Blood donor deferral: time for change? An evidence-based analysis

Figures & data

Table 1 Seven categories of donor deferral criteria

I: Conditions that may increase the risk of a serious adverse donor reaction   Impaired cardiovascular compensatory mechanisms   Hemostatic disorders (hemorrhagic diathesis, thrombophilia)   Inadequate oxygen transport (bone marrow, pulmonary, or renal diseases)   Protein deficiency (liver failure, protein losing enteropathy, nephrotic syndrome)   Immune deficiencies II: Conditions that may interfere with the feasibility of the collection   Donor questioning (minimum age, communication problems, noncompliant donor)   Collection (difficult venous access, involuntary movements)   Donation testing (hepatitis B vaccine, unreliable serologic blood group typing) III: Conditions that may affect the quality of the blood products   Diseases   Medications (anticoagulant and antiplatelet drugs) IV-VII: Conditions that may increase the risk of a serious donor-related transfusion reaction IV: Conditions with proven transmissibility by transfusion TTIs     Allo-antibodies against red cell, leukocyte, and platelet antigens V: Exposure to conditions with proven transmissibility by transfusion   TTI risk factors by blood, sexual, or other contact   Allo-immunization by pregnancy or transfusion VI: Conditions with possible or unknown transmissibility by transfusion Infectious diseases other than TTIs   Live attenuated vaccines   Malignancy   Medication with a known teratogenic effect VII: Exposure to conditions with possible or unknown transmissibility by transfusion   Persons who have a family history which places them at risk of developing a TSE   Recipients of a corneal or dura mater graft or medicines made from human pituitary glands   Residence in the UK during 1980-1996   Blood transfusion in the UK   Contact with infectious diseases other than TTI

Abbreviations: TTI, transfusion-transmissible infection; TSE, transmissible spongiform encephalopathy.

Table 2 Number of systematic reviews, primary research studies, or HTAs containing evidence that (does not) supports blood donor selection criteria

Donor deferral categories	Systematic reviews	Primary research studies		HTA
		High quality/RCT	Low quality/observational studies
I: Conditions that may increase the risk of a serious adverse donor reaction	4^Citation6^–^Citation8,^a	–	8^Citation9−Citation16	1^Citation17
II: Conditions that may interfere with the feasibility of collection	–	–	–	1^Citation17
III: Conditions that may affect the quality of the blood products	1^Citation18	–	–	1^Citation17
IV: Conditions with proven transmissibility by transfusion	–	–	11^Citation19^–^Citation29	2^Citation17,Citation30
V: Exposure to conditions with proven transmissibility by transfusion	2^Citation31,^a	–	34^Citation19^–^Citation21, Citation23^–^Citation29,Citation32^–^Citation55	2^Citation17,Citation56
VI: Conditions with possible or unknown transmissibility by transfusion	l^Citation18	–	3^Citation26,Citation36,Citation54	1^Citation17
VII: Exposure to conditions with possible or unknown transmissibility by transfusion	–	–	–	1^Citation17

Notes: The primary studies are divided in a high-quality or low-quality category, based on their study design (RCTs or observational studies, respectively).

a Personal communication, Centre for Evidence-Based Practice, Belgian Red Cross-Flanders, 2016.

Abbreviations: HTA, health technology assessment; RCT, randomized controlled trial.

Table 3 Cost/QALY of safety measures used in the blood-banking sector

Intervention	Comparison	Country	Cost/QALY^#	References
Medical questionnaire (donor health questionnaire → prevention of HIV/HBV/HCV)	No medical questionnaire	the Netherlands	696,744 (315,422–1,611,681)	de Kort et al^Citation17
Laboratory testing
Individual-donor NAT + serologic tests (HBV/HCV/HIV)	Serologic tests	Sweden	3,726,637	Davidson et al^Citation63
Triplex NAT (HBV/HCV/HIV) + serologic tests	Serologic tests	the Netherlands	5,200,000	Borkent-Raven et al^Citation64
Minipool NAT (HBV/HCV/HIV) + serologic tests	Serologic tests	USA	2.055.000 (1,370,000–2,877,000)	Marshall et al^Citation65
Individual NAT (HBV/HCV/HIV) + serologic tests	Serologic tests		10.001.000
HIV antibody	No test		Cost saving 4,932	Eisenstaedt et al^Citation66
HIV NAT (+ antibody)	HIV antibody		2,693,420	AuBuchon et al^Citation67
HCV antibody	No screening		Cost saving	Busch et al^Citation68
HCV NAT (+ antibody)	Antibody	Spain	2,507,100	Pereira et al^Citation69
Bacterial testing	No bacterial testing	the Netherlands	124,254 (24,864-2,861,729)	Janssen et al^Citation70
Platelet preparation
Pathogen reduction technology (Intercept) + single-donor apheresis platelets (without bacterial testing)	Untreated single-donor apheresis platelets	USA	Range: 1,793,101–6,098,760	Bell et al^Citation71
Pathogen reduction technology (Intercept) + single-donor apheresis platelets (with bacterial testing)	Untreated single-donor apheresis platelets		Range: 6,520,379–31,466,250	Bell et al^Citation71
Pathogen reduction technology (Intercept) + random-donor pooled platelet concentrations	Untreated random- donor pooled platelet concentrations		626,892–2,488,002	Bell et al^Citation71
Pathogen reduction technology (Mirasol)	Current screens and interventions		1,748,000 (822,000–4,538,810)	Custer et al^Citation72
Pathogen reduction technology (type of technology: not reported)	No pathogen reduction technology	the Netherlands	680,443 (197,211–11,194,452)	Janssen et al^Citation70
Pathogen reduction technology (Intercept)	No pathogen reduction technology	Belgium	Range: 267,648–4,739,105	Moeremans et al^Citation73

Notes:

# Costs are presented in €. Costs were converted from $USD to € (1€=1.37$) if needed. Data is presented as mean (95% CI), unless otherwise indicated.

Abbreviations: QALY, quality-adjusted life-years; CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; NAT, nucleic acid test.

Table 4 Top 30 reasons of donor exclusion in Belgium

Top 30	Reason for donor exclusion	Category of deferral	% of total number of exclusions	Evidence available?
1	Low hemoglobin levels	I	41.82%	No
2	Asymptomatic visitor of an area outside Europe (Recommendation of the Belgian Superior Health Council)	V	6.82%	No
3	New sexual partner	V	6.75%	Low quality
4	Asymptomatic visitor to a malaria endemic area	V	4.76%	No
5	Non-specified infectious diseases	VI	4.50%	No
6	Dental treatment	V	4.09%	No
7	Endoscopic examination using flexible instruments	V	3.58%	Low quality
8	Minor surgery	V	3.16%	Low quality
9	Percutaneous needle contact (tattoo, body piercing, acupuncture) by a non-qualified practitioner	V	3.11%	Low quality
10	Specific infectious diseases (other than viral hepatitis, sexually transmitted diseases)	VI	2.66%	No
11	Pregnancy	I	2.16%	No
12	High blood pressure	I	1.88%	Low quality
13	Serious cardiovascular disease	I	1.62%	No
14	Low blood pressure	I	1.47%	Low quality
15	Asymptomatic visitor of an area with ongoing transmission of West Nile Virus to humans	V	1.22%	No
16	Malignant disease	VI	1.20%	No
17	Short interdonation interval	I	1.16%	No
18	Endoscopic examination using rigid instruments	V	1.11%	Low quality
19	Medication (with possible side effect for the recipient)	VI	0.98%	No
20	Major surgery	V	0.82%	Low quality
21	Body weight <50 kg	I	0.72%	Low quality
22	Tick bite (Lyme disease)	VII	0.65%	No
23	Serious hematological disease	I, III	0.65%	Low quality
24	Serious central nervous system disease	VI	0.63%	No
25	Hepatitis B vaccine	II	0.58%	No
26	Sexual risk behavior with temporary deferral	V	0.45%	Low quality
27	Bariatric surgery	I	0.43%	No
28	Chronic inflammatory diseases	VI	0.36%	No
29	Serious musculoskeletal system diseases	VI	0.32%	No
30	Mucosal splash or needle stick injury	V	0.32%	Low quality

Pauwels NS, Cusack L, De BE, Compernolle V, Vandekerckhove P. The effect of pre-donation hypotension on whole blood donor adverse reactions: a systematic review. J Am Soc Hypertens. 2014;8(6):429–436.

 Google Scholar

Stainsby D, Butler M. Recommendations for the Removal of the Upper Age Limit for Regular Whole Blood and Component Donors. Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee; 2008.

 Google Scholar

Callahan R, Edelman EB, Smith MS, Smith JJ. Study of the incidence and characteristics of blood donor “reactors”. Transfusion. 1963;3:76–82.

 PubMed Web of Science ®Google Scholar

Wiltbank TB, Giordano GF, Kamel H, Tomasulo P, Custer B. Faint and prefaint reactions in whole-blood donors: an analysis of predonation measurements and their predictive value. Transfusion. 2008;48(9):1799–1808.

 Google Scholar

de Kort W, van den Burg P, Geerligs H, Pasker-de JP, Marijt-van der Kreek T. Cost-effectiveness of questionnaires in preventing transfusion-transmitted infections. Transfusion. 2014;54(3 Pt 2):879–888.

 Web of Science ®Google Scholar

De Buck E, Pauwels NS, Dieltjens T, Compernolle V, Vandekerckhove P. Is blood of uncomplicated hemochromatosis patients safe and effective for blood transfusion? A systematic review. J Hepatol. 2012;57(5):1126–1134.

 Google Scholar

Cardoso MD, Koerner K, Dengler T, Kubanek B. Identification of infection routes for HCV in blood donors from Germany. Infusionsther Transfusionsmed. 1998;25(6):370–372.

 Google Scholar

Zou S, Fujii K, Johnson S, et al. Prevalence of selected viral infections among blood donors deferred for potential risk to blood safety. Transfusion. 2006;46(11):1997–2003.

 Google Scholar

Shehata N, Kohli M, Detsky A. The cost-effectiveness of screening blood donors for malaria by PCR. Transfusion. 2004;44(2):217–228.

 Google Scholar

De Buck E, Dieltjens T, Compernolle V, Vandekerckhove P. Is having sex with other men a risk factor for transfusion-transmissible infections in male blood donors in Western countries? A systematic review. PLoS One. 2015;10(4):e0122523.

 Google Scholar

Esteban JI, Lopez-Talavera JC, Genesca J, et al. High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus. Ann Intern Med. 1991;115(6):443–449.

 Web of Science ®Google Scholar

Neal KR, Jones DA, Killey D, James V. Risk factors for hepatitis C virus infection. A case-control study of blood donors in the Trent Region (UK). Epidemiol Infect. 1994;112(3):595–601.

 Web of Science ®Google Scholar

Allain JP, Mihaljevic I, Gonzalez-Fraile MI, et al. Infectivity of blood products from donors with occult hepatitis B virus infection. Transfusion. 2013;53(7):1405–1415.

 Web of Science ®Google Scholar

Wong P-Y, Dodd R, Kiely P, Carroll C, Whyte G. Characteristics of hepatitis C-positive blood donors in Victoria, Australia. Transfus Med. 1999;9(1):15–19.

 Web of Science ®Google Scholar

Kaplan EH. Implicit valuation of a blood-exclusion decision. Med Decis Making. 1999;19(2):207–213.

 Google Scholar

Serfaty L, Giral P, Elghouzzi MH, Jullien AM, Poupon R. Risk factors for hepatitis C virus infection in hepatitis C virus antibody ELISA-positive blood donors according to RIBA-2 status: a case-control survey. Hepatology. 1993;17(2):183–187.

 Web of Science ®Google Scholar

Christensen PB, Titlestad IL, Homburg KM, Georgsen J, Kristensen T. Hepatitis B core antibodies in Danish blood donors: a surrogate marker of risk behaviour. Vox Sang. 2001;81(4):222–227.

 Google Scholar

van der Poel C, Cuypers H, Reesink H, et al. Risk factors in hepatitis C virus-infected blood donors. Transfusion. 1991;31(8):777–779.

 Web of Science ®Google Scholar

Davidson T, Ekermo B, Gaines H, Lesko B, Akerlind B. The cost-effectiveness of introducing nucleic acid testing to test for hepatitis B, hepatitis C, and human immunodeficiency virus among blood donors in Sweden. Transfusion. 2011;51(2):421–429.

 Web of Science ®Google Scholar

Borkent-Raven BA, Janssen MP, van der Poel CL, Bonsel GJ, van Hout BA. Cost-effectiveness of additional blood screening tests in the Netherlands. Transfusion. 2012;52(3):478–488.

 Google Scholar

Marshall DA, Kleinman SH, Wong JB, et al. Cost-effectiveness of nucleic acid test screening of volunteer blood donations for hepatitis B, hepatitis C and human immunodeficiency virus in the United States. Vox Sang. 2004;86(1):28–40.

 Web of Science ®Google Scholar

Eisenstaedt RS, Getzen TE. Screening blood donors for human immunodeficiency virus antibody: cost-benefit analysis. Am J Public Health. 1988;78(4):450–454.

 Web of Science ®Google Scholar

AuBuchon JP. Cost-effectiveness of preoperative autologous blood donation for orthopedic and cardiac surgeries. Am J Med. 1996;101(2A):38S–42S.

 Google Scholar

Busch MP, Korelitz JJ, Kleinman SH, Lee SR, AuBuchon JP, Schreiber GB. Declining value of alanine aminotransferase in screening of blood donors to prevent posttransfusion hepatitis B and C virus infection. The Retrovirus Epidemiology Donor Study. Transfusion. 1995;35(11):903–910.

 Web of Science ®Google Scholar

Pereira A, Sanz C. A model of the health and economic impact of posttransfusion hepatitis C: application to cost-effectiveness analysis of further expansion of HCV screening protocols. Transfusion. 2000;40(10):1182–1191.

 Google Scholar

Janssen MP, van der Poel CL, Buskens E, Bonneux L, Bonsel GJ, van Hout BA. Costs and benefits of bacterial culturing and pathogen reduction in the Netherlands. Transfusion. 2006;46(6):956–965.

 Web of Science ®Google Scholar

Bell CE, Botteman MF, Gao X, et al. Cost-effectiveness of transfusion of platelet components prepared with pathogen inactivation treatment in the United States. Clin Ther. 2003;25(9):2464–2486.

 PubMed Web of Science ®Google Scholar

Custer B, Agapova M, Martinez RH. The cost-effectiveness of pathogen reduction technology as assessed using a multiple risk reduction model. Transfusion. 2010;50(11):2461–2473.

 PubMed Web of Science ®Google Scholar

Moeremans K, Warie H, Annemans L. Assessment of the economic value of the INTERCEPT blood system in Belgium. Transfus Med. 2006;16(1):17–30.

 Web of Science ®Google Scholar