Acute painful crisis is a common sequela that can cause significant morbidity and negatively impact the quality of life of patients with sickle cell disease (SCD). Plasma levels of several chemokines and cytokines including tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), and interferon γ (IFN-γ) in patients with SCD showed a distinct and statistically significant rise either during painful crisis or at steady state. Plasma levels of various growth factors, including human vascular endothelial growth factor (VEGF), human basic fibroblast growth factor (FGF), and human hepatocyte growth factor (HGF), showed a sustained 2- to 3-fold increase either during painful crisis or at steady state in patients with SCD. Furthermore, plasma levels of the biomarker d-Dimer, a marker of hypercoagulation, showed a 2- to 3-fold increase either during painful crisis or at steady state in patients with SCD as compared to that in healthy participants, suggesting an increased risk of thrombosis.