My name is Brad Dengler, and I'm currently a neurosurgeon and neurointensivist at Walter Reed National Military Medical Center. Today, I'm going to cover the latest research into venous thromboembolism chemoprophylaxis. In some other sessions, you've likely already heard about the latest guidelines and recommendations for chemoprophylaxis in cranial and spinal surgery. Since they usually lag behind the latest research and most recent publications, I thought it would be best to go over the latest studies evaluating different methods of chemoprophylaxis in the neurosurgical patient population. I have no disclosures. I am currently a government employee on active duty in the Army, and the views expressed here do not represent the views of the Department of Defense, United States Army, or Walter Reed National Military Medical Center, and represent only my own views and thoughts. As you can see here, here's the agenda for today's talk. We will evaluate the type of VTE prophylaxis, the time to initiate that VTE prophylaxis, mechanistic issues involved in starting and stopping the VTE prophylaxis, and then finally some other beneficial effects to placing patients on unfractionated heparin medication in regard to aneurysmal subarachnoid hemorrhage. There has been longstanding evidence to both sides of the argument about which type of chemoprophylaxis is better overall for the patient. In most medical and trauma intensive care units, low molecular weight heparin has risen to the top as a better drug because it has shown to decrease both mortality and the overall rate of venous thromboembolic events. There has been consistent concern in our community about the risks of giving low molecular weight heparin given it is not as easily reversed as unfractionated heparin. There have been several large retrospective studies comparing both unfractionated heparin and low molecular weight heparin. I will get into them in more detail and explore the findings and recommendations from each study. These two studies include the 2012 study from Quatt et al along with a more recent evaluation by Benjamin in 2017. Both are fairly large retrospective studies using trauma databases with a significant number of patients in each. Going into more detail in the Quatt study, this is a retrospective cohort study that includes 7 level 1 trauma centers over a 4 year period. All patients with penetrating brain injuries were excluded and they only included blunt trauma patients with a head AIS greater than 3. Patients were 18 years of age or older and they had an initial head CT on admission along with at least one other head CT. Patients who received low molecular weight heparin were required to have another head CT after they started their chemoprophylaxis. Patients requiring any emergent general surgery or vascular surgery on admission were excluded from the analysis, along with patients who were anticoagulated at home on warfarin or therapeutic low molecular weight heparin, had a history of venous thromboembolic events in the past, or were hospitalized for less than 48 hours. They divided patients into two groups, those receiving low molecular weight heparin and those receiving unfractionated heparin, and looked at the primary outcome as expansion of intracranial hemorrhage on the repeat head CT. There was a total of 1,215 patients included in the study. Of these, 220 received low molecular weight heparin and the remaining 995 received unfractionated heparin. On the left side of the slide is the chart describing the clinical characteristics between the two groups. Of note, there was a statistically significant difference between the groups. The low molecular weight heparin group had a significantly lower Glasgow Coma score, longer length of stay in the hospital, and intensive care unit. Control group patients were older and more likely to be on antiplatelet agents at home. On the right is a breakdown of hemorrhages by type between the two groups, and as you can see, the low molecular weight heparin group had more parenchymal hematomas, contusions and intraventricular hemorrhages. Epidural hematomas and subdural hematomas were the same between groups, but the low molecular weight heparin group had more surgeries on presentation. So overall, the patients in the low molecular weight heparin group were sicker and more likely to have intraparenchymal contusions than the unfractionated heparin group, which is interesting given that the majority of us would consider unfractionated heparin the safer drug in these sicker patients. This slide demonstrates the odds ratio of progression of the hemorrhage by group. In this study, there was a statistically significant increase in hemorrhage progression in the low molecular weight heparin group on follow-up CT scan. 42% of the low molecular weight heparin versus 24% in the control group had progression of their hemorrhage. There was also a significant difference in the rate of operative intervention in the low molecular weight heparin group versus the control group, 14.5% versus 4.9% respectively. There was no difference in the rate of hemorrhage progression comparing when the low molecular weight heparin was initiated. They compared less than 48 hours, greater than 48 hours, or at 7 days. As you can see, the odds of hemorrhage progression in this study increased with low molecular weight heparin dosing, the presence of an extra-axial hemorrhage, male sex, and a GCS less than 9. Overall, the low molecular weight heparin group had less episodes of venous thromboembolic which were at 3.1% versus the control group at 9%. Only 42% of the low molecular weight heparin group compared to 11% of the control group had duplex ultrasounds, so these rates are likely underrepresented in the control group. The findings in this study are interesting as they include all patients while other studies showing less progression of hemorrhage had excluded patients with larger size hemorrhages. Additionally, one of the major faults in this study is that the control group did not consistently get a CT after the initiation of prophylaxis while the low molecular weight heparin group was mandated to have one after initiation. This in my view includes considerable bias as this is a retrospective review and the exclusion of people without a repeat head CT is likely biasing the group towards patients who had hemorrhage progression in the low molecular weight heparin group. This questions whether or not this study can be generalizable to the entire trauma population as they did not compare the rate of hemorrhage progression after the initiation of unfractionated heparin. We can now move on to a different and more recent study that directly conflicts with the results that we previously discussed. In this study by Benjamin et al. from 2017, they searched the Trauma Quality Improvement Database or TQIP from 2013 to 2014. They identified all patients with a severe traumatic brain injury who received chemical venous thromboembolic prophylaxis. They included patients with a head AIS greater than or equal to 3 and no other body area was allowed to have an AIS greater than 3 which is how they define an isolated head injury. Patients were discharged with a hospital length of stay that less than 48 hours were excluded along with patients with missing VTE prophylaxis data or those receiving any agent other than unfractionated heparin or low molecular weight heparin. All patients were divided into 3 groups based on when their prophylaxis was started, less than 48 hours, 49-72 hours, or greater than 72 hours. The primary outcome of the study was VTE events, pulmonary embolism, deep vein thrombosis, or unplanned emergency surgical interventions which they were using as a marker for a bleed after initiating chemical VTE prophylaxis. Overall, as you can see from the chart on the left, this was a much more robust patient population including 20,417 patients. The balance between patients who received heparin or low molecular weight heparin were equal and the majority of patients received VTE chemoprophylaxis within 48 hours. They showed a 1% unplanned emergency surgery rate which is much lower compared to other studies. There was about a 10% rate of VTE with less than 1% rate of pulmonary embolism. In the multivariate analysis, unfractionated heparin was an independent risk factor for increased mortality. Delayed prophylaxis greater than 72 hours was also an independent risk factor for both VTE and mortality. Increasing AIS continued to be a risk factor for VTE. Low molecular weight heparin did not show an increased risk of returning to the operating room. Of note, regardless of AIS, low molecular weight heparin was an independent predictor of improved mortality. Looking at both the studies together, we now have evidence for both low molecular weight heparin or unfractionated heparin, but in a deep dive I would argue the second study is more robust with more realistic outcomes and low molecular weight heparin is the clear winner. The first study looked at radiograph progression alone in only patients who had repeat CT scans after initiating low molecular weight heparin. While this study evaluated a more clinically useful endpoint in that it looked at patients who returned emergently to the operating room unexpectedly, which additionally, the clear mortality benefit due to low molecular weight heparin is hypothesized to be due to multiple different effects including decreased inflammation, decreased blood-brain barrier permeability, and improvement in cerebral edema that have been shown after the initiation of low molecular weight heparin in animal models. After evaluating cranial trauma, we can take a brief look at spine trauma to determine if this carries the same ideas and results as the evaluation in cranial trauma. This is a recent publication from 2020 that evaluates the differences between low molecular weight heparin and unfractionated heparin in spine trauma patients. The same TQIP database was searched from 2013 to 2015 using the AIS for a spine. Patients were excluded that had an AIS of 6, discharged in less than 24 hours, and who had polytrauma, again defined as an AIS greater than 3 in any other system except for spine. Additionally, patients who had no records of DVT prophylaxis were also excluded. The primary outcome of the study was in-hospital mortality following injury with secondary outcomes including composite thromboembolic complications, total complications for the length of stay, unplanned return to the OR, which again was used as a proxy for the risk of epidural hematoma formation after the initiation of chemoprophylaxis. This table shows the characteristics of patients receiving low molecular weight heparin versus unfractionated heparin for VTE prophylaxis. As you can see, there were 27,513 patients who met the inclusion criteria, 20,341 received low molecular weight heparin, and 7,172 received unfractionated heparin. Age was not different between the groups but the low molecular weight heparin group had more males. Unfractionated heparin was more likely to be used in patients who had altered mental status, hypotension on arrival, and were more likely to undergo a stabilization procedure or have a spinal cord injury. There was no difference in the mean length of stay but a higher mortality rate in the unfractionated heparin group who additionally had a higher rate of VTE events. No differences were discovered between unplanned return to the OR between the two groups. So overall, it seems like the unfractionated heparin group was sicker with more neurological injuries, which is consistent in what we would generally see in the cranial population in that the sicker patients generally received unfractionated heparin versus low molecular weight heparin. This slide demonstrates the primary outcome from the study, which was mortality. Patients who had received low molecular weight heparin had a lower odds ratio of mortality, VTE events, and complications. Surprisingly, the return to the operating room was the same between the two groups with no difference, which is important given the same finding occurred in the prior paper discussing cranial trauma. So it appears that low molecular weight heparin might be the winner when looking at DVT prophylaxis in the trauma population. This slide breaks the patients into two groups for comparison. Table 3 on the top is an analysis of the complications in patients who underwent surgical stabilization. In this subgroup, there was a lower mortality rate in patients who received low molecular weight heparin versus unfractionated heparin without a difference in VTEs. There was a higher complication rate in the group receiving low molecular weight heparin, but that did not result in a difference between the groups in return to the operating room. Stratifying by spinal cord injury showed that patients had a lower mortality rate and lower thromboembolic complications with the same rate of total complications between the two groups. This data, although retrospective, is large and had a large number of complications, making it a better comparison overall. It shows an overall benefit to low molecular weight heparin without a significant increase in unplanned returns to the operating room. Although they used a rather broad category of unplanned return to the operating room as a surrogate marker for epidural hematoma, it seems that given this data, there are no increased risks of using low molecular weight heparin in the spinal trauma population. After comparing whether or not heparin versus low molecular weight heparin is better at preventing adverse events in patients, we can now move on to evaluate whether the time it takes to initiate the DVT prophylaxis impacts the overall outcome of the patient. Again, the first study we look at is from the trauma population. It seems that in the vast majority of the literature, the majority of these studies come from the trauma population, and this is likely due to the fact that this is where the vast amount of data lives. In addition, trauma patients are usually seen and evaluated by multiple different subspecialties and services within the hospital, making the argument over VTE chemoprophylaxis a significant concern as each service has competing interests, but all want what's best for the patient. In this study, this is a systematic review that was founded on the PICO question, do patients who present with traumatic intracranial hemorrhage and receive pharmacological prophylaxis early compared to those who receive pharmacological prophylaxis later differ in hemorrhagic progression or VTE based on comparative studies? They set an arbitrary time frame for early as less than 72 hours, which 72 hours is still pretty late compared to most other centers who seem to be starting DVT prophylaxis much earlier. They included prophylactic dosing of low molecular weight heparin at 40 mg daily or unfractionated heparin at 5000 units BID or TID. All DVT or PE events were diagnosed as new by routine ultrasonography and ventilation perfusion or CT angiography. They included all articles where traumatic intracranial hemorrhage patients were managed with prophylactic medications during admission where the administration was delineated and clinical course details reported throughout the chart. Traumatic bleeding was defined as any volume of blood occurring intracranially after a traumatic event. Studies were excluded that included patients with spinal cord injuries, lower extremity injuries, or pre-existing coagulopathies or already anticoagulated at home. Additionally, they excluded series that were reported with less than 10 patients or case reports. Each study selected was graded using the grade methodology and additionally received a bias score. 29 studies were initially included in their literature search but 18 were excluded due to various reasons including no comparison on timing or they had previously published overlapping cohorts of patients in multiple studies. As you can see in the chart on the left there is no difference in hemorrhage expansion between the early or late prophylaxis groups. This is a pooled analysis of all studies so includes both unfractionated heparin and low molecular weight heparin. They define progression for the purposes of this study as new hemorrhage or document an increase in hemorrhage volume on standard repeat imaging. Even breaking down the analyzed studies into three groups evaluating patients at less than 24 hours, less than 48 hours, and less than 72 hours for starting the DVT prophylaxis they did not show a difference in hemorrhage expansion. In evaluating VTEs in the same population there is an overall VTE rate of 5.2 percent and 9.2 percent in the two groups with a statistically significant difference favoring early prophylaxis overall. This result was significant in the less than 48 hour group but not in either of the less than 24 or 72 hour groups likely due to lack of number of patients in those groups. Breaking down these pooled VTE results into DVT and PE show similar results with significant difference in the early group for both DVT and PE overall meaning that the earlier to DVT prophylaxis was initiated the less likely they were to have a DVT or PE event. In this slide you will see the pooled mortality data overall in the early versus late groups. Overall there was no statistically significant difference between early versus late. In the less than 48 hour subgroup there was a statistically significant trend in favor of early DVT chemoprophylaxis. Moving along to a more recent literature that does not involve a meta-analysis is the next paper by Coleman et al. This is a retrospective study of five different trauma centers including patients with moderate to severe head injuries admitted over a two-year period. Patients were included who had a head AIS greater than or equal to two, hospital length of stay greater than 72 hours, and two or more head CTs after admission. Patients less than 18 years old, a history of previous vena cava filter, or isolated concussion were excluded. The primary outcome was VTE, including both PE or DVT during their hospital admission and additionally they included it three months post-discharge. Secondary outcomes included radiological TBI progression as defined as an increase on size of the hemorrhage on CT scan. Patients were classified as receiving no VTE, early VTE within 48 hours of admission, or late VTE which was greater than 48 hours after admission. So in this study they are including less injured patients since they included AIS scores greater than or equal to 2 instead of 3 as most of the prior studies. Additionally they excluded those patients who are on pre-existing anticoagulation which is consistent throughout multiple studies. In this study you can see that they included 1,803 patients. The patients were predominantly male at 69% with a median age of 55 and a median ISS of 22 with the majority being due to blunt trauma. The median systolic blood pressure was at 137 mmHg with only 3% of the total patients presenting in shock. 54% of the patients had a severe head injury with an AIS of 4 or 5 and 19% underwent craniotomy or craniectomy with the majority undergoing surgery on the day of admission. The median time to initiation of prophylaxis was 63 hours. 29% of patients never received chemoprophylaxis and 25% received early with 47% receiving late chemoprophylaxis. Only 3% had initiation of chemoprophylaxis within the first 24 hours of admission. And only 2% of patients developed a pulmonary embolism and 7% developed a deep vein thrombosis for an overall pooled rate of VTEs of 8%. The chart pictured shows the multivariate regression analysis for patients sustaining VTE during their hospital stay. The factors shown that put patients at higher risk of sustaining a VTE event during their hospital admission or 3 months post admission include a BMI greater than 30, pelvic or femur fractures, spinal cord injury, and missed doses of chemoprophylaxis. Additionally, there was a significant increase in thromboembolism in the delayed neurosurgical group instead of the immediate group, tending to favor earlier initiation of VTE chemoprophylaxis. In this study, there was an overall 32% radiologic progression of the hemorrhage on the repeat CT scans. This tends to be in line with the higher end of previously reported studies describing the normal progression of intracranial hemorrhage after trauma. But if we break it down further, we can see that only 25% of patients who never received chemoprophylaxis had an increase in their hemorrhage size. 13% of patients in the early group progressed compared with 47% of patients in the late group. But the late group had only 12% progress after the initiation of their prophylaxis. There was no significant difference in hemorrhage progression based on the timing of prophylaxis between the groups. Although this study does show a fairly high overall rate of hemorrhage progression, it is still able to demonstrate this was unrelated to the timing of prophylaxis as the majority of patients tended to progress whether or not they received prophylaxis or not. I think it is safe to say that given this high rate of hemorrhage progression in the non-treated group, it is likely that these patients were the most severely injured with other injuries and therefore likely were going to progress with or without DVT chemoprophylaxis. Additionally, it doesn't actually evaluate the impact on patients, only the radiological progression, which may or may not have impacted the patient's overall clinical outcome and morbidity. After reviewing the latest data on both the choice of agent and timing of initiation, the next piece of the puzzle we are going to evaluate is if the patients are being adequately dosed for their chemoprophylaxis. If we decide, based on the prior literature, that low molecular weight heparin is the best way to proceed, then the standard dosing is generally 40mg daily or 30mg twice a day. But is that good enough in all patients? The manufacturing recommendations for dosing low molecular weight heparin include dosing it at 1mg per kg Q12 hours or 1.5mg per kg every 24 hours. There have been many pharmacological studies showing that single dosing in patients less than 55kg led to higher anti-10A levels than were necessary to maintain a prophylactic range. Additionally, those patients on the other end of the weight spectrum will likely have lower levels as there is an indirect correlation between increasing body weight with anti-10A levels. Assuming that as the patients become more obese, it is likely that they are going to have decreased absorption of the low molecular weight heparin and have decreased anti-10A levels and will likely be sub-therapeutic or not in the prophylactic range for their anti-10A levels. The prophylactic anti-10A level is generally considered to be between 0.2 to 0.4 and some papers or studies will say up to 0.5. This is a study by Rodier et al. which evaluates the use of anti-10A levels in managing patients on low molecular weight heparin for DVT-PE chemoprophylaxis after cranial trauma. It was a retrospective observational analysis of adult patients with traumatic brain injury treated with low molecular weight heparin at a level 1 trauma center over the period of a year. The study group treated by evaluating the anti-10A levels was compared to a fixed dosing guided cohort from the 2016 TQIP database. They included patients over 18 years of age if they received chemoprophylaxis and had at least one repeat head CT available for comparison. The study center used low molecular weight heparin unless the patients had ongoing blood loss, allergy to medication, were older than 80 years of age, had a weight less than 50 kg or a GFR less than 30 mL per minute. Patients were also excluded if they did not meet the criteria for prophylaxis, had devastating brain injuries, or if they did not have a repeat head CT. They initiated the chemoprophylaxis once the patients met the following criteria. They were evaluated by the neurosurgical service and there was no reason for repeat head CT at which point the chemoprophylaxis would be initiated immediately. Therefore, they determined that they needed a repeat head CT and they obtained that repeat head CT six hours after the first one. Those patients included patients who had an epidural hematoma greater than 4 mm or any size temporal epidural hematoma, traumatic brain injury patients who were on clopidogrel or oral anticoagulants, and patients who had an intracranial hemorrhage but could not have a clinical exam that was easily followable or with a posterior fossa contusion. These patients were started on chemoprophylaxis after they had a stable repeat head CT. As you can see from the chart, the patients were initially treated with low molecular weight heparin dosing at 0.5 mg per kg with peak anti-10A activity measured four hours after the third dose with a goal between 0.2 to 0.5 IU per mL. Initially starting doses were not greater than 50 mg Q12 hours or less than 30 mg Q12 hours. After the anti-10A level was returned, if they were outside the goals the dose was adjusted by plus or minus 10 mg depending on if the anti-10A level was too high or too low. The primary outcome was comparison of intracranial hemorrhage progression rate in the assay guided group compared with the fixed dosing standard group at the same hospital. Additionally, secondary outcomes included VTE rates and time to prophylaxis. The outcomes were compared to two other historical groups. The TQIP sample from 2016 and the historical control group I previously discussed receiving either fixed dosing of either 5,000 units of unfractionated heparin every 8 or 12 hours or low molecular weight heparin 40 mg daily. Unfortunately, the study was not powered to detect a difference in VTE events, only a difference in hemorrhage expansion. The overall results of the study showed that the assay guided group contained patients with a lower GCS and higher ISS who were more severely injured. The groups had similar AIS scores along with the proportion of those scores that were greater than 3. The assay guided and TQIP groups had a higher percentage of subdural hematomas included. The assay guided group had the highest percentage of intracranial hemorrhage. Additionally, the assay guided and fixed dosing groups had chemoprophylaxis initiated earlier than the TQIP group. The mean anti-10A level was 0.31. Only 8% of patients required dose adjustments after the first anti-10A level was obtained. Additionally, and most importantly for this study, the rate of ICH progression between the assay guided and fixed dose group was the same. This study demonstrates that for the majority of patients, the dosing regimens as dosed here will likely be adequate to get the patient in the therapeutic range for DVT prophylaxis. This study, though, is limited by the lack of a widespread use of the lab ability to obtain anti-10A level along with the cost and labor intensiveness in monitoring those levels and making dose adjustments. In this last study to evaluate, the processes of care involved in the initiation and maintenance of chemoprophylaxis for VTE. This slide shows the paper by Yoon et al. who evaluated defects in the processes of care at their hospital. It was a retrospective observational study at a single center. The authors identified patients in their administrative database and included all patients who were admitted to the neurosurgical service with a diagnosis of VTE. They excluded patients who were admitted to the neurosurgical service but did not undergo a procedure or who were already on therapeutic anticoagulation. On the right of the slide is the chart defining this institution's evidence-based VTE risk assessment. The screening sheet was determined to be inaccurate if it contained greater than one incorrectly assessed variable based on retrospective review for the study. Since high risk of bleeding is a subjective concern, it was not assessed for accuracy during this study. The study evaluated potentially preventable thromboembolic events defined as patients who developed VTEs and were prescribed suboptimal prophylaxis and or missed greater than one dose. A total of 243 patients were found in the database with 120 excluded for various reasons including no surgical procedures performed or they were already on anticoagulation. This left 123 patients for analysis. There was an even split between cranial and spine procedures. The rates of DVT and PE were the same with only 6% of patients having both. The median time to initiation and prophylaxis was 42 hours. Overall, 16.5% of all doses were not administered and 53 patients missed greater than one of their prescribed doses. Most patients received unfractionated heparin 5,000 units Q12 hours. On average, VTE was diagnosed 96 hours after surgery. In about a quarter of the patients, VTE prophylaxis was not prescribed even though the protocol called for it to be. 50% of patients had inaccurate VTE risk assessments and of these, 25% would have had changed the regimen with 73% of those prescribing a more aggressive regimen. The overall evaluation of the study shows that 92% of VTE events could have been potentially prevented since 12% of the patients were not prescribed risk-appropriate VTE chemoprophylaxis and greater than 38% missed one dose and 42% had greater than 24 hours until their first dose was even administered. This study highlights the importance of close vigilance to DVT prophylaxis ordering, dosing, and avoiding holding of doses if at all possible. Finally, coming out in recent years has been increasing evidence that unfractionated heparin might actually be beneficial in some cases. This study evaluated a continuous heparin infusion protocol and compared it with a standard prophylactic sub-q heparin protocol. It is a 10-year retrospective study at a single institution that included patients who are greater than 18 years of age who had a subarachnoid hemorrhage secondary to a ruptured berry aneurysm. The aneurysm could have been secured by either clipping or coiling and the patients all had to survive the discharge. Patients were excluded if they had a mycotic aneurysm, a dissection, or aneurysms that were associated with an arteriovenous malformation. Aortic vasospasm was defined by an independent neuroradiologist and was defined and graded by characterizing the vessel as either having 0-33% stenosis for mild, moderate as 34-66% stenosis, or severe at greater than 66% stenosis. Delayed neurologic deficits were defined as any new neurological decline compared to baseline after the aneurysm was secured and included a change in mental status, a new pronator drift, or focal neurologic deficit that occurred in the absence of hydrocephalus, a mass lesion, or other medical cause. Patients who demonstrated delayed neurologic deficits were treated with IV fluid boluses and vasoactive medications to induce hypertension that increased the systolic blood pressure by 20-40%. If they did not improve with those measures, then they were taken for a DSA where intra-arterial calcium channel blockers were administered. The low-dose heparin protocol is defined in the slide and was started within 12 hours after the aneurysm was secured at 8 units per kilogram per hour of ideal body weight. The drip was then increased every 12 hours to a total dose of 12 units per kilogram per hour for the 12-14 day period of vasospasm risk. The study included 771 consecutive patients, with 556 meeting the inclusion criteria. They were fairly evenly matched, although the Heparin Infusion Group had worse World Federation of Neurological Surgery scores at admission and greater hemorrhage burden measured by a higher Fisher score, putting them at higher risk of vasospasm. Additionally, the Heparin Infusion Group had a higher rate of surgical clipping. This table shows that analysis of outcomes showed a rate of cerebral infarction in the Heparin Infusion Group that was half the standard prophylaxis group. There was no significant differences in the rate of delayed neurological deficits, intra-arterial rescue therapy, need for VP shunting, length of hospital stay, or discharge disposition. Their rate of DVTs was lower in the Heparin Infusion Group and trended toward statistical significance but did not reach it. And importantly, the Heparin Infusion Group, even though more patients underwent craniotomy in that group, did not have a higher rate of re-bleeding. In multivariate analysis, patients in the Heparin Infusion Group were 1.9 times less likely to develop a delayed neurologic deficit, 2.5 times less likely to develop cerebral infarction, and 2.2 times less likely to develop a DVT. In summary, studies are still ongoing to determine which kind of chemoprophylaxis is better for all patients. But I think laying out the studies involved and the vast majority of the data, it is likely safe to give neurotrauma patients certainly low molecular weight Heparin for DVT and PE prophylaxis after their trauma. Additionally, multiple risk factors such as obesity, long bone fractures, and worsening intracranial injuries makes patients at higher risk of having these events and that means that we should be extra careful in ensuring that these patients get adequate prophylaxis to prevent these adverse events. Additionally, the newer studies evaluating the use of low molecular weight Heparin and the anti-TAN-A levels show that we need to be cautious when dosing these medications at either end of the weight spectrum, as patients could be underdosed or overdosed depending on their exact weight. And certainly in obese patients, we should be more careful and ensure that they are being adequately prophylaxed since they are at higher risk to begin with. Overall, none of the studies were able to show a rate of hemorrhage progression that was statistically significant compared to some of the other studies and the general numbers reported in the literature, meaning that it appears to be safe and there actually could be a benefit to Heparin as we saw in the last study and then some of the other studies commented that their improved mortality seen with low molecular weight Heparin could be due to the effects of the medication itself, promoting decreased permeability in the blood brain barrier and decreased inflammation. So overall, there is no definitive study yet proving which is better, unfractionated Heparin or low molecular weight Heparin, but in my view, there is plenty of evidence to suggest that initiating low molecular weight Heparin is likely beneficial to patients and can be initiated within 24 hours of their initial event or surgery, pending they have a stable head CT.

VTE

chemoprophylaxis

neurosurgical patients

low molecular weight heparin

unfractionated heparin

mortality

traumatic brain injury