Blood transfusion: Non-infective complications

1. Blood transfusion:Non-infective complications Dr Dupe Elebute Consultant Haematologist

2. Learning objectives Complications of blood transfusion: • Haemolytic transfusion reactions • Febrile non-haemolytic reactions • Transmitted infections • Immunological complications • Transfusion haemosiderosis • Errors in transfusion (SHOT)

3. Indications for red cell transfusions • To replace blood loss • Trauma • Surgery • Chronic gastrointestinal haemorrhage • To correct anaemia • Bone marrow failure: aplastic anaemia, post-chemotherapy • Haemoglobinopathies: Sickle cell disease, Thalassaemia • Severe haemolysis: HDN • Chronic disorders: renal failure, malignancy £130.22

4. Current mandatory testing • TPHA (since 1940s) • HBsAg (1971 - 72) • anti HIV (October 1985) • anti HCV (September 1991) • HCV NAT (April 2001) • anti HTLV (October 2002)

5. Complications of blood transfusion EARLY • Circulatory overload • Febrile non-haemolytic reactions • Allergic reactions • Haemolytic reactions: immediate or delayed • Effects of massive blood transfusion • Bacterial infections from contamination

6. Late Complications of BT • Transfusion transmitted infections (TTI) Viruses: • Hepatitis B, C; HIV I & II; HTLV I & II; CMV Bacteria: • Treponema pallidum (Syphilis); Salmonella Parasites: • Malaria; Toxoplasma; Microfilaria

7. Late complications of BT (2) • Immune sensitisation • Transfusion associated lung injury (TRALI) • Post-transfusion purpura (PTP) • Transfusion associated graft-versus-host disease (TA-GvHD) • Transfusion haemosiderosis (iron overload)

8. Early complications of BT…..

9. Circulatory overload • Blood transfused too rapidly for compensatory fluid redistribution to take place; more common in elderly and pts with chronic anaemia • Causes Acute LVF • Prevention: • Give packed red cells • Transfuse slowly • Give diuretic with transfusion e.g. Frusemide 20mg p.o. • Management of LVF: • IV Frusemide • Oxygen (patient propped up in sitting position) • IV Morphine

10. Febrile non-haemolytic transfusion reactions • Caused by white cells in blood bag reacting against anti-leucocyte antibodies in patient • Affects multi-transfused patients or parous women • Symptoms: Fever, rigors • Management: • Slow or stop transfusion • Antipyretic e.g. Paracetamol •  incidence following universal leuco-depletion of red cells (vCJD initiative)

11. Acute transfusion reactions Acute haemolytic transfusion reaction due to ABO incompatible blood or bacterial contamination • difficult to differentiate clinically • causes: • acute intravascular haemolysis • shock • acute renal failure • DIC • extremely serious, can be fatal

12. AHTR: 2 • most ABO mismatched transfusions due to human error • if wrong blood to wrong patient, 1:3 chance of ABO incompatibility 1:10 will be fatal! • may occur after infusion of small volume of blood • usually occurs soon after start of transfusion

13. AHTR: Symptoms & Signs • Patient feels unwell and agitated • Symptoms • Fever, rigors • Headache, SOB • Loin/back pain • Pain at infusion site • Signs • Hypotension • Reduced urine output  acute renal failure • Bleeding from venepuncture sites due to DIC • Urinalysis: haemoglobinuria

14. Management of AHTR A medical emergency: • Stop transfusion immediately • Keep line open with N/Saline using new giving set • Monitor pulse, BP, temp • Call member of medical staff • Check identity of patient against blood bag • Take urgent blood samples: FBC, cross-match, U & Es, clotting screen, blood cultures • Save any urine • Send blood unit back to the blood bank

15. Allergic reactions • Occurs within minutes of starting transfusion • More commonly with plasma-containing components (platelets, FFP) • Symptoms: urticaria, itching • Management: • slow/stop transfusion • Give antihistamine (Piriton, Hydrocortisone) • Can give pre-med prior to future transfusions • If still problematic, use saline-washed components

16. Allergic reactions: 2 • Severe reactions/anaphylaxis are rare but potentially life-threatening • May be due to anti-IgA in patients with severe IgA deficiency • NBS can provide IgA deficient blood components for future transfusions

17. Delayed haemolytic transfusion reactions Due to secondary immune response following re-exposure to a red cell antigen • Patient previously sensitised to a red cell antigen by transfusion or pregnancy • Antibody not detected on routine screening for X-match • Patient given transfusion with blood containing same antigen • Provokes an anamnestic (secondary immune) response • Within days, antibody level rises and transfused red cells removed from circulation

18. Delayed transfusion reactions (2) • Occurs 24hr after transfusion (7-10 days) • Causes extravascular haemolysis • Red cells destroyed in liver, spleen; occurs slowly • Few clinical signs: fever, anaemia, jaundice • Re-testing of patient’s serum will now detect antibody • In future, patient must be transfused with antigen negative blood

19. Massive blood loss • Medical emergency • Loss of one blood volume within 24 hour period • 50% blood volume loss within 3 hours • Rate of blood loss  150ml/min • Any blood loss >2L (SGH) • Usually occurs in A&E, operating theatre or obstetric department • High morbidity & mortality

20. Massive Blood Loss (2) • Ensure adequate venous access • Attempt to maintain blood volume with saline, plasma expanders • ‘Flying squad’ blood (O Rh Neg, CMV neg) available if blood required in 15 minutes

21. Massive Blood Loss:A Vicious Cycle Haemorrhage Dilution of clotting factors and thrombocytopenia Massive Blood Transfusion

22. Massive Transfusion: complications • Hypothermia  acidosis • Hyperkalaemia: K+ leaks out of rbcs during storage • Citrate toxicity: red blood cells kept in citrate plus additive solution (SAG-M) • Hypocalcaemia: Ca2+ ions bound by citrate • Depletion of platelets and coagulation factors • Fluid overload  acute respiratory distress syndrome (ARDS)

23. Late complications of BT…..

24. Transfusion infection risks in UK HIV (1987) 1 : 1m donations (1993) <1 :1m (2003) 1: 10m HBV (1993) 1 : 20,000 (2003) 1: 1m HCV (1990) 1 : 1,300 (1993) 1 : 13,000 (2003) 1 : 33m

25. Immunological complications • Transfusion related acute lung injury (TRALI) • Post transfusion purpura (PTP) • Transfusion associated graft-versus-host disease (TA-GvHD) • Immunomodulation • Post surgical infection • Tumour reoccurrence

26. TRALI • Potent white cell antibodies in donor’s plasma which react strongly with the recipient’s granulocytes • Donors usually multi-parous females • Causes ‘ARDS-like’ syndrome: • Fever • Non-productive cough • Acute breathlessness • CXR: bilateral infiltrates • Donors removed from panel

27. TRALI: 2 • Mainly supportive treatment • High concentration oxygen • IV fluids and inotropes • Mechanical ventilatory support may be required urgently • Improvement within 48 hours with adequate respiratory support/ITU management

28. Post Transfusion Purpura • Rare but potentially lethal complication • Caused by allo-antibodies to human platelet antigens • Most commonly anti-HPA-1a (in HPA-1a-neg individual) • Typically occurs in parous females 7-10 days following transfusion • Presents as severe platelets, with haemorrhage Treatment: • High dose intravenous immunoglobulins • Steroids and plasma exchange also effective • Platelet transfusions ineffective

29. TA-GvHD • Transfused donor lymphocytes that are compatible with recipient but recognise recipient as foreign engraft and initiate a ‘GvH’ response • Syndrome of rash, diarrhoea, deranged liver function tests and pancytopenia • Typically occurs 10-14 days post transfusion • Bone marrow failure and resistant infections result in mortality rates 90% !

30. TA-GvHD: 2 • No effective treatment • Can be prevented by gamma-irradiation of cellular blood components to be transfused (inactivates donor leucocytes) • Leucodepletion alone not effective • Irradiation recommended for: • BMT patients • Intra-uterine transfusions • Hodgkin’s disease and patients with congenital cellular immune deficiencies

31. Transfusion haemosiderosis • Each unit of blood contains 200-250mg of iron • Body excretes approx. 1mg/day • Frequent transfusions e.g. Thalassaemia major, Sickle cell patients can lead to iron overload • Clinical features caused by iron deposition in organs • Poor growth and sexual development • Diabetes • Liver cirrhosis • Hypoparathyroidism • Cardiomyopathy  cardiac failure, arrythmias: major cause of death!

32. Transfusion haemosiderosis: 2 Treatment: • Iron chelation using subcutaneous desferrioxamine over 8-12 hours on 5-7 nights/week • Oral iron chelator, Deferiprone available but significant side effects • Vitamin C enhances iron excretion

33. O † Errors in transfusion Wrong blood to wrong patient 1:3 ABO incompatible 1:10 fatal Fatal errors in approx 1: 600 000 (UK, USA) Non-fatal 1:12000 B blood  :

34. Reporting of errors in transfusion • Immediate internal reporting • Should be recorded in hospital notes • Contact hospital transfusion department or blood bank • If confirmed error or ‘near miss’, incident form filled • Reported to Hospital Transfusion Committee • External reporting scheme (SHOT)

35. Where do the errors occur? • incorrect blood sampling • incorrect/inadequate labelling of request forms • collecting the wrong blood from the blood bank fridge • errors in the blood bank laboratory • failure/incorrect checking of blood at the bedside

36. Distribution of errors (n=552) from SHOT report 2001-2002

37. Further reading • Essential Haematology • ABC of Transfusion (BMJ books) • SGH handbook of blood transfusion policies and procedures