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 ( )
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 Any blood loss >2L (SGH)
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 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 mg 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. 1:3 ABO incompatible 1:10 fatal Errors in transfusion
Wrong blood to wrong patient
1:3 ABO incompatible
1:10 fatal
Fatal errors in approx 1: (UK, USA)
Non-fatal 1:12000 O †
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

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