# VTE Prophylaxis in the Hospitalized Patient

## Introduction

Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of preventable death in hospitalized patients. Despite strong evidence supporting thromboprophylaxis, VTE prevention remains inconsistently applied. Every internist must systematically assess VTE risk, select appropriate prophylaxis, and balance the competing risk of bleeding.

## Epidemiology

- Hospital-acquired VTE accounts for approximately **50-60% of all VTE events** in the United States
- Without prophylaxis, VTE occurs in 10-40% of medical and surgical inpatients
- PE is the most common preventable cause of hospital death
- VTE risk persists for weeks after discharge, especially following surgery or acute medical illness

## Risk Assessment

### VTE Risk Factors

- **Patient factors**: age > 40, obesity (BMI > 30), prior VTE, active malignancy, thrombophilia
- **Medical conditions**: heart failure, acute respiratory failure, stroke with limb paresis, sepsis, inflammatory bowel disease
- **Immobility**: bedrest > 3 days, paralysis, critical illness
- **Iatrogenic**: central venous catheters, surgery, estrogen therapy, mechanical ventilation

### Risk Assessment Models

- **Padua Prediction Score** (medical patients): score >= 4 indicates high VTE risk warranting pharmacologic prophylaxis

| Padua Score Component | Points |
|----------------------|--------|
| Active cancer | +3 |
| Prior VTE | +3 |
| Reduced mobility (≥ 3 days) | +3 |
| Known thrombophilia | +3 |
| Recent trauma or surgery (≤ 1 month) | +2 |
| Age ≥ 70 years | +1 |
| Heart and/or respiratory failure | +1 |
| Acute MI or ischemic stroke | +1 |
| Acute infection and/or rheumatic disorder | +1 |
| Obesity (BMI ≥ 30) | +1 |
| Ongoing hormonal therapy | +1 |
| **Score ≥ 4: High risk — pharmacologic prophylaxis indicated** | |

- **Caprini Score** (surgical patients): stratifies VTE risk from very low to high
- **IMPROVE VTE score**: validated for acutely ill medical patients

### Bleeding Risk Assessment

- **IMPROVE Bleeding Score**: assesses bleeding risk to guide prophylaxis decisions
- Risk factors for bleeding: active GI ulcer, bleeding within 3 months, platelet count < 50,000, hepatic/renal failure, ICU/CCU stay, central venous catheter, rheumatic disease, active cancer, age >= 85
- High bleeding risk does not automatically preclude prophylaxis; consider mechanical prophylaxis

![Risk stratification flowchart for VTE prophylaxis in medical inpatients](/images/residency/vte-risk-stratification.jpg)

## Pharmacologic Prophylaxis

### Options for Medical Patients

| Agent | Dose | Preferred Setting |
|-------|------|-------------------|
| Enoxaparin (LMWH) | 40 mg SQ daily | Most medical patients (first-line) |
| UFH | 5,000 units SQ q8-12h | CrCl < 30 mL/min, anticipated procedures |
| Fondaparinux | 2.5 mg SQ daily | History of HIT |

- **Low-molecular-weight heparin (LMWH)**: enoxaparin 40 mg SQ daily (preferred in most patients)
- **Unfractionated heparin (UFH)**: 5,000 units SQ every 8-12 hours (preferred in renal insufficiency, CrCl < 30)
- **Fondaparinux**: 2.5 mg SQ daily (alternative for HIT history)
- Duration: throughout the period of immobility or acute illness; typically until discharge
- **Extended post-discharge prophylaxis** is NOT routinely recommended for medical patients (MARINER, APEX trials showed modest benefit but increased bleeding)

### Options for Surgical Patients

- LMWH or UFH starting preoperatively or within 12-24 hours postoperatively
- **Extended prophylaxis post-discharge**: recommended for major orthopedic surgery (total hip/knee, hip fracture) for up to 35 days
- Major abdominal/pelvic surgery for cancer: extended prophylaxis for 4 weeks (ENOXACAN II)
- **Direct oral anticoagulants (DOACs)**: rivaroxaban and apixaban approved for extended prophylaxis after hip/knee replacement

### Special Populations

- **Renal insufficiency (CrCl < 30 mL/min)**: use UFH; if LMWH used, dose-adjust and monitor anti-Xa levels
- **Obesity (BMI > 40 or weight > 120 kg)**: consider higher-dose LMWH (enoxaparin 40 mg SQ BID)
- **Heparin-induced thrombocytopenia (HIT)**: contraindication to all heparins; use fondaparinux or argatroban
- **Pregnancy**: LMWH is the agent of choice; UFH is an alternative
- **Active bleeding or very high bleeding risk**: mechanical prophylaxis only; reassess daily

## Mechanical Prophylaxis

- **Intermittent pneumatic compression (IPC) devices**: first-line when pharmacologic prophylaxis is contraindicated
- **Graduated compression stockings (GCS)**: less effective than IPC; contraindicated in peripheral arterial disease
- Mechanical prophylaxis alone is inferior to pharmacologic prophylaxis and should be used only when anticoagulation is contraindicated
- Combination mechanical + pharmacologic may be considered in very high-risk patients (e.g., major trauma)

![Comparison of pharmacologic and mechanical VTE prophylaxis options with dosing](/images/residency/vte-prophylaxis-options.jpg)

## Common Clinical Scenarios

### Acute Ischemic Stroke

- **Pharmacologic prophylaxis** with LMWH or UFH; timing depends on hemorrhagic transformation risk
- IPC devices should be initiated immediately on admission
- Early mobilization when safe

### Active Bleeding

- Mechanical prophylaxis with IPC
- Reassess daily for transition to pharmacologic prophylaxis once bleeding is controlled
- Do not reflexively withhold pharmacologic prophylaxis indefinitely

### Critical Illness

- Most ICU patients warrant pharmacologic prophylaxis
- UFH preferred if procedures or renal replacement therapy anticipated
- LMWH may be superior to UFH in critically ill patients (PROTECT trial)

### COVID-19 Hospitalization

- Standard-dose thromboprophylaxis for non-critically ill patients
- Therapeutic-dose anticoagulation (ACTIV-4a/ATTACC): improved outcomes in non-critically ill patients but not in ICU patients

## Quality Improvement and Implementation

- **VTE prophylaxis should be assessed on every patient at admission and daily thereafter**
- Electronic health record alerts and order sets improve compliance
- VTE is a **CMS hospital-acquired condition**; lack of prophylaxis is considered a preventable harm
- Nursing-driven protocols for IPC compliance (devices must be on whenever in bed)
- Risk assessment tools embedded in admission order sets

![Quality improvement framework for hospital-wide VTE prophylaxis compliance](/images/residency/vte-quality-improvement.jpg)

## Key Clinical Pearls

- Assess VTE risk on every patient at admission; use the Padua score for medical patients
- LMWH is preferred over UFH in most medical patients; use UFH for CrCl < 30
- Mechanical prophylaxis alone is only acceptable when pharmacologic prophylaxis is truly contraindicated
- Extended post-discharge prophylaxis is routine after major orthopedic and cancer surgery but not standard for medical patients
- Reassess prophylaxis daily; bleeding risk and VTE risk change throughout the hospitalization

## References

1. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP evidence-based clinical practice guidelines. *Chest*. 2012;141(2 Suppl):e195S-e226S.
2. Schunemann 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;2(22):3198-3225.
3. PROTECT Investigators. Dalteparin versus unfractionated heparin in critically ill patients. *N Engl J Med*. 2011;364(14):1305-1314.
4. ATTACC Investigators. Therapeutic anticoagulation with heparin in noncritically ill patients with COVID-19. *N Engl J Med*. 2021;385(9):790-802.