Publications by authors named "Michael J Ferrara"

8 Publications

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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.
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August 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.
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March 2021

Principles and Strategies for Effective Teaching: A Workshop for Pre- and Postdoctoral Trainees in the Biomedical Sciences.

J Microbiol Biol Educ 2019 18;20(3). Epub 2019 Dec 18.

University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045.

The 2012 National Institutes of Health (NIH) Biomedical Workforce Working Group Report documented that graduate training in the biomedical sciences predominantly prepares people for academic research positions. The report recommended that NIH provide funds for institutions to develop broader career development opportunities, including training related to teaching. Indeed, teaching is not only a required component of any faculty position, it is the primary task for trainees who seek employment at small liberal arts colleges and other primarily undergraduate institutions. NIH funding for the BEST (Broadening Experiences in Scientific Training) programs allowed us to develop a six-week training workshop for bioscience trainees to introduce participants to research-based, student-centered pedagogies and instructional design techniques and to inspire them to view teaching as an intellectual endeavor. The methods and outcomes of our case study should be applicable in a variety of programs and organizations, especially those with a separate health science campus, where faculty mentors often do not teach many classes and there are few, if any, apprenticeship-teaching opportunities for trainees.
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December 2019

What is the effect of a decision aid in potentially vulnerable parents? Insights from the head CT choice randomized trial.

Health Expect 2020 02 23;23(1):63-74. Epub 2019 Nov 23.

Department of Emergency Medicine, Mayo Clinic, Rochester, MN, USA.

Objective: To test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust.

Methods: This was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy-two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site.

Results: The decision aid did not increase knowledge more in parents with high numeracy (P for interaction [P ] = 0.14) or physician trust more in parents with low health literacy (P  = 0.34). The decision aid decreased decisional conflict more in non-white parents (decisional conflict scale, -8.14, 95% CI: -12.33 to -3.95; P  = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35-14.83; P  = 0.04).

Conclusions: Use of the Head CT Choice decision aid resulted in less decisional conflict in non-white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents.
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February 2020

Effect of the Head Computed Tomography Choice Decision Aid in Parents of Children With Minor Head Trauma: A Cluster Randomized Trial.

JAMA Netw Open 2018 09 7;1(5):e182430. Epub 2018 Sep 7.

Department of Pediatric Emergency Medicine, Children's Hospitals and Clinics of Minnesota, Minneapolis.

Importance: The Pediatric Emergency Care Applied Research Network prediction rules for minor head trauma identify children at very low, intermediate, and high risk of clinically important traumatic brain injuries (ciTBIs) and recommend no computed tomography (CT) for those at very low risk. However, the prediction rules provide little guidance in the choice of home observation or CT in children at intermediate risk for ciTBI.

Objective: To compare a decision aid with usual care in parents of children at intermediate risk for ciTBI.

Design, Settings, And Participants: This cluster randomized trial was conducted in 7 geographically diverse US emergency departments (EDs) from April 1, 2014, to September 30, 2016. Eligible participants were emergency clinicians, children ages 2 to 18 years with minor head trauma at intermediate risk for ciTBI, and their parents.

Interventions: Clinicians were randomly assigned (1:1 ratio) to shared decision-making facilitated by the Head CT Choice decision aid or to usual care.

Main Outcomes And Measures: The primary outcome, selected by parent stakeholders, was knowledge of their child's risk for ciTBI and the available diagnostic options. Secondary outcomes included decisional conflict, parental involvement in decision-making, the ED CT rate, 7-day health care utilization, and missed ciTBI.

Results: A total of 172 clinicians caring for 971 children (493 decision aid; 478 usual care) with minor head trauma at intermediate risk for ciTBI were enrolled. The patient mean (SD) age was 6.7 (7.1) years, 575 (59%) were male, and 253 (26%) were of nonwhite race. Parents in the decision aid arm compared with the usual care arm had greater knowledge (mean [SD] questions correct: 6.2 [2.0] vs 5.3 [2.0]; mean difference, 0.9; 95% CI, 0.6-1.3), had less decisional conflict (mean [SD] decisional conflict score, 14.8 [15.5] vs 19.2 [16.6]; mean difference, -4.4; 95% CI, -7.3 to -2.4), and were more involved in CT decision-making (observing patient involvement [OPTION] scores: mean [SD], 25.0 [8.5] vs 13.3 [6.5]; mean difference, 11.7; 95% CI, 9.6-13.9). Although the ED CT rate did not significantly differ (decision aid, 22% vs usual care, 24%; odds ratio, 0.81; 95% CI, 0.51-1.27), the mean number of imaging tests was lower in the decision aid arm 7 days after injury. No child had a missed ciTBI.

Conclusions And Relevance: Use of a decision aid in parents of children at intermediate risk of ciTBI increased parent knowledge, decreased decisional conflict, and increased involvement in decision-making. The intervention did not significantly reduce the ED CT rate but safely decreased health care utilization 7 days after injury.

Trial Registration: Identifier: NCT02063087.
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September 2018

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.
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September 2017

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.
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November 2015

Immediate post-resection diabetes mellitus after pancreaticoduodenectomy: incidence and risk factors.

HPB (Oxford) 2013 Mar 10;15(3):170-4. Epub 2012 Sep 10.

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

Background: New-onset diabetes mellitus after a pancreaticoduodenectomy (PD) remains poorly defined. The aim of this study was to define the incidence and predictive factors of immediate post-resection diabetes mellitus (iPRDM).

Methods: Retrospective review of patients undergoing PD from January 2004 through to July 2010. Immediate post-resection diabetes mellitus was defined as diabetes requiring pharmacological treatment within 30 days post-operatively. Logistic regression was conducted to identify factors predictive of iPRDM.

Results: Of 778 patients undergoing PD, 214 were excluded owing to pre-operative diabetes (n= 192), declined research authorization (n= 14) or death prior to hospital discharge (n= 8); the remaining 564 patients comprised the study population. iPRDM occurred in 22 patients (4%) who were more likely to be male, have pre-operative glucose intolerance, or an increased creatinine, body mass index (BMI), pre-operative glucose, operative time, tumour size or specimen length compared with patients without iPRDM (P < 0.05). On multivariate analysis, pre-operative impaired glucose intolerance (P < 0.001), pre-operative glucose ≥ 126 (P < 0.001) and specimen length (P= 0.002) were independent predictors of iPRDM. A predictive model using these three factors demonstrated a c-index of 0.842.

Discussion: New-onset, post-resection diabetes occurs in 4% of patients undergoing PD. Factors predictive of iPRDM include pre-operative glucose intolerance, elevated pre-operative glucose and increased specimen length. These data are important for patient education and predicting outcomes after PD.
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March 2013