Novel concepts for damage control resuscitation in trauma.

PURPOSE OF REVIEW: Traumatic injuries are a major cause of mortality worldwide. Damage control resuscitation or balanced transfusion of plasma, platelets, and red blood cells for the management of exsanguinating hemorrhage after trauma has become the standard of care. We review the literature regarding the use of alternatives to achieve the desired 1 : 1:1 ratio as availability of plasma and platelets can be problematic in some environments. RECENT FINDINGS: Liquid and freeze dried plasma (FDP) are logistically easier to use and may be superior to fresh frozen plasma. Cold storage platelets (CSPs) have improved hemostatic properties and resistance to bacterial contamination. Low titer type O whole blood can be transfused safely in civilian patients. SUMMARY: In the face of hemorrhagic shock from traumatic injury, resuscitation should be initiated with 1 : 1 : 1 transfusion of plasma, platelets, and red blood cells with limited to no use of crystalloids. Availability of plasma and platelets is limited in some environments. In these situations, the use of low titer type O whole blood, thawed or liquid plasma, cold stored platelets or reconstituted FDP can be used as substitutes to achieve optimal transfusion ratios. The hemostatic properties of CSPs may be superior to room temperature platelets.

Contemporary thromboprophylaxis of trauma patients.

PURPOSE OF REVIEW: The traumatically injured patient is at high risk for developing venous thromboembolism. Clinical practice guidelines developed by the American College of Chest Physicians and the Eastern Association for the Surgery of Trauma recognize the importance of initiating thromboprophylaxis, but the guidelines lack specific recommendations regarding the timing and dose of pharmacologic thromboprophylaxis. We review the literature regarding initiation of thromboprophylaxis in different injuries, the use of inferior vena cava filters, laboratory monitoring, dosing regimens, and the use of antiplatelet therapy. RECENT FINDINGS: Use of pharmacologic thromboprophylaxis with invasive intracranial monitors is not associated with increased bleeding complications. The initiation of low-molecular-weight heparin (LMWH) prophylaxis 48 h postinjury in blunt solid organ injury is not associated with an increase in the rate of failed nonoperative management. Antiplatelet therapy in conjunction with LMWH may help to prevent venous thromboembolism. SUMMARY: In the setting of blunt traumatic brain and solid organ injury, initiation of pharmacologic thromboprophylaxis 48 h after injury is not associated with increased bleeding complications. There is no consensus or clear data showing which dosing regimen of LMWH is most effective or whether routine laboratory measurements are beneficial for determining effective thromboprophylaxis.

Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial.

Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30 mg twice daily) with TEG-adjusted enoxaparin dosing (35 mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89 were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35 mg vs 30 mg twice daily; P < .001). Anti-Factor Xa levels in intervention patients were not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, which was similar between the control and intervention groups (10.4% vs 13.5%; P = .68). The time to enoxaparin initiation was similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dose was also similar (43 [48.3%] vs 54 [56.3%]; P = .30). Rates of VTE (6 [6.7%] vs 6 [6.3%]; P > .99) were similar, but the difference in bleeding complications (5 [5.6%] vs 13 [13.5%]; P = .08) was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated as weight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5%; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported. Trial Registration: clinicaltrials.gov Identifier: NCT00990236.

Hematologic issues in the geriatric surgical patient.

Geriatric patients are at higher risk for hemorrhagic complications after surgery and traumatic injuries. The geriatric population is more likely to take anticoagulant or antiplatelet medications. Chronic disease, autoimmune disease, and nutritional deficiencies can lead to coagulation factor and platelet disorders. One must be familiar with the current anticoagulant and antiplatelet medications, their mechanism of action, and reversal agents to properly care for this group of patients. The new oral anticoagulants do not have Food and Drug Administration (FDA) approved reversal agents, but known procoagulant agents with other FDA indications may be effective.

Correlation of missed doses of enoxaparin with increased incidence of deep vein thrombosis in trauma and general surgery patients.

IMPORTANCE: Enoxaparin sodium is widely used for deep vein thrombosis (DVT) prophylaxis, yet DVT rates remain high in the trauma and general surgery populations. Missed doses during hospitalization are common. OBJECTIVE: To determine if missed doses of enoxaparin correlate with DVT formation. DESIGN, SETTING, AND PARTICIPANTS: Data were prospectively collected among 202 trauma and general surgery patients admitted to a level I trauma center. MAIN OUTCOMES AND MEASURES: Deep vein thrombosis screening was performed using a rigorous standardized protocol. RESULTS: The overall incidence of DVT was 15.8%. In total, 58.9% of patients missed at least 1 dose of enoxaparin. The DVTs occurred in 23.5% of patients who missed at least 1 dose and in 4.8% of patients who did not (P < .01). On univariate analysis, the need for mechanical ventilation (71.8% vs 44.1%), the performance of more than 1 operation (59.3% vs 40.0%), and male sex (75% vs 56%) were associated with DVT formation (P < .05 for all). A bivariate logistic regression was then performed, which revealed age 50 years or older and interrupted enoxaparin therapy as the only independent risk factors for DVT formation. The DVT rate did not differ between trauma and general surgery populations or in patients receiving once-daily vs twice-daily dosing regimens. CONCLUSIONS AND RELEVANCE: Interrupted enoxaparin therapy and age 50 years or older are associated with DVT formation among trauma and general surgery patients. Missed doses occur commonly and are the only identified risk factor for DVT that can be ameliorated by physicians. Efforts to minimize interrupted enoxaparin prophylaxis in patients at risk for DVT should be optimized.

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

BACKGROUND: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. METHODS: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. RESULTS: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. CONCLUSION: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.

Uncontrolled hemorrhagic shock results in a hypercoagulable state modulated by initial fluid resuscitation regimens.

BACKGROUND: Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. METHODS: Fifty swine were anesthetized, intubated, and ventilated and had monitoring lines placed. A Grade V liver injury was performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer's solution, 250 mL of 7.5% saline with 3% Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen as well as serum interleukin 6, interleukin 8, and tumor necrosis factor α levels were drawn at baseline and after 1 hour and 2 hours. RESULTS: The NF group had less posttreatment blood loss compared with other groups (p < 0.01). Blood loss was similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p < 0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5% saline with 3% Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p < 0.02). All fluids except lactated Ringer's solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p < 0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. CONCLUSION: Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.

The use of lyophilized plasma in a severe multi-injury pig model.

BACKGROUND: Shock and severe tissue injury lead to an endogenous coagulopathy mediated by activation of Protein C and hyperfibrinolysis known as acute traumatic coagulopathy. Together, hemodilution, acidosis, inflammation, and hypothermia result in a global trauma-induced coagulopathy. Coagulopathy in trauma is associated with mortality. Early and effective hemostatic resuscitation is critical in restoring perfusion, correcting coagulopathy, and saving lives in exsanguinating trauma. Lyophilized plasma (LP) provides a logistically superior alternative to fresh frozen plasma (FFP). STUDY DESIGN AND METHODS: Plasma was lyophilized following whole blood collection from anesthetized swine. A series of studies were performed using anesthetized swine subjected to a validated model of polytrauma and hemorrhagic shock including a Grade V liver injury. Animals were randomized to resuscitation using reconstituted LP fluids. Physiologic data and blood loss were measured. Coagulation status and inflammatory mediators were evaluated. RESULTS: Full volume reconstituted LP (100%LP) retains on average 86% coagulation factor activity compared to fresh plasma and when used in 1:1 ratios with red blood cells demonstrated superior hemostatic efficacy compared to FFP. Hypertonic LP reconstituted using 50% of the original plasma volume (50%LP) had higher coagulation factor concentrations, was well tolerated in swine, and equally effective compared to 100%LP with respect to physiologic and hemostatic properties. Buffering with ascorbic acid resulted in significant reductions in serum levels of tumor necrosis factor alpha and interleukin-6. CONCLUSION: By minimizing the volume of reconstituted LP and optimizing its anti-inflammatory properties, an LP resuscitation fluid may be created to provide effective hemostatic resuscitation with superior logistical properties.

Incidence of deep vein thrombosis is increased with 30 mg twice daily dosing of enoxaparin compared with 40 mg daily.

BACKGROUND: The purpose of this study was to analyze whether 2 standard dosing regimens of enoxaparin (30 mg twice daily vs 40 mg once daily) would result in different deep vein thrombosis (DVT) rates and anti-factor Xa activity (anti-Xa) in surgical patients. METHODS: Patients who required enoxaparin for prophylaxis were followed prospectively. Demographics were recorded. Patients underwent standardized duplex screening. Peak anti-Xa levels were drawn on 4 consecutive days. RESULTS: Sixty-three patients were followed up (28 patients on 30 mg twice daily, 35 patients on 40 mg once daily). There was no significant difference in demographics between groups. Twenty-five percent of patients on 30 mg twice daily developed a DVT, whereas 2.9% of patients on 40 mg once daily developed a DVT. Patients on 30 mg twice daily had significantly lower anti-Xa levels. CONCLUSIONS: The incidence of DVT is increased in surgical patients who receive 30 mg twice daily dosing of enoxaparin compared with 40 mg daily. Dosing of 40 mg once daily results in significantly higher peak anti-Xa levels compared with 30 mg twice daily.

Hextend and 7.5% hypertonic saline with Dextran are equivalent to Lactated Ringer's in a swine model of initial resuscitation of uncontrolled hemorrhagic shock.

BACKGROUND: The optimal fluid strategy for the early treatment of trauma patients remains highly debated. Our objective was to determine the efficacy of an initial bolus of resuscitative fluids used in military and civilian settings on the physiologic response to uncontrolled hemorrhagic shock in a prospective, randomized, blinded animal study. METHODS: Fifty anesthetized swine underwent central venous and arterial catheterization followed by celiotomy. Grade V liver injury was performed, followed by 30 minutes of uncontrolled hemorrhage. Then, liver packing was completed, and fluid resuscitation was initiated over 12 minutes with 2 L normal saline (NS), 2 L Lactated Ringer's (LR), 250 mL 7.5% hypertonic saline with 3% Dextran (HTS), 500 mL Hextend (HEX), or no fluid (NF). Animals were monitored for 2 hours postinjury. Blood loss after initial hemorrhage, mean arterial pressure (MAP), tissue oxygen saturation (StO2), hematocrit, pH, base excess, and lactate were measured at baseline, 1 hour, and 2 hours. RESULTS: NF group had less post-treatment blood loss compared with other groups. MAP and StO2 for HEX, HTS, and LR at 1 hour and 2 hours were similar and higher than NF. MAP and StO2 did not differ between NS and NF, but NS resulted in decreased pH and base excess. CONCLUSIONS: Withholding resuscitative fluid results in the least amount of posttreatment blood loss. In clinically used volumes, HEX and HTS are equivalent to LR with regard to physiologic outcomes and superior to NF. NS did not provide a measurable improvement in outcome compared with NF and resulted in increased acidosis.

Gender-based differences in mortality in response to high product ratio massive transfusion.

BACKGROUND: Recent data suggest that patients undergoing massive transfusion have lower mortality rates when ratios of plasma and platelets to red blood cells (RBCs) of ≥ 1:2 are used. This has not been examined independently in women and men. A gender dichotomy in outcome after severe injury is known to exist. This study examined gender-related differences in mortality after high product ratio massive transfusion. METHODS: A retrospective study was conducted using a database containing massively transfused trauma patients from 23 Level I trauma centers. Baseline demographic, physiologic, and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (≥ 1:2) or low (<1:2) ratios of plasma or platelets to RBCs was compared in women and men independently. RESULTS: Seven hundred four patients were analyzed. In males, mortality was lower for patients receiving a high plasma:RBC ratio at 24 hours (20.6% vs. 33.0% for low ratio, p = 0.005) and at 30 days (34.9% vs. 42.8%, p = 0.032). Males receiving a high platelet:RBC ratio also had lower 24-hour mortality (17.6% vs. 31.5%, p = 0.004) and 30-day mortality (32.1% vs. 42.2%, p = 0.045). Females receiving high ratios of plasma or platelets to RBCs had no improvement in 24-hour mortality (p = 0.119 and 0.329, respectively) or 30-day mortality (p = 0.199 and 0.911, respectively). Use of high product ratio transfusions did not affect 24-hour RBC requirements in males or females. CONCLUSION: Use of high plasma:RBC or platelet:RBC ratios in massive transfusion may benefit men more than women. This may be due to gender-related differences in coagulability. Further study is needed to determine whether separate protocols for women and men should be established.

Lyophilized plasma with ascorbic acid decreases inflammation in hemorrhagic shock.

BACKGROUND: Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown. METHODS: Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals. RESULTS: No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p < 0.05), but less so at 2 hours in the AA group compared with CA and HCl. CONCLUSION: In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.

Advanced hemostatic dressings are not superior to gauze for care under fire scenarios.

BACKGROUND: Advanced hemostatic dressings perform superior to standard gauze (SG) in animal hemorrhage models but require 2 minutes to 5 minutes application time, which is not feasible on the battlefield. METHODS: Twenty-four swine received a femoral artery injury, 30 seconds uncontrolled hemorrhage and randomization to packing with SG, Combat Gauze (CG), or Celox Gauze (XG) without external pressure. Animals were resuscitated to baseline mean arterial pressures with lactated Ringers and monitored for 120 minutes. Physiologic and coagulation parameters were collected throughout. Dressing failure was defined as overt bleeding outside the wound cavity. Tissues were collected for histologic and ultrastructural studies. RESULTS: All animals survived to study end. There were no differences in baseline physiologic or coagulation parameters or in dressing success rate (SG: 8/8, CG: 4/8, XG: 6/8) or blood loss between groups (SG: 260 mL, CG: 374 mL, XG: 204 mL; p > 0.3). SG (40 seconds ± 0.9 seconds) packed significantly faster than either the CG (52 ± 2.0) or XG (59 ± 1.9). At 120 minutes, all groups had a significantly shorter time to clot formation compared with baseline (p < 0.01). At 30 minutes, the XG animals had shorter time to clot compared with SG and CG animals (p < 0.05). All histology sections had mild intimal and medial edema. No inflammation, necrosis, or deposition of dressing particles in vessel walls was observed. No histologic or ultrastructural differences were found between the study dressings. CONCLUSIONS: Advanced hemostatic dressings do not perform better than conventional gauze in an injury and application model similar to a care under fire scenario.

Lyophilized plasma reconstituted with ascorbic acid suppresses inflammation and oxidative DNA damage.

BACKGROUND: Lyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model. METHODS: Thirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2'-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage. RESULTS: No differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24). CONCLUSIONS: Resuscitation with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.

Blood volume analysis can distinguish true anemia from hemodilution in critically ill patients.

BACKGROUND: Peripheral hematocrit (pHct) is traditionally used as a marker for blood loss. In critically ill patients who are fluid resuscitated, pHct may not adequately represent red blood cell volume (RBCV). We hypothesize that the use of pHct alone may overestimate anemia, potentially leading to unnecessary interventions. METHODS: Patients admitted to the intensive care unit underwent blood volume analysis. Serial blood samples were collected after injection of I-albumin. Samples were then processed by the Blood Volume Analyzer-100. RBCV and total blood volume (TBV) were calculated using the directly measured plasma volume (PV) and pHct. A computed normalized hematocrit (nHct) adjusts pHct to the patient's ideal blood volume. RESULTS: Thirty-six patients (21 men), aged 49.8 years ± 18.4 years, Acute Physiology And Chronic Health Evaluation II score 14.9 ± 8.1, and injury severity score 29.4 ± 12.4 had 84 blood volume analyses performed on 3 consecutive days. Using ratios of TBV compared with ideal TBV, patients were stratified into three separate groups: hypovolemic (16 of 84), normovolemic (23 of 84), and hypervolemic (45 of 84). Mean differences between pHct and nHct in each group were 4.5% ± 3.1% (p≤0.01), 0.0% ± 1.2% (p=0.85), and -6.5% ± 4.1% (p≤0.01), respectively. pHct, when compared with nHct, diagnosed anemia (Hct <30) nearly equal within the hypovolemic and normovolemic groups. However, pHct overdiagnosed anemia in 46.7% of hypervolemic patients. CONCLUSION: Use of blood volume analysis in critically ill patients may help to distinguish true anemia from hemodilution, potentially preventing unnecessary interventions.

Trauma induces a hypercoagulable state that is resistant to hypothermia as measured by thrombelastogram.

BACKGROUND: The aim of this study was to test the hypothesis that severely injured trauma patients would be hypercoagulable compared with controls measured by thromboelastography and that this hypercoagulability would persist over a broad range of temperatures. METHODS: A prospective study evaluating the effects of temperature on coagulation in trauma patients with Injury Severity Scores ≥ 15 and controls was completed. Thromboelastography was performed 24 hours after admission at 4 temperatures ranging from 32°C to 38°C. RESULTS: Ninety-two subjects (46 patients) were analyzed. Patients had a median Injury Severity Score of 20 (interquartile range, 16­26). Time to clot formation increased (P < .001) and fibrin cross-linking decreased (P < .01) in both groups as temperature decreased. Between groups, time to clot formation, fibrin cross-linking, and clot strength were significantly different at each temperature (P < .01), with patients being more hypercoagulable. Time to clot formation and fibrin cross-linking were more affected by temperature in controls compared with patients (P < .02). CONCLUSIONS: Severely injured patients are more hypercoagulable than controls throughout a broad range of temperature. Decreasing temperature has a greater effect on coagulation in controls compared with patients.

Red blood cells accelerate the onset of clot formation in polytrauma and hemorrhagic shock.

BACKGROUND: Hemorrhage and coagulopathy are major contributors to death after trauma. The contribution of red blood cells (RBCs) in correcting coagulopathy is poorly understood. Current methods of measuring coagulopathy may fail to accurately characterize in vivo clotting. We aimed to determine the effect of RBCs on clotting parameters by comparing resuscitation regimens containing RBCs and plasma with those containing plasma alone. METHODS: Thirty-two Yorkshire swine were anesthetized, subjected to a complex model of polytrauma and hemorrhagic shock, and resuscitated with either fresh frozen plasma, lyophilized plasma (LP), or 1:1 ratios of fresh frozen plasma:packed RBC (PRBC) or LP:PRBC. Activated clotting time, prothrombin time, partial thromboplastin time, and thrombelastography (TEG) were performed at 1 hour, 2 hours, 3 hours, and 4 hours after resuscitation. RESULTS: Animals treated with 1:1 LP:PRBC had less blood loss than the other groups (p < 0.05). The activated clotting time was shorter in the 1:1 groups when compared with the pure plasma groups at all time points (p < 0.05). The 1:1 groups had shorter TEG R times (time to onset of clotting) at 1 hour, 3 hours, and 4 hours compared with pure plasma groups (p < 0.05). Other TEG parameters did not differ between groups. Partial thromboplastin time was shorter in the pure plasma groups than the 1:1 groups at all time points (p < 0.05). CONCLUSIONS: Whole blood assays reveal that RBCs accelerate the onset of clot formation. Coagulation assays using spun plasma underestimate the effect of RBCs on clotting and do not completely characterize clot formation.

High transfusion ratios are not associated with increased complication rates in patients with severe extremity injuries.

BACKGROUND: High transfusion ratios of plasma to packed red blood cells (>1:2) have been associated with increased survival and increased complications in patients receiving massive transfusion (MT). We hypothesized that high ratio transfusion would be associated with no survival benefit and increased complications in combat victims with compressible hemorrhage. METHODS: A retrospective analysis of soldiers injured in the current conflict during 5 years (n = 2,105) who received blood was performed on those with isolated extremity (abbreviated injury scale extremity score > or = 3 and abbreviated injury scale score 0-2 in all other regions) injury comparing those who received a MT with those who did not. Transfusion ratios in the first 24 hours were correlated with outcomes. RESULTS: Injury severity score (14.6 vs. 12.1; p < 0.05), international normalized ratio (1.65 vs. 1.28; p < 0.05), and base deficit (8.0 vs. 3.7; p < 0.05) were higher in the MT group. High transfusion ratios were associated with a trend toward decreased mortality (17.2% vs. 6.9%; p = 0.07) in MT patients and no increased complications (20.7% vs. 26.4%; p > 0.05). In those receiving a non-MT, high ratios were associated with similar mortality (4.8% vs. 3.9%; p > 0.05) and complications (12.4% vs. 9.2%; p > 0.05). CONCLUSIONS: Extremity injured patients receiving MT may benefit from high transfusion ratios and do not experience increased complications. No change in mortality or complications was observed in non-MT patients across transfusions ratios. High transfusion ratios are not associated with increased complications in patients with isolated extremity injury regardless of whether a MT is required.

Thrombelastography versus AntiFactor Xa levels in the assessment of prophylactic-dose enoxaparin in critically ill patients.

BACKGROUND: A standard dose of enoxaparin is frequently used for deep venous thrombosis (DVT) prophylaxis. Evidence suggests inconsistent bioavailability in intensive care unit (ICU) patients. Antifactor Xa activity (anti-Xa) has been used to monitor enoxaparin dosing but its accuracy and availability are problematic. Thrombelastography (TEG) is used to evaluate coagulation in diverse settings. The purpose of this study was to analyze whether TEG could be used to predict which enoxaparin-treated patients would develop DVT. METHODS: Two hundred sixty-one simultaneous enoxaparin-active (active) and enoxaparin-neutralized (neutral) TEGs were performed in 61 surgical ICU patients over four consecutive days. Patient characteristics and anti-Xa were collected. DVT screening was per ICU protocol. RESULTS: Mean (+/-SEM) age was 54 (+/-2.3) years and Acute Physiology and Chronic Health Evaluation II score was 17 (+/-0.7). There were 30 trauma and 31 general surgery patients (69% men). The DVT rate was 28%. Time to clot formation (R) and percent lysis at 30 minutes were different between active versus neutralized blood (p < 0.001). R time was 1.5 minutes shorter in patients with DVT versus those without (p < 0.001) indicating hypercoagulability in DVT patients. Anti-Xa levels were similar in patients with (0.135 +/- 0.012) and without (0.135 +/- 0.007) DVT (p = 0.97). There were no differences in age, body mass index, injury severity score, Acute Physiology and Chronic Health Evaluation II score, or trauma status between DVT and non-DVT groups. CONCLUSIONS: TEG demonstrates differences between enoxaparin-neutralized and enoxaparin-active blood in ICU patients that may be used to guide dosing. TEG differentiates enoxaparin-treated patients who subsequently develop DVT while anti-Xa levels do not. TEG demonstrates an enoxaparin-related increase in fibrinolysis.

Malignant pericardial effusion--an uncommon complication of multiple myeloma: case report.

Multiple myeloma is a condition usually associated with lesions of the skeleton. However, under rare circumstances, the malignant plasma cells may infiltrate the pericardium, resulting in an effusion. If left untreated, the abnormal accumulation of pericardial fluid will result in cardiac tamponade, requiring drainage. The following report describes a multiple myeloma patient who developed secondary pericardial and pleural effusions, which were surgically drained via a pleuropericardial window.