Transfusion Transmitted Injuries

About Risks of Blood Transfusion

Although blood transfusion saves lives and reduces morbidities in many clinical diseases and conditions, it is associated with certain risks. A transfusion-related adverse event, also called transfusion reaction, is any unfavourable event occurring in a patient during or after blood transfusionFootnote 1. About 0.5% to 3% of all transfusions result in some adverse events, but the majority of them are minor reactions with no significant consequences. In general, transfusion-related adverse events are categorized as infectious and noninfectious. However, there are other classifications in the literature based on time of occurrence (i.e. acute versus delayed) or physiological mechanism (i.e. immune mediated versus nonimmune mediated) (Table 1)Footnote 2,Footnote 3. A significant proportion of adverse events may occur as a result of errors in preparation, ordering or administration of blood and blood products.

Infectious Risks of Transfusion

Currently, the risk of transmission of infectious diseases through transfusion in Canada is minimal, because effective preventive strategies, including new laboratory tests, have been implemented. Nevertheless, many infectious agents, including viruses, bacteria, and parasites, can be transmitted through blood transfusion. Well-recognized viruses include hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis G virus/GB-C virus (HGV/GBV-C), human immunodeficiency virus types 1 and 2 (HIV-1/2), human T-cell lymphotropic virus types I and II (HTLV-I/II), cytomegalovirus (CMV), Epstein-Barr virus (EBV), TT virus (TTV), human herpesvirus type 6 (HHV-6), SEN virus (SEN-V), and human parvovirus (HPV-B19). Bacteria such as Treponema pallidum (the agent of syphilis), Yersinia enterocolitica, and Staphylococcus and Streptococcus species (common agents of bacterial contamination), and parasites such as Plasmodium species (the agent of malaria), Trypanosoma cruzi (agent of Chagas' disease), and Babesia microti (agent of babesiosis) have also been reported to be transmitted through blood transfusion. In addition, emerging blood-borne pathogens such as hepatitis E virus (HEV), human herpesvirus type 8 (HHV-8), Borrelia burgdorferi (agent of Lyme disease), and the unknown agent of Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) may pose a threat to the safety of blood.

Infectious agents may be classified into five categories based on transmissibility through transfusion, pathogenicity of the agent, availability of donor serologic test, and effectiveness of pathogen inactivation (Table 2)Footnote 4-8. The risk of transmission for the first group of agents is minimal because of donor screening and testing, and is normally associated with donations collected during the window period. For example, the risk of transmission of HIV and HCV in Canada through blood transfusion was estimated to be 1 in 752,000 and 1 in 225,000 donations respectivelyFootnote 9. Infections caused by agents in the second and third group usually present clinical diseases in high-risk recipients, such as immunocompromised individuals; however, the transfusion transmission risk is also very small because of preventive strategies such as universal leukodepletion and solvent-detergent treatment. Transfusion Transmitted bacterial reaction resulting from bacterial contamination of blood components is the most common infectious adverse event. Approximately 1 in 2,000-3,300 units of platelets and 1 in 38,500 units of red cells are contaminated with bacteria; however, not every contaminated component causes reactions. The incidence of Transfusion Transmitted bacterial reaction is estimated to range from 1 in 500,000 units of red cells to 1 in 50,000 units of plateletsFootnote 10.

Infectious agents in the fourth and fifth group may pose a potential risk following transfusion. Although agents in the fourth group have been proved to be transfusion transmissible, the pathogenicity of these agents is currently not established. Similarly, even though agents in the last group usually cause disease, their transfusion transmissibility has not been established.

Noninfectious Risks of Transfusion

Although Transfusion Transmitted infections have received the greatest attention, noninfectious adverse events remain the most common complications associated with transfusion. The majority of these noninfectious adverse events are immune mediated. Acute immune mediated reactions include acute hemolytic transfusion reaction (AHTR), transfusion-related acute lung injury (TRALI), febrile nonhemolytic transfusion reaction (FNHTR), urticarial reaction and anaphylaxis. Delayed immune mediated reactions consist of delayed hemolytic transfusion reaction (DHTR), transfusion associated graft-versus-host disease (TA-GVHD), and posttransfusion purpura (PTP)Footnote 3,Footnote 11.

FNHTR and urticarial reaction are the most frequent non life-threatening acute transfusion reactions; however, AHTR is the most frequent severe reaction and the leading cause of death associated with transfusionFootnote 12. On the other hand, TRALI and TA-GVHD are rare and the most fatal transfusion reactions. The case fatality rate is 5% to 14% for TRALI and over 90% for TA-GVHDFootnote 13,Footnote 14. TRALI has been recognized as the third leading cause of death associated with transfusionFootnote 12.

ABO incompatibility accounts for about 80% of AHTR-related deaths and occurs as a result of error. Well recognized errors include patient misidentification, sample error, wrong blood issued, transcription error, administration error, technical error and storage error. Identification and prevention of these errors have become an increasingly important issue in transfusion safetyFootnote 3.

In general, nonimmune mediated transfusion reactions result in minor clinical manifestations. These include hemoglobinuria, hyperkalemia, hypocalcemia, hypothermia, and iron overload. However, air embolus and circulatory overload may also be life threatening. Again, these reactions are mostly error related and can usually be prevented by proper preparation and storage of components, and better transfusion practicesFootnote 11.

Despite the risks associated with transfusion, the Canadian blood supply is one of the safest blood systems in the world. Effective strategies and laboratory test procedures are being implemented to further prevent and/or reduce transfusion-related adverse events.

Table 1. Classification of transfusion-related adverse events
  • aAcute adverse event is defined as any unfavourable event occurring in a patient during or within 24 hours after transfusion, but the definition has minor variations in the literature.
  • bDelayed adverse event is defined as any unfavourable event occurring in a patient more than 24 hours and up to 3 months after transfusion, but the definition has minor variations in the literature.
Time of Occurrence Mechanism Infectious Reaction Noninfectious Reaction
Acutea Immune mediated  -- Acute hemolytic transfusion reaction
Transfusion-related acute lung injury
Febrile nonhemolytic transfusion reaction
Urticarial reaction
Anaphylactic
Nonimmune mediated Bacterial contamination Nonimmune hemolysis (e.g. hemoglobinuria)
Circulatory overload
Metabolic (e.g. hyperkalemia)
Embolic
Delayedb Immune mediated -- Delayed hemolytic transfusion reaction
Transfusion associated graft-versus-host disease
Posttransfusion purpura
Nonimmune mediated Transfusion Transmitted infections (viral, bacterial and parasitic) Hemochromatosis (iron overload)


Table 2. Categories of infectious agents according to transfusion transmissibility, pathogenicity, donor test and pathogen inactivation
First
Group
Second Group Third
Group
Fourth Group Fifth
Group
Agents HBV,
HCV,
HIV-1/-2,
HTLV-I/-II,
Treponema pallidum
CMV,
EBV,
Yersinia enterocolitica, Staphylococcus and Streptococcus species,
Trypanosoma cruzi
HAV,
HPV-B19,
HHV-6,
Plasmodium species,
Babesia microti,
Rickettsia rickettsii,
Leishmania donovani,
Toxoplasma gondii
HGV/GBV-C,
TTV,
SEN-V
HEV,
HHV-8,
Borrelia burgdorferi,
Ehrlichia phagocytophila,
prions
Transfusion
transmissibility
Established Established Established Established Not established
Pathogenicity Cause diseases Cause diseases largely in high risk individuals Cause diseases largely in high risk individuals Not established Cause diseases
Donor serologic test Available Not available Not available Not available Not available
Effectiveness of pathogen inactivation Largely inactivated Largely inactivated Largely not inactivated Unknown Unknown
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