Continuing Education Activity

Deep vein thrombosis (DVT) is the formation or presence of a thrombus in the deep veins. DVT occurs mostly in the lower extremities and, to a lesser extent, in the upper extremities. Pulmonary embolism (PE) is an obstruction of the pulmonary artery or its branches by a thrombus (sometimes due to fat or air). The most likely source of thrombus in pulmonary arteries is an embolization from deep veins in the legs. This activity reviews the causes of DVT and highlights the role of the interprofessional team in the prophylaxis against DVT.

Objectives:

• Identify the cause of DVT.
• Develop strategies to increase compliance with the use of DVT prophylaxis.
• Apply best practices when emergent and ongoing management in prophylaxis is unsuccessful.
• Coordinate with the interprofessional team to enhance prophylaxis against DVT and improve patient outcomes.

Introduction

Deep vein thrombosis (DVT) is the formation or presence of a thrombus in the deep veins. DVT occurs mainly in the lower extremities and, to a lesser extent, in the upper extremities. Pulmonary embolism (PE) is an obstruction of the pulmonary artery or its branches by a thrombus (sometimes due to fat or air). The most likely source of thrombus in pulmonary arteries is an embolization from deep veins of the legs. This occurs in one-third of patients with DVT. Prevention of DVT thereby decreases the incidence of PE, a serious and life-threatening condition.

Venous thromboembolism (VTE) includes DVT and PE. DVT is a major preventable cause of mortality and morbidity worldwide. DVT and PE account for 60,000 to 100,000 deaths annually in the United States.[1]

Normally, a balance of procoagulant and anticoagulant factors in the blood prevents thrombus formation intravascularly. One or more factors of the triad of Virchow can lead to the formation of DVT.

Triad of Virchow

1. Venous stasis (eg, immobility and congestive heart failure)
2. Endothelial injury (eg, surgery and trauma)
3. Hypercoagulability (eg, OCP, cancer, and thrombophilia)[2]

Venous stasis is the most crucial factor, but endothelial injury or hypercoagulability increases the risk of DVT. Hospitalized patients are at risk of venous stasis, and with the presence of other factors, they are at increased risk of DVT compared to patients in the community.

DVT prophylaxis targets either venous stasis (mechanical methods) or hypercoagulability (pharmacological prophylaxis).

Hospitalized patients are at increased risk of developing DVT (approximately 50%), increasing the risk of PE. PE is one of the most common but preventable causes of death in hospitalized patients.

Only 50% of hospitalized patients receive DVT prophylaxis. Prevention of DVT in hospitalized patients decreases the risk of DVT and PE, decreasing mortality and morbidity.

DVT prophylaxis can be primary or secondary. Primary prophylaxis is preferred, using medications and mechanical methods to prevent DVT. Secondary prophylaxis is a less commonly used method that includes early detection with screening methods and the treatment of subclinical DVT.

Anatomy and Physiology

Deep Veins of the Lower Extremities

• Common femoral vein
• Deep femoral vein
• Superficial femoral vein
• Popliteal vein
• Anterior tibial vein
• Posterior tibial vein
• Peroneal vein 

Deep Veins of the Upper Extremities

• Paired radial vein
• Paired ulnar vein
• Interosseous vein
• Brachial vein
• Axillary vein
• Subclavian vein

Indications

DVT Prophylaxis in Hospitalized Patients

Hospitalized patients are at increased risk of VTE when compared to patients in the community. Therefore, DVT prophylaxis should be considered in every hospitalized patient. A full history and physical examination are warranted to assess the risk of VTE and bleeding.

Patients with Increased Thrombosis Risk

• Elderly (older than 70)[3]
• Immobile patients
• History of DVT/PE
• Critical ill patients admitted to the intensive care unit 
• Stroke with lower extremity paralysis
• Advanced congestive heart failure 
• Active cancer[4]
• Acute respiratory failure
• Thrombophilia
• Recent surgery or trauma
• Obesity[5]
• Ongoing hormonal therapy

Based on thrombosis risk, patients are classified into low risk, moderate risk, and high risk for VTE. 

1. Low-risk patients: Young patients with no risk factors for VTE. No need for prophylaxis.
2. Moderate-risk patients: With at least one risk factor, pharmacological prophylaxis is preferred with or without mechanical prophylaxis.
3. High-risk patients: With multiple risk factors, pharmacological prophylaxis is preferred with mechanical prophylaxis.

Commonly used pharmacological agents for prophylaxis in hospitalized patients are:

1.  Low-molecular-weight heparins (LMWH)
2.  Unfractionated heparin (UFH)
3.  Fondaparinux[6]

LMWH is preferred to UFH due to ease of administration (once daily versus 2 to 3 times per day) and decreased incidence of DVT.[7] A number of LMW heparin preparations are available, all of which have almost equal efficacy against VTE. Their dosages are listed in the table below:

Table 1. Common dosages for VTE prophylaxis in hospitalized patients[8][9]

* Prophylactic dosages are suggested for medical patients with a creatinine clearance greater than 30 mL/min with no extremes in body weight. Platelet counts should be monitored regularly to detect the development of heparin-induced thrombocytopenia.

UFH is used in patients with low GFR. Prophylactic dosage for UFH is usually 5000 units given subcutaneously twice or thrice a day. This may be increased to 5000 to 7500 units 3 times a day in a patient with obesity. UFH is typically less expensive than low-molecular-weight heparin. However, it is also contraindicated in patients with HIT, and platelet counts need to be monitored regularly in all patients receiving low-dose UFH.

Direct oral anticoagulants have been shown to reduce mortality (betrixaban compared with subcutaneous enoxaparin). Betrixaban and rivaroxaban are currently approved for use in hospitalized patients.

Mechanical methods are used in patients with moderate-to-high risk for DVT with an increased risk of bleeding. They include intermittent pneumatic compression, graduated compression stockings, and venous foot pump.

DVT Prophylaxis in Hospitalized Cancer Patients

Patients with active cancer but no additional thrombosis risk factors do not need DVT prophylaxis in outpatient settings. If they have additional risk factors), either LMWH or UFH is used.

Table 2. Parenteral venous thromboembolism (VTE) prophylaxis in patients with cancer[10]

DVT Prophylaxis in Ambulatory Cancer Patients

The guidelines published by the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and an international consensus group do not recommend routine VTE prophylaxis in ambulatory patients with cancer, except for those at very high risk of VTE (eg, patients with multiple myeloma receiving lenalidomide or thalidomide plus chemotherapy or dexamethasone). In this case, either a direct factor Xa inhibitor or LMW heparin may be used.

DVT Prophylaxis in Long-Distance Travellers

Long-distance travelers with risk factors for VTE can use properly fitted below-knee graduated compressive devices at 15 to 30 mm Hg of pressure, along with frequent ambulation and calf muscle exercises. Pharmacological prophylaxis is not recommended.

DVT Prophylaxis in Patients Undergoing Orthopedic Surgeries

VTE (DVT and PE) risk is high in patients undergoing major orthopedic surgeries like knee or hip surgeries. In patients undergoing total hip arthroplasty and total knee arthroplasty, LMWH, apixaban, and rivaroxaban are used. Fondaparinux, UFH, and warfarin are used if the above agents cannot be used or are contraindicated. LMWH, UFH, and fondaparinux are used for DVT prophylaxis in patients undergoing hip fracture surgery.

Duration:

• At least 10 to 14 days, preferably 35 days from the day of surgery (especially for patients undergoing total hip arthroplasty) in the absence of risk factors for bleeding.
• LMWH typically started 12 hours before and/or 12 hours after surgery. The rest of the medications are typically started 12 hours postoperatively.
• Aspirin alone is not generally recommended for DVT prophylaxis. Aspirin is efficacious compared to placebo in preventing DVT, but no comparison studies have been done with either UFH or LMWH.[11] Aspirin can be used in hybrid therapy, where other agents are used initially while in the hospital and switched to aspirin at discharge.
• Patients with a high risk of bleeding are placed on mechanical prophylaxis unless contraindicated.
• Patients undergoing an arthroscopic procedure without a prior history of DVT/PE rarely need DVT prophylaxis.
• Patients undergoing isolated lower extremity orthopedic surgery requiring immobilization do not require DVT prophylaxis as long as they can ambulate early and adequately.

DVT Prophylaxis in Patients Undergoing Non-Orthopedic Surgeries

VTE risk is based on the type of surgery and underlying patient risk factors. Major surgeries are categorized as moderate to high risk for VTE and need DVT prophylaxis. When in doubt about the risk of VTE, a modified Caprini risk assessment score can be used. This tool scores risk factors from 1 to 5. Based on this assessment score, a patient undergoing surgery can be categorized below.

• Very low-risk patients: No DVT prophylaxis is needed.
• Low risk: Mechanical methods are preferred.
• Moderate to high-risk patients: Pharmacological agents are used with or without mechanical methods.

LMWH is preferred, but UFH is used in patients with renal insufficiency. Fondaparinux is used in patients with heparin-induced thrombocytopenia. Other agents are typically not used for DVT prophylaxis. The duration of DVT prophylaxis is typically for a few days or until patients can ambulate or discharge from the hospital. A prolonged duration of prophylaxis, even after discharge from the hospital, is not typically recommended. In patients undergoing abdominal or pelvic surgery for cancer and with a low risk of bleeding, pharmacological prophylaxis is extended to a total of 4 weeks.

Pharmacological Agents

• Low-molecular-weight heparin: Enoxaparin, 40 mg subcutaneously once daily, or dalteparin, 5000 units subcutaneously once daily
• Unfractionated heparin: 5000 units subcutaneously every 8 to 12 hours
• Fondaparinux: 2.5 mg subcutaneously daily
• Direct oral anticoagulants: betrixaban or rivaroxaban[12][13]
• Warfarin

Mechanical Agents

• Intermittent pneumatic compressions (IPC)[14]
• Graduated compression stockings (GCS)
• Venous foot pump[15]

DVT Prophylaxis in Pregnancy

The incidence of venous thromboembolism is increased during or trimester of pregnancy and is highest during the postpartum period. Most pregnant patients do not require therapy other than observation. Pharmacological prophylaxis is considered in individual cases, particularly in those with the following risk factors:

• A prior history of VTE
• Hospitalization for an acute illness or cesarean delivery
• The presence of an inherited thrombophilia (eg, factor V Leiden mutation, prothrombin gene mutation, or antithrombin III, protein C, or protein S deficiencies).

Antepartum pharmacological prophylaxis is continued throughout the pregnancy. The optimal duration of outpatient postpartum prophylaxis is unknown. However, the American College of chest physicians suggests at least 6 weeks postpartum, with a longer duration of up to 3 months for those at greater risk. Inpatient from prophylaxis is continued until the patient is ambulatory, provided there is no need for outpatient prophylaxis.

Contraindications

Contraindications for Pharmacological DVT Prophylaxis

• Active bleeding or recent bleeding or high risk for bleeding (active PUD)
• Patients with coagulopathy (INR greater than 1.5)
• A planned surgical procedure in the next 6 to 12 hours
• Thrombocytopenia (Less than 50,000, sometimes less than 100,000)
• Bleeding disorders

 Contraindications for Mechanical Prophylaxis

• Limb ischemia due to peripheral vascular disease
• Skin breakdown

Complications

The complications from pharmacological prophylaxis include:

• Disturbed renal function
• Bleeding
• Heparin-induced thrombocytopenia (HIT)

Clinical Significance

DVT increases the risk of pulmonary embolism by 50% and also leads to post-thrombotic syndrome. Using DVT prophylaxis in hospitalized patients decreases the risk of DVT anywhere from 10 to 80%. DVT prophylaxis decreases the risk of DVT/PE in both hospitalized medical and surgical patients. However, mortality benefits have been reported in surgical patients but not medical patients.[16]

Enhancing Healthcare Team Outcomes

Interprofessional teamwork is essential in preventing DVT in hospitalized patients. Good interprofessional communication among attending clinicians, surgeons (for surgical patients), nursing staff, and pharmacists is vital in using the appropriate prophylaxis methods. All hospitals should have a formal strategy that increases compliance with DVT prophylaxis.

Nursing is on the "front lines" and is especially important in DVT prophylaxis, as they can spot patients who might be at risk but not receiving prophylaxis and alert the attending clinician. Pharmacists are valuable in consulting regarding appropriate agent selection and dosing based on various factors, including patient parameters and other medications. Open communication among clinicians, nursing, and pharmacy is vital in preventing DVT and successfully managing the condition should prophylaxis fail. The interprofessional approach to care, where all team members are empowered to provide input on the case, is the optimal paradigm in DVT prophylaxis. [Level 5]