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Blood transfusion safety,tti testing ,rational use of blood products

1. BLOOD CENTER OPERATIONS & TRANSFUSION SAFETY

2. Introduction Overview of blood transfusion services. The Importance of Organized blood centers in Healthcare . Objectives: Safe supply, proper testing, rational use, and management of transfusion reactions.

3. Overview of Blood transfusion services This is a drug manufacturing facility in our hospital which is monitored by Central Govt.’s Food and Drug Administration and NBTC. The drugs here include Red cell concentrate(RCC) , Fresh Frozen Plasma(FFP), Platelets and Cryoprecipitate.

4. Importance of Blood centers In this center, whole Blood is properly collected from healthy donors voluntarily. Properly tested for physical properties of blood along with testing for transfusion transmitted infections like HIV, Hepatitis B/C , Syphilis , malaria etc. by advanced antibody detection technology.

5. Objectives For the safe blood supply. Accurate verification, checking and reliability of recipient and donor is very crucial. Proper Immunological tests like blood grouping , crossmatching and Coombs tests (ICT, DCT).

6. Rational use of Blood It is implemented all over the country by NBTC for minimizing exposure risk which will be further discussed in the session.

7. RATIONAL USE OF BLOOD

8. Good clinical transfusion practices Blood transfusion is one of the most frequently performed procedures in the hospital. Yet, it has also been identified as one of the commonly overused interventions. Thus, good clinical transfusion practices cannot be overemphasized so far as the patient safety is concerned. National Institute of Biologicals, MOHFW, GOI.

9. Appropriate and rational blood use - World Health Organization (WHO) The appropriate use of blood and blood products means the transfusion of safe blood products only to treat a condition leading to significant morbidity or mortality that cannot be prevented or managed effectively by other means. Rational use of blood and blood products is to reduce unnecessary transfusions and minimize the risks associated with transfusion, the use of alternatives to transfusion where possible, and safe and good clinical transfusion practices, including patient blood management.

10. Whole blood Indications: a. Exchange transfusion in neonates. b. When hypovolemia is not corrected after infusion of IV fluids (Crystalloids/Colloids) and packed red blood cells are not available, whole blood can be used with in acute bleeding conditions, e.g. road traffic injuries, battle field injuries etc. National Institute of Biologicals, MOHFW, GOI.

11. Rationality of use: Red cell concentrate replacing the whole blood in most of the situations, there are very few clinical and practice circumstances where whole blood use can be justified. Platelet function is rapidly lost during the whole blood storage and there is no useful platelet function left after 24 hours of cold storage. Routine use of whole blood should thus be discouraged, as better and more specific therapy in the form of component transfusion is available. National Institute of Biologicals, MOHFW, GOI.

12. Packed Red Blood Cells Indications and dosage : a. PRBC transfusion is not indicated until the Hb level is 7 g/dL(restrictive transfusion threshold) and is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients (strong recommendation, moderate quality evidence) . b. A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). AABB TECH. MANUAL, RGOG GTG 47

13. c. Above recommendations do not apply to the patients with acute coronary syndrome, severe thrombocytopenia and chronic transfusion–dependent anemia. d. Patients, including neonates, should receive PRBC units, irrespective of duration of storage in blood centre , rather than limiting patients to transfusion of only fresh PRBC units (strong recommendation, moderate quality evidence). e. Adults without any active bleeding should be transfused single-unit red blood cell transfusions (or equivalent volumes calculated on the body weight basis for children or low body weight adults). In these patients, clinical reassessment and Hb levels should be done before further transfusions are given. AABB TECH. MANUAL, RGOG GTG 47

14. 1. Rational PRBC use in Obstetrics and Gynecology The WHO guidelines for blood transfusion in Obstetric patients published more than 15 years back recommended that blood transfusion should not be based on the Hb levels alone. There were no specific recommendation regarding the trigger for blood transfusion in these patients. In view of absence of any specific recommendations/ guidelines from the Indian obstetrics and gynecology bodies/ societies (e.g. FOGSI, ICOG) till December 2019, the below mentioned practice points have been taken from the RCOG, UK guidelines (2018).

15. For normocytic or microcytic anemia , a trial of oral iron should be considered as the first step and further tests should be undertaken if there is no demonstrable rise in Hb at 2 weeks and compliance has been checked. Pregnant women should be offered screening for anemia at booking and at 28 weeks. Women with multiple pregnancies should have an additional full blood count done at 20–24 weeks. Pre-delivery autologous blood deposit is not recommended. Anemic women who are not actively bleeding intrapartum or immediate post-partum, an Hb less than 7gm/dl is an indication for PRBC transfusion.

16. There should be a clear protocol on how to manage major obstetric hemorrhage. The decision to provide blood transfusion should be made on clinical and hematological grounds. FFP at a dose of 12–15 ml/kg should be administered for every 6 units of red cells during major obstetric hemorrhage . Subsequent FFP transfusion should be guided by the results of clotting tests. Aim to maintain the platelet count above 50,000/ microliter in the acutely bleeding patient. A platelet transfusion trigger of 75,000/ microliter is recommended to provide a margin of safety.

17. Postpartum Hemorrhage Postpartum hemorrhage, defined as a cumulative blood loss of greater than or equal to 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process. Additional important secondary sequelae from hemorrhage exist and include adult respiratory distress syndrome, shock, disseminated intravascular coagulation, acute renal failure, loss of fertility, and pituitary necrosis ( Sheehan syndrome ).

18. Resuscitation in minor and major PPH Hypotensive resuscitation Among the initial strategies, the administration of crystalloids in small boluses of 500 ml is recommended. Because administering small crystalloid volumes reduces the risk of dilutional coagulopathy. Aggressive resuscitation may worsen coagulopathy and hemorrhage by increasing intravascular hydrostatic pressures, diluting coagulation factors An excessive rise in blood pressure could also result in higher red blood cell loss leading to more hypoxia and acidosis in tissues.

19. Measures for minor PPH Measures for minor PPH (blood loss 500–1000 ml) without clinical shock. Warmed crystalloid infusion is recommended. Blood transfusion is generally not required in cases of blood transfusion. Measures for major PPH Full protocol for major PPH (blood loss greater than 1000 ml) and continuing to bleed or clinical shock. Until blood is available, infuse up to 3.5 liters of warmed clear fluids, initially 2 liters of warmed isotonic crystalloid. Further fluid resuscitation can continue with additional isotonic crystalloid or colloid (succinylated gelatin).

20. Blood Components In hemostatic resuscitation, PRBC, FFP, and PLT are applied in a 1:1:1 ratio due to the resemblance with whole blood and because a “high ratio” is related to fewer complications and better patient survival outcomes.  If PRBC is not available, then whole blood can be used instead in case of massive hemorrhage .(FIGO Guidelines ,2022) FFP at a dose of 12–15 ml/kg should be administered for every 6 units of red cells during major obstetric hemorrhage. Subsequent FFP transfusion should be guided by the results of clotting tests if they are available in a timely manner, aiming to maintain prothrombin time (PT) and activated partial thromboplastin time (APTT) ratios at less than 1.5 x normal .(RCOG Green-top Guideline No. 47, 2016 Royal College of Obstetricians and Gynecologists)

21. 2. Rationale PRBC use in ICU, Surgery and Orthopedics [ source: Red Blood Cell Transfusion: 2016 clinical practice guideline from AABB,Transfusion.2016

22. 5. Rationale PRBC use in neonates and pediatric patients. AABB Tech. Manual, 19th ed.

23. AABB Tech. Manual, 19th ed.

24. 6. Rationale PRBC use in common Hemoglobinopathies in India. Thalassemia and Sickle cell diseases are two common Hemoglobinopathies in India that require long and specialized treatment. Blood transfusion in Thalassemia: In thalassemia, excess iron due to these repeated blood transfusions, needs to be removed by the use of the expensive chelation treatment . Thalassemia intermedia and Hb E thalassemia patients may not need regular red cell transfusions. Even in thalassemia major patients, regular transfusions are not justified only on the basis of Hb levels. Indian Journal of Human Genetics, 2014, National Institute of Biologicals, MOHFW, GOI.

25. Following parameters suggest that the patient will need chronic red cell transfusions. Hb level <7 g/dl on two successive occasions separated by at least 2 weeks (the patient should be on folic acid replacement and there should be no other aggravating cause, i.e. infection, bleeding, etc.) Even if Hb level is >7 g/dl and <10 g/dl, and above clinical features are present, the patient may need chronic transfusion therapy.

26. Red cell transfusions should be given at an interval of 2-5 weeks. This interval is optimized based on: The amount of red cells transfused so that pre-transfusion Hb remains >9 g/dl but post-transfusion Hb does not go above 12 g/dl There is no fluid overload. Transfusion process is over within a reasonable time (within 4 hours). Frequency of transfusions is not such that it interferes with patient’s normal activities.

27. Reducing the number of venipuncture (as lifelong transfusion is needed, peripheral veins need to be preserved well). Amount of PRBC to be transfused: Pretransfusion Hb is to be estimated along with the weight of the patient and recorded. If the hematocrit of the red cell concentrate used is 0.65,then 3-4 ml/kg will raise the Hb by 1 g/dl in the absence of hypersplenism. Generally in a single transfusion an attempt is made to raise the Hb by 4 g/dl if transfusions are scheduled at 3‑ to 5 weekly intervals.

28. Blood transfusion in Sickle cell disease: PRBC transfusions play an important role in the treatment of some acute illnesses in patients with sickle cell disease. PRBC should be transfused if the Hb is >1-2 g/dl, below baseline and the patient shows any signs of cardiovascular compromise. Indications for red cell transfusions include acute exacerbation of the patient’s baseline anemia (e.g. hyperhemolysis , hepatic sequestration, splenic sequestration, aplastic crisis) Indian Journal of Human Genetics, 2014, National Institute of Biologicals, MOHFW, GOI.

29. PRBC transfusion in a dose of 10 ml/kg for Hb <4-5 g/dl and signs of cardiovascular compromise should be done. Transfusion may be needed for Hb <7-8 g/dl for patients with relatively high baseline Hb Sickle levels. A post-transfusion Hb level <8-9 g/dl is generally recommended to avoid the risk of hyperviscosity that may occur several days later when RBCs sequestered in the spleen may return to the circulation and increase the Hb 1-2 g/dl above the post-transfusion levels. Conditions that requires increased oxygen carrying capacity , acute life or organ‑threatening vaso ‑occlusive episodes (e.g. stroke, acute chest syndrome, severe infection, multiorgan failure, etc.) and preparation for surgical or radiographic procedures.

30. Fresh Frozen plasma (FFP) FFP is conventionally transfused to patient with active bleeding or prophylactically to patients with modest to severe abnormality in the various coagulations tests like Prothrombin time, International normalized ratio (INR) and activated partial thromboplastin time ( aPTT ).

31. Therapeutic Indications with Active bleeding : Indications of FFP transfusion (British Journal of Hematology guidelines 2018). Patient with massive bleed like trauma or obstetric cases may develop multiple coagulation factor deficiency require FFP transfusion along with other blood components for maintaining the haemostatic and hemodynamic stability. Disseminated Intravascular Coagulation or consumptive coagulopathy with active bleeding. Immediate correction of Vitamin K deficiency and warfarin reversal. Thrombotic thrombocytopenic Purpura. Patient with congenital factor deficiency like factor V deficiency when no alternative therapies are available.

32. Prophylactic Indications abnormal coagulation tests (INR >1.5) in the absence of bleeding: FFP transfusion before an invasive procedure : Abnormal coagulation test are poor predictors of bleeding risks in non-bleeding patients prior to an invasive procedure. Various studies have shown that mild to moderate abnormalities in the coagulations tests is not associated with bleeding and prophylactic plasma transfusion in these patients does not affect bleeding outcomes (AABB).

33. BSH (British Committee for Standards in Hematology) recommends that coagulations tests should be considered in patients undergoing procedures with a moderate or high bleeding risk, any patient on anticoagulant , or those who have a personal/family bleeding history. Patients on anticoagulants like warfarin to correct the INR prior to an invasive procedure. Severe sepsis, particularly in neonates (independent of DIC).

34. Inappropriate use of FFP Plasma products are associated with the highest rate of inappropriate utilization ( upto 50%) with evidence of inappropriate practice based on local audits. The main reason for this inappropriate use of FFP is non availability of national/local guidelines in various countries like India. National Institute of Biologicals, MOHFW, GOI.

35. FFP transfusion is not indicated in the following conditions: 1. Use of FFP for volume replacement in patients who are not bleeding. 2. Use of FFP for nutritional purposes like hypoproteinemia. 3. Lack of evidence based local guidelines for FFP transfusion 4. Prophylactic FFP transfusion for invasive procedures with normal or mildly (INR <1.5) deranged coagulation tests. 5. FFP transfusion in patient with bleed with normal coagulation tests.

36. Platelet components Platelet components are required for patients with bleeding due to thrombocytopenia. However, they are also given prophylactically in conditions with low platelet count with the potential to cause bleeding. Indications : Treatment of bleeding due to: Thrombocytopenia. Platelet function defects. Prevention of bleeding due to thrombocytopenia as in bone marrow failure.

37. Contraindications: Absolute : Thrombotic thrombocytopenic purpura (TTP). British Journal of Haematology recommends platelet transfusion in cases of TTP only during life threatening bleeds. Relative : Idiopathic autoimmune thrombocytopenic purpura (ITP). Untreated DIC. Thrombocytopenia associated with septicaemia, or in cases of hypersplenism

38. Cryoprecipitate Cryoprecipitate is a blood component which is derived from FFP. It has relatively higher concentration per milliliter for fibrinogen, factor VIII, Von Willebrand factor ( vWF ), faxtor XIII and fibronectin. Indications: a. Hemophilia A (when pathogen inactivated antihemophilic concentrate factors are not available) b. Von Willebrand’s disease c. Congenital or acquired fibrinogen deficiency (when pathogen inactivated fibrinogen is not available or cannot be used) d. Acquired factor VIII deficiency (when pathogen inactivated antihemophilic concentrate factors are not available) e. Factor XIII deficiency.

39. Massive Transfusion Protocol Replacement of a blood volume equivalent within 24 hours. >10 units within 24 hours. Transfusion >4 units in 1 hour. Replacement of 50% of blood volume in 3‐4 hours. A rate of loss >150 ml/hour. Massive transfusion in patients with, or at risk of, massive hemorrhage should initially be transfused empirically with a 1:1:1 ratio of plasma: red cells: platelets. These patients with, or at risk of major hemorrhage, should be given tranexamic acid as soon as possible after injury.

40. BTR Management & Investigations It is very necessary for saving the life of patient and investigation for further evaluation of the control of the BTRs which will be discussed further in detail .

41. BLOOD SAFETY

42. Transfusions can transmit infectious agents: HIV, HBV, HCV, syphilis, malaria, etc. We follow stringent testing protocols that reduce transmission risk. Unsafe transfusions can have devastating medical and legal implications. Public confidence in blood transfusion is built on trust in safety protocols. The samples are initially tested by advanced antibody detection techniques.

43. Overview of Transfusion Safety Nearly 120 million units of blood are donated every year. However, this is not sufficient to meet the global need many patients requiring a transfusion do not have timely access to safe blood. Blood cannot be stored indefinitely, meaning there is a constant need for donations. Regular donations are required to ensure there is always a supply for those in need. Despite global need, donation rates differ around the world, and some high-income countries see up to seven times more donations than low-income countries. 

44. Blood transfusions are needed for a wide range of health conditions, including anemia, complications during pregnancy and childbirth, severe trauma due to accidents, and surgical procedures. They are also regularly used for patients with conditions such as sickle cell disease and thalassemia, as well as for products to treat hemophilia. Maintaining safe and effective procedures around the collection, storage, and use of donated blood is essential. Collectively called hemovigilance, these procedures cover the entire blood transfusion chain and are used to standardize the use of blood in healthcare. 

45. Importance of blood transfusion Blood transfusions are vital for replacing blood or blood components lost due to injury, surgery, or certain medical conditions, ensuring the body receives the necessary oxygen, clotting factors, and immune support.  A blood transfusion can save your life. You may need a blood transfusion if you've lost blood from an injury or during surgery, or if you have certain medical conditions, including: Anemia. Certain cancers. Hemophilia. Sickle cell anemia.

46. Blood transfusion reactions Introduction Definition – A blood transfusion reaction is any adverse reaction occurring as a result of a blood transfusion. These reactions can range from mild to severe and potentially life-threatening, and may be either acute (occurring during or shortly after the transfusion) or delayed (occurring days or weeks later)

47. CLASSIFICATION

48. Types - Immediate Reactions: Acute hemolytic reaction (ABO incompatibility) Febrile non-hemolytic reaction Allergic/anaphylactic reaction Transfusion-related acute lung injury (TRALI) Transfusion-associated circulatory overload (TACO) Delayed Reactions: Delayed hemolytic transfusion reaction(DHTR) Alloimmunization (red cell, platelet, HLA antibodies) Post-transfusion purpura (PTP) Transmission of infections (TTI)

49. Cause Category Examples Symptoms Immunological ABO incompatibility, minor antigen mismatch Fever, chills, back pain, and hemoglobinuria. Non – Immunological Bacterial contamination, iron overload Rise in temperature, mild discomfort Allergic Plasma proteins (IgA deficiency) Urticaria, itching, mild rash Volume overload TACO Severe allergy, hypotension, bronchospasm. Cytokine Accumulation Febrile non-hemolytic reactions Respiratory distress, hypoxemia Storage Lesions Lysis, potassium increase Hypertension, pulmonary edema . BLOOD TRANSFUSION REACTIONS - ACUTE

50. BLOOD TRANSFUSION REACTIONS – DELAYED Types: Delayed Hemolytic Reaction: Destruction of transfused red cells days after transfusion. Transfusion-Transmitted Infections: Hepatitis, HIV, malaria, syphilis. Post-Transfusion Purpura: Thrombocytopenia occurring 5–12 days post transfusion. Iron Overload: In patients with repeated transfusions. Graft-vs-Host Disease: In immunocompromised patients receiving non-irradiated blood.

51. Cause category Examples Symptoms Delayed Hemolytic Transfusion Reaction (DHTR) Anamnestic immune response to red cell antigens (e.g., Kidd, Duffy, Kell). Mechanism: Patient was previously sensitized (e.g., pregnancy or earlier transfusion); antibody levels had declined and were undetectable. Re-exposure causes rapid antibody production → hemolysis of transfused red cells. Mild fever, jaundice, falling hemoglobin days after transfusion. Alloimmunization Immune response to foreign antigens on transfused red cells, white cells, or platelets. Types: Red cell alloimmunization (anti-Kell, anti-E, anti-D, etc.). Platelet alloimmunization (HLA antibodies), Neutrophil alloimmunization (rare). Consequence: Difficulty finding compatible units in the future; risk of transfusion failure. Fever, chills, urticaria, itching, respiratory distress, low blood pressure, and hematuria DELAYED BTR

52. Examples Cause categories Symptoms Post-Transfusion Purpura (PTP) Antibodies against platelet antigens (especially HPA-1a)Typical in: Previously sensitized individuals (often women). Leads to: Severe thrombocytopenia 5–10 days after transfusion. Purpura, petechiae, and bleeding from mucous membranes or the gastrointestinal or urinary tracts. Transfusion-Transmitted Infections (TTIs) :- HIV, HBV, HCV, Syphilis, malaria, Cytomegalovirus (CMV) in immunocompromised patients. Undetected or window-period infections in donated blood.

53. Examples Cause category Symptoms Graft-versus-Host Disease (TA-GvHD) (rare but fatal) Transfusion of viable donor lymphocytes into an immunocompromised recipient. Typically prevented by: Using irradiated blood in at-risk patients. Occurs: 1–2 weeks post-transfusion. Fever ,Rigors , Tachycardia, Fall of systolic BP>30mm Hg , Backache Abdominal pain , vomiting and hypothermia. Missed Minor incompatibilities Antibodies to less common antigens not routinely tested. May cause subtle hemolysis, jaundice, or falling hemoglobin days later.

54. Investigations for BTR Diagnosis Repeat ABO/Rh grouping of pre- and post-transfusion samples. Direct antiglobulin (Coombs) test. Hemolysis markers: plasma hemoglobin, bilirubin, LDH, haptoglobin. Urine examination for hemoglobinuria. Blood cultures and gram stain (if fever/chills present). Screen for possible clerical/administrative errors. Serological testing for TTI markers in delayed reactions.

55. MANAGEMENT OF BTRs

56. TRANSFUSION TRANSMISSIBLE INFECTION

57. Blood Transfusion Process Blood transfusion – Life saving medical intervention procedure, essential role in patient management. All donated blood screened for transfusion transmissible infections, core component of every national blood transfusion program.

58. Common pathogens which can be transmitted through transfusion of blood or blood components :

59. Transfusion Transmissible Infections Transfusion therapies generally involve large volumes of blood or blood components being given to patients. Blood unit with a low viral load - capable of causing infection in the recipient. Effective screening systems - to detect, segregate, and remove reactive blood donations. All components derived from these reactive blood donations - removed from the quarantined usable stock.

60. Transfusion Transmissible Infections Every TTI have one or more window periods , ranging from a few days to months, and depends on the infectious agents , the screening marker. Testing facilities – to reduce window period. In this period, the particular screening marker is not yet detectable in a recently infected individual, even though the individual may be infectious. Nucleic acid represents the first detectable target to appear, followed within a few days by antigen, and subsequently by antibody as the immune response develops.

61. Transfusion Transmissible Infections One or more infection markers can be used to detect a particular infection during the screening process. Various assay systems developed for blood screening detect: Antibodies that indicate an immune response to the infectious agent Antigens that are produced by the infectious agent and indicate the presence of that agent Nucleic acid (RNA/DNA) of the infectious agent.

62. Transfusion Transmissible Infections Alternative strategies may however be required in non-endemic countries, where blood donor population includes travelers to or migrants from endemic areas. This is based on selective blood donor deferral and/or screening tests, if suitable assays are available. Only non-reactive blood and blood components should however be released for clinical or manufacturing use.

63. Transfusion Transmissible Infections Infections - capable of causing chronic diseases with possible serious consequences, greatest infection risk to transfusion recipients include: Human immunodeficiency virus (HIV) Hepatitis B virus (HBV) Hepatitis C virus (HCV) Treponema pallidum (syphilis). Routine screening - recommended as being mandatory for the provision of a safe blood supply.

64. Transfusion Transmissible Agents Human immunodeficiency virus (HIV) : Prevalence in India: The HIV 1 subtype C is the most commonly transmitted subtype in India and southern African countries. As per the National AIDS Control Organization (NACO) report 2017, the prevalence of HIV in the adult population and blood donors was 0.22% and 0.12%, respectively.

65. Transfusion significance: A seropositive unit can transmit HIV infection at a 90% rate to recipients. Window period: Viral RNA is detected within 3-10 days on different platforms of nucleic acid amplification test (NAT). Around 95% of donors show the presence of p24 antigens within 1-8 weeks, which is detected using enzyme-linked immunosorbent assay (ELISA) and rapid testing. Seroconversion is seen within 4 weeks in 95% of the individuals. HIV

66. HIV HIV antibodies can be detected by 20-28 days with 4th generation ELISA or rapid test, and more than 99% of individuals are completely positive for HIV antibodies by 3 months.

67. Laboratory diagnosis Serological tests: Enzyme-linked immunosorbent assay (ELISA) testing: Gold standard test for TTI screening in India, more sensitivity and specificity compared to rapid test. The sensitivity and specificity increase with the generation of ELISA test kits, and fourth-generation ELISA is almost 100% sensitive and specific. HIV

68. Chemiluminescence or Electro-chemiluminescence Testing: Similar to ELISA in principle, sensitivity and specificity. The advantage over ELISA testing is that it has a short turnover time and a facility for spot testing is present. HIV

69. Hepatitis B virus It is the causative agent of hepatitis B infection, resulting in both acute and chronic hepatitis infections. Transfusion significance: HBV can be transmited through transfusion of infected blood or blood products. Incubation period: The average incubation period for HBV infection is 60-90 days but it can range from 24- 180 days.

70. Laboratory diagnosis Serological testing: HBsAg can be identified in an infected donor’s serum or plasma by EIA, chemiluminescence, radioimmunoassay or other immunological based assays. Hepatitis B virus

71. Hepatitis C Prevalence in India: The prevalence of HCV infection in India is 0.9 to 1.9%. According to the NACO 2017 report, the prevalence of HCV in blood donors in India was 0.30%.

72. Transfusion significance: HCV is mainly transmitted by blood components and incompletely inactivated plasma fractionation products including IVIG, anti-D Ig for intravenous use and factor VIII concentrate and has never been transmitted by albumin concentrates or anti-D for intramuscular use. Incubation period: The incubation period is 2 to 26 weeks. The average incubation period is 7 to 8 weeks, followed by seroconversion occurring in 8 to 9 weeks. Hepatitis C

73. Laboratory diagnosis Serology testing: The diagnosis of HCV infection is essentially based on detecting antibodies against the core protein and the non-structural proteins NS3 to NS5. This can be done by rapid test, ELISA, chemiluminescence test etc. In ELISA or chemiluminescence tests, the first-generation test detects only anti-HCV antibodies against the NS4 (c100-3) antigen, which has a window period of around 12 to 26 weeks. The second generation test detects antibodies against two antigens, one core antigen and the second NS3 antigen. It reduces the window period up to 10 to 24 weeks. Hepatitis C

74. The third-generation test detects an additional antibody against NS5 antigen and further reduces the window period by 1 week. The recent fourth-generation test detects both HCV antigen and antibody, it increases the sensitivity and specificity of the test and the average window period is 26.8 days. Hepatitis C

75. Syphilis Treponema pallidum Transfusion significance: The organism can survive for 1 to 5 days at 4ºC in red blood cells. Platelets stored at 20 to 24ºC provide a more hospitable temperature for T. pallidum; but it does not survive for a longer time at high-oxygen tension in modern platelet storage bags.

76. Incubation period: Donors at any stage of disease, including late, latent syphilis, can transmit the infection with a variable incubation period from 4 weeks to 4.5 months, averaging 9–10 weeks. Syphilis

77. Laboratory diagnosis Serological testing : The serological tests are of two types: Non-specific test or non-treponemal tests: Non-treponemal tests include the venereal disease research laboratory (VDRL) test and rapid plasma reagin (RPR) test. Syphilis

78. Treponemal specific tests: These tests are based upon the detection of antibodies directed against specific treponemal antigens. Treponemal tests includes Treponema pallidum haemagglutination test (TPHA), Fluorescent treponemal antibody absorption test (FTA-ABS), Treponema pallidum immobilization test (TPI), Enzyme immuno assay (EIA) and Chemiluminescence assay (CLIA) etc. Syphilis

79. Malaria Prevalence in India: India has the 3rd largest burden of malaria, and about 89% of the cases reported from the South-East Asian regions are from India.

80. Transfusion significance: Transmission occurs mainly through red cell components, liquid or frozen plasma, platelets, and granulocyte concentrates and cryopreserved red cell units can also transmit the parasite. Plasma fractionated products like albumin, IV Ig and factor VIII do not transmit the parasite. At 4–6 C storage, P. malariae is viable for less than five days while P. falciparum is viable for up to ten days. Incubation period: For P. falciparum and P. vivax, incubation period may be 1 week to 1 month but may require several months for P. malariae. Malaria

81. Laboratory diagnosis: Serological test: The detection of circulating antibodies or antigens of malaria parasite aims to screen blood donors. Antibody testing is mainly done by indirect immunofluorescence assay (IFAT) or ELISA. Microbiological examination: For detecting the parasite, a thick or thin smear of peripheral blood film is the most commonly used method, but it has a low sensitivity. Malaria

82. Other Transfusion Transmissible Agents Notable points: In endemic areas, specific risks include the transmission of malaria, Chagas disease and HTLV. In non-endemic areas, specific risks are posed by the donation of blood by individuals who have lived in or visited areas that are endemic for malaria, Chagas disease or HTLV. Specific recipient groups are at risk from the transmission of certain infections such as human cytomegalovirus (CMV).

83. Modes of Minimizing TTIs To minimize the risk of the transmission of infection through transfusion: All whole blood and apheresis donations should be screened for evidence of the presence of infection prior to the release of blood and blood components for clinical or manufacturing use.

84. Screening of all blood donations should be mandatory for the following infections and using the following markers: HIV-1 and HIV-2 : screening for either a combination of HIV antigen-antibody or HIV antibodies. Hepatitis B : screening for hepatitis B surface antigen (HBsAg) Hepatitis C : screening for either a combination of HCV antigen-antibody or HCV antibodies Syphilis ( Treponema pallidum ): screening for specific treponemal antibodies.

85. Modes of Minimizing TTIs Screening should be performed using highly sensitive and specific assays. Only blood and blood components from donations that are nonreactive in all screening tests for all markers should be released for clinical or manufacturing use. All screen reactive units should be marked, removed from the quarantined stock, and stored separately.

86. Modes of Minimizing TTIs They should be kept securely until disposed of safely, kept for quality assurance or research purposes, in accordance with national policies. Confirmatory testing of screen reactive donations should be undertaken for donor notification, counselling, and referral for treatment, deferral, or recall for future donation. Revisit previous donations if necessary.

87. CLIA

88. ELISA

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