When a blood vessel is injured, a coagulation cascade is activated to form an organized clot to retain moisture and begin a healing process. Unlike a clot, a thrombus occurs in the blood vessel as a result of endothelial damage, altered blood flow or a hypercoagulation state that triggers platelet activation and a coagulation cascade (1). About one in 1,000 adults develop thrombosis annually (2).
Endothelial damage
Contributing to risk of thrombosis, endothelial damage can occur from hemodynamic stress (normal wear and tear). Hemodynamic stress is accentuated by conditions such as hypertension or infection (1). The stress eventually strips away endothelial cells exposing subendothelial collagen (1). This may occur, for example, on endocardial surface (1). The change can lead to platelet adherence, activation, aggregation and eventually a thrombus (1). Endothelial damage may occur from iatrogenic disease (a disease result of medical or surgical intervention) such as can be caused by an intravenous needle. Endothelial damage can also occur from trauma such as from an auto accident, a fall, or by radiation, high cholesterol or smoking (1).
Altered blood flow
The abnormal pattern of blood flow leads to thrombosis because it increases platelet contact with endothelium (1). It can occur from reduction in rate or turbulence, principally caused by cardiac damage or increased blood viscosity (1). At times, also, reduced venous blood flow is due to weakened vein walls, varicose veins, which disrupts functioning of leaflet valves (1). A malformed heart can cause blood flow turbulence that may create a thrombus in a cardiac chamber, called a mural thrombus (1). Lastly, a tumor causing inflammation or swelling can compress a vessel causing turbulence (1). Increased pressure from arterial pressure can eventually push out a weakened arterial wall causing a pouchlike bulge called an aneurysim (1). Blood swirls into the aneurism, platelets smash against the endothelium and thrombosis follows (1).
Blood Hypercoagulation
Hypercoagulation is suspected when turbulent blood flow or endothelial damage don’t appear the case in thrombosis (1). Genetic defects can lead to malfunction and overproduction of coagulation promoters or lack of coagulation inhibitors (1). A deficiency, for example of PG-I(2), a coagullaation inhibitor, leads to the liver overproducing clotting factors (1). Those with such “thrombophilic disorders” can applaud the discovery of factor V Leiden since its occurrence is most common in these disorders and subject to intense research (3).
Other Risk factors
Apart from genetic predisposition, thrombosis risk increases with advancing age, being male, being obese, after surgery, trauma, cancer, immobilization, pregnancy and exogenous hormones (2;4).
Consequences
The sequela of thrombosis can resolve itself by being broken down or reduced, with the help of moderate exercise and cardiopulmonary fitness (1). A second consequence is organization where phagocytic digestion a couple or more days after the thrombus forms and with platelets and fibrin replaced by connective tissue; essentially the thrombus becomes part of the the vessel wall with endothelium formed over it and recanalization allows blood to flow through the thrombus (1). Propagation may occur when a thrombus enlarges, extends and continued coagulation produces a red cap that extends a significant distance (1). The major consequence is infarction, when ischemia forms a region of necrosis that completely occludes the lumen of a vessel (1). Infarction mainly can occur due to tissue vulnerability to hypoxia, pattern of vascular supply, capacity of oxygen delivery and the rate of occlusion (1).
Reference List
1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
2. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol 2007;44:62-9.
3. Cushman M. Inherited risk factors for venous thrombosis. Hematology Am Soc Hematol Educ Program 2005;452-7.
4. Olson N, O'Meara ES, Jenny NS et al. Lipoprotein-associated phospholipase A2 and risk of venous thrombosis in older adults. Am J Hematol 2008;83:524-7.
