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Module 6: Complications of blood transfusion. Transfusion Training Workshop KKM 2012. Complications of blood transfusion. Early Acute transfusion reactions Major life-threatening Haemolysis (ABO incompatibility) Gram-negative Bacteremia Anaphylaxis/ Acute Hypotension Minor Urticaria
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Module 6: Complications of blood transfusion Transfusion Training Workshop KKM 2012
Complications of blood transfusion • Early • Acute transfusion reactions • Major life-threatening • Haemolysis (ABO incompatibility) • Gram-negative Bacteremia • Anaphylaxis/ Acute Hypotension • Minor • Urticaria • Febrile non-haemolytic transfusion reaction • Transfusion-associated acute lung injury (TRALI) • Delayed/ Late • Delayed haemolytic transfusion reaction • Transfusion-associated graft vs. host disease (TA-GVHD) • Transfusion-transmitted infections (TTI) • Iron overload
Minor transfusion reactions • Febrile non-haemolytic transfusion reaction • Commonest type of transfusion reaction • Especially frequent in multi-transfused patients • Urticarial reaction
Case 1 • 30 year old man • Known to have a peptic ulcer • Presented with severe epigastric pain • OGDS done immediately • Forrest 1b ulcer noted • Admitted for observation • Day 6, noted Hb dropped to 7 g/dL • 2 pint PRBC were requested
Case 1 • 45 minutes into 1st PRBC • T 38.30C • BP 145/88 • HR 95/min
1. Febrile reactions- what to do? • Sudden rise in temperature >1oC ± rigors • No fall in BP • Occur during or within 4 hours of transfusion • Temporarily stop blood • Check for clerical error • Give paracetamol1 g poReview 30 minutes • Continue transfusion slowly • If symptoms do not settle or recur once transfusion resumed, contact the BB • If in doubt, treat/ investigate as a major reaction
Febrile reactions • Antibodies against donor leucocytes in PRBC • Cytokines that accumulate in PRBC with storage • Usually in multiply transfused patients • Can be reduced or prevented by leuko-depletion at collection centre
Case 2 • 56 year old lady • Known to have Myelodysplastic Syndrome • Was regularly transfused for the last 1 year • Presented with petechiae and gum bleeding • PLT noted 7 x 109/L
Case 2 • 4 units of platelets was requested • During the 3rd unit of platelet transfusion, patient c/o rash and itchiness • BP 134/70 • HR 86/min
2. Urticarial reaction – what to do? • Temporarily stop blood • Give IV piriton 10 mg ± IV hydrocortisone 50-100 mg (repeat 4 – 6 hourly) • Review 30 minutes • Continue transfusion if settling
(Allergic) Urticarial reaction • Generally mild reaction • Pre-existing IgE antibody against donor plasma proteins in platelets or FFP • Primed mast cells degranulate and release chemical mediators including histamine
Major transfusion reactions • Acute Haemolysis (ABO incompatibility) • Gram-negative bacteremic shock • Anaphylaxis
Case 3 • 28 year-old lady • G3 P2, came in labour • Noted Hb 7.5 post-delivery • GXM 2 PC
Case 3 – cont’d • 1st PC transfused uneventful • 10 minutes into the 2nd PC • c/o severe back pain • BP 80/50 PR 110 T 400C
1. Acute Haemolysis (ABO incompatibility)2. Gram-negative bacteremic shock • Suspect if ≥1 are present: • Shortness of breath/ chest pain not due to cardiac problems or pulmonary oedema • Back pain/ loin tenderness • Profound hypotension • Disconnect blood & giving set ; put up saline infusion • Check for clerical error • Report to blood bank + specialist • Take essential samples: • EDTA: FBC • EDTA/plain: 10 mLs for re-GXM, Coomb’s test and antibody screen • DIC screen • Renal Profile, serum bilirubin • Blood culture • First urine passed for haemoglobinuria • Send samples to transfusion lab with unit giving set + all previous units + completed transfusion reaction form
Acute Haemolysis (ABO incompatibility)= Acute Haemolytic Transfusion Reaction (AHTR) • Recipients antibody against donor red cells • ABO antibodies are good complement binders • Activation of complement results in intravascular haemolysisand cytokine release • Haemoglobinuria (vs. bacteremic shock), renal failure
Bacterial sepsis • Bacterial contamination of donor blood • inadequate aseptic technique during collection • coring of the skin with the venipuncture needle • transient asymptomatic donor bacteremia • chronic low grade donor infection • improper refrigeration of RBCs during storage or transportation • contamination during the processing of pooled products • contamination by infected water baths during thawing of frozen components • defects in blood bags
Bacteremic shock • More frequent in platelet transfusion – stored at room temperature • Both gram positive or negative contamination can occur • Symptoms appear during or immediately after blood transfusion • Symptoms of septicaemia, may result in hypotension and shock esp. with gram negative bacteremia
Inappropriate & unnecessary (I&U) transfusion has lead to a major transfusion reaction and mortality! Inappropriate transfusion to correct iron deficiency anaemia
3. Anaphylaxis (Acute hypotension) • Rare • Immediate generalised hypersensitivity reaction • Recipient IgE to serum proteins/ drugs/ in donor blood • IgG antibodies to IgA in patients with congenital IgA deficiency • Clinical features: • Acute bronchospasm • Oedema • Circulatory collapse • Stop blood • Maintain venous access with 0.9% saline • Oxygen by mask • Adrenaline 1:1000 0.5 or 1.0 ml i/m repeated every 10 min as necessary • Piriton 10-20 mg IV slowly • Disconnect blood and investigate as for 1 & 2 • Also investigate for congenital IgA deficiency
Case 4 • 35 years old Chinese man • PRCA, transfusion-dependent • Hb 5.1, GXM 4 units PC over 2 days • 3 units – no complication • After 120 mLs of 4th unit • c/o headache & SOB
Case 4 – cont’d • BP 60/40 > un-recordable feeble pulse • Resuscitated with i/m adrenaline and fluids • Cardiac monitoring – sinus tachycardia, no acute changes • BP 100/60 PR 93/min • Admitted to ICU for observation
Looking back • 4th PC, nurse decided to use bedside filter • 15 minutes later, hypotensive shock • Patient on ARB (valsartan) for cardiomyopathy
Acute Hypotensive Transfusion Reaction • Contact activation on negative charged surface (blood filters) • Bradykinin release from HMWK • Acts on B2 receptors on endothelium • Releases prostaglandins, NO and proinflammatory cytokines • Vasodilatation and acute hypotension
Acute hypotension with ACE-I • 1st reported in 1996 • ACE hydrolyses bradykinin • ACE-I prevents breakdown of bradykinin • Has also been reported with ARB
Case 5 • 40 year-old man with Paroxysmal Nocturnal Haemoglobinuria (PNH) • Transfused 2 PC for anaemia Hb 8.5 • 4 h later developed SOB • T 38.50C BP 130/80 PR 100
Transfusion-related acute lung injury (TRALI) (non-cardiogenic pulmonary oedema) • During or within 6 hours of a transfusion • Usually with WB or FFP • Rapid onset of dyspnea and tachypnea • Fever, cyanosis, and hypotension • Respiratory distress and pulmonary crackles may be present • CXR bilateral pulmonary oedema with bilateral patchy infiltrates • Indistinguishable from Acute Respiratory Distress Syndrome (ARDS)
TRALI - pathophysiology • Infusion of donor antibodies directed against recipient leukocytes • anti-HLA (human leukocyte antigens) • anti-HNA (human neutrophil antigens) • cause complement activation, neutrophil activation and release of cytotoxic agents • Causing endothelial damage and capillary leak • Treatment: supportive • Prevention: exclude donor from registry
Case 6 • 30 year-old Nigerian lady • Known sickle cell disease • Last crisis 20 years ago • G1P0 @ 14 weeks • Hb 7.0 in private hospital • GXM 2PC requested and transfused
Case 6 – cont’d • 10 days later, presented with lower abdominal pain, dyspnoea and back pain • Referred to Ampang hospital on 1st day of CNY • GCS deteriorated • Pale+++ Jaundice++ Haemoglobinuria • Hb 2.0 Bil ID 400 LDH 2300
Normal plasma Patient’s icteric plasma 10 days later Group O cDe/cDe = R0R0 Antibodies detected: Anti-E, anti-Jkb and anti-Fya
Case 6 – cont’d • Delay getting matched blood • Exchange transfusion performed after 24 hours • Patient died 8 hours later • Cause of death: Delayed haemolytic transfusion reaction
Delayed haemolytic transfusion reaction (DHTR) • Exposure to certain red cell antigens • Development of alloantibodies and titres may diminish with time • Re-exposure results in amnestic response • Especially with Kidd (anti-Jka and anti-Jkb) and Duffy (anti-Fya and anti-Fyb) antigens • Haemolysis occurs within hours, days or weeks (typically 10 – 14 days)
Patients at risk for DHTR • Patients at risk for allo-immunization • Sickle cell disease • Thalassaemia • AIHA • Patients requiring repeated transfusions • How to prevent? • Request for red cell phenotyping before transfusion • Talk to your blood bank specialist • Transfuse phenotype-matched blood
Transfusion-associated GVHD • Transfused T lymphocytes can mount an immune reaction towards an immuno-compromised recipient • Can occur if donor and recipient has shared HLA antigens • Higher risk in patients receiving lympholytic chemotherapy e.g. Fludarabine and following BM transplant • High mortality – almost 100% • Prevention : Gamma irradiation 2500 cGy (lowest dose delivered to any portion of the canister should be 1500 cGy)
Indications for irradiated PRBC or platelets • Premature babies • Intrauterine/ neonatal exchange transfusions • Congenital immuno-deficiencies • Recipients receiving blood from directed donors (blood relatives) • Recipients with lymphomas esp. Hodgkin’s Lymphomas • Recipients receiving lympholytic therapy (e.g. fludarabine, cladribine, clofarabine, campath) • Recipients undergoing autologous or allogenic stem cell transplants
Case 7 • 28 year-old lawyer • c/o fever x 4 days • Hb 12.5 Hct 36 Plt 18 • No evidence of plasma leakage • Having her menses • Diagnosis: Dengue fever • Transfused 4 units random platelets (I&U)
Case 7 – cont’d • 6 months later… • Medical check-up • Found to be HIV positive • No risk factors
Transfusion-transmitted infections • Risk of TTI: • HIV 1:2 million donations • HCV 1:2 million donations • HBV 1: 200,000 - 500,000 donations Susan L, Arch Pathol Lab ed 2007
Blood is never 100% safe Always a risk of transmission of virus and bacteria
Inappropriate & unnecessary (I&U) transfusion has lead to transmission of an infectious disease and its consequences
The next time you decide to transfuse Stop, think and ask yourself … Is it really necessary?