Haemovigilance:Acute transfusion

reactions

Paula Bolton-Maggs

Medical Director

Serious Hazards of Transfusion

SHOT Cumulative data: 18 years n=14822

TANEC=transfusion-associated necrotising enterocolitisABOi=ABO-incompatible transfusion

Deaths related to transfusion reported in 2015

Total n=26

Adverse reactions associated with plasma

• Infection – very rare• Transfusion-associated circulatory

overload – one to watch for• Transfusion-related acute lung injury - rare• Allergic/febrile – the most common• Haemolysis

Transfusion-transmitted infections in UK 1996–2015 (SHOT)

• Only 6 infection transmissions from FFP– HIV in 1996– HBV in 2011– HEV 4 cases 2011-2014

• One HEV transmission from cryoprecipitate• No bacterial transmissions• Total infection transmissions 87 from 76

incidents to 2016

Bacterial transmissions reported to SHOT 1996-2014

0

1

2

3

4

5

6

1996

/97

1997

/98

1998

/99

1999

/00

2000/

01

2001

/02*

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

Num

ber

of r

epor

ts

Year of report

red cells platelets

Bacterial screening2010

Diversion pouch2003

Changes to arm

cleansing

Changes to arm

cleansing

Changing pattern of pulmonary complications 2008-2015

Transfusion-related deaths 2010 to 2015 n=93

Errors now account for the majority of reports

Critical points in the transfusion process

Critical points:Critical points:Positive patient Positive patient identification essentialidentification essential

Clinical errors

Laboratory errors

Near miss – 1466 detected

Wrong transfusions 2014 and 2015

Multiple errors are common – incorrect blood components transfused 2013-2015

Serious Adverse Reactions –WHEN?

• Immediate and life-threatening : ABO-incompatibility; anaphylaxis

• Hours: pulmonary complications, bacterial infections, transfusion reactions

• Days: haemolytic reactions• Late (months or years): viral infections;

iron overload

Acute transfusion reactions

• Allergic or anaphylactic reactions are unpredictable and usually occur early

• This is why all patients having blood products must be monitored

• Adrenaline (IM) is the treatment of choice and should be available in all areas where transfusions take place

Pathogen-inactivated FFP

• Recommended for those born after 1 January 1996 (BSE no longer in food chain)

• Methylene blue-treated single units• Solvent detergent-treated pooled

(recommended for plasma exchange in thrombotic thrombocytopenic purpura)

What about MB-FFP?

• Withdrawn in France (2012) because of concern about ATR

• For UK, updated statistical analysis for data 2007-2013 no difference between MB-FFP and other components

ATR Platelets – allergic type

Reduction in reactions with platelets suspended in PAS

ATR Platelets - febrile

11.9

1.5 1.2 02.2

10

2

4

6

8

10

12

Incidence per 100,000 units

issued

Allergicreactions

Febrile reactions Other reactions

Standard FFP SDFFP

SD FFP is associated with fewer allergic reactions

2010 to 2012: 863,847 units of standard FFP, and 198,370 units of SD FFP were issued by UK Blood Services. 132 acute reactions associated with transfusion of standard FFP and 5 with SD FFP

Allergic reaction to FFP

• Transfusion reaction during plasma exchange with 7 units of FFP with pyrexia, hypotension, chest pain and rash on the arms, trunk and neck with mild swelling around the lips and eyes. Reaction and rash resolved following administration of hydrocortisone and piriton. No harm caused.

• Chronic inflammatory polyneuropathy – decided to use albumin in future

Immediate management• Recognise patient experiencing adverse reaction• Stop transfusion, keep line open, retain

component• Airway, Breathing, Circulation and Bag, Band,

Blood• How severe is this reaction?

– Minor- e.g. itch. Should you restart the transfusion?– More serious. Do not restart the transfusion. Establish

most likely cause

• Monitor urine output and observe for haemoglobinuria

How common are ATRs in the UK?

A. 1 in 30 units?

B. 1 in 100?

C. 1 in 1000?

D. 1 in 10,000?

• SHOT collects reports on moderate and severe ATRs

• Incidence varies according to component type

• Are all cases reported?

SHOT ATR reports, 2013

Fever

Fever, chills and rigors during or soon after transfusion: possible causes

• Febrile non-haemolytic transfusion reaction

• Acute haemolytic reaction

• Bacterial contamination

• Underlying condition

Case History• A patient with myelodysplasia has a 2 unit red cell transfusion as a day case

• History of complex red cell antibodies

• With the second unit, she complains of feeling unwell, with mild nausea and chills

• Her temperature rises from 37.8 to 39oC, BP and pulse both increase

• The transfusion is stopped and symptoms and signs improve within 30 minutes

What is this most likely to be?

A. A haemolytic transfusion reaction due to complex red cell antibodies

B. A haemolytic reaction due to incorrect component transfused

C. A febrile transfusion reaction

D. Bacterial contamination of the unit

This is most likely to be a non-haemolytic febrile reaction

BUTConsider other causes

Case history• Patient with haematuria being transfused with platelets

• 20 minutes into transfusion:–2.2oC rise in temperature, vomiting, tachycardia, chest pain

–Hypoxia

• Rigors prevented BP measurement

• Urine positive for haemoglobin but patient has haematuria

Which investigations would you do?

A. Blood cultures of the patient, send the platelet unit for culture

B. Repeat group and antibody screen the patient

C. All the above

D. None of the above

Culturing the platelet unit:

A. Perform culture in hospital lab, refer to blood service if positive result

B. Contact nearest blood service to discuss next steps

C. Perform culture locally but at the same time inform blood service

Learning point

• With a severe febrile reaction such as this, the most important step is to contact the blood service

• Any associated components can be withdrawn from issue

• Unit sampling and culture requires expertise

Learning points

• Febrile reactions are more commonly seen with red cell transfusions

Learning points

• Febrile reactions are more commonly seen with red cell transfusions

• The incidence has been reduced since universal leucodepletion

• Less severe reactions can be treated with paracetamol or anti-inflammatory medication

• In severe reactions the most important differential diagnosis is transfusion-transmitted infection although very uncommon

Respiratory symptoms

TACO in relation to PEX• 16 year old child with atypical HUS having

plasma exchange with SD FFP developed acute hypoxia, rigors, chest crackles, fluid in the lungs following treatment

• Occurred on 3 separate days requiring CPAP• 2500mL positive fluid balance• Background of acute lymphoblastic leukaemia• No more exchange

Case history

• 67 year old female with myelodysplasia

• Transfused 3 units of red cells as a day case

• Felt ill on her journey home and returned immediately to A and E

• Had respiratory arrest

Most likely cause?

A. Transfusion Related Acute Lung Injury (TRALI)

B. Allergic reaction

C. Transfusion Associated Circulatory Overload (TACO)

D. Unrelated to transfusion

Outcome• Chest X ray appearances consistent with left ventricular failure

• Probable TACO

• Patient made a full recovery with treatment

TACO

• Acute respiratory distress, tachycardia, hypertension, acute or worsening pulmonary oedema, evidence of positive fluid balance

– At least 4 of the above features

– Occurring within 6 hours of transfusion

• Tends to be seen in over 70s

• Almost certainly under-reported• Recent series of 8/247 transfusions in this age group (3%) Bartholomew and Watson, 2014

Learning points

• TACO is much more common than TRALI and it can be difficult to confirm the cause of acute respiratory symptoms

• Elderly patients are particularly at risk of TACO

• Even small transfusions may be enough• All patients need careful monitoring and

appropriate investigation

Reduction in TRALI with move away from female donors for FFP

139 cases29 deaths

No cases from FFP since 2009

1 case in 2014 associated with

transfusion of cryo: 3 female donors

Respiratory symptoms 2

Case history

• Patient with PPH received a unit of FFP

• Previously, 3 units red cells and 1 FFP transfused without problems

• 8 minutes into transfusion, she began to cough and had swollen eyes, lips and throat

• Bronchospasm

• Oxygen saturation dropped

• Blood pressure unrecordable and briefly lost consciousness

• Responded well to treatment

What was the reaction likely to be?

A. TRALI

B. TACO

C. Moderate allergic reaction

D. Anaphylaxis

What was the reaction likely to be?

A. TRALI

B. TACO

C. Moderate allergic reaction

D. Anaphylaxis

What is the immediate management?

A. Call the haematologist

B. Hydrocortisone and antihistamine

C. Dopamine

D. Adrenaline

What is the immediate management?

A. Call the haematologist

B. Hydrocortisone and antihistamine

C. Dopamine

D. Adrenaline

Learning point

• Anaphylaxis is characterised by

– rash and/or mucous membrane involvement

– followed rapidly by respiratory and/or circulatory distress

• A medical emergency

• Treatment is adrenaline: IM unless you are an anaesthetist or intensivist

Minor reactions excluded

Acute transfusion reactions and anaphylaxis in relation to total SHOT reports

Although anaphylaxis is rare, patients should only be transfused when and where there is the ability to recognise and manage a reaction

Management of patients who have reacted before

• A female patient with bone marrow failure and epistaxis has regular (appropriate) platelet transfusions

• With last two transfusions, she complained of itch

• Now has urticaria

How can you avoid future reactions?

A. Give HLA-matched platelets

B. Give hydrocortisone premed

C. Give washed platelets

D. Give antihistamine premed

How can you avoid future reactions?

A. Give HLA-matched platelets

B. Give hydrocortisone premed

C. Give washed platelets

D. Give antihistamine premedAnd ensure appropriate transfusion

Learning points• 25% of women, and at least 10% of multitransfused male patients have HLA antibodies

• No evidence that reactions are reduced with HLA-matched platelets

• Washed platelets do reduce reactions

• IV hydrocortisone takes 8 hours to act

• Little evidence for antihistamine but if washed platelets do not work, worth trying

• Appropriate use underpins everything we do

What have we learnt from review of ATRs?

• Adrenaline is the treatment of anaphylaxis and should be available wherever transfusions are given

• Widespread use of steroids and antihistamines without literature evidence of benefit

• Febrile reactions are uncommon with FFP• Severe allergic or anaphylactic reactions

more likely with FFP than other components

Haemolysis

Group AB FFP has no ABO antibodies

Group O FFP is only suitable for Group O patients

FFP use and abuse

• Plasma exchange in TTP is lifesaving• Widely used with little evidence

– Systematic reviews* show no benefit either for prophylaxis or treatment of bleeding

– FFP ‘transfusion practice is habitual, often rooted in tradition and associated with strong beliefs’ (Shih and Arnold, 2015)

*Stanworth et al. 2006; Yang et al. 2012

Acknowledgements

• Hazel Tinegate, Helen New, Janet Birchall• The SHOT team• The vigilant reporters and hospital staff

who share their incidents with us

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SHOT Symposium 2017

Rothamsted Centre for Research & Enterprise,

Harpenden, Hertfordshire, AL5 2JQ

Wednesday 12th July 2017

Keynote speaker: Dr Phil Hammond

Additional InformationFollowing documents available on website

Teaching slide set

SHOT cases

SHOT reporting definitions

Clinical lessons

Laboratory lessons

SHOT Bites

Also available:

Previous SHOT reportsSHOT summaries

www.shotuk.org