In Focus
Imputability assessment in Haemovigilance
Current challenges and the need for objective causality frameworks
Imputability assessment is a crucial requirement in the haemovigilance systems. It functions as a systematic approach to establish a causal relationship between blood transfusion or donation events and adverse reactions.1
This article demonstrates that a structured imputability assessment approach is not only crucial for technical risk assessment but also for patient safety, regulatory compliance, and medico-legal implications. Although widely implemented, current subjective assessment methods exhibit significant limitations. Evidence-based objectification of imputability criteria presents a promising opportunity for standardization and enhanced clinical decision-making in haemovigilance, such as the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and Naranjo scale in pharmacovigilance.2, 3 The integration of a patient-centred approach with the scientific method presents a viable path towards the development of a more comprehensive and effective haemovigilance system.
Presently, the imputability assessment is predicated upon the identification of an adverse reaction following an event such as a blood transfusion or donation, which may be attributable to a multitude of other factors. These factors encompass blood component-specific, blood donor-specific, recipient-specific, procedural-specific, and environmental factors.4 The multifaceted nature of this event necessitates a structured approach to discern genuine transfusion-related adverse events from alternative causes.
The Haemovigilance Working Party of the International Society of Blood Transfusion (ISBT) has established a comprehensive set of standardized definitions, underscoring the temporal correlation between transfusion and adverse reactions. These definitions encompass five primary imputability categories: definite (certain), probable (likely), possible, unlikely (doubtful), and excluded.5
Regulatory bodies such as the UK Serious Hazards of Transfusion (SHOT), the US National Healthcare Safety Network (NHSN), and the Haemovigilance Program of India (HvPI), have implemented robust reporting systems that rely on imputability assessment for effective haemovigilance.6 Imputability assessments also carry legal liability, as numerous healthcare institutions are subject to growing scrutiny regarding adverse reactions in transfusion recipients and blood donors.
Both donor and patient haemovigilance systems demonstrate numerous instances where structured evidence-based approaches facilitate the identification of risk factors and the development of effective mitigation strategies for adverse reactions.
The identification of the transfusion related acute lung injury (TRALI) risk factors serves as a prominent example of how systematic imputability assessment drives efforts to enhance patient safety. It has been demonstrated that transfusion of female donor plasma carries an unusual odds ratio of 4.5 (95% CI: 1.85-11.2) for the development of TRALI.7 The two hit theory for TRALI demonstrates systematic understanding in the imputability assessment. The patient’s underlying risk factors, including liver surgery, chronic alcohol abuse, shock, current smoking, and elevated cytokines, develop an inflammatory condition that causes acute lung injury when combined with antibody-mediated HNA activation. This approach resulted in a reduction in the incidence of TRALI from 2.57 per 10,000 transfused units in 2006 to 0.81 per 10,000 units in 2009.7
Analogous to TRALI, a systematic imputability assessment conducted on blood donors revealed the risk factors associated with vasovagal reactions (VVR). Demographic factors, such as younger age (18-30 years), female sex (4-5 times higher incidence), and first-time donation, consistently demonstrated a pattern of association with VVR. Psychological factors, including donation-related anxiety (OR: 4.1, 95% CI: 2.4-7.7) and poor sleep quality the night prior to donation (OR: 4.4, 95% CI: 2.8-6.9), were identified as modifiable risk factors through the imputability assessment.8
The current approach to imputability assessment is primarily subjective. This subjectivity leads to significant variability between different observers, making the assessment process inconsistent. As a result, the outcomes are often limited to “possible” or “probable” correlations, rather than providing definitive conclusions. Despite these limitations, there are future possibilities for improving imputability assessment. The development and adoption of more objective, structured, and standardized criteria could address current challenges. Such advancements are expected to reduce inter-observer variability, provide clearer categorization of adverse event causality, and enhance the overall effectiveness of haemovigilance systems (Figure 1).
Figure 1: Current limitations, future possibilities and expected benefits of Imputability assessment.
Conclusion
Imputability assessment is a crucial component of an effective haemovigilance system. It fulfils multiple critical functions, including risk identification, quality assurance, regulatory compliance, and medico-legal considerations. The objectivity of the imputability criteria presents an opportunity for substantial improvement in the haemovigilance system. Analogous to pharmacovigilance and epidemiological imputability assessment principles, objective scoring systems can enhance the reliability, consistency, and clinical utility of imputability assessment.
References
1. de Vries RR, Faber JC, Strengers PF; Board of the International Haemovigilance Network. Haemovigilance: an effective tool for improving transfusion practice. Vox Sang 2011; 100:60–7.
2. World Health Organization (WHO)-Uppsala Monitoring Centre. The use of the WHO-UMC system for standardized case causality assessment. https://www.who.int/docs/default-source/medicines/pharmacovigilance/whocausality-assessment.pdf; accessed on 20/08/2025
3. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.
4.https://www.cdc.gov/nhsn/pdfs/biovigilance/bv-hv-protocol-current.pdf accessed on 20/08/2025
5. Proposed standard definitions for surveillance of non infectious adverse transfusion reactions, Haemovigilance working party;https://www.isbtweb.org/asset/0FA5485B-5DCC-4E85-A3D61CE8DB17D504/ Accessed on 20/08/2025
6.https://nib.gov.in/haemovigilance/HvPI_website/toolkit_imputability.html;
7. Toy P, Gajic O, Bacchetti P, et al, for the TRALI Study Group; Transfusion-related acute lung injury: incidence and risk factors. Blood 2012; 119 (7): 1757–1767.
8. Wu Y, Qi H, Di Angelantonio E, Kaptoge S, Wood AM, Kim LG. Risk factors for vasovagal reactions in blood donors: A systematic review and meta-analysis. Transfusion. 2025 Jan;65(1):211-223.
