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

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

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

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)

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

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

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)

Early complications of BT…..

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

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)

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

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

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

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

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

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

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

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

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

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

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

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)

Late complications of BT…..

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

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

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

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

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

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% !

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

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!

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

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: 600 000 (UK, USA) Non-fatal 1:12000 O † B blood  :

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)

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

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

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