What is the role of inherited factor deficiency in the pathophysiology of thrombophlebitis?

Updated: Aug 31, 2020
  • Author: Padma Chitnavis, MD; Chief Editor: Dirk M Elston, MD  more...
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Answer

Although endothelial damage is speculated to be necessary for symptomatic thrombosis to occur, venous thrombosis may be associated with a deficiency in 1 of several anticoagulant factors. [11] In otherwise healthy patients younger than 45 years who are referred for evaluation of venous thrombosis, the prevalence of antithrombin III, protein C, and protein S deficiency is approximately 5% for each. [12, 13]

Antithrombin (antithrombin III) deficiency occurs in 1 person per 2000-5000 people in the general population and is the most prothrombotic of all inherited thrombophilias. [14, 15, 16] Acquired antithrombin deficiency can occur with liver disease and as a result of oral contraceptive use. Antithrombin combines with coagulation factors, blocking biologic activity and inhibiting thrombosis.

Protein C and protein S, 2 vitamin K–dependent proteins, are other important anticoagulant factors. Protein S is a cofactor for the effect of APC on factors Va and VIIIa. In the United States, the prevalence of heterozygous protein C deficiency is estimated to be 1 case in 60-300 healthy adults. [17] Greater than 95% of the patients are asymptomatic. However, a significant deficiency in either protein can predispose an individual to DVT. In fact, 75% of patients with homozygosity for protein S deficiency have venous thrombosis before age 35 years. [18]

Although factor deficiency can cause venous thrombosis, a genetic alteration in factor V, which results in APC resistance, is at least 10 times more common than other alterations. This genetic alteration is found in approximately one third of patients referred for an evaluation of DVT. [19, 20, 21] Precipitating factors for thrombosis, such as pregnancy and the use of oral contraceptives, are present in 60% of these patients. APC resistance is discussed at the beginning of the Pathophysiology section under Hypercoagulable states.

Defects in the fibrinolytic system, specifically plasminogen, occur in as much as 10% of the healthy population. [22] When the defects occur alone, the risk of thrombosis is small. Under certain circumstances, abnormal plasminogen levels may also predispose an individual to thrombosis.

Antiphospholipid antibodies are a cause of both venous and arterial thrombosis, as well as recurrent spontaneous abortion. [4] They may manifest in a primary thrombophilic disorder, or they may be related secondarily to autoimmune disorders. Lupuslike anticoagulants are present in 16-33% of patients with lupus erythematosus, as well as in many patients with a variety of autoimmune disorders. [23, 24, 25] Thrombosis may occur in 30-50% of patients with circulating lupuslike anticoagulants. [25, 26, 27]


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