Approach

Thrombotic risk varies with the reason for admission to hospital and the characteristics of the patient. Physicians should evaluate the risk of VTE in all patients admitted to hospital, while also considering bleeding risk and any contraindications to pharmacological VTE prophylaxis. Baseline investigations include renal function and full blood count (FBC), with coagulation profile if coagulation disorder is suspected.

Risk stratification for venous thrombosis

General guidelines address options for prophylaxis according to the type of patient (medical or surgical) and the type of surgery. Thromboprophylaxis must then be tailored to the individual patient in terms of additional VTE risk factors.[52]

Key risk factors include previous VTE (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]), thrombophilia, malignancy, postoperative setting, trauma, indwelling central catheter (upper or lower extremity), and immobility. Other risk factors include chronic medical conditions, admission to intensive care, neurological disease with extremity paresis, increasing age, obesity, oestrogen-containing contraceptive pills and hormone replacement therapy (HRT), androgen-deprivation therapy, varicose veins, pregnancy and up to 6 weeks postnatal, first-degree relative with a history of VTE, and extended travel. However, these often have conflicting evidence.

Risk stratification for bleeding (patient-related factors, spinal anaesthesia, neurosurgical procedures)

Because pharmacological anticoagulation agents are considered the mainstay of VTE prophylaxis, risk stratification for bleeding must be assessed. Pharmacological agents are contraindicated if the patient presents with active bleeding, severe thrombocytopenia, or a coagulation disorder.[3]​ Baseline FBC and coagulation parameters (if a coagulation disorder is suspected) help rule out these contraindications. Non-pharmacological agents, including graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) devices, are recommended in patients at high risk of bleeding.[3]​ Clinical scores can help assess the risk of bleeding and guide clinical decisions. The IMPROVE bleeding risk score has been prospectively validated and can help make the decision whether to administer a pharmacological thromboprophylaxis.[53][54]

An assessment of bleeding risk must also consider the presence of neuraxial anaesthesia and analgesia. Spinal haematoma (symptomatic bleeding within the spinal neuraxis) is a rare, but potentially catastrophic complication of spinal or epidural anaesthesia, and the risk varies with factors such as age, associated abnormalities of the spine, underlying coagulopathy, and an indwelling neuraxial catheter during sustained anticoagulation.[55] Care must be taken to avoid giving anticoagulants close to catheter insertion and removal so that no clinically significant anticoagulant effect is present at the time of the procedure.

Other contraindication to pharmacological agents

A past history of heparin-induced thrombocytopenia (HIT) is an important contraindication to unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Even if serum antiplatelet factor 4 (anti-PF4) antibodies are not detectable, avoiding UFH or LMWH for thromboprophylaxis is advisable if alternative agents are available.[56]

Hypersensitivity to a pharmacological agent is another contraindication requiring the use of an alternative agent.

Baseline tests

Before initiating thromboprophylaxis, all patients should have the following tests performed.

  • Renal function: agents such as LMWH and fondaparinux are eliminated through the kidney and must be used with caution in patients with chronic kidney disease.[57][58] Before starting thromboprophylaxis, creatinine should be measured and creatinine clearance subsequently calculated.

  • FBC: this will rule out an acute drop in haemoglobin or severe thrombocytopenia, which are contraindications to pharmacological thromboprophylaxis.

  • Coagulation profile: this should be ordered if a coagulation disorder is suspected.

  • Serum anti-PF4 antibodies: this should be ordered if there is a clinical suspicion of HIT while the patient is receiving UFH or LMWH (>50% drop in platelet counts, arterial or venous thrombosis while the patient is receiving heparin).

Medical patients

In general, VTE prophylaxis consists of pharmacological and non-pharmacological measures to diminish the risk of DVT and PE. Pharmacological thromboprophylaxis is indicated if the patient is admitted for pulmonary or cardiovascular decompensation; or acute infectious, rheumatic, or inflammatory conditions; or is immobilised due to a medical illness and has one or more additional VTE risk factors.[51]​​[59]

Recommendations for special medical patients (intensive care unit, cancer [ambulatory], catheter-related)

Almost all critical-care patients should receive thromboprophylaxis.[51]​

For low risk ambulatory patients with cancer receiving chemotherapy, thromboprophylaxis is generally not indicated.[51]​​[60]​​​[61]​​​ However, the American Society of Clinical Oncology and the International Initiative on Thrombosis and Cancer guidelines now recommend offering thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer (Khorana score ≥2 prior to starting a new systemic chemotherapy regimen) provided there are no significant risk factors for bleeding and no drug interactions.[62][63]​​ In the AVERT trial, apixaban demonstrated efficacy in preventing thromboembolic events in patients with cancer undergoing chemotherapy and intermediate to high thrombotic risk (Khorana score ≥2).[64] However, major bleeding was significantly increased in this study, particularly in patients with gynaecological and gastrointestinal cancer. In the CASSINI trial, rivaroxaban did not reduce the incidence of thromboembolic disease and death compared with placebo in ambulatory high-risk cancer patients.[65] It should be noted that patients receiving thalidomide or lenalidomide with chemotherapy or dexamethasone have a high risk of venous thrombosis. The American Society of Clinical Oncology, the European Society for Medical Oncology, and the International Myeloma Working Group recommend thromboprophylaxis in these patients.[25][60][62]

Prophylaxis is not recommended for preventing catheter-related thrombosis.[51]​​[66]

Surgery

In vascular surgery, thromboprophylaxis is recommended only in patients with additional VTE risk factors or for major procedures (e.g., aortic aneurysm repair, aortofemoral bypass surgery).[3]​​[52]

In gynaecological, urological, or general surgery, 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]​ International consensus guidelines suggest GCS in these low-risk patients.[66] No prophylaxis is recommended after an elective abortion; however, an increased risk of venous thrombosis has been documented.[67] Prophylaxis is recommended after major surgery or if the patient has additional VTE risk factor(s).[3]​​[68][Evidence C][Evidence B]​​​​​

In thoracic surgery and coronary artery bypass graft (CABG), thromboprophylaxis should be routinely used.[3]​​

Patients undergoing neurosurgery (such as resection of meningioma) are a special population because of the bleeding risk and potential serious consequences of bleeding. Routine mechanical thromboprophylaxis (GCS and IPC devices) is recommended, with the addition of a pharmacological agent in high-risk patients who are at low risk of bleeding.[3]​​[52][66][68][Evidence C]

High-risk groups include trauma patients, orthopaedic surgery patients, and patients with acute spinal cord injury. Major trauma patients should routinely receive pharmacological prophylaxis unless contraindicated. Mechanical prophylaxis may be added in high-risk patients.[3]​​[66] In high-risk patients undergoing spinal surgery, pharmacological prophylaxis is combined with mechanical prophylaxis if there is no contraindication.

Patients undergoing orthopaedic surgery are an extremely high-risk population.[69][70] The risk of developing an asymptomatic DVT after a hip or knee replacement is about 40% to 60% without prophylaxis.[3]​ For hip fracture, total hip replacement, and total knee replacement, routine prophylaxis is warranted. If surgery for hip fracture is delayed, prophylaxis should be given before the surgery.[49][66] Thromboprophylaxis for lower-extremity fractures of the tibia, fibula, or ankle is generally not recommended but can be considered if there are additional risk factors for VTE.[49][66]

The incidence of proximal DVT is very low after arthroscopic surgery, regardless of receiving prophylaxis. Thromboprophylaxis after arthroscopic surgery cannot currently be recommended.[71][72] [ Cochrane Clinical Answers logo ]

Bariatric surgery patients are also thought to be a high-risk population, although fewer data are available. Routine thromboprophylaxis is recommended with weight-adjusted dosing of pharmacological agents.[3]​​

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