Blood transfusion Reactions Path - SLIDE SHARE.pptx

A ppt on blood transfusion reactions essential for students doing residency in transfusion medicine.

1. BLOOD TRANSFUSION REACTIONS Presenter: DR s vishnu prasad

2. RECAP A transfusion reaction is defined as any transfusion-related adverse event that occurs during or after the transfusion of whole blood, blood components, or human-derived plasma products. Blood units transfused per year is 11 million against demand of 15 million. Blood transfusions are considered medical therapies and Blood components are considered drugs (Drugs and Cosmetics Act 1940 & Rules 1945) Inherent risks of adverse effects as with other medical therapies

3. DEFINITIONS Adverse event - Undesirable and unintended occurrence before, during or after transfusion Incident : Did not meet all the requirements for a suitable transfusion for that patient, or that were intended for another patient. Near miss: Error or deviation from standard operating procedures (SOPs) Adverse reaction : An undesirable response or effect in a patient temporally associated with the administration of blood or blood component.

4. TAD/TAH PTP

5. ACUTE/IMMEDIATE (<24 hours) IMMUNOLOGICAL Hemolytic Transfusion Reaction (HTR) Febrile Non- Hemolytic Transfusion Reaction (FNHTR) Allergic Transfusion Reaction Transfusion Associated Acute Lung Injury (TRALI)

6. FNHTR Presence of one or more of: Fever (≥38 ºC oral or equivalent and a change of ≥1 O C from pretransfusion value) Chills/rigors Due to Abs in recipient against Ags of donor platelets or WBC Human Leukocyte Antigens Granulocyte specific Antigens Platelet specific Antigens Presence of cytokines in blood components

7. MANAGEMENT If mild :– Slow down the infusion Use Antipyretic If severe : – Stop transfusion Antipyretics and symptomatic treatment Usually reactions are self limiting Can be prevented by:- Leucoreduced / leucodepleted blood components Antipyretic cover /slow transfusion

8. LEUKOREDUCTION Washing (saline washed red cells) Freezing and thawing Buffy coat method of component preparation Leucodepletion filters Low leucocyte apheresis device (cell separators)

9. LEUCODEPLETION FILTERS Prestorage leukoreduction is preferred. Transfused component should have <5 X 10 6 leukocytes/unit Leucocyte removal with Leucofilters can significantly reduce posttransfusion CMV infections

10. ALLERGY & ANAPHYLAXIS

11. Most common reactions seen with platelet & plasma transfusions 2 nd to FNHTRs in RBC transfusions Plasma contaminants (proteins, drugs) are potent allergens. Type I hypersensitivity reactions: can be serious and life threatening. Atopic individuals are at higher risk especially those with previous h/o allergies.

12. Ig E Soluble Ag in donor plasma Increased Vascular Permeability IgE Mast Cell/Basophil Release of Histamine

13. Allergic Reactions (Uncomplicated) Anaphylactoid Reactions Anaphylactic Reactions IgE mediated Non IgE mediated IgE mediated Cutaneous symptoms predominantly - Urticaria - Pruritis - Angioedema Cutaneous + Respiratory + GI symptoms Respiratory + GI symptoms + Life threatening Cardiac symptoms

14. CLINICAL FEATURES Mild/Moderate Urticaria (localized / generalized) Pruritus Erythema Laryngeal / lid edema Occasional angioedema Severe Hypotension Shock Tachycardia Breathlessness Laryngeal spasm

15. MANAGEMENT Stop infusion Antihistamine, Epinephrine Airway support Vasopressors IV steroids & Fluids H1- receptor antagonist

16. PREVENTION Saline-washed RBC and platelet preparations. Previous history of reaction: Next transfusion administered slowly after premedication with H1 & H2 blockers & a glucocorticoid.

17. Transfusion Associated Acute Lung Injury (TRALI)

18. CRITERIA FOR DIAGNOSIS

19. A lloantibodies thought to be responsible for TRALI: Anti-Neutrophil antibodies. A nti-Human leukocyte antigen (anti-HLA) class I, class II antibodies. Reference: Popovsky MA, Moore SB. Diagnostic and pathogenetic considerations in transfusion-related acute lung injury. Transfusion 1985;25:573–577. Kopko PM, Popovsky MA, MacKenzie MR, et al. LA class II antibodies in transfusion-related acute lung injury. Transfusion 2001;41:1244–1248 Engelfriet CP, Reesink HW, Brand A, et al. Transfusion-related acute lung injury (TRALI). Vox Sang 2001;81:269–283.

20. CLINICAL FEATURES Acute respiratory distress: Dyspnea Tachypnea Hypoxemia Fever with rigors Tachycardia Hypothermia & Hypotension

21. On auscultation : Widespread crepitations On suction : copious frothy tracheal exudate, much like lightly whipped egg white CXR : Bilateral lung infiltrates (Bat wings) Sparing of lung bases

22. 2 hours after onset of TRALI symptoms 24 hours after onset of TRALI symptoms Ref: Rossi’s Principles of Transfusion Medicine, Sixth Edition.p570

23. D IFFERENTIAL DIAGNOSIS Acute MI TACO Sepsis Anaphylaxis Other causes of acute lung injury MANAGEMENT Respiratory support (oxygen, may be intubation)

24. ACUTE/IMMEDIATE (<24 hours) NON- IMMUNOLOGICAL Transfusion Associated Circulatory Overload (TACO) Transfusion Associated Dyspnoea (TAD) Transfusion Associated Hypotension (TAH) Transfusion Associated Sepsis (TAS)

25. TRANSFUSION ASSOCIATED CIRCULATORY OVERLOAD

26. DEFINITION A cute respiratory distress from pulmonary edema caused by increased intravascular volume due to excessive transfused fluid or too rapid infusion rate & the inability of the patient to accommodate the transfused products volume due to impaired pulmonary, cardiac, or renal function. Incidence : 1% to 8%

27. Excessive transfused fluid Increased pulmonary capillary pressure Hydrostatic pulmonary edema FACTORS AFFECTING Volume of transfused product Rate of transfusion Patient factors

28. CLINICAL FEATURES Hypertension Tachycardia Respiratory distress Jugular venous distention Crepitations on auscultation CXR : Cardiomegaly & interstitial infiltrates

29. MANAGEMENT Stop infusion (other IV fluids also) Upright position O2 support with positive airway pressure Diuretics Dialysis – in renal failure patient

30. PREVENTION Avoid unnecessary Transfusion. Pretransfusion assessment for risk factors : in low body weight cases & patient with comorbidities. In small patients : not more than 4 ml/kg Body weight

31. TAD Characterized by respiratory distress within 24 hours of transfusion. Does not meet the criteria of TRALI, TACO, or allergic reaction. It is self-limiting and may require supportive management in few cases. The pathophysiology of TAD is not clear as it is intermediate between TACO and TRALI.

32. TRANSFUSION ASSOCIATED HYPOTENSION Hypotension during/within 1 hr of transfusion Drop in SBP>30 mmHg or SBP < 80 mm Hg Children: SBP 25% drop from baseline Increased bradykinin in stored blood

33. TRANSFUSION ASSOCIATED SEPSIS Bacterial infection following transfusion, with evidence of blood product contamination or infection in the donor and in the absence of infection in the recipient before transfusion. Infection risk for other diseases(HIV, HBV & HCV) has decreased due to better donor testing. Psychrophilic bacteria - Yersinia enterocolitica Plasma and cryoprecipitate are associated with P. cepacia and P. aeruginosa Yersinia enterocolitica

34. Platelets Red blood cells Plasma Cryoprecipitate Decreasing order of Incidence

35. Quality Control 1% of total collected collected bags/month or 4 units/month whichever is greater to be sent for culture every month.

36. Donor arm preparation and diversion pouch To prevent bacterial contamination Skin disinfection : effective for skin commensals unless done improperly One step procedure Two step procedure Sample pouch : Best to prevent for skin commensal entry into the blood bag

37. DELAYED (After 24 hours) IMMUNOLOGICAL Delayed Hemolytic Transfusion Reaction (DHTR) Transfusion Associated Graft v Host Disease ( TAGvHD ) Post Transfusion Purpura

38. DELAYED HEMOLYTIC TRANSFUSION REACTION After 24 hours upto 28 days after transfusion Diagnosed by a positive DAT or newly identified allo -ab in the plasma. Rh or minor blood group antibodies causing extra vascular haemolysis Mostly seen in patients of Sickle Cell Disease Prevention –screening for alloantibodies & selection of appropriate red cells

39. TA-GvHD

40. A lloimmune complication mediated by Donor T cells . Allogeneic donor lymphocytes, which subsequently engraft, proliferate, and attack recipient tissues. Associated with destruction of the recipient’s bone marrow. TA-GVHD have never been attributed to transfusions with plasma, cryoprecipitate, factor concentrates, albumin, intravenous immunoglobulin

41. GVHD TA GVHD O ccurs after allogeneic bone marrow transplantation L ethal complication of blood transfusion R esponds to immunosuppressive therapy D oes not respond to immunosuppressive therapy M ore common U ncommon D oes not cause marrow aplasia C auses profound marrow aplasia N ot that fatal as it responds to immunosuppressive agents H ighly fatal with mortality rate of 90% H igher incidence in unmatched or unrelated donors Higher incidence in related donors

42. CLINICAL FEATURES

43. PREVENTION- IRRADIATION Exposure of cellular components to ionizing radiation Damage to nuclear DNA Generation of ions and free radicals Inactivation of T cells

44. INDICATIONS OF IRRADIATION

45. POST TRANSFUSION PURPURA Thrombocytopenia after 5-12 days of transfusion Ab’s in patient against the Human Platelet Antigen system Signs and symptoms of mucocutaneous bleeding Usually resolve spontaneously Treatment with IVIG or steroids

46. DELAYED (After 24 hours) NON-IMMUNOLOGICAL Transfusion Associated Iron Overload Transfusion Transmissible Infections

47. TRANSFUSION ASSOCIATED IRON OVERLOAD

48. A major concern in management of patients with severe anemic syndromes One unit of transfused blood – 200-250 mg of iron Serum ferritin – inexpensive marker Prophylactic iron chelation therapy

49. TRANSFUSION TRANSMITTED INFECTIONS

50. Microbial agents of importance to blood transfusion services are those that are transmissible by blood transfusion and can cause morbidity and mortality in recipients. For patients: Worldwide - The overall prevalence of transfusion transmitted infections ranges from 2.79% to 18.7% India HIV HBV HCV SYPHILIS MALARIA 0.14% 0.82% 0.02% 0.13% 0.03% Divyashree B N, Sankar S , Khanna R M , Sero -prevalence and trends of transfusion transmissible infections among blood donors in a rural tertiary care centre- A 7 years study.  Indian J Pathol Oncol  2020;7(4):576-581

51. S trategies for prevention of TTIs Legally mandated as per Drugs & Cosmetics Act 1940 and Rules 1945. Media scrutiny Court cases

52. Agents of TTIs India World HIV HBV HCV SYPHILLIS MALARIA CMV West Nile Virus Chaga’s Disease HTLV Zika Virus Babesia

53. Tests for infectious Diseases All mandatory tests shall be carried out on blood samples taken at time of collection Serological tests- ELISA/Chemiluminescence Small centres which do not have provisions to do ELISA/ CLIA may release blood after rapid tests Blood Centre shall repeat the test using the same technique using the pilot tube National Standards for Blood Banks, 2022

54. TTI SCREENING MARKER Methodology Additional HIV-1 and HIV-2 HIV antigen-antibody or HIV antibodies ELISA/ CLIA NAT Hepatitis B Hepatitis B surface antigen (HBsAg) ELISA/ CLIA NAT Hepatitis C HCV antigen-antibody or HCV antibodies ELISA/ CLIA NAT Syphilis ( Treponema pallidum ) Specific treponemal antibodies VDRL/ RPR Method / TPHA/ ELISA / CLIA - Malaria Malarial Parasite Ag ( Pf HRP-2 and Pan pLDH ) Rapid/ELISA -

55. ELISA (Enzyme-linked Immunosorbent Assay) M ost commonly used screening test at blood centers. S ensitive, specific, and cost effective. E asy to perform, adaptable to large number of samples. At our centre : 4th generation ELISA : detects both HIV antibodies and p24 antigen by using combination of recombinant/synthetic peptides as well as monoclonal antibodies respectively.

56. CHEMILUMINESCENCE Chemiluminescent immunoassay (CLIA) is an immunoassay technique where the label, i.e. the true “indicator” of the analytic reaction, is a luminescent molecule Chemiluminescent methods can be direct—using luminophore markers—or indirect—using enzyme markers. Either method may be competitive or non-competitive.

57. RAPID T ESTS W ork on various principles such as: Dot blot assays (or Immuno-concentration or flow through method, e.g., Tridot test. Immunochromatography (or ICT, lateral flow assay) Particle agglutination assays (using latex, gelatin , RBCs) Dip stick/Comb tests (Enzyme immune assay-based tests) .

58. SYPHILLIS: Venereal Disease Research Laboratory (VDRL) This test was named after Venereal Disease Research Laboratory (VDRL), New York, where the test was developed. It works on the principle of precipitation (slide flocculation) test. Uses: VDRL test is cheaper and preferred as a screening test for laboratory with higher sample load and for batch testing (e.g., antenatal screening) and also to monitor treatment response.

59. Rapid Plasma Reagin (RPR) RPR is another slide flocculation test using disposable plastic cards having clearly defined circles. It is like VDRL test with some differences: Prolonged shelf-life - preferred for individual sample (less sample load) VDRL is preferred when samples are tested in batches (large sample load). Results can be read in naked eyes, without the need of a microscope, as the clumps formed are bigger in size.

60. MALARIA Microscopic tests Peripheral blood smear —gold standard Fluorescence microscopy (Kawamoto’s technique) Quantitative buffy coat examination —parasitized RBCs appear as brilliant green dots. Non-microscopic tests Antigen detection tests (RDTs) —detect pan malarial Ag (LDH, aldolase), falciparum specific Ag (HRP-II) Molecular diagnosis — PCR

61. Schematic diagram of rapid diagnostic test kit showing negative, non-falciparum, pure or mixed infection with Plasmodium falciparum and invalid result of malaria.

62. NUCLEIC ACID AMPLIFICATION TEST Can be done as an additional test It is more sensitive and decreases the window period leading to an early detection.

63. Technology Window Period HIV HCV HBV ELISA – III Generation 20.6 days 58.3 days 36.3 days ELISA – IV Generation 13.7 days 9.4 days 24 days ID NAT 5.6 days 4.9 days 20.6 days

64. SCREENING AT BLOOD CENTRE: STRATEGY – I GUIDELINES

65. Donors who have consented-recalled to the Blood Centre so as to inform them S ero -reactive result of transfusion-transmitted infection (TTI) Provide post-donation counselling R eferring to appropriate medical services for confirmation of diagnosis Process should be documented on record RECALL AND REFERRAL

66. Referral Slip for TTI positive donors HIV – Nearest ICTC HBV/HCV – Gastro OPD Syphillis – Skin OPD Malaria – Med OPD

67. REFERENCES Modern blood banking and Transfusion practices, 7 th edition, Denise M Harmening. National Guidelines for HIV Testing by NACO, 2016 DGHS Technical Manual 3 rd edition 2023 Rossi’s Principles of Transfusion medicine, 5 th edition, Toby L Simon, McCullough, Ronald G Strauss, Edward L Snyder. National Standards of Blood Centres - 2 nd Edn

68. THANK YOU