Thrombosis & embolus

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Thrombosis & Embolism

Source: Robbins, Cotran & Kumar - Pathologic Basis of Disease

THROMBOSIS

A thrombus is a solid mass of blood constituents (platelets, fibrin, RBCs, WBCs) formed within the vascular system during life. It is pathological clot formation - distinct from normal hemostasis.

Virchow's Triad

The three primary abnormalities leading to thrombosis form Virchow's triad:

1. Endothelial Injury

The most important factor, especially for arterial and cardiac thrombosis where high flow rates impede clot formation. Platelet adherence and activation is a necessary prerequisite under high shear stress.

Mechanisms of injury:

Physical injury, infectious agents, abnormal blood flow
Inflammatory mediators and cytokines
Metabolic abnormalities (hypercholesterolemia, homocystinemia)
Toxins from cigarette smoke

Prothrombotic endothelial changes:

Procoagulant changes: Downregulation of thrombomodulin, protein C, and tissue factor pathway inhibitor (TFPI) - shifts balance toward coagulation
Antifibrinolytic effects: Secretion of plasminogen activator inhibitors (PAIs), reduced tissue plasminogen activator (t-PA) expression
Platelet-activating effects: Increased expression of vWF and tissue factor

2. Abnormal Blood Flow (Stasis or Turbulence)

Turbulence promotes arterial and cardiac thrombosis by causing endothelial injury/dysfunction
Stasis is the dominant factor in venous thrombosis

Turbulence and stasis promote thrombosis by:

Disrupting laminar flow, bringing platelets into contact with endothelium
Preventing dilution of activated clotting factors by fresh blood
Retarding influx of clotting factor inhibitors
Promoting endothelial cell activation

Clinical examples:

Atrial fibrillation - blood stasis in the atrial appendage
Aneurysms - turbulence and stasis in the sac
Atherosclerotic plaques - turbulence around stenoses
Prolonged bed rest / immobility - venous stasis in lower limbs
Hyperviscosity states (polycythemia, sickle cell disease)

3. Hypercoagulability

Defined as any alteration in the coagulation pathways that predisposes to thrombosis.

Type	Examples
Primary (Inherited)	Factor V Leiden mutation (most common hereditary thrombophilia), Prothrombin gene mutation (G20210A), Antithrombin III deficiency, Protein C or S deficiency
Secondary (Acquired)	Prolonged bed rest/immobility, MI, atrial fibrillation, tissue damage (surgery, fracture), cancer (Trousseau syndrome), antiphospholipid antibody syndrome, HIT (heparin-induced thrombocytopenia), pregnancy, OCP use, nephrotic syndrome

Morphology of Thrombi

Arterial thrombi (white thrombi):

Rich in platelets and fibrin
Typically at sites of endothelial injury (atherosclerotic plaques)
Grow in a retrograde direction from point of attachment
Show lines of Zahn - pale platelet/fibrin layers alternating with darker RBC-rich layers (pathognomonic of antemortem thrombus)

Venous thrombi (red/stasis thrombi):

Rich in RBCs (hence "red")
Occur in slower-flow venous circulation
Most commonly in deep veins of lower extremity (DVT)
Lines of Zahn are less distinct

Mural thrombi:

In heart chambers or aortic lumen
Post-MI (endocardial injury), atrial fibrillation (stasis), aortic aneurysm

Fate of a Thrombus

Thrombi have four possible fates:

Fate	Description
Propagation	Accumulates more platelets and fibrin, enlarges
Embolization	Dislodges and travels to distant sites
Dissolution (lysis)	Fibrinolytic activity dissolves the clot (most desirable)
Organization and recanalization	Older thrombi become organized by ingrowth of endothelial cells, smooth muscle, fibroblasts; may eventually recanalize to restore flow

Consequences of Thrombosis

Local vascular occlusion - ischemia/infarction distal to the clot
Distal embolization - thrombus fragment travels and blocks a distant vessel
Venous congestion - in venous thrombosis, backup of blood causing edema, pain, and ulceration

EMBOLISM

An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by blood from its point of origin to a distant site, where it causes partial or complete vascular occlusion.

Most emboli are dislodged thrombi - hence the collective term thromboembolism.

Types of Emboli

1. Pulmonary Embolism (PE)

Origin: 70-80% arise from deep vein thrombosis (DVT) of the legs
Incidence: ~60-120 cases/100,000 per year (US); 60,000-100,000 deaths/year
~20% die before or shortly after diagnosis

Pathophysiology by size:

Embolus Size	Effect
Large/massive	Occludes main pulmonary artery or saddle embolus at bifurcation → sudden death, acute cor pulmonale
Medium	Occludes a medium pulmonary artery → pulmonary hemorrhage (rarely infarction due to dual lung supply)
Small/multiple	Multiple small emboli over time → pulmonary hypertension, right heart failure
Paradoxical	Crosses patent foramen ovale → systemic embolization

Pulmonary infarction occurs in <10% because the lung has a dual blood supply (pulmonary + bronchial arteries). It occurs when bronchial flow is also compromised (left heart failure, pneumonia).

Clinical features:

Pleuritic chest pain, dyspnea, tachycardia, hemoptysis
Large emboli: sudden-onset shock, right heart failure
Multiple small emboli: progressive dyspnea, pulmonary HTN

2. Systemic Thromboembolism

Most arise from intracardiac mural thrombi (2/3 associated with left ventricular MI; 25% with dilated left atrium in atrial fibrillation)
Also from aortic aneurysms, ulcerated atherosclerotic plaques, valvular vegetations
Travel to: legs (most common ~75%), brain, intestines, kidneys, spleen

3. Fat Embolism

Source: Fat globules from bone marrow after fracture of long bones (femur, tibia) or severe burns
Enters pulmonary circulation via torn marrow vessels
Fat embolism syndrome: Occurs 1-3 days after injury
- Pulmonary insufficiency (dyspnea, tachypnea)
- Neurological symptoms (irritability, restlessness, coma)
- Petechial rash (thrombocytopenia + anemia)
- Mortality: ~10%

4. Air Embolism

Gas bubbles in the circulation obstruct flow
Can occur from entry of air during surgery (neurosurgical, cardiac), obstetric procedures, IV catheter placement, chest trauma
Decompression sickness (Caisson disease): Rapid decompression from high-pressure environments causes nitrogen gas bubbles to form in tissues and blood
- Acute: bends (joint pain), chokes (pulmonary symptoms)
- Chronic: aseptic necrosis of bone (especially femoral head)

5. Amniotic Fluid Embolism

Rare but catastrophic obstetric complication
Amniotic fluid (with fetal cells, hair, vernix) enters maternal circulation through uterine tears or ruptured cervical veins
Triggers: pulmonary vascular obstruction, anaphylactoid reaction, DIC
Mortality: up to 80%

6. Cholesterol (Atheroembolism)

Showers of cholesterol crystals from ulcerated atherosclerotic plaques
Affects small arteries of kidneys, brain, extremities
Often triggered by arterial catheterization

Comparison: Thrombosis vs. Embolus

Feature	Thrombus	Embolus
Definition	Clot formed in situ	Detached mass traveling in blood
Composition	Platelets, fibrin, RBCs	Usually dislodged thrombus; can be fat, air, tumor
Formation	Virchow's triad (injury, stasis, hypercoag)	Usually from thrombosis elsewhere
Attachment	Attached to vessel wall	Not attached - free-floating
Lines of Zahn	Present (arterial)	Absent
Location	Where formed	Distal, at branch points or narrowings
Consequence	Local occlusion, embolism	Distal infarction/obstruction

Key points to remember:

Virchow's triad (endothelial injury, stasis/turbulence, hypercoagulability) underlies all thrombosis
Arterial thrombi = platelet-rich, white; venous thrombi = RBC-rich, red
Lines of Zahn distinguish antemortem thrombus from postmortem clot
PE is the most common and clinically significant form of embolism
Fat embolism presents 1-3 days post-fracture with the triad of respiratory failure, neurologic symptoms, and petechiae

- Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 126-137

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