Thrombosis and thromboembolisms

Thrombosis

Definition: formation of clots inside a blood vessel, focally associated to the underlying vascular surface

• Thrombi can develop anywhere but arterial and cardiac thrombi typically arise at sites of endothelial injury, whereas venous thrombi occur at sites of stasis

Pathogenesis of thrombosis

The 3 primary abnormalities that lead to intravascular thrombosis make up Virchow’s triad:

• Endothelial injury: leads to platelet activation and thrombus formation
  • Ex: hypertension, turbulent blood flow, hypercholesterolemia, smoking, vasculitis, inflammation and other prothrombotic states
• Alteration of blood flow (stasis vs. turbulent flow): causes endothelial injury or dysfunction by forming countercurrents and local pockets of stasis
  • Ex: ulcerated atherosclerosis, aneurysms, mitral valve stenosis, sick cell anemia
• Hypercoagulability: abnormally high tendency of the blood to clot, and is typically caused by alterations in coagulation factors
  • Can be primary, most often caused by mutations of factor V and prothrombin genes, or secondary, caused by the use of some drugs (i.e., oral contraceptives), smoking, obesity, advanced age + some disseminated cancers release procoagulant tumor products (e.g., mucin from adenocarcinoma)

Types of thrombi

• Arterial: arise at sites of endothelial injury or turbulence - frequently occlusive
  • Macroscopic: gray-white, friable
  • Microscopic: rich in platelets (processes underlying their development lead to platelet activation) + fibrin, RBCs + WBCs
• Venous: invariably occlusive - most commonly (90%) affects the veins of the lower extremities and pelvic plexus; particularly dangerous since dislodged thrombus → pulmonary emboli
  • Can be mistaken for postmortem clots: gelatinous red center + yellow fat supernatant + not attached to underlying vessel wall (vital sign)
  • Macroscopic: firm, red, attached to vessel wall
  • Microscopic: RBCs + fibrin
• Mural thrombi: occur in heart chambers, atrial auricles or aortic lumen → not occlusive
  • Can be caused by abnormal myocardial contraction (arrythmias, dilated cardiomyopathy, myocardial infarction) or endomyocardial injury (myocarditis, catheter trauma)
  • Can also be present on heart valves - vegetations - which can be caused by bacterial/fungal infections, Libman-Sacks endocarditis in the setting of SLE

Thromboembolism

Embolus:detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction

• Most emboli are derived from a dislodged thrombus → thromboembolism (99%)

Types of thromboembolism

• Pulmonary embolism: origin: deep veins of lower extremities + pelvic plexus → vena cava inferior → right heart → pulmonary artery
  • Most pulmonary emboli (60%–80%) are small and clinically silent → with time, undergo organization and become incorporated into the vascular wall
  • Multiple emboli occurring through time can cause pulmonary hypertension and right ventricular failure (cor pulmonale)
  • Symptoms: chest pain, cough, chronic dyspnoea, chronic right heart failure → right heart hypertrophy → heart will fail in time
  • Large embolus → blocks major major pulmonary artery can cause sudden death, acute right heart failure, i.e., saddle embolus is a life-threatening condition characterized by a large blood clot that lodges at the bifurcation of the pulmonary artery, obstructing blood flow to both lungs
  • Risk factors: prolonged bed rest, surgery (esp. otheropedic surgery of knee or hips), severe trauma, congestive heart failure, birth, oral contraceptives, disseminated cancer, primary disorders of hypercoagulability
• Systemic thromboembolism: most arise from intracardiac mural thrombi (80%)
  • Can travel virtually anywhere → final resting place depends on their point of origin and the relative flow rates of blood to the downstream tissues (lower extremities (75%) + CNS (10%), intestines, kidneys and spleen are less common targets)
  • Consequences depend on caliber of occluded vessel, collateral supply, and the affected tissue’s vulnerability to anoxia
• Paradoxical embolism: venous thromboembolism (especially due to deep vein thrombosis) in patients w/ right-to-left cardiac shunt (i.e., persistent foramen ovale or an atrial septal defect) → enters systemic circulation and can lead to systemic infarction

Deep vein thrombosis (DVT)

Sources

• Amboss
• Pathology lectures
• Kumar, Abbas, Aster. Robbins Basic Pathology.
• Guyton & Hall. Textbook of Medical Physiology.
• Stefan Silbernagl, Florian Lang. Color Atlas of Pathophysiology.