Reference Work Entry

Encyclopedia of Molecular Mechanisms of Disease

pp 2056-2057


  • Henri BounameauxAffiliated withAngiology and Hemostasis, University Hospitals of Geneva
  • , Marc RighiniAffiliated withAngiology and Hemostasis, University Hospitals of Geneva



Definition and Characteristics

STP is a usually benign thrombosis [1] of a superficial, varicose or nonvaricose vein characterized by local inflammatory signs (Fig. 1, left). Most of these events are located in the lower (the vast majority) or upper (most of them secondary to injections) extremities. In a minority of cases, STP may extend in the deep venous system and occasionally cause pulmonary embolism (PE).
Thrombophlebitis. Figure 1

Clinical picture of superficial thrombophlebitis (left) and of iliofemoral deep vein thrombosis (right).

DVT is a thrombosis occurring in the deep vein system of the lower [2] (the vast majority) or upper (most of them secondary to central venous catheter or pacemaker) extremities. Other locations are exceptional. DVT of the lower extremities (Fig. 1, right) can be complicated by early (PE) or late (postthrombotic syndrome of the lower limbs or chronic pulmonary hypertension) complications.

Proximal DVT is defined as lower limb DVT that includes the popliteal or more proximal veins; it is associated with (mostly asymptomatic) PE in 50% of the cases. More distal or muscle vein thromboses as well as upper extremity thromboses are associated with less complications.


The precise incidence of STP is unknown. Annual incidence of DVT is about one in 1,000 people in western countries, ranging from 1 in 100,000 people in childhood to 1% in old age.


Mutations in the genes encoding for blood coagulation inhibitors (antithrombin, protein C, protein S) or factors (factor V, factor II or prothrombin, and changes in the regulation of gene activity can cause quantitative or qualitative deficiencies or higher concentrations of the proteins (factor VIII, factor IX), which will all result in an increased thrombotic risk. The most frequent genetic abnormalities are the factor V Leiden mutation and the prothrombin mutation. When factor V has a mutation at one of the cleavage sites (at position 506) for activated protein C, it is less sensitive to the protein C–protein S inhibiting pathway, the so-called resistance to activated protein C. A mutation in the prothrombin gene (at position 20210) is associated with an increased plasma concentration of the protein. Antithrombin, protein C and protein S deficiencies are quite rare in the population (0.02–0.4% in caucasians) and are present in only 1–3% of patients with thrombosis. On the other hand, the factor V Leiden and the prothrombin mutations are present in 5 and 2%, respectively, in the general population, and in 20 and 6%, respectively, in the patient population with venous thrombosis. Of note, the prevalence of factor V Leiden in patients with pulmonary embolism seems to be about half of that in patients with DVT, an intriguing “factor V Leiden paradox” [3].

Molecular and Systemic Pathophysiology

Venous thrombosis occurs in the presence of some combination of environmental and/or genetic risk factors that leads to some form of venous stasis, abnormality of the blood composition, and/or lesion of the vessel wall, the Virchow’s triad. Environmental, acquired risk factors include: immobilization, surgery, trauma, obesity, pregnancy, postpartum, malignancy, female hormones (used for contraception or substitution), and the antiphospholipid syndrome. Thromboses occurring in the context of surgery or trauma are called secondary or provoked while all other events are named idiopathic or unprovoked with or without triggering factors. Secondary events are five times less likely to recur than idiopathic events.

A dynamic age-dependent multicausal model of venous thrombosis [2] allows for various forms of interaction of risk factors: intercurrent factors occurring during one’s life (e.g. surgery, infection, or use of oral contraceptives) add to the individual’s thrombosis potential, and transiently increase the risk, which, combined with increasing age, may at some time exceed the thrombosis threshold.

Diagnostic Principles

Several noninvasive diagnostic strategies have been validated [4]. STP is diagnosed clinically or with compression ultrasonography (CUS). In suspected DVT, diagnosis relies on CUS of proximal veins, combined with a clinical prediction rule and/or plasma D-Dimer measurement. In suspected PE, combination of a clinical prediction rule, D-dimer, and multi-row chest computed tomography is probably the most convenient and cost-effective sequential approach [5]. All these strategies are associated with a low (2% or less) 3-month thromboembolic risk, similar to that observed in suspected patients left untreated following a normal venogram or pulmonary angiogram.

Therapeutic Principles

STP treatment remains controversial, from local or systemic NSAIDs to short periods of anticoagulant therapy (subcutaneous low-molecular weight heparin LMWH for 10 days to 6 weeks at prophylactic or therapeutic dosage). DVT and PE treatment consists of LMWH or fondaparinux at therapeutic dose (at least for 5 days) overlapped and followed by oral anticoagulants (vitamin K antagonists, VKA) for 3 (distal DVT or secondary event) to 6 (first idiopathic event) to 12 (first recurrent event) months and even long-term treatment (recurrent events, special situations), with an intensity corresponding to an INR of 2–3. In thrombosis associated with malignancy, long-term anticoagulant therapy with subcutaneous LMWH may be more efficacious than VKA. Novel, synthetic, orally active anticoagulants directed against thrombin or activated factor X are currently being developed.

Active prophylaxis with LMWH or fondaparinux in all patients at risk (i.e., mainly those hospitalized for surgery or acute medical illness) might reduce substantially the venous thromboembolic burden.

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© Springer-Verlag GmbH Berlin Heidelberg 2009
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