Recombinant Neorudin for the Prevention of Deep-Vein Thrombosis After Spinal-Cord Injury

Drug Des Devel Ther. 2023 Aug 23:17:2523-2535. doi: 10.2147/DDDT.S408078. eCollection 2023.

Abstract

Background: Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI.

Methods: A rat model of SCI was developed by Allen's method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose-response and time-effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI.

Results: EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose EH group compared with that in the normal-saline group, but were lower than those in the LMWH group.

Conclusion: EH can reduce thrombus formation in a rat model of SCI, and bleeding is decreased significantly compared with that using LMWH. EH may prevent thrombosis after SCI or spinal surgery.

Keywords: low-bleeding anticoagulation; rat model; recombinant neorudin; spinal-cord injury; thrombosis.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Anticoagulants / pharmacology
  • Anticoagulants / therapeutic use
  • Heparin, Low-Molecular-Weight
  • Hirudins
  • Rats
  • Spinal Cord Injuries* / drug therapy
  • Venous Thrombosis* / drug therapy
  • Venous Thrombosis* / prevention & control

Substances

  • Heparin, Low-Molecular-Weight
  • Anticoagulants
  • Hirudins