In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces (see Hemostasis: Overview of Hemostasis). Numerous genetic, acquired, and environmental factors can tip the balance in favor of coagulation, leading to the pathologic formation of thrombi in veins (eg, deep venous thrombosis [DVT]), arteries (eg, MI, ischemic stroke), or cardiac chambers. Thrombi can obstruct blood flow at the site of formation or detach and embolize to block a distant blood vessel (eg, pulmonary embolism, embolic stroke).

Etiology

Genetic defects that increase the propensity for venous thromboembolism include

• Factor V Leiden mutation, which causes resistance to activated protein C (APC)
• Prothrombin 20210 gene mutation
• Deficiency of protein C, protein S, protein Z, or antithrombin

Acquired defects also predispose to venous and arterial thrombosis (see Table 1: Thrombotic Disorders: Acquired Causes of Thromboembolism).

Other disorders and environmental factors can increase the risk of thrombosis, especially if a genetic abnormality is also present.

Table 1
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Acquired Causes of Thromboembolism Condition Comments Antiphospholipid antibodies — Atherosclerosis Increases risk of arterial thrombi Higher risk in patients with preexisting stenosis When atherosclerotic plaques rupture, they release tissue factor into the blood, activate coagulation, initiate local platelet adhesion and aggregation, and cause thrombosis Cancer (promyelocytic leukemia; lung, breast, prostate, pancreas, stomach, and colon tumors) May activate coagulation by secreting a factor X–activating protease, by expressing tissue factor on exposed membrane surfaces, or both HeparinSome Trade Names HEPFLUSH-10 Click for Drug Monograph -induced thrombocytopenia Associated with platelet aggregation and increased risk of thrombosis Hyperhomocysteinemia Possible cause Due to folate, vitamin B12, or vitamin B6 deficiency Infection, if severe (eg, sepsis) Increases risk of venous thrombosis Increases expression of tissue factor by monocytes and macrophages Oral contraceptives that contain estrogen Low risk with low-dose regimens More frequent in patients who have a genetic abnormality that predisposes for venous thromboembolism Stasis Due to surgery, orthopedic or paralytic immobilization, heart failure, pregnancy, or obesity Tissue injury Due to trauma or surgery

Diagnosis

Diagnoses are summarized elsewhere in The Manual specific to the location of the thrombus.

Predisposing factors: Predisposing factors should always be considered. In some cases, the condition is clinically obvious (eg, recent surgery or trauma, prolonged immobilization, cancer, generalized atherosclerosis). If no predisposing factor is readily apparent, further evaluation should be conducted in patients with

• Family history of venous thrombosis
• More than one episode of venous thrombosis
• Venous or arterial thrombosis before age 50
• Unusual sites of venous thrombosis (eg, cavernous sinus, mesenteric veins)

As many as half of all patients with spontaneous DVT have a genetic predisposition.

Testing for predisposing congenital factors includes measurements of the quantity or activity of natural anticoagulant molecules in plasma and tests for specific gene defects. Testing begins with a group of screening tests, followed (if necessary) by specific assays.

Treatment

Treatment is summarized elsewhere in The Manual specific to the location of the thrombus.

Last full review/revision January 2013 by Joel L. Moake, MD

Content last modified January 2013