Primary Prevention of Venous Thromboembolism

Chapter: Primary Prevention of Venous Thromboembolism
McMaster Section Editor(s): James Douketis
Section Editor(s) in Interna Szczeklika: Krystyna Zawilska, Anetta Undas, Wiktoria Leśniak
McMaster Author(s): James Douketis
Author(s) in Interna Szczeklika: Krystyna Zawilska, Rafał Niżankowski
Additional Information

Methods of Prevention Top

The choice of the 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. Anticoagulants (contraindications and complications: see Anticoagulant Treatment):

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

2) Selective factor Xa inhibitors: Fondaparinux, rivaroxaban, apixaban.

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

4) An oral direct thrombin inhibitor: Dabigatran.

Patients after Surgery or Trauma Top

Prevention of VTE is usually started before the surgery or within 24 hours afterwards and is continued until the patient is completely mobilized; in the case of major orthopedic surgery, prevention continues for ≥10 to 14 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. PubMed PMID: 22315265; PubMed Central PMCID: PMC3278063.

Because of high incidence of VTE after discharge from hospital, it is suggested to continue the prophylactic anticoagulation (optimally with LMWHs) 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. PubMed PMID: 22315265; PubMed Central PMCID: PMC3278063. and it is recommended to continue prophylaxis up to 4 weeks in high-risk patients (eg, with prolonged immobilization) after abdominal or pelvic cancer surgery, as long as these patients are not at 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. PubMed PMID: 22315263; PubMed Central PMCID: PMC3278061. The choice of the prevention method depends on the individual risk of thrombosis (Table. A modified Caprini risk assessment...).

Medical Patients Top

Risk factors: Table. Risk factors for venous thromboembolism....

Principles of prevention: Table. Prevention of venous thromboembolism in....

Drug dosage: Table. Prophylactic doses of low-molecular-weight heparin....

Patients with Cancer Top

1. The risk of VTE in patients with cancer is approximately 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. Risk assessment score for venous....

2. Recommended prevention of VTE in outpatients with solid tumors:

1) Consider a prophylactic dose of an LMWH in the following patients:

a) Patients with additional risk factors of VTE (see above) or risk factors included in the Khorana score (Table. Risk assessment score for venous...), and at 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 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 acetylsalicylic acid 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 patients:

1) In medical patients: Table. Prevention of venous thromboembolism in....

2) In surgical patients: Table. A modified Caprini risk assessment....

Long-Distance Travel Top

Overall, there is only low-quality evidence regarding the use of intervention to prevent VTE during long-distance travel (>6 hours) 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.

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 developed 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. Prevention of venous thromboembolism in....

3. LMWHs are the drugs of choice (agents: Table. Dosage of low-molecular-weight heparin in..., dosage: Table. Prophylactic doses of low-molecular-weight heparin...), but UFH may also be used (5000 U administered subcutaneously every 12 hours), because—unlike VKAs—heparins do not cross the placenta and do not cause fetal malformations or bleeding. 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, oral factor Xa inhibitors, and thrombin inhibitors 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.

TablesTop

Table. A modified Caprini risk assessment score

Each risk factor represents 1 point

Each risk factor represents 2 points

Each risk factor represents 3 points

Each risk factor represents 5 points

– Age 41-60 years

– Minor surgery planned

– BMI >25 kg/m2

– Lower limb edema

– Varicose veins in lower limb

– Pregnancy or postpartum

– History of unexplained or recurrent miscarriage/stillborn infant

– Oral contraceptives or HRT

– Sepsis (<1 month)

– Serious lung disease, including pneumonia (<1 month)

– Abnormal pulmonary function

– Acute myocardial infarction

– Onset or exacerbation of heart failure (<1 month)

– History of inflammatory bowel disease

– Medical patient currently at bed rest

– Age 61-74 years

– Arthroscopic surgery

– Major surgery (>45 min)

– Laparoscopic surgery (>45 min)

– Malignancy

– Patient confined to bed (>72 h)

– Limb immobilized in plaster cast

– Central venous access

– Age ≥75 years

– History of VTE

– Family history of VTE

– Positive factor V Leiden

– Positive prothrombin 20210a

– Positive lupus anticoagulant

– Positive anticardiolipin antibodies

– Positive anti–beta2-GPI antibodies

– Elevated serum homocysteine

– HIT

– Other congenital or acquired thrombophilia

– Stroke (<1 month)

– Elective arthroplasty

– Hip, pelvis, or leg fracture

– Acute spinal cord injury (<1 month)

Interpretation of risk level:

Score 0: Very low risk

Score 1-2: Low risk

Score 3-4: Moderate risk

Score ≥5: High risk

Anti–beta2-GPI, anti–beta2-glycoprotein I; BMI, body mass index; HIT, heparin-induced thrombocytopenia; HRT, hormone replacement therapy; VTE, venous thromboembolism.

Table. Risk factors for venous thromboembolism in hospitalized patients: the Padua risk assessment score
Baseline features Score

Active cancer (patients with regional lymph node involvement or distant metastases who received chemotherapy or radiotherapy in the prior 6 months)

3 points

A history of VTE (except for superficial vein thrombosis)

3 points

Immobilization (bed rest with bathroom privileges, either due to patient’s limitations or physician order, for at least 3 days)

3 points

Previous diagnosis of thrombophilia (deficiencies of antithrombin, protein C, protein S, or factor V Leiden, prothrombin gene G20210A mutation, or antiphospholipid syndrome)

3 points

Recent (≤1 month) trauma or surgery

2 points

≥70 years of age

1 point

Heart failure or respiratory failure

1 point

Acute myocardial infarction or ischemic stroke

1 point

Acute infection or rheumatologic disorder

1 point

Obesity (BMI ≥30 kg/m2)

1 point

Hormonal therapy

1 point

Interpretation:

Score ≥4: High risk of VTE

Adapted from: Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010 Nov;8(11):2450-7.

BMI, body mass index; VTE, venous thromboembolism.

Table. Prevention of venous thromboembolism in medical patients

Clinical condition

Recommended prevention

Ischemic stroke with impaired mobilitya

Options:

– Adequate prophylactic dose of LMWHb (preferred)

– UFH 5000 U sc every 12 hours

– IPC and/or graduated compression elastic stockings in patients with contraindications to anticoagulant treatment

Note: You can safely use a prophylactic dose of heparin in combination with ASA. However, do not use heparin in the first 24 hours after thrombolytic treatment of stroke

Hemorrhagic strokea

– Use IPC in early treatment

– In clinically stable patients at very high risk of VTE you may use LMWH at an adequate prophylactic doseb (preferred dose) or UFH 5000 sc every 12 h, starting on day 2-4 after the bleeding, if considered safe (documented cessation of bleeding)

Note: The time for starting heparin administration depends on the evaluation of the risk of thrombosis and the risk of recurrent bleeding in the patient

Hospitalized acutely ill medical patients at high risk of VTE (Padua Score ≥4)c

Options:

– Adequate prophylactic dose of LMWHb

– UFH 5000 U sc every 12 h

– Fondaparinux 2.5 mgd sc every 24 h

– In the case of bleeding or high risk of bleedinge, use IPC and/or graduated compression elastic stockings at least in early treatment until the risk of bleeding is reduced

Use pharmacologic prophylaxis during the time of the patient’s immobilization or hospitalization

Long-term immobilized patients remaining at home or in an institution

Do not use VTE prevention routinely

a Recommendations for the management of patients with stroke apply to VTE prophylaxis only, and not to the anticoagulant and thrombolytic treatment of stroke.

b Agents: see Deep Vein Thrombosis. Dosage: see Table. Prophylactic doses of low-molecular-weight heparin....

c See Table. Risk factors for venous thromboembolism....

d 1.5 mg in patients with a creatinine clearance <50 mL/min.

e The risk of bleeding is highest in patients with active gastric or duodenal ulcers, a history of severe bleeding within the prior 3 months, platelet counts of <50 × 109/L, or liver failure (INR >1.5). Other risk factors of bleeding: ≥85 years of age (vs <40 years), severe renal failure (GFR <30 mL/min/1.73 m2), admission to an intensive care unit or coronary care unit, insertion of a central venous catheter, chronic arthritis, cancer, male sex. The coexistence of several of these factors indicates a significant increase in the risk of bleeding. Moreover, these factors often increase the risk of VTE. Hence the decision to start anticoagulant treatment should be based on a joint evaluation of all these risks.

ASA, acetylsalicylic acid; GFR, glomerular filtration rate; INR, international normalized ratio; IPC, intermittent pneumatic compression; LMWH, low-molecular-weight heparin; sc, subcutaneous; UFH, unfractionated heparin; VTE, venous thromboembolism.

Table. Prophylactic doses of low-molecular-weight heparin in medical patients and pregnant women

Low-molecular-weight heparina

Prophylactic doses

Medical patients

Pregnant women

Dalteparin

5000 U every 24 h

5000 U subcutaneously every 24 h

Enoxaparin

40 mg every 24 h

40 mg subcutaneously every 24 hb

Nadroparin

2850 U every 24 h

3800 U subcutaneously every 24 h

a Agents: see Deep Vein Thrombosis and Table. Dosage of low-molecular-weight heparin in....

b Dose adjustment may be necessary in the case of extremely low or extremely high body weight.

Table. Risk assessment score for venous thromboembolism in outpatients with cancer treated with chemotherapy (Khorana score)

Clinical features

Score

Type of cancer

Stomach, pancreas (very high risk)

2

Lung, lymphoma, gynecologic, genitourinary (high risk)

1

Platelet count before chemotherapy ≥350,000/microL

1

White blood cell count before chemotherapy >11,000/microL

1

Hemoglobin level before chemotherapy <10 g/dL and/or planned use of erythropoiesis stimulating agents

1

Body mass index ≥35 kg/m2

1

Interpretation:

Score 0: Low risk

Score 1-2: Intermediate risk

Score ≥3: High risk

Adapted from: Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008 May 15;111(10):4902-7. doi: 10.1182/blood-2007-10-116327. Epub 2008 Jan 23.

Table. Prevention of venous thromboembolism in high-risk pregnant women

Clinical setting

Recommended prevention

During pregnancy

Postpartum

History of 1 VTE episode associated with a transient risk factor (except pregnancy and estrogen use)

Careful monitoringa

LMWHb or VKAc

History of 1 VTE episode associated with pregnancy or estrogen use

LMWHd/UFHd

LMWHb or VKAc

History of 1 idiopathic VTE episode (in a patient without thrombophilia and currently not receiving long-term anticoagulant treatment)

LMWHd/UFHd or careful monitoringa

LMWHb or VKAc

History of 1 VTE episode in a patient with low-risk thrombophiliae (currently not receiving long-term anticoagulant treatment)

LMWHd/UFHd or careful monitoringa

LMWHb or VKAc

History of 1 VTE episode in a patient with high-risk thrombophiliaf (currently not receiving long-term anticoagulant treatment)

LMWHg/UFHg

LMWHb or VKAc or LMWH/UFHh

Negative history of VTE in a patient with low-risk thrombophilia

Careful monitoringa

Careful monitoringa or anticoagulant treatment if positive family history of VTE (LMWHb or VKAc)i

Negative history of VTE in a patient with high-risk thrombophiliag

LMWHd/UFHd

LMWHb or VKAc

History of ≥2 VTE episodes in a patient receiving long-term anticoagulant treatment

LMWHj/UFHj

Continuation of long-term treatment used before pregnancy

History of ≥2 VTE episodes (currently not receiving long-term anticoagulant treatment)

LMWHg/UFHg

LMWHb or VKAc or LMWH/UFHh

a Plus prompt diagnostic workup in patients with suspected DVT/PE.

b At a prophylactic dose (see Table. Prophylactic doses of low-molecular-weight heparin...) for 4-6 weeks. Do not reduce the dose of LMWH used during pregnancy.

c For 4-6 weeks, INR 2.0-3.0 (initially together with LMWH/UFH until the INR is ≥2.0 for 2 consecutive days).

d At a prophylactic dose.

e Heterozygotes for factor V Leiden, heterozygotes for the prothrombin G20210A gene, deficiency of protein C or protein S.

f Antithrombin deficiency, double heterozygotes for the prothrombin G20210A gene and factor V Leiden, homozygotes for factor V Leiden or homozygotes for the prothrombin G20210A gene.

g Adjusted or prophylactic dose.

h Adjusted dose for 6 weeks.

i If additional risk factors are present (a first-degree relative with an episode of VTE before 50 years of age or other major risk factors for thrombosis, eg, obesity, prolonged immobilization).

j Adjusted dose.

Note: In patients with a history of DVT, use adequately fitted graduated compression stockings during pregnancy, labor, and postpartum.

DVT, deep vein thrombosis; INR, international normalized ratio; LMWH, low-molecular-weight heparin; PE, pulmonary embolism; UFH, unfractionated heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism.

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