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This study investigated changes in plasma fibrinogen metabolism and changes in coagulation in severely burned adults. Ten patients (27 ± 3 years; 91 ± 6 kg) with 51 ± 3% TBSA were consented and enrolled into an institutional review board-approved prospective study. On the study day, stable isotope infusion of 1-13C-phenylalanine and d5-phenylalanine was performed to quantify fibrinogen production and consumption. During the infusion, vital signs were recorded and blood samples were drawn every hour. Coagulation was measured by thromboelastograph (TEG). Ten normal healthy volunteers (37 ± 7 years; 74 ± 4 kg) were included as the control group. Burned adults had elevated heart rates (120 ± 2 vs 73 ± 5 [control] beats/minute), respiration rates (23 ± 2 vs 15 ± 1 breaths/minute), plasma glucose (127 ± 10 vs 89 ± 2 mg/dl), and fibrinogen levels (613 ± 35 vs 239 ± 17 mg/dl); and decreased albumin (1.3 ± 0.2 vs 3.7 ± 0.1 g/dl) and total protein (4.4 ± 0.2 vs 6.8 ± 0.1 g/dl, all P < .05). Fibrinogen breakdown was elevated in the burn group (2.3 ± 0.4 vs. 1.0 ± 0.3 µmol/kg/minute); and fibrinogen synthesis was further enhanced in the burn group (4.4 ± 0.7 vs 0.7 ± 0.2 µmol/kg/minute, both P < .05). Clotting speed (TEG-alpha) and clot strength (TEG-MA) were increased in the burn group (62 ± 4 vs 50 ± 4°, and 76 ± 2 vs 56 ± 2 mm, respectively, both P < .05). Fibrinolysis of TEG-LY60 was accelerated in the burn group (16 ± 6 vs 3 ± 1) and so was the increase in D-dimer level in the burn group (4.5 ± 0.4 vs 1.9 ± 0.3 mg/l, both P < .05). The hypercoagulable state postburn is in part a result of increased fibrinogen synthesis, over and above increased fibrinogen breakdown., (Published by Oxford University Press on behalf of the American Burn Association 2019.)

Objectives: This study was designed to assess the stability and functional activity of fibrinogen concentrates subjected to the changes in temperature and duration observed in field conditions., Methods: Fibrinogen concentrate was stored at -20°C (12 vials), 22°C (12 vials), and 50°C with 80% humidity (12 vials), for up to 6 mo. At each temperature, three vials of fibrinogen concentrate were taken out at 0, 1, 3, and 6 mo and reconstituted. On analysis days, blood samples were taken from a single healthy donor to collect plasma samples. The donor plasma was mixed with commercial fibrinogen-deficient plasma to make fibrinogen-adjusted plasma (FAP). An aliquot of the reconstituted fibrinogen concentrate was used for quantification of stored fibrinogen content (using STA-R) and function (Rotem - Fibtem) in FAP., Results: At 22°C for 0, 1, 3, and 6 mo, there were no significant changes observed in fibrinogen content (1,223 ± 42 mg/vial, 1,286 ± 86 mg/vial, 1,234 ± 76 mg/vial, and 1,178 ± 64 mg/vial), prothrombin time (13.5 ± 0.1 s, 13.7 ± 0.6 s, 13.3 ± 0.4 s, and 13.7 ± 0.2 s), or activated partial thromboplastin time (31.1 ± 0.2 s, 32.0 ± 0.2 s, 31.5 ± 0.2 s, and 32.0 ± 0.8 s), respectively. There were also no significant changes observed in any of the Fibtem measurements. Similarly, no differences were observed in these variables over time at -20°C and 50°C with 80% humidity., Conclusions: Fibrinogen concentrate maintained its content and function when stored at -20°C to 50°C with up to 80% humidity for 6 mo.

Introduction: Platelet apheresis is a routine clinical practice, but the physiological impact on the donors has been incompletely characterized. This study measured the effects of platelet apheresis on hemodynamics, oxygen metabolism, and coagulation in pigs to assess its impact before employing the animals in experimental studies., Methods: Forty pigs (39.8 ± 0.6 kg) were anesthetized and catheterized with an apheresis catheter in the femoral vein. During the platelet apheresis process, blood was withdrawn from the pig to separate platelets, and the remaining red blood cells and plasma returned back to the pigs, using the Haemonetics MCS+9000 system. A total of 12 cycles of blood withdrawn and return were performed during the entire apheresis procedure to reduce platelet counts to a target of 50% of baseline. During the process, hemodynamics was recorded in each cycle. Blood samples were collected before and after apheresis to assess changes in oxygen metabolism and coagulation by prothrombin time, activated partial thromboplastin time (STA-R Evolution Stago), and using Rotem thrombelastometry, and platelet aggregation using a Chrono-Log 700 aggregometer., Results: During each cycle of the apheresis, mean arterial pressure (MAP) was decreased and heart rate was increased by blood withdrawal, but both recovered after blood return. On the completion of the apheresis, platelet count decreased from baseline 345 ± 15 10 9 /L to 141 ± 14 10 9 /L and fibrinogen levels were reduced from 124 ± 5 to 99 ± 4 mg/dL (both p < 0.05). Although oxygen delivery remained unchanged, oxygen consumption was decreased from 4.0 ± 0.2 to 3.2 ± 0.0 mL O 2 /kg/min (p < 0.05). Rotem alpha (clotting speed) decreased from 79 ± 0 to 69 ± 1° and maximum clot firmness (MCF or clot strength) decreased from 71 ± 1 to 57 ± 1 mm (both p < 0.05). No changes were observed in prothrombin time or activated partial thromboplastin time. Platelet aggregation induced by arachidonic acid or collagen was decreased to 28 ± 6% or 71 ± 3% of baseline values (p < 0.05), respectively., Conclusion: Platelet apheresis caused significant fluctuations in hemodynamics, reduced oxygen consumption, in addition to the compromised platelet aggregation and clotting function expected. The observations warrant consideration in humans undergoing apheresis over extended periods., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Introduction: Ibuprofen is commonly used by warfighters in the deployed environment. This study investigated its dose effects on in vitro coagulation in human and pig blood., Methods: Blood samples were collected from 6 normal volunteers and 6 healthy pigs and processed to make platelet-adjusted samples (100 × 10(3)/μL, common transfusion trigger in trauma). Ibuprofen was added to the samples at concentrations of 0 μg/mL (control), the concentration from the highest recommended oral dose (163 μg/mL, 1×), and 2×, 4×, 8×, 10×, 12×, 16×, and 20×. Platelet aggregation by Chrono-Log aggregometer and coagulation by rotational thrombelastogram (Rotem) were assessed at 15 minutes after the addition of ibuprofen., Results: A robust inhibition of ibuprofen on arachidonic acid-induced platelet aggregation was observed at all doses tested in human or pig blood. Collagen-stimulated platelet aggregation was inhibited starting at 1× in human blood and 4× in pig blood. Rotem measurements were similarly compromised in pig and human blood starting at 16×, except clot formation time was prolonged at 1× in human blood (all p < 0.05)., Conclusion: Ibuprofen inhibited platelet aggregation at recommended doses, and compromised coagulation at higher doses. Human blood was more sensitive to ibuprofen inhibition. Further effort is needed to investigate ibuprofen dose responses on coagulation in vivo., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

The aim of this study was to determine whether visceral protein levels increase under positive nitrogen balance during times of decrease in acute-phase reactant levels in patients with burn injury. This was a post hoc analysis of a prospective, interventional study approved by the local institutional review board. A total of 10 subjects between the ages of 18 and 72 with ≥ 20% total body surface area burn were enrolled over a 14-month period. Data were collected for five subjects (average age of 28 ± 8 years and total body surface area burn of 69 ± 15%) who met the inclusion criteria. Changes in visceral protein levels were examined along with nitrogen balance and acute-phase reactants when the subjects were on enteral nutrition, and the proteins were not examined during times of acute kidney injury. Descriptive statistics were performed, and linear regression was used to analyze the association of visceral proteins and nitrogen balance during times that acute-phase reactant levels were decreasing. The subjects received an average of 3044 ± 1613 kcal/day (39 ± 20 kcal/kg), meeting 72% of caloric goals and achieving positive nitrogen balance during 68% of the 40 weekly measurements, with 174 ± 85 g of protein intake per day (2.2 ± 1.1 g/kg). There was a weak relationship between nitrogen balance and changes in visceral protein levels during times that the acute-phase reactant levels were decreasing (P > .05). Visceral proteins were found to be poor markers of nutritional status. This study is unique because the subjects were able to achieve positive nitrogen balance despite severe burns.

Introduction: Ibuprofen is commonly used by Soldiers in the deployed environment. This study investigated its dose-effects on in vitro coagulation., Methods: Blood samples were collected from 4 normal healthy pigs and were processed to make platelet-adjusted (100×10(3)/μL) blood samples. Ibuprofen was added to the samples at doses of 0 μg/mL (control), recommended oral dose (163 μg/mL, 1×), 2×, 4×, 8×, 10×, 12×, 16×, and 20×. Arachidonic acid or collagen-stimulated platelet aggregation was assessed at 15 minutes after the addition of ibuprofen. Coagulation was assessed with measurements of prothrombin time (PT) and activated partial thromboplastin time (aPTT), and thrombelastography by Rotem., Results: A robust inhibition of ibuprofen on arachidonic acid-induced platelet aggregation was observed at all doses tested. Collagen-stimulated platelet aggregation was inhibited to 71%±5% and 10%±5% of the control values at ibuprofen doses of 4× and 20×, respectively (both p<0.05). No changes were observed in PT at any dose, but aPTT was prolonged at dose of 16× and 20×. Rotem measurements of coagulation time, clot formation time, maximum clot firmness, and A10 were compromised at dose 16× and 20× (all p<0.05)., Conclusion: Ibuprofen inhibited platelet aggregation at recommended doses, but did not compromise aPTT or coagulation profile until at 16 times the recommended doses and higher. Further effort is needed to clarify whether there are different dose-responses between human and pig blood samples in trauma situations., (Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.)