Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

all at-risk patients

1st line – early mobilisation

Back
INITIAL
|
all at-risk patients
1st line – 

early mobilisation

Early mobilisation should be encouraged to diminish the likelihood of developing a VTE.[30]

ACUTE

trauma patients

1st line – low molecular weight heparin or unfractionated heparin

Back
ACUTE
|
trauma patients
1st line – 

low molecular weight heparin or unfractionated heparin

Major trauma patients should receive thromboprophylaxis with low molecular weight heparin (LMWH) or low-dose unfractionated heparin (UFH) until discharge unless contraindicated.[3]​​[66]

In surgery for acute spinal cord injury, prophylaxis with UFH or LMWH is started after surgery if haemostasis is adequate and continued for 3 months or until the patient is fully ambulatory.[3]

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best medication to use in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.​​[3]

Final choice of agent to be used should be based on evidence-based data as well as local preferences.

If spinal/epidural anaesthesia is considered, thromboprophylaxis must be discussed with the anaesthetist.

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
trauma patients
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

For trauma patients at high risk for VTE (including patients with acute spinal cord injury, traumatic brain injury, and spinal surgery for trauma), adding mechanical prophylaxis, such as graduated compression stockings and intermittent pneumatic compression (IPC) devices, to pharmacological prophylaxis is recommended when not contraindicated by lower-extremity injury.[3]​​[52][139][140][Evidence C] IPC devices are preferred in patients with acute spinal cord injury and in trauma patients.[3]​​[66]

2nd line – graduated compression stockings or intermittent pneumatic compression devices alone

Back
ACUTE
|
trauma patients
2nd line – 

graduated compression stockings or intermittent pneumatic compression devices alone

Non-pharmacological agents such as graduated compression stockings and intermittent pneumatic compression (IPC) devices are not as effective as pharmacological agents.[3]​ They should be used alone only if pharmacological agents are contraindicated. Once the contraindication has resolved, the patient should receive pharmacological prophylaxis. IPC devices are preferred in patients with acute spinal cord injury and in trauma patients.[3]​​[66]

surgical patients

1st line – anticoagulation

Back
ACUTE
|
surgical patients
|
major lower extremity orthopaedic surgery
1st line – 

anticoagulation

Patients undergoing orthopaedic surgery are an extremely high-risk population.[69][70]​​​

For total hip replacement and total knee replacement, society guidelines all agree that some form of prophylaxis is necessary and that pharmacological prophylaxis should be used first-line; however, there is no consensus on choice of agent or duration. Options include: LMWH, fondaparinux, apixaban, rivaroxaban, dabigatran, low-dose UFH, warfarin, or aspirin.[49][66]​​​​​ Minimum duration of thromboprophylaxis is 10-14 days. Extended prophylaxis up to 35 days is recommended for total hip replacement. Extended prophylaxis should also be considered after knee surgery, but the recommendation is much weaker.[49][50][66]

  • The 2012 American College of Chest Physicians (ACCP) guidelines recommend the use of one of the following for a minimum of 10-14 days (ideally extended in the outpatient period to 35 days) for both total hip and knee arthroplasty procedures: LMWH (the preferred option), aspirin, fondaparinux, apixaban, dabigatran, UFH, warfarin, aspirin, and/or an intermittent pneumatic compression (IPC) device.[49]​ In patients who receive LMWH, prophylaxis should be started at least 12 hours preoperatively or postoperatively. Dual prophylaxis with an antithrombotic agent and IPC device should be used during the hospital stay. In patients who are at increased risk for bleeding, an IPC device or no prophylaxis is favoured over pharmacological prophylaxis. For patients who decline injections or an IPC device, apixaban or dabigatran (or, if these are unavailable, rivaroxaban or adjusted-dose warfarin) can be used. Warfarin should be started the night before surgery or on the night of the surgery.

  • The 2019 American Society of Hematology (ASH) guidelines recommend using aspirin or anticoagulants for a minimum of 3 weeks. When anticoagulants are used, direct oral anticoagulants (DOACs) are preferred over LWMH, which is preferred over warfarin or UFH.[68]​ Any of the DOACs approved for use are acceptable, as they have not been directly compared head-to-head in clinical trials.

  • The 2018 UK National Institute of Health and Care Excellence (NICE) guidelines recommend offering prophylaxis for patients whose risk of VTE outweighs the risk of bleeding.[52]​ For hip replacement, first-line options are: LMWH for 10 days followed by aspirin for 28 days; LMWH for 28 days; or rivaroxaban for 35 days. If none of these options are possible, apixaban or dabigatran can be used. For knee replacement, first-line options are: LMWH for 14 days; aspirin for 14 days; or rivaroxaban for 14 days. If none of these options are possible, apixaban or dabigatran can be used.

DOACs have varying degrees of approval worldwide. Based on four randomised trials, dabigatran has been approved in Europe, Canada, and Australia for thromboprophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA).[118][119][120][121]​​​ In the US, dabigatran has been approved by the Food and Drug Administration in patients who have undergone THA only.[122]​ Rivaroxaban and apixaban have been approved in the US and Europe for thromboprophylaxis after both THA and TKA.[122]​ The RECORD (REgulation of Coagulation in ORthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism) series of phase 3 studies of rivaroxaban showed a significant decrease in total VTE without an increase in bleeding compared with enoxaparin for TKA and THA.[123][124][125][126]​​ The evidence for apixaban was based on the ADVANCE-2 and ADVANCE-3 trials.[127][128]

One randomised controlled trial found that in the prevention of symptomatic VTE after THA or TKA, extended prophylaxis with aspirin was not significantly ​different from rivaroxaban in patients who had already received 5 days of rivaroxaban.[129]​ Another study, however, found that in patients undergoing hip or knee arthroplasty for osteoarthritis, use of aspirin resulted in a significantly higher rate of symptomatic VTE within 90 days compared with enoxaparin.[130]

For hip fracture surgery, LMWH, fondaparinux, low-dose UFH, warfarin, aspirin, or an IPC device are recommended for prophylaxis, with preference for LMWH. DOACs should not be used.[49][66][68][Evidence C][Evidence C]​​​​​​​ Again, society guidelines all agree that some form of prophylaxis is necessary; however, there is no consensus on choice of agent or duration​​​​: 

  • ACCP guidelines recommend one of the following for a minimum of 10-14 days, and ideally up to 35 days: LMWH, aspirin, fondaparinux, UFH, and vitamin K antagonist.[49]

  • ASH guidelines advise LMWH or UFH for a minimum of 3 weeks.[68]

  • UK NICE guidelines recommend offering VTE prophylaxis for a month if the risk of VTE outweighs the risk of bleeding.[52]​ Options are: LMWH, starting 6-12 hours after surgery; or fondaparinux, starting 6 hours after surgery, providing there is low risk of bleeding. If surgery is delayed beyond the day after admission, preoperative VTE prophylaxis should be considered. For LMWH, the last dose should be given no less than 12 hours before surgery; for fondaparinux this is extended to 24 hours. If surgery for hip fracture is delayed, LMWH or UFH should be given at least 12 hours before the surgery.

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation, as these agents have a long half-life and no antidote.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.[3]​ Fondaparinux is contraindicated in patients with severe renal insufficiency (creatinine clearance [CrCl] <30 mL/minute). Dabigatran is not recommended in patients with a CrCl <30 mL/minute, especially if it is co-administered with a P-glycoprotein inhibitor. Rivaroxaban is also not recommended in patients with a CrCl <30 mL/minute. Apixaban should be used with caution in patients with a CrCl <30 mL/minute.

If surgery is under spinal/epidural anaesthesia, postoperative thromboprophylaxis must be discussed with the anaesthetist.

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

OR

fondaparinux

OR

warfarin

OR

rivaroxaban

OR

dabigatran

OR

apixaban

Secondary options

aspirin

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
surgical patients
|
major orthopaedic surgery
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

Adding non-pharmacological agents such as graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices to pharmacological prophylaxis is recommended when there is no contraindication.[140] IPC is preferred over GCS.[49][52][66]​ Although select reports show some benefit of using IPC devices in the prevention of VTE, the evidence is of low quality.[91]

2nd line – graduated compression stockings or intermittent pneumatic compression devices alone

Back
ACUTE
|
surgical patients
|
major orthopaedic surgery
2nd line – 

graduated compression stockings or intermittent pneumatic compression devices alone

Non-pharmacological agents such as graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices are not as effective as pharmacological agents.[49] Although select reports show some benefit of using IPC devices in the prevention of VTE, the evidence is of low quality.[91] Therefore, GCS or IPC devices should be used alone only if pharmacological agents are contraindicated. Once the contraindication has resolved, the patient should receive pharmacological prophylaxis.

1st line – graduated compression stockings

Back
ACUTE
|
surgical patients
|
minor orthopaedic surgery without additional VTE risk factors
1st line – 

graduated compression stockings

Thromboprophylaxis is generally not indicated for minor orthopaedic surgery (including surgery for lower extremity fractures and arthroscopic procedures) if the patient does not have additional VTE risk factors.[49][141]

In consensus guidelines, graduated compression stockings are usually recommended in these patients.[66] Early ambulation should be encouraged.

1st line – low molecular weight heparin

Back
ACUTE
|
surgical patients
|
minor orthopaedic surgery with additional risk factors for VTE
1st line – 

low molecular weight heparin

Thromboprophylaxis is generally not indicated for minor orthopaedic surgeries (including surgery for lower extremity fractures and arthroscopic procedures) but can be considered if there are additional risk factors for VTE (previous VTE, thrombophilia, malignancy, trauma, indwelling central catheter [upper or lower extremity], immobility, chronic medical conditions, neurological disease with extremity paresis, increasing age, obesity, oestrogen-containing contraceptive pills and hormone replacement therapy, history of varicose veins, pregnancy, extended travel).

UK NICE guidelines advise that while VTE prophylaxis is generally not needed for people undergoing arthroscopic knee surgery, low molecular weight heparin (LMWH) (started 6-12 hours after surgery and continued for 14 days) should be considered if total anaesthesia time is more than 90 minutes or the person's risk of VTE outweighs their risk of bleeding.[52]

If surgery is under spinal/epidural anaesthesia, postoperative thromboprophylaxis must be discussed with the anaesthetist.

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
surgical patients
|
minor orthopaedic surgery with additional risk factors for VTE
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

Non-pharmacological agents such as graduated compression stockings and intermittent pneumatic compression devices can be added to treatment with pharmacological agents.

1st line – low molecular weight heparin or unfractionated heparin or fondaparinux

Back
ACUTE
|
surgical patients
|
bariatric surgery
1st line – 

low molecular weight heparin or unfractionated heparin or fondaparinux

Probably a high-risk population, although fewer data are available. Thromboprophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin (UFH) or fondaparinux is recommended with the possible addition of mechanical devices until the patient is mobile.[3]​​ [ Cochrane Clinical Answers logo ] [Evidence A] Fondaparinux should not be started preoperatively. Thromboprophylaxis should continue until the risk of VTE has diminished and the patient is mobile.

The UK National Institute for Health and Care Excellence guidelines recommend mechanical VTE prophylaxis for all patients undergoing bariatric surgery, with the addition of LMWH or fondaparinux for at least 7 days in patients whose risk of VTE outweighs their risk of bleeding.[52]

Higher doses of LMWH and UFH may be required in obese patients.[3]​ It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.[3]​​

Fondaparinux is contraindicated in patients with severe renal insufficiency (creatinine clearance <30 mL/minute).

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

fondaparinux

OR

dalteparin

OR

heparin

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
surgical patients
|
bariatric surgery
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

Non-pharmacological agents such as graduated compression stockings or intermittent pneumatic compression devices can be added to treatment with pharmacological agents in selected high-risk patients. UK National Institute of Health and Care Excellence guidelines recommend mechanical VTE prophylaxis for all patients undergoing bariatric surgery, with the addition of low molecular weight heparin (LMWH) or fondaparinux for at least 7 days in patients whose risk of VTE outweighs their risk of bleeding.[52]

A Cochrane review found that mechanical combined with pharmacological prophylaxis, compared to mechanical prophylaxis alone, started 12 hours before bariatric surgery, may reduce the incidence of VTE. However, the evidence was of low certainty and the authors could not assess the effect of this intervention on the incidence of major bleeding, pulmonary embolism, death, or adverse events. The authors concluded that there is a need for high-quality, large randomised controlled trials to determine the best way to prevent VTE in this patient group.[132]

2nd line – graduated compression stockings or intermittent pneumatic compression devices alone

Back
ACUTE
|
surgical patients
|
bariatric surgery
2nd line – 

graduated compression stockings or intermittent pneumatic compression devices alone

Non-pharmacological agents such as graduated compression stockings (GCS) or intermittent pneumatic compression (IPC) devices are not as effective as pharmacological agents.[3]​ Therefore, GCS or IPC devices should be used alone only if pharmacological agents are contraindicated. Once the contraindication has resolved, the patient should receive pharmacological prophylaxis.

1st line – low molecular weight heparin or unfractionated heparin

Back
ACUTE
|
surgical patients
|
vascular surgery
1st line – 

low molecular weight heparin or unfractionated heparin

Thromboprophylaxis with low molecular weight heparin (LMWH) and unfractionated heparin (UFH) is recommended until discharge only in patients with additional VTE risk factors, after major procedures (e.g., repair of aortic aneurysm), and at low risk of major bleeding.[3]​​[52]

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.[3]​​

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
surgical patients
|
vascular surgery
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

Non-pharmacological agents such as graduated compression stockings (GCS) or intermittent pneumatic compression (IPC) devices can be added to treatment with pharmacological agents in selected high-risk patients if there is no peripheral arterial disease.

The current authors recommend the addition of IPC devices rather than GCS to pharmacological thromboprophylaxis in patients undergoing elective surgery considered at moderate to high risk of VTE. In the GAPS study, the use of pharmacological thromboprophylaxis alone was found non-inferior to the combination of pharmacological thromboprophylaxis and GCS for the prevention of VTE.[116]

2nd line – graduated compression stockings and intermittent pneumatic compression devices alone

Back
ACUTE
|
surgical patients
|
vascular surgery
2nd line – 

graduated compression stockings and intermittent pneumatic compression devices alone

Non-pharmacological agents such as graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices are not as effective as pharmacological agents.[3]​ Therefore, GCS or IPC devices should be used alone only if pharmacological agents are contraindicated. Once the contraindication has resolved, the patient should receive pharmacological prophylaxis.

1st line – graduated compression stockings

Back
ACUTE
|
surgical patients
|
minor gynaecological, urological, or general surgery, including laparoscopic surgery, without additional VTE risk factors
1st line – 

graduated compression stockings

Pharmacological thromboprophylaxis is not indicated if it is a minor procedure (e.g., transurethral procedure) and the patient does not have additional VTE risk factors.[3]​ In consensus guidelines, graduated compression stockings are usually recommended in low-risk patients.[66] Early ambulation should be encouraged.

1st line – low molecular weight heparin or unfractionated heparin

Back
ACUTE
|
surgical patients
|
major gynaecological, urological, or general surgery or with additional VTE risk factors
1st line – 

low molecular weight heparin or unfractionated heparin

Prophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin (UFH) is recommended in patients at low risk of major bleeding if it is major surgery or the patient has additional VTE risk factor(s).[3]​​[52][68]

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.[3]​​

If spinal/epidural anaesthesia is considered, thromboprophylaxis must be discussed with the anaesthetist.

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

Consider – extended prophylaxis and/or intermittent pneumatic compression devices or graduated compression stockings

Back
ACUTE
|
surgical patients
|
major gynaecological, urological, or general surgery or with additional VTE risk factors
Consider – 

extended prophylaxis and/or intermittent pneumatic compression devices or graduated compression stockings

Additional treatment recommended for SOME patients in selected patient group

For high-risk gynaecological or general surgery patients (e.g., previous history of VTE or major surgery in a cancer patient), extended prophylaxis up to 28 days can be considered, as well as the addition of intermittent pneumatic compression (IPC) devices or graduated compression stockings (GCS).[3][30]​​​[52][63][66][117][140]​​

The current authors recommend the addition of IPC rather than GCS to pharmacological thromboprophylaxis in patients undergoing elective surgery considered at moderate to high risk of VTE. In the GAPS study, the use of pharmacological thromboprophylaxis alone was found non-inferior to the combination of pharmacological thromboprophylaxis and GCS for the prevention of VTE.[116]

2nd line – graduated compression stockings or intermittent pneumatic compression devices alone

Back
ACUTE
|
surgical patients
|
major gynaecological, urological, or general surgery or with additional VTE risk factors
2nd line – 

graduated compression stockings or intermittent pneumatic compression devices alone

Non-pharmacological agents such as graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices are not as effective as pharmacological agents.[3]​ Therefore, GCS or IPC devices should be used alone only if pharmacological agents are contraindicated. Once the contraindication has resolved, the patient should receive pharmacological prophylaxis.

1st line – low molecular weight heparin or unfractionated heparin or fondaparinux

Back
ACUTE
|
surgical patients
|
thoracic surgery
1st line – 

low molecular weight heparin or unfractionated heparin or fondaparinux

Most thoracic surgery patients are considered to be at least at moderate risk for VTE and thromboprophylaxis should be routinely used.[3] Mechanical prophylaxis (preferably intermittent pneumatic compression [IPC]; graduated compression stockings are an alternative) is recommended for most patients undergoing thoracic surgery and should be started on admission and stopped when the patients ambulate.[52]​ For patients at moderate or high risk for VTE who are not at high risk for major bleeding, guidelines recommend the addition of pharmacological prophylaxis with unfractionated heparin, low molecular weight heparin (LMWH), or dalteparin for a minimum of 7 days.[3][52]​​ For patients who are at high risk for major bleeding, mechanical prophylaxis alone, preferably with IPC, should be used. Once bleeding risk diminishes, pharmacological prophylaxis should be initiated.[3]​ ​

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ The dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.​[3]

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

Secondary options

fondaparinux

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
surgical patients
|
thoracic surgery
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

Most thoracic surgery patients are considered to be at least at moderate risk for VTE and thromboprophylaxis should be routinely used.[3]​ Mechanical prophylaxis (preferably intermittent pneumatic compression; graduated compression stockings are an alternative) is recommended for most patients undergoing thoracic surgery and should be started on admission and stopped when the patients ambulate.[52]​ Mechanical prophylaxis can be added to treatment with pharmacological agents in selected high-risk patients.[3][52][140]

2nd line – graduated compression stockings or intermittent pneumatic compression devices alone

Back
ACUTE
|
surgical patients
|
thoracic surgery
2nd line – 

graduated compression stockings or intermittent pneumatic compression devices alone

Non-pharmacological agents such as graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices are not as effective as pharmacological agents.[3]​ Therefore, GCS or IPC devices (IPC being the preferred option over GCS) should be used alone if pharmacological agents are contraindicated. Once the contraindication has resolved, the patient should receive pharmacological prophylaxis.

1st line – intermittent pneumatic compression devices

Back
ACUTE
|
surgical patients
|
cardiac surgery
1st line – 

intermittent pneumatic compression devices

For patients undergoing coronary artery bypass graft with a high risk of bleeding, the American College of Chest Physicians recommends the optimal use of mechanical thromboprophylaxis.[3]

Intermittent pneumatic compression devices are preferred over graduated compression stockings.

Consider – low molecular weight heparin or unfractionated heparin or fondaparinux

Back
ACUTE
|
surgical patients
|
cardiac surgery
Consider – 

low molecular weight heparin or unfractionated heparin or fondaparinux

Additional treatment recommended for SOME patients in selected patient group

The American College of Chest Physicians (ACCP) recommends adding unfractionated heparin (UFH) or low molecular weight heparin (LMWH) to mechanical prophylaxis in patients with a prolonged hospital course with 1 or more non-haemorrhagic surgical complications.[3]​ ASH guidelines suggest considering LMWH or UFH for patients undergoing cardiac surgery when there is a higher baseline risk for VTE.[68][Evidence C]​​​​​ UK National Institute of Health and Care Excellence (NICE) guidelines recommend considering the addition of LMWH to mechanical prophylaxis for at least 7 days in patients who are not receiving other anticoagulation therapy.[52][Evidence C]​​​​​​ Fondaparinux should be used second-line if LMWH is contraindicated.​

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. However, UFH is sometimes used for the surgical procedure once the anti-platelet factor 4 antibodies have disappeared. Exposure to heparin is then minimised by choosing an alternative agent. Consultation with a thrombosis specialist may be warranted to determine the best option, as these agents have a long half-life and no antidote.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.​[3]

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

Secondary options

fondaparinux

1st line – intermittent pneumatic compression devices

Back
ACUTE
|
surgical patients
|
neurosurgery
1st line – 

intermittent pneumatic compression devices

Patients undergoing neurosurgery (such as resection of meningioma) are a special population because of the bleeding risk and potential serious consequences of bleeding. Routine thromboprophylaxis with mechanical measures such as intermittent pneumatic compression (IPC) devices is recommended.[3]​​[52][66][Evidence C]​ 

Consider – low molecular weight heparin or unfractionated heparin

Back
ACUTE
|
surgical patients
|
neurosurgery
Consider – 

low molecular weight heparin or unfractionated heparin

Additional treatment recommended for SOME patients in selected patient group

In patients at low risk of bleeding, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) should be added to intermittent pneumatic compression devices if not contraindicated.[3]​​[66][68]

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted heparin dosing was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.​​​[3]

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

1st line – intermittent pneumatic compression devices

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ACUTE
|
surgical patients
|
elective spinal surgery
1st line – 

intermittent pneumatic compression devices

Routine thromboprophylaxis with intermittent pneumatic compression devices is recommended.[3]​​[52][66]

Consider – low molecular weight heparin or unfractionated heparin

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ACUTE
|
surgical patients
|
elective spinal surgery
Consider – 

low molecular weight heparin or unfractionated heparin

Additional treatment recommended for SOME patients in selected patient group

If additional VTE risk factors are present, a combination of pharmacological methods (low molecular weight heparin [LMWH] or unfractionated heparin [UFH]) with intermittent pneumatic compression devices can be used once adequate haemostasis is established and the risk of bleeding decreases.[3]​​

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted dose heparin was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.​[3]​​

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.[3]​​

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

medical patients

1st line – low molecular weight heparin or fondaparinux or unfractionated heparin

Back
ACUTE
|
medical patients
|
with pulmonary or cardiovascular decompensation, or acute infectious, rheumatic, or inflammatory conditions, or immobilised with one or more additional VTE risk factors
1st line – 

low molecular weight heparin or fondaparinux or unfractionated heparin

If the patient is 1) admitted for pulmonary or cardiovascular decompensation, or acute infectious, rheumatic, or inflammatory conditions, or is immobilised due to a medical illness and 2) has one or more additional VTE risk factors, thromboprophylaxis with low molecular weight heparin (LMWH) or fondaparinux is preferred over unfractionated heparin (UFH), until either full mobility is restored or the patient is discharged from hospital.[82] 

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted dosing of heparin was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.[3]​​

The American Society of Hematology guidelines do not recommend direct oral anticoagulants. Rivaroxaban is approved by the US Food and Drug Administration for VTE prevention in acutely ill hospitalized medical patients; however, data from clinical trials of apixaban and rivaroxaban as thromboprophylaxis in medical patients found increased bleeding risk with these agents, and the current authors do not recommend their use.[86][87]

A past history of heparin-induced thrombocytopenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.[3]​ Fondaparinux is contraindicated in patients with severe renal insufficiency (creatinine clearance <30 mL/minute).

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

fondaparinux

Secondary options

heparin

1st line – low molecular weight heparin or unfractionated heparin

Back
ACUTE
|
medical patients
|
ICU patient
1st line – 

low molecular weight heparin or unfractionated heparin

Critical-care patients should receive thromboprophylaxis. Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are both accepted.[51]​​ No agent has been clearly shown superior in terms of efficacy or bleeding.[103]​ In the PROTECT trial, where 3675 critical care patients were randomly assigned to receive prophylactic dose of dalteparin versus UFH, dalteparin was not superior to UFH in preventing thrombosis.[103]​ There are no data on fondaparinux or direct oral anticoagulants in this population. The American Society of Hematology (ASH) guidelines suggest using LMWH over UFH due to a lower incidence of heparin-induced thrombocytopenia (HIT) with LMWH.[82][Evidence B]​​​ 

It has been suggested that weight-based dosing of LMWH might be preferable to fixed-dosing for obese patients (body mass index >30 kg/m²).[136] However, one meta-analysis concluded that for hospitalised obese patients, weight-adjusted dosing of heparin was not associated with a decreased risk of VTE, compared with fixed-dose heparin.[137]​ Dose can be adjusted empirically for patients <50 kg who are at risk of bleeding, but guidelines do not address this issue.​[3]

A past history of heparin-induced thrombocytopaenia is an important contraindication to LMWH or UFH. Consultation with a thrombosis specialist is warranted to determine the best treatment option in this situation.

In patients with renal insufficiency, unfractionated heparin or LMWH (e.g., enoxaparin, dose-adjusted according to the manufacturer's instructions) may be used. No level of anti-Xa has been shown to be effective and safe for prophylactic doses of LMWH.​[3]

Consult specialist or local protocols for guidance on dose.

Primary options

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

heparin

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
medical patients
|
ICU patient
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

Non-pharmacological agents such as graduated compression stockings or intermittent pneumatic compression devices can be added to treatment with pharmacological agents in selected higher-risk patients.

2nd line – graduated compression stockings or intermittent pneumatic compression devices alone

Back
ACUTE
|
medical patients
|
ICU patient
2nd line – 

graduated compression stockings or intermittent pneumatic compression devices alone

Non-pharmacological agents such as graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices are not as effective as pharmacological agents.[51]​​ Therefore, GCS or IPC devices should be used alone if pharmacological agents are contraindicated. Once the contraindication has resolved, the patient should receive pharmacological prophylaxis.

1st line – anticoagulation

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ACUTE
|
medical patients
|
ambulatory cancer patients at high risk
1st line – 

anticoagulation

Thromboprophylaxis is generally not recommended for low-risk ambulatory patients with cancer.[51][60][61][62] [104]

However, the American Society of Clinical Oncology (ASCO), the International Initiative on Thrombosis and Cancer, the American Society of Hematology (ASH), and the European Society of Medical Oncology (ESMO) recommend that high-risk outpatients with cancer (Khorana score ≥2 prior to starting a new systemic chemotherapy regimen) may be offered thromboprophylaxis with apixaban, rivaroxaban, or low molecular weight heparin (LMWH) provided there are no significant risk factors for bleeding and no drug interactions.[60][62][63][104]​​ ​The American College of Chest Physicians guidelines suggest thromboprophylaxis in cancer outpatients with solid tumours who are at low risk of bleeding with one or more additional VTE risk factors. Additional risk factors include previous VTE, immobilisation, hormonal therapy, angiogenesis inhibitors, and thalidomide or lenalidomide therapy.[51]​ Evidence for this suggestion is weak and further trials are needed to clarify this question.

Patients with multiple myeloma are at particularly increased risk of VTE as a result of treatments (thalidomide-, lenalidomide-, and pomalidomide-containing regimens; dexamethasone; erythropoieitin), and also other factors, such as characteristics of the malignancy.[60] The highest risk for VTE is in the first 6 months following diagnosis.[111]​ Use of VTE prophylaxis in these patients is guided using risk stratification scores, such as IMPEDE or SAVED.​[112][113]​​ Both scores require future validation. Generally, guidelines recommend aspirin in low-risk patients and prophylaxis-dose LMWH, warfarin, or low-dose direct oral anticoagulants (rivaroxaban or apixaban) in high-risk patients. Specifically, the American Society of Clinical Oncology recommends aspirin or LMWH for lower-risk patients and LMWH for higher-risk patients; the 2008 International Myeloma Working Group guidelines recommend aspirin in low-risk myeloma patients with one VTE risk factor and LMWH or warfarin in high-risk patients with two or more risk factors;​​​​​ Guidelines from the National Comprehensive Cancer Network also recommend aspirin for low-risk patients and LMWH, warfarin, rivaroxaban, apixaban, or fondaparinux for high-risk patients; the European Society of Medical Oncology recommends aspirin for low-risk patients, with LMWH for high-risk patients, or rivaroxaban or apixaban as an alternative; and the American Society of Hematology suggests using either prophylactic LMWH, low-dose aspirin, or low dose warfarin for patients receiving thalidomide, lenalidomide, or pomalidomide.​​[25][60][62][104][111]​​

Consult specialist or local protocols for guidance on dose.

Primary options

apixaban

OR

rivaroxaban

OR

enoxaparin

OR

tinzaparin

OR

dalteparin

OR

fondaparinux

OR

warfarin

OR

aspirin

Consider – graduated compression stockings or intermittent pneumatic compression devices

Back
ACUTE
|
medical patients
|
ambulatory cancer patients at high risk
Consider – 

graduated compression stockings or intermittent pneumatic compression devices

Additional treatment recommended for SOME patients in selected patient group

Non-pharmacological agents such as graduated compression stockings or intermittent pneumatic compression devices can be added to treatment with pharmacological agents in selected high-risk patients.

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