William Geerts, Abdulaziz Aljurayyan, Malin Carling.
Response/Recommendation: In patients with fractures and visceral injuries, mechanical and/or chemical venous thromboembolism (VTE) prophylaxis should be commenced as soon as bleeding risk allows. Mechanical prophylaxis should be administered to patients who are awaiting surgery or at high-risk of bleeding.
Strength of Recommendation: Strong.
Rationale: Orthopaedic trauma patients frequently have concomitant visceral and/or brain injuries1–4. In general, major fractures significantly increase the risk of VTE in polytrauma1,4–8 while non-orthopaedic injuries (except spinal cord injuries) generally have a much lower impact on the risk of VTE associated with fractures8,9. Conversely, bleeding risk in patients with polytrauma is largely dictated by the presence of visceral and brain injuries.
In polytrauma, VTE risk is relatively high5,10, and use of mechanical and/or chemical prophylaxis should be considered10–13. However, there is wide variability in thromboprophylaxis practice among orthopaedic trauma centers at least in part because of the paucity of direct evidence in this specific group14.
Timing of the initiation of anticoagulant thromboprophylaxis: In major trauma patients, the transition to a hypercoagulable state usually occurs early and is often seen at the time of admission15–17. Furthermore, numerous studies have shown that early initiation of anticoagulant thromboprophylaxis is associated with decreased risk of VTE. There is also evidence to suggest that there is not an increased risk of bleeding among trauma patients anticoagulated early, including those with pelvic trauma18–20, spine fractures21–24, solid abdominal organ injuries25–28, and head injuries8,29,30. Among 2,752 patients with isolated, severe pelvic fractures, commencement of anticoagulant thromboprophylaxis within 48 hours after admission was associated with no difference in deep venous thrombosis (DVT) rate, but a five-fold lower pulmonary embolism (PE) rate; overall mortality was also lower among patients anticoagulated early within 48 hours. However, patients with more severe injuries or who received blood transfusions were less likely to get early prophylaxis, thus limiting evaluation of bleeding risk in those groups18. Another study showed a significant decrease in VTE if thromboprophylaxis was started within the first 24 hours compared with a later start without an increase in bleeding events. However, this database study included patients with injury severity score (ISS) as low as 5, did not report the number of extremity injuries and adjusted for abbreviated injury scale (AIS) of only 2 for extremity31. Rostas et al., found that early anticoagulant thromboprophylaxis in patients with blunt liver or spleen injuries was safe and was associated with reduced rates of VTE32. A double-blind randomized trial demonstrated the effectiveness and safety of low-molecular-weight heparin (LMWH) thromboprophylaxis started within 36 hours of injury in 344 major trauma patients; LMWH was also shown to be significantly more effective than low-dose heparin, with both having equivalent risk of major bleeding33. Another trial showed that among trauma patients at high-risk for VTE who were randomized to receive enoxaparin within 24 hours of admission or only mechanical thromboprophylaxis, major and minor bleeding did not differ between groups34. For patients with high-risk of bleeding or in whom clinical evidence of hemostasis has not yet occurred, the initial use of sequential compression devices (SCD) is recommended10,11,35.
Patients with traumatic brain injury: The main barrier to early anticoagulant thromboprophylaxis in patients with orthopaedic trauma is the presence of traumatic brain injury (TBI)8,30,36. Although patients with TBI have an increased risk of VTE37,38, anticoagulant thromboprophylaxis is often delayed because of concerns about progression of intracranial bleeding (ICB). Some studies have reported a greater risk of ICB associated with early anticoagulant thromboprophylaxis39 while the majority have not8,29,30,36,40–45. Coleman et al., reported that among 1,803 patients with moderate or severe TBI (head AIS > 2), those who started anticoagulant thromboprophylaxis within 48 hours after injury were three times less likely to develop VTE than those who started later without increased bleeding risk8. Three systematic reviews have each shown that VTE was significantly decreased with early anticoagulant thromboprophylaxis in TBI without an increased risk of ICB progression41,45,46. A possible limitation of most of the studies on this topic is that patients with the most severe head injuries may have been excluded or had delayed anticoagulant thromboprophylaxis. However, a large Trauma Quality Improvement Project (TQIP) study in 2,468 severe TBI patients propensity-matched those who had early (< 72 hours) or later (> 72 hours) anticoagulant thromboprophylaxis29. The early group had a lower risk of PE (odds ratio [OR], 0.48) and DVT (OR, 0.51) without an increase in either mortality or neurosurgical intervention. In the only randomized trial addressing this issue, enoxaparin started within 24 hours after injury in 681 TBI patients with stable head computed tomography (CT) was not associated with an increased risk of hemorrhagic progression compared with placebo47. Finally, a systematic review of 21 studies found no relationship between the timing of anticoagulant thromboprophylaxis initiation and hemorrhagic progression in patients with TBI43.
The Neurocritical Care Society (NCS) recommends that TBI patients commence anticoagulant thromboprophylaxis within 24-48 hours of presentation48. The American Association for the Surgery of Trauma (AAST) 2021 guidelines on VTE prophylaxis in TBI also recommends initiation of thromboprophylaxis as soon as possible, generally within 24-72 hours after admission13. We agree with early initiation of LMWH thromboprophylaxis in most TBI patients with the provision that serial head CT after the admission scan should demonstrate stability of ICB. The presence of an intracranial pressure measurement device is not considered a contraindication to anticoagulant thromboprophylaxis49.
Patients with solid organ injury: The majority of solid organ injuries (liver, spleen, kidney, pancreas) are now treated nonoperatively50. Anticoagulant thromboprophylaxis started within 48 hours after blunt solid organ injury in addition to SCD was associated with significantly fewer DVT than a later start (0 vs 9%, p=0.024) without an increased risk for bleeding requiring intervention26. The American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) database was accessed to identify 36,187 patients with nonoperative solid organ injuries27. Patients who received thromboprophylaxis within 48 hours had significantly fewer DVT and PE than those who started later with no increase in bleeding complications or transfusion. These findings were confirmed in a subgroup analysis comparing a start of thromboprophylaxis within 24 hours compared to within 48 hours. Among 3,223 patients with isolated abdominal solid organ injuries, late initiation of anticoagulant thromboprophylaxis was an independent predictor of VTE (OR 3.2; 95% confidence interval [CI] 1.9-5.2) while AIS scores of 3-5 for liver or spleen injuries were associated with increased bleeding rates regardless of the timing of thromboprophylaxis28. The 2021 AAST guidelines recommend that LMWH start within 48 hours after solid organ injury if there is evidence that active bleeding has stopped13. This is based on multiple studies showing no increase in bleeding with early initiation of anticoagulant thromboprophylaxis in patients with solid organ injuries12,26,27,32,51.
- We recommend that every polytrauma patient be evaluated on admission for both bleeding and thrombosis risks. Unstable with active bleeding are usually managed surgically or by endovascular embolization.
- Once there is evidence that there is no active bleeding, we recommend VTE prophylaxis with mechanical and/or chemical agents. For patients with TBI, we recommend VTE prophylaxis when serial imaging is stable for ICB (usually 24-36 hours after injury).
- For patients at high-risk for bleeding, we recommend immediate use of SCD in unaffected lower extremities.
- Early mobility and daily physiotherapy should be encouraged in all cases where there is no contraindication52,53; for example, increased risk of DVT was seen after spinal injuries in which spinal precautions persisted beyond 72 hours compared with a shorter time in spite of routine use of SCD in both groups54.
- The recommended duration of chemical VTE prophylaxis in polytrauma is uncertain but is commonly restricted to the hospitalization period. VTE risk is generally more influenced by orthopaedic and spinal cord injuries than by visceral injuries.
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