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Background <p>The risk of intracerebral hemorrhage (ICH) hematoma expansion (HE) is highest in the first hours after onset, and coagulopathy is believed to further increase this risk. However, there is a paucity of data comparing the risk of HE over time for various antithrombotic agents.</p> Methods <p>We conducted a retrospective study of spontaneous ICH patients enrolled at a comprehensive stroke center between December 2016 and May 2022, excluding those who underwent surgical evacuation. ICH volumes were calculated using ABC/2 methodology and HE was coded for a ≥ 33% and/or ≥ 6-mL increase in ICH volume. Multivariable logistic regression and Cox proportional hazards models were constructed to evaluate risk of HE among patients exposed to the following antithrombotics: aspirin, P2Y12 inhibitors, aspirin + P2Y12 inhibitors, warfarin, oral factor Xa inhibitors, direct thrombin inhibitors, full dose heparinoids, and combined antiplatelet + anticoagulant.</p> Results <p>Of 319 patients with ICH, 141 (44%) were on an antithrombotic at the time of ICH and 65 (20%) had HE in a median of 10&#xa0;h (interquartile range (IQR) 7–21) from last known normal (LKN). In multivariable logistic regression analyses, the odds of HE decreased by 2% for every hour from LKN (adjusted odds ratio (aOR) 0.98, 95% CI 0.97–0.99, <i>P</i> = 0.038), and HE occurred significantly more often in patients taking combined antiplatelet + anticoagulant (9/24, 38%) compared with those who were not (56/295, 19%, aOR 2.71, 95% CI 1.09–6.73, <i>P</i> = 0.032). No other antithrombotic was significantly associated with HE. In multivariable Cox analysis adjusting for admission National Institutes of Health Stroke Scale (NIHSS), only antiplatelet + anticoagulant use was associated with significantly increased rates of HE (adjusted HR (aHR) 2.33, 95% CI 1.14–4.75, <i>P</i> = 0.020), with the highest probability of HE occurring immediately after ICH onset.</p> Conclusions <p>Use of combined antiplatelet + anticoagulant was associated with a twofold increased hazard of HE, with the highest probability of expansion occurring early after ICH onset. No increased rate of HE was observed for other antithrombotics.</p>

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Risk and Timing of Intracerebral Hemorrhage Expansion Among Patients Treated with Antithrombotic Agents

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Jennifer A. Frontera,
  • Joanna M. Marmo,
  • Bavica Gummadi,
  • Nicholas Mulchan,
  • Harpaul S. Bhamra,
  • Benjamin Brush,
  • D. Ethan Kahn,
  • Lindsey Kuohn,
  • Sok Lee,
  • Ariane Lewis,
  • Melanie Li,
  • Aaron Lord,
  • Rajanandini Muralidharan,
  • Nirmala Raghunath,
  • Ting Zhou,
  • Kara R. Melmed

摘要

Background

The risk of intracerebral hemorrhage (ICH) hematoma expansion (HE) is highest in the first hours after onset, and coagulopathy is believed to further increase this risk. However, there is a paucity of data comparing the risk of HE over time for various antithrombotic agents.

Methods

We conducted a retrospective study of spontaneous ICH patients enrolled at a comprehensive stroke center between December 2016 and May 2022, excluding those who underwent surgical evacuation. ICH volumes were calculated using ABC/2 methodology and HE was coded for a ≥ 33% and/or ≥ 6-mL increase in ICH volume. Multivariable logistic regression and Cox proportional hazards models were constructed to evaluate risk of HE among patients exposed to the following antithrombotics: aspirin, P2Y12 inhibitors, aspirin + P2Y12 inhibitors, warfarin, oral factor Xa inhibitors, direct thrombin inhibitors, full dose heparinoids, and combined antiplatelet + anticoagulant.

Results

Of 319 patients with ICH, 141 (44%) were on an antithrombotic at the time of ICH and 65 (20%) had HE in a median of 10 h (interquartile range (IQR) 7–21) from last known normal (LKN). In multivariable logistic regression analyses, the odds of HE decreased by 2% for every hour from LKN (adjusted odds ratio (aOR) 0.98, 95% CI 0.97–0.99, P = 0.038), and HE occurred significantly more often in patients taking combined antiplatelet + anticoagulant (9/24, 38%) compared with those who were not (56/295, 19%, aOR 2.71, 95% CI 1.09–6.73, P = 0.032). No other antithrombotic was significantly associated with HE. In multivariable Cox analysis adjusting for admission National Institutes of Health Stroke Scale (NIHSS), only antiplatelet + anticoagulant use was associated with significantly increased rates of HE (adjusted HR (aHR) 2.33, 95% CI 1.14–4.75, P = 0.020), with the highest probability of HE occurring immediately after ICH onset.

Conclusions

Use of combined antiplatelet + anticoagulant was associated with a twofold increased hazard of HE, with the highest probability of expansion occurring early after ICH onset. No increased rate of HE was observed for other antithrombotics.