Pharmacological Correction of Cisplatin-Induced Hemostatic Disorders

Bull Exp Biol Med. 2021 Mar;170(5):623-626. doi: 10.1007/s10517-021-05119-1. Epub 2021 Mar 31.

Abstract

A single intraperitoneal administration of cisplatin in the MTD to outbred female mice disturbed hemostasis and formed the procoagulant phenotype of hemostatic potential on days 7-10 culminating in a pronounced hypocoagulation on day 15. Hemostasis was corrected with warfarin and an extract containing furocoumarins composed of isopimpinellin (42.97%), bergapten (35.18%), and xanthotoxin (15.41%). The extract was standardized with gas chromatography-mass spectrometry, thin-layer chromatography, and HPLC. Furocoumarins and reference drug warfarin were administered intragastrically during 4 days starting on day 6 after the administration of cisplatin. Both furocoumarins and warfarin corrected hypercoagulation on days 7-10. On day 10, furocoumarins normalized coagulation, whereas warfarin resulted in hypocoagulation. On days 15-30, no effects of warfarin were observed. furocoumarins corrected hypocoagulation on days 15-20 with prolongation of this effect up to experimental day 30.

Keywords: cisplatin; furocoumarins; hemostatic potential; low-frequency piezothromboelastography; outbred mice.

MeSH terms

  • 5-Methoxypsoralen / therapeutic use
  • Animals
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Cisplatin / toxicity*
  • Female
  • Furocoumarins / therapeutic use*
  • Gas Chromatography-Mass Spectrometry
  • Hemostatic Disorders / chemically induced*
  • Hemostatic Disorders / drug therapy*
  • Methoxsalen / therapeutic use
  • Mice
  • Rats
  • Warfarin / therapeutic use*

Substances

  • Furocoumarins
  • isopimpinellin
  • 5-Methoxypsoralen
  • Warfarin
  • Cisplatin
  • Methoxsalen