Hemorrhage: etiopathogenesis and morphology

Definition

Etiopathogenesis

• Trauma, the most common cause.
• Atherosclerosis, or rupture of an aneurysm or aortic dissection.
• Inflammatory erosion, for example peptic ulcer, tuberculous cavity or vasculitis.
• Neoplastic erosion of a vessel wall.
• Chronic venous congestion, where capillary bleeding can occur.
• The bleed may be massive if the damaged vessel is a large artery or vein.

• These are disorders in which bleeding follows a trivial injury or occurs spontaneously.
• The three components of hemostasis must all work properly, so the causes are grouped by component:
  • Vessel wall defects: scurvy (vitamin C deficiency), Ehlers-Danlos syndrome, vasculitis, amyloid, and infections such as meningococcemia.
  • Platelet defects: thrombocytopenia (ITP, marrow failure, DIC, drugs) or abnormal function (aspirin, uremia, von Willebrand disease).
  • Coagulation factor defects: hemophilia A and B, vitamin K deficiency, liver disease, DIC, anticoagulants.
• Broadly, platelet and vessel defects cause mucocutaneous bleeding: petechiae, purpura and epistaxis. Factor defects cause deep bleeding: hemarthrosis and large hematomas.

1. Transient vasoconstriction.
2. Platelet adhesion through von Willebrand factor, activation and aggregation (primary hemostasis).
3. The coagulation cascade, which produces fibrin (secondary hemostasis).
4. Counter-regulation by antithrombotic factors, so the clot stays localized.

Morphology

• External bleeding, or accumulation within a tissue as a hematoma.
• Hematomas range from trivial (a bruise) to fatal (a massive retroperitoneal hematoma from a ruptured dissecting aortic aneurysm).
• Bleeding into body cavities is named by site:
  • hemothorax
  • hemopericardium
  • hemoperitoneum
  • hemarthrosis (joints)
• Large hemorrhages can occasionally cause jaundice, as macrophages break down the red cells and hemoglobin.

• Macrophages phagocytose and degrade the extravasated red cells.
• Hemoglobin (red-blue) is converted to bilirubin (blue-green) and finally hemosiderin (golden-brown).
• Microscopically, an old hemorrhage shows hemosiderin-laden macrophages. These are the basis of the Prussian blue stain.

Clinical significance

• Volume and rate:
  • Rapid loss of up to 20% of blood volume is usually tolerated by healthy adults.
  • It can cause cardiovascular decompensation in people with heart or lung disease.
  • Greater loss causes hemorrhagic (hypovolemic) shock.
• Site: a small subcutaneous bleed is trivial, but the same bleed in the brain, or in the pericardium (tamponade), can be fatal.
• Chronic or recurrent external blood loss (peptic ulcer, menstruation) leads to iron deficiency anemia.
• Internal bleeding (a hematoma) does not cause iron deficiency, because iron is recycled from phagocytosed red cells.

Recent evidence check

Hemorrhage: etiopathogenesis and morphology

1. Etiopathogenesis

A. Mechanisms of bleeding

B. Hemorrhagic diatheses

• Hemorrhagic diatheses are disorders in which bleeding often follows a seemingly insignificant injury. - Robbins & Kumar Basic Pathology
• They arise from inherited or acquired defects in vessel walls, platelets or coagulation factors. All three must function properly for hemostasis.
• Vessel wall defects (purpura with normal platelets and coagulation tests):
  • scurvy
  • Ehlers-Danlos syndrome
  • vasculitis (Henoch-Schönlein purpura)
  • amyloid
  • meningococcemia
  • steroid or senile purpura
• Platelet defects:
  • Quantitative: thrombocytopenia from ITP, marrow failure, DIC, TTP or drugs.
  • Qualitative: aspirin, uremia, von Willebrand disease, Glanzmann thrombasthenia.
  • Uremic platelet dysfunction gives skin bleeding (bruising, ecchymoses) and mucosal bleeding (epistaxis, GI and gum bleeding). It can rarely cause hemopericardium or hemothorax. - Comprehensive Clinical Nephrology, 7th ed.
• Coagulation factor defects:
  • hemophilia A and B
  • vitamin K deficiency
  • liver failure
  • DIC
  • anticoagulants

• Platelet and vessel disorders give mucocutaneous bleeding: petechiae, purpura, epistaxis, gum bleeding. Bleeding starts immediately after injury.
• Coagulation factor disorders give deep bleeding: hemarthrosis and large hematomas, often delayed after injury.

C. Hemostasis, briefly

1. Vasoconstriction.
2. Platelets adhere through von Willebrand factor, then activate and aggregate (primary plug).
3. The coagulation cascade generates fibrin (secondary stabilization).
4. Counter-regulatory antithrombotic mechanisms limit the clot.

2. Morphology

A. Gross patterns

• External bleeding, or accumulation within a tissue as a hematoma. Hematomas range from trivial (a bruise) to fatal (a massive retroperitoneal hematoma from a ruptured dissecting aortic aneurysm).
• Body cavity hemorrhage, named by site:
  • hemothorax
  • hemopericardium
  • hemoperitoneum
  • hemarthrosis
• Large hemorrhages can occasionally cause jaundice as macrophages break down the red cells and hemoglobin.

B. Size-based terminology

• Petechiae: 1 to 2 mm, in skin, mucous membranes or serosa. Causes are thrombocytopenia, defective platelet function and loss of vascular wall support (scurvy).
• Purpura: 3 to 5 mm. Causes are the same as for petechiae, plus trauma, vasculitis and increased vascular fragility.
• Ecchymoses: 1 to 2 cm, subcutaneous hematomas ("bruises").

C. Microscopy and fate of extravasated blood

• Extravasated red cells lie outside the vessels in the tissue. Fresh hemorrhage shows RBCs with little or no inflammatory reaction.
• Macrophages phagocytose and degrade the red cells. The bruise changes color as hemoglobin (red-blue) is converted to bilirubin (blue-green) and finally hemosiderin (golden-brown). - Robbins & Kumar Basic Pathology
• Late lesions show hemosiderin-laden macrophages, which stain blue with Prussian blue. Forensic texts note coarse hemosiderin granules in histiocytes at the end of healing, and hematoidin crystals that can persist at the site of a bruise. - Essentials of Forensic Medicine and Toxicology
• A large hematoma may be resorbed, become organized (fibrosis) or calcify. Brain hemorrhages leave a cystic, brown-stained cavity.

3. Consequences

• Volume and rate:
  • Rapid loss of up to 20% of blood volume is usually tolerated by healthy adults.
  • It can cause cardiovascular decompensation in people with heart or lung disease.
  • Greater loss causes hemorrhagic (hypovolemic) shock.
• Site: a trivial subcutaneous bleed can kill if it is intracranial. Hemopericardium can cause tamponade.
• Chronic or recurrent external blood loss (peptic ulcer, menstruation) leads to iron deficiency anemia.
• Internal bleeding (a hematoma) does not cause iron deficiency, because iron is recycled from phagocytosed red cells.

4. Summary

• The mechanisms are rhexis, erosion and diapedesis.
• Causes are either local vessel injury or a systemic hemorrhagic diathesis (vessel, platelet or factor defect).
• Morphology depends on size: petechiae (1 to 2 mm), purpura (3 to 5 mm), ecchymoses (1 to 2 cm), hematoma or cavity bleeding.
• Resolution runs through macrophage removal and hemosiderin.
• The outcome depends on volume, rate, site and host reserve.

• The rhexis, erosion and diapedesis classification and the specific diathesis lists come from standard teaching and my own knowledge, not a textbook page I quoted.
• The image search for bruise color evolution returned nothing.
• In my earlier screen of recent systematic reviews (PMIDs 39826291, 40508117, 38472247), none changed these basic pathology concepts.