Bleeding in haemorrhagic fever with renal syndrome: A systematic review characterising the loss of haemostasis in hantavirus infections

A1 PLOS Neglected Tropical Diseases · 2026-07-15 · PUUV

by Matthew J. Riley, Aliza Hudda, Miša Korva, Tatjana Avšič-Županc, Beverley J. Hunt, Tom E. Fletcher Background Haemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses and is associated with variable thrombocytopenia, coagulation abnormalities, and bleeding manifestations. While clinical features have been described in multiple studies, no previous systematic review has synthesised evidence on haemostatic dysfunction in HFRS. This review aimed to characterise the clinical and laboratory features of coagulation disturbances in HFRS to inform understanding of disease mechanisms and future research. Methodology/principal findings We systematically searched MEDLINE, PubMed, CINAHL, Web of Science, and Scopus on 12 December 2024 for studies reporting clinical or laboratory evidence of haemostatic dysfunction in confirmed HFRS. The review protocol was prospectively registered on PROSPERO (CRD42024618760). Observational studies and case series meeting predefined inclusion criteria were eligible. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools and, for one before–after cohort study, the National Institutes of Health (NIH) quality assessment tool. Studies were graded from 1 (lowest) to 3 (highest) based on methodological quality. Due to heterogeneity in study design and outcome reporting, meta-analysis was not feasible. Weighted averages were calculated for laboratory parameters, and data were visualised using bubble and bar plots. Fifty-five studies comprising 7,950 patients were included. Thrombocytopenia was the most consistent abnormality, typically more pronounced in infections with Hantaan (HTNV), Dobrava (DOBV), and Seoul (SEOV) viruses compared with Puumala (PUUV), which was associated with milder disease. Mild prolongation of activated partial thromboplastin time and elevated D-dimer were variably reported. Limited paediatric data suggested milder disease and less pronounced coagulation abnormalities. Conclusions/significance This review provides the first systematic synthesis of haemostatic dysfunction in HFRS. Findings highlight more severe thrombocytopenia and bleeding in HTNV, DOBV, and SEOV infections compared with PUUV. Variable study quality and incomplete reporting limit firm conclusions, underscoring the need for standardised, prospective studies of coagulation and bleeding outcomes.

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