Fibrinogen and prothrombin complex concentrate in trauma coagulopathy

Hannon, Matthew; Quail, Jacob; Johnson, Matthew D.; Pugliese, Cara; Chen, Kejian; Shorter, Heidi; Riffenburgh, Robert H.; Jackson, Ronald L.

doi:10.1016/j.jss.2015.03.013

Cited by 7 publications

(5 citation statements)

References 23 publications

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“… 33 , 34 One last finding of interest is the strong association of reduced plasma fibrinogen level and activated coagulation time (ACT). 3 , 5 , 35 – 38 When taking this into account, the ratio 1:1:1:1, which includes fibrinogen, seems to be very smart and advantageous. 3 , 5 , 14 , 21 , 25 , 36 – 38 …”

Section: Component Therapymentioning

confidence: 99%

“… 5 , 3 , 35 – 38 Therefore a single injection of fibrinogen concentrate at a dose of 2–4 g intravenously seems to be a smart and useful intervention. 3 , 5 , 14 , 21 , 25 , 36 – 38 There is no evidence that cryoprecipitate would improve the outcome of patients with low fibrinogen levels caused by massive bleeding. 43 Hypothermic coagulopathy is very challenging to treat in bleeding patients, but it was shown that coagulopathy caused by hypothermia can be reversed and successfully corrected by fibrinogen concentrate.…”

Section: Fibrinogenmentioning

confidence: 99%

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Massive hemorrhage management – a best evidence topic report

Vymazal¹

2015

TCRM

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IntroductionMassive hemorrhage remains a major cause of potentially preventable deaths. Better control of bleeding could improve survival rates by 10%–20%. Transfusion intervention concepts have been formulated in order to minimize acute traumatic coagulopathy. These interventions still have not been standardized and vary among medical centers.Materials and MethodsBased on a literature search using free term keywords and Medical Subject Heading (MeSH) index, we analyzed published articles addressing massive hemorrhage, component therapy, fresh whole blood, and fibrinogen from the year 2000 onward, in journals with impact factor >1.000, in Medline, PubMed, and Google Scholar. The evidence was grouped into topics including laboratory testing and transfusion interventions/viscoelastic assays vs standard laboratory tests, the effect of component therapy on patient outcome, the effect of warm fresh whole blood on patient outcome, and the effects of fibrinogen in severe bleeding. The obtained information was compared, evaluated, confronted, and was focused on to present an adequate and individual-based massive hemorrhage management approach.ResultsViscoelastic whole-blood assays are superior to standard coagulation blood tests for the identification of coagulopathy and for guiding decisions on appropriate therapy in patients with severe bleeding. Replacement of plasma, red blood cells, platelets, and fibrinogen in a ratio of 1:1:1:1 has appeared to be the best substitution for lost whole blood. There is no evidence that cryoprecipitate improves the outcome of patients with severe hemorrhage. Current literature promotes the transfusion of warm fresh whole blood, which seems to be superior to the component therapy in certain clinical situations. Some authors recommend that fibrinogen and other coagulation factors be administered according to the viscoelastic attributes of the blood clot.ConclusionThis best-evidence topic report brings comprehensive information about massive hemorrhage management.

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Section: Component Therapymentioning

confidence: 99%

Section: Fibrinogenmentioning

confidence: 99%

Massive hemorrhage management – a best evidence topic report

Vymazal¹

2015

TCRM

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“…Fibrinogen and prothrombin complex concentrates (PCC) have drawn significant interest as potential treatments for trauma induced coagulopathy (TIC). Fibrinogen levels are depleted during trauma, , and studies suggest that signs of coagulopathy are reversed with fibrinogen therapy. − Transfusion of plasma and platelets does not increase fibrinogen levels, but transfusion with cryoprecipitate or fibrinogen does . While the studies looking at fibrinogen transfusion are relatively small, they have been promising.…”

Section: Introductionmentioning

confidence: 99%

Engineering Intravenously Administered Nanoparticles to Reduce Infusion Reaction and Stop Bleeding in a Large Animal Model of Trauma

et al. 2018

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Bleeding from traumatic injury is the leading cause of death for young people across the world, but interventions are lacking. While many agents have shown promise in small animal models, translating the work to large animal models has been exceptionally difficult in great part because of infusion-associated complement activation to nanomaterials that leads to cardiopulmonary complications. Unfortunately, this reaction is seen in at least 10% of the population. We developed intravenously infusible hemostatic nanoparticles that were effective in stopping bleeding and improving survival in rodent models of trauma. To translate this work, we developed a porcine liver injury model. Infusion of the first generation of hemostatic nanoparticles and controls 5 min after injury led to massive vasodilation and exsanguination even at extremely low doses. In naïve animals, the physiological changes were consistent with a complement-associated infusion reaction. By tailoring the zeta potential, we were able to engineer a second generation of hemostatic nanoparticles and controls that did not exhibit the complement response at low and moderate doses but did at the highest doses. These second-generation nanoparticles led to cessation of bleeding within 10 min of administration even though some signs of vasodilation were still seen. While the complement response is still a challenge, this work is extremely encouraging in that it demonstrates that when the infusion-associated complement response is managed, hemostatic nanoparticles are capable of rapidly stopping bleeding in a large animal model of trauma.

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“…Studies in hemodiluted pigs have shown that PCC administration reduced blood loss after liver 13,14 or bone 15 , but not spleen 15 injury, compared to placebo. In hemodiluted rabbit models, PCC reduced blood loss from the injured kidney to a greater extent than saline or recombinant factor VIIa 16 , while neither PCC nor fibrinogen concentrates reduced blood losses from the injured liver 17 .…”

Section: Introductionmentioning

confidence: 83%

Prothrombin, alone or in complex concentrates or plasma, reduces bleeding in a mouse model of blood exchange-induced coagulopathy

Eltringham-Smith

Qadri

et al. 2019

Sci Rep

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Prothrombin complex concentrates (PCC) are fractionated plasma protein drugs that reverse warfarin anticoagulation. PCC may control more general bleeding. We sought to identify the dominant procoagulant factor in PCC in vivo. We tested PCC or coagulation factor (F) treatment in CD1 mice made coagulopathic by exchange of whole blood for washed red cells. Anesthetized mice were transfused with murine fresh-frozen plasma (mFFP), PCC, mixtures of human vitamin K-dependent proteins (VKDP) (prothrombin, FVII, FIX, or FX), or purified single human VKDP, immediately prior to tail transection (TT), liver laceration (LL), or intravascular laser injury (ILI). Plasma donor mice were treated with vehicle or control antisense oligonucleotide (ASO-CON) or ASO specific for prothrombin (FII) (ASO-FII) to yield mFFP or ASO-CON mFFP or ASO-FII mFFP. Blood losses were determined spectrophotometrically (TT) or gravimetrically (LL). Thrombus formation was quantified by intravital microscopy of laser-injured arterioles. PCC or four factor- (4F-) VKDP or prothrombin significantly reduced bleeding from TT or LL. Omission of prothrombin from 4F-VKDP significantly reduced its ability to limit bleeding. Mice transfused with ASO-FII mFFP demonstrated inferior haemostasis versus those transfused with ASO-FII following TT, LL, or ILI. Prothrombin is the dominant procoagulant component of PCC and could limit bleeding in trauma.

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Fibrinogen and prothrombin complex concentrate in trauma coagulopathy

Cited by 7 publications

References 23 publications

Massive hemorrhage management – a best evidence topic report

Massive hemorrhage management – a best evidence topic report

Engineering Intravenously Administered Nanoparticles to Reduce Infusion Reaction and Stop Bleeding in a Large Animal Model of Trauma

Prothrombin, alone or in complex concentrates or plasma, reduces bleeding in a mouse model of blood exchange-induced coagulopathy

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Fibrinogen and prothrombin complex concentrate in trauma coagulopathy

Cited by 7 publications

References 23 publications

Massive hemorrhage management &ndash; a best evidence topic report

Massive hemorrhage management &ndash; a best evidence topic report

Engineering Intravenously Administered Nanoparticles to Reduce Infusion Reaction and Stop Bleeding in a Large Animal Model of Trauma

Prothrombin, alone or in complex concentrates or plasma, reduces bleeding in a mouse model of blood exchange-induced coagulopathy

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Massive hemorrhage management – a best evidence topic report

Massive hemorrhage management – a best evidence topic report