Thromboembolic Disease After Orthopedic Trauma




Orthopedic trauma results in systemic physiologic changes that predispose patients to venous thromboembolism (VTE). In the absence of prophylaxis, VTE incidence may be as high as 60%. Mechanical and pharmacologic thromboprophylaxis are effective in decreasing rates of VTE. Combined mechanical and pharmacologic thromboprophylaxis is more efficacious for decreasing VTE incidence than either regimen independently. If pharmacologic thromboprophylaxis is contraindicated, mechanical prophylaxis should be used. Patients with isolated lower extremity fractures who are ambulatory, or those with isolated upper extremity trauma, do not require pharmacologic prophylaxis in the absence of other VTE risk factors.


Key points








  • Traumatic musculoskeletal injury results in systemic physiologic changes that predispose patients to venous thromboembolism (VTE).



  • Combined mechanical and pharmacologic thromboprophylaxis is most efficacious for decreasing VTE incidence.



  • Low molecular weight heparin is the preferred agent for pharmacologic thromboprophylaxis.



  • Pharmacologic prophylaxis should be initiated as soon as possible, and should be continue for a minimum of 14 days.



  • Patients with isolated lower extremity fractures who are ambulatory do not require pharmacologic prophylaxis in the absence of other VTE risk factors.






Physiology and epidemiology of venous thromboembolism in trauma


Basic Science and Physiology of Trauma and Coagulation


Traumatic injury results in significant physiologic changes. Serum levels of inflammatory cytokines including interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-α) are increased following traumatic injury and result in a hypercoagulable state. In addition to inflammatory markers, serum levels and activity of procoagulant microparticles are significantly increased following blunt trauma, and peak thrombin levels are correlated to injury severity. The systemic inflammatory response triggered by traumatic injury results in a hypercoagulable state that places patients at increased risk of venous thromboembolism (VTE). This hypercoagulability combined with endothelial injury and venous stasis, 2 other conditions often noted in trauma patients, completes the Virchow Triad. The presence of all 3 elements contributes to venous thrombosis.


Venous Thromboembolism Following Major Trauma


Before the implementation of routine thromboprophylaxis, reported rates of VTE following major trauma were extremely high. Using bilateral lower extremity venography, Geerts and colleagues reported a 58% incidence of lower extremity deep vein thrombosis (DVT) in 349 patients admitted for major traumatic injuries who did not receive thromboprophylaxis. DVT rates varied by anatomic region injured, ranging from 50% in patients with major injuries to the face, chest, or abdomen to 80% in patients with femur fractures. The rate of fatal pulmonary embolism (PE) was 0.9%, and independent risk factors for DVT identified included age, blood transfusion, surgery, fracture of the femur or tibia, and spinal cord injury. Despite its relatively low incidence, PE is still the third most common cause of in-hospital death among trauma patients.


Thromboprophylaxis for Venous Thromboembolism in Trauma Patients


Both chemical and mechanical thromboprophylaxis has been shown to decrease rates of VTE in the setting of trauma. Pharmacologic prophylaxis with low molecular weight heparin (LMWH) was shown to significantly decrease the incidence of both DVT and PE in a large cohort of more than 2200 trauma patients. Mechanical prophylaxis with pneumatic sequential compression devices (SCDs) significantly decreased VTE incidence from 11% to 4% ( P = .02) in a prospective randomized controlled trial of 300 orthopedic trauma patients compared with no VTE prophylaxis. A growing understanding of the importance of thromboprophylaxis in trauma patients has led to the development of institutional protocols for VTE prophylaxis at trauma centers around the world. Additionally, several professional organizations have published clinical guidelines for thromboprophylaxis in trauma patients, which are summarized in Table 1 .



Table 1

Evidence-based guidelines for venous thromboembolism prophylaxis in orthopedic trauma





















Organization Summary of Findings and Recommendations
Cochrane database systematic review


  • Mechanical and pharmacologic prophylaxis independently reduce risk of DVT, RR = 0.43



  • Pharmacologic prophylaxis is more effective than mechanical at reducing DVT risk, RR = 0.48



  • Combined mechanical and pharmacologic prophylaxis results in the lowest risk of DVT, RR = 0.34



  • LMWH reduces DVT risk more effectively than unfractionated heparin, RR = 0.68



  • No high-quality evidence that thromboprophylaxis reduces mortality or PE



  • Recommend the use of any DVT prophylactic method for patients with severe trauma

American College of Chest Physicians (ACCP)


  • In patients undergoing major orthopedic surgery:




    • Recommend using a pharmacologic thromboprophylaxis agent (Grade 1B) or IPCDs (Grade 1C) for a minimum of 10–14 d and considering extending pharmacologic thromboprophylaxis for up to 35 d (Grade 2B).



    • Suggest using LMWH in preference to other pharmacologic agents (Grade 2B/2C) and adding an IPCDs to pharmacologic prophylaxis during the inpatient hospital stay (Grade 2C)



    • Suggest IPCDs or no prophylaxis for patients at increased bleeding risk (Grade 2C)



    • Suggest against “prophylactic” IVC filter placement (Grade 2C) and recommend against duplex ultrasound screening for DVT before hospital discharge (Grade 1B)




  • In patients with isolated lower extremity injuries below the knee requiring immobilization without a history of VTE:




    • Suggest no thromboprophylaxis (Grade 2B)


Eastern Association for the Surgery of Trauma (EAST)


  • Risk Factors for VTE: Spinal fractures or SCI (level I), older age, ISS, blood transfusion, long-bone fracture, pelvic fracture, head injury (level II)



  • Little evidence to support low-dose unfractionated heparin as sole thromboprophylaxis agent (level II)



  • IPCDs (or foot pumps if the calf is inaccessible) may have some benefit in patients with spine injuries or head trauma (level III)



  • LMWH may be used in patients with pelvic fractures requiring surgery, complex lower extremity fractures, or complete SCI with motor involvement (level II)



  • LMWH should be used as primary prophylaxis in trauma patients with ISS >9 and should be considered for several weeks after injury in patients at high risk for VTE (level III)



  • IVC filters should be inserted for the following indications:




    • Recurrent PE, proximal DVT, or progression of iliofemoral DVT while on full anticoagulation (level I)



    • Large/free-floating IVC/iliac thrombi, following massive PE, during/after surgical embolectomy (level II)




  • “Prophylactic” IVC filters should be considered if anticoagulation is contraindicated in patients with the following high-risk injury patterns:




    • Severe closed head injury (GCS<8), incomplete SCI with motor involvement, complex pelvic fracture with associated long-bone fracture, multiple long-bone fractures (level III)




  • Duplex ultrasound should be used to assess symptomatic trauma patients with suspected DVT (level I) but should not be used for screening asymptomatic patients (level III)



  • Ascending venography may be useful for confirming a diagnosis of DVT when ultrasound is equivocal (level II), and there may be a role for MR venography in the diagnosis of DVT in the acute setting, especially in areas in which venography and ultrasound are less reliable (level III)

Orthopedic Trauma Association (OTA)


  • In hospitalized orthopedic trauma patients:




    • In the absence of contraindications, LMWH is the agent of choice and should be initiated as soon as possible, preferably within 24 h (Strong)



    • Combined LMWH and IPCDs are preferable to either regimen alone (Strong)



    • If anticoagulation is contraindicated, patients at low risk for VTE should be treated with IPCDs (Moderate) and those at high risk should be considered candidates for prophylactic IVC filter placement (Limited)



    • Continuation of VTE prophylaxis for at least 1 mo after discharge may be considered (Limited)



    • Screening for DVT in asymptomatic patients is not recommended (Strong)



    • Anticoagulation can be initiated safely after 24 h in the setting of hemodynamically stable solid organ injuries or closed head injuries in the absence of ongoing bleeding or injury progression. Approval from the treating general or neurosurgeon should be obtained before initiating treatment. (Limited)




  • In patients with isolated unilateral lower extremity injury who are ambulatory:




    • Anticoagulation on hospital discharge is not required in the absence of other VTE risk factors (Moderate)





  • Recommendation Strengths:




    • ACCP: 1B = strong recommendation, moderate-quality evidence, benefits clearly outweigh risk and burdens or vice versa; 1C = strong recommendation, low-quality or very low quality evidence, benefits clearly outweigh risks and burdens or vice versa; 2B = weak recommendation, moderate-quality evidence, benefits closely balanced with risks and burdens; 2C = weak recommendation, low-quality or very low quality evidence, uncertainty in the estimates of benefits, risks, and burdens; benefits, risk, and burden may be closely balanced



    • EAST: Level I recommendation = convincingly justifiable on the basis of scientific information alone through class I data; level II recommendation = reasonably justifiable on the basis of a preponderance of class II data; level III recommendation = supported only by class III data; Class I data = prospective randomized controlled trial; Class II data = clinical study with prospectively collected data or large retrospective analyses with reliable data; Class III data = retrospective data, expert opinion, or a case report.



    • OTA: Strong = >2 high-quality (level I) studies to support the recommendation; Moderate: 1 high-quality (level I) or 2 moderate-quality (level II or III) studies to support the recommendation; Limited = 1 moderate-quality (level II or III) or 2 low-quality (level IV) studies to support the recommendation; Inconclusive = 1 low-quality (level IV) study or lack of evidence to support the recommendation; Consensus = expert work-group opinion (no studies)



Abbreviations: DVT, deep venous thrombosis; GCS, Glasgow Coma Scale; IPCD, intermittent pneumatic compression device; ISS, Injury Severity Score; IVC, inferior vena cava; LMWH, low molecular weight heparin; MR, magnetic resonance; PE, pulmonary embolism; RR, relative risk; SCI, spinal cord injury; VTE, venous thromboembolism.

Data from Refs.


More recent literature using larger patient cohorts and routine thromboprophylaxis protocols has better defined the true incidence of clinically relevant VTE following severe trauma. A retrospective review of a multicenter trauma registry containing nearly 8000 major trauma patients identified a VTE incidence of only 1.8% when institutional thromboprophylaxis protocols were used. Despite the relatively low incidence, the presence of VTE (either DVT or PE) nearly doubled the mortality rate (13.7% vs 7.4%), and among patients who developed a PE, the mortality rate was 25.7%. A single-center retrospective review of more than 1300 major trauma patients treated at a level 1 trauma center revealed a 2.3% incidence of PE. All PEs occurred within 15 days of injury, with most being diagnosed within the first week. Age older than 55 years, multisystem injury, cannulation of central veins, and pelvic fractures (but not long-bone fractures) were independent risk factors for developing a PE. Using a statewide trauma database over a 5-year period, Tuttle-Newhall and colleagues reported an overall PE incidence of 0.3% among more than 300,000 trauma patients receiving standard VTE prophylaxis. Age older than 55 was a significant risk factor for development of PE, with an incidence of 0.7% in this demographic. Increasing Injury Severity Score (ISS) and Abbreviated Injury Scale (AIS) for the extremities, soft tissue, and chest regions were also associated with significantly increased risk of PE.




Physiology and epidemiology of venous thromboembolism in trauma


Basic Science and Physiology of Trauma and Coagulation


Traumatic injury results in significant physiologic changes. Serum levels of inflammatory cytokines including interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-α) are increased following traumatic injury and result in a hypercoagulable state. In addition to inflammatory markers, serum levels and activity of procoagulant microparticles are significantly increased following blunt trauma, and peak thrombin levels are correlated to injury severity. The systemic inflammatory response triggered by traumatic injury results in a hypercoagulable state that places patients at increased risk of venous thromboembolism (VTE). This hypercoagulability combined with endothelial injury and venous stasis, 2 other conditions often noted in trauma patients, completes the Virchow Triad. The presence of all 3 elements contributes to venous thrombosis.


Venous Thromboembolism Following Major Trauma


Before the implementation of routine thromboprophylaxis, reported rates of VTE following major trauma were extremely high. Using bilateral lower extremity venography, Geerts and colleagues reported a 58% incidence of lower extremity deep vein thrombosis (DVT) in 349 patients admitted for major traumatic injuries who did not receive thromboprophylaxis. DVT rates varied by anatomic region injured, ranging from 50% in patients with major injuries to the face, chest, or abdomen to 80% in patients with femur fractures. The rate of fatal pulmonary embolism (PE) was 0.9%, and independent risk factors for DVT identified included age, blood transfusion, surgery, fracture of the femur or tibia, and spinal cord injury. Despite its relatively low incidence, PE is still the third most common cause of in-hospital death among trauma patients.


Thromboprophylaxis for Venous Thromboembolism in Trauma Patients


Both chemical and mechanical thromboprophylaxis has been shown to decrease rates of VTE in the setting of trauma. Pharmacologic prophylaxis with low molecular weight heparin (LMWH) was shown to significantly decrease the incidence of both DVT and PE in a large cohort of more than 2200 trauma patients. Mechanical prophylaxis with pneumatic sequential compression devices (SCDs) significantly decreased VTE incidence from 11% to 4% ( P = .02) in a prospective randomized controlled trial of 300 orthopedic trauma patients compared with no VTE prophylaxis. A growing understanding of the importance of thromboprophylaxis in trauma patients has led to the development of institutional protocols for VTE prophylaxis at trauma centers around the world. Additionally, several professional organizations have published clinical guidelines for thromboprophylaxis in trauma patients, which are summarized in Table 1 .



Table 1

Evidence-based guidelines for venous thromboembolism prophylaxis in orthopedic trauma





















Organization Summary of Findings and Recommendations
Cochrane database systematic review


  • Mechanical and pharmacologic prophylaxis independently reduce risk of DVT, RR = 0.43



  • Pharmacologic prophylaxis is more effective than mechanical at reducing DVT risk, RR = 0.48



  • Combined mechanical and pharmacologic prophylaxis results in the lowest risk of DVT, RR = 0.34



  • LMWH reduces DVT risk more effectively than unfractionated heparin, RR = 0.68



  • No high-quality evidence that thromboprophylaxis reduces mortality or PE



  • Recommend the use of any DVT prophylactic method for patients with severe trauma

American College of Chest Physicians (ACCP)


  • In patients undergoing major orthopedic surgery:




    • Recommend using a pharmacologic thromboprophylaxis agent (Grade 1B) or IPCDs (Grade 1C) for a minimum of 10–14 d and considering extending pharmacologic thromboprophylaxis for up to 35 d (Grade 2B).



    • Suggest using LMWH in preference to other pharmacologic agents (Grade 2B/2C) and adding an IPCDs to pharmacologic prophylaxis during the inpatient hospital stay (Grade 2C)



    • Suggest IPCDs or no prophylaxis for patients at increased bleeding risk (Grade 2C)



    • Suggest against “prophylactic” IVC filter placement (Grade 2C) and recommend against duplex ultrasound screening for DVT before hospital discharge (Grade 1B)




  • In patients with isolated lower extremity injuries below the knee requiring immobilization without a history of VTE:




    • Suggest no thromboprophylaxis (Grade 2B)


Eastern Association for the Surgery of Trauma (EAST)


  • Risk Factors for VTE: Spinal fractures or SCI (level I), older age, ISS, blood transfusion, long-bone fracture, pelvic fracture, head injury (level II)



  • Little evidence to support low-dose unfractionated heparin as sole thromboprophylaxis agent (level II)



  • IPCDs (or foot pumps if the calf is inaccessible) may have some benefit in patients with spine injuries or head trauma (level III)



  • LMWH may be used in patients with pelvic fractures requiring surgery, complex lower extremity fractures, or complete SCI with motor involvement (level II)



  • LMWH should be used as primary prophylaxis in trauma patients with ISS >9 and should be considered for several weeks after injury in patients at high risk for VTE (level III)



  • IVC filters should be inserted for the following indications:




    • Recurrent PE, proximal DVT, or progression of iliofemoral DVT while on full anticoagulation (level I)



    • Large/free-floating IVC/iliac thrombi, following massive PE, during/after surgical embolectomy (level II)




  • “Prophylactic” IVC filters should be considered if anticoagulation is contraindicated in patients with the following high-risk injury patterns:




    • Severe closed head injury (GCS<8), incomplete SCI with motor involvement, complex pelvic fracture with associated long-bone fracture, multiple long-bone fractures (level III)




  • Duplex ultrasound should be used to assess symptomatic trauma patients with suspected DVT (level I) but should not be used for screening asymptomatic patients (level III)



  • Ascending venography may be useful for confirming a diagnosis of DVT when ultrasound is equivocal (level II), and there may be a role for MR venography in the diagnosis of DVT in the acute setting, especially in areas in which venography and ultrasound are less reliable (level III)

Orthopedic Trauma Association (OTA)


  • In hospitalized orthopedic trauma patients:




    • In the absence of contraindications, LMWH is the agent of choice and should be initiated as soon as possible, preferably within 24 h (Strong)



    • Combined LMWH and IPCDs are preferable to either regimen alone (Strong)



    • If anticoagulation is contraindicated, patients at low risk for VTE should be treated with IPCDs (Moderate) and those at high risk should be considered candidates for prophylactic IVC filter placement (Limited)



    • Continuation of VTE prophylaxis for at least 1 mo after discharge may be considered (Limited)



    • Screening for DVT in asymptomatic patients is not recommended (Strong)



    • Anticoagulation can be initiated safely after 24 h in the setting of hemodynamically stable solid organ injuries or closed head injuries in the absence of ongoing bleeding or injury progression. Approval from the treating general or neurosurgeon should be obtained before initiating treatment. (Limited)




  • In patients with isolated unilateral lower extremity injury who are ambulatory:




    • Anticoagulation on hospital discharge is not required in the absence of other VTE risk factors (Moderate)





  • Recommendation Strengths:




    • ACCP: 1B = strong recommendation, moderate-quality evidence, benefits clearly outweigh risk and burdens or vice versa; 1C = strong recommendation, low-quality or very low quality evidence, benefits clearly outweigh risks and burdens or vice versa; 2B = weak recommendation, moderate-quality evidence, benefits closely balanced with risks and burdens; 2C = weak recommendation, low-quality or very low quality evidence, uncertainty in the estimates of benefits, risks, and burdens; benefits, risk, and burden may be closely balanced



    • EAST: Level I recommendation = convincingly justifiable on the basis of scientific information alone through class I data; level II recommendation = reasonably justifiable on the basis of a preponderance of class II data; level III recommendation = supported only by class III data; Class I data = prospective randomized controlled trial; Class II data = clinical study with prospectively collected data or large retrospective analyses with reliable data; Class III data = retrospective data, expert opinion, or a case report.



    • OTA: Strong = >2 high-quality (level I) studies to support the recommendation; Moderate: 1 high-quality (level I) or 2 moderate-quality (level II or III) studies to support the recommendation; Limited = 1 moderate-quality (level II or III) or 2 low-quality (level IV) studies to support the recommendation; Inconclusive = 1 low-quality (level IV) study or lack of evidence to support the recommendation; Consensus = expert work-group opinion (no studies)


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Feb 23, 2017 | Posted by in ORTHOPEDIC | Comments Off on Thromboembolic Disease After Orthopedic Trauma
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