Platelet Dysfunction and Intracerebral Hemorrhage in a Patient Treated with Empiric Piperacillin-Tazobactam in the Neurocritical Care Unit

World Neurosurg. 2018 Jun:114:204-210. doi: 10.1016/j.wneu.2018.03.080. Epub 2018 Mar 16.


Background: Piperacillin-tazobactam is common empiric antibiotic therapy. Hematologic laboratory test abnormalities were documented but rare in premarketing studies, and whether these alterations are of clinical significance has been studied little. Very few cases of piperacillin-induced bleeding, thrombocytopenia, or both have been reported; aberrations in platelet function have not been implicated.

Case description: A 55-year old Vietnamese man with hypertension presented for treatment of an Intracranial hemorrhage. Platelet function assays (PFAs) at the time of external ventricular drain and quad-lumen bolt placement were normal, and imaging showed no hemorrhage after placement. The patient was later started on empiric piperacillin-tazobactam due to high suspicion for aspiration pneumonia. After removal of the quad-lumen bolt and external ventricular drain on separate days, both follow-up computed tomography scans showed new hematomas in the devices' tracts, with significant intraventricular hemorrhage. Repeat PFAs were abnormally prolonged, representing a distinct change from baseline. A trend toward normalization of PFAs was observed 6 hours after discontinuation of piperacillin-tazobactam with progression toward baseline thereafter.

Conclusions: This is unique in that the significant bleeding that occurred was attributable to platelet dysfunction rather than thrombocytopenia. This is the first reported case of intracranial (periprocedural) hemorrhage potentially related to piperacillin-tazobactam; further research into this drug's impact upon qualitative platelet function is needed.

Keywords: Adverse drug reaction; Intracranial hemorrhage; Platelets.

Publication types

  • Case Reports

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Blood Platelet Disorders / chemically induced*
  • Blood Platelet Disorders / diagnostic imaging
  • Blood Platelet Disorders / therapy
  • Blood Platelets / drug effects
  • Blood Platelets / physiology
  • Cerebral Hemorrhage / chemically induced*
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / therapy
  • Critical Care / methods*
  • Empirical Research*
  • Humans
  • Male
  • Middle Aged
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / adverse effects
  • Penicillanic Acid / analogs & derivatives*
  • Piperacillin / administration & dosage
  • Piperacillin / adverse effects
  • Piperacillin, Tazobactam Drug Combination
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Piperacillin