Journal Article

Liver toxicity of intravenous heparin treatment in patients with acute ischemic stroke

Kamimura, Hidetoshi, Shibaguchi, Hirotomo, Oyabu, Kohei, Yasutaka, Yuki, Tsuboi, Yoshio, Fujioka, Shinsuke

2023

Overview

Serum alanine aminotransferase (ALT), which is an indicator of liver dysfunction, may increase during treatment in patients in the acute phase of stroke. However, the cause of the ALT elevation is unclear, as multiple medications are often being used. We investigated the relationship between medications used in acute ischemic stroke, including cerebral infarction and transient ischemic attack, and ALT elevation. The subjects were 230 patients who had been diagnosed with cerebral infarction or TIA and treated at the Stroke Care Unit of Fukuoka University Hospital. We investigated ALT abnormalities that occurred from the start of the treatment over the subsequent 14 days. We also followed patients for an additional seven days to confirm the peak ALT levels. A binomial logistic regression analysis was performed to evaluate the association between medications used during the period and ALT elevation. The incidence of ALT abnormality was 23.9% (55/230). ALT elevation was mostly mild and peaked within 21 days of treatment initiation in 93.2% of the patients, excluding indeterminate patients. A binary logistic regression analysis showed that unfractionated heparin (odds ratio [OR] 2.759, 95% confidence interval [CI] 1.328–5.729, p = 0.007) was extracted as a cause of ALT elevation. In a receiver operating characteristic (ROC) analysis for the administration period of unfractionated heparin, the cut-off value (area under the ROC curve) for ALT elevation was 6 days (0.575). Significant factors contributing to ALT elevation caused by unfractionated heparin included an unfractionated heparin administration period of ≥ 6 days (OR 2.951, 95% CI 1.244–7.000, p = 0.014) and edaravone combination (OR 2.594, 95% CI 1.159–5.808, p = 0.021). In the acute phase of stroke, we believe that unfractionated heparin discontinuation is not necessary when hepatotoxicity of unfractionated heparin is suspected. However, physicians should be aware of the risk of liver toxicity when unfractionated heparin is administered for more than six days or when edaravone is used in combination. •The link between medications in the acute ischemic stroke patients and ALT abnormalities was assessed.•The clinical charts of 230 patients in the acute phase of cerebral infarction or transient ischemic attack were reviewed.•A binary logistic regression analysis showed that unfractionated heparin was extracted as a cause of ALT elevation.•Changes in ALT levels should be monitored when heparin is used for more than six days or when edaravone is used in combination.

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Acute ischemic stroke / Alanine aminotransferase / Alanine transaminase / Anticoagulants / Anticoagulants - therapeutic use / Aspirin / Cerebral infarction / Cerebral Infarction - drug therapy / Comparative analysis / Critical care / Edaravone / Enoxaparin / Heparin / Hepatotoxicity / Hospitals / Humans / Intensive care / Ischemia / Ischemic Stroke - drug therapy / Liver / Liver diseases / Liver toxicity / Medical prognosis / Neurology / Neurosurgery / Patients / Regression analysis / Sodium / Stroke / Stroke - epidemiology / Transient ischemic attack / Treatment Outcome / Unfractionated heparin