{"doi":"10.1002/jmv.29907","title":"Retroactive blood‐borne pathogens detection of archival clotting factor concentrates throughout the 1970s and 1980s highlights virus contaminations","abstract":"Blood coagulation relies on a cascade of protein-protein interactions that comprise two primary downstream pathways (intrinsic and extrinsic1). Individuals deficient in certain coagulation pathway proteins, also known as clotting factors, may present with primary or secondary bleeding disorders (coagulopathies). For example, hemophilia results from genetic alterations to factors VIII, IX or XI,2 while secondary bleeding disorders may result from dysregulation of clotting factors caused by underlying conditions,3-5 medication use,6 or infection.7-9 Concentrated coagulation factors derived from human blood donations have been made available for treating bleeding disorders since the 1970s.10, 11 However, therapeutic coagulation-factor use was found in the 1980s to be associated with a significantly increased risk of developing disease from the then newly discovered blood-borne pathogens (BBPs), such as human immunodeficiency virus-1 (HIV-1, discovered in 1983) and hepatitis C virus (HCV, discovered in 1990).12-15 Measures were subsequently put into place throughout the mid-to-late 1980s and early 1990s to limit BBP spread to patients, who were using clotting factor products. Those practices included viral detection, viral exclusion and inactivation, and blood donor screening. The degree of viral burden carried by clotting factor products before viral exclusion practices remained unknown with regard to contamination with HCV, HIV-1 and/or other BBPs that had since been found in patients with hemophilia (PWHs).16-19 The authors of a newly published article in the Journal of Medical Virology20 retrospectively identified BBPs present in 24 lyophilized clotting factor samples (14 commercially produced clothing factors and 10 from non-remunerated blood donors) taken from three time periods: 1974–1977, 1981–1985 and 1989–1992. Blood factor products (either single coagulation factor or a combination of the factors) came from commercial and nationalized (British and French blood bank) sources and were sorted by their listed expiration dates (Figure 1), as production date for each of them was not recorded. Using established or in-house developed qPCR assays, the authors intended to test those products for HIV-1, HIV-2, hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV), human pegiviruses 1 and 2 (HPgV1, HPgV2), and the parvoviruses B19V and PARV4. It is important to note that while the authors stated in the abstract that HIV-2 would be part of a panel of BBPs to be tested, they did not report the result of this test in the subsequent sections of the manuscript. It is, therefore, unclear whether this had been done for this study. Regardless, samples identified as positive for HCV or HIV-1 were subjected to Illumina or Sanger sequencing for virus strain detection and for comparison to historic and currently circulating strains of those BBPs. For products with an expiry date as early as 1976, all tested viruses were found, except for HEV. The authors theorized, however, that samples from 1974 to 1975 might all have been tested negative for viral burden due to smaller pools of plasma used for product purification during that period. HIV-1, HAV and HBV were also only identified in 3/24, 1/24 and 1/24 samples, respectively. By 1983-1984, HCV levels peaked several logs higher than 1976 levels and were identifiable in all samples from 1981 to 1985 and were present at relatively low levels in only one sample post 1989. HIV-1 was identified in two samples at relatively low levels (1983 and 1985) and one sample at relatively high levels (1983), which was consistent with the sporadic presence of HIV-121 in clotting factor products tested in the 1980s and was also corresponding with the period of time when the highest numbers of seroconverted PWHs were identified in the UK.22 HAV and HBV were only detected in a single sample each and none were positive for HEV. These findings suggest that while PWHs w","journal":"Journal of Medical Virology","year":2024,"id":502824,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":233282,"name":"Hinh Ly","orcid":"0000-0001-8271-2033","position":1,"is_corresponding":false},{"id":233278,"name":"Morgan Brisse","orcid":"0000-0002-7040-4495","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:10:27.781502Z","pmid":"39223958","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}