lack the H antigen and are designated as the “ Bombay” phenotype (group Oh). They make potent anti-H in addition to anti-A and anti-B and must be transfused blood only from other individuals with the Bombay group It is observed to occur in 1 out of every 250,000 people It was discovered by Y.M Bhende

19. RBC compatibility

20. ANTICOAGULANTS 1916 - First anticoagulant preservative was discovered by Rous and T urner – Citrate glucose 1943 – Acid citrate dextrose was introduced by Loutit and Mollison 1957 - Gibson et al developed citrate phosphate dextrose (CPD) 1978 – C itrate phosphate with adenine (CPDA-1 ) Acid Citrate Dextrose (ACD) Citrate Phosphate Dextrose (CPD) Citrate Phosphate Dextrose Adenine (CPDA-1) 15 ml of ACD, 14ml of CPD or CPDA is used for preserving 100ml of blood

21. PURPOSE : A To prevent coagulation. B To preserve the life and survival of RBCs so as to have the maximum post transfusion survival . CITRATE : Acts by chelating Calcium. DEXTROSE : Necessary for the metabolism of stored RBCs. It passes from plasma into the red cells and is utilized for energy production . CITRIC ACID: Prevents carmalization of glucose in citrate dextrose solution during autoclaving. ADENINE : Improves the viability of red cells.

22. COMPOSITIONS OF PRESERVATIVES/ANTICOAGULANTS

23. DONOR SELECTION Donor history and risk factor assessment Infectious disease testing ABO and Rh typing Cross matching Noting post donation information

24. DONOR HISTORY & EXAMINATION GENERAL PHYSICAL EXAMINATION : General Appearance : should appear to be in good health. Age : between 18 and 65 years. Weight : 45-55 Kg - 350 ml blood 55 Kg & above - 450 ml. Temperature : should not exceed 37.5 C / 99.5 F Pulse : 60 to 100 beats/min & regular pulse B l ood Pressure : S B P : b/w 100 and 160 mm of Hg DBP : b/w 60-90 mm of Hg Skin : free of any skin lesion or infections

25. MEDICAL HISTORY : History of malaria : accepted after 3 months . History of jaundice : deferred up to 1 year . History of being HIV, HBsAg / HCV antibody positive : permanently deferred. Intimate contact with HIV, HBsAg / HCV antibody positive individual : deferred for 1 year . History of measles/mumps/chickenpox : deferred for 8 weeks History of influenza : deferred till 1 week after treatment Having history of diarrhoea in preceding week particularly if associated with fever should be deferred

26. HISTORY OF VACCINATION V accination against TAB/TT/ Cholera/Hepatitis-A : accepted if free of symptoms. Hepatitis B vaccination : accepted after 7 days of vaccination. Yellow fever/measles/polio : deferred for 2 weeks Rabies vaccination : deferred for 1 year. Those bitten by any animal : deferred for one year. Hepatitis B Immunoglobulin : should be deferred for 1 year PREGNANCY N ot be accepted during period of pregnancy and till 12 months after full term delivery and also during lactation.

27. ASPIRIN INGESTION Ingestion of Aspirin or any related medicine within 3 days prior to donation should preclude use of donor as a source of platelet preparation. SURGICAL PROCEDURES Major : one year after the recovery Minor : 6 months LABORATORY EXAMINATION : Haemoglobin : not less than 12.0 gm/dl Hematocrit : not less than 36%

28. DONOR INFECTIOUS DISEASE TESTING Hepatitis B, HbsAg and anti-core antibody •Hepatitis C antibody •HIV 1 and 2 antibodies •HTLV [Human T-cell lymphotropic virus] 1 and 2 antibodies •Serologic Test for Syphilis •Nucleic Acid Testing (NAT) for HIV, HCV •Detection of Bacteria in platelet products •CMV [Cytomegalo virus] antibody for select recipients

29. C ROSS MATCHING Blood matching between a patient and a donor is a direct compatibility test RBCs and plasma are crossmatched through major and minor crossmatching process “ Major ” crossmatch is comparing donor erythrocytes to recipient serum where as the “ minor ” crossmatch is designed to test opposite compatibility which is the donor's serum/plasma with the recipient's red cells. Minor cross match has almost been eliminated in most blood banks, because the donor samples are screened before hand for antibodies

30. G ENERAL INDICATIONS OF BLOOD TRANSFUSION External bleeding Internal bleeding (i) non-traumatic (ii) traumatic RBC lysis : e.g. malaria, HIV Anaemia Bleeding disorders Burns 6. Anticipated need for blood

31. Method of estimation of blood loss Clinical estimation of blood loss in suction and gauzes and mops Vitals of the patient (BP, Pulse and temperature) Blood gas analysis Urine output 1ml/kg/hr Marino PL: Hemorrhage & Hypovolemia . N: The ICU Book. 2 nd ed. Baltimore: Williams and Wikins ; 1998 (207-27)

32. P HLEBOTOMY The maximum volume of blood that may be collected is 10.5 mL/kg of body weight About 350- 450 ml is taken each time The withdrawal of blood takes 10-15 mins

33. APHERESIS Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual components ( RBCs, platelets, plasma based on specific gravity) to use for transfusion in different patients. Here the required component is collected and the rest is returned to the donor Selective collection of RBCs/WBCs/platelets is called cytapheresis Selective collection of plasma is called plasmapheresis A nticoagulants such as citrate and heparin is used

34. B LOOD P RODUCTS

35. B ANKED W HOLE B LOOD No components have been removed Contains RBCs ,WBCs ,platelets and p lasma Can be stored for 5 weeks Transfusions of whole blood are rarely required They might be necessary in cases of acute blood loss in major surgeries > 15% blood loss It is a poor source of platelets and clotting factor 5 and 8

36. P ACKED RED CELLS Red cells from a donor unit diluted with plasma , to a hematocrit of 75% Volume is about 200ml Storing red cells just above freezing allows survival for about 42 days It is the product of choice for most clinical situations

37. INDICATIONS FOR PACKED RED CELLS In the field of orofacial surgery, a red blood cell transfusion (RBCT) is occasionally required during double jaw surgery, pan facial surgery and onco surgery T ransfusion is performed for the purpose of oxygen transfer to hypoxic tissues and plasma volume expansion when there is bleeding. RBCT can be a life-saving procedure for most patients with acute anemia caused by perioperative bleeding RBCT is the fastest way to increase the oxygen carrying capacity of blood A unit of RBCT will increase the Hct by 3% and Hb by 1- 1.5 gm/dl

38. TRANSFUSION STRATEGY & TRIGGER The indications and triggers for RBCT are on-going issues. There have been many studies and there are still on-going re search of an answer. Based on studies to date, there are two strategies : In 1988, the “ 10/30 Rule”( liberal strategy ) was presented at the National Institutes of Health Consensus Development Conference, which presented the level of RBCT during perioperative period to be less than Hb 10 g/dL and Hct 30% and transfusions were performed based on those values

39. Recently, the restrictive strategy ( Hb level below 7 g/ dL ) has become more accepted due to the accumulation of evidence regarding the negative impact on prognoses following RBCT per the liberal strategy as well as the complications and costs associated with RBCT

40. FROZEN RED CELLS Concentrations of red blood cells preserved frozen at -80ºC. It reduces the risk of transfusing antigens or foreign bodies that the body might regard as potentially dangerous in previously sensitized patients Not available for use in emergency situations RBC viability is improved A D P and 2,3 D PG ( 2 , 3 - diphos p hogl y cerate) is maintained

41. PLATELET CONCENTRATES Composed of platelets and 50 ml plasma Contains cellular components that help in the clotting process Platelets can be stored up to 5 days in room temperature Indicated in : Platelet disorders When massive blood loss has occurred One unit will usually raise the count to 5-10k / micro liter

42. FRESH FROZEN PLASMA Obtained from freshly donated blood Source of vit k dependent clotting factors Only source of factor 5 Indicated for coagulopathy and different clotting factors 1 unit FPP = 3% increase in clotting factors

43. CRYOPRECIPITATED ANTIHAEMOPHYLIC FACTOR Its an antihaemophyllic concentrate, Cryoprecipitate which is produced by allowing FFP to thaw slowly at 1– 6°C It is prepared from plasma and is rich in clotting factors It is used in people with haemoph i llia and Von willebrand disease to control bleeding Its contents are major portion of factor 8 which is present in freshly drawn and separated plasma Indications for transfusion of cryoprecipitate include repletion of fibrinogen levels activation of platelets; replacement of factor VIII, vWF, or factor XIII when recombinant factors are unavailable; and as part of a massive transfusion protocol

44. PROTHROMBIN COMPLEX CONCENTRATES PCCs are intermediate-purity pooled plasma products containing a mixture of vitamin K–dependent proteins that are used for the treatment of hemophilia A and B PCCs are produced by ionexchange chromatography Depending on the processing technique, either a 3-factor ( eg , factors II, IX, and X) or 4-factor ( eg , factors II , VII, IX, and X) concentrate contains a final overall clotting-factor concentration that is approximately 25 times higher than in normal plasma PCCs were originally indicated for the treatment of patients with hemophilia B. More recently, their indication has expanded as a replacement therapy for congenital or acquired deficiency of vitamin K–dependent clotting factors

45. FACTOR VIIA Factor VIIa is a recombinant agent that is used in the treatment of patients with factor VII deficiency and in patients with hemophilia A or B who have inhibitors . At present, the accepted indications for the use of rFactor VIIa are limited to hemophilia A and B with inhibitors, acquired hemophilia , and factor VII deficiency

46. FACTOR VIII Hemophilia A is an X-linked disorder. The major clinical manifestations in this disease are arthropathy secondary to spontaneous bleeding into joints with a risk of mortality from hemorrhagic bleeds ranging from 20% to 50 % of patients The currently available plasma-derived concentrates are classified as high purity (containing only the desired factor ) or intermediate purity (containing the desired factor as well as other factors)

47. Factor VIII replacement therapy in hemophilia A depends on the type of surgery or bleeding event . For minor surgery, a desired level of factor VIII replacement (20 U/kg) is greater than 30%, whereas replacement in the trauma or major surgical setting requires levels of 100 %. In general, the administration of 1 U of factor VIII concentrate increases the level by 2%. Factor VIII therapy is continued for 1 to 3 days postoperatively for minor procedures; however, 50% replacement for 10 to 14 days is usually required for major bleeds.

48. FACTOR IX Hemophilia B or Christmas disease is an X-linked disorder that affects 1 in 30,000 people. Three replacement therapies are presently available for the treatment of factor IX deficiency 1.Factor IX complex 2 . Coagulation factor IX concentrate, a high-purity plasma-derived product 3. Recombinant factor IX concentrate , a nanofiltered product that is produced without animal or human proteins

49. In patients with hemophilia B undergoing minor surgical procedures, the recommended replacement of factor IX is greater than 30% (40 U/kg). Patients with major bleeds, trauma, or requiring major surgical procedures should be replaced to 100 % (125 U/kg) and maintained throughout the postoperative period at a level of 50% or greater

50. FACTOR XIII Once a fibrin clot is formed via the coagulation cascade it must be stabilized in order to prevent premature fibrinolysis. The crosslinking of the alpha and beta chain fibrin monomers is catalyzed by factor XIII. Inherited factor XIII deficiency is an autosomal recessive condition that manifests with soft tissue bleeds, hemarthrosis , intracranial bleeding, bleeding during surgery, and poor wound healing . Factor XIII concentrate is administered intravenously to a level of 5% to 20%. Dosing is recommended at 10 to 75 IU every 4 to 6 weeks

51. P RINCIPLES OF BLOOD TRANSFUSION 1. Transfusion is only one part of the patient’s management. 2. Blood loss should be minimized to reduce the patient’s need for transfusion. 3. Acute blood loss should be given effective resuscitation while the need for transfusion is being assessed. 4. The patient’s haemoglobin value, although important, should not be the sole deciding factor for transfusion. 5. The clinician should be aware of the risks of transfusion- transmissible infections

52. P RECAUTIONS TO BE TAKEN DURING BLOOD TRANSFUSION Use of Sterile Apparatus. Blood bag should be checked Temperature of blood to be transfused must be same as body temperature. Transfusion rate must be slow in order to prevent increase load on heart. Care full watch on the recipients condition following transfusion

53. Bill No: Sticker No: Pre Transfusion Vitals BP PR Temp SPO2 Post Transfusion Vitals BP PR Temp SPO2 Time Started : Time Ended: Blood Transfusion N otes Bld Grp Hb

54. Transfuse blood at the rate of 2 drops/min for the first 5 mins. In case of no reaction to 4 drops/min. Transfuse blood at the rate of 4 drops/min for the first 5 mins. In case of no reaction to 8 drops/min . Transfuse blood at the rate of 8 drops/min for the first 5 mins. In case of no reaction to 16 drops/min. Transfuse blood at the rate of maximum 16 drops/min till transfusion is complete. Watch for any signs of anaphylaxis, hypotension, breathlessness etc. In case of any reaction stop blood transfusion immediately. Administer : Inj Pheniramine Maleate 45.5gm IV stat Inj hydrocortisone 100mg IV stat Inform blood bank

55. DONATION INTERVAL The interval b/w 2 donations : at least 12 weeks. At least 48 hours must elapse after plasmapheresis or cytapheresis before whole blood is collected from a donor. Apheresis should be done only after 90 days of whole blood collection or in an event when red cells are not returned at the end of apheresis.

56. Even though blood can supply a range of products useful in a variety of situations Perioperative blood loss and anaemia is best dealt with by reducing the amount of blood lost at surgery through minimizing trauma, improving mechanical haemostasis Limiting phlebotomy to essential diagnostic tests, using microsample laboratory techniques; and giving antifibrinolytics, such as tranexamic acid (or, for high-risk procedures, aprotinin) Erythropoietin can also help where blood has been lost but the replacement of blood by transfusion can be essential after severe haemorrhage . PREVENTION IS BETTER THAN CURE

57. Also known as Auto transfusion Defined as the collection and reinfusion of patients own blood / blood components Safest form of blood transfusion More cost effective than allogenic transfusion

58. HISTORY First Autologous transfusion was done by James Blundell in 1818 before the discovery of blood groups. Anglo-saxon was the first to publish an article reporting Autotransfusion in 1874. Blood salvage was first reported in American literature in 1917.

59. 3 Types of Autotransfusion Pre operative blood donation Intra operative and post operative blood recover Acute normovolemic Hemodilution

60. Predeposit autologous donation (PAD) With a red cell storage-life of 35 days at 4°C, most healthy adult patients can donate up to three red cell units before elective surgery. Patients may be given iron supplements, sometimes with erythropoietin. Given the current remote risk of viral transfusion- transmitted infection by donor blood in developed countries, the rationale, safety and cost-effectiveness of routine PAD has been questioned.

61. Indications for Predeposit autologous donation PAD- Rare blood groups/ multiple blood group antibodies where compatible allogenic (donor) blood is difficult to obtain. Psychiatric risk because of anxiety about exposure to donor blood. Patient refusal to donor blood transfusion but will accept PAD. Children undergoing scoliosis surgery (other options available). PAD should only be considered in surgery with a significant likelihood of requiring transfusion, The patient’s ability to donate safely assessed.

62. 68 Intraoperative cell salvage (ICS) For elective and emergency surgery with significant blood loss and management of major traumatic or obstetric haemorrhage. A 2010 Cochrane Collaboration review of randomised trials of ICS, mainly in cardiac and orthopaedic surgery, showed a 20% reduction in donor blood exposure (an average saving of 0.7 units per patient).

63. Blood lost into the surgical field is filtered to remove particulate matter and aspirated into a collection reservoir where it is anti-coagulated with heparin or citrate . If sufficient blood is collected and the patient loses sufficient blood to require transfusion, the salvaged blood can be centrifuged and washed in a closed, automated system . The red cells are transfused through a 200 µm screen filter, as in a standard blood administration set. The transfusion should be prescribed, documented and the patient monitored in the same way as for any transfusion. Patients undergoing elective procedures where ICS may be used should give informed consent after provision of relevant information.

64. Indications for ICS in adults and children (for whom low-volume processing bowls are available )- Surgery where anticipated blood loss is >20% of the patient’s estimated blood volume . Elective or emergency surgery in patients with risk factors for bleeding or low preoperative Hb concentration . Major haemorrhage . Patients with rare blood groups or multiple blood group antibodies for whom it may be difficult to provide donor blood . Patients who do not accept donor blood transfusions but are prepared to accept, and consent to, ICS (this includes most Jehovah’s Witnesses).

65. Postoperative cell salvage (PCS) Mainly used in orthopaedic procedures, especially after knee or hip replacement and in correction of scoliosis. Blood is collected from wound drains and then either filtered or washed in an automated system before reinfusion to the patient. The simple filtration systems for reinfusion of unwashed red cells are mainly used when expected blood losses are between 500 and 1000 mL.

66. Collection of salvaged blood must be completed within the specified time (usually 6 hours) and the reinfusion must be monitored and documented in the same way as donor transfusions. PCS is relatively cheap, has the potential to reduce exposure to donor blood and is acceptable to most Jehovah’s Witnesses.

67. BLOOD SALVAGE

68. Acute normovolaemic haemodilution (ANH) Several units of blood are collected into standard blood donation packs immediately before surgery (usually in the operating room) and the patient’s blood volume is maintained by the simultaneous infusion of crystalloid or colloid fluids . The blood is stored in the operating theatre at room temperature and reinfused at the end of surgery or if significant bleeding occurs . Often used in cardiac bypass surgery where the immediate postoperative transfusion of ‘fresh whole blood’ containing platelets and clotting factors is seen as an advantage.

69. 76 Reported hazards of ANH include fluid overload, cardiac ischemia and wrong blood into patient errors. Mathematical modelling suggests ANH is most effective as a blood conservation measure in surgery with major blood loss.

70. COMPLICATIONS OF BLOOD TRANSFUSION A carefully prepared and supervised blood transfusion is quite safe However 5-6% of transfusions , untoward complications occur, some of which are minor while others are more serious and at times fatal Adverse reactions of blood transfusion can be classified into: Immunological complications Non immunological complications Based on duration taken for the symptoms to occur they can be classified as: Acute Delayed They can also be classified as Non infectious complications Infectious complications

71. NON INFECTIOUS COMPLICATIONS Reactions associated with high morbidity Transfusion related acute lung injury Transfusion associated circulatory overload Hemolytic reactions Anaphylaxis Transfusion associated graft vs. host disease Post transfusion purpura Reactions associated with low morbidity Febrile non hemolytic transfusion reactions Mild allergic reactions Acute hypotensive transfusion reactions

72. TRANSFUSION RELATED ACUTE LUNG INJURY [TRALI] Transfusion-related acute lung injury (TRALI) was first recognized in 1926 and was previously known as pulmonary hypersensitivity reaction Pathophysiology : TRALI’s pathogenesis revolves around the transfusion of antibodies and/ or other non immunologic mediators to a susceptible patient The most frequently implicated antibodies are human leukocyte antigen (HLA) class I, HLA class II, and human neutrophil antibodies ( HNA); these antibodies activate the leukocytes, which bind to the endothelium in the lungs, causing endothelial injury and edema

73. TREATMENT OF TRALI As with all transfusion reactions , immediate cessation of the transfusion and stabilization of the patient are critical. Respiratory support may range from supplemental oxygen to intubation. Steroids have not been proven to be beneficial. TRALI reactions usually resolve over the course of a few days with only supportive measures being needed

74. TRANSFUSION ASSOCIATED CIRCULATORY OVERLOAD [ TACO] Transfusion-associated circulatory overload (TACO) is generally the most common high-morbidity transfusion reaction encountered in clinical practice Certain patient characteristics are known to increase the risk of TACO, including older age, renal disease, cardiac disease, and critically ill status Pathophysiology : Unlike the majority of transfusion reactions, which are immunologically mediated, TACO’s pathophysiology invokes simple physics—too much fluid is added to the system too quickly (or in volumes that cannot be tolerated) for the transfusion recipient. Because the circulatory system cannot cope with the additional volume of the transfused products, pulmonary edema and respiratory distress result as fluid “backs up” into the lungs

75. TREATMENT OF TACO If the transfusion is still running, it should be stopped immediately In some cases, the patient will improve with simply stopping the infusion patients will require some form of respiratory support, at least temporarily Diuretics are useful in the treatment of TACO; the decrease in circulatory volume relieves cardiovascular stress, improving the pulmonary edema TACO can be prevented ,patients at risk of fluid overload at increased risk of TACO and should be transfused at a slow rate

76. DIFFERENCE BETWEEN TRALI AND TACO

77. HEMOLYTIC REACTIONS Transfusions leading to RBC hemolysis can be among the most devastating and feared complications of blood product administration They represent a spectrum of signs and symptoms and, depending on the clinical scenario , may be acute or delayed, intra- or extra vascular , attributable to ABO or non-ABO antibodies, and in some circumstances, may even be caused by mechanical forms of hemolysis due to improper infusion techniques

78. INTRAVASCULAR HEMOLYSIS Pathophysiology : Once the complement cascade has been fixed and activated on the incompatible cells, the resulting membrane attack complex punches holes in the red cell, resulting in its lysis and destruction IgM class antibodies are most efficient at fixing complement and, therefore, acute intravascular hemolysis is strongly associated with incompatibilities within ABO antibodies (which are most likely to be IgM in nature ) Generation of free RBC membranes in the intravascular space can cause concomitant activation of the coagulation system, resulting in the development of disseminated intravascular coagulation (DIC)

79. Complement generation and RBC release of hemoglobin can induce acute kidney injury and renal failure, a particularly feared complication of hemolysis . Complement activation can also cause smooth muscle constriction, increased small vessel permeability, and leukocyte activation, contributing to the shock like symptom often seen in intravascular hemolytic reactions . Acute hemolytic transfusion incidence estimated at about 1 in 76,000 transfusions Prevention : Rigorous identification of patient blood group during , before and after testing has to be performed

80. EXTRAVASCULAR HAEMOLYSIS Pathophysiology : In contrast to intravascular hemolysis, which is typically acute in onset , extravascular hemolysis is generally associated with a more subdued, slower RBC clearance For this type of hemolytic reaction, RBC clearance occurs because incompatible cells are coated by IgG class antibodies, with antibody-coated cells subsequently phagocytosed As such, most extravascular reactions are mediated by non-ABO antibodies (e.g., anti-Jk, anti-K, and anti-E ) Because of the slower, extravascular nature of these reactions the likelihood of end organ damage and a shock like symptom is markedly reduced, particularly when compared with intravascular hemolysis

81. TREATMENT OF HEMOLYTIC DISEASES Approaches to managing these reactions include assessing their severity, providing supportive transfusions to overcome the acute anemia (and coagulation disorders, if they exist), and steps to preserve renal function . New unit(s) are to be administered which are fully compatible with the patient using the post- transfusion reaction specimen In urgent situations and gravely ill patients , O negative blood can be given until the cause of hemolysis is rectified . Renal function must be closely monitored both clinically and via laboratory assays such as creatinine

82. ANAPHYLAXIS Anaphylactic transfusion reactions represent the most severe and extreme reactions in the spectrum of allergic reactions Pathophysiology : Most anaphylactic reactions are associated with platelets or plasma but they can occur with the transfusion of any blood product It is caused by complement, mast cell, and basophil activation in response to a specific antigen/allergen Anaphylactic reactions are characterized by rapid onset of respiratory distress, laryngeal edema, hypotension, and/or gastrointestinal symptoms , often within minutes of starting a transfusion Other allergic symptoms such as rashes and urticaria may occur in conjunction with these more severe symptoms Diagnostic criteria : These symptoms must appear within 4 h of a transfusion to meet the criteria for an allergic transfusion reaction

83. TREATMENT OF ANAPHYLAXIS Blood transfusion must be stopped immediately, and the patient must be stabilized as necessary. Respiratory support is vital, and intubation may be required Epinephrine, intravenous diphenhydramine, and volume resuscitation are often helpful Patients who have anaphylactic reactions to blood products may require washed products in the future Any future transfusions in a patient with a history of anaphylactic transfusion reactions should be considered with great caution, and the patient must be closely monitored.

84. TRANSFUSION-ASSOCIATED GRAFT-VERSUS- HOST DISEASE It is a rare disease but serious complication of blood transfusion. People at risk include those who have: received blood transfusions from HLA-matched donors, including family members had a stem-cell transplant inherited immune defects a c q u ir e d immu n e d e fe c t s , s u c h as H o d gk in d is e as e be e n treated with purine analogues . Transfusion-associated graft-versus-host disease results from transfused leukocytes; gamma irradiation of the transfused blood will obviate the reaction Patients should be pre-warned and should carry a warning card themselves

85. POST-TRANSFUSION PURPURA Post transfusion purpura is a relatively uncommon complication of blood transfusion Pathophysiology : It can be thought of a delayed transfusion reaction involving platelets Here there is an immunological response to a previously encountered foreign platelet that leads to an increase in the production of antiplatelet antibodies by the recipient Treatment :The current treatment of choice is intravenous immunoglobulin (IVIG), along with consideration of corticosteroids

86. REACTIONS ASSOCIATED WITH LOW MORBIDITY 1. Mild allergic reactions Allergic reactions are the most common adverse events associated with transfusion The main factor in allergic transfusion reactions appears to be the transfer of either antigen or antibodies to the recipient via donor plasma Usually treatment is not necessary, but in some cases Diphenhydramine is the treatment of choice .

87. 2. Febrile non-hemolytic transfusion reactions common transfusion reaction Etiology is not known Diagnostic criteria : to qualify as an FNHTR the fever or chills/rigors must occur within 4 h ours of completion of the transfusion Treatment : transfusion should be stopped as soon as reaction is suspected Supportive care 3. Acute hypertensive transfusion reaction Characterized by sudden increase in the systolic blood pressure Attributable to the increase in bradykinin Treatment :Once the transfusion is stopped, the hypotension resolves nearly immediately

88. Hyperkalemia associated with blood transfusions Transfusion-associated hyperkalemic cardiac arrest is a serious complication in patients receiving packed red blood cell (PRBC) transfusions. Mortality from hyperkalemia increases with large volumes of PRBC transfusion, increased rate of transfusion, and the use of stored PRBCs The supernatant of stored RBCs usually contains more than 60 mEq/L of potassium . Potassium in stored blood increases due to decrease in ATP production and leakage of potassium into the supernatant. The initial high levels of potassium in stored blood predispose to post- transfusion hyperkalemia. Pre-washing of RBCs is an essential practice for reducing potassium load in irradiated PRBC

89. H YPOKALEMIA Hypokalemia is more common than the hyperkalemia after transfusion because donor red cells re- accumulate the ion intracellularly Citrate metabolism causes further movement of potassium into the cells. Catecholamine release and aldosterone urinary loss can also trigger hypokalemia in the setting of massive transfusion. No treatment or preventive strategy is usually necessary Flat prolonged t waves Inverted t wave

90. H YPOTHERMIA It may be caused by transfusion of large volume of cold blood products. It can cause cardiac arrhythmia and also interferes with platelet function, clotting factor interaction and bleeding time. Blood warmers may be used to prevent hypothermia

91. I NFECTIOUS COMPLICATIONS Based on the etiology , the infectious complications can be broadly classified into complications caused by : Viruses Bacteria Parasites Prions

92. N EW CONCEPTS IN TRANSFUSION MEDICINE Development of in vitro/ex vivo blood cells Laboratory-derived platelets Red blood cells in the setting of hemoglobinopathies Extending platelets’ shelf lives New testing approaches

93. D EVELOPMENT OF IN VITRO BLOOD CELLS

94. L ABORATORY DERIVED PLATELETS

95. REFERENCES Clinical principles of blood transfusion – 1 st Ed – Robert W Maitta Clinical laboratory blood banking and transfusion medicine Essential Pathology -4 th Ed – Harsh Mohan Human physiology –fourth Ed –A K Jain Perioperative red blood cell transfusion – NCBI Medical problems in dentistry -7 th Ed - Scully Oral & maxillofacial surgery Vol-1 – Laskin D M