---
title: "Unfractionated and Low‑Molecular‑Weight Heparin in Sepsis: Survival, Bleeding, and Biomarker Effec"
id: "pubmed-42765897"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42765897"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42765897/"
doi: "10.1002/jcla.70355"
published_at: "2026-09-21T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Unfractionated and Low‑Molecular‑Weight Heparin in Sepsis: Survival, Bleeding, and Biomarker Effec
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42765897
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42765897/)
- **DOI:** [10.1002/jcla.70355](https://doi.org/10.1002%2Fjcla.70355)
- **Published At:** 2026-09-21T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This retrospective propensity score–matched cohort study compared **unfractionated heparin (UFH)**, **low‑molecular‑weight heparin (LMWH)**, and no anticoagulation in 1,362 sepsis patients to evaluate anticoagulant and anti‑inflammatory effects. - After matching, comparisons included 109 patients for the UFH analysis and 394 patients for the LMWH analysis against no anticoagulation. - Both UFH and LMWH were associated with significantly improved survival versus no anticoagulation (p < 0.001) without an increased 90‑day bleeding risk. - Twenty‑two biomarkers were measured at baseline and on days 1, 3, and 7 after anticoagulation to track coagulation and inflammatory responses. - UFH was associated with significant reductions in **FDP**, **D‑dimer**, **IL‑6**, **IL‑8**, and **CRP** (FDR‑adjusted p < 0.001), indicating combined anticoagulant and anti‑inflammatory effects. - LMWH was associated with significant reductions only in **FDP** and **D‑dimer**, suggesting a predominantly anticoagulant effect. - Mediation analysis showed that UFH's survival benefit was partially mediated by reductions in **IL‑6** (30.9% of total effect, p = 0.012) and **IL‑8** (29.6% of total effect, p = 0.045). - LMWH's survival benefit was not significantly mediated by any measured biomarker in this analysis. - UFH was administered intravenously and LMWH subcutaneously at standard doses; detailed dosing and additional protocol specifics were not provided in the abstract. - Trial registration: Chinese Clinical Trial Registry ChiCTR2100045167 (retrospectively registered 06 April 2021).
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Online ahead of print. # Unfractionated Heparin and Low-Molecular-Weight Heparin in Sepsis: Anti-Inflammatory and Anticoagulant Effects Versus No Anticoagulation-A Propensity Score-Matched Analysis [Peili Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+P&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Yi Yao](https://pubmed.ncbi.nlm.nih.gov/?term=Yao+Y&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Bing Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+B&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Yuan An](https://pubmed.ncbi.nlm.nih.gov/?term=An+Y&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Jian Jiang](https://pubmed.ncbi.nlm.nih.gov/?term=Jiang+J&cauthor_id=42765897)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-2 "Department of Emergency, The First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China."), [Li Ma](https://pubmed.ncbi.nlm.nih.gov/?term=Ma+L&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Enqiang Mao](https://pubmed.ncbi.nlm.nih.gov/?term=Mao+E&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Yihui Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#full-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.") Affiliations Expand ### Affiliations * 1 Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. * 2 Department of Emergency, The First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. * PMID: **42765897** * DOI: [ 10.1002/jcla.70355 ](https://doi.org/10.1002/jcla.70355) Item in Clipboard # Unfractionated Heparin and Low-Molecular-Weight Heparin in Sepsis: Anti-Inflammatory and Anticoagulant Effects Versus No Anticoagulation-A Propensity Score-Matched Analysis Peili Chen et al. J Clin Lab Anal. 2026. Show details Display options Display options Format Abstract PubMed PMID J Clin Lab Anal Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Clin+Lab+Anal%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Clin+Lab+Anal%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42765897/) . 2026 Sep 21:e70355. doi: 10.1002/jcla.70355. Online ahead of print. ### Authors [Peili Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+P&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Yi Yao](https://pubmed.ncbi.nlm.nih.gov/?term=Yao+Y&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Bing Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+B&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Yuan An](https://pubmed.ncbi.nlm.nih.gov/?term=An+Y&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Jian Jiang](https://pubmed.ncbi.nlm.nih.gov/?term=Jiang+J&cauthor_id=42765897)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-2 "Department of Emergency, The First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China."), [Li Ma](https://pubmed.ncbi.nlm.nih.gov/?term=Ma+L&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Enqiang Mao](https://pubmed.ncbi.nlm.nih.gov/?term=Mao+E&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."), [Yihui Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42765897)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42765897/#short-view-affiliation-1 "Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.") ### Affiliations * 1 Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. * 2 Department of Emergency, The First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. * PMID: **42765897** * DOI: [ 10.1002/jcla.70355 ](https://doi.org/10.1002/jcla.70355) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Given the controversy surrounding anticoagulation therapy in sepsis, this study evaluated the efficacy of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) compared with no anticoagulation in sepsis management, considering their potential benefits beyond anticoagulation. **Methods:** In this retrospective cohort study, 1362 sepsis patients were stratified into no anticoagulation, UFH, or LMWH groups. Propensity score matching balanced baseline characteristics. UFH was administered intravenously and LMWH subcutaneously at standard doses. Twenty-two biomarkers were assessed at baseline and days 1, 3, and 7 post-anticoagulation. Survival and bleeding were evaluated using Kaplan-Meier curves. Generalized linear mixed models identified treatment-associated biomarkers, and mediation analysis evaluated their role in survival benefit. **Results:** After matching, 109 and 394 patients were included in the UFH and LMWH comparisons, respectively. Both UFH and LMWH were associated with significantly improved survival versus the no anticoagulation group (p < 0.001), without increased 90-day bleeding risk. UFH was associated with significant reductions in FDP, D-dimer, IL-6, IL-8, and CRP (FDR-adjusted p < 0.001), whereas LMWH was associated with significant reductions only in FDP and D-dimer. Mediation analysis demonstrated that UFH's survival benefit was partly mediated by IL-6 and IL-8 reduction, accounting for 30.9% (p = 0.012) and 29.6% (p = 0.045) of the total effect. LMWH's survival benefit was not significantly mediated by any measured biomarker. **Conclusions:** Both UFH and LMWH improved survival in sepsis patients without increasing bleeding risk. However, UFH demonstrated broader anti-inflammatory effects, with survival benefit partially explained by IL-6/IL-8 suppression. LMWH's benefit appeared primarily anticoagulant-mediated. **Trial registration:** Chinese Clinical Trial Registry, ChiCTR2100045167. Registered 06 April 2021, retrospectively registered. **Keywords:** anticoagulation; generalized linear mixed model; low‐molecular‐weight heparin; mediation effect; sepsis; unfractionated heparin. © 2026 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## References 1. 1. P. Chen, Y. Ge, H. Sheng, et al., “The Role of Early Changes in Routine Coagulation Tests in Predicting the Occurrence and Prognosis of Sepsis,” World The Journal of Emergency Medicine 16, no. 2 (2025): 136–143, [https://doi.org/10.5847/wjem.j.1920‐8642.2025.036](https://doi.org/10.5847/wjem.j.1920%E2%80%908642.2025.036). 2. 1. G. R. Bernard, J. L. Vincent, P. F. Laterre, et al., “Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis,” New England Journal of Medicine 344, no. 10 (2001): 699–709. 3. 1. B. L. Warren, A. Eid, P. Singer, et al., “Caring for the Critically Ill Patient. High‐Dose Antithrombin III in Severe Sepsis: A Randomized Controlled Trial,” Journal of the American Medical Association 286, no. 15 (2001): 1869–1878. 4. 1. A. Rhodes, L. E. Evans, W. Alhazzani, et al., “Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016,” Intensive Care Medicine 43, no. 3 (2017): 304–377, [https://doi.org/10.1007/s00134‐017‐4683‐6](https://doi.org/10.1007/s00134%E2%80%90017%E2%80%904683%E2%80%906). 5. 1. WHO‐2019‐nCoV‐clinical‐2020.5 [Internet], [https://www.who.int/zh/news‐room/detail/11‐05‐2020‐who‐statement‐tobacco...](https://www.who.int/zh/news%E2%80%90room/detail/11%E2%80%9005%E2%80%902020%E2%80%90who%E2%80%90statement%E2%80%90tobacco%E2%80%90use%E2%80%90and%E2%80%90covid%E2%80%9019). Show all 38 references ## Grants and funding * [ Ministry of Finance and National Administration of Traditional Chinese Medicine Project Clinical Study of Traditional "Chinese Medicine Intestinal MaManagement Program in the Treatment of Sepsis" ](https://pubmed.ncbi.nlm.nih.gov/?term=Ministry+of+Finance+and+National+Administration+of+Traditional+Chinese+Medicine+Project+Clinical+Study+of+Traditional+%22Chinese+Medicine+Intestinal+MaManagement+Program+in+the+Treatment+of+Sepsis%22%5BGrants+and+Funding%5D&sort=date&sort_order=desc "All articles for grant Ministry of Finance and National Administration of Traditional Chinese Medicine Project Clinical Study of Traditional "Chinese Medicine Intestinal MaManagement Program in the Treatment of Sepsis"") * [ 2-1-2/Three-Year Action Plan for Further Accelerating the Inheritance, Innovation and Development of Traditional Chinese Medicine (2025-2027) Project ](https://pubmed.ncbi.nlm.nih.gov/?term=2-1-2%2FThree-Year+Action+Plan+for+Further+Accelerating+the+Inheritance%2C+Innovation+and+Development+of+Traditional+Chinese+Medicine+%282025-2027%29+Project%5BGrants+and+Funding%5D&sort=date&sort_order=desc "All articles for grant 2-1-2/Three-Year Action Plan for Further Accelerating the Inheritance, Innovation and Development of Traditional Chinese Medicine \(2025-2027\) Project") * [ RKZ2023ZR-013[Z]/Natural Science Foundation (Joint) Project of Shigatse City ](https://pubmed.ncbi.nlm.nih.gov/?term=RKZ2023ZR-013%5BZ%5D%2FNatural+Science+Foundation+%28Joint%29+Project+of+Shigatse+City%5BGrants+and+Funding%5D&sort=date&sort_order=desc "All articles for grant RKZ2023ZR-013\[Z\]/Natural Science Foundation \(Joint\) Project of Shigatse City") * [ XZ2023ZR-ZY35[Z]/Xizang Autonomous Region Natural Science Foundation Group Medical Aid Project ](https://pubmed.ncbi.nlm.nih.gov/?term=XZ2023ZR-ZY35%5BZ%5D%2FXizang+Autonomous+Region+Natural+Science+Foundation+Group+Medical+Aid+Project%5BGrants+and+Funding%5D&sort=date&sort_order=desc "All articles for grant XZ2023ZR-ZY35\[Z\]/Xizang Autonomous Region Natural Science Foundation Group Medical Aid Project") * [ 24DX2800200/Clinical efficacy and mechanism study of high-dose intravenous vitamin C in the treatment of severe acute pancreatitis ](https://pubmed.ncbi.nlm.nih.gov/?term=24DX2800200%2FClinical+efficacy+and+mechanism+study+of+high-dose+intravenous+vitamin+C+in+the+treatment+of+severe+acute+pancreatitis%5BGrants+and+Funding%5D&sort=date&sort_order=desc "All articles for grant 24DX2800200/Clinical efficacy and mechanism study of high-dose intravenous vitamin C in the treatment of severe acute pancreatitis") [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM **Send To** * [Clipboard](https://pubmed.ncbi.nlm.nih.gov/42765897/) * [Email](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42765897%2F%23open-email-panel) * [Save](https://pubmed.ncbi.nlm.nih.gov/42765897/) * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42765897%2F%23open-bibliography-panel) * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42765897%2F%23open-collections-panel) * [Citation Manager](https://pubmed.ncbi.nlm.nih.gov/42765897/) [x] NCBI Literature Resources [MeSH](https://www.ncbi.nlm.nih.gov/mesh/) [PMC](https://www.ncbi.nlm.nih.gov/pmc/) [Bookshelf](https://www.ncbi.nlm.nih.gov/books) [Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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