Donald Moe, MD, Michael Lallemand, MD, John McClellan, MD, Joshua Smith, DO, Shannon Marko, DVM, Matthew Eckert, MD, Matthew Martin, MD. Madigan Army Medical Center
Objectives: Bleeding remains the leading cause of preventable death following severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse vitamin-K antagonists, but are proposed for use in “factor-based” resuscitation strategies and in austere/military environments. There is a paucity of controlled studies for this indication, or that compare 3-factor (3PCC) versus 4-factor (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy.
Methods: 25 adult Yorkshire swine underwent 35% volume hemorrhage, an ischemia-reperfusion injury and protocolized resuscitation to produce dilutional coagulopathy. 17 animals were randomized at 4-hours following model creation to receive a 45 IU/kg dose of either 3PCC or 4PCC. In order to better characterize PCC use in trauma, following interim analysis an additional 8 animals received 4PCC with the addition of fresh plasma transfusion. Individual factor levels were drawn at 4 and 6 hours.
Results: The model created significant physiologic derangement with hematocrit of 16, pH of 7.21, and a lactate of 9.6. Following administration of PCC, 66.7% of 3PCC animals and 25% of 4PCC animals (regardless of plasma administration) developed disseminated intravascular coagulation (DIC). Prior to PCC the animals developing DIC had manifested the "lethal triad" with significantly lower temperatures (97.4°F vs 100°F), greater degrees of acidosis (pH 7.14 vs 7.27), and coagulopathy (INR 1.47 vs 1.19, all P<0.05). Fibrinogen levels prior to PCC administration correlated significantly with development of DIC [Figure]. In the absence of DIC when compared with controls, both 3PCC and 4 PCC, again regardless of plasma administration, transiently improve prothrombin time and individual clotting factors [Figure]. Despite the improvement in individual factors, there was significant depletion of fibrinogen and platelets with no lasting improvement of coagulopathy.
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Conclusion: In a severe hemorrhagic shock model PCC successfully replaced individual clotting factors, but was associated with fibrinogen depletion and failure to correct coagulopathy. Of greater concern, PCC administration in this setting resulted in rapid onset DIC in the more severely ill animals. The incidence of DIC was markedly increased with 3PCC versus 4PCC, and these products should be used with caution in this setting.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 80684
Program Number: MSS21
Presentation Session: Full-Day Military Surgical Symposium – Trauma/Critical Care Presentations
Presentation Type: MSSPodium