Platelet-delivered therapeutics

J Thromb Haemost. 2015 Jun:13 Suppl 1:S143-50. doi: 10.1111/jth.12938.

Abstract

We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches.

Keywords: factor VIII; fibrinolysis; gene therapy; hemophilia; platelet; urokinase.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / genetics
  • Blood Coagulation Disorders / therapy*
  • Blood Coagulation Factors / biosynthesis
  • Blood Coagulation Factors / genetics
  • Blood Platelet Disorders / blood
  • Blood Platelet Disorders / genetics
  • Blood Platelet Disorders / therapy*
  • Blood Platelets / metabolism*
  • Factor V Deficiency / blood
  • Factor V Deficiency / genetics
  • Factor V Deficiency / therapy
  • Gene Transfer Techniques*
  • Genetic Predisposition to Disease
  • Genetic Therapy / methods*
  • Hemophilia A / blood
  • Hemophilia A / genetics
  • Hemophilia A / therapy
  • Humans
  • Platelet Transfusion*
  • Treatment Outcome
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / blood
  • Urokinase-Type Plasminogen Activator / genetics

Substances

  • Blood Coagulation Factors
  • Urokinase-Type Plasminogen Activator

Supplementary concepts

  • Quebec platelet disorder