Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs

Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability

Towards patient-specific management of trauma hemorrhage: the effect of resuscitation therapy on parameters of thromboelastometry.

This is the peer reviewed version of the following article: Juffermans, N. , Wirtz, M. , Balvers, K. , Baksaas‐Aasen, K. , van Dieren, S. , Gaarder, C. , Naess, P. , Stanworth, S. , Johansson, P. , Stensballe, J. , Maegele, M. , Goslings, J. , Brohi, K. and , (2019), Towards patient‐specific management of trauma hemorrhage: the effect of resuscitation therapy on parameters of thromboelastometry. J Thromb Haemost. Accepted Author Manuscript. doi:10.1111/jth.14378, which has been published in final form at https://doi.org/10.1111/jth.14378. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsTo determine the response of ROTEM profiles to therapy in bleeding trauma patients. Patients/Methods Prospective multicentre study in bleeding trauma patients (receiving ≥ 4 red blood cell units). Blood was drawn on the emergency department, after administration of 4, 8 and 12 RBCs and 24 hours post injury. The response of ROTEM to plasma, platelets (PLTs), tranexamic acid (TXA) and fibrinogen products was evaluated in the whole cohort as well as in the subgroup of patients with ROTEM values indicative of TIC. Results 309 bleeding and shocked patients were included. A mean dose of 3.8 grams of fibrinogen increased FIBTEMCA5 with 5.2 mm (4.1–6.3). TXA administration decreased lysis by 5.4%(4.3–6.5). PLT transfusion prevented further derangement of parameters of clot formation. The effect of PLTs on EXTEMCA5 values was more pronounced in patients with a ROTEM value indicative of TIC compared to the whole cohort. Plasma transfusion decreased EXTEM CT with 3.1 sec (‐10–3.9) in the whole cohort and with 10.6 sec (‐45–24) in the subgroup of patients with a ROTEM value indicative of TIC. Conclusion Effects of therapy on ROTEM values were small, but prevented further derangement of test results. In patients with ROTEM values corresponding to TIC, efficacy of PLT and plasma to correct deranged ROTEM parameters is possibly more robust.European Commission under the FP7 HEALTH-Contract No. F3-2013-602771 and from TEM international Gmb

The use of viscoelastic haemostatic assays in the management of major bleeding: A British Society for Haematology Guideline.

BSH paid the expenses incurred during the writing of this guidance

The microcirculation: linking trauma and coagulopathy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96284/1/trf12034.pd