Venous Thromboembolism: Primary Prevention

Methods of PreventionTop

The choice of method depends on the patient’s characteristics (risk of venous thromboembolism [VTE], of bleeding, and of other complications) as well as the feasibility of the method (availability, cost, ability to monitor the anticoagulant effect).

1. Early mobilization.

2. Mechanical treatment:

1) Graduated compression stockings (or appropriately applied short-stretch bandages).

2) An intermittent pneumatic compression device, which facilitates outflow of venous blood from the lower extremities. The device consists of a cuff applied to the lower or upper extremity and an electrical pneumatic pump, which periodically fills segments of the cuff with compressed air.

3. Anticoagulant terminology (contraindications and complications: see Anticoagulant Treatment):

1) Heparins: Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs).

2) Selective factor Xa inhibitors: Fondaparinux, apixaban, edoxaban, rivaroxaban, betrixaban (available in the United States only).

3) Direct thrombin inhibitors: Dabigatran (oral; the other are parenteral), bivalirudin, argatroban, desirudin.

3) Vitamin K antagonists (VKAs): Acenocoumarol, warfarin.

4) Direct oral anticoagulants (DOACs): Apixaban, dabigatran, edoxaban, rivaroxaban.

Patients after Surgery or TraumaTop

Prevention of VTE is usually started before the surgery or within 24 hours afterwards and is continued until the patient is fully mobile; in the case of major orthopedic surgery, prevention continues for ≥10 to 14 days and up to 35 days.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to indirectness (asymptomatic deep vein thrombosis) and imprecision in some of the critical outcomes. Falck-Ytter Y, Francis CW, Johanson NA, et al; American College of Chest Physicians. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e278S-325S. doi: 10.1378/chest.11-2404. PMID: 22315265; PMCID: PMC3278063.

Because of high incidence of VTE after discharge from the hospital, it is suggested to continue the VTE prophylaxis, typically with a LMWH, for up to 35 days in patients after major orthopedic surgeryEvidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to imprecision. Falck-Ytter Y, Francis CW, Johanson NA, et al; American College of Chest Physicians. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e278S-325S. doi: 10.1378/chest.11-2404. PMID: 22315265; PMCID: PMC3278063.. Anderson DR, Morgano GP, Bennett C, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019 Dec 10;3(23):3898-3944. doi: 10.1182/bloodadvances.2019000975. PMID: 31794602; PMCID: PMC6963238. and it is recommended to continue prophylaxis up to 4 weeks in other high-risk patients (eg, with prolonged immobilization) after abdominal or pelvic cancer surgery, as long as these patients are not at a high risk of bleeding.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to imprecision, indirectness, and potential bias (unclear blinding and concealment). Gould MK, Garcia DA, Wren SM, et al; American College of Chest Physicians. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e227S-77S. doi: 10.1378/chest.11-2297. Erratum in: Chest. 2012 May;141(5):1369. PMID: 22315263; PMCID: PMC3278061. Schünemann HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018 Nov 27;2(22):3198-3225. doi: 10.1182/bloodadvances.2018022954. PMID: 30482763; PMCID: PMC6258910. The choice of the prevention method depends on the individual risk of thrombosis (Table 1).

After elective hip or knee replacement surgery, prophylaxis with a DOAC can be considered, using apixaban 2.5 mg bid, dabigatran 150 mg to 220 mg daily, or rivaroxaban 10 mg daily. An alternative option involves a hybrid approach comprising 5 days of rivaroxaban 10 mg daily followed by 14 to 28 days of acetylsalicylic acid (ASA) 75 to 100 mg daily.

Also see Perioperative DOAC Management.

Medical PatientsTop

Risk factors: Table 2.

Principles of prevention: Table 3.

Drug dosage: Table 4.

Patients with CancerTop

1. The risk of VTE in patients with cancer is ~6-fold higher than in patients without cancer; this concerns in particular patients with malignant brain tumors and adenocarcinomas of the ovary, pancreas, colon, stomach, lung, prostate, or kidney, as well as with hematologic malignancies. It is further increased by immobilization, hospitalization, treatment with angiogenesis inhibitors (thalidomide, lenalidomide, bevacizumab), erythropoietin, darbepoetin, chemotherapy (particularly with platinum analogues), and surgical procedures. VTE in patients with cancer can be asymptomatic (so-called incidental VTE) and it is diagnosed as a result of imaging performed for the staging of cancer or evaluation of the effects of cancer therapy. Both incidental and symptomatic thrombosis are independent risk factors for recurrent VTE and reduced survival of the patients. Risk score: Table 5.

2. Recommended prevention of VTE in outpatients with solid tumors: VTE prophylaxis can be considered in selected high-risk outpatients with solid tumors who are receiving chemotherapy. Treatment options include LMWH or selected DOACs:

1) Consider a prophylactic-dose anticoagulant in the following patients:

a) Patients with additional risk factors of VTE (see above) or risk factors included in the Khorana score (Table 5), and at a low risk of bleeding (do not use prophylactic anticoagulant treatment in patients with none of these features).

b) Patients receiving chemotherapy for pancreatic cancer or lung cancer who are at a low risk of bleeding (such prophylactic treatment is ineffective in patients with metastatic breast cancer, and it increases the risk of intracranial hemorrhage in patients with brain tumors).

c) Patients treated with angiogenesis inhibitors combined with glucocorticoids or doxorubicin (other therapeutic options in this group of patients include low-dose ASA (eg, 75-100 mg/d) or a VKA at a low dose or at a dose maintaining the international normalized ratio [INR] in the range of 2.0-3.0).

2) Do not use routine prophylactic anticoagulant treatment to prevent central venous catheter–associated thrombosis in patients with no additional risk factors for VTE.

3. Recommended prevention of VTE in hospitalized medical patients: Table 3.

Long-Distance TravelTop

Overall, there is only low-quality evidence regarding the use of intervention to prevent VTE during long-distance travel (>6 h) and all statements below represent suggestions.

1. For long-distance air travelers, suggest wearing loose-fitting clothing that does not compress the lower extremities or the waist, drinking plenty of nonalcoholic beverages, avoiding alcohol and caffeinated beverages, frequent tightening of the muscles of the calf during the flight, flexing the toes or standing on tiptoes, and avoiding sleeping in a sitting position with knees flexed >90 degrees.

2. For long-distance air travelers at increased risk for VTE, suggest frequent ambulation, calf muscle exercises, or sitting in an aisle seat, if feasible. The use of knee-high graduated compression socks with 15 to 30 mm Hg compression at the ankle level is suggested in the following groups: individuals with a history of VTE, recent (<6 weeks) trauma, or surgery; patients with cancer; women who are pregnant or receive estrogens; elderly persons; physically handicapped or obese persons; patients with thrombophilia. A single prophylactic dose of a LMWH before departure can be used in selected patients at increased risk for VTE (eg, VTE within the past year). The prophylactic use of antiplatelet agents is not recommended.

3. For long-distance travel by car, bus, or train, in addition to the above-mentioned propositions we suggest periodic ambulation during car stops or while travelling.

PREGNANCYTop

1. Appropriate prevention of VTE in pregnant patients is very important. In resource-rich countries, PE is the most common cause of death in women during pregnancy and the postpartum period.

2. Recommended methods of prevention in pregnant women at increased risk of VTE: Table 6.

3. LMWHs are the drugs of choice (agents: Table 2, dosage: Table 4), but UFH may also be used (5000 IU administered subcutaneously every 12 h) because—unlike VKAs—heparins do not cross the placenta and do not cause fetal malformations. New oral anticoagulants (factor Xa inhibitors and thrombin inhibitors) have not been studied in pregnant women and thus are not recommended.

4. The use of LMWHs, UFH, or VKAs by a mother is not a contraindication to breastfeeding; however, fondaparinux and DOACs should not be administered during lactation.

5. In women receiving long-term VKA treatment who plan to become pregnant, frequent pregnancy testing is recommended. Once the patient becomes pregnant, she should be switched from VKAs to UFH or LMWHs. An alternative approach is to switch from a VKA to an LMWH before attempting to become pregnant. This does not apply to women with implanted mechanical heart valves, who should be referred to a specialist center.

6. DOACs should be avoided during pregnancy because they cross the placenta and their effects on the developing fetus are uncertain.

TablesTop