Prevention and Management of Deep Vein Thrombosis and Pulmonary Embolism

Pathophysiology

The three mechanisms for venous thrombosis were originally described by Rudolph Virchow in 1856: hypercoagulability, stasis, and injured endothelium, known as Virchow triad. Initially, in response to endothelial injury or stasis, platelets begin aggregating and subsequently activate procoagulant factors while simultaneously inhibiting those that promote fibrinolysis. This process commonly begins in the calf veins, most notably the soleal vein, and almost exclusively occurs within the venous valves. More recent research has also focused on the role neutrophils play in clot formation.

Several risk factors, both inherited and acquired, can increase VTE risk. Common inheritable causes of hypercoagulable states include non-O blood group, deficiencies of protein C and protein S, factor V Leiden deficiency, antithrombin III deficiency, and prothrombin G20210A. In addition, methylene tetrahydrofolate reductase 677T and hyperhomocysteinemia also have increased risks of clotting. Both protein C and protein S are vitamin K–dependent natural anticoagulant proteins that are activated by thrombi via thrombomodulin and work in concert to inhibit the activation of factors V and VIII. When deficient, patients have a 10-fold increase in the risk of developing VTE. Factor V Leiden is a mutated form of factor V, which prevents protein C from binding and thereby leads to a procoagulant state. This can occur in both heterozygous and homozygous forms, the latter of which is associated with an incidence of venous thrombosis 80 times that of the general population. Antithrombin III is a protein that under normal conditions binds to and inactivates both factor II (thrombin) and factor X. Interestingly, deficiency of antithrombin III can be both inherited and acquired. The acquired form is associated with increased excretion as seen in renal failure, decreased production (which occurs in liver failure), and increased consumption as can happen in severe trauma. It may also be deficient after major surgeries, most specifically those requiring cardiopulmonary bypass. The prothrombin gene mutation (G20210A) leads to higher levels of prothrombin in the blood and therefore enhances the risk of clotting. The presence of antibodies to antiphospholipid also has a 10-fold higher risk of developing venous thrombosis. Finally, non-O blood groups express higher levels of FVIII and vWf conferring a smaller increase in VTE risk.

Acquired risk factors for the development of VTE are varied and consist of age greater than 40 years, prior VTE, varicose veins, malignancy, major surgery, increased surgical duration, prolonged anesthesia, trauma, sepsis, pregnancy, major fracture, obesity, prolonged immobility/paralysis, stroke, inflammatory bowel disease (IBD), estrogen use, and congestive heart failure, among others. Certain hematologic conditions can also create a hypercoagulable state and are associated with VTE. Examples are thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), polycythemia vera, heparin-induced thrombocytopenia (HIT), and various other myeloproliferative disorders or malignancies. Although pregnancy is associated with an increased risk of VTE, men are more likely to develop recurrent VTE.

Prevention

The Caprini Score is a validated risk assessment tool developed to stratify patients into very low, low, moderate, and high-risk groups for developing DVT and thereby to guide the choice of prevention strategy. It designates point values to various risk factors, such as: age; type of surgery; body mass index (BMI); presence of malignancy, lung disease, cardiac disease (myocardial infraction, congestive heart failure), and IBD; stroke; hip, pelvis, or leg fracture; and inherited coagulopathies, among others. It then creates an estimate of VTE risk based on the total point value. It is important to note that this method was only validated for general, abdominal–pelvic, bariatric, vascular, and plastic/reconstructive surgery patients; however, it can be applied to other surgical populations. For patients who fall into the very low category, the risk of VTE without any prophylaxis is < 0.5%, and for those who fall into the high-risk category, this increases to 6%.

For patients who are at very low risk of VTE, the American College of Chest Physicians recommends neither mechanical nor chemoprophylaxis for DVT and instead suggests early ambulation as a means for prevention. For those at low risk of VTE, recommendations are to utilize mechanical prophylaxis alone. Mechanical prophylaxis includes both elastic compression stockings and sequential compression devices (SCDs). Compared with no prophylaxis, studies have demonstrated that elastic stockings reduce the rate of both asymptomatic and symptomatic DVT by 31%–65% but can be associated with skin complications. SCDs are intermittent pneumatic compression devices, which promote blood circulation through the veins of the legs, and have been shown to have a 60% reduction in the rate of VTE in various trials, although compliance can be difficult. Preference is usually for SCDs over compression stockings. Once patients enter the moderate and high-risk categories for VTE, chemoprophylaxis becomes the preferred method; however, the risk of bleeding must also be considered.

Patients at moderate to high risk of developing VTE should receive chemoprophylaxis as long as their risk of bleeding is acceptably low. Low molecular weight heparins (LMWHs; i.e., enoxaparin, dalteparin) and unfractionated heparin are the preferred agents for pharmacologic prevention based on guidelines. In high-risk patients, it is suggested to add mechanical prophylaxis. If patients are moderate to high risk but have a significant risk of bleeding, mechanical prophylaxis can be used as a sole agent until it is safe to start pharmacologic prophylaxis. If chemoprophylaxis is indicated but there are contraindications to either LMWH or unfractionated heparin (UFH), fondaparinux, dabigatran, or aspirin may be utilized instead.

Regular surveillance with Doppler ultrasound and prophylactic placement of inferior vena cava (IVC) filters have been described as methods of screening and prevention of VTE. They are not routinely recommended but remain a rare option.

Diagnosis

The Wells score is a validated tool used to assess the pretest probability of a patient having a DVT. It was initially studied in patients with a suspected first DVT and assigns point values to various clinical findings, such as recent immobility, localized tenderness, calf swelling, pitting edema, recent or active cancer, and stratifies patients into low, moderate, and high probability of DVT. The modified Wells score incorporates previous DVT into the algorithm and distinguishes patients as either unlikely or likely to have a DVT. Performance of diagnostic tests to confirm the presence of DVT should only be undertaken after determining a patient’s probability of having a DVT.

In patients for whom the Wells score identifies a low probability of DVT, recommendations are to perform a D-dimer test. A low D-dimer level effectively rules out the possibility of a DVT. If the D-dimer is elevated or if the patient would be expected to have an elevated D-dimer for any other reason, ultrasonography should be performed. In those with moderate probability of DVT, D-dimer is nonspecific and ultrasound is preferred.