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REVIEW ARTICLE
Year : 2014  |  Volume : 58  |  Issue : 5  |  Page : 552-557  

Transfusion transmitted diseases in perioperative and intensive care settings


Department of Anaesthesiology, Acharya Harihar Regional Cancer Centre, Cuttack, Odisha, India

Date of Web Publication14-Nov-2014

Correspondence Address:
Dr. Rekha Das
Department of Anaesthesiology, Acharya Harihar Regional Cancer Centre, Cuttack - 753 007, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5049.144651

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Patients in the perioperative period and intensive care unit are commonly exposed to blood transfusion (BT). They are at increased risk of transfusion transmitted bacterial, viral and protozoal diseases. The risk of viral transmission has decreased steadily, but the risk of bacterial transmission remains same. Bacterial contamination is more in platelet concentrates than in red cells and least in plasma. The chances of sepsis, morbidity and mortality depend on the number of transfusions and underlying condition of the patient. Challenges to safe BT continue due to new emerging pathogens and various management problems. Strategies to restrict BT, optimal surgical and anaesthetic techniques to reduce blood loss and efforts to develop transfusion alternatives should be made. Literature search was performed using search words/phrases blood transfusion, transfusion, transfusion transmitted diseases, transfusion transmitted bacterial diseases, transfusion transmitted viral diseases, transfusion transmitted protozoal diseases or combinations, on PubMed and Google Scholar from 1990 to 2014.

Keywords: Blood transfusion, transfusion, transfusion transmitted bacterial diseases, transfusion transmitted diseases, transfusion transmitted viral diseases


How to cite this article:
Das R, Hansda U. Transfusion transmitted diseases in perioperative and intensive care settings. Indian J Anaesth 2014;58:552-7

How to cite this URL:
Das R, Hansda U. Transfusion transmitted diseases in perioperative and intensive care settings. Indian J Anaesth [serial online] 2014 [cited 2020 Nov 30];58:552-7. Available from: https://www.ijaweb.org/text.asp?2014/58/5/552/144651


   Introduction Top


One of the adverse effects of allogenic blood transfusion (BT) is the transmission of infectious agents. Although Transfusion transmitted diseases (TTDs) have reduced significantly over the past decade the risk still exists. Perioperative BT is mandatory in situations where patient's haemoglobin has to be built up to an optimum level prior to Surgery and the surgical procedure entails significant blood loss. The patients requiring BT in intensive care unit (ICU) are those with coagulation abnormalities, haematologic disorders, severe sepsis and on-going blood loss. In a multicentric observational study, it was found that anaemia is commonly present in critically ill patients and require a large amount of BT. [1] Various studies have shown that, there is frequent use of transfusion of blood and its components in post-operative period. [2] The organisms responsible for TTD can be bacteria, virus and protozoa. The manifestations of infection can be immediate or delayed. It may lead to a chronic carrier state or asymptomatic infection; all of these invariably contribute to patient's morbidity or mortality.

To be transmitted by BT, the infective agent: [3]

  • must be present in the blood stream of donors
  • must be able to withstand the processing in the production of blood components
  • must retain viability during storage
  • must retain infectivity and the receiver should be sero-negative, to generate infection in the blood receiver.



   Transfusion Transmitted Bacterial Infections Top


The incidence of transfusion transmitted bacterial infection (TTBI) has been found to be 24.7/million platelet concentrates (PCs) and 0.39/million red cells transfusion. The incidence of fatal TTBI is 5.14/million in PCs transfusion. [4] Bacterial contamination is more common in PCs as these are stored at 20-24°C, the temperature that favours the growth of bacteria. [5] The rate of contamination of PCs is 0.02-1.2% and for packed red blood cells (PRBCs) is 0.1-0.2%. [6] Sources of bacteria are donors, environment of blood bank or hospitals, contaminated bag and tubing, skin of the donor or recipient (insufficient skin preparation of venipuncture site). The bacteria are mainly skin contaminants like coagulase negative staphylococcus although both staphylococcus and streptococcus are transmitted through stored platelets.

Next to platelets, the red cells are more likely to be contaminated. The longer the red cells are stored, more is the chance of infection. Bacthem study shows that organisms that mostly grow are Gram-negative bacteria like Yersinia, Serratia, Escherichia, Pseudomonas, Proteus, Klebsiella, and Acinetobacter. [7] These bacteria are capable of growth at 1-6°C the temperatures at which red cells are stored. Bacterial contamination of plasma is uncommon for the temperature at which it is stored. Only few cases of contamination were reported in Canada and Germany. [8],[9] Organisms identified are staphylococcus, Klebsiella, Propionobacterium and Pseudomonas. Water baths that are used to thaw plasma are the potential source. [10]

Transfusion transmitted bacterial infection can manifest as high fever, chills, rigor, tachycardia, hypotension, nausea, vomiting, dyspnoea, backache and abdominal pain [7] which may be confused with febrile non-haemolytic transfusion reaction. Gram-negative endotoxaemia can cause abrupt symptoms with temperature as much as 109°F, progressing to fulminant sepsis, shock, disseminated intravascular coagulation and even death. A high mortality rate of 60% has been reported. [11]

A systematic review by Guinet et al. reported that transfusion recipients who were already anaesthetised or in sepsis before transfusion was initiated had blurring of clinical symptoms of Yersinia enterocolitica post-transfusion sepsis and these patients also had higher mortality rate. [12] On suspicion of TTBI, transfusion should be stopped immediately, followed by administration of broad spectrum antibiotics and symptomatic management of the patient. The blood bank should be informed. Gram-staining, bacterial culture of both donor and recipient, should be done. Coombs test of recipient blood is necessary to rule out haemolytic transfusion reaction. Transmission of syphilis has become very rare after implementation of serological test for antibodies to Treponema pallidum.


   Transfusion Transmitted Viral Diseases Top


Transfusion-transmitted viral infection may not pose an immediate threat in the perioperative period or in ICU, but definitely is a matter of great concern due to its potential transmission in the window period. Transfusion-transmitted viruses are human immunodeficiency virus 1 and 2 (HIV-1 and 2), hepatitis B virus (HBV), hepatitis C virus (HCV), other hepatitis viruses, Cytomegalovirus
(CMV), Dengue virus, Chikungunya virus, human T-cell leukaemia virus, parvovirus, Epstein-Barr virus, human herpes virus and West Nile virus. Most developing countries practice the serological test for HIV as a routine practice, but it is a low sensitivity test. The HIV-1 p24 antigen test is considered superior because it reduces the window period by 6 days. It has been replaced by Mini Pool and individual donation nucleic acid amplification test (MP- and ID-NAT) because it reduces the residual risk of infectious window period by 11 days. However, this current technology cannot detect HIV ribonucleic acid in the first 1-2 weeks. [13]

Commonly HBV surface antigen (HBsAg) and less commonly antibody for HBV core antigen (anti-HBcAg) detection test are done in most countries. NAT is not practical because of slow viral replication and very low level of viraemia and hence may be implemented along with serological testing to provide safe blood. The routine donor screening of anti-HCV antibodies has grossly reduced the risk of post-transfusion acute HCV infection. The HCV NAT reduces the window period to 15 days. Rare cases of transmission of HAV and HEV through transfusion have been reported. [14],[15]

The clinical features and detection methods of transfusion transmitted viral and protozoal diseases that have been reported are shown in [Table 1] and [Table 2]. Around 68 infectious agents have been identified and described in detail in an analysis done on TTD and published in detail. [16] It is beyond the scope of this article to describe all of these.
Table 1: Transfusion transmitted viral diseases

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Table 2: Transfusion transmitted protozoal diseases

Click here to view



   Effect of Blood Transfusion in Perioperative and Intensive Care Unit Setting Top


In an analysis, it was found that there was increased morbidity and mortality after BT in ICU, trauma and surgical patients. [17] Red cells are transfused in critically ill patients with the aim to improve tissue oxygenation, but in reality they rather lead to worse clinical outcome. [18] In a recent study, Mahdi et al. found that perioperative BT was one of the risk factors for surgical site infection (SSI). [19] In a prospective study, SSI and reduced graft survival had been found in kidney transplanted patients who received intraoperative BT. [20] The risk of post-operative infection was present both in leukocyte-depleted and non-leukocyte-depleted transfusion. [21] Although leukocyte-depleted red cells have not been proven to be superior over non-leukocyte-depleted, nonetheless, they increase the microcirculatory flow in septic patients. [22] Transfusion of more than 5 PRBCs in both operating room and during the first post-operative day in ICU was found to be an independent predictor of nosocomial infection in cardiac surgery. The majority of nosocomial infections were respiratory tract infection and central venous catheter related infections. [23] In comparison to homologous BT, there was decreased incidence of complications, early extubation and shorter ICU stay after autologous transfusion in cardiac surgery. [24] BT was one of the independent risk factors for post-operative infectious complications in hepatectomy patients. [25] Moderate degree of trauma patients with injury severity score of <25 had ventilator-associated pneumonia, acute respiratory distress syndrome and death after delayed BT beyond 48 h. [26] In major burn injury, there was increased risk of infection and mortality which depends on the number of transfusions. [27] There was increased risk of sepsis in patients with severe burns (>60% total body surface area with inhalational injury) paediatric patients who received higher (PRBCs >20/fresh frozen plasma >5) amount of blood products. [28]

Rosland et al., found in their prospective multicentre cohort study that patients with sepsis who received PRBC transfusion had higher simplified acute physiology score II, sepsis related organ failure assessment score, more length of stay in ICU and higher 90 days mortality. [29] There was a two-fold increase in blood stream infection after PRBC transfusion and it was dose dependent. [30] Critically ill patients on ventilatory support and in severe sepsis who receive BT are more prone to CMV activation leading to increase in morbidity and mortality. [31] There was increased incidence of opportunistic infection in immunocompromised patients like HIV after BT. Sloand et al. found in their retrospective study an increased incidence of CMV and bacterial infections who received BT. Also there was significant bacterial infection that occurred in patients with CMV infection and increased death rate after BT. [32] The risk of transmission of diseases and occurrence of sepsis is enhanced due to immunosuppressive effect of BT. In fact this immunomodulatory effect of allogenic BT is due to associated pro-inflammatory burden in the recipient which is found to be proportional to the stored age of blood. This effect is also linked with recurrence in cancer surgery. [33]


   Threat to Safe Blood Transfusion Top


A challenge to safe BT is lack of preventive measure for new emerging pathogens. Current screening methods based on culture like BacT/ALERT system sometimes do not detect bacterial contamination. [34] Many countries still do not implement either ID or MP-NAT and continue to use rapid test or enzyme-linked immunosorbent assay for anti-HIV 1 and 2, HBsAg and anti-HCV. BT service is highly decentralized and lacks vital resources like skilled manpower, adequate infrastructure and financial support in India. Lack of 100% blood donation from voluntary non-remunerated donors and a significant percentage of replacement donors result in high prevalence of TTD.


   Prevention of Transfusion Transmitted Diseases Top


Restrictive BT strategy should aim at transfusing blood components based on individual needs rather than transfusing on the basis of transfusion trigger. Autologous blood donation, using recombinant human erythropoietin and optimal surgical and anaesthetic technique to reduce blood loss should be adopted. TTD can be largely prevented by ensuring safety steps like deferring the donors with recent dental treatments, minor surgery or fever at presentation, proper donor screening and testing, optimal blood product handling, processing and storage, carrying out proper skin disinfection of donor arm and ensuring diversion of first 30-40 ml of whole blood from collection bag. Bacterial detection methods should be applied to stored blood closer to the transfusion time. Gram-staining, screening for markers of contamination and culture of stored blood before transfusion should be done. Blood should yield a negative culture at least 24-48 h before it is released for transfusion. Application of pathogen reduction technology like use of synthetic psoralen, riboflavin, prestorage leukocyte reduction and apheresis derived platelet to reduce transmissible pathogens should be carried out. [35] Efforts should be taken to improve on patient blood management modalities and multicomponent apheresis, a patient centre paradigm in transfusion medicine that attempts to reduce the transfusion risk to a level of as low as reasonably achievable risk. [36] Mass vaccination of the population will offer protection against some TTD. 'Look Back' programmes may be adopted in developing countries. Efforts should be made to develop artificial oxygen carrier and recombinant clotting factors.



There is a potential risk of transmission of diseases and immunosuppression after BT. Patients in perioperative period and ICU are more vulnerable to TTD due to increased number of transfusions, low immune status and comorbidities. The transfused patients carry high risk of morbidity and mortality due to bacterial infection and sepsis. Early diagnosis of TTD by sound, vigilant clinical acumen and detection methods followed by prompt management will reduce the morbidity and mortality. Applying the principle of restricted BT, use of transfusion alternatives, improving BT service and implementing newer technologies are the methods to prevent TTD.

 
   References Top

1.Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, et al. Anemia and blood transfusion in critically ill patients. JAMA 2002;288:1499-507.  Back to cited text no. 1
    
2.Walsh TS, Lee RJ, Maciver CR, Garrioch M, Mackirdy F, Binning AR, et al. Anemia during and at discharge from intensive care: The impact of restrictive blood transfusion practice. Intensive Care Med 2006;32:100-9.  Back to cited text no. 2
    
3.Garraud O. Mechanisms of transfusion-linked parasite infection. Transfus Clin Biol 2006;13:290-7.  Back to cited text no. 3
    
4.Lafeuillade B, Eb F, Ounnoughene N, Petermann R, Daurat G, Huyghe G, et al. Residual risk and retrospective analysis of transfusion-transmitted bacterial infection reported by the French National Hemovigilance Network from 2000 to 2008. Transfusion 2014 (E Pub Ahead of print).  Back to cited text no. 4
    
5.Brecher ME, Hay SN. Bacterial contamination of blood components. Clin Microbiol Rev 2005;18:195-204.  Back to cited text no. 5
    
6.Walther-Wenke G. Incidence of bacterial transmission and transfusion reactions by blood components. Clin Chem Lab Med 2008;46:919-25.  Back to cited text no. 6
    
7.Perez P, Salmi LR, Folléa G, Schmit JL, de Barbeyrac B, Sudre P, et al. Determinants of transfusion-associated bacterial contamination: Results of the French BACTHEM Case-Control Study. Transfusion 2001;41:862-72.  Back to cited text no. 7
    
8.Public Health Agency of Canada. Transfusion Transmitted Injuries Surveillance System Program Report 2002-2003; 2005.  Back to cited text no. 8
    
9.Keller-Stanislawski B, Lohmann A, Günay S, Heiden M, Funk MB. The German Haemovigilance System - Reports of serious adverse transfusion reactions between 1997 and 2007. Transfus Med 2009;19:340-9.  Back to cited text no. 9
    
10.Pandey S, Vyas GN. Adverse effects of plasma transfusion. Transfusion 2012;52:65-79.  Back to cited text no. 10
    
11.Reading FC, Brecher ME. Transfusion-related bacterial sepsis. Curr Opin Hematol 2001;8:380-6.  Back to cited text no. 11
    
12.Guinet F, Carniel E, Leclercq A. Transfusion-transmitted Yersinia enterocolitica sepsis. Clin Infect Dis 2011;53:583-91.  Back to cited text no. 12
    
13.Fauci AS, Lane HC. Human Immunodeficiency Virus Disease: AIDS and Related Disorders. In: Frauci, Braunwald, Kasper, Hauser, Lange, Jameson, Localzo. Eds. Harrisons Principles of Internal Medicine. 17 th ed. New York, Mc Graw Hill Medical; 2008. p. 1138.  Back to cited text no. 13
    
14.Gowland P, Fontana S, Niederhauser C, Taleghani BM. Molecular and serologic tracing of a transfusion-transmitted hepatitis A virus. Transfusion 2004;44:1555-61.  Back to cited text no. 14
    
15.Boxall E, Herborn A, Kochethu G, Pratt G, Adams D, Ijaz S, et al. Transfusion-transmitted hepatitis E in a 'nonhyperendemic' country. Transfus Med 2006;16:79-83.  Back to cited text no. 15
    
16.Stramer SL, Hollinger FB, Katz LM, Kleinman S, Metzel PS, Gregory KR, et al. Emerging infectious disease agents and their potential threat to transfusion safety. Transfusion 2009;49(2):1S-29.  Back to cited text no. 16
    
17.Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: A systematic review of the literature. Crit Care Med 2008;36:2667-74.  Back to cited text no. 17
    
18.Lelubre C, Vincent JL. Red blood cell transfusion in the critically ill patient. Ann Intensive Care 2011;1:43.  Back to cited text no. 18
    
19.Mahdi H, Goodrich S, Lockhart D, DeBernardo R, Moslemi-Kebria M. Predictors of surgical site infection in women undergoing hysterectomy for benign gynecologic disease: A multicenter analysis using the national surgical quality improvement program data. J Minim Invasive Gynecol 2014;21:901-9.  Back to cited text no. 19
    
20.Freire MP, Antonopoulos IM, Piovesan AC, Moura ML, de Paula FJ, Spadão F, et al. Amikacin prophylaxis and risk factors for surgical site infection after kidney transplantation. Transplantation 2014. (E Pub Ahead of print)  Back to cited text no. 20
    
21.Vranken NP, Weerwind PW, Barenbrug PJ, Teerenstra S, Ganushchak YM, Maessen JG. The role of patient's profile and allogeneic blood transfusion in development of post-cardiac surgery infections: A retrospective study. Interact Cardiovasc Thorac Surg 2014;19:232-8.  Back to cited text no. 21
    
22.Donati A, Damiani E, Luchetti M, Domizi R, Scorcella C, Carsetti A, et al. Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: A pilot study. Crit Care 2014;18:R33.  Back to cited text no. 22
    
23.Michalopoulos A, Geroulanos S, Rosmarakis ES, Falagas ME. Frequency, characteristics, and predictors of microbiologically documented nosocomial infections after cardiac surgery. Eur J Cardiothorac Surg 2006;29:456-60.  Back to cited text no. 23
    
24.Oz BS, Arslan G, Kaya E, Gunay C, Cingoz F, Arslan M. Comparison of results of autologous versus homologous blood transfusion in open-heart surgery. Cardiovasc J Afr 2013;24:121-3, 9.  Back to cited text no. 24
    
25.Pessaux P, van den Broek MA, Wu T, Olde Damink SW, Piardi T, Dejong CH, et al. Identification and validation of risk factors for postoperative infectious complications following hepatectomy. J Gastrointest Surg 2013;17:1907-16.  Back to cited text no. 25
    
26.Croce MA, Tolley EA, Claridge JA, Fabian TC. Transfusions result in pulmonary morbidity and death after a moderate degree of injury. J Trauma 2005;59:19-23.  Back to cited text no. 26
    
27.Palmieri TL, Caruso DM, Foster KN, Cairns BA, Peck MD, Gamelli RL, et al. Effect of blood transfusion on outcome after major burn injury: A multicenter study. Crit Care Med 2006;34:1602-7.  Back to cited text no. 27
    
28.Jeschke MG, Chinkes DL, Finnerty CC, Przkora R, Pereira CT, Herndon DN. Blood transfusions are associated with increased risk for development of sepsis in severely burned pediatric patients. Crit Care Med 2007;35:579-83.  Back to cited text no. 28
    
29.Rosland RG, Hagen MU, Haase N, Holst LB, Plambech M, Madsen KR, et al. Red blood cell transfusion in septic shock - Clinical characteristics and outcome of unselected patients in a prospective, multicentre cohort. Scand J Trauma Resusc Emerg Med 2014;22:14.  Back to cited text no. 29
    
30.Michalia M, Kompoti M, Panagiotakopoulou A, Kallitsi G, Charitidi M, Trikka-Graphakos E, et al. Impact of red blood cells transfusion on ICU-acquired bloodstream infections: A case-control study. J Crit Care 2012;27:655-61.  Back to cited text no. 30
    
31.Tirumala S, Behera B, Lingala S, Kumar BV, Mishra PK, Gurunath JM, et al. Severe Cytomegalovirus infections in immunocompetent patients at admission as dengue mimic: Successful treatment with intravenous ganciclovir. Asian Pac J Trop Med 2012;5:920-2.  Back to cited text no. 31
    
32.Sloand E, Kumar P, Klein HG, Merritt S, Sacher R. Transfusion of blood components to persons infected with human immunodeficiency virus type 1: Relationship to opportunistic infection. Transfusion 1994;34:48-53.  Back to cited text no. 32
    
33.Cata JP, Wang H, Gottumukkala V, Reuben J, Sessler DI. Inflammatory response, immunosuppression, and cancer recurrence after perioperative blood transfusions. Br J Anaesth 2013;110:690-701.  Back to cited text no. 33
    
34.Larsen CP, Ezligini F, Hermansen NO, Kjeldsen-Kragh J. Six years' experience of using the BacT/ALERT system to screen all platelet concentrates, and additional testing of outdated platelet concentrates to estimate the frequency of false-negative results. Vox Sang 2005;88:93-7.  Back to cited text no. 34
    
35.Otsubo H, Yamaguchi K. Current risks in blood transfusion in Japan. Jpn J Infect Dis 2008;61:427-33.  Back to cited text no. 35
    
36.Vamvakas EC. Reasons for moving toward a patient-centric paradigm of clinical transfusion medicine practice. Transfusion 2013;53:888-901.  Back to cited text no. 36
    



 
 
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