Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury

Abstract

Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation. (Blood. 2011;118(7): [1943][1944][1945][1946][1947][1948][1949][1950][1951]

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

“…Two animals in the saline group had a singular lung arteriole thromboembolus of 1 to 2 mm in diameter, whereas 3 animals from the lower PCC dosing group had several thromboemboli each measuring 1 to 2 mm in diameter. 91 Interestingly in those receiving higher doses of PCCs (50 IU/kg), disseminated intravascular coagulation was observed based on the International Society of Thrombosis and Hemostasis criteria, 92 and all of these animals contained >4 mm of multiple lung arteriole thromboembolisms on autopsy. In addition, a net-like fibrinogen deposition was noted in the lung capillaries of the higher dosage group, which was present but not as well developed in the control and low-dosage animals.…”

“…In addition, a net-like fibrinogen deposition was noted in the lung capillaries of the higher dosage group, which was present but not as well developed in the control and low-dosage animals. 91 In an ongoing multicenter, randomized, controlled trial from The Netherlands, the utility of 4F-PCCs (Cofact) is being studied with respect to reducing allogeneic red blood cell transfusions during orthotopic liver transplantation in cirrhotic patients with INR ≥1.5 (PROTON Trial; Netherlands Trial Register: 3174). 93 …”

Management of traumatic haemorrhage – the European perspective

“…The diagnosis of compromised thrombin formation remains challenging. Neither prolonged PT or aPTT, nor an extended clotting time in viscoelastic tests, sufficiently portrays the magnitude of thrombin generation [68,70]. Indeed, Dunbar and Chandler found that trauma patients with prolonged PT (> 18 s), which is suggestive of TIC, had a threefold higher thrombin generation compared with individuals with normal PT (p = 0.01) [68].…”

Massive transfusion in multi-trauma patients

“…Innerhofer et al have recently shown in a prospective cohort study that prothrombin complex concentrates (PCC) are effective in correcting coagulopathy and reducing the need for transfusion in patients with severe blunt trauma [26]. However, larger randomized trials need to be conducted to evaluate this effect since an increased risk of thromboembolic events has been reported in the past as well [27]. We believe until that time has come, it is safer and more useful to have an uniform protocol.…”