Heparin-induced thrombocytopenia associated with low-molecular-weight heparin: clinical feature analysis of cases and pharmacovigilance assessment of the FAERS database

Leping Liu; Hong Zheng; Shanshan Chen; Shengfeng Wang; Minghua Yang

doi:10.3389/fphar.2023.1247253

Heparin-induced thrombocytopenia associated with low-molecular-weight heparin: clinical feature analysis of cases and pharmacovigilance assessment of the FAERS database

Front Pharmacol. 2023 Sep 20:14:1247253. doi: 10.3389/fphar.2023.1247253. eCollection 2023.

Authors

Leping Liu^#¹, Hong Zheng^#², Shanshan Chen³, Shengfeng Wang^{4

5

6}, Minghua Yang^{1

6

7}

Affiliations

¹ Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Pediatrics, The Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
⁴ Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Postdoctoral Research Station of Clinical Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁶ MOE Key Lab of Rare Pediatric Diseases, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁷ Hunan Clinical Research Center of Pediatric Cancer, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

^# Contributed equally.

Abstract

Background: Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are commonly used anticoagulants for the management of arterial and venous thromboses. However, it is crucial to be aware that LMWH can, in rare cases, lead to a dangerous complication known as heparin-induced thrombocytopenia (HIT). The objective of this study was to evaluate the pharmacovigilance and clinical features of HIT associated with LMWH, as well as identify treatment strategies and risk factors to facilitate prompt management. Methods: We extracted adverse event report data from the FDA Adverse Event Reporting System (FAERS) database for pharmacovigilance assessment. Case reports on LMWH-induced thrombocytopenia dated up to 20 March 2023 were collected for retrospective analysis. Results: Significantly elevated reporting rates of HIT were shown in adverse event (AE) data of LMWHs in the FAERS database, while tinzaparin had a higher proportional reporting ratio (PRR) and reporting odds ratio (ROR) than other LMWHs, indicating a greater likelihood of HIT. Case report analysis indicated that a total of 43 patients showed evidence of LMWH-induced thrombocytopenia with a median onset time of 8 days. Almost half of the events were caused by enoxaparin. LMWHs were mainly prescribed for the treatment of embolism and thromboprophylaxis of joint operation. Patients with a history of diabetes or surgery appeared to be more susceptible to HIT. Clinical symptoms were mostly presented as thrombus, skin lesion, and dyspnea. Almost 90% of the patients experienced a platelet reduction of more than 50% and had a Warkentin 4T score of more than 6, indicating a high likelihood of HIT. In all patients, LMWHs that were determined to be the cause were promptly withdrawn. Following the discontinuation of LMWHs, almost all patients were given alternative anticoagulants and eventually achieved recovery. Conclusion: LMWH-induced thrombocytopenia is rare but serious, with increased risk in patients with diabetes or a surgical history. Prompt recognition and management are crucial for the safe use of LMWHs.

Keywords: characteristics; heparin-induced thrombocytopenia; low-molecular-weight heparin; pharmacovigilance; treatments.

Grants and funding

This study was supported by the Hunan Provincial Natural Science Foundation of China (2022JJ30903) and National Natural Science Foundation of China (82202398).