Tuesday, I talked about a new notion of using profound hypothermia to save critically injured trauma patients. Since this concept is not yet ready for prime time, we still have to treat hypothermia as our enemy. Most trauma centers have established massive transfusion protocols that detail the use and ratios of specific blood components to avoid fatal anemia and coagulopathy. But do we pay enough attention to hypothermia?
A multicenter study was carried out that will be reported at the upcoming EAST meeting in January. They looked at patients who received massive transfusion (>= 10u PRBC in 24 hours) and looked at their lowest temperature during that 24 hour period.
They found that as temperature decreased, shock parameters, coagulopathy, injury severity and transfusion requirements increased significantly. Specifically, if a temperature of <34C doubled mortality risk, and this effect was most pronounced in patients who received relatively less plasma.
Bottom line: Temperature is still very important, and hypothermia must be avoided at all costs. This is true in the ED and the OR. Allowing temperature to drop below 34C significantly increases mortality and is at least as important as giving enough FFP to correct coagulopathy from dilution.
Reference: Hypothermia in massive transfusion: are we not paying enough attention to it? Poster 2, EAST 25th Annual Assembly, Jan 2012.
So what’s the INR of FFP? Or stated another way, what’s the lowest you can correct a patient’s INR using infusions of fresh frozen plasma?
One of the mainstays of correcting coagulopathy, either from hemorrhage or due to medication like warfarin, is transfusion of FFP. Frequently, clinicians will write orders to administer FFP until a certain INR is achieved. What is a reaonable INR?
A “normal” INR is 1.0, plus or minus about 0.2, depending on your laboratory. However, two separate studies have shown that transfusion of FFP will not reliably decrease the INR below about 1.7.
Bottom line: The answer to the question is about 1.6. If any clinician orders FFP transfusions with a goal INR below this, it probably won’t happen. And since transfusions of any product have risks, my “juice to squeeze” ratio of risk vs benefit begins to fail at an INR of 1.6. Below that point, the patient needs a normal temperature and good perfusion to drop their INR further.
- Toward rational fresh frozen plasma transfusion: the effect of plasma transfusion on coagulation test results. Am J Clin Pathol 126(1):133-139, 2006.
- Effect of fresh frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 46(8):1279-1285, 2006.
Coagulopathy is a frequent occurrence after severe traumatic brain injury (TBI). There are high levels of tissue factor (TF) in the brain, which can be released with severe injury. This in turn triggers a cascade which can lead to generalized coagulopathy.
The trauma group at LAC+USC looked at the time course of coagulopathy after isolated severe TBI. They identified 278 patients over a 1.5 year period and retrospectively review a number of demographic and outcome variables. Coagulopathy was defined as a platelet count < 100,000/mm3, INR > 1.4, or PTT > 36 sec.
They found the following:
- 46% with blunt trauma and 82% with penetrating injury developed a coagulopathy
- Presence of coagulopathy increased with increasing head injury severity
- Thromobocytopenia as a cause of coagulopathy was less common (17%) than clotting factor problems
- As brain injury severity increased from AIS=3 to AIS=5, median onset of coagulopathy became increasingly earlier (26 hrs, 22 hrs, 10 hrs)
- Mortality increased with earlier coagulopathy (23% after 24 hrs, 39% between 12 and 24 hrs, 56% less than 12 hrs)
- Prehospital: Coagulopathy should be suspected if the patient is bleeding profusely from multiple sites, including your IV needle sticks. This indicates severe brain injury and demands triage to a trauma center with immediate neurosurgical support.
- In-hospital: Coagulopathy that is noted in the ED portends severe injury and poor prognosis. Rapid access to CT scan and your neurosurgical consultant is critical.
Related post: Controlling fever in head injury
Reference: Time course of coagulopathy in isolated severe traumatic brain injury. Injury 41:924-928, 2010.
Recombinant Factor VIIa was initially approved for bleeding in hemophiliac patients back in 1999. Over the years, there has been a big move toward off-label use. There appeared to be obvious utility in using it as an emergency hemostatic agent in trauma patients. But as with many new drugs and devices, early enthusiasm slowly gave way to more balanced judgment. Reviews during the past few years are less glowing than they were early on. So what’s really been happening over the past decade?
Researchers at Stanford tapped into a large database of patient level records from 600 hospitals around the US. They identified over 18,000 uses of Factor VIIa during a 9 year time period. By the end of the study period (2008), 97% of use was off-label! Approved use (hemophilia) increased 4-fold, while off-label use increased by 140-fold. Cardiovascular surgery and trauma tied in their amount of off-label use (both about 29% of the sample).
Does it do any good? This paper can’t directly address that question, since it does not have a good comparison group. However, looking at in-hospital mortality is revealing. Use for hemophilia (FDA approved) results in a 4% mortality rate. For trauma, the in-house mortality is 33%. The worst outcomes were with patients with an aortic aneurysm (55% mortality).
Bottom line: This review details the administration of about $175 million worth of recombinant Factor VIIa over 9 years. Off-label use has skyrocketed despite a dearth of good reports that it actually saves lives. The Number Needed to Treat to prevent one additional bad outcome keeps getting larger with every study published. With a price tag of nearly $10,000 per dose, it’s getting harder to justify using it. I think we are seeing the beginning of the end (at least in trauma) for this powerful drug.
Reference: Off-label use of recombinant Factor VIIa in US hospitals: analysis of hospital records. Annals of Int Med 154(8):516-522, 2011.