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Background: This study compared the resuscitation effects of platelets and fibrinogen concentrate (FC) on coagulation and hemodynamics in pigs with traumatic hemorrhage and reduced platelet counts., Methods: Thirty pigs (40 ± 3 kg) were anesthetized and catheterized with an apheresis catheter to remove platelets using the Haemonetics 9000 (Haemonetics, Braintree, MA). Afterward, a femur fracture was induced, followed by hemorrhage of 35% the estimated blood volume. Pigs were then randomized to be resuscitated with 5% human albumin (12.5 mL/kg), FC (250 mg/kg, 12.5 mL/kg), or platelets collected from apheresis (11.0 ± 0.5 mL/kg). Animals were monitored for 2 hours or until death. Blood samples were collected before (baseline [BL]) and after apheresis, after hemorrhage, and after resuscitation to assess changes in hemodynamics and coagulation using Rotem., Results: No change in mean arterial pressure (MAP) or heart rate (HR) was observed by platelet apheresis. Hemorrhage reduced MAP to 57% ± 5% and elevated HR to 212% ± 20% of BL (both p < 0.05). Resuscitation with albumin, FC, or platelets did not revert MAP or HR to BL. Platelet counts were reduced by apheresis from BL 383 ± 20 × 10/μL to 141 ± 14 × 10/μL and were reduced further after resuscitation with albumin (88 ± 18 × 10/μL) or FC (97 ± 13 × 10/μL, all p < 0.05), but improved with platelet resuscitation (307 ± 24 × 10/μL). Fibrinogen concentration was reduced by apheresis from BL 225 ± 9 mg/dL to 194 ± 8 mg/dL, fell after albumin infusion (134 ± 11 mg/dL), increased to 269 ± 10 mg/dL after FC resuscitation (all p < 0.05), and was not affected by platelet resuscitation. Rotem α-angle decreased from 79 ± 2 degrees to 69 ± 1 degrees by apheresis and hemorrhage (p < 0.05), and recovered similarly by resuscitation with FC (87 ± 1 degrees) or platelets (78 ± 2 degrees), but not by albumin (63 ± 3 degrees). Similar responses were observed in Rotem maximum clot firmness., Conclusion: In this traumatic hemorrhage swine model, low-volume resuscitation with FC or platelets was similarly effective in restoring coagulation.

Background: This study compared coagulation function after resuscitation with Hextend and lactated Ringer's (LR) solution in pigs with tissue injury and hemorrhagic shock., Methods: Pigs were randomized into control (n = 7 each), LR, and Hextend groups. Femur fracture was induced using the captive bolt stunner at midshaft of the pigs' left legs, followed by hemorrhage of 60% total blood volume and resuscitation with either Hextend (equal to bled volume) or LR to reach the same mean arterial pressure. Pigs in the control group were not bled or resuscitated. Hemodynamics was monitored hourly for 6 hours. Blood samples were taken at baseline (BL), after hemorrhage, 15 minutes, 3 hours, and 6 hours after resuscitation for blood and coagulation measurements., Results: Mean arterial pressure decreased to 50% of BL by the 60% hemorrhage but returned to near BL within 1 hour after LR or Hextend resuscitation. Heart rate was increased (from 91 ± 4 beats per minute to 214 ± 20 beats per minute) by hemorrhage and decreased after resuscitation but remained elevated above BL in both groups. Resuscitation with Hextend (42 mL/kg) or LR (118 ± 3 mL/kg) reduced hematocrit, total protein, fibrinogen, and platelet counts, with greater decreases shown in the Hextend group. Clot strength was lower but returned to BL by 3 hours in the LR group, whereas it remained reduced for the 6-hour period after Hextend. The overall clotting capacity after LR was decreased after hemorrhage and resuscitation but returned to BL by 3 hours, whereas it remained low after Hextend for the 6-hour experiment period., Conclusion: After traumatic hemorrhage, coagulation function was restored within 6 hours with LR resuscitation but not with Hextend. The lack of recovery after Hextend is likely caused by greater hemodilution and possible effects of starches on coagulation substrates and further documents the need to restrict the use of high-molecular-weight starch in resuscitation fluids for bleeding casualties.

This study's objective was to investigate the daily dynamics of fibrinogen metabolism and coagulation function for 5 days after hemorrhagic shock in pigs. Sixteen pigs were randomized into the control (C) and the hemorrhage (H) groups. On day 1, hemorrhage was induced in H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer's solution at three times the bled volume. Then, a primed constant infusion of stable isotopes was performed in both groups daily for 5 days to measure changes in fibrinogen metabolism, together with changes in hemodynamics and coagulation function. Hemorrhage caused a decrease in mean arterial pressure and an increase in heart rate. Fluid resuscitation corrected these changes. Compared with baseline day 1, fibrinogen levels in H were decreased to 76% ± 6% by hemorrhage and resuscitation on day 1, increased to 217% ± 16% on day 2, and remained elevated afterward; clot strength in H was decreased by hemorrhage on day 1 and returned to baseline values on day 2 and afterward. Compared with day 1 control value (1.3 ± 0.1 mg/kg per hour), fibrinogen synthesis in H was increased to 3.6 ± 0.1, 5.1 ± 0.5, 2.6 ± 0.4, 2.7 ± 0.5, and 2.3 ± 0.3 mg/kg per hour on days 1 through 5 (all P < 0.05); fibrinogen breakdown in H was elevated on days 1 and 2 but returned to control values afterward. Hemorrhage caused acute decreases in fibrinogen concentration and clot strength, followed by an increase in fibrinogen concentration and recovery of clot strength. The increase in fibrinogen appeared primarily due to a sustained increase in fibrinogen synthesis.

Hemorrhagic coagulopathy (without neurological injuries) constitutes 40% of injury-related death in civilian hospitals and on the battlefield, and the underlying contributing mechanisms remain unclear. The purpose of this study is to investigate the effects of fibrinogen availability on coagulation function after hemorrhage in pigs. Sixteen crossbred commercial Yorkshire swine were randomized into the control group (group C) (n = 8) and hemorrhage group (group H) (n = 8). Hemorrhage was induced in group H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer solution at three times the bled volume. Pigs in group C were not hemorrhaged or resuscitated. Blood samples were withdrawn at baseline, 15 min, 3 h, 6 h, and 24 h after hemorrhage and lactated Ringer (LR) resuscitation (H-LR). Coagulation was assessed by using thrombelastography. All baseline measurements were similar between groups C and H. Hemorrhage caused a decrease in mean arterial pressure and an increase in heart rate in group H, but LR resuscitation corrected these changes within 1 h. Compared to baseline values, fibrinogen concentrations in group H decreased at 15 min, 3 h and 6 h after H-LR, but increased to double that of the baseline value at 24 h; platelet counts decreased throughout the study; clot strength was decreased at 15 min, 3 h and 6 h, but returned to baseline value at 24 h after H-LR. Hemorrhage caused decreases in fibrinogen and platelets, and compromised clot strength. The rebound of fibrinogen at 24 h restored clot strength despite platelet deficit. These data suggest the potential compensatory role of fibrinogen in restoring coagulation function in vivo after hemorrhagic shock.

Hemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in fibrinogen metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.9+/-0.8 kg) were anesthetized and instrumented with arterial and venous catheters and a thermodilution cardiac output catheter. Pigs were randomized into control (C; n=6), hemorrhage (H; n=6), and hemorrhage and resuscitation (H-LR; n=6) groups. Hemorrhage was induced by bleeding 35% of total blood volume for 30 min in H and H-LR groups. Resuscitation in H-LR group was performed using lactated Ringer's solution (LR) at 3 times the bled volume for 30 min. Fibrinogen metabolism was quantified using a primed constant infusion of 1-13C-phenylalanine (6 h) and d5-phenylalanine (4 h) and subsequent analysis by gas chromatograph-mass spectrometry, together with measurements of hemodynamics (hourly) and coagulation by thromboelastography (at baseline and 4 h after hemorrhage and resuscitation). Hemorrhage caused decreases in arterial pH and base excess, and an increase in arterial lactate content. Fluid resuscitation corrected these changes toward normal levels. Fibrinogen level was unchanged in C and decreased to 76%+/-4% in H and to 73%+/-3% in H-LR (both P<0.05, compared with baseline) after hemorrhage and resuscitation. Fibrinogen breakdown was increased from 3.0+/-0.4 mg kg-1 h-1 in C to 5.4+/-0.6 mg kg-1 h-1 in H and to 5.6+/-0.5 mg kg-1 h-1 in H-LR (both P<0.05, compared with control), but synthesis was unchanged. The clotting reaction time was unchanged in C and shortened to 93%+/-3% in H and to 91%+/-1% in H-LR (both P<0.05, compared with baseline). We conclude that hemorrhagic shock caused accelerated fibrinogen breakdown and coagulation. The LR resuscitation reduced tissue hypoxia indexes but did not affect the changes in fibrinogen metabolism and coagulation from hemorrhage. Thus, effective treatment of hemorrhage should include combining standard-of-care resuscitation with interventions to correct alterations in coagulation.

Background Ongoing improvements in trauma care now recommend earlier use of blood products as part of damage control resuscitation, but generally these products are not available at far forward battlefield locations. For the military, questions continue to arise regarding efficacy of normal saline (NS) vs. lactated Ringer's (LR). Thus, this study compared the effects of LR and NS after severe hemorrhage in pigs. Methods 20 anesthetized pigs were randomized into control (n = 6), LR (n = 7), and NS (n = 7) groups. Hemorrhage of 60 % estimated total blood volume was induced in LR and NS groups by removing blood from the left femoral artery using a computer-controlled pump. Afterwards, the pigs were resuscitated with either LR at 3 times the bled volume or the volume of NS to reach the same mean arterial pressure (MAP) as in LR group. Hemodynamics were measured hourly and blood samples were taken at baseline (BL), 15 min, 3 h and 6 h after resuscitation to measure changes in coagulation using thrombelastography®. Results MAP was decreased by hemorrhage but returned to BL within 1 h after resuscitation with LR (119 ± 7 ml/kg) or NS (183 ± 9 ml/kg, p < 0.05). Base excess (BE) was decreased by hemorrhage; resuscitation with LR recovered BE but not with NS. Total peripheral resistance was decreased with NS and LR, with a larger drop shown in NS. Serum potassium was increased with NS, but not affected with LR. Coagulation changes were similar between LR and NS. Conclusions NS may be inferior to LR in resuscitation due to its vasodilator effects and the risks of metabolic acidosis and hyperkalemia. [ABSTRACT FROM AUTHOR]