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The article focuses on clinical safety and efficacy of the use of idarucizumab monoclonal antibody and andexanet alfa molecular mimic mimic factor Xa in preventing bleeding associated with direct oral anticoagulants (DOAC). Topics discussed include a comparison of prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP), the use of FFP and vitamin K in reversing warfarin-associated bleeding, properties of DOAC. The benefits of warfarin over DOAC are mentioned.

Tumor thrombus, the intravascular extension of tumor into adjacent blood vessels, is frequently encountered in patients with renal cell carcinoma and hepatocellular carcinoma, and often involves the abdominal vasculature including the renal vein, portal vein, and the inferior vena cava. While a bland thrombus is composed of platelets and fibrin, in contrast, a tumor thrombus refers to an organized collection of tumor cells. Though oftentimes detected incidentally on imaging, tumor thrombus may have significant clinical implications and can be challenging to differentiate from bland thrombus. Additionally, the optimal management of tumor thrombus, including the use of anticoagulation, remains poorly described. This review summarizes common causes of tumor thrombus, as well as its impact on staging, prognosis, and treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JJ. Shatzel reports receiving consulting fees from Aronora Inc. The remaining authors have nothing to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Intranasal, subcutaneous, or intravenous desmopressin can be utilized to release von Willebrand Factor and Factor VIII into circulation, enhance platelet adhesion and shorten bleeding time. Due to these properties, desmopressin can be effective in controlling bleeding in mild hemophilia A, certain subtypes of von Willebrand disease and in acute bleeding from uremia, end stage renal disease, and liver disease. Its use, however, can be complicated by hyponatremia and rarely arterial thrombotic events. While desmopressin has also been used as a prophylactic blood sparing agent in orthopedic, renal, and hepatic procedures, clinical studies have shown limited benefit in these settings. The purpose of this article is to review the evidence for desmopressin in primary hematologic disorders, discuss its mechanism of action and evaluate its utility as a hemostatic and blood sparing product in various bleeding conditions., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Venous thromboses are well-established complications of hormonal therapy. Thrombosis risk is seen with both hormonal contraceptive agents and with hormone replacement therapy for menopause and gender transition. Over the past several decades, large epidemiological studies have helped better define these risks., Objectives: To review and discuss the differences in thrombosis risk of the many of hormonal preparations available as well as their interaction with patient-specific factors., Methods: We conducted a narrative review of the available literature regarding venous thrombosis and hormonal therapies including for contraception, menopausal symptoms, and gender transition., Results: Thrombosis risk with estrogen-containing compounds increases with increasing systemic dose of estrogen. While progesterone-only-containing products are not associated with thrombosis, when paired with estrogen in combined oral contraceptives, the formulation of progesterone does impact the risk. These components, along with patient-specific factors, may influence the choice of hormonal preparation. For patients who develop thrombosis on hormonal treatment, anticoagulation is protective against future thrombosis. Duration of anticoagulation is dependent on ongoing and future hormone therapy choice. Finally, the optimal management of hormone therapy for individuals diagnosed with prothrombotic illnesses such as COVID-19 remains unclear., Conclusions: When contemplating hormonal contraception or hormone replacement therapy, clinicians must consider a variety of factors including hormone type, dose, route, personal and family history of thrombosis, and other prothrombotic risk factors to make informed, personalized decisions regarding the risk of venous thrombosis., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Introduction: Splanchnic vein thrombosis (SVT) occurs in a heterogenous group of patients secondary to a variety of risk factors including liver disease. Minimal data regarding natural history and outcomes of SVT exists to inform management decisions. As such, there is equipoise regarding the utility of anticoagulation in cirrhotic patients with SVT. We sought to identify clinical factors predictive of new or progressive thrombosis in a cohort of patients with untreated SVT., Methods: We conducted a retrospective cohort study of cirrhotic patients over 18 years of age diagnosed with SVT at the Oregon Health & Science University from 2015 to 2020, excluding those initially treated with anticoagulation. The primary study endpoint was a composite of the following: imaging-confirmed progression of SVT, development of cavernous transformation, intestinal ischemia, portal cholangiopathy or new venous or arterial thrombosis., Results: 261 patients were included in the analysis (median age 61 years, 68% male, 32% female). Forty percent of all patients experienced the primary composite endpoint. Multivariable logistic regression found that only the presence of pancreatitis or abdominal infection at diagnosis was associated with an increased likelihood of experiencing thrombus progression in patients with untreated SVT (OR 3.61, P = 0.02). There was a statistically significant overall survival difference between patients that did and did not experience the primary composite endpoint after controlling for confounding variables. (p = 0.0068)., Conclusions: Overall, only the presence of pancreatitis or intrabdominal infection were found to be significantly associated with thrombotic progression, with varices identified as marginally non-significant risk factor. Notably, thrombotic progression was associated with a significant reduction in overall survival., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Long-distance travel is assumed to be a risk factor for venous thromboembolism (VTE). However, the available data have not clearly demonstrated the strength of this relationship, nor have they shown evidence for the role of thromboprophylaxis., Methods: We performed a systematic review of the literature. We also summarized available guidelines from 5 groups., Results: We found 18 studies that addressed this question. Based on the data presented in the review, we conclude that there is an association between VTE and length of travel, but this association is mild to moderate in effect size with odds ratios between 1.1 and 4. A dose-response relationship between VTE and travel time was identified, with a 26% higher risk for every 2 h of air travel (P=0.005) starting after 4 h. The quality of evidence for both travel length and thromboprophylaxis was low. However, low-risk prophylactic measures such as graduated compression stockings were shown to be effective in VTE prevention. There is heterogeneity among the different practice guidelines. The guidelines generally concur that no prophylaxis is necessary in travelers without known thrombosis risk factors and advocate for conservative treatment such as compression stockings over pharmacologic prophylaxis., Conclusions: We conclude air travel is a risk factor for VTE and that there is a dose relationship starting at 4 h. For patients with risk factors, graduated compression stockings are effective prophylaxis., (Copyright © 2022 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

The quality and quantity of nutrition impact health. However, chrononutrition, the timing, and variation of food intake in relation to the daily sleep-wake cycle are also important contributors to health. This has necessitated an urgent need to measure, analyze, and optimize eating patterns to improve health and manage disease. While written food journals, questionnaires, and 24-hour dietary recalls are acceptable methods to assess the quantity and quality of energy consumption, they are insufficient to capture the timing and day-to-day variation of energy intake. Smartphone applications are novel methods for information-dense real-time food and beverage tracking. Despite the availability of thousands of commercial nutrient apps, they almost always ignore eating patterns, and the raw real-time data is not available to researchers for monitoring and intervening in eating patterns. Our lab developed a smartphone app called myCircadianClock (mCC) and associated software to enable long-term real-time logging that captures temporal components of eating patterns. The mCC app runs on iOS and android operating systems and can be used to track multiple cohorts in parallel studies. The logging burden is decreased by using a timestamped photo and annotation of the food/beverage being logged. Capturing temporal data of consumption in free-living individuals over weeks/months has provided new insights into diverse eating patterns in the real world. This review discusses (1) chrononutrition and the importance of understanding eating patterns, (2) the myCircadianClock app, (3) validation of the mCC app, (4) clinical trials to assess the timing of energy intake, and (5) strengths and limitations of the mCC app., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: Although iron deficiency is common, it remains unclear which iron repletion strategy is associated with the lowest rate of infusion-related adverse events, and how patients with history of infusion reaction should be managed., Objective: To evaluate rates of infusion reactions among 4 commonly used intravenous iron repletion strategies and determine how readministration was managed in patients with history of reaction., Design, Setting, and Participants: This cohort study included all patients receiving intravenous iron infusion from January 1, 2015, to September 7, 2021, at 6 centers in Portland, Oregon. Participants included a total of 12 237 patients with iron deficiency, not restricted by etiology. Statistical analysis was performed from September to October 2021., Exposures: Type of intravenous iron formulation and concurrent administration of diphenhydramine, epinephrine, famotidine, and/or hydrocortisone, used as surrogate maker of infusion reaction., Main Outcomes and Measures: Incidence of adverse events, including severe events requiring epinephrine, stratified by type of iron formulation, and in patients who received premedication or with history of infusion-related reaction receiving subsequent doses., Results: Among 35 737 unique iron infusions (12 237 patients [9480 (77.5%) women; 717 (5.9%) Black; 10 250 (83.7%) White; mean (SD) age of 51 (20) years]), comprising 22 309 iron sucrose doses, 9067 iron dextran total doses (1771 preceded by test dose, 56 test doses alone), 3147 ferumoxytol doses, and 1214 ferric carboxymaltose doses, incidence of adverse events was 3.9% (n = 1389; 95% CI, 3.7%-4.1%). Rate of infusion events differed among iron formulations: 4.3% (n = 970; 95% CI, 4.1%-4.6%) iron sucrose, 3.8% (n = 345, 95% CI: 3.4%-4.2%) iron dextran (test and full doses or test dose alone), 1.8% (n = 57; 95% CI, 1.4%-2.3%) ferumoxytol, and 1.4% (n = 17, 95% CI, 0.8%-2.3%) ferric carboxymaltose (P < .001). Severe adverse events were exceedingly rare with only 2 documented epinephrine administrations, both associated with iron dextran. Incidence of adverse events among those who received premedication was 23-fold higher compared with those who did not (38.6% vs 1.7%, χ21 = 7324.8; P < .001). Among 873 patients with history of infusion reaction who underwent readministration, the majority received the same formulation, which was associated with significantly higher reaction rate particularly if premedication was administered (68% [95% CI, 64%-72%] vs 32% [95% CI, 26%-41%], respectively), compared with those who received an alternate formulation (21% [95% CI, 11%-35%] vs 5% [95% CI, 2%-12%], respectively) (P < .001)., Conclusions and Relevance: These data, and the preponderance of published evidence, suggest that intravenous iron is generally well tolerated with exceedingly low risk of severe reaction, use of premedication and test doses are unnecessary, and that optimal prevention and management of infusion-related reactions warrant further study.

Hepatic cirrhosis leads to numerous hematologic derangements resulting in a complex and tenuously rebalanced hemostatic milieu. The utility of common hematologic tests including the INR and aPTT in assessing hemostatic and thrombotic risk in patients with cirrhosis is limited, and consensus on transfusion thresholds and proper management of thrombotic complications continues to evolve. This review summarizes the pathophysiology of key derangements of hemostasis including those of platelets, von Willebrand factor, pro- and anticoagulation factors, and fibrin. Additionally, the pathogenesis, consequences, optimal management, and prevention of major thrombotic and bleeding complications in cirrhosis arte discussed., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A fever of unknown origin is often pursued diagnostically under the framework of infectious, rheumatologic, and neoplastic causes. When encephalopathy ensues, the differential diagnosis narrows, but can remain elusive, particularly when dealing with rare diseases. We present the case of a patient with fever of unknown origin and intermittent encephalopathy that spanned multiple hospital admissions and ultimately yielded a diagnosis of intravascular large B cell lymphoma complicated by hemophagocytic lymphohistiocytosis. We review the varying presentations of this disease, when to consider this as a diagnosis, and how to most accurately make the diagnosis.

Bleeding related to portal hypertension and coagulopathy is a common complication in patients with cirrhosis. Complications and management of bleeding is a significant source of healthcare cost and utilization, as well as morbidity and mortality. Due to the scarcity of evidence surrounding transfusion strategies and hemostatic interventions in patients with cirrhosis, there has been significant debate regarding the best practice. Emerging data suggest that evidence supporting transfusion of packed red blood cells to a hemoglobin threshold of 7-8 g/dL is strong. thrombopoietin (TPO) receptor agonists have shown promise in increasing platelet levels and reducing transfusions preprocedurally, although have not specifically been found to reduce bleeding risk. Data for viscoelastic testing (VET)-guided transfusions appear favorable for reducing blood transfusion requirements prior to minor procedures and during orthotopic liver transplantation. Hemostatic agents such as recombinant factor VIIa, prothrombin complex concentrates, and tranexamic acid have been examined but their role in cirrhotic patients is unclear. Other areas of growing interest include balanced ratio and whole blood transfusion. In the following manuscript, we summarize the most up to date evidence for threshold-guided, VET-guided, balanced-ratio, and whole blood transfusions as well as the use of hemostatic agents in cirrhotic patients to provide practice guidance to clinicians., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Direct oral anticoagulants (DOACs) have been shown to be superior to vitamin K antagonists (VKAs) in regards to safety and efficacy in numerous clinical trials and are now the preferred oral anticoagulant by multiple professional societies. However, patients with significant levels of organ dysfunction were excluded from all major clinical trials, leaving the clinical benefit in these subsets uncertain. Patients with chronic kidney disease (CKD) specifically often require anticoagulation for acute or long-term indications such as venous thromboembolism, atrial fibrillation, or mechanical heart valves. The efficacy and safety of anticoagulation in patients with renal failure is less certain, however, particularly with DOACs which have altered pharmacokinetics in patients with renal failure and limited observational data on their use in this population. In this review, we compile the most up to date data on the DOAC use in patients with CKD. DOAC use in patients with ESRD and advanced CKD is increasing despite the presence of a clear benefit, and with the potential for increased risk of bleeding compared to warfarin. Apixaban has the greatest amount of outcomes research supporting its use over warfarin in this patient population; however, further research on DOAC safety and efficacy in those with advanced CKD is still needed., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Anticoagulation has multiple roles in the treatment of cardiovascular disease, including in management of acute myocardial infarction, during percutaneous coronary intervention, as stroke prophylaxis in patients with atrial arrhythmias, and in patients with mechanical heart valves. Clinical anticoagulation choices in the aforementioned diseases vary widely, due to conflicting data to support established agents and the rapid evolution of evidence-based practice that parallels more widespread use of novel oral anticoagulants. This review concisely summarizes evidence-based guidelines for anticoagulant use in cardiovascular disease, and highlights new data specific to direct oral anticoagulants., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acute limb ischemia (ALI) is generally secondary to cardioembolism or progression of peripheral vascular disease, however, a discrete population of patients with ALI exists in which no precipitant is ever established. Unlike cryptogenic arterial occlusion in other arenas, such as cryptogenic stroke, cryptogenic acute limb ischemia (cALI) has not been well-described, and no routine management has been established. The aim of this study is to describe patients with cALI, and the risk of recurrence based on the treatment they received. We performed a retrospective cohort study of patients evaluated for ALI at a single academic center, excluding patients with known peripheral artery disease, polytrauma, critical illness, or a history of recent vascular access. Out of 608 individual patients analyzed, 37 were deemed to have cALI on their initial presentation. After extended follow up, 29 patients were eventually found to have a precipitating cause, with 8 patients remaining cryptogenic. On follow up, the overall rate of recurrent ALI was 13% in the group eventually found to have a precipitating cause, and 25% in the cALI group. The median time to recurrence was 16.5 months in the precipitated acute limb ischemia (pALI) group, and 23.3 months in the cALI group. Of pALI patients who recurred, 40% did so despite being therapeutic on anticoagulation. None of the recurring cALI patients were therapeutically anticoagulated. Based on our analysis, nearly 20% of patients presenting with ALI in the absence of known risk factors will remain cryptogenic. Rates of recurrent ALI in patients who present with cALI are significant, particularly in patients who are not maintained on anticoagulation. This suggests that the etiology of ALI in patients without peripheral vascular disease may not have a strong bearing on treatment decisions, and that indefinite anticoagulation may be warranted in patients with no obvious cause on presentation. Future studies are needed to better gauge the risk for bleeding complications and to provide a better understanding of the risks and benefits of recurrence and complications of anticoagulation over time.

Background: Acute leukemia is known to confer an elevated risk of both hemorrhagic and thrombotic complications, but the development of stroke in this population is poorly characterized. This study assesses clinical and epidemiologic factors in a population of inpatients with acute myeloid leukemia (AML) and stroke., Methods: Using the 2012 National Inpatient Sample, demographic and clinical data including age, gender, race, length of stay, in-hospital procedures, discharge diagnosis, disposition, and mortality incidence were extracted., Results: Of 7,296,968 admissions, 10,984 patients with active AML were analyzed. Of these, 65 patients had a concomitant cerebrovascular accident (CVA) (hemorrhagic or ischemic). There was a 50-fold increase in the risk of stroke in patients with active AML compared with all admissions. Patients with AML and CVAs were found to have significantly higher inpatient mortality than for all admitted patients with stroke (36.9% vs. 6.7%; odds ratio, 5.5; 95% confidence interval, 2.3-8.8; P < .0001). Multivariate logistic regression, after controlling for confounding variables, identified acute renal failure with tubular necrosis, hypernatremia, urinary tract infection, and secondary thrombocytopenia as significant predictors of stroke., Conclusions: Patients with AML have an elevated risk of CVA compared with all inpatients, and mortality in this population is high. Better characterization of risk factors of stroke in this vulnerable population is still needed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib., (© 2017 International Society on Thrombosis and Haemostasis.)

The phrase "unmet medical need" has important regulatory implications, but there is no empirical analysis of its real world usage. We sought to determine the annual US incidence, 5-year survival, and number of National Comprehensive Cancer Network (NCCN)-recommended regimens for indications described in the literature as an "unmet medical need." We queried Google Scholar to identify publications where authors used the phrase "unmet medical need" to refer to a specific cancer indication. For each indication, we investigated the annual US incidence, 5-year survival, and number of NCCN recommended regimens. We identified 237 cancer indications considered by authors an "unmet medical need." The term was found most frequently appended to breast cancer indications comprising 30 of the 237 citations (12.7%). This was followed by lung 24/237 (10.1%), hepatocellular 18/237 (7.6%), and prostate cancer 13/237 (5.4%). In 55 of 237 (23.2%) instances where an indication was described by the authors as an unmet medical need, the incidence was 1,000 cases per year, there were five regimens recommended by NCCN, and there was a 50% or greater 5-year survival. Forty-three of 237 (18.1%) indications had at least an incidence of 10,000 cases a year, 10 recommended regimens, and a 50% 5-year survival. In conclusion, "unmet medical need" has been used to describe cancer indications that are rare, and have few options and poor survival outcomes. However, the term has also been used to describe indications that occur commonly, have many treatment alternatives, and are clinically indolent with more encouraging expectations for survival. Some standardization is needed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.

Gynecomastia-like hyperplasia of orthotopic female breast tissue is a rare entity. We present the singularly unique case of a 22-year-old female who presented with a small axillary mass subsequently discovered to be a discrete deposit of ectopic breast tissue with gynecomastia-like hyperplasia. This case highlights the etiology, variable presentation, and evaluation of ectopic breast tissue.

Although rare, extra-pulmonary inflammatory myofibroblastic tumors (IMTs) are becoming increasingly recognized. While surgical resection is currently an effective and accepted treatment for IMTs, the optimal management of unresectable or residual IMTs remains a clinical dilemma. We present the case of an incompletely resected IMT treated successfully with anti-inflammatory therapy alone, and describe the rationale for this approach.