The vaso-occlusive pain crisis in sickle cell disease: Definition, pathophysiology, and management

Eur J Haematol. 2020 Sep;105(3):237-246. doi: 10.1111/ejh.13430. Epub 2020 May 19.


Early diagnosis, treatment, and prevention of a vaso-occlusive crisis (VOC) are critical to the management of patients with sickle cell disease. It is essential to differentiate between VOC-associated pain and chronic pain, hyperalgesia, neuropathy, and neuropathic pain. The pathophysiology of VOCs includes polymerization of abnormal sickle hemoglobin, inflammation, and adhesion. Hydroxyurea, L-glutamine, crizanlizumab, and voxelotor have been approved by the US Food and Drug Administration for reducing the frequency of VOCs; the European Medicines Agency has approved only hydroxyurea. Other novel treatments are in late-stage clinical development in both the United States and the European Union. The development of agents for prevention and treatment of VOCs should be driven by our understanding of its pathophysiology.

Keywords: L-glutamine; P-selectin; hydroxyurea; pain; sickle cell disease.

Publication types

  • Review

MeSH terms

  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / complications*
  • Anemia, Sickle Cell / drug therapy
  • Antisickling Agents / pharmacology
  • Antisickling Agents / therapeutic use
  • Biomarkers
  • Clinical Decision-Making
  • Diagnosis, Differential
  • Disease Management
  • Disease Susceptibility*
  • Humans
  • Pain / diagnosis*
  • Pain / etiology*
  • Pain / prevention & control
  • Pain Management*
  • Pain Measurement*
  • Prognosis
  • Risk Factors
  • Treatment Outcome


  • Antisickling Agents
  • Biomarkers