Resolution of a Hematoma from Contusion Injury

Phase 1 - Hemostasis (Minutes to Hours)

• Injured endothelium exposes collagen (types I and IV), which binds platelets via the glycoprotein Ia/IIa receptor complex
• Platelets activate, flatten, and discharge their granule contents - releasing PDGF, TGF-β, VEGF, and von Willebrand factor (vWF)
• Platelet aggregation + circulating fibrinogen polymerizes into a stable fibrin clot (the hematoma itself)
• Concurrent local vasoconstriction limits further extravasation

Phase 2 - Inflammation: Clot and Debris Clearance (Day 1 - ~1 Week)

• First cells recruited to the site
• Release chemokines (CXCL12, etc.) that attract circulating monocytes
• Perform early débridement of dead cells and fibrin fragments
• Begin to undergo apoptosis by 48 hours, signaling monocyte arrival

• Circulating monocytes recruited by neutrophil-derived chemokines differentiate into macrophages at the site
• M1-type macrophages (proinflammatory) phagocytose:
  • Apoptotic neutrophils
  • Red blood cells (RBCs) trapped in the clot
  • Fibrin fragments
  • Dead tissue and cell debris
• As apoptotic cells are cleared, macrophages transition to an M2-type (anti-inflammatory/reparative) phenotype, secreting IL-4, IL-10, IL-13, and TGF-β - signaling the wound to shift from destruction to repair

• Hemoglobin → oxyhemoglobin (bright red, freshly bruised skin)
• → deoxyhemoglobin (dark blue-purple, ~1-2 days)
• → methemoglobin → biliverdin (green tinge, ~4-6 days)
• → bilirubin (yellow-brown tinge, ~6-10 days)
• The iron component is stored locally as hemosiderin (golden-brown granules) in macrophages, which may persist at the site for weeks to months
• These color changes on the skin surface are the visible clinical sign of hematoma resolution

Phase 3 - Proliferation: Rebuilding (Days 3 - Weeks)

• Fibroblasts are recruited by macrophage-derived growth factors (PDGF, TGF-β, VEGF)
• They deposit new collagen (type III initially, then type I) and extracellular matrix (ECM) to replace the clot scaffold
• Angiogenesis provides new microvasculature to support tissue repair
• The organizing clot is progressively replaced by granulation tissue - a provisional matrix of collagen, fibronectin, and new capillaries

Phase 4 - Remodeling and Maturation (Weeks to ~1 Year)

• Fibroblasts differentiate into myofibroblasts, which contract the repair zone
• Type III collagen is replaced by stronger type I collagen, cross-linked by lysyl oxidase
• Excess vasculature regresses
• Over 6-12 months, tensile strength increases toward - but does not fully reach - pre-injury levels (~80% of original)

Summary Table

When Hematomas Fail to Resolve Normally

• Organize - fibroblasts invade and replace the hematoma with fibrous/scar tissue
• Calcify - dystrophic calcification develops (myositis ossificans in muscle hematomas)
• Become infected (abscess formation)
• Liquefy into a seroma-like collection that may require aspiration

• Mulholland and Greenfield's Surgery: Scientific Principles and Practice, 7e - Chapter 5 (Wound Healing)
• SCHWARTZ'S Principles of Surgery, 11e - Chapter 9 (Wound Healing)

Skin Color Changes During Hematoma/Bruise Healing

The Biochemical Pathway

Hemoglobin (red)
     ↓  [heme oxygenase]
  Heme + globin
     ↓
  Biliverdin (green) + CO + Fe²⁺
     ↓  [biliverdin reductase]
  Bilirubin (yellow)
     ↓  [cleared via lymphatics/venules]
  Normal skin color restored

  Fe²⁺ + ferritin → Hemosiderin (golden-brown) — may persist for weeks-months

Color Stages with Timeline

Key Points on Each Color

Red (immediate)

• Reflects oxyhemoglobin - the same bright red of arterial blood
• Tissue vasodilation from the acute inflammatory response adds to the redness
• The skin may also look swollen and feel warm

Blue-Purple (days 1-2)

• Blood loses oxygen to the surrounding hypoxic tissue
• Deoxyhemoglobin absorbs red light, so it appears blue-purple through the skin
• This is often the most visually alarming stage - the "classic bruise" color
• Deeper bruises look bluer; more superficial ones look redder

Green (days 4-6)

• Heme oxygenase (induced in macrophages) cleaves the porphyrin ring of heme, releasing:
  • Biliverdin - a water-soluble green pigment
  • Carbon monoxide (CO)
  • Free iron (Fe²⁺)
• Biliverdin has a distinct green color visible through the skin

Yellow (days 6-10)

• Biliverdin reductase rapidly converts biliverdin → bilirubin
• Bilirubin is yellow-orange; it is the same compound responsible for jaundice
• At this stage the bruise is fading and often tender no more

Brown (days 10-14, sometimes persisting)

• Some of the released iron combines with ferritin to form hemosiderin
• Hemosiderin is a golden-brown, insoluble iron-storage compound
• In large hematomas (e.g., traumatic muscle injury), hemosiderin may persist for months and is visible on MRI as a dark susceptibility artifact

Visual Summary

Day 0-1       Day 1-2          Day 4-6       Day 6-10      Day 10-14
  RED    →  BLUE/PURPLE  →    GREEN    →    YELLOW   →  BROWN/FADE  →  NORMAL
(OxyHb)   (DeoxyHb/MetHb)  (Biliverdin)  (Bilirubin)  (Hemosiderin)

Factors That Affect the Color Sequence

Clinical note: The color of a bruise is used in forensic medicine to approximately "age" an injury. However, the timeline is variable enough that color alone cannot precisely date a bruise - it can only indicate a minimum age. The presence of yellow/green indicates at least 4-6 days have passed since the injury.

• Pfenninger and Fowler's Procedures for Primary Care, 3e (ecchymosis color sequence)
• Dermatology 2-Volume Set, 5e (hematoma and ecchymosis management)
• StatPearls - Biochemistry, Biliverdin (NCBI Bookshelf)
• Journal of Indian Forensic Medicine & Toxicology - Ageing of Bruise: Review of Histo-Chemical Changes with Time