Using routine health-care data to search for unknown transfusion-transmitted disease: a nationwide, agnostic...

Identification and prevention of transfusion-transmitted disease is essential for blood transfusion safety. However, current surveillance systems are largely driven by reports of sentinel events, which is an approach that might be inadequate for identifying transmission of pathogens not known to be transmissible or pathogens with long incubation periods. Using a combination of health-data registers and blood-bank databases, we aimed to perform an agnostic search for potential transfusion-transmitted diseases and to identify unknown threats to the blood supply.

In this nationwide, agnostic retrospective cohort study, we developed a systematic algorithm for performing a phenome-wide search for transfusion-transmitted disease without consideration of any a-priori suspicion of blood-borne transmissibility. We applied this algorithm to a nationwide Swedish transfusion database (SCANDAT-3S) to test for possible transmission of 1155 disease entities based on all relevant diagnostic coding systems in use during the period. We ascertained health outcomes of blood donors and transfusion recipients from the Swedish National Inpatient Register, Swedish Cause of Death Register, and Swedish Cancer Register. Analyses were two-pronged, studying both disease diagnosis concordance between donors and recipients and a possible shared increased disease risk among all recipients of a given donor. For both approaches, we used Cox proportional hazards regression models with time-dependent covariates. Adjustment for multiple comparisons was done using a false discovery rate method.

The analyses included data on 1·72 million patients who had received 18·97 million transfusions (red blood cell, plasma, platelet, or whole blood units) between Jan 1, 1968, and Dec 31, 2017, from 1·04 million blood donors. The median follow-up was 4·5 (IQR 0·9-11·4) years for recipients and 18·5 (8·3-26·2) years for donors. We found evidence of transfusion-transmission for 15 diseases, of which 13 were validated using a second conceptually different approach. We identified transmission of viral hepatitis and its complications (eg, oesophageal varices) but also transmission of other conditions (eg, pneumonia of unknown origin). The diseases that could not be validated in this second approach, HIV and abnormal findings in specimens from male genital organs, were not statistically significant after adjustment for multiple testing. The effect sizes were small (close to 1) for other conditions.

We find no strong evidence of unexpected, widespread transfusion-transmitted disease. This novel approach serves as a proof-of-concept for agnostic, data-driven surveillance for transfusion-transmitted disease using routinely collected blood-bank and health-care data.

Department of Health and Human Services, US National Heart, Lung, and Blood Institute, US National Institutes of Health, Swedish Research Council and Region Stockholm.