Prevention of Deep Venous Thrombosis Post ABI

Several interventions have been examined for the prevention of DVT after an ABI, including mechanical therapy, pharmaceuticals, or a combination of both. To date, the recommendation for treating those who sustain a DVT post ABI is the administration of medication (Elliott et al. 2006; Scudday et al. 2011). However, there is no agreement for the administration of these medications in terms of timing, dose, and/or which medication.

Mechanical Interventions to Prevent Deep Venous Thrombosis Post ABI

Mechanical interventions used to prevent the development of DVT post ABI include: the insertion of vena cava filters, thromboembolism deterrent stocking, intermittent pneumatic compression devices including arteriovenous foot pumps and sequential compression devices (SCDs). These devices operate primarily through two distinct mechanisms of action. The first is mechanical, in which the device increases the velocity of venous return to decrease venous stasis. The second, and perhaps more important, mechanism involves the systemic activation of the fibrinolytic system, which during compression, leads to the breakdown of fibrin clots associated with thromboembolism (Macatangay et al. 2008). The exception is vena cava filters, which operate by another method of mechanical VTE prevention (Watanabe & Sant 2001). These filters are inserted into the inferior vena cava to prevent the passage of distal emboli into the lungs. Some reports have demonstrated success rates as high as 96% in the prevention of pulmonary emboli (Greenfield & Michna 1988). However, the use of vena cava filters is carry some associated with some risk. They can become blocked or dislodged which can increase the risk of an embolism. Some have also reported increased risks for repeated DVT in patients with vena cava filters compared with patients without such devices (Decousus et al. 1998).

Table: Mechanical Interventions used to Prevent Deep Venous Thrombosis post ABI

Discussion

Gersin et al. (1994) investigated the effectiveness of SCDs. Of 32 patients admitted the surgical intensive care unit with severe TBI, a total of eight patients developed DVT or PE following injury, half of whom had received prophylactic SCDs (showing no significant difference between SCDs and no intervention). The effectiveness of prophylactic SCDs in the prevention of post-TBI DVT or PE thus remains questionable.

Davidson et al. (1993) conducted a study to evaluate the possibility that intermittent pneumatic compression could aggravate intracranial hemodynamics in severe brain injury patients. The authors reported that the use of intermittent compression devices to prevent the occurrence of DVT was not associated with any significant changes in intracranial pressure or cerebral perfusion pressure in stable patients in whom intracranial pressure was controlled by conventional measures (Davidson et al. 1993). These findings suggest that there is no contraindication to the use of pneumatic compression for the prevention of DVT in severe acute patients with brain injury who are responsive to conventional intracranial management measures.  

Conclusions

There is Level 2 evidence from one small study to suggest that SCDs are not entirely effective in reducing the risk of developing DVT or PE post ABI.

There is Level 4 evidence that intermittent compression devices do not cause acute elevations in intracranial pressure in patients with severe ABI.  

 

SCDs alone do not reduce the risk of developing DVT or PE post ABI.

 

Intermittent compression devices do not aggravate intracranial hemodynamics in patients with severe ABI.

 

Pharmaceutical Therapies

Oral agents have been investigated for their prophylactic potential against DVT. Warfarin (Coumadin), a well-established anticoagulant with a predictable duration of action, is sometimes avoided as a prophylactic alternative for DVT due to its elevated bleeding side effects (Watanabe & Sant 2001). To illustrate, Albrecht and colleagues (2014) report that warfarin use is associated with lower rates of DVT and PE, but comes at the cost of the risk of increased hemorrhagic bleeding. However, some experts felt the use of warfarin was advisable, especially for high risk patients due to its benefit in treating undetected thrombosis; the therapeutic concentration for prophylaxis and treatment of thromboembolism are the same (Hirsh et al. 1992; Hyers et al. 1992; Landefeld & Goldman 1989).

In a recent study with a sample of 932 patients, 71% were given LMWH, 23% heparin, 1% Coumadin, and 3% were given both LMWH and Low-dose unfractionated heparin, none of which were associated with increased intracranial or systemic hemorrhage (Carlile et al. 2010). The most recent guidelines on DVT prophylaxis recommend using LMWH or Low-dose unfractionated heparin in addition to mechanical prophylaxis (Elliott et al. 2006; Reiff et al. 2009). There is also evidence from a meta-analysis, that aspirin has positive effects in the reduction of both DVT and PE, by 40% and 60% respectively (Antiplatelet Trialists’ Collaboration 1994). Clinically there remains concern that chemical DVT prophylaxis may result in increased intracranial bleeding post ABI.

Overall, there is a lack of persuasive evidence to guide decisions about when to administer anticoagulant prophylaxis in those who sustain traumatic intracranial hemorrhage. Clinicians often make decisions based on their own assessments of the risks and benefits (Scales et al. 2010). To date no national standard of care exists for the administration of the pharmacological prophylaxis treatment of DVT post TBI (Phelan, Eastman, et al. 2012). 

Low Molecular Weight Heparin vs Low-Dose Unfractionated Heparin

Subcutaneous heparin in low doses has been reported to be both safe and effective as prophylaxis against DVT development post ABI (Watanabe & Sant 2001). The route of delivery may also affect the efficacy of anticoagulant prophylaxis (Watanabe & Sant 2001). For this reason, intravenously delivered heparin may be more effective in the prevention of thromboembolism compared with subcutaneous administration, although this method of delivery might increase the risk of bleeding (Green et al. 1988). Low-molecular weight heparins, which are injected subcutaneously, have gained popularity due to the ease of administration and dosage adjustment. Of note, low-molecular weight variants of unfractionated heparin are significantly more expansive, and thus the risks, benefits, and costs need to be balanced out on an individual basis (Watanabe & Sant 2001). Carlile et al. (2006) found that 15 of the 16 rehabilitation centers surveyed reported routinely initiating treatment with either LMWH or Low-dose unfractionated heparin. In a study with a mixed trauma population, low-dose heparin was compared to enoxaparin (LMWH) for the treatment of DVT (Geerts et al. 1996). Of those receiving low-dose heparin 44% suffered a DVT compared to 31% of patients receiving enoxaparin (p=0.014) (Geerts et al. 1996). 

Individual Studies

Table: Unfractionated Heparin or Low-Molecular Weight Heparin vs Placebo for Prevention

Discussion

The effect of administering chemical prophylaxis for DVT post ABI has been reviewed. Results indicate that early treatment (within the first 72 hours) may reduce the risk of developing DVT post injury (Byrne et al. 2016; Farooqui et al. 2013; Kim et al. 2002; Kim et al. 2014; Norwood et al. 2008; Salottolo et al. 2011; Scudday et al. 2011) without increasing the risk of intracranial hemorrhagic injury (Byrne et al. 2016; Koehler et al. 2011; Scudday et al. 2011) or deterioration on neurological examination (Kim et al. 2002). 

Patients with ABI who were started on unfractionated heparin within three days of injury onset, compared to those who started after this time period, did not differ significantly in terms of the number of thromboembolic events (Kim et al. 2002; Kim et al. 2014). However, individuals who were administered heparin within three days of injury had slower progression of neurological impairments on computed tomography scans compared to late administration (Kim et al. 2014).

Norwood and colleagues conducted two studies examining the benefits of administering enoxaparin (LMWH) prophylaxis to those who sustain a severe ABI within the first 48 hours post injury (Norwood et al. 2008; Norwood et al. 2002). Results from both studies indicate that administering enoxaparin post ABI reduces the risk of developing DVT and PE, without increasing the risk of bleeding post injury. Scudday et al. (2011) also found that patients who received chemical prophylaxis within 72 hours of injury had a significantly lower incidence of developing VTE post ABI (p<0.019) compared to those not receiving chemical prophylaxis (Kim et al. 2014) Overall, a meta-analysis by Jamjoom and colleagues (2013) conclude that individuals who begin pharmacological thromboprophylaxis within 72 hours of injury have half the risk of VTE without significant risk of intracranial hemorrhage progression, than those who start after 72 hours.

On the contrary, few studies have demonstrated these medications may not be beneficial or superior treatments. In one study with individuals who underwent a craniotomy post-ABI, no significant differences were reported for rate of DVT and PE when comparing those administered enoxaparin prophylaxis compared to those without (Daley et al. 2015). Further, Kwiatt et al. (2012) reported patients’ receiving LMWH were at higher risk for hemorrhage progression and the risk of using LMWH may exceed its benefit. Similarly for heparin, Lin et al. (2013) did not find a reduction in DVT or PE once individuals with a severe TBI were administered a heparin prophylaxis protocol.

In conclusion, a systematic review of twelve studies report that evidence is insufficient to determine effectiveness of these medications for VTE prevention; however despite the aforementioned studies without significant findings, overall evidence supports the use of enoxaparin for reduction of DVT and UFH for decreased mortality rates compared to no chemoprophylaxis (Chelladurai et al. 2013).  

Conclusions

There is Level 2 evidence supporting the administration of LMWH within the first 72 hours post ABI to reduce the risk of developing DVTs and PEs post injury.

There is Level 2 evidence that administering LMWH (enoxaparin) or heparin post ABI does not increase the risk of intracranial bleeding, compared to no treatment.

There is Level 4 evidence that the use of chemoprophylaxis 24 hours after stable head computed tomography scan decreases the rate of DVT formation post ABI.

 

Although the administration of chemical DVT prophylaxis within the first 72 hours post ABI has been shown to be effective in reducing the risk of developing DVT or PE without increasing the risk of intracranial bleeding, more research is needed to determine its true effectiveness.

 

Enoxaparin is effective for the prevention of VTE after elective neurosurgery and has not been found to cause excessive bleeding.

 

Combination Interventions

Compression stockings and pneumatic compression devices are the major strategies used for the prevention of DVT in trauma patients (Watanabe & Sant 2001). Such mechanical methods are generally more advisable than the use of anticoagulants due to the increased risk of bleeding in patients with multiple fractures and injuries (Watanabe & Sant 2001). These mechanical strategies have demonstrated positive results in the prophylaxis of DVT in neurosurgical patients (Turpie et al. 1989). There is some evidence that the effectiveness of these mechanical devices in the prevention of DVT could also be increased in combination with carefully selected low molecular weight anticoagulants that carry low bleeding risks. For example, Agnelli et al. (1998) reported an additive reduction in thromboembolism, without a significant increase in bleeding risks, in patients with brain injury treated with both enoxaparin and compression stockings compared with patients treated with mechanical compression alone.   

Individual Studies

Table: Physical and Pharmaceutical Methods to Prevent Deep Venous Thrombosis post ABI

Discussion

Studies investigating the benefits of using compression stockings and medication to prevent or treat DVTs post ABI were reviewed. In a RCT conducted by Agnelli et al. (1998) patients due to undergo elective neurosurgery within 24 hours were placed on LMWH or a placebo, and were also fitted with combination compression stockings. DVTs were more common in the placebo group than the intervention group (p<0.004). The combination of both the compression stockings and LMWH appeared to be more beneficial than the compression stockings alone (Agnelli et al. 1998). However, when intermittent pneumatic compression devices were compared to prophylactic LMWH for the prevention of VTE, no significant differences in the development of PEs or DVTs were found between groups (Kurtoglu et al. 2004). 

Conclusion

There is Level 1b evidence that low-molecular-weight heparin combined with compression stockings is more effective than compression stockings alone for the prevention of venous thromboembolism following elective neurosurgery, and that the use of low-molecular-weight heparin in this setting does not cause excessive bleeding. 

There is Level 2 evidence that intermittent pneumatic compression devices alone are as effective as low molecular weight heparin for the prevention of DVT in patients with ABI.

 

 

Compression stockings are more effective at preventing venous thromboembolisms when combined with low-molecular weight heparin than alone. 

 

 

Overall Conclusions

The evidence tends to favor prophylactic anticoagulation, which reduces the risk of suffering a DVT without increasing the risk of intracranial bleeding. LMWH used prophylactically appears to be effective in preventing DVTs without causing increased risk of intracranial bleeding. Unfortunately, due to the limited amount of research available that is directly related to the development of DVTs post ABI, the decision to begin pharmacological prophylaxis post ABI remains a subjective one (Norwood et al. 2008).