Thromboprophylaxis in neurosurgical patients

This issue has never been explored by the college. However, it is a common enough question in the day-to-day practice of intensive care medicine. When can I give this TBI patient their subcutaneous heparin?

There is a lot of literature of this topic, and if one were to choose only one article to read, it should probably be this 2015 review from Critical Care by Abdel-Aziz. The brief summary below is based to a considerable extent on the recommendations made in this review.

In brief:

  • Neurosurgical and neurotrauma patients are at increased risk of DVT/PE.
  • VTE prophylaxis halves the risk of DVT/PE.
  • VTE prophylaxis doubles the risk of bleeding.
  • In TBI, one can safely start s/c heparin if the follow-up CT is unchanged (i.e. the haemorrhage is not progressing).
  • In the case of low-risk small haemorrhages, managed nonoperatively, chemical VTE prophylaxis is very safe and can be started early.
  • In moderate and high risk TBI patients, the prophylaxis can wait until Day 3.
  • The prophylaxis should be started before Day 7.
  • The agent of choice is low molecular weight heparin.

In detail:

Risk of DVT and PE in the neurosurgical population

Risk of anticoagulant-associated bleeding in the neurosurgical population

  • Among contusions and haematomas, about 38% will enlarge between the first and second CT.
  • The risk of this progression is related to the size of the initial bleed and the presence of a subarachnoid or subdural haemorrhage.
  • There is concern that in the presence of prophylactic anticoagulation, the risk of progression will increase.
  • This risk has been confirmed by some of the studies mentioned below; the question remains as to whether the progression of ICH is clinically relevant or not, and whether the benefit of being protected from VTE outweights the risk of clinically relevant ICH.
  • There seems to be some difference in efficacy to guide our choice of agents; a 2011 study by Minshall et al had detected a lower rate of ICH progression among the patients treated with low molecular-weight heparin (the risk of progression was 9.2% with unfractionated heparin and 3.9% with enoxaparin).

Evidence for and against thromboprophylaxis

Norwood paper (2008):

  • Prospective observational study, 525 patients.
  • Excluded anybody interesting: large ICH, multiple contusions, large subdural or extradural collections, or patients with a raised ICP. Weirdly, "trauma surgeon reluctance to initiate early pharmacologic VTE prophylaxis" was an exclusion criterion, irrespective of how rational or irrational this reluctance may have been. Overall, 1,446 patients were excluded from the study.
  • In the remaining carefully selected population, 3.4% of the patients had a progression of haemorrhage after receiving heparin, and though 0.2% (one patient) died as a result, the rest had largely no change to their treatment or outcome.
  • The authors concluded that the risk of clinically significant haemorrhagic complications is much lower than the historical risk of DVT and PE, and that TBI patients should be offered thromboprophylaxis.

Reiff paper (2009):

  • Prospective observational study of all TBI patients in one trauma centre, except for those who died or were discharged within 24 hours.
  • Those patients had a 3-4 fold increase in the risk of DVT or PE, irrespective of whether anticoagulation was used, or how soon it was started.
  • The authors stressed the need for surveillance and "alternate means for pulmonary thromboembolism prevention", rather than any prophylaxis (i.e. "it's going to happen anyway, and the real art is knowing when to shove an IVC filter up into them").

Levy paper (2010):

  • Retrospective study of 342 patients with TBI
  • Two groups were considered: those with a stable follow-up CT, and those whose follow-up CT demonstrated the progression of haemorrhage.
  • The progressing-haemorrhage group turned out to be more exposed to anticoagulant thromboprophylaxis.
  • The authors then inferred that the anticoagulants were causally associated with haemorrhage, and reported that the odds ratio was 13 (i.e. subcutaneous heparin is associated with a 13-fold increase in haemorrhage progression).
  • Interestingly, many of the patients with no haemorrhage progression on the follow-up CT were also exposed to various anticoagulant prophylaxis, but did not seem to have any adverse events associated with it.
  • The authors concluded that you can safely give heparin if the second head CT looks unchanged.

Saadeh paper (2012):

  • Retrospective case series of 205 patients with TBI, of whom 122 had a "stable" second CT.
  • No patients had progression of intracranial hemorrhage after initiation of chemical VTE prophylaxis, and no patients developed VTE.
  • So there was neither harm, nor was there really any benefit.

DEEP I study (2012):

  • A randomised controlled trial of low risk patients (classified by some modified Berne-Norwood criteria). Again, interesting patients were excluded: those undergoing craniotomy or ICP monitoring, for instance.
  • The risk of progression in the treatment arm was negligible, and similar to placebo.
  • The authors concluded that in low-risk TBI, the use of VTE prophylaxis is quite safe.

Meta-analysis publications

  • A Journal of Neurotrauma meta-analysis from 2013 "tentaively concluded" that early VTE chemoprophylaxis (i.e. commenced less than 72 hours post injury) reduces the risk of VTE without affecting progression of intracranial haemorrhage. Unfortunately, these conclusions were reached on the basis of nothing better than five eligible cohort studies.
  • A BJS meta-analysis from 2014 found 25 studies to be eligible, albeit "of low quality".
    The ultimate finding was that TEDs and anticoagulation used together halved the risk of DVT/PE, and doubled the risk of bleeding.

Consensus of experts and established guidelines

  • The old Brain Trauma Foundation recommended (with 2007 evidence) the combined used of chemical and mechanical VTE prophylaxis in TBI patients. In the 2016 edition they aintained thsi recommendation, without making any specific sggestions because "insufficient evidence to support recommendations regarding the preferred agent, dose, or timing". The only thing they point out is that the brain injury must be "stable" for you to consider heparin (one might interpret this as a call to scan the head a second time to ensure nonprogression of the contusions and haematomas).
  • The 2015 review by Abdel-Aziz refines this recommendation further:
    • Chemoprophylaxis should not be given within 3 days of injury for moderate-risk or high-risk ICH.
    • Chemoprophylaxis is reasonable when low-risk patients have not developed ICH expansion within 48 hours post-injury.
    • Chemoprophylaxis is also acceptable after day 3, when low-risk patients develop ICH expansion within 48 hours post-injury.
    • In diffuse axonal injury patients who have not developed ICH within 72 hours, chemoprophylaxis is reasonable.
    • Deep vein thrombosis proportions significantly increase when chemoprophylaxis is withheld for greater than 7 days
  • Australian NHMRC guidelines (2009) make very vague suggestions, mentioning that neurosurgeons should "use thromboprophylaxis with extreme caution" and only if it is "appropriate and not contraindicated". One boggles at such recommendations; it implies that in the absence of NHMRC guidelines neurosurgical specialists would use inappropriate anticoagulation in circumstances when it is contraindicated.
  • The 4th edition of the Australia and New Zealand "Prevention of Venous Thromboembolism" guidelines, assembled by a multidisciplinary Working Party, does not make any specific recommendations regarding neurosurgical or neutrotrauma patients.


Norwood, Scott H., et al. "Early venous thromboembolism prophylaxis with enoxaparin in patients with blunt traumatic brain injury." Journal of Trauma and Acute Care Surgery 65.5 (2008): 1021-1027.

Geerts, William H., et al. "A prospective study of venous thromboembolism after major trauma." New England Journal of Medicine 331.24 (1994): 1601-1606.

Zareba, P., et al. "Meta‐analysis of randomized trials comparing combined compression and anticoagulation with either modality alone for prevention of venous thromboembolism after surgery." British Journal of Surgery 101.9 (2014): 1053-1062.

Denson, Kent, et al. "Incidence of venous thromboembolism in patients with traumatic brain injury." The American journal of surgery 193.3 (2007): 380-384.

Jamjoom, Aimun AB, and Abdulhakim B. Jamjoom. "Safety and efficacy of early pharmacological thromboprophylaxis in traumatic brain injury: systematic review and meta-analysis." Journal of neurotrauma 30.7 (2013): 503-511.

Levy, Andrew Stewart, et al. "Pharmacologic thromboprophylaxis is a risk factor for hemorrhage progression in a subset of patients with traumatic brain injury." Journal of Trauma and Acute Care Surgery 68.4 (2010): 886-894.

Phelan, Herb A., et al. "A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury: The Delayed Versus Early Enoxaparin Prophylaxis I (DEEP I) study." Journal of Trauma and Acute Care Surgery 73.6 (2012): 1434-1441.

Daley, Mitchell J., Sadia Ali, and Carlos VR Brown. "Late Venous Thromboembolism Prophylaxis after Craniotomy in Acute Traumatic Brain Injury." The American Surgeon 81.2 (2015): 205-209.

Abdel-Aziz, Hiba, et al. "Timing for deep vein thrombosis chemoprophylaxis in traumatic brain injury: an evidence-based review." (2015).

Chang, Edward F., Michele Meeker, and Martin C. Holland. "Acute traumatic intraparenchymal hemorrhage: risk factors for progression in the early post-injury period." Neurosurgery 58.4 (2006): 647-656.

Saadeh, Yamaan, et al. "Chemical venous thromboembolic prophylaxis is safe and effective for patients with traumatic brain injury when started 24 hours after the absence of hemorrhage progression on head CT." Journal of Trauma and Acute Care Surgery 73.2 (2012): 426-430.

Minshall, Christian T., et al. "Safety and efficacy of heparin or enoxaparin prophylaxis in blunt trauma patients with a head abbreviated injury severity score> 2." Journal of Trauma and Acute Care Surgery 71.2 (2011): 396-400.