Definitive management of the exsanguinating patient continues to challenge providers in multiple specialties. Significant hemorrhage may be encountered in a variety of patient care circumstances. ...Over the past two decades, the vast majority of data and evidence regarding transfusion in the exsanguinating patient has been based upon the trauma literature, and a large amount of recent research has investigated this subject area. In addition to the care of trauma patients, the data which have emerged can also be extrapolated to the treatment of nontrauma patients undergoing transfusion for major hemorrhage. The concept of massive transfusion is an evolving paradigm, and numerous investigations have challenged old principles while creating new controversies. The current review will examine the latest developments in the management of patients with profound hemorrhage. The challenges of dealing with the “lethal triad” will be discussed, as will the various aspects of damage control and hemostatic resuscitation. The latest literature and controversy regarding massive transfusions and massive transfusion protocols will be elucidated with inclusion of data from recent military experiences. Finally, adjuncts including the most recent advances in hemorrhage control, identification of early predictors for massive transfusion, and utilization of pharmacologic and complementary factor agent therapy will be discussed.
Abstract Background Prothrombin time-international normalized ratio (PT-INR) is widely utilized to guide plasma therapy and initiation of thromboprophylaxis after a hepatectomy. Thrombelastography ...(TEG) monitors shear elasticity, which is sensitive to cellular and plasma components in blood, allowing for functional assessment of the life of the clot. The objective of this study was to prospectively compare PT-INR and TEG in liver resection patients. Methods Forty patients were enrolled before undergoing an elective hepatectomy. Patients underwent a liver resection utilizing a low central venous pressure (CVP) anaesthetic technique and intermittent Pringle manoeuver. PT-INR and TEG were drawn prior to incision, post-operatively, and post-operative days 1, 3 and 5. Results All post-operative PT-INR values increased significantly when compared with pre-operative PT-INR ( P < 0.01). The time of onset to clot ( R -value) decreased significantly at the post-operative time point ( P = 0.04), consistent with a relative hypercoagulability. Subsequent R -values were not different compared with the pre-operative R -value. The strength of the clot (maximum amplitude, MA) was unchanged when comparing pre- and post-operative time points. Discussion In spite of an elevation in PT-INR, patients undergoing a liver resection demonstrated a brief hypercoagulable state, followed by normal coagulation function based on TEG. These data call into question the practice of utilizing PT-INR to guide plasma transfusion and timing of prophylactic anticoagulation after a liver resection.
The objective of this study was to determine whether cyclic strain could promote human umbilical vein endothelial cells (HUVECs) to express markers in common with the mature smooth muscle cell (SMC) ...phenotype, suggesting endothelial cell to SMC transdifferentiation. HUVECs were cultured on stretched membranes at 10% stretch and 60 cycles/min for 24–96 hr, and demonstrated elongation with enhanced and organized F-actin distribution. By using real-time polymerase chain reaction analysis, the mRNA levels of five specific SMC markers, SM22-α, α-smooth muscle actin (α-SMA), caldesmon-1, smooth muscle myosin heavy chain (SMMHC), and calponin-1 were significantly increased in cyclic strain-treated HUVECs as compared with those in static control cells. Protein levels of SM22-α and α-SMA were also substantially increased by Western blot and immunofluorescence staining. In addition, two specific endothelial markers, von Willebrand factor (vWF) and vascular endothelial growth factor receptor-2 (VEGFR-2), showed a reduction in mRNA expression. In addition, cyclic strain-induced increase of SM22-α and α-SMA expression were reversible when cells were cultured back to the static condition. These results demonstrate a possible endothelial cell to SMC transdifferentiation in response to cyclic strain. Hemodynamic forces in modulating endothelial phenotype may play an important role in the vascular system.
Smooth muscle cells (SMCs) under shear stress may alter their gene expression patterns to adapt to a new hemodynamic environment. Their plasticity may play an important role in vascular development, ...healing, and remodeling as well as vascular lesion formation under abnormal environmental conditions. A mouse vascular SMC line (P53LMACO1) cultured under shear stress significantly increased the mRNA levels of endothelial cell markers including Platelet-endothelial cell adhesion molecule-1 (PECAM-1), von Willebrand factor (vWF), and VE-cadherin, while significantly decreasing the mRNA levels of SMC markers including alpha-smooth muscle actin (α-SMA), calponin-1, smooth muscle myosin heavy chain (SMMHC), and transgelin as compared to static control cells. Protein levels of PECAM-1 and vWF were significantly increased, while protein levels of α-SMA were substantially decreased in the shear stress-cultured cells. In addition, shear stress-cultured cells showed an enhanced capability to form capillary-like structures on Matrigel. Thus, shear stress may promote endothelial cell transdifferentiation from SMCs.
To evaluate factors that are predictive of delayed abdominal closure in patients injured during military conflict.
Seventy-one patients managed with an open abdomen were identified from records at ...Landstuhl Regional Medical Center from 2005 and 2006. Follow-up data were available from Walter Reed Army Medical Center. Records were reviewed through all echelons of care. Ordinal logistic regression was used to predict delayed abdominal closure.
Patients sustained injury from blunt (n = 2), penetrating (n = 30), and blast (n = 39) mechanisms. The median Injury Severity Score was 25 (interquartile range, 17-34). Abdominal injury was observed in 85% of patients, and 48% underwent a massive transfusion. The median time to transfer to the United States was 5.3 days (interquartile range, 4.3-6.8 days). Abdomens were definitively closed downrange (11%), at Landstuhl Regional Medical Center (33%), or at Walter Reed Army Medical Center (56%). The median time until abdominal closure was 13 days (interquartile range, 4-40 days) in 2005 compared with 4 days (interquartile range, 1-14.5 days) in 2006 (P = .02). The multivariate model identified massive transfusion (odds ratio, 3.9), presence of complications (odds ratio, 5.1), and an injury date in 2005 (odds ratio, 3.4) as independently predictive variables for later abdominal closure.
Massive transfusion, occurrence of complications, and earlier injury date were predictive of delayed abdominal closure in casualties managed with an open abdomen. These data suggest an evolving approach to the management of severely injured combat casualties that involves earlier abdominal closure.
Background Hemodynamic forces play a crucial role in regulating vascular cell phenotype. However, the underlying molecular mechanisms are largely unknown. The objective of this study was to test our ...hypothesis that cyclic strain could affect smooth muscle cell (SMC) differentiation. Methods A murine embryonic mesenchymal progenitor cell line (C3H/10T1/2) was cultured with or without cyclic strain for 6 days. Changes in cell morphology were studied with fluorescence dye Calcein-AM staining. Expression of specific SMC markers, smooth muscle specific α-actin (α-SMA), and smooth muscle myosin heavy chain (SMMHC), was determined by real-time polymerase chain reaction (PCR) and Western blot. Transforming growth factor- β (TGF-β) was used as a positive control. Results With cyclic strain, CH3/10T1/2 cells demonstrated spindle-shaped morphology and parallel alignment. Cells exposed to cyclic strain illustrated significantly increased mRNA levels of α-SMA and SMMHC by 3- and 2-fold, respectively, compared with static cells ( P < .05). In addition, cells cultured under cyclic strain with TGF-β (2 ng/ml) supplementation demonstrated increased mRNA levels of α-SMA and SMMHC by 10- and 2-fold, respectively, compared with static cells ( P < .05). Furthermore, protein levels of α-SMA and SMMHC were also significantly increased by more than 3-fold in cyclic strain–treated cells compared with static cultures ( P < .05). TGF-β synergistically enhanced the effect of cyclic strain on α-SMA mRNA expression in CH3/10T1/2 cells. Conclusions This is the first study to demonstrate that cyclic strain significantly induces expression of two of the most important SMC markers in a murine embryonic mesenchymal progenitor cell line. Cyclic strain and TGF-β have a synergistic effect on α-SMA mRNA expression.
The goal of this study was to evaluate a low fixed-dose versus weight-based dosing strategy for four-factor prothrombin complex (4F-PCC) time to administration in intracranial hemorrhage (ICH) ...patients.
A retrospective analysis was conducted at a single rural Tertiary referral center in patients ≥18 years old on warfarin with ICH who received 4F-PCC. Continuous variables were summarized using mean (±95% CI) and compared using two-tailed tests;
values ≤0.05 were considered statistically significant.
A total of 46 ICH patients were reversed using 4F-PCC (Fixed, n = 27 and Weight, n = 19). Baseline characteristics were equivalent. Total units of 4F-PCC (mean dose units 2525.1 versus 1623.3) and dose per kg were significantly reduced in the fixed-dose group. Total time from order to delivery was significantly reduced with the fixed-dose strategy (mean time 43.0 versus 29.0 minutes). Hospital length of stay (LOS), intensive care unit LOS, and mortality were equivalent with a similar mechanism. International Normalized Ratio (INR) reversal success (≤1.5) and total INR change was comparable with no difference in adverse thromboses between groups.
A fixed-dosed strategy reduced time to 4F-PCC administration for warfarin reversal in ICH, as compared to a weight-based strategy; with no increase in LOS, mortality, or need for additional dosing. This also resulted in significant cost savings.
The isolation, differentiation, and expansion of endothelial progenitor cells (EPCs) from peripheral blood have potential applicability in areas of therapeutic neovascularization, vascular repair, ...and tissue engineering. The purpose of the current study was to elucidate a simple method of isolation and differentiation of EPCs by defining the endothelial morphology, surface marker expression, and proliferative capacity of EPC outgrowth from canine peripheral blood mononuclear cells (PBMCs).
PBMCs were isolated from fresh canine blood and cultured in fibronectin-coated plates in which EPCs were identified from cell morphology and outgrowth characteristics. Cell surface markers were determined with flow cytometry analysis to identify differentiation of cultured and subcultured colonies. A hematologic counter with phase contrast microscopy was used to study cell growth curves of EPCs as compared with mature human coronary artery endothelial cells.
During the first week of canine PBMC culture, cells were morphologically round and varied in size, but in the course of the second and third week of culture, the cells, respectively, became spindle-shaped and displayed an endothelium-like cobblestone morphology with outgrowth. CD34 was significantly decreased at 21 days as compared with 7 days culture (36.04% to 21.37%), whereas vWF (from 77.26% to 96.37%) and eNOS (from 0% to 14.97%) were significantly increased. VEGFR-2 was slightly increased, and P1H12 (CD146) was unchanged. Subcultured canine EPCs displayed a higher proliferation rate as compared to mature human coronary artery endothelial cells in the same culture conditions.
These data demonstrate that canine EPCs can be isolated and cultured from the canine PBMC fraction. These outgrowth cells displayed characteristics of endothelial morphology with endothelial cell-specific surface markers. Furthermore, it was revealed that canine EPCs have a greater growth potential as compared to mature endothelial cells. This study suggests that PBMCs could be used as a source of EPCs for potential applications in tissue engineering and vascular therapy.
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