Is “Thrombin Burst” Now the Worst Option in Trauma?
We read with great interest the manuscript by Cardenas et al. entitled “Plasma Resuscitation Promotes Coagulation Homeostasis Following Shock-Induced Hypercoagulability” and published in this journal (1). The reported study showed that, compared with with Ringer lactate, resuscitation with fresh frozen plasma (FFP) reduced thrombin generation, reduced transfusion volume, and improved metabolic indicators of shock. The authors considered plasma resuscitation to be superior and emphasized that FFP reduces the risk of both consumptive coagulopathy and thromboembolic events. Thus, increasing thrombin generation is not considered a priority in the management of trauma-induced coagulopathy any more. Thrombin generation is typically upregulated in response to trauma (1, 2). Consequently, the emphasis now is on balanced resuscitation, either with predefined ratios of allogeneic blood products (e.g., 1:1:1 for plasma, red blood cells, and platelets) (3) or with a concentrate-based approach where point-of-care coagulation monitoring is used to tailor treatment to the patient's specific needs (4).
This represents a transformation from the prevailing view 10 to 15 years ago. In that era, a “thrombin burst” (term first used in the literature in 1994 (5)) was considered to be beneficial in trauma patients. Accordingly, it was thought that recombinant activated factor VII (rFVIIa) could play a key role in managing trauma-induced coagulopathy and interest in this treatment gained considerable momentum (6). In layman's terms, our community had jumped onto the thrombin burst rocket but, in contrast, it is now on the balanced train!
What triggered the transformation? The principal issue was safety: reports of thromboembolic complications in patients treated with rFVIIa began to emerge (7). The effectiveness of rFVIIa in the management of trauma may also be questioned. For example, in two randomized placebo-controlled trials, rFVIIa had no significant effects versus placebo on mortality (6, 8).
While there remains a possible role for thrombin-generating drugs in trauma, the extent to which thrombin generation should be augmented is to be confirmed. The effectiveness of rFVIIa is considered to be unproven, and there is little evidence to support the use of prothrombin complex concentrates (PCCs) (9). Accordingly, the use of thrombin-generating drugs is restricted to specific situations. One approach is to use recombinant activated factor VII (rFVIIa) to “jump-start” coagulation when there is insufficient time to administer allogeneic blood products. Another approach is to use PCCs as part of coagulation factor concentrate-based treatment; PCCs are used second-line, for patients in whom fibrinogen supplementation has been performed as needed (10).
The transformation in our views on managing trauma-induced coagulopathy is philosophically interesting. Our job as scientists is to appraise the available evidence impartially and treat our patients with the aim of optimizing clinical outcomes. In the early days of using rFVIIa for trauma, it could be argued that our community responded too quickly to the apparent benefits of this treatment. Over the longer term, the weight of evidence has led to a more considered approach where the potential benefits and harms of each intervention receive due consideration.