I. Problem / Challenge.

Pulmonary embolism (PE) resulting from deep venous thrombosis (DVT) is considered the most common preventable cause of hospital death. Without prophylaxis, estimated venous thromboembolism (VTE) incidence in hospitalized patients ranges from 10-26% in general medical patients, to 40-60% in those undergoing knee or hip surgery, to as much as 80% in patients with major trauma or spinal cord injury.

Although there does not appear to be an impact on overall mortality, as many as two-thirds of cases of hospital-acquired VTE can be prevented with appropriate prophylaxis, and this cost-effective intervention is rated by the Agency for Healthcare Research and Quality (AHRQ) as the “number one patient safety practice.” Despite this, omission of VTE prophylaxis is all too common and occurs most often among medical patients not in intensive care units (ICU).

II. Identify the Goal Behavior.

All hospitalized patients should receive appropriate VTE prophylaxis after taking into consideration individual patient thromboembolic risk factors and bleeding risk.

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III. Describe a Step-by-Step Approach / Method to this Problem.

All hospitalized patients are at risk for developing venous thromboembolism, and tackling the issue of prevention warrants a systematic institutional approach. The first step is development of a hospital-wide VTE prevention policy, including such components as computerized support systems and dedicated order sets incorporating current best evidence. Once such measures are in place, audit and feedback should inform the ongoing quality improvement process.

When approaching the individual patient, practitioners should follow a step-wise approach to initiating VTE prophylaxis.

  • Assess VTE risk.

  • Assess bleeding risk.

  • Select appropriate VTE prophylaxis.

  • Determine timing and duration of prophylaxis.

  • Monitoring.

VTE risk assessment

VTE risk should be assessed at the time of admission, any time there is a change in the level of care, and prior to discharge. One option is to individualize risk assessment. Ideally, a prospectively validated risk assessment model would allow individualized estimation of both VTE and bleeding risk, with a net assessment of risk versus benefit and links to appropriate and available options for prophylaxis in the electronic record.

While tools for individual VTE risk assessment exist, some are limited by lack of prospective validation or other factors. Externally-validated risk assessment tools include the Caprini Risk Assessment for surgical patients, and the IMPROVE risk assessment model for general medicine inpatients. The Padua Predictive Score, which was validated in a prospective cohort study, is another tool that can be done on general medical patients.

Consistently, a number of factors have been identified that increase risk for VTE in hospitalized patients, such as age greater than 60, prior VTE, active cancer, inherited thrombophilia, prolonged immobilization. These factors are covered in more detail elsewhere [see the chapter on venous hypercoagualability (red factors)]. The presence of any of these risk factors suggests the patient is not low risk for VTE.

A simpler approach by the American College of Chest Physicians groups patients in terms of VTE risk based primarily on the reason for their presentation to the hospital:

Low risk (VTE risk without prophylaxis is less than 10%)—minor surgery in ambulatory patients and fully ambulatory medical patients.

Moderate risk (VTE risk without prophylaxis 10-40%)—most general, open gynecologic and urologic surgical patients; medical patients that are sick or those less than fully ambulatory.

High risk (VTE risk without prophylaxis 40-80%)—patients undergoing hip or knee arthroplasy, hip fracture surgery, or those with major trauma or spinal cord injury.

Bleeding risk assessment

Even in prophylactic doses, anticoagulants used for VTE prevention increase the likelihood of major bleeding. Prior to initiation of prophylaxis, patients’ individual bleeding risk should be assessed to insure a favorable risk/benefit ratio. While assessment tools have been developed for calculating bleeding risk in individual patients, currently only one has been externally validated – the IMPROVE bleeding risk score (BRS).

The IMPROVE BRS takes into account multiple factors and weighs each factor differently. The factors measured are: glomerular filtration rate (GFR), gender, age, active cancer, rheumatic disease, central venous catheter, ICU/CCU admission, hepatic failure based off of INR, platelet count, history of bleeding in the last 3 months and active gastroduodenal ulcer.

Upon review of other bleeding risk scores, the factors associated with bleeding vary considerably from study to study. Among those that are not already used in the IMPROVE BRS are active bleeding, inherited or acquired bleeding disorder, procedure with high bleeding risk (such as neurosurgery, spinal surgery, spinal puncture within 24 hours, ongoing epidural / spinal anesthesia), concurrent use of anticoagulants or antiplatelet drugs, uncontrolled hypertension, diabetes, anemia, and use of statins, fibrates, or steroids. The clinician’s challenge is to determine whether the presence of one or more of these factors places patients at high enough bleeding risk to preclude VTE prophylaxis.

Selecting appropriate VTE prophylaxis

Following assessment of VTE and bleeding risks, the next step is to ensure an appropriate regimen for VTE prophylaxis. There are three options: early and frequent ambulation (important to consider in all hospitalized patients, but not always feasible), additional mechanical prophylaxis (there is better evidence for intermittent pneumatic compression [IPC] than graduated compression stockings [GCS], at least in surgical patients), or pharmacologic prophylaxis. Even in high-risk patients, current guidelines recommend against inferior vena cava (IVC) filter placement for thromboprophylaxis.

Incorporating VTE and bleeding risk, the following recommendations can be made:

Low VTE risk (regardless of bleeding risk): early ambulation only.

Moderate VTE risk: early ambulation plus one of the following for pharmacologic prophylaxis:

Dalteparin 2500-5000 units subcutaneous (subQ) every 24 hours (dose varies by indication).

Enoxaparin 40 mg subQ every 24 hours.

Fondaparinux 2.5 mg sub Q every 24 hours.

Low dose unfractionated heparin (UFH) 5000 every 8 hours or every 12 hours (there is no strong evidence that a three times a day dosing regimen is more effective than a twice a day dosing regimen).

High VTE risk: early ambulation plus consider addition of mechanical thromboprophylaxis plus one of the following for pharmacologic prophylaxis:

Dalteparin 2500-5000 units subQ every 24 hours (dose varies by indication).

Enoxaparin 30 mg subQ every 12 hours.

Fondaparinux 2.5 mg subQ every 24 hours.

Rivaroxaban 10 mg per os (PO) daily (FDA approved only for hip and knee replacement; more effective than enoxaparin.

Adjusted dose vitamin K antagonist (VKA), such as warfarin, with target international normalized ratio (INR) 2.5.

High risk for bleeding regardless of VTE risk: early ambulation plus mechanical thromboprophylaxis if moderate or high VTE risk. Switch to pharmacologic prophylaxis when/if bleeding risk declines.

Note, aspirin should never be used as monotherapy for VTE prophylaxis, but new evidence does exist that the use of aspirin in addition to pharmacological prophylaxis in ICU patients may decrease the rate of VTE.

Approaches for special populations of patients are given below.

Cancer patients

Assess risk and treat same as other patients.

Critical care

Unfractionated heparin (UFH) or low molecular weight heparin (LMWH) for those at moderate risk; LMWH for those at high risk.

Neuraxial blockade

Due to risk of spinal and epidural hematoma, the Institute for Clinical Systems Improvement (ICSI) guideline recommends:


Insert catheter at least 12 hours after last dose; subsequent dose after at least 4 hours after catheter insertion.

Remove catheter at least 12 hours after last dose; subsequent dose at least 4 hours after catheter removal.

Do not use epidural catheters with twice daily dosing regimen, once catheter removed, wait 4 hours and then may do twice daily dosing.


Not recommended prior to catheter insertion

Remove catheter at least 36 hours after last dose; subsequent dose at least 12 hours after catheter removal


Insert catheter at least 18 hours after the last dose; subsequent dose at least 6 hours after catheter insertion.

Remove catheter at least 18 hours after the last dose; subsequent dose at least 6 hours after catheter removal.

If trauma with puncture, delay administration for 24 hours UFH.

Insert catheter at least 4 hours after last dose.

Remove catheter at least 4 hours after last dose; subsequent at least 1 hour after catheter removal.


No consensus about highest acceptable INR for insertion.

Removal within 48 hours of initiation of warfarin and INR less than or equal to 1.5.


Data is limited, but dosing should be weight-based using actual body weight. Consider monitoring peak anti-Xa levels, measured 4 hours after dosing (reasonable target 0.2-0.4 IU/mL).

  • Dalteparin 7500 units subQ daily (weight-based dosing guidelines are not available for dalteparin).

  • Enoxaparin 0.5 mg/kg subQ daily (some recommend dividing the dose and administering twice a day).


Some advocate anti-Xa monitoring, but this is controversial.

  • LMWH: pregnancy category B.

  • Fondaparinux: category B, but safety data is insufficient.

  • Rivaroxaban: category C, but safety data is insufficient.

  • UFH: category C.

  • Warfarin: contraindicated in pregnancy.

Renal impairment

Patients with a creatinine clearance less than 30 mL/min/1.73 m2.

  • Dalteparin: no dose adjustment.

  • Enoxaparin: use alternate agent or reduce dose to 30 mg subQ every 24 hours. With reduced dose, some recommend monitoring peak anti-Xa levels with target 0.2-0.4 IU/mL.

  • Fondaparinux is contraindicated.

  • Rivaroxaban is contraindicated.

  • UFH: no dose adjustment.

  • Warfarin: no dose adjustment.


VTE prophylaxis should be initiated within 24 hours of admission in medical patients for whom it is indicated. In surgical patients, there is debate regarding the best timing for initiation of prophylaxis. Earlier initiation/resumption of prophylaxis postoperatively is associated with lower risk of VTE, but higher risk of bleeding. In surgical patients at high risk of bleeding, a reasonable approach is resumption of prophylaxis 12-24 hours after surgery and after primary hemostasis has been achieved at the surgical site.

The optimal duration of prophylaxis is unclear. Most studies evaluate prophylaxis only up until hospital discharge for the general medical patient.

  • In the orthopedic patient who has undergone total hip or knee arthroplasty, LMWH, fondaparinux, rivaroxaban, apixaban or warfarin are recommended for 10-14 days. There may be additional benefit for extending treatment to a total of 35 days from the date of surgery. Aspirin 81mg daily, starting 10-14 days after LMWH and continued for 28 days, may be an alternative regimen for prophylaxis in hip replacement patients.

  • For those undergoing major cancer surgery, or for surgical patients with a prior history of VTE, extended prophylaxis is recommended for up to 28 days. Recent studies also suggest a possible benefit of extended duration prophylaxis in certain high-risk medical patients, but further trials are needed before making formal recommendations

  • For medical patients, current guidelines recommend against extending the duration of prophylaxis beyond the acute hospitalization.


As mentioned above, anti-Xa levels can be monitored in certain special populations requiring adjusted dose LMWH for prophylaxis.

For patients on low-dose unfractionated or low molecular weight heparin prophylaxis, clinicians should perform a platelet count at baseline. Thereafter, the likelihood of heparin-induced thrombocytopenia (HIT) should be estimated utilizing a risk assessment tool, preferably the 4Ts score (see chapter on HIT). Patients deemed to have a risk of HIT of less than 1% do not require further platelet monitoring. Those with a risk of HIT of greater than 1% should have a platelet count monitored every 2-3 days from days 4-14 of therapy or until heparin is discontinued, whichever occurs first.

For those started on a warfarin (such as high-risk orthopedic patients), INR should be obtained at baseline, repeated 2-3 days after starting therapy, then daily thereafter until INR stabilizes in the therapeutic range.

IV. Common Pitfalls.

In the absence of a systematic process to implement appropriate prophylaxis in every hospitalized patient, it is inevitable that the occasional patient will “slip through the cracks.”

Once prophylaxis has been initiated, clinicians should avoid interruption during transitions of care, such as following surgery or other inpatient procedures, during transfer in or out of the ICU, and following discharge from the acute care setting in patients requiring extended prophylaxis.

Postoperative patients receiving unfractionated heparin (UFH) for prophylaxis are at highest risk for heparin-induced thrombocytopenia (incidence greater than 1%) and should have their platelet count monitored at least every other day during days 4-14 of therapy or until UFH is stopped, whichever comes first. This is particularly easy to miss in patients that continue VTE prophylaxis following hospital discharge.

Finally, thoughtful planning and communication with the patient and primary care provider is essential to ensure continuation of proper prophylaxis following discharge of postoperative patients after knee and hip surgery. LMWH, in particular, can be quite expensive, and it is worth the effort to ensure patients will be able to obtain the medication on discharge. Patients receiving UFH or LMWH at the time of discharge will also need nursing instruction to ensure comfort with administration of subcutaneous injections.

V. National Standards, Core Indicators and Quality Measures.

The three Joint Commission and National Quality Forum (NQF) quality measures relating to VTE prophylaxis are listed below.

VTE-1/NQF 0371: VTE prophylaxis within 24 hours of arrival “assesses the number of patients who received VTE prophylaxis or have documentation why no VTE prophylaxis was given the day of or the day after hospital admissions or surgery end date for surgeries that start the day of or the day after hospital admission.” This applies to most adult inpatients without a principal diagnosis of VTE.

VTE-2/NQF 0372: ICU VTE prophylaxis “assesses the number of patients who received VTE prophylaxis or have documentation why no VTE prophylaxis was given the day of or the day after the initial admission (or transfer) to the intensive care unit (ICU) or surgery end date for surgeries that start the day of or the day after ICU admission (or transfer).” This applies to most adult inpatients without a principal diagnosis of VTE.

VTE-6/NQF 0376: Incidence of potentially preventable VTE “assesses the number of patients diagnosed with confirmed VTE during hospitalization (not present on arrival) who did not receive VTE prophylaxis between hospital admission and the day before VTE diagnostic testing order date.” This applies to most adult inpatients with an ICD-9 “other” diagnosis code of VTE, but without a principal diagnosis of VTE.

There are several methods of both pharmacological and mechanical VTE prophylaxis that satisfy each of these core indicators.

VI. What's the Evidence?