Publications by authors named "Myung S Park"

38 Publications

Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma.

Thromb Res 2021 08 31;204:22-28. Epub 2021 May 31.

Division of Hematology, Department of Medicine and Blood Research Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address:

Activation of the fibrinolytic system plays a central role in the host response to trauma. There is significant heterogeneity in the degree of fibrinolysis activation at baseline that is usually assessed by whole blood thromboelastography (TEG). Few studies have focused on plasma markers of fibrinolysis that could add novel insights into the frequency and mechanisms of fibrinolytic activation in trauma. Global fibrinolysis in plasma was assessed using a modified euglobulin clot lysis time (ECLT) assay in 171 major trauma patients and compared to commonly assessed analytes of fibrinolysis. The median ECLT in trauma patients was significantly shorter at 8.5 h (IQR, 1.3-19.5) compared to 19.9 h (9.8-22.6) in healthy controls (p < 0.0001). ECLT values ≤2.5th percentile of the reference range were present in 83 (48.5%) of trauma patients, suggesting increased fibrinolytic activation. Shortened ECLT values were associated with elevated plasmin-antiplasmin (PAP) complexes and free tissue plasminogen activator (tPA) levels in plasma. Sixteen (9.2%) individuals met the primary outcome for massive transfusion, here defined as the critical administration threshold (CAT) of 3 units of packed red cells in any 60-minute period within the first 24 h. In a univariate screen, plasma biomarkers associated with CAT included D-dimer (p < 0.001), PAP (p < 0.05), free tPA (p < 0.05) and ECLT (p < 0.05). We conclude that fibrinolytic activation, measured by ECLT, is present in a high proportion of trauma patients at presentation. The shortened ECLT is partially driven by high tPA levels and is associated with high levels of circulating PAP complexes. Further studies are needed to determine whether ECLT is an independent predictor of trauma outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2021.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277746PMC
August 2021

Quantification of von Willebrand factor and ADAMTS-13 after traumatic injury: a pilot study.

Trauma Surg Acute Care Open 2021 5;6(1):e000703. Epub 2021 Apr 5.

Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Background: Von Willebrand factor (VWF) is an acute phase reactant synthesized in the megakaryocytes and endothelial cells. VWF forms ultra-large multimers (ULVWF) which are cleaved by the metalloprotease ADAMTS-13, preventing spontaneous VWF-platelet interaction. After trauma, ULVWF is released into circulation as part of the acute phase reaction. We hypothesized that trauma patients would have increased levels of VWF and decreased levels of ADAMTS-13 and that these patients would have accelerated thrombin generation.

Methods: We assessed plasma concentrations of VWF antigen and ADAMTS-13 antigen, the Rapid Enzyme Assays for Autoimmune Diseases (REAADS) activity of VWF, which measure exposure of the platelet-binding A1 domain, and thrombin generation kinetics in 50 samples from 30 trauma patients and an additional 21 samples from volunteers. Samples were analyzed at 0 to 2 hours and at 6 hours from the time of injury. Data are presented as median (IQR) and Kruskal-Wallis test was performed between trauma patients and volunteers at both time points.

Results: REAADS activity was greater in trauma patients than volunteers both at 0 to 2 hours (190.0 (132.0-264.0) vs. 92.0 (71.0-114.0), p<0.002) and at 6 hours (167.5 (108.0-312.5.0) vs. 92.0 (71.0-114.0), p<0.001). ADAMTS-13 antigen levels were also decreased in trauma patients both at 0 to 2 hours (0.84 (0.51-0.94) vs. 1.00 (0.89-1.09), p=0.010) and at 6 hours (0.653 (0.531-0.821) vs. 1.00 (0.89-1.09), p<0.001). Trauma patients had accelerated thrombin generation kinetics, with greater peak height and shorter time to peak than healthy volunteers at both time points.

Discussion: Trauma patients have increased exposure of the VWF A1 domain and decreased levels of ADAMTS-13 compared with healthy volunteers. This suggests that the VWF burst after trauma may exceed the proteolytic capacity of ADAMTS-13, allowing circulating ULVWF multimers to bind platelets, potentially contributing to trauma-induced coagulopathy.

Level Of Evidence: Prospective case cohort study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/tsaco-2021-000703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030476PMC
April 2021

Exploring the utility of a novel point-of-care whole blood thrombin generation assay following trauma: A pilot study.

Res Pract Thromb Haemost 2021 Mar 8;5(3):395-402. Epub 2021 Mar 8.

Mayo Clinic Rochester MN USA.

Introduction: Plasma thrombin generation kinetics as measured by the calibrated automated thrombogram (CAT) assay is a predictor of symptomatic venous thromboembolism after trauma. We hypothesized that data from a new prototype assay for measurement of thrombin generation kinetics in fresh whole blood (near patient testing of thrombin generation), will correlate with the standard CAT assay in the same patients, making it a potential tool in the future care of trauma patients.

Methods: Patients were enrolled from June 2018 to February 2020. Within 12 hours of injury, blood samples were collected simultaneously for both assays. Variables compared and correlated between assays were lag time, peak height, time to peak, and endogenous thrombin potential. Data are presented as median with interquartile range (IQR). Spearman and Pearson correlations were estimated and tested between both assays; a value of <0.05 was considered to be significant.

Results: A total of 64 trauma patients had samples analyzed: injury severity score = 17 (IQR), 10-26], hospital length of stay = 7.5 (IQR), 2-18) days, age = 52 (IQR, 35-63) years, 71.9% male, and 42.2% of patients received a transfusion within 24 hours of injury. Thrombin generation parameters between plasma and whole blood were compared and found that all parameters of the two assays correlate in trauma patients.

Conclusion: In this pilot study, we have found that a novel point-of-care whole blood thrombin generation assay yields results with modest but statistically significant correlations to those of a standard plasma thrombin generation assay. This finding supports studying this device in a larger, adequately powered study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035795PMC
March 2021

Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding are Increased after Trauma.

Shock 2021 Jan 28. Epub 2021 Jan 28.

Trauma, Critical Care, and General Surgery, Department of Surgery, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905 Clinical Statistics and Biostatistics, Department of Health Sciences Research, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905 Shock Trauma Center, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD, 21201 Biochemistry and Molecular Biology, Department of Hematology, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905 Division of Hematology, University of Washington School of Medicine, Bloodworks Research Institute, 1551 Eastlake Avenue E, Seattle, WA, 98102 Division of Hematology and UNC Blood Research Center, Department of Medicine, University of North Carolina at Chapel Hill, NC, 27514 EpiCypher Inc., Durham, NC, 27709.

Background: Damage associated molecular patterns (DAMPs) stimulate endothelial syndecan-1 shedding and neutrophil extracellular traps (NET) formation. The role of NETs in trauma and trauma-induced hypercoagulability is unknown. We hypothesized that trauma patients with accelerated thrombin generation would have increased NETosis and syndecan-1 levels.

Methods: In this pilot study, we analyzed 50 citrated plasma samples from 30 trauma patients at 0 h (n = 22) and 6 h (n = 28) from time of injury (TOI) and 21 samples from healthy volunteers, for a total of 71 samples included in analysis. Thrombin generation was quantified using calibrated automated thrombogram (CAT) and reported as lag time (LT), peak height (PH), and time to peak (ttPeak). Nucleosome calibrated (H3NUC) and free histone standardized (H3Free) ELISAs were used to quantify NETs. Syndecan-1 levels were quantified by ELISA. Results are presented as median [interquartile range] and Spearman rank correlations.

Results: Plasma levels of H3NUC were increased in trauma patients as compared to healthy volunteers both at 0 h (89.8 ng/mL [35.4, 180.3]; 18.1 ng/mL [7.8, 37.4], p = 0.002) and at 6 h (86.5 ng/mL [19.2, 612.6]; 18.1 ng/mL [7.8, 37.4], p = 0.003) from TOI. H3Free levels were increased in trauma patients at 0 h (5.74 ng/mL [3.19, 8.76]; 1.61 ng/mL [0.66, 3.50], p = 0.002) and 6 h (5.52 ng/mL [1.46, 11.37]; 1.61 ng/mL [0.66, 3.50], p = 0.006). Syndecan-1 levels were greater in trauma patients (4.53 ng/mL [3.28, 6.28]; 2.40 ng/mL [1.66, 3.20], p < 0.001) only at 6 h from TOI. H3Free and syndecan-1 levels positively correlated both at 0 h (0.376, p = 0.013) and 6 h (0.583, p < 0.001) from TOI. H3NUC levels and syndecan-1 levels were positively correlated at 6 h from TOI (0.293, p = 0.041). TtPeak correlated inversely to H3 NUC (-0.358, p = 0.012) and syndecan-1 levels (-0.298, p = 0.038) at 6 h from TOI.

Conclusions: Our pilot study demonstrates that trauma patients have increased NETosis, measured by H3NUC and H3Free levels, increased syndecan-1 shedding, and accelerated thrombin generation kinetics early after injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316482PMC
January 2021

A Review of Pathophysiology, Clinical Features, and Management Options of COVID-19 Associated Coagulopathy.

Shock 2021 06;55(6):700-716

Division of Trauma, Critical Care, and General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.

Abstract: There is increasing evidence that novel coronavirus disease 2019 (COVID-19) leads to a significant coagulopathy, a phenomenon termed "COVID-19 associated coagulopathy." COVID-19 has been associated with increased rates of both venous and arterial thromboembolic events, a source of significant morbidity and mortality in this disease. Further evidence suggests a link between the inflammatory response and coagulopathy associated with COVID-19. This presents a unique set of challenges for diagnosis, prevention, and treatment of thrombotic complications. In this review, we summarize and discuss the current literature on laboratory coagulation disruptions associated with COVID-19 and the clinical effects of thromboembolic events including pulmonary embolism, deep vein thrombosis, peripheral arterial thrombosis, and acute ischemic stroke in COVID-19. Endothelial injury and augmented innate immune response are implicated in the development of diffuse macro- and microvascular thrombosis in COVID-19. The pathophysiology of COVID-19 associated coagulopathy is an important determinant of appropriate treatment and monitoring of these complications. We highlight the importance of diagnosis and management of dysregulated coagulation in COVID-19 to improve outcomes in COVID-19 patients with thromboembolic complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122038PMC
June 2021

Thrombin Generation Kinetics are Predictive of Rapid Transfusion in Trauma Patients Meeting Critical Administration Threshold.

Shock 2021 Mar;55(3):321-325

Department of Surgery, Mayo Clinic, Rochester, Minnesota.

Introduction: We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24 h after injury, independent of international normalized ratio (INR).

Methods: In a prospective cohort study, trauma patients were enrolled over a 4.5-year period and serial blood samples collected at various time points. We retrospectively stratified pts into three categories: CAT+, CAT- but receiving some pRBC Tx, receiving no Tx within the first 24 h. Blood collected prior to Tx was analyzed for thrombin generation parameters and prothrombin time (PT)/INR.

Results: A total of 484 trauma pts were analyzed: injury severity score = 13 [7,22], age = 48 [28, 64] years, and 73% male. Fifty pts met criteria for CAT+, 64 pts CAT-, and 370 received no Tx. Risk factors for meeting CAT+: decreased arrival systolic blood pressure (OR 2.82 [2.17, 3.67]), increased INR (OR 2.09, [1.66, 2.62]) and decreased time to peak OR 2.27 [1.74, 2.95]). These variables remained independently associated with increased risk of requiring Tx in a multivariable logistic model, after adjusting for sex and trauma type.

Conclusions: Pts in hemorrhagic shock, who meet CAT+ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970628PMC
March 2021

Development and application of global assays of hyper- and hypofibrinolysis.

Res Pract Thromb Haemost 2020 Jan 6;4(1):46-53. Epub 2019 Nov 6.

Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill North Carolina.

Numerous methods for evaluation of global fibrinolytic activity in whole blood or plasma have been proposed, with the majority based on tissue-type plasminogen activator (t-PA) addition to initiate fibrinolysis. We propose that such an approach is useful to reveal hypofibrinolysis, but t-PA concentrations should be kept to a minimum. In this paper, we describe a low-concentration t-PA plasma turbidity assay to evaluate several congenital factor deficiencies, including plasminogen activator inhibitor-1 (PAI-1) and plasminogen deficiency, as well as hemophilia A and B. In addition, we demonstrate a threshold dependency on endogenous PAI-1 levels. To assess endogenous hyperfibrinolysis, we suggest that assays that avoid t-PA addition are preferable, with assays based on euglobulin fractionation remaining a viable choice. We describe a euglobulin fraction clot lysis time (ECLT) assay with spectrophotometric readout and other modifications, and evaluate it as a tool to measure hyperfibrinolysis in inherited clotting factor deficiency states. We demonstrate that the ECLT is predominantly driven by residual amounts of PAI-1, t-PA, and α-antiplasmin. These assays should be further evaluated for the detection of hypo- or hyperfibrinolysis in acquired thrombotic or hemorrhagic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971323PMC
January 2020

Endogenous Procoagulant Activity in Trauma Patients and Its Relationship to Trauma Severity.

TH Open 2019 Jan 7;3(1):e10-e19. Epub 2019 Jan 7.

Department of Biochemistry, University of Vermont, Colchester, Vermont, United States.

 It has been observed that trauma patients have elevated plasma procoagulant activity that could be assigned to an elevated concentration of tissue factor (TF). However, in many instances there is a discrepancy between the levels of TF and the procoagulant activity observed. We hypothesized that factor XIa (FXIa) could be responsible for this additional activity and that the presence and levels of both proteins could correlate with trauma severity.  Citrate plasma from 98 trauma patients (47 blunt, 17 penetrating, and 34 thermal) were evaluated in clotting assays for the presence of FXIa and TF activity using respective inhibitory antibodies.  When the three trauma patient groups were divided into two cohorts (Injury Severity Score [ISS] > 25 and ISS ≤ 25), higher frequencies and concentrations of both TF and FXIa were observed for all the more severe injury subgroups.  The majority of trauma patients have active FXIa in their plasma, with a significant fraction having active TF as well. Additionally, both TF and FXIa frequency and concentration directly relate to trauma severity. These data suggest the use of these two proteins as potential markers for the stratification of trauma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1677030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524897PMC
January 2019

Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma: A prospective cohort study.

J Trauma Acute Care Surg 2017 09;83(3):381-387

From the Department of Trauma and Critical Care Surgery (M.S.P., D.H.J., S.P.Z.), Department of Health Sciences Research (G.M.S., K.R.B., W.S.H., A.A.A., J.A.H.), Hematology Research (A.X., A.A.A., J.A.H.), Department of Surgery (M.J.F., S.K.D.), and Department of Internal Medicine (A.A.A., J.A.H.), Mayo Clinic, Rochester, Minnesota.

Background: Reliable biomarkers predictive of venous thromboembolism (VTE) after acute trauma are uncertain. The objective of the study was to identify risk factors for symptomatic VTE after trauma, including individual plasma coagulome characteristics as reflected by thrombin generation.

Methods: In a prospective, case-cohort study, trauma patients were enrolled over the 4.5-year period, 2011 to 2015. Blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and at hospital discharge. Platelet poor plasma was stored at -80 °C until analysis. Thrombin generation, as determined by the calibrated automated thrombogram (CAT) using 5 pM tissue factor (TF)/4 μM phospholipid (PS), was reported as peak height (nM thrombin) and time to peak height (ttPeak [minutes]). Data are presented as median [IQR] or hazard ratio with 95% CI.

Results: Among 453 trauma patients (injury severity score = 13.0 [6.0, 22.0], hospital length of stay = 4.0 [2.0, 10.0] days, age = 49 [28, 64] years, 71% male, 96% with blunt mechanism, mortality 3.2%), 83 developed symptomatic VTE within 92 days after injury (35 [42%] after hospital discharge). In a weighted, multivariate Cox model that included clinical and CAT characteristics available within 24 hours of admission, increased patient age (1.35 [1.19,1.52] per 10 years, p < 0.0001), body mass index ≥30 kg/m (4.45 [2.13,9.31], p < 0.0001), any surgery requiring general anesthesia (2.53 [1.53,4.19], p = 0.0003) and first available ttPeak (1.67 [1.29, 2.15], p < 0.00001) were independent predictors of incident symptomatic VTE within 92 days after trauma (C-statistic = 0.799).

Conclusion: The individual's plasma coagulome (as reflected by thrombin generation) is an independent predictor of VTE after trauma. Clinical characteristics and ttPeak can be used to stratify acute trauma patients into high and low risk for VTE.

Level Of Evidence: Prognostic, level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000001466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573638PMC
September 2017

Risk factors for venous thromboembolism after acute trauma: A population-based case-cohort study.

Thromb Res 2016 Aug 29;144:40-5. Epub 2016 Mar 29.

Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, United States.

Background: Predictors of venous thromboembolism (VTE) after trauma are uncertain.

Objective: To identify independent predictors of VTE after acute trauma.

Methods: Using Rochester Epidemiology Project (REP) resources, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE within 92days after hospitalization for acute trauma over the 18-year period, 1988-2005. We also identified all Olmsted County residents hospitalized for acute trauma over this time period and chose one to two residents frequency-matched to VTE cases on sex, event year group and ICD-9-CM trauma code predictive of surgery. In a case-cohort study, demographic, baseline and time-dependent characteristics were tested as predictors of VTE after trauma using Cox proportional hazards modeling.

Results: Among 200 incident VTE cases, the median (interquartile range) time from trauma to VTE was 18 (6, 41) days. Of these, 62% cases developed VTE after hospital discharge. In a multiple variable model including 370 cohort members, patient age at injury, male sex, increasing injury severity as reflected by the Trauma Mortality Prediction Model (TMPM) Mortality Score, immobility prior to trauma, soft tissue leg injury, and prior superficial vein thrombosis were independent predictors of VTE (C-statistic=0.78).

Conclusions: We have identified clinical characteristics which can identify patients at increased risk for VTE after acute trauma, independent of surgery. Almost two thirds of all incident VTE events occurred after initial hospital discharge (18day median time from trauma to VTE) which questions current practice of not extending VTE prophylaxis beyond hospital discharge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2016.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124558PMC
August 2016

Botulinum toxin A-induced paralysis of the lateral abdominal wall after damage-control laparotomy: A multi-institutional, prospective, randomized, placebo-controlled pilot study.

J Trauma Acute Care Surg 2016 Feb;80(2):237-42

From the Department of Surgery (M.D.Z., M.K., X.Z., M.A.K., B.Z., S.F.P., M.F., W.S.H., K.S.B., M.S.P., H.J.S., D.H.J.), Mayo Clinic, Rochester; and Department of Surgery (A.E.Z., D.D.), University of Minnesota, Minneapolis, Minnesota.

Background: Damage-control laparotomy (DCL) is a lifesaving operation used in critically ill patients; however, interval primary fascial closure remains a challenge. We hypothesized that flaccid paralysis of the lateral abdominal wall musculature induced by botulinum toxin A (BTX) would improve rates of primary fascial closure, decrease duration of hospital stay, and enhance pain control.

Methods: Consenting adults who had undergone a DCL at two institutions were prospectively randomized to receive ultrasound-guided injections of their external oblique, internal oblique, and transversus abdominus muscles with either BTX (150 mL, 2 U/mL) or placebo (150-mL 0.9% NaCl). Patients were excluded if they had a body mass index of greater than 50, remained unstable or coagulopathic, were home O2 dependent, or had an existing neuromuscular disorder. Outcomes were assessed in a double-blinded manner. Univariate and Kaplan-Meier estimates of cumulative probability of abdominal closure were performed.

Results: We randomized 46 patients (24 BTX, 22 placebo). There were no significant differences in demographics, comorbidities, and physiologic status. Injections were performed on average 1.8 ± 2.8 days (range, 0-14 days) after DCL. The 10-day cumulative probability of primary fascial closure was similar between groups: 96% for BTX (95% confidence interval [CI], 72-99%) and 93% for placebo (95% CI, 61-99%) (HR, 1.0; 95% CI, 0.5-1.8). No difference between BTX and placebo groups was observed for hospital length of stay (37 days vs. 26 days, p = 0.30) or intensive care unit length of stay (17 days vs. 11 days, p = 0.27). There was no difference in median morphine equivalents following DCL. The overall complication rate was similar (63% vs. 68%, p = 0.69), with two deaths in the placebo group and none in the BTX group. No BTX or injection procedure complications were observed.

Conclusion: The use of BTX after DCL was safe but did not seem to affect primary fascial closure, hospital length of stay, or pain modulation after DCL. Given higher-than-expected rates of primary fascial closure, Type II error may have occurred.

Level Of Evidence: Therapeutic study, level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000000917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730909PMC
February 2016

Thrombin generation and procoagulant microparticle profiles after acute trauma: A prospective cohort study.

J Trauma Acute Care Surg 2015 Nov;79(5):726-31

From the Department of Trauma and Critical Care Surgery (M.S.P., D.H.J.), Department of Surgery (M.J.F., M.M.K., S.K.D.), Hematology Research (A.X., T.M.H.), Department of Health Sciences Research (G.M.S., W.S.H., K.V.B.), and Department of Internal Medicine (J.A.H.), Mayo Clinic, Rochester, Minnesota; and University of Birmingham Medical School (P.H.), Birmingham, United Kingdom.

Objective: The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma.

Methods: Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/μL) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]).

Results: Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7% male; 95% with blunt mechanism; mortality, 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/μL plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible "hypercoagulable state" (lag time ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible "hypocoagulable state" (lag time ≥ 18.6, peak height ≤ 17.8, and ttPeak ≥ 29.45) were not reached until 1 day to 3 days.

Conclusion: Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters.

Level Of Evidence: Epidemiologic study, level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000000839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621757PMC
November 2015

Clinical assessment of trauma-induced coagulopathy and its contribution to postinjury mortality: A TACTIC proposal.

J Trauma Acute Care Surg 2015 Sep;79(3):490-2

From the Department of Surgery (M.D.N., J.L.S., B.S.Z.), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Surgery (H.B.M., E.E.M.), University of Colorado Denver, Denver, Colorado; Department of Emergency Medicine (K.F.), University of Vermont, Burlington, Vermont; Department of Surgery (M.J.C.), University of California San Francisco, San Francisco, California; and Department of Surgery (M.S.P.), Mayo Clinic, Rochester, Minnesota.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000000793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292045PMC
September 2015

Direct medical costs attributable to venous thromboembolism among persons hospitalized for major operation: a population-based longitudinal study.

Surgery 2015 Mar 26;157(3):423-31. Epub 2015 Jan 26.

Division of Cardiovascular Diseases and Gonda Vascular Center, Department of Internal Medicine, Mayo Clinic, Rochester, MN; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN. Electronic address:

Background: We estimated medical costs attributable to venous thromboembolism (VTE) among patients currently or recently hospitalized for major operation.

Methods: Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN, residents with objectively diagnosed incident VTE within 92 days of hospitalization for major operation during an 18-year period, 1988-2005 (n = 355). One Olmsted County resident hospitalized for major operation without VTE was matched to each case on event date (±1 year), type of operation, duration of previous medical history, and active cancer status. Subjects were followed in Rochester Epidemiology Project provider-linked billing data for standardized, inflation-adjusted direct medical costs from 1 year before index (case's VTE event date and control's matched date) to earliest of death, emigration, or December 31, 2011. We used generalized linear modeling to predict costs for cases and controls and used bootstrapping methods to assess uncertainty and significance of mean adjusted cost differences.

Results: Adjusted mean predicted costs were more than 1.5-fold greater for cases ($55,956) than for controls ($32,718) (P ≤ .001) from index to up to 5 years postindex. Cost differences between cases and controls were greatest within the first 3 months after index (mean difference = $12,381). Costs were greater for cases than controls (mean difference = $10,797) from 3 months to up to 5 years postindex and together accounted for about half of the overall cost difference.

Conclusion: VTE during or after recent hospitalization for major operation contributes a substantial economic burden; VTE-attributable costs are greatest in the initial 3 months but persist for up to 5 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2014.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346535PMC
March 2015

Stability of tranexamic acid in 0.9% sodium chloride, stored in type 1 glass vials and ethylene/propylene copolymer plastic containers.

Int J Pharm Compd 2014 Sep-Oct;18(5):432-7

Mayo Clinic, Rochester, MN 55902, USA.

Tranexamic acid has recently been demonstrated to decrease all-cause mortality and deaths due to hemorrhage in trauma patients. The optimal administration of tranexamic acid is within one hour of injury, but not more than three hours from the time of injury. To aid with timely administration, a premixed solution of 1 gram tranexamic acid and 0.9% sodium chloride was proposed to be stocked as a medication in both the aeromedical transport helicopters and Emergency Department at Mayo Clinic Hospital--Rochester Saint Marys Campus. Since no published stability data exists for tranexamic acid diluted with 0.9% sodium chloride, this study was undertaken to determine the stability of tranexamic acid diluted with 0.9% sodium chloride while being stored in two types of containers. Stability was determined through the use of a stability-indicating high-performance liquid reverse phase chromatography assay, pH, and visual tests. Tranexamic acid solutions of 1 gram in 0.9% sodium chloride 65 mL were studied at predetermined intervals for 90 days in ethylene/propylene copolymer plastic containers, protected from light, and at both controlled room and refrigerated temperatures. Tranexamic acid solutions of 1 gram in 0.9% sodium chloride 50 mL were studied at predetermined intervals for 180 days in clear Type 1 borosilicate glass vials sealed with intact elastomeric, Flourotec-coated stoppers, stored protected from light at controlled room temperature. Solutions stored in the ethylene/propylene copolymer plastic containers at both storage temperatures maintained at least 98% of initial potency throughout the 90-day study period. Solutions stored in glass vials at controlled room temperature maintained at least 92% of initial potency throughout the 180-day study period. Visual and pH tests revealed stable, clear, colorless, and particulate-free solutions throughout the respective study periods.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2015

Transfusion of stored red blood cells in trauma patients is not associated with increased procoagulant microparticles.

J Trauma Acute Care Surg 2014 Nov;77(5):674-678

From the Departments of Trauma and Critical Care Surgery (S.K.D., M.L.H., D.H.J., M.S.P.), Health Sciences Research (J.K.R., W.S.H.), and Hematology Research (T.M.H.), Mayo Clinic, Rochester. Minnesota.

Background: We set out to determine the effects of transfusing stored red blood cells (RBCs) on the levels of procoagulant microparticles (MPs) in the blood of trauma patients.

Methods: Blood was drawn and processed to platelet poor plasma for MP analysis for 409 injured patients seen in the trauma bay from February 2011 to January 2013. Blood from 27 noninjured volunteers was also analyzed. Quantification of total procoagulant MP (per microliter plasma) using a direct plasma analysis via flow cytometry was performed. Demographic data, Injury Severity Score (ISS), overall mortality, and units of transfused packed RBCs were collected. Data are presented as median (interquartile range [IQR]). Transfusion groups were assessed using t test or Wilcoxon rank-sum test as appropriate. The α level was set as 0.05 for statistical significance.

Results: Median ISS was 12 (IQR, 5-19), 12% were transfused, median age was 48 years (IQR, 29-62 years), 68% were male, and overall mortality was 3%. Median units transfused were 3 (IQR, 2-5). The median number of all procoagulant MP was greater in trauma patients (median 758; IQR, 405-1,627) when compared with our control subjects (median, 232; IQR, 125-372; p < 0.0001). This difference remained significant after adjusting for age and sex (p < 0.0001). In 39 patients who had MP levels measured before transfusion with RBC, the procoagulant MP levels did not change after transfusion (p = 0.07). Patients transfused with RBCs that were 14 days or older did not have increased procoagulant MP levels when compared with those that received RBCs that were younger than 14 days (p = 0.5).This was also true for those who received RBCs that were 28 days or older when compared with those that received RBCs that were younger than 28 days (p = 0.84).

Conclusion: Procoagulant MP is significantly greater in trauma patients as compared with volunteers, even after adjusting for age and sex. We did not observe any change in the levels of procoagulant MPs after transfusion of stored RBCs.

Level Of Evidence: Epidemiologic/prognostic study, level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000000420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337406PMC
November 2014

The development and feasibility of a remote damage control resuscitation prehospital plasma transfusion protocol for warfarin reversal for patients with traumatic brain injury.

Transfusion 2013 Jan;53 Suppl 1:59S-64S

Department of Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.

Background: The rapid reversal of warfarin in the setting of traumatic brain injury (TBI) has been associated with improved outcomes. Until now, remote reversal of hypocoagulable states has not been possible in the prehospital environment. This manuscript describes the development and analysis of a prehospital plasma transfusion protocol to reverse warfarin at the earliest possible moment after TBI.

Study Design And Methods: A retrospective review of all TBI patients receiving plasma transfusion(s) in the prehospital environment for warfarin reversal between February 2009 and September 2010 was conducted. Thawed plasma was carried on every air ambulance flight centered at the main campus.

Results: A total of 2836 flights carried over 2500 units of thawed plasma throughout the study period. During this time, 16 patients received prehospital plasma resuscitation, five of who were on warfarin with a concurrent TBI. The median Injury Severity Score was 17 (8.5-27.5) with a median Glasgow Coma Score of 13 (8-15) and a mortality rate of 40%. A median of 2 (1.5-2.0) units of thawed plasma and 0 (0-0) units of RBCs were transfused en route. The pretransfusion point-of-care international normalized ratio improved from 3.1 (2.3-4.0) to 1.9 (1.3-3.6) upon trauma center admission (serum sample). One hundred percent of the transported, but unused, thawed plasma underwent subsequent transfusion prior to expiration.

Conclusions: Remote prehospital plasma transfusions effectively reverse anticoagulation secondary to warfarin administration in TBI patients. It is feasible to transfuse thawed plasma in the prehospital setting via remote damage control techniques without increasing waste. Prospective studies are needed to determine if this practice can improve outcomes in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.12037DOI Listing
January 2013

Quantification of hypercoagulable state after blunt trauma: microparticle and thrombin generation are increased relative to injury severity, while standard markers are not.

Surgery 2012 Jun 7;151(6):831-6. Epub 2012 Feb 7.

Department of Surgery, Mayo Clinic, Rochester, MN, USA.

Background: Major trauma is an independent risk factor for developing venous thromboembolism. While increases in thrombin generation and/or procoagulant microparticles have been detected in other patient groups at greater risk for venous thromboembolism, such as cancer or coronary artery disease, this association has yet to be documented in trauma patients. This pilot study was designed to characterize and quantify thrombin generation and plasma microparticles in individuals early after traumatic injury.

Methods: Blood was collected in the trauma bay from 52 blunt injured patients (cases) and 19 uninjured outpatients (controls) and processed to platelet poor plasma to allow for (1) isolation of microparticles for identification and quantification by flow cytometry, and (2) in vitro thrombin generation as measured by calibrated automatic thrombography. Data collected are expressed as either mean ± standard deviation or median with interquartile range.

Results: Among the cases, which included 39 men and 13 women (age, 40 ± 17 years), the injury severity score was 13 ± 11, the international normalized ratio was 1.0 ± 0.1, the thromboplastin time was 25 ± 3 seconds, and platelet count was 238 ± 62 (thousands). The numbers of total (cell type not specified) procoagulant microparticles, as measured by Annexin V staining, were increased compared to nontrauma controls (541 ± 139/μL and 155 ± 148/μL, respectively; P < .001). There was no significant difference in the amount of thrombin generated in trauma patients compared to controls; however, peak thrombin was correlated to injury severity (Spearman correlation coefficient R, 0.35; P = .02).

Conclusion: Patients with blunt trauma have greater numbers of circulating procoagulant microparticles and increased in vitro thrombin generation. Future studies to characterize the cell-specific profiles of microparticles and changes in thrombin generation kinetics after traumatic injury will determine whether microparticles contribute to the hypercoagulable state observed after injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2011.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356502PMC
June 2012

Comparison of massive blood transfusion predictive models in the rural setting.

J Trauma Acute Care Surg 2012 Jan;72(1):211-5

Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Background: Hemorrhage is the leading cause of preventable death in trauma patients, of which 3% require massive transfusion (MT). MT predictive models such as the Assessment of Blood Consumption (ABC), Trauma-Associated Severe Hemorrhage (TASH), and McLaughlin scores have been developed, but only included patients requiring blood transfusion during their hospital stay, excluding a large percentage of trauma patients. Our purpose was to validate these MT predictive models in our rural Level I trauma center patient population, using all major trauma victims, regardless of blood product requirements.

Methods: Review of all Level I trauma patients admitted in 2008 to 2009 was performed. ABC, TASH, and McLaughlin scores were calculated using 80% probability for the need for MT.

Results: Three hundred seventy-three patients were admitted; 13% had a penetrating mechanism and 52% were scene transports. MT patients had higher Injury Severity Score (median, 43 vs. 13; p < 0.001) and lower Trauma-Injury Severity Score (0.310 vs. 0.983; p < 0.001). Mortality was higher in MT patients (18.4% vs. 5.4%; p < 0.009). Thirty-eight (10%) required MT; 34 were predicted by ABC, one by TASH, and six by McLaughlin. ABC (area under the receiver operating characteristic [AUROC] = 0.86) was predictive of MT, whereas TASH (AUROC = 0.51) and McLaughlin (AUROC = 0.56) were not.

Conclusions: The ABC score correctly identified 89% of MT patients and was predictive of MT in major trauma patients at our rural Level I trauma center; the TASH and McLaughlin scores were not. The ABC score is simpler, faster, and more accurate. Based on this work, we strongly recommend adoption of the ABC score for MT prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e318240507bDOI Listing
January 2012

Differential expression of the immunoinflammatory response in trauma patients: burn vs. non-burn.

Burns 2012 Jun 21;38(4):599-606. Epub 2011 Nov 21.

U.S. Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA.

Rationale: Cytokines are central mediators of the immune-inflammatory response to injury and subsequent multiple organ dysfunction syndrome (MODS). Although previous studies evaluated cytokine levels after trauma, differences between patients with burn and non-burn trauma have not been assessed systematically.

Methods: A prospective database of trauma patients admitted between May 2004 and September 2007 to the burn or surgical intensive care units within 24 h of injury with an anticipated stay of at least 72 h was analyzed. Sequential clinical and laboratory parameters were collected in the first week, including multiplex analysis data for plasma levels of inflammatory cytokines (IL-6, and IL-8). Patients with known pre-injury coagulopathy were excluded. A Marshall score of 10 or greater was defined as MODS.

Results: A total of 179 patients were enrolled (67 burn and 112 non-burn). Plasma IL-6 and IL-8 levels were markedly elevated in both burn and non-burn patients compared to healthy volunteers. Burn subjects had higher levels of IL-6 and IL-8 than the non-burn on days 1 through 7 after injury. Subjects with burns and at least 30% total body surface area were older and had a lower injury severity score, a higher prevalence of MODS, and correspondingly higher mortality. Multivariate analysis of injury type, MODS, and time did not demonstrate an influence of MODS.

Conclusions: Burns were associated with a greater and more sustained immune-inflammatory response than non-burn trauma as evidenced by elevated plasma IL-6 and IL-8 levels during the first week. There was no association between MODS and plasma cytokine levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.burns.2011.10.013DOI Listing
June 2012

Factors associated with clinically significant head injury in children involved in motor vehicle crashes.

Traffic Inj Prev 2010 Dec;11(6):600-5

Department of Surgery and the Center for Injury Research and Prevention, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

Objective: Head injury is the most common cause of death for child occupants in motor vehicle crashes (MVCs). The morbidity associated with nonlethal MVC-related head injuries is of great clinical consequence as well. The purpose of this study was to identify the frequency of, and risk factors for, clinically significant head injury (CSHI) in child occupants in MVCs.

Methods: A large, child-specific crash surveillance system linking insurance claims data to telephone survey data was utilized. Qualifying crashes involved model year 1990 or newer vehicles in crashes with one or more child occupants (age 4 to 15 years) occurring in 15 U.S. states. Data were accrued between March 2000 and December 2007. A probability sample of crashes was selected for telephone survey with the driver of the insured vehicle. A clinically significant head injury, as reported by the child's parent using a validated survey, included concussions, skull fractures, and intracranial hemorrhages. Multivariate logistic regression was used to identify factors associated with a CSHI.

Results: During the period of study, completed interviews were obtained on 19,075 children aged 4-15, representing 318,527 children involved in 219,511 crashes. The overall rate of CSHI in child occupants was 1.08 percent. Factors associated with an increased risk of head injury included rollover (odds ratio [OR] = 8.60, 95% confidence interval [CI] 6.40-11.57) and near-side impact crashes (OR = 2.39, 95% CI 1.73-3.30) vs. frontal impact; lack of restraint (OR = 3.13, 95% CI 2.26-4.33) vs. restrained; and driver age < 25 years (OR = 1.43, 95% CI 1.12-1.81) vs. driver age ≥ 25 years. Some factors varied based on occupant age, and younger child age had a protective effect on the risk for head injury.

Conclusion: The risk of CSHI for 4- to 15-year-old child occupants was 1.08 percent. Several demographic and crash factors were associated with CSHI in child occupants. This information may help inform design safety initiatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15389588.2010.513072DOI Listing
December 2010

Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time.

J Trauma 2009 Aug;67(2):266-75; discussion 275-6

U S Army Institute of Surgical Research, Fort Sam Houston, Texas, USA.

Objectives: To investigate the hemostatic status of critically ill, nonbleeding trauma patients. We hypothesized that a hypercoagulable state exists in patients early after severe injury and that the pattern of clotting and fibrinolysis are similar between burned and nonburn trauma patients.

Materials: Patients admitted to the surgical or burn intensive care unit within 24 hours after injury were enrolled. Blood samples were drawn on days 0 through 7. Laboratory tests included prothrombin time (PT), activated partial thromboplastin time (aPTT), levels of activated factor XI, D-dimer, protein C percent activity, antithrombin III percent activity, and thromboelastography (TEG).

Results: Study subjects were enrolled from April 1, 2004, to May 31, 2005, and included nonburn trauma patients (n = 33), burned patients (n = 25), and healthy (control) subjects (n = 20). Despite aggressive thromboprophylaxis, three subjects (2 burned and 1 nonburn trauma patients [6%]) had pulmonary embolism during hospitalization. Compared with controls, all patients had prolonged PT and aPTT (p < 0.05). The rate of clot formation (alpha angle) and maximal clot strength were higher for patients compared with those of controls (p < 0.05), indicating a hypercoagulable state. Injured patients also had lower protein C and antithrombin III percent activities and higher fibrinogen levels (p < 0.05 for all). Activated factor XI was elevated in 38% of patients (control subjects had undetectable levels).

Discussion: Thromboelastography analysis of whole blood showed that patients were in a hypercoagulable state; this was not detected by plasma PT or aPTT. The high incidence of pulmonary embolism indicated that our current prophylaxis regimen could be improved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e3181ae6f1cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415284PMC
August 2009

Abdominal complications after severe burns.

J Am Coll Surg 2009 May 26;208(5):940-7; discussion 947-9. Epub 2009 Mar 26.

United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.

Background: Abdominal catastrophe in the severely burned patient without abdominal injury has been described. We perceived an alarming recent incidence of this complication in our burn center, both during acute resuscitation and later in the hospital course. We sought to define incidence, outcomes, and associated factors, such as excessive resuscitation volume and treatment issues.

Study Design: We examined all severely burned military and civilian patients with abdominal pathology between March 2003 and February 2008. Data included age, gender, total body surface area burn, inhalation injury, Injury Severity Score, disposition, resuscitation volume, time from injury to diagnosis, use of recombinant factor VIIa, vasopressors, and early tube feedings. We assembled a Delphi panel of surgeons experienced in abdominal catastrophes to review these data.

Results: Among 1,825 patients admitted to the US Army Institute of Surgical Research Burn Center, 120 (6.6%) were diagnosed with abdominal pathology (burn size 48% +/- 19%), of which 51 (2.8%) had abdominal catastrophe. The majority of these occurred in the first days after injury with associated abdominal compartment syndrome (32 of 51) and increased linearly to burn size. We noted another group of patients who presented primarily with ischemic bowel later in the course, with the same clinical presentation. Resuscitation volume was 6.02 mL/kg/percent total body surface area burned. Vasopressors were used in 71% of patients and tube feedings in 57% before diagnosis.

Conclusions: Abdominal catastrophe without abdominal trauma occurs in 2.8% of our population. Associated mortality was 78% without obvious cause. Delphi panel experts recommended more aggressive monitoring of abdominal compartment pressures and earlier operative management to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamcollsurg.2008.12.023DOI Listing
May 2009

Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients.

Ann Surg 2008 Sep;248(3):447-58

United States Army Institute of Surgical Research, Ft Sam Houston, TX 78234, USA.

Objective: To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization.

Summary Background Data: Civilian guidelines for massive transfusion (MT > or =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear.

Methods: Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed.

Results: Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (> or =1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (> or =1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio.

Conclusions: Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0b013e318185a9adDOI Listing
September 2008

Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs.

J Trauma 2008 Sep;65(3):535-43

The US Army Institute of Surgical Research, 3400 Rawley E. Chambers Avenue, Ft. Sam Houston, TX 78234, USA.

Background: Hypothermia and hemorrhagic shock contribute to coagulopathy after trauma. In this study, we investigated the independent and combined effects of hypothermia and hemorrhage with resuscitation on coagulation in swine and evaluated clinically relevant tests of coagulation.

Methods: Pigs (n = 24) were randomized into four groups of six animals each: sham control, hypothermia, hemorrhage with resuscitation, and hypothermia, hemorrhage with resuscitation combined. Hypothermia to 32 degrees C was induced with a cold blanket. Hemorrhage was induced by bleeding 35% of total blood volume followed by resuscitation with lactated Ringer's solution. Coagulation was assessed by thrombin generation, prothrombin time (PT), activated partial thromboplastin time (aPTT), activated clotting time (ACT), and thrombelastography (TEG) from blood samples taken at baseline and 4 hour after hypothermia and/or hemorrhage with resuscitation. Data were compared with analysis of variance.

Results: Baseline values were similar among groups. There were no changes in any measurements in the control group. Compared with baseline values, hemorrhage with resuscitation increased lactate to 140% +/- 15% (p < 0.05). Hypothermia decreased platelets to 73% +/- 3% (p < 0.05) with no effect on fibrinogen. Hemorrhage with resuscitation reduced platelets to 72% +/- 4% and fibrinogen to 71% +/- 3% (both p < 0.05), with similar decreases in platelets and fibrinogen observed in the combined group. Thrombin generation was decreased to 75% +/- 4% in hypothermia, 67% +/- 6% in hemorrhage with resuscitation, and 75% +/- 10% in the combined group (all p < 0.05). There were no significant changes in PT or aPTT by hemorrhage or hypothermia. ACT was prolonged to 122% +/- 1% in hypothermia, 111% +/- 4% in hemorrhage with resuscitation, and 127% +/- 3% in the combined group (all p < 0.05). Hypothermia prolonged the initial clotting time (R) and clot formation time (K), and decreased clotting rapidity (alpha) (all p < 0.05). Hemorrhage with resuscitation only decreased clot strength (maximum amplitude [MA], p < 0.05). TEG parameters in the combined group reflected the abnormal R, K, MA, and alpha observed in the other groups.

Conclusion: Hypothermia inhibited clotting times and clotting rate, whereas hemorrhage impaired clot strength. Combining hypothermia with hemorrhage impaired all these clotting parameters. PT, aPTT were not sensitive whereas ACT was not specific in detecting these coagulation defects. Only TEG differentiated mechanism related to clotting abnormalities, and thus may allow focused treatment of clotting alterations associated with hypothermia and hemorrhagic shock.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e31818379a6DOI Listing
September 2008

Global evacuation of burn patients does not increase the incidence of venous thromboembolic complications.

J Trauma 2008 Jul;65(1):19-24

Clinical Division, U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas, USA.

Background: Case-control studies have suggested that air travel may be a risk factor for the development of Venous Thromboembolism (VTE). Burned patients from the current war in Iraq and Afghanistan, are transported across three continents to our Burn Center with total ground and air transport time being approximately 24 hours spread over 3 days to 4 days. We hypothesized global evacuation results in increased VTE rates.

Methods: Retrospective review of 1,107 consecutive patients admitted to our burn center from January 2003 to December 2005.

Results: In the time period evaluated, no detectible differences were found in incidence of VTE between air-evacuated soldiers and those admitted to our facility from South Texas (1.31% vs. 0.83%, p = ns). The air-evacuated soldiers were younger (26 +/- 7 vs. 41 +/- 19, p < 0.0001) but had a higher incidence of inhalation injury (14.4% vs. 8.0%, p < 0.0001) and higher Injury Severity Score (10.9 +/- 13.0 vs. 6.5 +/- 9.2, p < 0.0001). No difference in average percent total body surface area involvement was found (15.8 +/- 19.4 vs. 15.5 +/- 18.4, p = ns). Overall, 11 of 1,107 (0.99%) burned patients developed VTE.

Conclusion: Prolonged global evacuation is not associated with increased risk of VTE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e3181271b8aDOI Listing
July 2008

A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries.

J Trauma 2008 Feb;64(2 Suppl):S64-8

Pittsburgh Tissue Engineering Initiative, Pittsburgh, Pennsylvania, USA.

Background: Bleeding is a major cause of death in patients with traumatic injuries. Recently, thrombelastography (TEG) has been suggested as an additional means of evaluating coagulation in trauma patients. We hypothesized that TEG data would aid in defining the coagulopathy of trauma in patients with penetrating traumatic injuries.

Methods: A retrospective study was performed of patients (n = 44) with penetrating injuries admitted to a combat support hospital during a 2-month period in 2004. Recorded data included standard laboratory data, TEG parameters, and blood product use in the first 24 hours after admission. Values were compared with clinically accepted ranges and those obtained from the Haemoscope Corporation.

Results: At admission, International Normalization Ratio, prothrombin time, and partial thromboplastin time were increased in 39% (>or=1.5), 31% (>16 seconds), and 37% (>40 seconds) of patients, respectively, suggesting hypocoagulation, but these variables did not correlate with the use of blood products (p > 0.05). TEG values obtained within 24 hours of admission (6 hours +/- 5.7 hours; median of 4.5 hours) demonstrated hypocoagulation based on delayed propagation of the clot (increased K time and reduced alpha-angle) and decreased clot strength (reduced maximal amplitude [MA]). MA correlated (r = 0.57, p < 0.01) with blood product use as well as platelet count (r = 0.61, p < 0.01). Patients with reduced MA (n = 23) used more blood products and had reduced platelet counts and hematocrit.

Conclusion: Thrombelastography was a more accurate indicator of blood product requirements in our patient population than prothrombin time, partial thromboplastin time, and International Normalization Ratio. Thrombelastography enhanced by platelet count and hematocrit can guide blood transfusion requirements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e318160772dDOI Listing
February 2008

Combining early coagulation and inflammatory status improves prediction of mortality in burned and nonburned trauma patients.

J Trauma 2008 Feb;64(2 Suppl):S188-94

US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA.

Background: After injury, there is a synergistic response between inflammation and coagulation systems. We hypothesized that combining markers of these processes and standard clinical indices would improve early prediction of in- hospital mortality in burned and nonburned trauma patients.

Methods: Patients admitted to the surgical or burn intensive care unit within 24 hours of injury with an anticipated stay >or=3 days were enrolled during a one year period. Upon admission, blood was drawn for thromboelastography, plasma-based clotting assays, and cytokine levels. Clinical indices and multiple organ dysfunction syndrome (MODS) scores were recorded. Candidate variables evaluated included age, percentage third degree burns, inhalation injury, percentage total body surface area burns, interleukin-6, tumor necrosis factor alpha, interleukin-8, prothrombin time, partial thromboplastin time (PTT), maximal amplitude reflective of clot strength, group (burn or nonburn) and admission MODS. Multiple logistic regression with stepwise selection and likelihood ratio test was performed to identify predictors for mortality. A receiver operating characteristic (ROC) curve was constructed to assess the diagnostic performance of identified predictors. Validation of the model with an additional cohort was performed.

Results: For model development, we enrolled 25 burned and 33 nonburned trauma patients (20 blunt and 13 penetrating injuries). Fifteen deaths occurred. Multiple logistic regression analysis identified six independent risk factors for death: age, percentage third degree burns, inhalation injury, tumor necrosis factor alpha level, maximal amplitude, and MODS score with an area under ROC curve of 0.961 (95% confidence interval: 0.891, 1.000, p < 0.05). The area under the ROC curve for the validation cohort (n = 66) was 0.936 (95% confidence interval: 0.875, 0.997, p < 0.001).

Conclusion: Our model improves prediction of in-hospital mortality in comparison to previous methods for burn and nonburn trauma patients. Furthermore, our model is equally applicable to all patients regardless of type of traumatic injury (nonburn or burn). This improvement is because of the inclusion of patient's early coagulation and inflammatory status in addition to standard clinical indices. These data provide a baseline within which to measure incremental improvements in care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e318160a5a3DOI Listing
February 2008

Continuous renal replacement therapy improves survival in severely burned military casualties with acute kidney injury.

J Trauma 2008 Feb;64(2 Suppl):S179-85; discussion S185-7

United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX 78234, USA.

Background: Acute kidney injury in severely burned patients is associated with high mortality. We wondered whether early use of continuous renal replacement therapy (CRRT) changes outcomes in severely burned military casualties with predetermined criteria for acute kidney injury.

Methods: Between November 2005 and June 2007, casualties admitted to our burn intensive care unit after sustaining burns in Iraq and Afghanistan, who subsequently developed acute kidney injury or circulatory shock or both, underwent CRRT. Baseline demographic, laboratory, and hemodynamic parameters were recorded. Both 28-day mortality and in- hospital mortality were evaluated and compared with a consecutive group of burn casualties with greater than 40% total body surface area (TBSA) burns, acute kidney injury, or nephrology consultation in the 2 years before the existence of our CRRT program.

Results: One hundred forty-seven severely burned military casualties were admitted to our intensive care unit before CRRT program initiation, and 102 were admitted after CRRT program initiation. Before the CRRT program, 16 patients were identified as having >40% TBSA burns with kidney injury with or without nephrology consultation (control group); 18 were treated with CRRT since (CRRT group). Groups were similar for %TBSA, %full-thickness TBSA, incidence of inhalation injury, blood urea nitrogen, creatinine, and Injury Severity Score. Of the CRRT patients, seven soldiers were treated for isolated acute kidney injury, whereas 11 were treated for a combination of acute kidney injury and shock. The dose of therapy was 50.2 +/- 13 mL/kg/h with a treatment course of 5.2 +/- 3 days. Of the 11 patients in the CRRT group treated for shock, eight were off vasopressors by 24 hours and the remaining three within 48 hours. None of the patients in the control group were placed on renal replacement therapy with nephrology consultation in eight patients. Both 28-day mortality (22% vs. 75%, p = 0.002) and in-hospital mortality (56% vs. 88%, p = 0.04) were lower in the CRRT group compared with that in the control group.

Conclusion: Aggressive application of CRRT in severely burned casualties with kidney injury significantly improves survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0b013e3181608676DOI Listing
February 2008
-->