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Failure to recognize heparin-induced thrombocytopenia (HIT) can lead to devastating thrombotic events, including pulmonary embolism and stroke. In most cases, the problem develops within 5 to 14 days after a first-time exposure to heparin. HIT can occur with either unfractionated heparin or low molecular weight heparin (LMWH), but the incidence is much lower with LMWH. When HIT is suspected clinically, a functionl assay and immunoassy should be performed. However, treatment should not be delayed while waiting for laboratory confirmation. All forms of heparin should be eliminated, and treatment with an alternative anticoagulant should be initiated to prevent new thromboembolic events. Argatroban and lepirudin are the direct thrombin inhibitors that have been approved for the treatement of HIT. Because of the risk of warfarin-induced venous limb gangrene or skinnecrosis, warfarin should be avoided in patients with acute HIT until their platelet counts have recovered and they are improving clinically. [ABSTRACT FROM AUTHOR]

Discusses the findings of a study, which investigated the effectiveness of computer-based science modules for instructing high school students in South Carolina. Standards of the modules used in the study; Objectives of the South Carolina Earth Physics Project; Factors that have affected the outcome of the study.

Recommendations for transitioning from therapy with heparin or a low-molecular-weight heparin preparation to therapy with an oral anticoagulant in patients with acute venous or arterial thromboembolism have undergone several changes during the last two decades. Physicians are now comfortable with beginning treatment with an oral anticoagulant once the diagnosis is confirmed, and loading doses are no longer considered to be necessary. Exceptions to early transition may be necessary in patients with an extensive iliofemoral or axillary-subclavian vein thrombosis or pulmonary embolism where thrombolytic agents may be indicated, or in individuals who require surgery or other invasive procedures, or if there are concerns about bleeding. The avoidance of early transition to oral anticoagulants in patients with acute heparin-induced thrombocytopenia also has been advised because of the potential for further thrombotic complications, including venous limb gangrene and warfarin-induced skin necrosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Desirudin, a bivalent direct thrombin inhibitor (DTI), is approved by the US Food and Drug Administration for the prevention of deep vein thrombosis, which may lead to pulmonary embolism, in patients undergoing elective hip replacement surgery. It became available in the United States in March 2010. OBJECTIVE: The goal of the present article was to provide an overview of the rationale and design of the PREVENT-HIT study, a randomized, prospective, open-label, active drug-controlled, exploratory trial comparing the clinical and economic utility of desirudin versus argatroban in patients with suspected heparin-induced thrombocytopenia (HIT), with or without thrombosis. SUMMARY: The PREVENT-HIT study was designed to enroll approximately 120 patients from 20 to 25 US centers. All eligible patients were required to be aged >or=18 years. Patients with suspected HIT with or without thrombosis were divided into 2 treatment arms and randomized to receive treatment with desirudin or argatroban in a 1:1 ratio using a block randomization method. Arm A comprised patients who were naive to DTI therapy; arm B included patients whose condition was previously stabilized with intravenous argatroban. Desirudin was administered as a fixed-dose injection (15 or 30 mg SC q12h in patients without or with thrombosis, respectively). Argatroban was administered by continuous intravenous infusion in accordance with approved prescribing information or institutional prescribing guidelines at each study site. The primary efficacy outcome measure included the occurrence of any of the following up to 30 days after study drug discontinuation: new-onset or worsening thrombosis requiring discontinuation of study drug; amputation; or all-cause mortality. Other outcomes that were assessed included platelet recovery, bleeding, and pharmacoeconomic parameters. In addition, adverse events and other safety parameters were evaluated. Study enrollment began in November 2008 and ended in December 2009 due to slow enrollment (N = 16). The study results will be published separately. CONCLUSION: The results from the PREVENT-HIT study should enhance understanding of the comparative clinical and economic utility of desirudin and argatroban in patients with HIT with or without thrombosis. ClinicalTrials.gov identifier: NCT00787332. [ABSTRACT FROM AUTHOR]

Lymphedema and lipedema are chronic debilitating disorders that most commonly affect the upper and lower extremities. Although they can appear similar, they differ in important ways, which the authors of this article review and contrast., (Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.)

Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with lymphedema and lipedema share physical exam findings that may lead to misdiagnosis. Poor mobility is common in patients with obesity and patients with lymphedema and lipedema. This may constitute a risk factor for venous thromboembolism (VTE). Our objective was to evaluate the association of VTE in obese patients with lymphedema and lipedema., Methods: The National Inpatient Sample (NIS) was searched from 2016 to 2020 to identify hospital admissions of obese female patients with lymphedema and lipedema. Patients were analyzed in the context of presence or absence of VTE while adjusting for complex cluster sampling techniques. Predictors of VTE were accessed by multivariable regression., Results: Lymphedema was identified in 189,985 patients and lipedema in 50,645 patients. VTE was observed in 3.12% ( n = 374,210) of patients with obesity. In patients with obesity, VTE was more common in patients with lymphedema than without (2.6% vs 1.6%; p < 0.01). Similarly, VTE was more common in patients with lipedema than without (0.6% vs 0.4%; p < 0.01). After multivariable logistic regression, VTE events in obese patients with lymphedema were higher versus without (OR 1.6; CI 1.08-2.43; p = 0.02). Similarly, VTE events were more common in obese patients with lipedema versus obese patients without lipedema (OR 1.20; CI 1.03-1.41; p = 0.02)., Conclusions: In this hypothesis-generating study, lymphedema and lipedema show a positive association with VTE after adjusting for baseline patient characteristics such as obesity, which is a known independent risk factor for VTE. Mechanisms whereby lymphedema and lipedema are associated with VTE should be investigated., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: There is a paucity of data on how race affects the clinical presentation and short-term outcome among hospitalized patients with SARS-CoV-2, the 2019 coronavirus (COVID-19)., Methods: Hospitalized patients ≥ 18 years, testing positive for COVID-19 from March 13, 2020 to May 13, 2020 in a United States (U.S.) integrated healthcare system with multiple facilities in two states were evaluated. We documented racial differences in clinical presentation, disposition, and in-hospital outcomes for hospitalized patients with COIVD-19. Multivariable regression analysis was utilized to evaluate independent predictors of outcomes by race., Results: During the study period, 3678 patients tested positive for COVID-19, among which 866 were hospitalized (55.4% self-identified as Caucasian, 29.5% as Black, 3.3% as Hispanics, and 4.7% as other racial groups). Hospitalization rates were highest for Black patients (36.6%), followed by other (28.3%), Caucasian patients (24.4%), then Hispanic patients (10.7%) (p &lt; 0.001). Caucasian patients were older, and with more comorbidities. Absolute lymphocyte count was lowest among Caucasian patients. Multivariable regression analysis revealed that compared to Caucasians, there was no significant difference in in-hospital mortality among Black patients (adjusted odds ratio [OR] 0.53; 95% confidence interval [CI] 0.26-1.09; p = 0.08) or other races (adjusted OR 1.62; 95% CI 0.80-3.27; p = 0.18). Black and Hispanic patients were admitted less frequently to the intensive care unit (ICU), and Black patients were less likely to require pressor support or hemodialysis (HD) compared with Caucasians., Conclusions: This observational analysis of a large integrated healthcare system early in the pandemic revealed that patients with COVID-19 did exhibit some racial variations in clinical presentation, laboratory data, and requirements for advanced monitoring and cardiopulmonary support, but these nuances did not dramatically alter in-hospital outcomes., (© 2021. W. Montague Cobb-NMA Health Institute.)

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of antiplatelet agents in attenuating thrombosis is unknown. We aimed to determine if the antiplatelet effect of aspirin may mitigate risk of myocardial infarction, cerebrovascular accident, and venous thromboembolism in COVID-19. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. Thus, aspirin does not appear to prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appear distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

Background: Lipedema is a loose connective tissue disease predominantly in women identified by increased nodular and fibrotic adipose tissue on the buttocks, hips and limbs that develops at times of hormone, weight and shape change including puberty, pregnancy, and menopause. Lipedema tissue may be very painful and can severely impair mobility. Non-lipedema obesity, lymphedema, venous disease, and hypermobile joints are comorbidities. Lipedema tissue is difficult to reduce by diet, exercise, or bariatric surgery., Methods: This paper is a consensus guideline on lipedema written by a US committee following the Delphi Method. Consensus statements are rated for strength using the GRADE system., Results: Eighty-five consensus statements outline lipedema pathophysiology, and medical, surgical, vascular, and other therapeutic recommendations. Future research topics are suggested., Conclusion: These guidelines improve the understanding of the loose connective tissue disease, lipedema, to advance our understanding towards early diagnosis, treatments, and ultimately a cure for affected individuals.

Background Certain echocardiographic parameters may serve as early predictors of adverse events in patients with hemodynamically compromising pulmonary embolism (PE). Methods and Results An observational analysis was conducted for patients with acute pulmonary embolism evaluated by a Pulmonary Embolism Response Team (PERT) between 2014 and 2020. The performance of clinical prediction algorithms including the Pulmonary Embolism Severity Index and Carl Bova score were compared using a ratio of right ventricle and left ventricle hemodynamics by dividing the pulmonary artery systolic pressure by the left ventricle stroke volume. The primary outcome of in-hospital mortality, cardiac arrest, and the need for advanced therapies was evaluated by univariate and multivariable analyses. Of the 343 patients meeting the inclusion criteria, 215 had complete data. Pulmonary artery systolic pressure/left ventricle stroke volume was a clear predictor of the primary end point (odds ratio [OR], 2.31; P =0.005), performing as well or better than the Pulmonary Embolism Severity Index (OR, 1.43; P =0.06) or the Bova score (OR, 1.28; P =0.01). Conclusions This study is the first study to demonstrate the utility of early pulmonary artery systolic pressure/left ventricle stroke volume in predicting adverse clinical events in patients with acute pulmonary embolism. Pulmonary artery systolic pressure/left ventricle stroke volume may be a surrogate marker of ventricular asynchrony in high-risk pulmonary embolism and should be prognostically evaluated.

The manuscript discusses the application of CT pulmonary angiography, ventilation-perfusion scan, and magnetic resonance angiography to detect acute pulmonary embolism and to plan endovascular therapy. CT pulmonary angiography offers high accuracy, speed of acquisition, and widespread availability when applied to acute pulmonary embolism detection. This imaging modality also aids the planning of endovascular therapy by visualizing the number and distribution of emboli, determining ideal intra-procedural catheter position for treatment, and signs of right heart strain. Ventilation-perfusion scan and magnetic resonance angiography with and without contrast enhancement can also aid in the detection and pre-procedural planning of endovascular therapy in patients who are not candidates for CT pulmonary angiography.

The optimal management of a submassive or massive pulmonary embolism (PE) during pregnancy is unclear because of a lack of large clinical trials. Evaluation of the patient who may be a candidate for more aggressive therapy includes the use of biomarkers and echocardiogram for risk stratification. PE Response teams (PERTs) have gained increasing acceptance by the medical community and are being implemented in hospitals in the United States and worldwide. PERTs bring together a team of specialists from different disciplines to enhance decision-making in the patient with acute submassive and massive PE., Competing Interests: Disclosure The author have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fibrosing mediastinitis (FM) is a rare disorder of inflammation and fibrosis involving the mediastinum. The formation of fibroinflammatory mass in the mediastinum can lead to obstruction of mediastinal structures and cause severe debilitating and life-threatening symptoms. Superior vena cava syndrome (SVCS) is a dreaded complication of FM with no medical therapy proven to be efficacious. Spiral vein grafting has long been utilized as first-line therapy for SVC syndrome due to FM. Endovascular repair with stents and angioplasty for malignant causes of SVC syndrome is well established. However, there are limited data on their utility in SVC syndrome due to FM. We present two cases of SVC syndrome due to FM treated with endovascular stenting and a detailed review of current literature on its utility in SVCS due to benign causes.

We aimed to characterize the plasma metabolome of chronic thromboembolic pulmonary hypertension patients using a high-throughput unbiased omics approach. We collected fasting plasma from a peripheral vein in 33 operable chronic thromboembolic pulmonary hypertension patients, 31 healthy controls, and 21 idiopathic pulmonary arterial hypertension patients matched for age, gender, and body mass index. Metabolomic analysis was performed using an untargeted approach (Metabolon Inc. Durham, NC). Of the total of 862 metabolites identified, 362 were different in chronic thromboembolic pulmonary hypertension compared to controls: 178 were higher and 184 were lower. Compared to idiopathic pulmonary arterial hypertension, 147 metabolites were different in chronic thromboembolic pulmonary hypertension: 45 were higher and 102 were lower. The plasma metabolome allowed us to distinguish subjects with chronic thromboembolic pulmonary hypertension and healthy controls with a predictive accuracy of 89%, and chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension with 80% accuracy. Compared to idiopathic pulmonary arterial hypertension and healthy controls, chronic thromboembolic pulmonary hypertension patients had higher fatty acids and glycerol; while acyl cholines and lysophospholipids were lower. Compared to healthy controls, both idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients had increased acyl carnitines, beta-hydroxybutyrate, amino sugars and modified amino acids and nucleosides. The plasma global metabolomic profile of chronic thromboembolic pulmonary hypertension suggests aberrant lipid metabolism characterized by increased lipolysis, fatty acid oxidation, and ketogenesis, concomitant with reduced acyl choline and phospholipid moieties. Future research should investigate the pathogenetic and therapeutic potential of modulating lipid metabolism in chronic thromboembolic pulmonary hypertension., (© The Author(s) 2020.)

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy. Heparin is generally avoided in patients with a history of HIT; however, it remains the anticoagulant of choice for cardiac surgery requiring cardiopulmonary bypass (CPB) because of limited experience with alternative anticoagulants such as direct thrombin inhibitors (DTIs) during CPB. We report outcomes of surgery requiring CPB (30-day mortality, rate of thrombosis, and hemorrhage) in patients with prior HIT who received either heparin or a DTI intraoperatively. Seventy-two patients with a prior diagnosis of HIT confirmed by a positive serotonin release assay underwent CBP with a positive HIT antibody at the time of surgery. Thirty-day mortality was 0 and 8.5% in the DTI and heparin cohorts ( p  = 0.277). Thrombotic events occurred in 1 (7.7%) of the patients treated with DTI and 15 (25.4%) receiving heparin ( p  = 0.164). In the DTI cohort, 7 (53.8%) had minimal bleeding, 5 (38.5%) had mild bleeding, 1 (7.8%) had moderate bleeding, and none had severe bleeding. In the heparin group, 16 (27.1%) had minimal bleeding, 14 (23.7%) had mild bleeding, 25 (42.4%) had moderate bleeding, and 4 (6.8%) had severe bleeding ( p  = 0.053). DTI was associated with a lower rate of moderate to severe hemorrhage than heparin (odds ratio 0.097 [95% confidence interval 0.011-0.824], p  = 0.033) in a logistic regression model adjusted for thrombocytopenia and length on bypass. DTI appears to be safe in selected patients undergoing CPB after a diagnosis of HIT, and was not associated with higher rates of 30-day mortality, thrombosis, or hemorrhage., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Treatment strategies for complex patients with pulmonary embolism (PE) are often debated given patient heterogeneity, multitude of available treatment modalities, and lack of consensus guidelines. Although multidisciplinary Pulmonary Embolism Response Teams (PERT) are emerging to address this lack of consensus, their impact on patient outcomes is not entirely clear. This analysis was conducted to compare outcomes of all patients with PE before and after PERT availability. We analyzed all adult patients admitted with acute PE diagnosed on computed tomography scans in the 18 months before and after the institution of PERT at a large tertiary care hospital. Among 769 consecutive inpatients with PE, PERT era patients had lower rates of major or clinically relevant nonmajor bleeding (17.0% vs 8.3%, p = 0.002), shorter time-to-therapeutic anticoagulation (16.3 hour vs 12.6 hour, p = 0.009) and decreased use of inferior vena cava filters (22.2% vs 16.4%, p = 0.004). There was an increase in the use of thrombolytics/catheter-based strategies, however, this did not achieve statistical significance (p = 0.07). There was a significant decrease in 30-day/inpatient mortality (8.5% vs 4.7%, p = 0.03). These differences in outcomes were more pronounced in intermediate and high-risk patients (mortality 10.0% vs 5.3%, p = 0.02). The availability of multidisciplinary PERT was associated with improved outcomes including 30-day mortality. Patients with higher severity of PE seemed to derive most benefit from PERT availability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Management of intermediate and high risk acute pulmonary embolism (PE) is challenging. The role of multidisciplinary teams for the care of these patients is emerging. Herein, we report our experience with a pulmonary embolism response team (PERT). We conducted a retrospective chart review on all patients admitted to the Cleveland Clinic main campus who required activation of the (PERT) from October 1, 2014 to September 1, 2016. We extracted data pertaining to clinical presentation, bleeding complications, and pre- and post-discharge imaging. Patients were classified as low, intermediate or high risk PE. Descriptive and continuous variables were collected and analyzed. There were 134 PERT activations. PE was confirmed by CT-PA in 118 patients. Fifteen (13%) patients were classified as low risk, 80 (68%) intermediate risk PE and 23 (19%) high risk PE. Fourteen (12%) patients were treated with catheter directed rtPA, 6 (5%) received full dose (100 mg rtPA), 16 (13%) received systemic half-dose (50 mg rtPA), 6 (5%) underwent a surgical embolectomy and 4 (3%) underwent mechanical thrombectomy. 65 (55%) patients received anticoagulation only, and 8 (7%) patients were managed conservatively without any anticoagulation or advanced therapy. 11 (9%) patients died while during the hospitalization. Fourteen patients had major bleeding events. There were no bleeding events among patients who received systemic low dose or full dose rtPA. A multidisciplinary approach to cases of intermediate risk and high risk PE can be implemented successfully. We saw a relatively low rate of bleeding events with use of rtPA.

In the article, "Update on the management of venous thromboembolism" (Bartholomew JR, Cleve Clin J Med 2017; 84[suppl 3]:39-46), 2 sentences in the text regarding dose reduction for body weight have errors. The corrected sentences follow: On page 42, left column, the last 5 lines should read: "The recommended dose should be reduced to 2.5 mg twice daily in patients that meet 2 of the following criteria: age 80 or older; body weight of 60 kg or less; or with a serum creatinine 1.5 mg/dL or greater." And on page 42, right column, the sentence 10 lines from the top should read: "Edoxaban is given orally at 60 mg once daily but reduced to 30 mg once daily if the CrCL is 30 mL/min to 50 mL/min, if body weight is 60 kg or less, or with use of certain P-glycoprotein inhibitors."

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism, is a common cardiovascular disease associated with significant morbidity ranging from painful leg swelling, chest pain, shortness of breath, and even death. Long-term complications include recurrent VTE, postpulmonary embolism syndrome, chronic thromboembolic pulmonary hypertension, and postthrombotic syndrome (PTS). Management of VTE requires immediate anticoagulation therapy based on a risk assessment for bleeding. Direct oral anticoagulants (DOACs) have become an important option for patients as reflected in the most recent American College of Chest Physician treatment guidelines., (Copyright © 2017 Cleveland Clinic.)

Bleeding is one of the most feared complications of flexible bronchoscopy. Although infrequent, it can be catastrophic and result in fatal outcomes. Compared to other endoscopic procedures, the risk of morbidity and mortality from the bleeding is increased, as even a small amount of blood can fill the tracheobronchial tree and lead to respiratory failure. Patients using antithrombotic agents (ATAs) have higher bleeding risk. A thorough understanding of the different ATAs is critical to manage patients during the peri-procedural period. A decision to stop an ATA before bronchoscopy should take into account a variety of factors, including indication for its use and the type of procedure. This article serves as a detailed review on the different ATAs, their pharmacokinetics and the pre- and post-bronchoscopy management of patients receiving these medications., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Pulmonary embolism (PE) is a common thrombotic event that is variable in its presentation. Depending on the patients' risk for mortality, guidelines provide several treatment strategies including thrombolysis, catheter-directed therapies, pulmonary embolectomy, anticoagulation, and inferior vena cava filters. However, there is considerable disagreement between guidelines regarding the optimal treatment strategy for patients, particularly for those with intermediate-risk PE. In order to provide rapid and individualized care, PE response teams (PERT) have been developed. These teams consist of members from different specialties with a particular interest in PE, varying technical skills, and clinical experience, thereby allowing for a multidisciplinary approach. PERT allows for consensus decision making, and for rapid intervention in patients whose conditions worsen. In this review, we provide an overview of treatment guidelines for PE, and of results from recent clinical trials involving patients with submassive PE. In addition, we discuss an outline of our approach and use of PERT.

Surgical embolectomy in acute pulmonary embolism is usually reserved for patients with massive pulmonary embolism presenting with cardiogenic shock, or for whom thrombolysis is absolutely contraindicated or has failed. Incomplete removal of thrombotic material lodged in the distal pulmonary arterial bed is considered an important cause of persistent pulmonary hypertension. Retrograde pulmonary embolectomy is an adjunct to conventional pulmonary embolectomy, resulting in more complete embolectomy, specifically of material lodged in the distal pulmonary arterial bed. We describe our simplified technique of retrograde pulmonary embolectomy as a safe adjunct to conventional pulmonary embolectomy., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Venous thromboembolism (VTE), which includes deep venous thrombosis and pulmonary embolism, is a major public health problem associated with increased morbidity and mortality. Despite the high recurrence risk associated with unprovoked VTE, extended anticoagulation remains controversial. Oral antithrombotic agents for extended VTE treatment comprise the vitamin K antagonists, aspirin, and the direct oral anticoagulants (also known as target-specific oral anticoagulants and formerly known as the new or novel oral anticoagulants) including rivaroxaban, dabigatran, apixaban, and edoxaban. The efficacy of these anticoagulants in reducing the risk of VTE recurrence (>80%-90% relative risk reduction) is offset by the risk of major bleeding that approaches 3% per year. Stratifying risks of recurrence and bleeding to identify patients at low, intermediate, or high risk and carefully considering the pharmacologic profile of the antithrombotic agents will help clinicians in choosing the optimal anticoagulant and duration and/or surveillance strategy. This review will discuss the current guidelines for extended VTE treatment, review the clinical trials involving the direct oral anticoagulants, and present the clinical considerations and concerns involving extended therapy.