@ Kamo Weasel

OBJECTIVE

Establish a hospital guide for thromboembolism prophylaxis in patients admitted to our center, aiming to increase safety in its indication, reduce the incidence of venous thrombosis events in at-risk patients, and minimize adverse effects related to thromboprophylaxis.

SCOPE

All patients over 16 years of age admitted to our institution.

RESPONSIBILITIES

Institution physicians from Hematology Services, Surgical Services, Medical Clinic Service, Intensive Care Unit (ICU), and Coronary Unit (CCU). Nursing Coordination. Nursing Department Head. Pharmacy Service.

REFERENCES AND BIBLIOGRAPHY

1. Updated recommendations for prophylaxis of venous thromboembolic disease in Argentina. Fernando J. Vazquez et al. MEDICINA (Buenos Aires) 2020; 80: 69-80.
2. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Advances. Holger J. Schünemann et al. DOI 10.1182/bloodadvances.2018022954
3. High-dose versus low-dose venous thromboprophylaxis in hospitalized patients with COVID-19: a systematic review and meta-analysis. Emanuele Valeriani et al. Internal and Emergency Medicine (2022) 17:1817–1825. https://doi.org/10.1007/s11739-022-03004-x
4. Recommendations for the use of thromboprophylaxis in hospitalized COVID-19 patients in Argentina. Fernando J. Vazquez et al. MEDICINA (Buenos Aires) 2020; Vol. 80 (Suppl. III): 65-66. ISSN 1669-9106

INTRODUCTION

Thromboembolic prophylaxis in hospitalized patients is a critical intervention to reduce the risk of thrombotic events, one of the leading causes of morbidity and mortality in hospitals. Prolonged immobilization, along with other risk factors such as surgeries, trauma, comorbidities, and specific treatments, significantly increases the possibility of developing deep vein thrombosis (DVT) or pulmonary embolism (PE), which are serious conditions requiring rapid intervention and can threaten the patient's life.

In Argentina, the incidence of venous thromboembolism in hospitalized patients is high and represents a significant clinical challenge. It is estimated that hospitalization increases the likelihood of a thromboembolic event by 10 times compared to the general population. Implementing effective thromboprophylaxis strategies can reduce this incidence, optimizing patient safety and reducing both the costs associated with complications and the duration of hospitalization.

This guide aims to standardize the use of thromboprophylaxis in our institution, improving the identification of at-risk patients and promoting safe interventions based on updated scientific evidence.

GENERAL RECOMMENDATIONS FOR THROMBOPROPHYLAXIS

General indications for thromboprophylaxis are essential to ensure safety and effectiveness in preventing thromboembolic events. The following general recommendations are provided:

Patients without prior anticoagulation: Recommendations apply only to patients who were not receiving oral anticoagulation before hospitalization.
Initial Evaluation: Prior to starting prophylaxis, a complete blood count, prothrombin time, aPTT, platelet count, and an estimation of renal function through creatinine clearance should be obtained.
Conditions for Surgical Patients: All recommendations for surgical patients assume no intraoperative hemorrhagic complications and adequate hemostasis.
Special Cases Evaluation: Prophylaxis in patients with extreme weight (under 40 kg or over 100 kg) or renal insufficiency with a clearance of less than 30 ml/min should be evaluated by a Hematology specialist.
Early Mobilization: Routine early mobilization is recommended for all patients, as long as it is safe.

RISK SCALE APPLICATION

The assessment of thromboembolic event risk should begin with correct categorization of the patient.

Risk Factors for Venous Thromboembolism (VTE) during hospitalization include: prolonged immobility (more than 2 days in bed), active neoplasms, stroke, heart failure, chronic obstructive pulmonary disease, acute infections, rheumatoid arthritis, ANCA-positive vasculitis, and inflammatory bowel disease. These clinical conditions account for approximately 75% of fatal pulmonary thromboembolisms (PE), highlighting the importance of adequate antithrombotic prophylaxis.
Risk scales are designed to categorize both thromboembolic risk and bleeding risk associated with thromboprophylaxis. The bleeding risk, whether major or clinically relevant, increases with the use of pharmacological prophylaxis. However, fatal bleeding is 10 times less frequent than fatal PE.

CONTRAINDICATIONS FOR THROMBOPROPHYLAXIS

General contraindications for pharmacological thromboprophylaxis in hospitalized patients aim to prevent hemorrhagic complications. The main contraindications are:

Clinically significant active hemorrhage.
Platelet count less than 30,000 platelets/ml.
Major bleeding disorders.
Active intracranial hemorrhage.
Recent peri-spinal hemorrhage.
Recent surgery with a high risk of bleeding.

It is crucial to carefully evaluate these contraindications before initiating any thromboprophylaxis protocol.

INDICATION FOR THROMBOPROPHYLAXIS IN NON-SURGICAL HOSPITALIZED PATIENTS

Validated scales help categorize the risk and indication for venous thromboembolism (VTE) in hospitalized patients with non-surgical conditions: the IMPROVE-VTE scale, which considers a high risk for scores above 2 and very high risk for scores above 4, with additional factors such as elevated D-dimer, advanced age, cancer history, or previous VTE.

To assess bleeding risk, the IMPROVE-Bleed scale identifies high risk with scores of 7 or higher. Patients with high VTE risk and low bleeding risk should receive prophylaxis until discharge, and in high-risk cases, it should be extended afterward.

Improve VTE Scale Risk Factors and Points

Patient History
    Previous VTE: 3 points
    Recent surgery (within 30 days): 2 points
    Active cancer: 2 points
    History of trauma: 1 point

Clinical Factors
    Age 40-60 years: 1 point
    Age over 60 years: 2 points
    Obesity (BMI > 30): 1 point
    Prolonged immobility (e.g., bed rest for more than 3 days): 2 points

Laboratory Findings
    Elevated D-dimer: 1 point

Medication Use
    Hormonal therapy (e.g., oral contraceptives, hormone replacement therapy): 1 point
    Recent chemotherapy: 2 points

Physical Examination
    Signs of deep vein thrombosis (DVT) such as swelling, pain, or tenderness in the legs: 2 points

Scoring and Risk Levels

Total Score Calculation: Add the points from all applicable categories.

Risk Levels:
    0-2 points: Low Risk - Standard care; consider early mobilization.
    3-5 points: Moderate Risk - Consider mechanical prophylaxis (e.g., compression stockings) and/or pharmacologic prophylaxis.
    6+ points: High Risk - Strongly consider pharmacologic prophylaxis (e.g., anticoagulants) and close monitoring.

IMPROVE-Bleed Scale for Bleeding Risk Assessment Risk Factors and Points

Creatinine clearance < 60 ml/min: 1 point
Creatinine clearance < 30 ml/min: 2.5 points
Male sex: 1 point
Age > 40: 1.5 points
Age > 85: 3.5 points
Active cancer: 2 points
Rheumatic disease: 2 points
Central venous catheter: 2 points
Admission to Intensive Care Unit or Coronary Care Unit: 2.5 points
Liver failure (INR > 1.5): 2.5 points
Platelets < 50,000/µl: 4 points
Bleeding in the last 3 months: 4 points
Active gastroduodenal ulcer: 4.5 points

Score Interpretation

Total Score:
    7 or more: High bleeding risk, with a bleeding probability of 4% or more.

General Recommendations for Thromboprophylaxis in Hospitalized Patients with Medical Conditions Without Surgery

Population: High or moderate risk of thrombosis and low risk of bleeding
    Recommendation: Critical: Enoxaparin 40 mg every 24 hours; Non-critical: Enoxaparin 40 mg every 24 hours.
    Alternative: Unfractionated heparin 5000 U every 8 or 12 hours.
    Comments: Until discharge; may consider prolonging in very high-risk patients.

Population: High risk of thrombosis and high risk of bleeding
    Recommendation: IPC or CG.
    Alternative: -
    Comments: -

Population: Patients with creatinine clearance less than 30 ml/min
    Recommendation: Unfractionated heparin 5000 U every 8 or 12 hours.
    Alternative: -
    Comments: Reassess pharmacological prophylaxis when there is low bleeding risk. Until discharge; may consider prolonging in very high-risk patients.

Population: Patients with ischemic stroke
    Recommendation: Enoxaparin 40 mg every 24 hours.
    Alternative: IPC.
    Comments: Initiate within the first 24 hours. Until discharge; may consider prolonging in very high-risk patients.

Population: Patients with intracranial hemorrhage (ICH)
    Recommendation: IPC or CG for 48 to 72 hours after stabilization of bleeding, then Enoxaparin 40 mg every 24 hours.
    Alternative: IPC.
    Comments: Hemorrhage control should be monitored with imaging and evolution. Until discharge; may consider prolonging in very high-risk patients.

Population: Patients with subarachnoid hemorrhage (SAH)
    Recommendation: IPC or CG for 48 to 72 hours after vascular exclusion or surgical resolution of the aneurysm, then Enoxaparin 40 mg every 24 hours.
    Alternative: IPC.
    Comments: Hemorrhage control should be monitored with imaging and evolution. Until discharge; may consider prolonging in very high-risk patients.

References

UFH: unfractionated heparin
IPC: intermittent pneumatic compression
CG: graduated compression stockings
CVA: cerebrovascular accident
ICH: intracranial hemorrhage
SAH: subarachnoid hemorrhage

RECOMMENDATIONS FOR THROMBOPROPHYLAXIS IN HOSPITALIZED PATIENTS WITH NON-SURGICAL CLINICAL DISEASES

Population Recommendation Alternative Comments Duration High or moderate VTE risk with low bleeding risk Enoxaparin 40 mg every 24 hours (critical); Enoxaparin 40 mg every 24 hours (non-critical) Unfractionated heparin (UFH) 5000 U every 8 or 12 hours Until discharge, may be extended for very high-risk patients High VTE risk and high bleeding risk CNI or MCG
Creatinine clearance < 30 ml/min UFH 5000 U every 8 or 12 hours Reevaluate when bleeding risk is low Until discharge, may be extended for very high-risk patients

INDICATION FOR THROMBOPROPHYLAXIS IN SURGICAL PATIENTS WITH NON-ORTHOPEDIC SURGERY

In non-ambulatory surgeries, the risk of venous thromboembolism (VTE) varies depending on the patient's risk factors and the type of surgery. Thus, individual risk stratification using the Caprini scale is imperative. Patients undergoing general surgery with moderate or higher thrombotic risk (3 points or more) and no increased bleeding risk should receive pharmacological thromboprophylaxis.

CAPRINI SCALE

Caprini Risk Assessment Model Risk Factors and Points

History of VTE
    Previous VTE: 3 points

Active Cancer
    Current or recent cancer (within 6 months): 3 points
    Receiving treatment for cancer: 3 points

Surgery/Trauma
    Major surgery (e.g., orthopedic, abdominal) with general anesthesia: 2 points
    Trauma with hospitalization: 2 points
    Minor surgery with general anesthesia: 1 point

Age
    Age 41-60 years: 1 point
    Age 61-74 years: 2 points
    Age 75 years or older: 3 points

Obesity
    BMI 30-39: 1 point
    BMI 40 or greater: 2 points

Immobility
    Bed rest for more than 3 days: 2 points
    Paraplegia or quadriplegia: 2 points

Hormonal Therapy
    Current use of estrogen-containing medications (e.g., oral contraceptives, hormone replacement therapy): 1 point

Other Risk Factors
    History of heart failure or chronic lung disease: 1 point
    History of inflammatory bowel disease: 1 point
    History of stroke: 1 point
    Varicose veins: 1 point
    Recent travel (long-distance travel > 4 hours): 1 point

Scoring and Risk Levels

Total Score Calculation: Add the points from all applicable categories.

Risk Levels:
    0-1 points: Low Risk - Standard care; consider early mobilization.
    2-3 points: Moderate Risk - Consider mechanical prophylaxis (e.g., compression stockings).
    4-5 points: High Risk - Consider pharmacologic prophylaxis (e.g., anticoagulants) and mechanical methods.
    6+ points: Very High Risk - Strongly consider pharmacologic prophylaxis and close monitoring.

Interpretation of Caprini Scale Score: Total Score Risk Level Recommendation Comments Duration 0-1 Low Early ambulation Until discharge 2-3 Moderate CNI or MCG Begin before surgery Until discharge 4 or more High Enoxaparin 40 mg every 24 hours or UFH 5000 U every 8 or 12 hours Administer the dose 12 hours before abdominal or pelvic surgery, restart 12 hours post-procedure Minimum 7-10 days; extend up to 28 days post-surgery for oncologic patients or those with low bleeding risk

INDICATION FOR THROMBOPROPHYLAXIS IN ORTHOPEDIC SURGERY PATIENTS

Major orthopedic surgeries, including total hip arthroplasty (THA), total knee arthroplasty (TKA), and hip fracture surgery (HFS), pose a high risk of thrombotic complications (40%-60% without proper thromboprophylaxis). Pharmacological prophylaxis is always recommended regardless of individual risk factors.

Special Considerations:

In outpatient knee arthroscopy, early ambulation is encouraged. Prophylaxis with low molecular weight heparin (LMWH) for at least 7 days should be considered only in patients with high thrombotic risk (e.g., cancer, prior VTE, obesity, pregnancy, or postpartum).
For immobilization lasting more than 7 days due to fractures, tendinous/cartilaginous ruptures, or soft tissue injuries below the patella with risk factors, pharmacological prophylaxis with LMWH is recommended.
In spinal surgeries, mechanical prophylaxis with graduated compression stockings (GCS) and early ambulation are advised. For prolonged procedures (> 1 hour) with risk factors, pharmacological prophylaxis (Enoxaparin 40 mg/day or UFH 5000 U every 8-12 hours) is recommended 24 hours post-surgery until discharge.
Major trauma patients should receive mechanical prophylaxis (CNI or GCS) combined with Enoxaparin 40 mg/day, provided there is no increased bleeding risk, from admission to discharge, including the rehabilitation period.

Recommendations for Orthopedic Surgery: Population Recommended Indication Alternative Comments Duration Scheduled hip and knee surgery Apixaban 2.5 mg every 12 hours None Start 12 hours after surgery 28-35 days (hip), 14 days (knee), extend up to 35 days Dabigatran 220 mg every 24 hours None Start 110 mg 4 hours after surgery, then continue with 220 mg
Enoxaparin 40 mg every 24 hours None Start 12 hours after surgery
Rivaroxaban 10 mg every 24 hours None Start 6 hours after surgery Hip fracture Enoxaparin 40 mg every 24 hours UFH 5000 U every 8 or 12 hours Administer from admission and 8-12 hours before surgery; restart 8-12 hours post-surgery 14-35 days

INDICATION FOR THROMBOPROPHYLAXIS IN OBSTETRICS

Postpartum hemorrhage is the leading cause of maternal death in developing countries, while venous thromboembolic disease (VTE) is the leading cause in developed countries. Pregnant women are 4-10 times more likely to develop VTE than non-pregnant women. Although the incidence of VTE during pregnancy is low (1-2 per 1000 pregnancies), it is considered a preventable cause of maternal death.

INDICATION FOR THROMBOPROPHYLAXIS IN COVID-19 HOSPITALIZED PATIENTS

COVID-19 infection is associated with an increased risk of venous thromboembolism, particularly in ICU patients. These patients are considered at high thrombotic risk during hospitalization, with significantly elevated D-dimer levels linked to greater risk of severe complications, including death and disseminated intravascular coagulation.

Recommendations:

Thromboprophylaxis with subcutaneous Enoxaparin 40 mg/day is suggested for all hospitalized patients with severe COVID-19, provided no contraindications exist, throughout their hospital stay.