Healing: the vascular response

Sep 29, 2021

The vascular response: Hemostasis and coagulation

The first stage of healing

The first stage of physiological wound healing is devoted to hemostasis (the process of stopping bleeding) and the formation of a temporary wound matrix . It occurs immediately after the injury and ends after a few hours. Also, this phase initiates the inflammatory process . Sometimes this phase is also described as the "latency phase". During this phase, the body must manage the recruitment of the many cells and factors necessary for the wound healing process . When a skin injury reaches the epidermal layer , blood and lymphatic vessels are also damaged. This will then clean the wound and eliminate microorganisms.

Coagulation cascades

The different coagulation cascades (formation of blood clots) are initiated by coagulation factors (extrinsic system) and platelets . They are activated to allow blood to clump together and limit bleeding (intrinsic system). At the same time, injured vessels undergo a 5-10 minute vasoconstriction (tightening), triggered by platelets, to reduce blood loss and fill the tissue void with a blood clot composed of cytokines and growth factors .

Provisional matrix

The blood clot contains molecules of fibrin, fibronectin, vitronectin and thrombospondins. These molecules form the temporary matrix , a scaffolding structure for the migration of leukocytes (white blood cells), keratinocytes (skin cells), fibroblasts (precursor of connective tissue) and endothelial cells. This vasoconstriction, however, is responsible for local perfusion failure with consequent lack of oxygen , increased glycolysis (loss of energy) and changes in pH. Vasoconstriction is then followed by vasodilation, during which platelets invade the temporary wound matrix . In addition, platelets influence white blood cell infiltration through the release of several factors. Both platelets and leukocytes release cytokines and growth factors to:
  • activate the inflammatory process (IL-1α, IL-1β, IL-6 and TNF-α),
  • stimulate collagen synthesis (FGF-2, IGF-1, TGF-β),
  • activate the transformation of fibroblasts into myofibroblasts (TGF-β),
  • trigger angiogenesis (FGF-2, VEGF-A, HIF-1α, TGF-β) and,
  • already support the skin reconstruction process (EGF, FGF-2, IGF-1, TGF-α).
Vasodilation can also be recognized by local redness (hyperemia) and wound edema.

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