Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel.

Bleeding is the most common complication of anticoagulant use. The evaluation and management of the bleeding patient is a core competency of emergency medicine. As the prevalence of patients receiving anticoagulant agents and variety of anticoagulants with different mechanisms of action, pharmacokinetics, indications, and corresponding reversal agents increase, physicians and other clinicians working in the emergency department require a current and nuanced understanding of how best to assess, treat, and reverse anticoagulated patients. In this project, we convened an expert panel to create a consensus decision tree and framework for assessment of the bleeding patient receiving an anticoagulant, as well as use of anticoagulant reversal or coagulation factor replacement, and to address controversies and gaps relevant to this topic. To support decision tree interpretation, the panel also reached agreement on key definitions of life-threatening bleeding, bleeding at a critical site, and emergency surgery or urgent invasive procedure. To reach consensus recommendations, we used a structured literature review and a modified Delphi technique by an expert panel of academic and community physicians with training in emergency medicine, cardiology, hematology, internal medicine/thrombology, pharmacology, toxicology, transfusion medicine and hemostasis, neurology, and surgery, and by other key stakeholder groups.

Pre-analytical practices for routine coagulation tests in European laboratories. A collaborative study from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM).

Background Correct handling and storage of blood samples for coagulation tests are important to assure correct diagnosis and monitoring. The aim of this study was to assess the pre-analytical practices for routine coagulation testing in European laboratories. Methods In 2013-2014, European laboratories were invited to fill in a questionnaire addressing pre-analytical requirements regarding tube fill volume, citrate concentration, sample stability, centrifugation and storage conditions for routine coagulation testing (activated partial thromboplastin time [APTT], prothrombin time in seconds [PT-sec] and as international normalised ratio [PT-INR] and fibrinogen). Results A total of 662 laboratories from 28 different countries responded. The recommended 3.2% (105-109 mmol/L) citrate tubes are used by 74% of the laboratories. Tube fill volumes ≥90% were required by 73%-76% of the laboratories, depending upon the coagulation test and tube size. The variation in centrifugation force and duration was large (median 2500 g [10- and 90-percentiles 1500 and 4000] and 10 min [5 and 15], respectively). Large variations were also seen in the accepted storage time for different tests and sample materials, for example, for citrated blood at room temperature the accepted storage time ranged from 0.5-72 h and 0.5-189 h for PT-INR and fibrinogen, respectively. If the storage time or the tube fill requirements are not fulfilled, 72% and 84% of the respondents, respectively, would reject the samples. Conclusions There was a large variation in pre-analytical practices for routine coagulation testing in European laboratories, especially for centrifugation conditions and storage time requirements.

Osteomyelitis: A Context for Wound Management.

GENERAL PURPOSE: To provide an overview of osteomyelitis. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After completing this continuing education activity, you should be able to:1. Distinguish the pathogenesis of osteomyelitis in children and adults.2. Identify practical considerations for diagnosis and evidence-based treatment of osteomyelitis. ABSTRACT: This educational activity reviews the pathogenesis of osteomyelitis and discusses practical considerations for diagnosis, treatment, and functional rehabilitation of pediatric and adult patients with osteomyelitic wounds. Antibiotic, surgical, and adjunctive treatments will be addressed. Emphasis is placed on consulting with infectious disease specialists and using evidence-based guidelines for antibiotic prescribing.

Salt Disproportionation in the Solid State: Role of Solubility and Counterion Volatility.

Disproportionation propensity of salts (HCl, HBr, heminapadisylate) and adipic acid cocrystal of corticotropin releasing hormone receptor-1 antagonist was studied using model free kinetics. Using thermogravimetic weight loss profile or heat flow curves from differential scanning calorimetry, an activation energy plot for salts and cocrystal was generated based on model free kinetics. This activation energy of disproportionation provided qualitative information about the solid state salt stability. To ensure the stability throughout the shelf life, "prototype" formulations of salts and cocrystal in tablet form were stored at 40 °C and several water vapor pressures. Disproportionation kinetics were studied in these prototype tablet formulations using two-dimensional X-ray diffractometry. Formulations containing the adipic acid cocrystal or heminapadisylate salt did not show disproportionation of API when stored at 40 °C/75% RH for 300 days. On the other hand, formulations containing HCl or HBr salt disproportionated. Though isostructural, the disproportionation propensity of HBr and HCl salts was quite different. The HCl salt highlighted the important role that volatility of the counterion plays in the physical stability of the formulations. Solution state stability (i.e., in dissolution medium) of salts and cocrystal was also assessed and compared with solid state stability, by determining their solubility at different pH's, and intrinsic dissolution rate.

Bridging the gap between point-of-care testing and laboratory testing in hemostasis.

Point-of-care (POC) testing within hemostasis is an expanding field, with the most widely used test being POC international normalized ratio (INR). Many of these devices are being used in a nonlaboratory setting by staff with no laboratory training. In the United Kingdom, external quality assessment (EQA) is provided by the organization UK National External Quality Assessment Scheme for Blood Coagulation (UK NEQAS BC). Participants within the UK NEQAS BC POC INR program are largely based in primary care (77%), with the majority of EQA samples and patients tests being performed by nurses (70%). Many of these centers do not have support from the laboratory staff and may, therefore, not understand the requirement for a robust quality control (QC) system comprising both internal quality control (IQC) and EQA. From data acquired through a questionnaire of these UK NEQAS BC users, we observed that 2% of the centers never perform IQC tests, only 29% perform IQC tests when starting a new batch of test strips, and just 15% carry out IQC with each clinic as recommended by the UK guidelines. The imprecision of EQA tests was greater for POC users than in the UK NEQAS BC hospital laboratory program, with average coefficients of variation for a 2-year period of 11.0 and 7.3%, respectively. This may reflect the handling of EQA samples rather than the imprecision of the method, due to the lack of laboratory training amongst POC staff. POC INR in the UK could greatly benefit from more interaction and support from laboratories to these POC testers.

Prevalence of Trauma-Induced Hypocalcemia in the Prehospital Setting.

BACKGROUND: Recent data published by the Special Operations community suggest the Lethal Triad of Trauma should be changed to the Lethal Diamond, to include coagulopathy, acidosis, hypothermia, and hypocalcemia. The purpose of this study is to determine the prevalence of trauma-induced hypocalcemia in level I and II trauma patients. METHODS: This is a retrospective cohort study conducted at a level I trauma center and Special Operations Combat Medic (SOCM) training site. Adult patients were identified via trauma services registry from September 2021 to April 2022. Patients who received blood products prior to emergency department (ED) arrival were excluded from the study. Ionized calcium levels were utilized in this study. RESULTS: Of the 408 patients screened, 370 were included in the final analysis of this cohort. Hypocalcemia was noted in 189 (51%) patients, with severe hypocalcemia identified in two (<1%) patients. Thirty-two (11.2%) patients had elevated international normalized ratio (INR), 34 (23%) patients had pH <7.36, 21 (8%) patients had elevated lactic acid, and 9 (2.5%) patients had a temperature of <35°C. CONCLUSION: Hypocalcemia was prevalent in half of the trauma patients in this cohort. The administration of a calcium supplement empirically in trauma patients from the prehospital environment and prior to blood transfusion is not recommended until further data prove it beneficial.

Examining Food Security, Choices and Barriers among Community Supported Agriculture participants during COVID- 19 in Kentucky.

The coronavirus disease (COVID-19) pandemic is challenging food security. Our study's purpose was to examine relationships among food security status, eating patterns and perceived barriers to food choices among shareholders (N= 209) in a Community Supported Agriculture (CSA) program during stay-at-home restrictions due to the pandemic. The food insecure group (n= 33) reported lower consumption of fruits/vegetables, whole grains and greater consumption of fast foods and more barriers to food choices compared to the food secure group (p<.05). A low food insecure proportion (16%) among the CSA participants suggests a potential role of a CSA program to prevent food insecurity.

A teaching encounter card to evaluate clinical supervisors across clerkship rotations.

BACKGROUND: Evaluation of faculty teaching is critical to improving the educational experience for both students and faculty. AIM: Our objectives were to implement an evaluation system, using the teaching encounter card, across multiple rotations in the clerkship and determine the feasibility, reliability and validity of this evaluation tool in this expanded setting. METHODS: Students were asked to rate clinical supervisors on nine teaching behaviours using a 6-point rating scale and asked whether they would like to nominate the teacher for a clinical teaching award. RESULTS: A total of 3971 cards for 587 clinical supervisors across seven clerkship rotations were analyzed. There was an average of 7.3 cards per supervisor (median = 5, range 2-66). There was high internal consistency between items on the card (Cronbach's alpha 0.965). The reliability was fair at 0.63. Seventeen cards per supervisor would be required to achieve a reliability >0.8 (G study). Ratings were higher for encounters that occurred in the operating room and within the anaesthesia rotation. The teachers who had a positive recommendation for teaching award nomination received higher scores than their colleagues. CONCLUSION: We successfully implemented a faculty evaluation card across clerkship rotations that was flexible enough to use in multiple learning environments and allowed the identification of outstanding clinical teachers.

Supravalvular aortic membrane with severe aortic regurgitation: an unusual presentation in adults.

Aortic stenosis due to supravalvular membrane usually presents in children. It may be associated with fusion of the left coronary leaflet and the supravalvular membrane, causing obstruction of the left coronary ostium, and resulting in myocardial ischemia. Despite the immobilization of the left coronary leaflet, these patients present in childhood with aortic stenosis and not regurgitation, with or without accompanying myocardial ischemia. The case is described of an adult patient with supravalvular aortic membrane presenting with severe aortic regurgitation and myocardial infarction due to fusion of the left coronary leaflet with the supravalvular membrane.

Left atrial volume measurement with automated border detection by 3-dimensional echocardiography: comparison with Magnetic Resonance Imaging.

OBJECTIVE: Left atrial size is an important marker for adverse cardiovascular events. There is general consensus that left atrial volume index (LAVI) is the best measurement of size. The current LAVI measurement techniques are laborious. Semi-automated measurement with a 3-dimensional echocardiography (3DE) system may be a practical clinical alternative to measure LAVI, but it has not been adequately evaluated against Magnetic Resonance Imaging (MRI) gold standard. The aim of this study was to compare the accuracy of a commercially available 3D algorithm for measurement of LAVI against LAVI obtained from MRI and Area Length Method (ALM). DESIGN: In 27 consecutive subjects referred for cardiac MRI (age 54 +/- 13 years, 63% male), LAVI was measured using 3 imaging modalities: 3DE, ALM, MRI and the results were correlated. ALM was measured using standard American Society of Echocardiography guidelines. The time required to measure LAVI by 3DE and ALM were compared. RESULTS: There was a significant correlation in systolic and diastolic LA volumes and left atrial ejection fraction between 3DE and MRI (r = 0.86 for systole, r = 0.76 for diastole, r = 0.88 for ejection fraction, P < 0.0001 for all). There was also significant correlation of diastolic volumes between 3DE and ALM (r = 0.77, P < 0.0001). The time to obtain LAVI was shorter using 3DE versus ALM (56 +/- 8 vs 135 +/- 55 seconds, P < 0.0001). CONCLUSION: Three-dimensional echocardiography with semiautomatic border detection is a practical alternative for obtaining the left atrial volume in a time-efficient manner compared to the current standard.

Optimizing photophoresis and asymmetric force fields for grading of Brownian particles.

We discuss a scheme that incorporates restricted spatial input location, orthogonal sort, and movement direction features, with particle sorting achieved by using an asymmetric potential cycled on and off, while movement is accomplished by photophoresis. Careful investigation has uncovered the odds of sorting between certain pairs of particle sizes to be solely dependent on radii in each phase of the process. This means that the most effective overall sorting can be achieved by maximizing the number of phases. This optimized approach is demonstrated using numerical simulation to permit grading of a range of nanometer-scale particle sizes.

The importance of commutability in material used for quality control purposes.

External Quality Assessment (EQA) is an important part of laboratory quality assurance. Spiking of normal plasma is sometimes employed to mimic clinical samples. It is important that spiked material gives similar results to clinical samples (ie, is commutable) to ensure appropriate conclusions can be drawn from EQA exercises. We describe here data from UK National External Quality Assessment Scheme for Blood Coagulation (NEQAS BC) exercises where spiked samples were tested alongside samples from patients to explore commutability of artificial material. Normal plasma was spiked with unfractionated heparin (UFH), low molecular weight heparin (LMWH), Dabigatran or Rivaroxaban. Factor VIII (FVIII) deficient plasma was spiked with FVIII concentrate. Spiked samples and ex vivo patient material were sent to laboratories for testing. For LMWH, good agreement was seen between results for samples from patient plasma and plasma spiked with heparin. For UFH, APTT ratios differed between spiked and patient samples for the same drug concentration, with no correlation in ranking of reagents. Precision for patient and spiked material for Rivaroxaban and Dabigatran assays was comparable. However, the pattern of results for some Dabigatran assay kits differed between spiked and patient samples. For FVIII assays, results obtained with spiked and postinfusion samples gave comparable results. Spiked material is suitable for EQA if commutability is demonstrated. Our data show commutability for plasma spiked with Rivaroxaban, LWMH and some FVIII concentrates. For some tests, notably APTT for UFH, marked differences between patient and spiked samples indicate not all tests can be evaluated using artificial samples.

Clotting and chromogenic factor VIII assay variability in post-infusion and spiked samples containing full-length recombinant FVIII or recombinant factor VIII Fc fusion protein (rFVIIIFc).

INTRODUCTION: Variability in FVIII measurement is a recognized problem. There are limited data for samples containing recombinant Factor VIII Fc fusion protein (rFVIIIFc). Many studies use samples for which factor concentrate has been spiked into FVIII deficient plasma in vitro. This approach requires validation. AIM/METHODS: Four samples were distributed in a UK National External Quality Assessment Scheme for Blood Coagulation (NEQAS BC) survey. One contained Advate (full-length recombinant FVIII) (rFVIII) added to FVIII deficient plasma, one was from a severe haemophilia A patient after infusion of Advate, one was prepared by addition of rFVIIIFc (marketed as Elocta/Eloctate) to FVIII deficient plasma and the fourth was collected from a severe haemophilia A patient following rFVIIIFc (Eloctate) infusion. Fifty-three haemophilia centres (UK and Scandinavia) performed one-stage FVIII assays and 27 performed chromogenic FVIII assays. RESULTS/CONCLUSIONS: One-stage assays gave significantly lower results than chromogenic assays by 7% (P < 0.01) and 13%(P < 0.001) for post-Advate and Advate spiked samples, and by 22% (P < 0.001) and 23% (P < 0.001) for post-rFVIIIFc and rFVIIIFc spiked samples. The interlaboratory variation was similar for all samples, with CVs of 12%-16% (chromogenic) and 10%-13% (one stage). The data indicate that either product can be safely monitored by one-stage or chromogenic assay. Spiked samples behaved in a similar way to post-infusion samples for both products and could be substituted for post-infusion samples for use in proficiency testing exercises (ie, samples were commutable).

Intraventricular dyssynchrony in light chain amyloidosis: a new mechanism of systolic dysfunction assessed by 3-dimensional echocardiography.

BACKGROUND: Light chain amyloidosis (AL) is a rare but often fatal disease due to intractable heart failure. Amyloid deposition leads to diastolic dysfunction and often preserved ejection fraction. We hypothesize that AL is associated with regional systolic dyssynchrony. The aim is to compare left ventricular (LV) regional synchrony in AL subjects versus healthy controls using 16-segment dyssynchrony index measured from 3-dimension-al (3D) echocardiography. METHODS: Cardiac 3D echocardiography full volumes were acquired in 10 biopsy-proven AL subjects (60 +/- 3 years, 5 females) and 10 healthy controls (52 +/- 1 years, 5 females). The LV was subdivided into 16 segments and the time from end-diastole to the minimal systolic volume for each of the 16 segments was expressed as a percent of the cycle length. The standard deviations of these times provided a 16-segment dyssynchrony index (16-SD%). 16-SD% was compared between healthy and AL subjects. RESULTS: Left ventricular ejection fraction was comparable (control vs. AL: 62.4 +/- 0.6 vs. 58.6 +/- 2.8%, p = NS). 16-SD% was significantly higher in AL versus healthy subjects (5.93 +/- 4.4 vs. 1.67 +/- 0.87%, p = 0.003). 16-SD% correlated with left ventricular mass index (R 0.45, p = 0.04) but not to left ventricular ejection fraction. CONCLUSION: Light chain amyloidosis is associated with left ventricular regional systolic dyssynchrony. Regional dyssynchrony may be an unrecognized mechanism of heart failure in AL subjects.

Complications after fasciotomy revision and delayed compartment release in combat patients.

BACKGROUND: Incomplete or delayed fasciotomies are associated with muscle necrosis and death in civilian trauma. Combat explosions severely damage tissue and distort normal anatomy making fasciotomies challenging. Rapid air evacuation may delay treatment of patients with evolving extremity compartment syndrome. We investigated the impact of fasciotomy revision and delayed compartment release on combat casualties after air evacuation. METHODS: A retrospective review was performed of combat casualties who underwent fasciotomies in Iraq, Afghanistan, or at Landstuhl Regional Medical Center between January 1, 2005 and August 31, 2006. Outcomes were rates of muscle excision, major amputation, and mortality. RESULTS: A total of 336 patients underwent 643 fasciotomies. Most were to the lower leg (49%) and forearm (23%). Patients who underwent a fasciotomy revision had higher rates of muscle excision (35% vs. 9%, p < 0.01) and mortality (20% vs. 6%, p < 0.01) than those who did not receive a revision. The anterior and deep compartments of the lower leg were the most commonly unopened. Patients who underwent fasciotomy after evacuation had higher rates of muscle excision (25% vs. 11%), amputation (31 vs. 15%), and mortality (19% vs. 5%) than patients who received their fasciotomies in the combat theater (p < 0.01). Patients who underwent revisions or delayed fasciotomies had higher Injury Severity Score and larger burns as well as lower systolic blood pressure, acidosis, and more pressor use during air evacuation. These patients also received more blood products at Landstuhl Regional Medical Center. CONCLUSION: Fasciotomy revision was associated with a fourfold increase in mortality. The most common revision procedures were extension of fascial incisions and opening new compartments. The most commonly unopened compartment was the anterior compartment of the lower leg. Patients who underwent delayed fasciotomies had twice the rate of major amputation and a threefold higher mortality.

Use of saline contrast echo timing to distinguish intracardiac and extracardiac shunts: failure of the 3- to 5-beat rule.

Patent foramen ovale (PFO) is thought to be associated with cryptogenic stroke and migraine headache. Saline contrast echocardiography (SCE) is the gold standard for identifying the presence of right-to-left shunt, whether from PFO or pulmonary arteriovenous malformation (PAVM). The timing of left heart contrast entry during SCE is used to distinguish a PFO from a PAVM, a method that is not as specific as previously thought. In this report, we describe a patient with a SCE demonstrating the early appearance of left heart bubbles during good effort Valsalva injections that is ultimately proven to be due to a PAVM. The case illustrates the limited specificity of left heart contrast timing during SCE as the sole criteria for differentiating intracardiac and extracardiac shunts.

Spontaneous Rupture of Sinus of Valsalva Aneurysm Presenting as Perivalvular Hematoma.

Acute rupture of sinus of Valsalva often presents as an acute emergency with significant hemodynamic compromise whereas contained rupture of sinus of Valsalva with a perivalvular hematoma formation is rarely seen. We describe the case of a 63-year-old male who presented with acute shortness of breath and was found to have rupture of sinus of Valsalva aneurysm (SVA) with a perivalvular hematoma and severe aortic regurgitation. We also review the presentation, diagnosis, and management of SVAs.

Differential sensitivity of von Willebrand factor activity assays to reduced VWF molecular weight forms: A large international cross-laboratory study.

INTRODUCTION: von Willebrand disease (VWD), the most common inherited bleeding disorder, is due to deficiencies/defects in von Willebrand factor (VWF). Effective diagnosis requires testing for FVIII, VWF antigen and one or more VWF 'activity' assays. Classically, 'activity' is assessed using ristocetin cofactor (VWF:RCo), but collagen binding (VWF:CB) and/or other assays are used by many laboratories. This extensive international cross-laboratory study has specifically evaluated contemporary VWF activity assays for comparative sensitivity to reduction in high molecular weight (HMW) VWF, and their ability to differentiate type 1 vs 2A VWD-like samples. MATERIALS AND METHODS: A set of four samples representing step wise reduction in HMW VWF were tested by over 400 laboratories worldwide using various assays. A second set of two samples representing type 1 or type 2A VWD-like plasma was tested by a subset of 251 laboratories. RESULTS: Combined data identified some differences between VWF activity assays, with sensitivity for reduction of HMW being highest for VWF:CB and VWF:GPIbM, intermediate for VWF:RCo and VWF:GPIbR, and lowest for VWF:Ab. 'Within' method analysis identified the Stago method as the most sensitive VWF:CB assay. A large variation in inter-laboratory CV (e.g., 7-24% for the normal sample) was also demonstrated for various methods. Although performance of various methods differed significantly, most laboratories correctly differentiated between type 1 and 2 samples, irrespective of VWF activity assay employed. CONCLUSIONS: These results hold significant clinical implications for diagnosis and therapy monitoring of VWD, as well as potential future diagnosis and therapy monitoring of thrombotic thrombocytopenic purpura (TTP).