Gabapentin and pregabalin can be associated with clinically relevant bleeding due to disturbed platelet function – Two case reports

Introduction: Gabapentin and pregabalin both act via binding to the α₂δ subunit of voltage gated Ca2+channels. Pan et al. 2007 described that gabapentin inhibits platelet aggregation in vitro through the IP₃-thromboxane A2-Ca2+pathway. Baglio et al. 2020 published an acquired platelet defect associated with gabapentin. Here we report 2 patients with clinically relevant bleeding starting with the intake of gabapentin or pregabalin, respectively.

Method: Platelet aggregation (LTA) and flow cytometry were carried out as part of the patient’s routine diagnostic workup.

Results:Case1 A 39-year-old male patient, who had an amputation accident 3/21 developed a neuropathic pain syndrome. Clinically, the patient reported bleeding onset concomitant with gabapentin intake. Before introducing the drug (tooth extractions 2010, surgery of meniscus 2011 and nasal septum 2016), no bleeding occurred. Medication at examination: Gabapentin 500 mg/day; Metamizole on demand; Ferro sanol. He experienced spontaneous severe epistaxis and bleeding gums nearly every third day, which occurred mainly during sleep and reported occasional bleeding of the anal mucosa. Consecutively he had pallor and iron deficiency. Petechiae were clearly visible under the upper lip and on other mucous membranes. All routine tests of coagulation, vwf and FXIII platelet counts were in the normal range. Flow cytometry revealed normal expression of main platelet membrane receptors and normal activation by strong agonists, TRAP-6, collagen, convulxin, ristocetin. The LTA-pattern was similar as in “aspirin like disease”. The patient discontinued gabapentin for 7 days in 5/24. The clinical course was characterised by a rapid disappearance of the bleeding after 7 days without gabapentin. Platelet LTAs almost normalised. Case 2 A 70-year-old female patient came with nose bleeding, and recurrent haematomas. She reported to have these problems since the start of therapy with pregabalin around 20 years ago, when she was diagnosed with multiple sclerosis, and had no prior uncontrolled bleeding or easy bruising. After a kneearthroplasty in 2004, she suffered massive haemorrhaging, which was treated with red blood cell concentrates and in 2015, she had shoulder surgery accompanied by an extensive haematoma. Medication: pregabalin 325mg/day. Analysis of her platelets and plasma revealed normal coagulation including FXIII, vWf and platelet counts and normal routine platelet flow cytometry parameters. LTA analyses gave an “aspirin like“picture. As the patient needed surgery the therapy with pregabalin was slowly phased out. After 10 days total pregabalin suspension bleeding problems complained of had almost completely disappeared. The patient’s platelets showed now normal functional tests. 3 weeks later her gallbladder was removed without any complications [1] [2].

Conclusion: As bleeding started with gabapentinoid treatment and stopped with discontinuation and in parallel the platelet function tests normalized, these drugs probably play a causal role.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025

• References

• 1 Pan CF. et al. Inhibitory mechanisms of gabapentin, an antiseizure drug, on platelet aggregation. Pharmacy and Pharmacology 2007;
• 2 Baglo T. et al. Acquired platelet defect associated with gabapentin treatment: a case-report. Platelets 2020;