Serious hazards of transfusion

Dr Kenneth S Charles
MB.BS (UWI), FRCP (UK), FRCPath(UK)
Senior Lecturer in Haematology

Introduction

Case study
Definition of adverse effect
Classification
Pathophysiology
Management
Prevention

Red cell concentrate

Cryoprecipitate

Platelet concentrate

Fresh frozen
plasma

When do patients require

transfusion?
Red cells Hb < 7.0 or acute blood loss
- Hb < 9.0 pre-op
Platelets - Active bleeding + platelets < 50
- Prophylactic/ platelets < 10
Fresh frozen plasma prolonged PT and/or
APTT + active
bleeding
or planned procedure

Cryoprecipitate no response to FFP

Case study

26 year old man

Relapsed Hodgkins Lymphoma
Chemotherapy
Sepsis/Disseminated Intravascular
Coagulation
2 U RBC, 6 U platelets, 6 U FFP
6 hours later, dyspnoea, hypoxia

Adverse reaction
Any untoward event occurring within a few
hours, weeks or months of and as a direct
result of administration of a blood
component

Classification

Immediate/Delayed
Infectious/Non-infectious
Immune/Non-immune
Clinical presentation

Adverse reactions classified by

clinical presentation
Febrile
Haemolysis
Acute haemolytic transfusion reaction
Delayed haemolytic transfusion reaction
Sepsis
Bacterial contamination of component
Antileucocyte antibodies

Adverse reactions classified by

clinical presentation
Dyspnoeic
Transfusion related acute lung injury
Congestive cardiac failure
Anaphylaxis caused by IgA deficiency

Adverse reactions classified by

clinical presentation
Urticarial
Allergy to plasma proteins

Adverse reactions classified by

clinical presentation
Other
Iron overload
Transfusion Transmissible infections
HIV
HBV
HCV
Syphilis
HTLV1

Graft versus host disease

Posttransfusion purpura

FEBRILE

Acute Haemolytic Febrile Transfusion

Reaction (AHFTR)

As little as 20 mls incompatible RBCs

1 in 7 000 transfusions
Mortality 10%
Anti-A, anti-B, anti-Kell, anti-Kidd, antiDuffy, anti-Lewis

AHFTR contd
Abs in recipients serum activate
complement to initiate intravascular lysis
Catecholamines and kinins released
DIC in 30-50%
Fever, chills, nausea, pain at IV site,
chest and back pains (intravascular
occlusion by agglutinated red
cells),hypotension, dark urine
Nephrotoxic effects of anti-red cell stroma

AHFTR
Stop transfusion
IV hydration - Normal Saline to systolic BP
> 100 mmHg, UO > 100 ml/hr
Diuresis - +/- IV Frusemide or mannitol
Appropriate samples to blood bench

Conditions mimicking AFHTR

Improperly warmed blood
Blood piggy-backed

(D)Some technical aspects of the

administration of blood and blood
components: blood warming
Rarely indicated
Only with specifically designed blood warmers
with visible thermometer and audible warning
NOT hot water bath, microwave, radiator.
Massive transfusions in adults, exchange
transfusions in neonates, clinically
significant cold agglutinins
BCSH, 1998

Delayed Haemolytic Transfusion

Reaction (DHTR)

Clinically occult
Occur 2-21 days after transfusion
1 in 500 transfusions
Death rare
Anti- Kell, Duffy, Kidd, Rhesus in patients
sensitized by transfusion, pregnancy
Low grade fever, jaundice, no rise in Hb, positive
DCT, spherocytes
Acute Renal Failure rare. Most self-limiting

Direct Coombs Test

Bacterial contamination
Especially platelet concentrate
Sources donor bacteraemia, donor arm,
contamination during processing
Fever, chills, shock, ARF, DIC
G- and G+ bacteria
Mortality 26%

Fate of unused red cells

1

Domestic refrigerator
Returned to Blood
Bench

25

(B) Collection of blood or blood components from

the hospital blood bank or blood transfusion issue
refrigerator and its delivery to the ward or operating
theatre
The transfusion of blood and blood components should
begin as soon as possible after delivery to the ward or
operating theatre. If not possible, return to blood
transfusion refrigerator. If > 30 mins return to hospital
blood bank for disposal (risk of bacterial infection)
If the ward or operating room does not have a
refrigerator that is approved for storing blood, the
blood should not be released from the blood bank
until immediately before transfusion
BCSH, 1999

Wastage: Blood returned from

wards

DYSPNOEIC

Non-haemolytic febrile
transfusion reactions (NHFTR)
Most common type of transfusion reaction
Granulocyte and HLA-specific
antileucocyte Abs develop in recipient by
pregnancy, previous transfusion
Lysis of donor WBCs and release of
cytokines
1 in 200-500 transfusions

Leucocyte antigens
HLA Class I and II
Neutrophil specific antigens NA-1, NA-2,
NB

HLA Antigens

Febrile Non-haemolytic Transfusion

Reaction (FNHTR)
Fever, otherwise well
Stop transfusion
Exclude haemolysis, bacterial
contamination
Acetominophen 650 mg
Resume transfusion
If recurs, leucocyte filter

Non-cardiogenic pulmonary oedema

(TRALI)
1 in 5 000 transfusions
Donor antileucocyte Abs (previous
transfusions, pregnancy) passively
transfused to recipient
Any blood component
Ag/Ab complexes trapped in pulmonary
vasculature
Dyspnoea, hypoxia, chills, fever

TRALI

TRALI

CXR bilateral lower-lobe infiltrates

Donor antileucocyte Abs demonstrated
Rx D/C transfusion, O2, IV methylpred
Most resolve within 12-24 hrs
If not, IPPV until resolved
Donor excluded from future donation

TRALI

Congestive Cardiac Failure

(CCF)
Safe rate for 1U RBCs 2-3 hrs

Anaphylaxis
Hereditary IgA deficiency 1 in 700 in USA
Complement-fixing IgG anti-IgA through
pregnancy or transfusion
Dyspnoea, chest pain, nausea, abdo
cramps, hypotension
IV epinephrine, methylprednisolone
Washed red cells, IgA deficient donors

URTICARIAL

Urticaria

Allergic reaction to plasma proteins

Usually FFP but any component
Skin rash, pruritis
Antihistamine and continue transfusion

OTHER

Infective risks of blood transfusion

Risk factor

Estimated frequency

Hepatitis A

1 in 1 000 000

Hepatitis B

1/30 000-1/250 000

Hepatitis C

1/30 000 1/150 000

HIV

1/200 000 1/2 000 000

HTLV1

1/250 000-1/2000 000

Centralized screening for TTIs

HIV, HBsAg

Syphilis,
HCV
HTLV1, Chagas

NBTS - Day after accident

Risk of HIV seropositivity per 100,000 donors

350
300
250
200
150
100
50
0
Voluntary

WHO,2002

Replacement

Paid

Serological markers NBTS

Year

Sample HIV
(no)

HBsAg

HTLV1

HCV

TP

Chagas

2000

14 882 0.19

0.83

0.94

0.37

0.55

ND

2004

13742

0.58

1.46

0.77

2.16

0.05

0.21

ANNUAL DONATIONS BY TYPE

25000
106

NUMBER

95

165

20000

15000

95

78

66
18055

19589

1551

1322

19209

19867

2707

2908

AUTOLOGOUS
REPLACEMENT
VOLUNTARY

10000
11275

11817

1866

1808

5000

0
2004

2005

2006

2007

YEAR

2008

2009

Seropositivity in blood donors

1.6

1.46

1.4

Percentage

1.2
1
T&T
UK

0.77

0.8
0.58

0.6
0.4
0.21
0.2

0.15

0.1

0.004

0.005

0
HIV

HBsAg

HCV

HTLV1

TTIs 2009

HIV

HBV

HCV

SYPH

HTLV

CHAGAS

ALL

REPLACEMENT

43(0.21)

68(0.33)

41(0.20)

275(1.3)

195(0.97)

11(0.05)

633(3.2)

VOLUNTARY

3(0.14)

1(0.05)

5(0.23)

5(0.23)

14(0.64)

0(0)

28(1.3)

Voluntary donor %

HIV in donors
%

1.2
1
0.8

JAM
0.6

TRT

0.4

CUR

0.2

0
2005

HBsAg in donors %
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0

2007

HCV in donors
%
BAR
JAM
TRT
CUR

2005 2006 2007 2008 2009

2006

2008

2009

Window period/days
Virus

ELISA

NAT (PCR)

HCV

88

23

HBV

56

31

HIV

22

12

VIP Blood Screening LATAM meeting, Pleasanton, CA, Oct 2007

Blood donation rate per 10,000 inhabitants and

proportion of units reactive/positive for
infectious markers in 2005
Country

Donation rate

% TTI markers

Jamaica

83.6

5.0

Trinidad and Tobago

104.4

4.69

Curacao

368.6

0.03

From : PAHO, CD 48/11 Annex

A

Wastage: Seropositive units for

discard

Transfusion Associated Graft

Versus Host Disease
Engraftment of donor lymphocytes in the
blood of patients with impaired cellular
immunity
Congenital SCID, organ transplant
recipients, Intrauterine Transfusions,
Hodgkins Disease, purine analogues
7-10 days. Skin, gut, liver, pancytopaenia
90% mortality. No effective Rx
15 Gy irradiation of blood components

Post Transfusion Purpura (PTP)

Middle aged, multiparous
PlA1 negative
Severe thrombocytopenia 7-10 days after
transfusion
AlloAb to PlA1 destroys transfused and
recipient platelets
Rx - IVIg

Iron overload

IU red cells contains 250 mg iron

No iron excretion mechanism
Skin, joints, liver, heart, endocrine glands
Iron chelation intravenous, s/c
- oral
thalassaemia major patients

Case study

26 year old man

Relapsed Hodgkins Lymphoma
Salvage chemotherapy
Sepsis/Disseminated Intravascular
Coagulation
2 U RBC, 6 U platelets, 6 U FFP
6 hours later, dyspnoea, hypoxia

Case study

TRALI
IPPV
Later succumbed to malignancy
Female donor anti NA-1 Abs

WHO integrated strategies to

promote global blood safety
Establishment of nationally co-ordinated
BTSs
Voluntary non-remunerated blood
donors
Testing of all donated blood, screening
for TTIs, blood grouping, compatibility
testing
Reduction in unnecessary transfusions
WHO (2006a) Aide memoire on Blood Safety for National Blood Safety for
National Blood Programmes. Information sheet.

Summary

Case study
Definition of adverse effect
Classification
Pathophysiology
Management
Prevention

When do patients require

transfusion?
Red cells Hb < 7.0 or acute blood loss
- Hb < 9.0 pre-op
Platelets - Active bleeding + platelets < 50
- Prophylactic/ platelets < 10
Fresh frozen plasma prolonged PT and/or
APTT + active
bleeding
or planned procedure

Cryoprecipitate no response to FFP