Current Strategies for the Management of Bleeding Associated with Direct Oral Anticoagulants and a Review of Investigational Reversal Agents.

BACKGROUND: The management of life-threatening bleeding in patients who are receiving direct oral anticoagulants (DOACs) is a serious medical concern. OBJECTIVE: This review provides a concise, balanced overview of the current and future approaches for reversing the anticoagulation effects of DOACs, particularly factor Xa (FXa) inhibitors. DISCUSSION: The anticoagulant activity of the direct thrombin inhibitor dabigatran can be reversed by idarucizumab, but until recently, options for the management of major bleeding in patients who were receiving FXa inhibitors were limited to nonspecific strategies, including supplementation of clotting factors with prothrombin complex concentrates (PCCs) or activated PCCs for attenuating anticoagulation effects. They appear as a treatment option in many hospital guidelines despite the lack of approval by the U.S. Food and Drug Administration and the lack of rigorous medical evidence supporting their use in this setting. The development of specific reversal agents may provide improved strategies for the management of bleeding. Andexanet alfa is a modified FXa molecule approved in the United States to reverse the anticoagulant effects of FXa inhibitors (rivaroxaban and apixaban) in patients with life-threatening or uncontrolled bleeding. Ciraparantag is a small-molecule inhibitor of multiple anticoagulants that has been investigated in healthy subjects. CONCLUSION: The current guidelines for management of DOAC-associated bleeding are being updated to reflect that the reversal agent for rivaroxaban and apixaban is now available. For other FXa inhibitors, in the absence of a reversal agent, nonspecific strategies that include PCCs are recommended. The population of patients anticoagulated with DOACs is growing, and we hope that specific reversal agents will improve the approach to management of major bleeding in this population.

Emergency Reversal of Anticoagulation.

Owing to the propensity of anticoagulated patients to bleed, a strategy for reversal of anticoagulation induced by any of the common agents is essential. Many patients are anticoagulated with a variety of agents, including warfarin, low molecular weight heparin, and the direct oral anticoagulants such as factor Xa and factor IIa inhibitors. Patients may also be using antiplatelet agents. Recommendations to reverse bleeding in these patients are constantly evolving with the recent development of specific reversal agents. A working knowledge of hemostasis and the reversal of anticoagulation and antiplatelet drugs is required for every emergency department provider. This article reviews these topics and presents the currently recommended strategies for dealing with bleeding in the anticoagulated patient.

Hyperbaric oxygen: applications in infectious disease.

This article reviews the applications of hyperbaric oxygen (HBO) as an adjunctive treatment of certain infectious processes. Infections for which HBO has been studied and is recommended by the Undersea and Hyperbaric Medicine Society include necrotizing fasciitis, gas gangrene, chronic refractory osteomyelitis (including malignant otitis externa), mucormycosis, intracranial abscesses, and diabetic foot ulcers that have concomitant infections. In all of these processes, HBO is used adjunctively along with antimicrobial agents and aggressive surgical debridement. This article describes the details of each infection and the research that supports the use of HBO.

Rapid Fire: Acute Blast Crisis/Hyperviscosity Syndrome.

Emergency providers are likely to encounter patients with acute and chronic leukemias. In some cases, the first presentation to the emergency department may be for symptoms related to blast crisis and leukostasis. Making a timely diagnosis and consulting a hematologist can be life saving. Presenting symptoms are caused by complications of bone marrow infiltration and hyperleukocytosis with white blood cell counts over 100,000. Presentations may include fatigue (anemia), bleeding (thrombocytopenia), shortness of breath, and/or neurologic symptoms owing to hyperleukocytosis and subsequent leukostasis. Treatment of symptomatic cases involves induction chemotherapy and/or leukapheresis. Asymptomatic hyperleukocytosis can be treated with hydroxyurea.

Anticoagulation Reversal.

Today a variety of anticoagulants and antiplatelet agents are available on the market. Given the propensity for bleeding among patients prescribed these medications, the emergency medicine physician must be equipped with a working knowledge of hemostasis, and anticoagulant and antiplatelet reversal. This article reviews strategies to address bleeding complications occurring secondary to warfarin, low-molecular-weight heparin, and direct oral anticoagulant therapy.

Validation of the STA-Liatest DDi assay for exclusion of proximal deep vein thrombosis according to the latest Clinical and Laboratory Standards Institute/Food and Drug Administration guideline: results of a multicenter management study.

: Recommended strategy for venous thromboembolism (VTE) diagnosis includes the use of sensitive D-dimer (DDi) assays along with pretest probability (PTP) assessment. The Clinical and Laboratory Standards Institute (CLSI) recently issued a guideline (US FDA endorsed) on DDi in VTE exclusion. Such guideline specifies the ideal D-dimer assay characteristics and target population. Demonstrate STA-LiatestD-Di performance combined with a PTP score for proximal deep vein thrombosis (pDVT) exclusion in a CLSI compliant study. International, multicenter, prospective nonrandomized, noninterventional clinical outcome management study conducted in a standard-of-care setting. DDi was measured in DVT-suspected consecutive low/moderate PTP outpatients, without conditions possibly impacting DDi values independently of thrombosis presence (age >80, pregnancy, postoperative, cancer) using a 0.5 µg/ml (FEU) threshold for DVT exclusion. Results were used to determine test performance. One thousand two hundred and thirty-four patients (17 centers) signed informed consent. Nine hundred and eighty (mean age: 55) with valid results (494 negative DDi) completed the study (DVT prevalence: 8.7%). STA-LiatestD-Di performance exceeded CLSI/FDA requirements: sensitivity: 100% (95% CI 95.8-100%), NPV: 100% (95% CI 99.3-100%). STA-LiatestD-Di associated with PTP score showed excellent performance for pDVT exclusion, as recently demonstrated for pulmonary embolism. The assay allows safe VTE exclusion, avoiding unnecessary imaging tests.

Cranial Neuropathies and Neuromuscular Weakness: A Case of Mistaken Identity.

We describe a case of wound botulism initially thought to represent Miller-Fisher variant Guillain-Barré syndrome (MFS). Botulism classically presents with the so-called "four D's" (diplopia, dysarthria, dysphagia, dry mouth) with symmetric, descending weakness. MFS presents with a triad of limb-ataxia, areflexia, and ophthalmoplegia, with variable cranial nerve and extremity involvement. The distinction can be difficult but is important as early initiation of botulinum antitoxin is associated with improved patient outcomes in cases of botulism. Furthermore, it is important to recognize intravenous drug use as a risk factor in the development of botulism, especially given an increase in injection drug use.

Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission.

IMPORTANCE: Patients with potentially ischemic chest pain are commonly admitted to the hospital or observed after a negative evaluation in the emergency department (ED) owing to concern about adverse events. Previous studies have looked at 30-day mortality, but no current large studies have examined the most important information regarding ED disposition: the short-term risk for a clinically relevant adverse cardiac event (including inpatient ST-segment elevation myocardial infarction, life-threatening arrhythmia, cardiac or respiratory arrest, or death). OBJECTIVE: To determine the incidence of clinically relevant adverse cardiac events in patients hospitalized for chest pain with 2 troponin-negative findings, nonconcerning initial ED vital signs, and nonischemic, interpretable electrocardiographic findings. DESIGN, SETTING, AND PARTICIPANTS: We conducted a blinded data review of 45,416 encounters obtained from a prospectively collected database enrolling adult patients admitted or observed with the following inclusion criteria: (1) primary presenting symptom of chest pain, chest tightness, chest burning, or chest pressure and (2) negative findings for serial biomarkers. Data were collected and analyzed from July 1, 2008, through June 30, 2013, from the EDs of 3 community teaching institutions with an aggregate census of more than 1 million visits. We analyzed data extracted by hypothesis-blinded abstractors. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of life-threatening arrhythmia, inpatient ST-segment elevation myocardial infarction, cardiac or respiratory arrest, or death during hospitalization. RESULTS: Of the 45,416 encounters, 11,230 met criteria for inclusion. Mean patient age was 58.0 years. Of the 11 230 encounters, 44.83% of patients arrived by ambulance and 55.00% of patients were women. Relevant history included hypertension in 46.00%, diabetes mellitus in 19.72%, and myocardial infarction in 13.16%. The primary end point occurred in 20 of the 11 230 patients (0.18% [95% CI, 0.11%-0.27%]). After excluding patients with abnormal vital signs, electrocardiographic ischemia, left bundle branch block, or a pacemaker rhythm, we identified a primary end point event in 4 of 7266 patients (0.06% [95% CI, 0.02%-0.14%]). Of these events, 2 were noncardiac and 2 were possibly iatrogenic. CONCLUSIONS AND RELEVANCE: In adult patients with chest pain admitted with 2 negative findings for serial biomarkers, nonconcerning vital signs, and nonischemic electrocardiographic findings, short-term clinically relevant adverse cardiac events were rare and commonly iatrogenic, suggesting that routine inpatient admission may not be a beneficial strategy for this group.

The 9th annual INDUS-EM 2013 Emergency Medicine Summit, "Principles, Practices, and Patients," a level one international meeting, Kerala University of Health Sciences and Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India, October 23-27, 2013.

INDUS-EM is India's only level one conference imparting and exchanging quality knowledge in acute care. Specifically, in general and specialized emergency care and training in trauma, burns, cardiac, stroke, environmental and disaster medicine. It provides a series of exchanges regarding academic development and implementation of training tools related to developing future academic faculty and residents in Emergency Medicine in India. The INDUS-EM leadership and board of directors invited scholars from multiple institutions to participate in this advanced educational symposium that was held in Thrissur, Kerala in October 2013.