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Overview of Thrombotic Disorders

By Joel L. Moake, MD, Professor Emeritus of Medicine; Senior Research Scientist and Associate Director, Baylor College of Medicine; J. W. Cox Laboratory for Biomedical Engineering, Rice University

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In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. 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, myocardial infarction, 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).


Genetic defects that increase the propensity for venous thromboembolism include

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

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

Acquired Causes of Thromboembolism



Autoimmune disorder with increased risk of venous or arterial thrombi


Increases risk of arterial thrombi

Higher risk in patients with preexisting stenosis

When atherosclerotic plaques rupture, they expose or release tissue factor, 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/exposing tissue factor on exposed membrane surfaces, or both

Heparin-induced thrombocytopenia

Associated with platelet aggregation and increased risk of thrombosis

Possible cause

Due to folate, vitamin B12, or vitamin B6 deficiency

Infection, if severe (eg, sepsis)

Increases risk of venous thrombosis

Increases expression/exposure 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 to venous thromboembolism and in women who smoke

Tissue injury

Due to trauma or surgery

Venous stasis

Due to surgery, orthopedic or paralytic immobilization, heart failure, pregnancy, or obesity

Symptoms and Signs

Common manifestations of a thrombotic disorder include unexplained deep venous thrombosis and pulmonary embolism (PE). Superficial thrombophlebitis can also develop. Other consequences may include arterial thrombosis (eg, causing stroke or mesenteric ischemia). Symptoms depend on the location of the clot, as in the following examples:

  • Chest pain and shortness of breath: Possible PE

  • Leg warmth, redness, and swelling: DVT

  • Weakness/numbness of one side of the body, problems speaking, and problems with balance and walking: Possible ischemic stroke

  • Abdominal pain: Possible mesenteric ischemia

Most of the inherited disorders do not begin to cause an increased risk of clotting until young adulthood, although clots can form at any age. Women may have a history of multiple spontaneous abortions.


Diagnoses are summarized elsewhere in The Manual specific to the location of the thrombus (eg, deep venous thrombosis, pulmonary embolism, ischemic stroke).

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 specific assays that measure the quantity or activity of natural anticoagulant molecules in plasma, and screening for specific gene defects, as follows:

  • Clotting assay for lupus anticoagulant

  • Clotting assay for resistance to activated protein C

  • Genetic test for factor V Leiden

  • Genetic test for prothrombin gene mutation (G20210A)

  • Functional assay of antithrombin

  • Functional assay of protein C

  • Functional assay of protein S

  • Antigenic assays of total and free protein S.

  • Measurement of plasma homocysteine levels

  • Immunoassays for antiphospholipid antibodies


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

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