Military Medicine (Saturdays) - Novel agents to stop bleeding

(Caveat - military medicine posts aren't an endorsement of the military, but an acknowledgement that significant advances occur through their research).

Trauma victims frequently die from exsanguination, so there's ample research on how to avert this problem.  Three strategies exist:

1. Stop trauma
2. Decrease bleeding
3. Replace blood.

George Santanaya refutes the possibility of #1 when he says that, 'only the dead have seen the end of war.'  Meanwhile, DARPA's Blood Pharming program may be a near-future option for strategy #3, but is still currently unavailable and cost-prohibitive.  

This leaves 'decreasing bleeding' as the best current option.  Novel synthetic dressings (QuikClot, HemCon) and granular agents (Celox and WoundStat) have not been shown to make much of a difference.  In fact, they may be somewhat harmful, as Quikclot may produce superficial burns and the military suspended the use of Woundstat as it may cause vascular injury and may embolize.  The military currently favors the use of Combat Gauze (a kaolin impregnanted gauze) as the primary pre-hospital hemostatic gauze.  

Yet, the best current solution may be a simple medication called tranexamic acid.  It's an amino acid derivative which blocks the clotting cascade (technically, it inhibits the activation of plasminogen to plasmin) and thereby prevents further bleeding.  The CRASH-2 trial showed that definitely within 1 hour, and likely up to 3 hours, tranexamic acid can have statistically significant decreases in trauma bleeding (past 3 hours, it's likely harmful):

FINDINGS:

10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0.0001). Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (198/3747 [5.3%] events in tranexamic acid group vs 286/3704 [7.7%] in placebo group;relative risk [RR] 0.68, 95% CI 0.57-0.82; p<0.0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3037 [4.8%] vs 184/2996 [6.1%]; RR 0.79, 0.64-0.97; p=0.03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4.4%] vs 103/3362 [3.1%]; RR 1.44, 1.12-1.84; p=0.004). We recorded no evidence that theeffect of tranexamic acid on death due to bleeding varied by systolic blood pressure, Glasgow coma score, or type of injury.

While the decreases in bleeding deaths may seem small (<1h - 2.4% absolute decrease, 1-3h - 1.3% absolute decrease), these values are real and when extrapolated over millions of trauma victims each year, they could save dozens of thousands of lives.  The best part: it's a cheap drug!!! and modeling the costs estimates that each life-year saved is less than $70.  

This is far less than the marginal benefits of the synthetic agents above and one of the reasons the WHO added tranexamic acid to its list of essential medicines.   

 

 

 

Comments

[Anjali]

This is a great drug, frequently used in treating menorrhagia, and has shown mixed (with more recent favorable) results when used for postpartum hemorrhage.

High-dose tranexamic acid reduces blood loss in postpartum haemorrhage.
Ducloy-Bouthors AS, Jude B, Duhamel A, Broisin F, Huissoud C, Keita-Meyer H, Mandelbrot L, Tillouche N, Fontaine S, Le Goueff F, Depret-Mosser S, Vallet B; EXADELI Study Group, Susen S.