Combination Therapy Using Prothrombin Complex Concentrate and Vitamin K in Anticoagulated Patients with Traumatic Intracranial Hemorrhage Prevents Progressive Hemorrhagic Injury: A Historically Controlled Study

Neurol Med Chir (Tokyo). 2021 Jan 15;61(1):47-54. doi: 10.2176/nmc.oa.2020-0252. Epub 2020 Nov 19.

Abstract

Warfarin remains crucially involved in the treatment of patients at thrombotic or thromboembolic risk. However, warfarin increases the mortality rate among patients with traumatic intracranial hemorrhage (TICH) through progressive hemorrhagic injury (PHI). Therefore, a rapid anticoagulation reversal could be required in patients with TICH to prevent PHI. Differences in the warfarin reversal effect between combination therapy of prothrombin complex concentrate (PCC) with vitamin K (VK) and VK monotherapy remain unclear. However, studies have reported that PCC has greater effectiveness and safety for warfarin reversal compared with fresh frozen plasma (FFP). This retrospective study aimed to evaluate the warfarin reversal effects of combination therapy of PCC with VK and VK monotherapy on TICH. We compared the clinical outcomes between the periods before and after the PCC introduction in our hospital. There were 13 and 7 patients who received VK monotherapy and PCC with VK, respectively. PHI predictors were evaluated using univariate regression analyses. Warfarin reversal using PCC had a significant negative association with PHI (odds ratio: 0.03, 95% confidence interval: 0.00-0.41, P = 0.004). None of the patients presented with thrombotic complications. Warfarin reversal through a combination of PCC with VK could be more effective for inhibiting post-trauma PHI compared with VK monotherapy. This could be attributed to a rapid and stable warfarin reversal. PCC should be administered to patients with TICH taking warfarin for PHI prevention.

Keywords: Vitamin K; progressive hemorrhagic injury; prothrombin complex concentrate; traumatic intracranial hemorrhage; warfarin reversal.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Blood Coagulation / drug effects*
  • Blood Coagulation Factors / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Historically Controlled Study
  • Humans
  • Intracranial Hemorrhage, Traumatic / drug therapy*
  • Japan
  • Male
  • Retrospective Studies
  • Vitamin K / therapeutic use*
  • Warfarin / adverse effects*
  • Warfarin / antagonists & inhibitors*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Blood Coagulation Factors
  • Vitamin K
  • prothrombin complex concentrates
  • Warfarin