Hemorrhage

Definition

Causes

1. Trauma - physical injury to vessel walls
2. Atherosclerosis - weakening of vessel walls by disease
3. Inflammatory or neoplastic erosion of a vessel wall
4. Chronic congestion - allows capillary bleeding
5. Hemorrhagic diatheses - inherited or acquired defects in vessel walls, platelets, or coagulation factors (e.g., thrombocytopenia, haemophilia, vitamin C deficiency/scurvy)

Morphological Forms / Types

Clinical Significance

1. Volume of blood lost - Rapid loss of >20% blood volume causes hemorrhagic (hypovolemic) shock; up to 20% may be tolerated in healthy adults
2. Rate of bleeding - Rapid bleeding is less tolerated than slow, chronic bleeding
3. Location of bleed - A trivial bleed in the brain can be fatal; the same volume in subcutaneous tissue is insignificant
4. Health of the individual - Patients with underlying cardiac or lung disease decompensate at lower blood loss

• Large hemorrhages can cause jaundice as red cells are broken down by macrophages
• Chronic external blood loss (e.g., peptic ulcer, menstrual) leads to iron deficiency anemia (iron in hemoglobin is lost)
• Internal bleeding (hematoma) does NOT cause iron deficiency because iron is efficiently recycled from phagocytosed red cells

Summary Mnemonic: "HEMORR"

• Hematoma / Hemothorax / Hemopericardium
• Ecchymoses (1-2 cm bruises)
• Microvascular (capillary) bleeding in congestion
• Output compromised - hypovolemic shock if >20% lost
• Risk factors - diatheses, trauma, vasculitis
• Recycling - internal bleeds don't cause iron deficiency

THROMBOSIS - Essay (10 Marks)

Introduction / Definition

Pathogenesis - Virchow's Triad

1. Endothelial Injury (Most Important Factor)

• Procoagulant changes: Activated endothelium downregulates expression of coagulation inhibitors (thrombomodulin, endothelial protein C receptor, tissue factor pathway inhibitor) and increases expression of tissue factor, which activates the extrinsic coagulation cascade
• Antifibrinolytic effects: Secretion of plasminogen activator inhibitors (PAI) is increased, blocking t-PA and urokinase - limiting fibrinolysis

• Physical injury (trauma, surgery)
• Infectious agents (bacteria, viruses)
• Abnormal blood flow (turbulence)
• Inflammatory cytokines
• Metabolic abnormalities: hypercholesterolemia, homocystinemia
• Toxins from cigarette smoke
• Atherosclerosis (most common cause of arterial thrombosis)

2. Abnormal Blood Flow (Stasis and Turbulence)

• Allowing platelets and clotting factors to contact the endothelium
• Preventing dilution of activated clotting factors by fresh blood flow
• Retarding inflow of clotting factor inhibitors
• Promoting endothelial cell activation and dysfunction

3. Hypercoagulability

• Factor V Leiden mutation - most common; mutated Factor V is resistant to inactivation by protein C
• Prothrombin gene mutation (G20210A) - elevated prothrombin levels
• Antithrombin III deficiency
• Protein C or Protein S deficiency - cannot inactivate Factors Va and VIIIa
• Homocystinemia - causes endothelial injury

• High-risk: prolonged bed rest, MI, atrial fibrillation, cancer (Trousseau syndrome - migratory thrombophlebitis), prosthetic cardiac valves, DIC, heparin-induced thrombocytopenia (HIT)
• Lower-risk: oral contraceptive use, nephrotic syndrome, pregnancy, antiphospholipid antibody syndrome (lupus anticoagulant)

Morphology of Thrombi

• Mural thrombi: Form in the heart chambers (over infarcted myocardium) or the aorta (over atherosclerotic plaques)
• Vegetations: Thrombi on heart valves - infective (infective endocarditis), sterile (non-bacterial thrombotic endocarditis, Libman-Sacks endocarditis in SLE)

Fates of Thrombi

1. Propagation - enlarges by accretion of more platelets and fibrin → increases risk of occlusion and embolization
2. Embolization - part or all of the thrombus detaches and travels through the circulation (most dangerous fate)
3. Dissolution - fibrinolytic system (plasmin) may dissolve new thrombi. Older thrombi with extensive fibrin polymerization are resistant to lysis - hence thrombolytic drugs (t-PA) must be given within a few hours of formation to be effective
4. Organization and Recanalization - ingrowth of endothelial cells, smooth muscle cells, and fibroblasts converts the thrombus into organized connective tissue. Capillary channels form within it (recanalization), partially restoring blood flow. Eventually incorporated into the vessel wall

Clinical Features and Consequences

• Most common in deep veins of the leg (DVT) at or above the knee (popliteal, femoral, iliac veins)
• About 50% are asymptomatic - recognized only after pulmonary embolism
• Symptomatic DVT: unilateral leg pain, swelling, erythema, and warmth
• Greatest danger: pulmonary embolism (PE) - DVT is the source of >95% of PEs, which can cause sudden death
• Superficial venous thrombi (varicose veins) rarely embolize but cause local pain, congestion, and varicose ulcers

• Coronary artery → myocardial infarction
• Cerebral artery → ischemic stroke
• Mesenteric artery → intestinal infarction
• May also embolize (arterial embolism → ischemia of limbs, brain, kidneys)

• Mural thrombi over infarcted myocardium → systemic embolism
• Left atrial thrombus in AF → stroke

Summary

Thrombosis is a pathological process involving the interplay of endothelial injury, abnormal blood flow, and hypercoagulability (Virchow's Triad). Thrombi can be arterial (platelet-rich, cause occlusion/infarction) or venous (red cell-rich, cause embolism). The fate of a thrombus includes propagation, embolization, dissolution, or organization/recanalization. The major clinical consequences are myocardial infarction, stroke, and pulmonary embolism - making thrombosis one of the leading causes of death worldwide.