William Geerts, Abdulaziz Aljurayyan, Malin Carling.

Response/Recommendation: In patients with fractures and visceral injuries, anticoagulant-based thromboprophylaxis should be commenced as soon as bleeding risk allows. Bilateral mechanical thromboprophylaxis, if possible, should be administered to patients who are at high bleeding risk.

Strength of Recommendation: Strong.

Rationale: Orthopaedic trauma patients frequently have concomitant visceral and/or brain injuries^1–4. In general, major fractures significantly increase the risk of VTE in polytrauma^5–10 while non-orthopaedic injuries (except spinal cord injuries) generally have a much lower impact on the risk of VTE associated with fractures^11,12. Conversely, bleeding risk in patients with polytrauma is largely dictated by the presence of visceral and brain injuries.

In polytrauma, VTE risk is relatively high^13,14, and use of mechanical and/or chemical prophylaxis should be considered^15–18. 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 group¹⁹.

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 admission^20–22. Furthermore, numerous studies have shown that early initiation of anticoagulant thromboprophylaxis is associated with decreased risk of VTE in mixed trauma groups^2,3,12,18,19 and in subgroups, including pelvic trauma^20–23, spine fractures^24–27, solid abdominal organ injuries^28–31, and head injuries^8,32,33. At the same time, bleeding complications were not shown to be increased with early anticoagulant prophylaxis in most studies^{8,12,18–21,23–30}. Among 2,752 patients with isolated, severe pelvic fractures, commencement of anticoagulant thromboprophylaxis within 48 hours after admission was associated with a 49% decrease in VTE, a 5-fold lower pulmonary embolism (PE) rate, and reduced mortality with no bleeding complications compared with later commencement²¹. However, patients who received early anticoagulant thromboprophylaxis had less severe injuries. Another study, that included 79,386 trauma patients, showed a significant decrease in VTE if thromboprophylaxis was started within the first 48 hours compared with a later start without an increase in bleeding events¹⁹. In this database study, most of the patients had an injury severity score (ISS) of less than 16 and neither distribution of fractures nor surgical management were reported. 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 VTE¹⁸. 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 and as safe as low-dose heparin³⁴. Another trial showed that, among trauma patients who were randomized to receive enoxaparin within 24 hours of admission or only mechanical thromboprophylaxis, major and minor bleeding did not differ between groups³⁵.

For patients with high risk of bleeding or in whom evidence of hemostasis has not yet occurred, the initial use of sequential compression devices (SCD) is recommended, although the evidence for use of SCD in major trauma is weak^10,11,36.

Traumatic brain injury patients: The main barrier to early anticoagulant thromboprophylaxis in patients with orthopaedic trauma is the presence of traumatic brain injury (TBI)^8,33,37. Although patients with TBI have an increased risk of VTE^38,39, anticoagulant thromboprophylaxis is often delayed because of concerns about progression of intracranial bleeding (ICB). One study reported a greater risk of ICB associated with early anticoagulant thromboprophylaxis⁴⁰, while the vast majority did not^{8,32,37,41–46}. Among 1,803 patients with moderate or severe TBI (head Abbreviated Injury Scale > 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 progression^42,47,48. 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 used propensity-matching of those who had early (< 72 hours) or later (> 72 hours) anticoagulant thromboprophylaxis³². 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 computer tomography (CT) was not associated with an increased risk of hemorrhagic progression compared with placebo⁴⁹. Finally, a systematic review of 21 studies found no relationship between the timing of anticoagulant thromboprophylaxis initiation and hemorrhagic progression in patients with TBI⁴⁴.

The Neurocritical Care Society recommends that TBI patients commence anticoagulant thromboprophylaxis within 24 – 48 hours of presentation⁵⁰. The American Association for the Surgery of Trauma (AAST) 2021 guidelines on VTE prophylaxis in TBI also recommend 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 a repeat head CT after the admission scan should demonstrate stability of intracranial bleeding. The presence of an intracranial pressure measurement device is not a contraindication to anticoagulant thromboprophylaxis⁵¹.

Patients with solid organ injury: The majority of solid organ injuries (liver, spleen, kidney, and pancreas) are now treated nonoperatively⁵². 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) with no patient requiring an intervention for bleeding²⁹. The American College of Surgeons TQIP database was accessed to identify 36,187 patients with nonoperative solid organ injuries over a two-year period³⁰. 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 abbreviated injury scale (AIS) scores of 3 – 5 for liver or spleen injuries were associated with increased bleeding rates regardless of timing of thromboprophylaxis³¹. 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 injuries^18,29,30,53.

Conclusion: In polytrauma, the bleeding risk is highest immediately and in the early period after injury. Clearly, the initial clinical priority in such patients is to control active bleeding. The risk of VTE also begins early after injury although clinically important thrombosis is usually delayed. Both VTE and bleeding risks are modified by the combination of fractures and non-orthopaedic visceral injuries. Orthopaedic trauma patients are at relatively high risk of VTE while the risk of bleeding is generally dictated by the concomitant visceral and head injuries. In general, delayed thromboprophylaxis is associated with increased VTE rates. At the same time, early initiation of anticoagulant thromboprophylaxis does not appear to be associated with increased bleeding risk in patients with visceral and head injuries when there is evidence that there is no active bleeding.

Recommendations:

1. We recommend that every polytrauma patient be evaluated on admission for both bleeding and thrombosis risks¹².
2. Patients with active bleeding are usually managed surgically or by endovascular embolization. We recommend that anticoagulant thromboprophylaxis be delayed until the high bleeding risk resolves.
3. Once there is evidence that there is no active bleeding, we recommend anticoagulant thromboprophylaxis, generally with weight-based LMWH and generally within 24 hours after injury¹². For TBI, when consecutive brain imaging is stable for ICB (usually 24 – 36 hours after injury), we recommend starting anticoagulant thromboprophylaxis.
4. For patients at high risk for bleeding, we recommend starting SCD, although the high frequency of lower extremity fractures in polytrauma often precludes use of bilateral SCD. Once hemostasis occurs, we recommend replacing SCD with LMWH or adding LMWH to SCD.
5. We recommend early fixation of unstable fractures to reduce pain, promote mobility and decrease VTE risk²². If fracture repair will be delayed, we recommend that LMWH thromboprophylaxis not be delayed.
6. Since missed anticoagulant doses are associated with increased VTE risk, this should be avoided unless it is essential^8,53,54.
7. Early mobility and daily physiotherapy should also be encouraged^55,56; 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 groups⁵⁷.
8. The duration of thromboprophylaxis in polytrauma is uncertain and is generally more influenced by orthopaedic and spinal cord injuries than by visceral injuries. We recommend that thromboprophylaxis generally be limited to the length of hospital stay.
9. For patients undergoing in-patient rehabilitation, we recommend continuation of thromboprophylaxis with either a direct oral anticoagulant such as rivaroxaban (generally our preference) or with LMWH. However, we recommend against post-discharge primary thromboprophylaxis unless there are additional major risk factors (such as previous VTE or active cancer); this approach has not been carefully studied and, therefore, is at the clinical judgement of the care team⁵⁸. Further studies are underway⁵⁹.
10. We recommend the use of standardized VTE prophylaxis policies, embedded in routine order sets, as well as periodic audits of adherence to reduce unnecessary variability in practice and improve patient outcomes including VTE^12,13,60,61.

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