There is insufficient evidence to make a strong, moderate strength, or weak recommendation related to the benefits and harms of venous thromboembolism (VTE) prophylaxis.

Early initiation of pharmacological VTE prophylaxis within 48 hours of injury may be considered in adult patients with penetrating TBI who have not suffered an increase in incident hemorrhage volume without increasing the risk of consequent intracranial hemorrhage, emergent reoperation, or death. There is, however, insufficient evidence of efficacy and insufficient evidence to make recommendations about the choice of pharmacologic agent, time to initiation, dosage, and duration for VTE prophylaxis.

In the absence of direct scientific evidence, EXPERT CONSENSUS concluded that:

• Mechanical VTE prophylaxis should be considered for all adult patients with pTBI. (100% consensus)
• VTE chemoprophylaxis may be considered for all adult patients with pTBI 24 - 48 hours after cranial surgery and/or stable hemorrhage on CT scan. (96.7% consensus)

No evidence or expert opinion supported distinct recommendations based on patient gender, wounding mechanism, or military vs. civilian context, or for pediatric age groups.

The optimal type and timing of VTE prophylaxis is insufficiently understood across the breadth of TBI. It is a particularly deficient and underexplored area of critical care for pTBI patients. pTBI patients may be at higher risk of both VTE and hemorrhagic complications given the extent of brain tissue and vascular injury which these patients experience. Traumatic injury is well known to activate tissue factor and induce coagulopathy, whereas confinement in intensive care unit limits mobility increases risk of deep venous thrombosis and venous thromboembolism. Moreover, TBI severity increases risk of venous thrombosis, and presence of extracranial injuries further adds significantly to this risk.1,2 Defense forces must often transport patients long distances in acutely injured conditions, likely predisposing to unique VTE risks distinct from those faced by civilian patients.

Accurate diagnosis of DVT and VTE is also complex. If routine screening or high suspicion is not present, diagnosis of asymptomatic venous thrombosis may be missed. In the CRASH2 trial of 13,273 patients, administration of placebo or a procoagulant, tranexamic acid did not increase risk of symptomatic DVT or VTE and overall rates were low (0.9%) though patients were not routinely screened.3,4

The prior edition of the pTBI guidelines (2001) did not endeavor to review or report on this topic.

The data on venous thromboembolism (VTE) prophylaxis in penetrating traumatic brain injury (pTBI) is sparse. We identified one small retrospective study (N=67) of army blast victims published by Meyer et al that compared early VTE chemoprophylaxis in military patients injured in Afghanistan with no prophylaxis.3 The authors defined early prophylaxis as within 48 hours post-injury and the majority of patients received 30mg of enoxaparin (91%) twice daily. Early prophylaxis was associated with a 5% absolute risk reduction in DVT/PE though this different was not statistically significant. In this study early prophylaxis was not associated with either an increased incidence of hemorrhage expansion or VTE. There was also no association with increased rates of emergent reoperation or 30-day mortality. This study provides very low strength evidence that early deep vein thrombosis (DVT) prophylaxis results in little change in likelihood of VTE incidence, while 30-day mortality, likelihood of intracranial hemorrhage, and likelihood of emergent reoperation were not increased. This cohort was 100% male and military which limits generalizability. Additionally, the study was underpowered to demonstrate a difference between early prophylaxis and no prophylaxis for these outcomes and a larger study may have different findings.

As demonstrated above, data on VTE prophylaxis specific to pTBI is severely lacking. Only one study met inclusion criteria as detailed above. As a retrospective study, it is biased; it is unknown whether the patients who received VTE prophylaxis were deemed low risk for intracranial hemorrhagic complications. The sample size is small and underpowered. Furthermore, the study includes only male patients. Use of oral contraceptives is associated with increased thrombotic events, and it is quite possible the risk-benefit profile for females is quite different than men.

Given the paucity of evidence informing VTE prophylaxis in pTBI, it is necessary to consider data from the study of blunt TBI patients. Post-hoc analysis of data from the Erythropoeitin in TBI (EPO-TBI) study2 which excluded pTBI patients demonstrated a risk of deep venous thrombosis (DVT) of 16.9% and VTE risk of 4%, with a median time to diagnosis of 6 days. 91% of these patients received mechanical prophylaxis on day 1, 97% by day 3, and 98% by day 7. 5% of patients had received chemoprohlyaxis for VTE by day 1, 30% by day 3, and 57% by day 7. As per study protocol they all underwent twice weekly lower limb ultrasound screening for DVT. Of note, in this study development of VTE was not associated with increased mortality. However, it must be noted that this protocol of surveillance nor chemoprophylaxis is not routine in clinical practice.

Pediatric patients with TBI are also at risk of VTE. The BTF's pediatric TBI guidelines do not provide recommendations related to DVT prophylaxis; the decision to prescribe VTE prophylaxis in pediatric patients is more controversial than in adult. In a pediatric general trauma population of 753 children, DVT rates were 8.9% and PE rates of 0% while 0% developed DVT on chemoprophyaxis.6 TBI was a risk factor for VTE in this study. Treatment of diagnosed venous thrombosis was not associated with improved VTE outcomes, however. We did not find any evidence informing the VTE prophylaxis in pediatric pTBI patients.

In comparison, the BTF's parent adult coma guidelines make a level 3 recommendation that "Low molecular weight heparin (LMWH) or low-dose unfractioned heparin may be used in combination with mechanical prophylaxis. However, there is an increased risk for expansion of intracranial hemorrhage". However, compared to blunt TBI, pTBI is known to be associated with greater incidence of coagulopathy, and more prevalent neurovascular injuries. While this recommendation is inherently applicable to pTBI as written, is uncertain whether practitioners should consider modifying their practice in light of the unique risk profile of pTBI patients.

VTE are a significant source of morbidity and mortality in TBI patients. This pathology is particularly sinister as it often occurs just as a patient is beginning to show clinical improvement. Over the last decade there has been a shift to increasingly aggressive prophylaxis with earlier initiation of pharmacoprophylaxis. We feel that before initiating pharmacoprophylaxis repeat CT head imaging demonstrating stability of intracranial hemorrhage is advisable. Neurosurgeons are increasingly comfortable initiating pharmacoprophylaxis 24-48 hours after surgery and some report doing so within 24 hours. Many neurosurgeons prefer unfractionated heparin for DVT prophylaxis because the ease of instantaneous reversal with protamine if hemorrhagic complications are encountered.

Physical methods of DVT prophylaxis are safe and effective and should be liberally employed. Nonething in medicine is truly benign, however - beware of common peroneal nerve injuries from excessive pressure on the fibular head when this method is used. There are few contraindications to the use of anti-embolic stockings but such examples of contraindications could include associated limb injury, thrombosis, infection, etc.

VTE prophylaxis is relevant to every blunt TBI and pTBI patient and should be facile to study. Prospective randomized or comparative effectiveness studies should be easy to complete, though a multi-center approach would likely be necessary to have adequate sample size and power for such an investigation in pTBI patients. These studies would likely be low-cost to perform and could achieve very high impact given the paucity of evidence currently available to guide decision making. While hemorrhagic complications are easily detected in most instances, VTE can be occult so there would need to be careful decision-making related to the aggressiveness with which VTE will be sought and diagnosed. Key questions to be answered are the optimal agent and the optimal timing for prophylaxis. It is important to understand if optimal care of pTBI patients differs from patients with blunt TBI and whether all pTBI patients should be managed uniformly. Given the rising rates of pTBI as a public health problem, such a prospective study is not only feasible but essential.