Trauma professionals are always reluctant to anticoagulate TBI patients with demonstrated blood in their head. In recent years, we’ve become more comfortable providing prophylactic doses of low molecular weight heparin after a suitable period. This is typically 24-48 hours after a stable head CT in patients with select types of intracranial hemorrhage (ICH) who are at increased risk for venous thromboembolism.

But what about therapeutic dose anticoagulation in these patients? Let’s say that you have a patient with ICH who has developed a significant pulmonary embolism (PE)? Is is safe to give full dose anticoagulation? And if so, when?

The group at Shock Trauma in Baltimore attempted to answer this in one of the EAST Quick Shot presentations scheduled for this week. The did a retrospective review of 4.5 years of their own data on these patients. They specifically selected patients who had both ICH and PE and compared those who received full anticoagulation within 7 days of injury vs those who were dosed after 7 days. Outcomes studied included death, interventions for worsening ICH, and pulmonary complications.

Here are the factoids:

• A total of 50 patients had both ICH and PE, but only the 46 who received therapeutic anticoagulation were analyzed
• 19 patients (41%) received early anticoagulation, and 27 received it late (59%)
• There were 4 deaths in the early group (2 from the PE, 1 from multi-system organ failure, 1 from the TBI) vs none in the late group, and this was statistically significant
• 3 patients in the early group (18%) vs 2 in the late group (7%) had an increase in their ICH (p=0.3), and none required intervention

The authors concluded that their study failed to show any instances of clinically significant progression of ICH after anticoagulation, and that it is not associated with worse outcomes, even if started early. Thus they recommend that ICH should not preclude full anticoagulation, even early after injury.

My comment: I always say that you shouldn’t let one paper change your practice. Even a really good one. In order to ensure that you are providing the best care, more work must always be done to confirm (or refute) the findings of any provocative research. And this little Quick Shot, with little opportunity for questions from the audience, should definitely not change it!

The major issues to consider here are common ones: 

• This was a retrospective study and it does not appear that any guideline was followed to determine who got early vs late anticoagulation. So who knows what kind of selection bias was occurring and how the surgeon decided to prescribe anticoagulation? It’s very possible that patients with a “bad CT” were put into the late group, and the not so bad ones in the early group. This would bias the results toward better outcomes in the early anticoagulation group.
• It’s also a very small study that is extremely underpowered. The authors comment on the fact that the outcomes of the early group were not worse than the late group. However, looking at their sample size (46) shows that they would only be able to show differences if they were about 5x worse in the early group. They would realistically need about 350 total patients to truly show that the groups behaved the same. Their small numbers also preclude saying that there were no ICH progressions. There very well could have been if 300 more patients were added to the series.
• And isn’t death a significant outcome? The authors indicated that 2 of the 4 deaths were a result of the PE. Yet there was a significant association (p=0.02) of increased death in the early anticoagulation patients that can’t be discounted.

Bottom line: It’s way too early to consider giving early anticoagulation to patients with ICH and pulmonary embolism. It may very well be shown to be acceptable, eventually. But not yet. And a much bigger prospective study will be required to confirm it.

Reference: Therapeutic anticoagulation in patients with traumatic brain injuries and pulmonary emboli. EAST Annual Assembly Quick Shot #7, 2020.