What causes deep vein thrombosis of the lower extremities?

Many factors can contribute to deep vein thrombosis of the lower extremities. Deep vein thrombosis of the lower extremities most often results from decreased venous return (eg, in immobilized patients), endothelial damage, dysfunction (eg, after leg fractures), or hypercoagulability.

Risk factors for venous thrombosis

• Age over 60 years
• Smoking (including passive smoking)
• Estrogen receptor modulators (tamoxifen, raloxifene)
• Heart failure
• Hypercoagulability disorders
• Antiphospholipid antibody syndrome
• Antithrombin III deficiency
• Factor V mutation (activated protein C resistance)
• Hereditary fibrinolytic defects
• Hyperhomocysteinemia
• Sodium heparin-induced thrombocytopenia and thrombosis
• Increased factor VIII levels
• Increased factor XI levels
• Increased levels of von Willebrand factor
• Paroxysmal nocturnal hemoglobinuria
• Protein C deficiency
• Protein S deficiency
• Genetic variants of prothrombin G-A
• Tissue coagulation factor inhibitor
• Immobilization
• Insertion of venous catheters
• Limb injuries
• Malignant neoplasms
• Myeloproliferative diseases (increased blood viscosity)
• Nephrotic syndrome
• Obesity
• Taking oral contraceptives or estrogen therapy
• Pregnancy and postpartum period
• Previous venous thromboembolism
• Sickle cell anemia
• Surgical interventions within the last 3 months.

Deep vein thrombosis of the upper extremities most often occurs due to endothelial damage caused by central venous catheters, pacemakers, or drug injections. Deep vein thrombosis of the upper extremities is sometimes part of the superior vena cava syndrome (SVCS), in other cases it occurs as a result of increased coagulability or compression of the subclavian vein at the exit from the chest. Compression can occur due to a normal or additional 1st rib, fibrous constriction (thoracic outlet syndrome), or occur with strenuous manual work ("effort thrombosis", or Paget-Schroetter syndrome, which accounts for 1-4% of all deep vein thromboses of the upper extremity).

Many malignancies predispose to deep vein thrombosis, so DVT is a well-known marker of some occult tumors. However, 85-90% of patients with deep vein thrombosis do not have any malignancy.

Deep vein thrombosis typically begins in the area of the venous valves. The thrombi are composed of thrombin, fibrin, and red blood cells with relatively few platelets (red thrombi). Without treatment, these thrombi may spread proximally, embolize within a few days, or both.

Common complications include chronic venous insufficiency and postphlebitic syndrome, as well as pulmonary embolism. Much less frequently, acute deep vein thrombosis leads to white or blue phlegmasia. Both complications, if not promptly diagnosed and treated, provoke the development of venous (wet) gangrene.

In circulatory venous white gangrene, a rare complication of deep venous thrombosis during pregnancy, the leg becomes milky white. The pathophysiology is unclear, but edema may increase soft-tissue pressure without capillary perfusion pressure. Ischemia develops only if capillary blood flow becomes inadequate; wet gangrene results.

In circulatory venous cyanosis, massive iliofemoral venous thrombosis causes almost complete venous occlusion. The blood supply to the leg is disrupted, and it becomes extremely painful and cyanotic. The pathophysiology may involve complete stasis of venous and arterial blood in the lower extremity because venous outflow is impossible or massive edema stops arterial blood flow. Wet gangrene may result.

Other types of deep vein thrombosis are rare. Suppurative (septic) thrombophlebitis, a bacterial infection of a superficial peripheral vein, usually develops after venous catheterization, which leads to infection and thrombus formation. Suppurative thrombophlebitis of the jugular vein (Lemierre's syndrome) is a bacterial (usually anaerobic) infection of the internal jugular vein and surrounding soft tissues. It can result from tonsillitis and pharyngitis and is often complicated by bacteremia and sepsis. In septic pelvic thrombophlebitis, pelvic thromboses that occur in the postpartum period cause intermittent fever.

Thrombophlebitis without deep vein thrombosis is usually caused by venous catheterization, intravenous infusions, or intravenous drug use.