PDF

PRACTICE POINT

Transfusion and risk of infection in Canada: Update 2012

Posted: Dec 3 2012

The Canadian Paediatric Society gives permission to print single copies of this document from our website. For permission to reprint or reproduce multiple copies, please see our copyright policy.

Principal author(s)

Noni E MacDonald, Sheila F O’Brien, Gilles Delage; Canadian Paediatric Society, Infectious Diseases and Immunization Committee
Paediatr Child Health 17(10): e102-e111

Abstract

Although multiple critical steps are taken to minimize the risk of infection from transfusion of blood or blood products in developed countries, this risk can never be entirely eliminated. In Canada, the risks of noninfectious transfusion reactions, such as transfusion-related acute lung injury and major allergic or anaphylactic reactions, are greater than that of infection. This updated practice point provides an overview of transfusion infection risks in Canada. Infectious agents, systemic conditions, donor and recipient factors, and collection and infusion techniques are considered. Suggestions are offered to improve both system and process, and to help practitioners who are discussing informed consent with patients and parents before administering blood or a blood product.

Key Words: Blood; Blood products; Infections; Transfusion; Transfusion-related acute lung injury

In Canada and other developed countries, many steps are taken to minimize the risk of infection from transfusion of blood or blood products [1], but this risk is never reduced to zero because these biological products are taken from living donors who are never ‘germ free’.[2] However, the risk of noninfectious transfusion reactions, such as transfusion-related acute lung injury (TRALI) and major allergic or anaphylactic reactions, are greater than that of infection.[3] This updated practice point provides an update on transfusion infection risks in Canada. It replaces a 2006 note,[4] and may be helpful to practitioners in discussion with patients and parents toward informed consent before administering blood or blood products.

Steps to prevent infections from blood transfusion

Restrictive transfusion policies and effective blood conservation programs

A crucial step in enhancing safety is to assess carefully whether the patient is likely to benefit from administering blood or a blood product (ie, that potential benefits outweigh the potential risks).[3] This assessment is key in paediatrics because many adverse events in this age group are due to human error, such as overtransfusion or the inappropriate transfusion of neonates.[3] Studies of adults in critical care settings have shown that a restrictive transfusion policy is at least as effective as a liberal transfusion strategy in terms of outcome.[5] While outcomes of restrictive policies in neonatal and paediatric intensive care settings are not as clear-cut, preventative and/or intervention strategies that minimize the need for transfusion are recommended.[6]-[8]

Evidence-based effective policies for donor selection, screening, product collection, testing and infusion

While any infectious agent that has a blood phase has the potential to be transmitted by transfusing blood or blood products, the probability of infection in the recipient depends upon a number of factors, including:[9]

  • the prevalence of the agent in the blood of the donor population;
  • the tolerance of the agent to blood handling, storage and manufacturing processes;
  • the infectivity and pathogenicity of the agent;
  • the recipient’s health and immune status;
  • the effectiveness of donor screening or donor testing for the agent; and
  • the effectiveness of aseptic technique procedures used to collect the blood or blood product from the donor and to infuse the product into the recipient.

In Canada, the infectious disease risks of transfusion are minimized through multiple steps, including: blood collection from volunteer unpaid donors; donor interview and selection protocols; careful aseptic technique procedures for collection and infusion;[10][11] the diversion of the first 40 mL of blood collected into a diversion pouch [12] (ie, not used for transfusion); donor screening by serological and other tests, including bacterial detection in platelets [13] (Table 1); viral inactivation procedures used in manufacturing plasma-derived products (Table 2);[9] and leukocyte reduction techniques that reduce the transmission risk of white cell-associated viruses, such as cytomegalovirus (CMV).[9] Unfortunately, the solvent/detergent and inactivation by heat procedures noted in Table 2 cannot be used for red blood cells or platelets, because neither component can withstand these vigorous processes. Pathogen reduction methods for platelets are in development but not licensed in Canada. The solvent/detergent method of pathogen reduction is licensed for plasma, and was introduced in mid-2012.

TABLE 1
Testing of blood donors in Canada* by Canadian Blood Services (CBS) and Héma-Québec (HQ)

HIV-type 1/2 and subtype O

Antibody/NAT (HIV-1)

HBV

Hbs Ag, Anti-HBc, NAT

HTLV type I/II

Antibody

Syphilis

Treponemal test/PK-TP

HCV

Antibody/NAT

WNV

NAT all units year round at CBS; all units tested during the summer plus testing donors with travel risk of WNV in the winter at HQ

Other

CMV antibody on selected units only: Trypanosoma cruzi (agent for Chagas’ disease) antibody on at-risk donors

Bacteria

Bacterial culture on platelets

*Personal communications: Dr Gilles Delage, HQ and Dr Sheila O’Brien, CBS. CMV Cytomegalovirus; Hbs Ag Hepatitis B surface antigen; HBV Hepatitis B virus; HCV Hepatitis C virus; HTLV Human T-lymphotropic viruses; NAT Nucleic acid testing; WNV West Nile Virus

TABLE 2
Specific manufacturing procedures for virus inactivation or removal

Procedure

Agents inactivated

Agents not inactivated

Inactivation by heat

CMV, HAV, HBV, HCV, HIV, WNV, Parvovirus B19

Inactivation by solvent/detergent

CMV, HBV, HCV, HIV, WNV

HAV, Parvovirus B19, enteroviruses

Ultrafiltration using 35 nm and 15 nm filters

Removes even small viruses but also macromolecules (eg, Factor VIII is decreased)

Leukocyte depletion

Decreases CMV, HTLV type I/II

Non-WBC associated viruses

CMV Cytomegalovirus; HAV Hepatitis A virus; HBV Hepatitis B virus; HCV Hepatitis C virus; HTLV Human T-lymphotropic viruses; WBC White blood cell; WNV West Nile virus

Table 3 identifies specific inactivation steps in the manufacture of different plasma-derived products that decrease viral infection risks. Of note, the majority of Factor VIII and Factor IX used in Canada are recombinant products, not plasma-derived, and hence do not have the infectious risks of a blood product. Of note, the majority of Factor VIII and Factor IX used in Canada are recombinant products, not plasma-derived, and hence do not have the infectious risks of a blood product.

The risk of bacterial contamination of platelets is greater than for red cells because platelets are stored at room temperature (22°C ± 2°C), which supports bacterial pathogen multiplication.[14][15] Initial aliquot diversion and bacterial detection have decreased the risk significantly,[13] as has the automated culture of platelet components, but bacterial contamination of platelet concentrates remains a concern.[16] The risk of bacterial contamination of frozen components, such as fresh frozen plasma and cryoprecipitates, is much lower because the usual microbes (Table 4) are killed by freezing and other storage conditions. While plasma contamination from the water bath used to thaw the product was a problem in the past, the use of microwave techniques or of appropriate plastic covering designed specifically for this purpose have minimized the risk.[17]

TABLE 3
Manufacturing steps to decrease infectious risks of plasma preparations and plasma-derived components

Plasma preparation

Virus risk pre-inactivation process(es)

Pools screened for HIV, HCV, HBV, and HTLV type I/II*

Further virus inactivation steps

Cryoprecipitate (a blood component – not a fractionation product)

++

Yes

None

Factor VII

+

Yes

Al(OH)3 ± nanofiltration ± vapour heat treatment

Factor VIII

+

Yes

Pasteurization process, solvent/detergent ± dry heat treatment

Factor IX

+

Yes

Vapour heating

Antithrombin concentrates

+

Yes

Sephadex A-50, solvent/detergent ± DEAE sepharose FF chromatography ± nanofiltration

Albumin

+

Yes

Isolation of filtrate ± isolation of filtrate IV ± isolation of filtrate d ± pasteurization ± cold ethanol fractionation ± heated treated

IVIG products

+

Yes

Cold ethanol fractionation, solvent/detergent ± caprylate ± column chromatography ± low pH treatment ± nanofiltration ± heat treatment ± octanoic acid fractionation ± depth filtration ± virus filtration

IMIG

+

Yes

Cold ethanol fractionation, solvent/detergent ± heat inactivation ± precipitation filtration ± ultra filtration ± diafiltration

Specific antibody products§

+

Yes

Cold ethanol fractionation or ion exchange column chromatography, solvent/detergent, virus filtration ± heat inactivation

Anion-exchange column chromatography ± Planova 20N Virus Filter ± solvent/detergent ± cold ethanol fractionation ± heat inactivation ± precipitation filtration ± ultra filtration ± diafiltration

*Human T-lymphotropic viruses (HTLV) type I/II are cell-associated viruses, so they are not found in manufactured plasma-derived products and serological screening of source plasma is not required. Similarly, cytomegalovirus (CMV) is primarily cell-associated, and the manufacturing processes remove risk; Hence the risk of transmission of infection from cryoprecipitate is similar to the risk from blood and blood products, and greater than from plasma-derived manufactured products; Very few patients in Canada are treated with plasma-derived Factor VIII or Factor IX. Please note: As there may be more than one product per plasma preparation, the above summarizes the inactivation steps of products in each preparation. §eg, Hepatitis B (HBV) immune globulin, Tetanus immune globulin, Rabies immune globulin, Rh (D) immune globulin, etc. DEAE Diethylaminoethanol; HCV Hepatitis C virus; IMIG Intramuscular immunoglobulin; IVIG Intravenous immunoglobulin. Adapted from manufacturers’ package information

TABLE 4
Bacterial agents associated with acute infection during blood product transfusion

Blood component

Storage

Bacterial agent

Packed red cells

1°C to 6°C for 35 to 42 days

Yersinia enterocolitica Gram-negative, including Pseudomonas species

Whole blood

1°C to 6°C for 35 to 42 days

Gram-negative organisms, including Pseudomonas species

Platelets

20°C to 24°C for 5 days

Skin flora (eg, Staphylococcus epidermidis, Streptococcus species, diphtheroids)

Salmonella species

Escherichia coli

Enterococci species

Clostridium species

Serratia marcescens

Plasma

Frozen, once thawed can be held
at 1°C to 6°C for 24 h

Staphylococcus aureus

Pseudomonas aeruginosa

Adapted from references 14 and 15

Adverse transfusion events in Canada

The Transfusion Transmitted Injuries Surveillance System (TTISS) (<www.phac-aspc.gc.ca/hcai-iamss/tti-it/index-eng.php>) now captures more than 80% of all transfusions in Canada, providing national data on transfusion transmitted injuries (ie, infectious diseases and noninfectious adverse events). The TTISS report for the year 2006 noted nine deaths for a rate of 1:130,122 units transfused; the reported rate of adverse events per product infused increased to 1:2950, up from 1:4091 in 2005.[18] The increase in the rate of reported adverse events was primarily due to increased recognition and reporting of transfusion-associated circulatory overload cases, regardless of their severity. Table 5 summarizes the types of reactions with blood product transfused for the 420 events reported in 2006, showing that the most common events were: transfusion-associated circulatory overload (46.2% of serious adverse events); severe/anaphylactic/anaphylactoid reactions (15.9%); hypotensive reaction (11.9%); and transfusion-related acute lung injury (8.1% + possible 1.9%).[18] Only five cases of bacterial contamination were reported for a rate of 1:292,775 units transfused. The TTISS program continues to verify a high degree of safety in the Canadian blood system and a very small risk of bacterial contamination, although both allergic/anaphylactic reactions and transfusion overload remain concerns.

Estimated per unit risks of bacterial, parasitic and viral contamination of blood and blood products

The estimated per unit risks of contamination in blood, blood products and manufactured plasma-derived products in Canada for a number of viral, bacterial, parasitic, prion and tick-borne agents are presented in Table 6 and Table 7. As the data in these Tables show, the risks of transmitting infectious agents by blood, and especially by manufactured plasma-derived products, are extremely low in Canada. For context, a 1:3,000,000 risk is similar to that of being hit by lightning.

The importance of documenting transfusions

No national electronic record of transfusions yet exists to facilitate potential future trace-back programs for a new transmissible agent. Therefore, it is important to ensure that:

  • transfused patients are aware they have received blood, blood products or manufactured plasma-derived products;
  • the discharge or outpatient note adequately documents these transfusions, recording label code numbers for specific products; and
  • hospital blood banks have such records.

Resources

Expanded discussion on the infectious diseases risks of transfusing blood and blood products can be found at the following websites:


TABLE 5
Incidence in Canada of adverse transfusion events according to blood component implicated, 2006

Red blood cells

Apheresis platelets

Whole blood platelets

Plasma

Cryoprecipitate

Multiple components

Rate per units transfused

Total

Severe allergic/anaphylactic reaction

22 (7.5)

15 (57.7)

13 (32.5)

15 (27.8)

2 (66.7)

1:18,017

67 (15.9)

Acute hemolytic transfusion reaction

20 (6.8)

2 (7.7)

2 (5)

1:50,917

24 (5.7)

Delayed hemolytic transfusion reaction

14 (4.8)

2 (5)

1:78,073

16 (3.8)

Transfusion-associated circulatory overload

154 (52.4)

5 (19.2)

7 (17.5)

2.7 (50)

1 (33.3)

1:6131

194 (46.2)

Transfusion-related acute lung injury

18 (6.1)

6 (15)

8 (14.8)

1 (33.3)

1 (33.3)

1:41,825

34 (8.1)

Possible transfusion-related acute lung injury

6 (2)

1 (2.5)

1 (33.3)

1:41,825

8 (1.9)

Transfusion-associated dyspnea

11 (3.7)

3 (11.5)

2 (5)

3 (5.6)

1:61,637

19 (4.5)

Bacterial contamination

3 (1)

2 (5)

1:292,775

5 (1.2)

Hypotensive transfusion reaction

44 (15)

1 (3.8)

4 (10)

1 (1.9)

1:23,900

50 (11.9)

Post-transfusion purpura

1 (2.5)

1:1,171,101

1 (0.2)

Others*

2 (0.7)

2 (0.5)

Total

294 (100)

26 (100)

40 (100)

54 (100)

3 (100)

3 (100)

1:2,950

420 (100)

Data presented as n (%) unless otherwise indicated. *eg, Hypertensive transfusion reaction (1) and post-transfusion thrombocytopenia (1). Adapted from reference 18

TABLE 6 Estimated risk of infectious agents in blood or blood products

Agents

Transfusion-transmitted

Pathogenic

Canadian estimated risk of contamination*

Agents for which all blood donors are tested

HIV

Yes

Yes

1 in 8 to 12 million

HCV

Yes

Yes

1 in 5 to 7 million

HBV

Yes

Yes

1 in 1.1 to 1.7 million

HTLV types I and II

Yes

Yes

1 in 1 to 1.3 million

WNV

Yes

Yes

No reported cases in Canada since screening was introduced in 2003

Bacteria

Yes

Yes

Apheresis platelets: 1 in 105,000
Platelet pools: 1 in 47,000

Syphilis

Yes

Yes

<1 in 100 million

Other agents tested on occasion

CMV

Yes

Yes

Risks vary with donor/recipient but rare§

Chagas (Trypanosoma cruzi)
Tested in high-risk donors

Yes

Yes

No new cases in the last five years; selective testing of at-risk donors implemented in 2009 (HQ) and 2010 (CBS)

Other agents not tested

Parvovirus B19

Yes

Yes

1 in 5000 to 1 in 20,000

GBV-C

Yes

Unknown

1 to 2 in 100; not known to be pathogenic

TTV

Yes

Unknown

1 in 100; rarely pathogenic

SEN-V

Yes

Unknown

1 in 100; not known to be pathogenic

HHV-8

Unknown

Yes

Unknown

Malaria

Yes

Yes

No new cases in over 10 years

Babesiosis (Babesia microti)

Yes

Yes

1 case reported in 2001

Prion

vCJD

Unknown

Yes

Risk unknown, extremely rare (<1 in 10 million)

*Risk of contamination refers to the potential residual risk of infection from the listed organisms in blood or blood products after proper screening and manufacturing processes have occurred; Based on residual risk calculations published by Canadian Blood Services (CBS) and Héma-Québec (HQ); West Nile virus (WNV) not tested in Quebec in winter except in donors with travel risk; §Cytomegalovirus (CMV) infection risk is decreased by leukoreduction procedures (see text). HBV Hepatitis B virus; HCV Hepatitis C virus; GBV-C formerly named Hepatitis G virus; HHV-8 Human herpes virus 8; HTLV Human T-lymphotropic viruses; SEN-V SEN virus; TTV Transfusion transmitted virus; vCJD Variant Creutzfeldt-Jakob disease. Adapted from reference 19

TABLE 7
Estimated risks of infectious agents in manufactured plasma-derived products

Agents

Historical evidence of transmission from plasma product

Pathogenic

Canadian estimated risk of contamination*

Viruses for which all blood donors are tested

HIV

Yes

Yes

<1 in 10 million

HCV

Yes

Yes

<1 in 10 million

HBV

Yes

Yes

<1 in 10 million

HTLV
types I
and II

Yes

Yes

Only a theoretical risk

Other viruses

CMV

No

Yes

Only a theoretical risk

Parvovirus B19

Yes

Yes

Only a theoretical risk if heat inactivation; otherwise 1 in 100,000 to 1 in 1 million

WNV

No

Yes

Only a theoretical risk

Parasites

Malaria

No

Yes

Only a theoretical risk

Chagas

No

Yes

Only a theoretical risk

Babesiosis

No

Yes

Only a theoretical risk

Prion

vCJD

Unknown

Yes

Theoretical risk of <1 in 100 million

*Risk of contamination refers to the potential residual risk of infection from the listed organisms in plasma-derived products after proper screening and correct manufacturing processes have taken place. CMV Cytomegalovirus; HBV Hepatitis B virus; HCV Hepatitis C virus; HTLV Human T-lymphotropic viruses; vCJD Variant Creutzfeldt-Jakob disease; WNV West Nile virus. Adapted from reference 20

Acknowledgements

Thanks to Cindy Hyson, RN, BScN, CON, MN, A/Associate Director Surveillance and Epidemiology, Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, for information on adverse events related to transfusion. This practice point has been reviewed by the Acute Care, and Fetus and Newborn Committees of the Canadian Paediatric Society.

CPS INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE

Members: Robert Bortolussi MD (Past Chair); Natalie A Bridger MD; Jane C Finlay MD; Susanna Martin MD (Board Representative);  Jane C McDonald MD; Heather Onyett MD; Joan Louise Robinson MD (Chair)
Liaisons: Upton Dilworth Allen MD, Canadian Pediatric AIDS Research Group; Michael Brady MD, American Academy of Pediatrics; Janet Dollin MD, The College of Family Physicians of Canada; Charles PS Hui MD, Committee to Advise on Tropical Medicine and Travel, Health Canada; Nicole Le Saux MD, IMPACT (Immunization Monitoring Program, ACTive); Dorothy Moore MD, NACI (National Advisory Committee on Immunization); John S Spika MD, Public Health Agency of Canada
Consultant: Noni E MacDonald MD
Principal authors: Noni E MacDonald MD; Sheila F O’Brien MD; Gilles Delage MD

 

 

 

References

  1. Lindholm PF, Annen K, Ramsey G. Approaches to minimize infection risk in blood banking and transfusion practice. Infect Disord Drug Targets 2011;11(1):45-56.
  2. Murphy WG. Disease transmission by blood products: Past, present and future. Pathophysiol Haemost Thromb 2002;32(Suppl 1):1-4.
  3. Lavoie J. Blood transfusion risks and alternative strategies in pediatric patients. Paediatr Anaesth 2011;21:14-24.
  4. Canadian Paediatric Society, Committee on Infectious Diseases and Immunization. Transfusion and risk of infection in Canada: Update 2006 (Principal authors: MacDonald NE, Scott JW, McCombie N, Robillard P, Giulivi T). Paediatr Child Health 2006;11(3):158-62.
  5. Tinmouth AT, McIntyre LA, Fowler RA. Blood conservation strategies reduce the need for red cell transfusion in critically ill patients. CMAJ 2008;178(1):49-57.
  6. Canadian Paediatric Society, Fetus and Newborn Committee. Red blood cell transfusions in newborn infants. Paediatr Child Health 2002;7(8):553-8.
  7. Crowley M, Kirpalani H. A rational approach to red blood cell transfusion in the neonatal ICU. Curr Opin Pediatr 2010;22(2):151-7.
  8. Lacroix J, Hébert PC, Hutchison JS, et al. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007;356(16):1609-19.
  9. American Academy of Pediatrics, Report of the Committee on Infectious Diseases, 28th edn. Blood safety: Reducing the risk of transfusion-transmitted infections. Elk Grove Village: AAP,
  10. 2009:106-18.
  11. McDonald C, McGuane S, Thomas J, et al. A novel rapid and effective donor arm disinfection method. Transfusion 2010;50(1):53-8.
  12. Ramirez-Arcos S, Goldman M. Skin disinfection methods: Prospective evaluation and postimplementation results. Transfusion 2010;50(1):59-64.
  13. McDonald CP, Roy A, Mahajan P, Smith R, Charlett A, Barbara JA. Relative values of the interventions of diversion and improved donor-arm disinfection to reduce the bacterial risk from blood transfusion. Vox Sang 2004;86(3):178-82.
  14. Robillard P, Delage G, Itaj NK, Goldman M. Use of hemovigilance data to evaluate the effectiveness of diversion and bacterial detection. Transfusion 2011;51(7):1405-11.
  15. Blajchman MA. Incidence and significance of the bacterial contamination of blood components. Dev Biol 2002;108:59-67.
  16. Blajchman MA, Goldman M, Baeza F. Improving the bacteriological safety of platelet transfusions. Transfus Med Rev 2004;18(1):11-24.
  17. Ramirez-Arcos S, Jenkins C, Dion J, Bernier F, Delage G, Goldman M. Canadian experience with detection of bacterial contamination in apheresis platelets. Transfusion 2007;47(3):421-9.
  18. Churchill WH, Schmidt B, Lindsey J, Greenberg M, Boudrow S, Brugnara C. Thawing fresh frozen plasma in a microwave oven. A comparison with thawing in a 37 degrees C waterbath. Am J Clin Pathol 1992;97(2):227-32.
  19. Public Health Agency of Canada. Transfusion Transmitted Injuries Surveillance System, Program Report 2006: http://publications.gc.ca/site/eng/359963/publication.html (Accessed June 29, 2012).
  20. O’Brien SF, Yi QGL, Fan W, et al. Current incidence and residual risk of HIV, HBV and HCV at Canadian Blood Services. Vox Sang 2012;101:83-6.
  21. Janssen MP, Over J, van der Poel CL, Cuijpers HT, van Hout BA. A probalistic model for analysing viral risk of plasma-derived medicinal products. Transfusion 2008;48(1):153-62.

Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.