Transfusion Registry at the Bundeswehr Hospital Berlin: Exploring the Long-term Effects of Blood Transfusions and Donations

Jennifer Jersch^a,c1, Katja Schneider^b1, Lorenz Wolf^c, Lars Stephan^d, Amelie Garmatter^e, Kai Zacharowski^a, Michael Benker^c, Rico Müller^d, Benjamin Friedrichson^a, Jan Andreas Kloka^a, Elina Nürenberg-Goloub^a

¹ Jennifer Jersch and Katja Schneider share joint first authorship of this article.

^a Clinic for Anesthesiology, Intensive Care Medicine, and Pain Therapy, University Medicine Frankfurt

^b Clinic for General and Visceral Surgery, Bundeswehr Hospital Berlin

^c Clinic for Anesthesia, Intensive and Emergency Medicine, Bundeswehr Hospital Berlin

^d Laboratory Medicine Department, Bundeswehr Hospital Berlin

^e Clinic for Internal Medicine, Bundeswehr Hospital Berlin

Summary

The transfusion of blood products has evolved from a life-saving emergency treatment into a broad therapeutic and scientific field with complex risks and interactions. Annually, millions of blood products are processed and administered in Germany alone. While modern hemovigilance systems effectively document acute reactions, there is a lack of comprehensive data on long-term health effects. The Blood Donor and Recipient Long-Term Outcome Study (LOS) is establishing a multidisciplinary long-term registry at the Bundeswehr Hospital Berlin to examine health outcomes and develop a scientific foundation for new guidelines in transfusion medicine. This article discusses the scientific basis, study design, and importance of the registry.

Keywords: blood transfusion; long-term outcomes; hemovigilance; blood donors; registry study

Introduction

Blood transfusions are a vital part of modern medicine. The European Union, through its new legislation regulating Substances of Human Origin (SoHO), sets a high standard for documenting all steps from blood donation to transfusion to ensure the best protection for donors and recipients [5]. Acute side effects of blood transfusions, such as febrile non-hemolytic reactions, transfusion-associated circulatory overload (TACO), or transfusion-related acute lung injury (TRALI), are consistently recorded because of national reporting requirements and hemovigilance systems [6]. However, the long-term effects on both recipients and donors are still largely unknown. Epidemiological studies show that transfused patients have a higher mortality rate years later compared to the general population [10]. For donors, questions about iron balance and the physiological and psychological long-term effects remain unanswered.

This article aims to clarify the medical background for long-term studies of donor and recipient populations and to present the Registry Study for Research of Blood Donor and Recipient Long-Term Outcomes (LOS), supported by the Bundeswehr Hospital Berlin to generate evidence-based insights. During crisis situations, when blood is a vital resource for treating the wounded, the epidemiological evidence, study design, and its relevance for Bundeswehr medical personnel are especially important.

Long-term Effects on Transfusion Recipients

Recent meta-analyses show that perioperative transfusions, especially during cardiac and thoracic surgeries, are linked to a long-term increase in mortality [16]. An analysis of 39 studies involving 180,074 patients found that early mortality among transfused patients was nearly four times higher than in non-transfused patients (odds ratio, OR 3.87) [16]. The elevated mortality risk persisted over the long term; follow-ups ranging from 1 to 15 years were included in the studies. After a median follow-up of 6.4 years, the risk of death after a transfusion-related surgery was still twice as high (OR 2.01). A Swedish registry study on gastroesophageal tumors showed that perioperative blood transfusions were associated with a 50% higher risk of death within three years (hazard ratio, HR 1.50), which remained even after excluding 30-day mortality (HR 1.30) [3]. Both analyses do not establish causality as confounding factors cannot be fully ruled out despite statistical adjustments. Accurate data on procedures, indications, and comorbidities are crucial to filling this knowledge gap regarding transfusions.

Beyond mortality, immunological complications are also becoming a focus of research. Alloimmunization against erythrocyte antigens can lead to delayed hemolysis, transfusion delays, and increased morbidity. The development of an immune response depends on patient-related factors such as acute inflammation, chronic diseases, and immunosuppression. Fever, infections, and inflammatory episodes (e.g., acute chest syndrome in sickle cell anemia) increase the risk of alloimmunization, while immunosuppression or asplenia reduce it. Product factors such as storage duration and leukocyte depletion also play a role [1]. These mechanisms underscore the necessity for long-term observations beyond the transfusion point and detailed medical data and records of interventions to understand the impacts of blood transfusions.

Long-term Effects on Blood Donors

Blood donations are for many individuals a recurring act of altruistic care. Ensuring donor health is not only an ethical obligation but also a key requirement for the sustainable continuation of transfusion medicine, as emphasized by the World Health Organization [6]. The “Healthy Donor Effect” (HDE) describes the phenomenon that blood donors are, on average, healthier than the general population. However, this selection can lead to a systematic underestimation of the potential health impacts of blood donation. A Scandinavian cohort study with over 1.18 million blood donors showed that, after adjusting for the HDE, there was a 7.5% lower mortality rate per additional annual donation [14]. Regarding specific diseases, a Chinese registry study in male donors found an adjusted relative risk (RR) for malignant diseases of 0.82; notably, a lower risk was observed for liver, lung, and esophageal cancers, while the risk for brain tumors was slightly higher (RR 1.19) [13]. An Australian study involving over 4,000 donors did not demonstrate an increased cardiovascular risk [9].

Of particular importance for donor safety is preventing iron deficiency, the most common result of regular blood donations [2]. Premenopausal female donors are also at increased risk due to menstrual bleeding: heavy menstrual bleeding was linked to a 3.56-fold higher risk of anemia in a Dutch study of 473 premenopausal donors [4]. A Finnish study of 79,157 donors who were deferred from donation because of low hemoglobin showed that 84.5% of those affected did not recover hemoglobin levels even with extended donation intervals, with women showing a lower recovery rate of 14.4% compared to 17.6% in men [11]. Women also reported more frequent negative post-donation symptoms such as fatigue and dizziness (19% vs. 8% in men) [12]. In addition to physiological factors, mental health also impacts the donor experience: donors with better self-reported mental health had a higher donation frequency [8].

The systematic quantification of physiological and psychological risks and risk factors is vital for developing evidence-based guidelines for all donors, especially vulnerable populations, to ensure that patients receive long-term access to essential blood and blood products. As whole blood donation becomes increasingly important, particularly in deployment-related situations, tracking donor and patient histories is becoming more critical. Systematic documentation in the transfusion registry allows for the identification, assessment, and translation of potential short- and long-term effects of whole blood donation into informed donor guidelines.

Methodology and Study Design of the LOS ­Registry

Objectives

The goal of the LOS is to systematically record and scientifically examine the long-term impacts of blood transfusions and donations. Data on interventions, transfusion indications, blood products, acute reactions, demographics, comorbidities, and long-term health measures (such as pregnancy outcomes, new oncological and cardiovascular diseases, neurological deficits, fitness, and frailty) will be collected. For donors, information on repeated donations, mental health, nutrition, activity, quality of life, psychosocial factors, and gender-specific health data will also be documented [7].

Structure, Process, and Data Storage

The registry is designed to be prospective and non-interventional; both national and international collaborations are encouraged. All blood donors and transfusion recipients, regardless of age or gender, can participate after providing consent. Exclusion criteria only apply in cases where consent is not given [7]. Patient data is managed in a digital system following the “Findable, Accessible, Interoperable, Reusable” (FAIR) principles. The transfusion registry is accessible online without requiring additional software installation. Medical staff enter patient information and relevant medical data into the system. Patients receive a link to a health questionnaire after three months of enrollment and then annually. This questionnaire is created to be understandable for laypersons and enables standardized data collection through multiple-choice questions (Figure 1). For blood donors, self-registration with regular automated reminders for the questionnaires is planned.

 

Figure 1: Structure and Workflow of the LOS:
(A) Medical personnel captures essential medical data in clinical episodes following patient consent, while patients regularly report their health status in standardized questionnaires.
(B) The collected data can be used for medical and health-economic research and to improve care.
(C) The document collection on the LOS website transfusionregistry.org contains all important forms and extensive informational material in PDF format (QR-Code). The website also informs doctors, patients, policymakers, scientists, and the public about the study, partner clinics, the current EU SoHO regulation, and many other relevant topics.

Participants’ medical and identifying data are stored separately on servers at Johann Wolfgang Goethe University Frankfurt and are linked by a pseudonym. The pseudonymized data is available for research and is strictly handled in accordance with the General Data Protection Regulation (GDPR). Clinic physicians can access their patients’ medical data, for example, to monitor recovery after certain procedures.

Ethics, Governance, and Data Use

The LOS has received a positive ethical approval from the University Medicine of Johann Wolfgang Goethe University Frankfurt. The study documents – such as information and consent forms, data protection details, flyers, and the data protection plan – have been reviewed by the Ethics Committee and the Data Protection Officer and have been provided to the participating centers. Data use follows a collaborative governance model involving study leadership, a scientific advisory board, and a general assembly, allowing participating centers to be involved. Participating centers receive detailed annual reports on blood products used and patient data. Additionally, independent research on extracted data is possible for participating clinics. The scientific advisory board, composed of physicians and scientists, reviews research proposals to ensure the protection and proper use of patient data.

Expected Results and Insights

Since the registry is still under development, no evaluated data is available yet. Based on existing literature, the following insights are anticipated:

• Survival rates and morbidity after transfusions: Registry data should quantify potential long-term mortality and identify key influencing factors such as transfusion indication, comorbidities, product type, storage duration, and transfusion environment [2][8][16].
• Immunological complications: The registry allows prospective recording of the effects of alloimmunizations and delayed hemolytic transfusion reactions. It can assess how inflammatory states, chronic diseases, and product characteristics influence alloantibody formation over time [14].
• Cancer and cardiovascular risk in donors: The large cohort enables refinement of the risk ratios for tumors and cardiovascular diseases reported in China and Australia [9][13].
• Donor health aspects: Important considerations such as mental health, well-being, donor behavior, and reproductive and gender health can be analyzed, and donors can participate in the research [2][4][8][11][12].
• Quality indicators and benchmarking: Comparing different clinics allows for deriving quality metrics such as transfusion frequency and complication rates. This facilitates data-driven improvements in transfusion medicine processes within the Bundeswehr.

Discussion

The studies presented highlight that while blood transfusions are acutely life-saving, they can have long-term effects on recipients. Mechanisms such as transfusion-associated immunosuppression, inflammatory reactions, and storage damage to erythrocytes may contribute to increased long-term mortality [1]. Most available evidence comes from retrospective registry analyses; randomized studies are absent because transfusions are often essential. However, prospective data collection helps control influencing factors and develop hypotheses. For donors, studies show mixed results: while mortality and overall cancer risk tend to be lower, certain tumor types [13] and iron deficiency leading to anemia [11][12] may be promoted by frequent donations. Mental health and donor satisfaction are crucial for sustainable transfusion medicine but have been rarely studied so far.

Conclusion

The inclusion of the Bundeswehr provides additional perspectives: Soldiers are transfused in specific operational situations, allowing the registry to also assess long-term trauma-related effects. For medical personnel, the registry offers practical feedback on transfusion indications, complications, and outcomes, supporting training and quality improvements to enhance patient safety. Health-economic insights can also be gained to sustainably improve care. To do this, patients must be informed, and their data collected by medical personnel in the transfusion registry.

Key Points

• Legal Situation: The EU strictly regulates all transfusion-related processes and mandates 30 years of data retention. The WHO highlights donor protection.
• Long-term Risks: Research indicates increased long-term mortality following transfusions, though the causes remain poorly understood.
• Immunological Complications: Alloimmunizations are influenced by patient and product factors; inflammation raises the risk.
• Donor Health: Blood donations are generally safe, but some groups benefit from tailored donor guidelines.
• Digital Registry (LOS): The registry seeks to bridge knowledge gaps on the long-term effects of transfusions and donations, adhering to high ethical and technical standards.
• Significance for the Bundeswehr: It aids in quality improvement, evidence-based decision-making, and research, contingent on consistent education and data collection.

References

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Manuscript Data

Citation

Jersch J, Schneider K, Wolf L, Stephan L, Garmatter A, Zacharowski K, Benker M, Müller R, Friedrichson B, Kloka JA, Nürenberg-Goloub E. Transfusion registry at the Military Hospital Berlin: Understanding the long-term effects of blood transfusions and donations.WMM 2026;70(5E):9.

DOI: https://doi.org/10.48701/opus4-874

For the Authors

Major (MC) Dr. Katja Schneider

Department of General Surgery

Bundeswehr Hospital Berlin

Scharnhorstsraße 13, 10115 Berlin

E-Mail: katjaschneider@bundeswehr.org

Major (MC) Dr. Jennifer Jersch

Department of Anesthesiology

Bundeswehr Hospital Berlin

Scharnhorstsraße 13, D-10115 Berlin

E-Mail: jenniferjersch@bundeswehr.org