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<p>Severe sepsis-associated thrombocytopenia creates a difficult clinical trade-off between thrombosis prevention and bleeding risk, yet evidence to guide pharmacological prophylaxis when platelet counts are 30,000–50,000/µL remains limited. We conducted a target trial emulation using the MIMIC-IV database, classifying eligible adults with sepsis upon first intensive care unit admission based on whether a predominantly unfractionated heparin (UFH)-based prophylaxis strategy was administered within a 24-hour grace period after platelet counts initially entered this range. Among 938 eligible patients (189 prophylaxis strategy, 749 control strategy), venous thromboembolism (VTE) occurred in 14 and 86 patients, respectively. In the inverse probability-weighted Cox analysis, early administration of this UFH-based prophylaxis was associated with a lower 28-day VTE hazard (adjusted hazard ratio 0.51, 95% confidence interval 0.28–0.92; <i>P</i> = 0.025), though this association was attenuated in certain prespecified sensitivity analyses. Electronic health record-derived major bleeding occurred in 22 and 95 patients, respectively, and no statistically higher hazard was observed under the prophylactic strategy (adjusted hazard ratio 0.74, 95% confidence interval 0.46–1.20; <i>P</i> = 0.220). These findings suggest that early administration of a predominantly UFH-based prophylactic strategy may be associated with a lower VTE risk, without a statistically higher hazard of the electronic health record-derived major bleeding endpoint. Given the observational design, this efficacy signal remains hypothesis-generating rather than definitive and warrants prospective validation.</p> Graphical Abstract <p>Severe sepsis-associated thrombocytopenia (platelet count 30–50 × 10^9/L) creates a difficult bedside trade-off between venous thromboembolism (VTE) prevention and bleeding risk. This graphical abstract summarizes the clinical gap, study rationale, target trial emulation design, and main findings. Using the MIMIC-IV database, 938 eligible adults with sepsis and severe thrombocytopenia on first ICU admission were classified according to whether a predominantly unfractionated heparin (UFH)-based prophylactic strategy was administered within a 24-hour grace period after the first platelet count entered the 30–50 × 10^9/L range (prophylaxis, <i>n</i>=189) or whether no early pharmacological prophylaxis was administered (control, <i>n</i>=749). Follow-up began after the 24-hour grace period and continued for 28 days. In inverse probability-weighted analyses, early administration of this predominantly UFH-based prophylactic strategy was associated with a lower 28-day VTE hazard (14/189 vs. 86/749; HR 0.51, 95% CI 0.28–0.92), while no statistically higher hazard was observed for the electronic health record-derived major bleeding endpoint (22/189 vs. 95/749; HR 0.74, 95% CI 0.46–1.20).</p> <p></p>

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Early prophylactic anticoagulation in patients with severe sepsis-associated thrombocytopenia: a target trial emulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月23日

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  • Mingqi Chen,
  • Jiazhen Xu,
  • Yufan Guo,
  • Yiming Shen,
  • Qiuhua Chen,
  • Xing Wang,
  • Hua Jiang,
  • Linfeng Dai

摘要

Severe sepsis-associated thrombocytopenia creates a difficult clinical trade-off between thrombosis prevention and bleeding risk, yet evidence to guide pharmacological prophylaxis when platelet counts are 30,000–50,000/µL remains limited. We conducted a target trial emulation using the MIMIC-IV database, classifying eligible adults with sepsis upon first intensive care unit admission based on whether a predominantly unfractionated heparin (UFH)-based prophylaxis strategy was administered within a 24-hour grace period after platelet counts initially entered this range. Among 938 eligible patients (189 prophylaxis strategy, 749 control strategy), venous thromboembolism (VTE) occurred in 14 and 86 patients, respectively. In the inverse probability-weighted Cox analysis, early administration of this UFH-based prophylaxis was associated with a lower 28-day VTE hazard (adjusted hazard ratio 0.51, 95% confidence interval 0.28–0.92; P = 0.025), though this association was attenuated in certain prespecified sensitivity analyses. Electronic health record-derived major bleeding occurred in 22 and 95 patients, respectively, and no statistically higher hazard was observed under the prophylactic strategy (adjusted hazard ratio 0.74, 95% confidence interval 0.46–1.20; P = 0.220). These findings suggest that early administration of a predominantly UFH-based prophylactic strategy may be associated with a lower VTE risk, without a statistically higher hazard of the electronic health record-derived major bleeding endpoint. Given the observational design, this efficacy signal remains hypothesis-generating rather than definitive and warrants prospective validation.

Graphical Abstract

Severe sepsis-associated thrombocytopenia (platelet count 30–50 × 10^9/L) creates a difficult bedside trade-off between venous thromboembolism (VTE) prevention and bleeding risk. This graphical abstract summarizes the clinical gap, study rationale, target trial emulation design, and main findings. Using the MIMIC-IV database, 938 eligible adults with sepsis and severe thrombocytopenia on first ICU admission were classified according to whether a predominantly unfractionated heparin (UFH)-based prophylactic strategy was administered within a 24-hour grace period after the first platelet count entered the 30–50 × 10^9/L range (prophylaxis, n=189) or whether no early pharmacological prophylaxis was administered (control, n=749). Follow-up began after the 24-hour grace period and continued for 28 days. In inverse probability-weighted analyses, early administration of this predominantly UFH-based prophylactic strategy was associated with a lower 28-day VTE hazard (14/189 vs. 86/749; HR 0.51, 95% CI 0.28–0.92), while no statistically higher hazard was observed for the electronic health record-derived major bleeding endpoint (22/189 vs. 95/749; HR 0.74, 95% CI 0.46–1.20).