Silent cerebral infarction during immune TTP remission: prevalence, predictors, and impact on cognition.

Immune thrombotic thrombocytopenic purpura (iTTP) survivors have increased risk of cardiovascular disease, including strokes, and report persistent cognitive difficulties during remission. We conducted this prospective study involving iTTP survivors during clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neurodeficits. We also tested the hypothesis that SCI is associated with cognitive impairment, assessed using the National Institutes of Health ToolBox Cognition Battery. For cognitive assessments, we used fully corrected T scores adjusted for age, sex, race, and education. Based on the diagnostic and statistical manual 5 criteria, we defined mild and major cognitive impairment as T scores with a 1 or 2 standard deviation (SD) and >2 SD below the mean on at least 1 test, respectively. Forty-two patients were enrolled, with 36 completing MRIs. SCI was present in 50% of the patients (18), of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs 27.7%; P = .026), including major cognitive impairment (50% vs 5.6%; P = .010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment (odds ratio [OR] 10.5 [95% confidence interval (95% CI), 1.45-76.63]; P = .020) and major cognitive impairment (OR 7.98 [95% CI, 1.11-57.27]; P = .039) after adjusting for history of stroke and Beck depression inventory scores. MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these silent infarcts are neither silent nor innocuous.

Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination-United States, December 2020 to August 2021.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. MEASUREMENTS: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. RESULTS: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%). LIMITATIONS: Underreporting and incomplete case follow-up. CONCLUSION: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.

BACKGROUND: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODS: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding. RESULTS: Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49). CONCLUSIONS: In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).

Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS.

The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies, including anti-ß2-glycoprotein-I (anti-ß2GPI), that are considered central to APS pathogenesis. Based on animal studies showing a role of complement in APS-related clinical events, we used the modified Ham (mHam) assay (complement-dependent cell killing) and cell-surface deposition of C5b-9 to test the hypothesis that complement activation is associated with thrombotic events in APS. A positive mHam (and corresponding C5b-9 deposition) were present in 85.7% of catastrophic APS (CAPS), 35.6% of APS (and 68.5% of samples collected within 1 year of thrombosis), and only 6.8% of systemic lupus erythematosus (SLE) sera. A positive mHam assay was associated with triple positivity (for lupus anticoagulant, anticardiolipin, and anti-ß2GPI antibodies) and recurrent thrombosis. Patient-derived anti-ß2GPI antibodies also induced C5b-9 deposition, which was blocked completely by an anti-C5 monoclonal antibody, but not by a factor D inhibitor, indicating that complement activation by anti-ß2GPI antibodies occurs primarily through the classical complement pathway. Finally, patients with CAPS have high rates of rare germline variants in complement regulatory genes (60%), compared with patients with APS (21.8%) or SLE (28.6%) or normal controls (23.3%), and have mutations at a rate similar to that of patients with atypical hemolytic uremic syndrome (51.5%). Taken together, our data suggest that anti-ß2GPI antibodies activate complement and contribute to thrombosis in APS, whereas patients with CAPS have underlying mutations in complement regulatory genes that serve as a "second hit," leading to uncontrolled complement activation and a more severe thrombotic phenotype.

Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis.

There may be many predictors of venous thromboembolism (VTE) and bleeding in hospitalized medical patients, but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception through May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of 69 410 citations, we included 17 studies in our analysis: 14 that reported on VTE, and 3 that reported on bleeding. For VTE, moderate-certainty evidence showed a probable association with older age; elevated C-reactive protein (CRP), D-dimer, and fibrinogen levels; tachycardia; thrombocytosis; leukocytosis; fever; leg edema; lower Barthel Index (BI) score; immobility; paresis; previous history of VTE; thrombophilia; malignancy; critical illness; and infections. For bleeding, moderate-certainty evidence showed a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication, and presence of a central venous catheter. Elevated CRP, a lower BI, a history of malignancy, and elevated heart rate are not included in most VTE risk assessment models. This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding; it also informs guidelines for VTE prevention and future research.

Update on Guidelines for the Prevention of Cancer-Associated Thrombosis.

Patients with cancer are at high risk of developing arterial and venous thromboembolism (VTE). They constitute 15% to 20% of the patients diagnosed with VTE. Depending on the type of tumor, cancer therapy, and presence of other risk factors, 1% to 25% of patients with cancer will develop thrombosis. The decision to start patients with cancer on primary thromboprophylaxis depends on patient preference, balancing risk of bleeding versus risk of thrombosis, cost, and adequate organ function. Currently, guidelines recommend against the use of routine primary thromboprophylaxis in unselected ambulatory patients with cancer. Validated risk assessment models can accurately identify patients at highest risk for cancer-associated thrombosis (CAT). This review summarizes the recently updated NCCN Guidelines for CAT primary prophylaxis, with a primarily focus on VTE prevention. Two main clinical questions that providers commonly encounter will also be addressed: which patients with cancer should receive primary thromboprophylaxis (both surgical and medical oncology patients) and how to safely choose between different anticoagulation agents.

Optimizing Thromboembolism Prophylaxis for the Contemporary Age of Multiple Myeloma.

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.

Effectiveness of Healthcare Delivery, Quality, and Safety a Patient Education Bundle on Venous Thromboembolism Prophylaxis Administration by Sex.

INTRODUCTION: Venous thromboembolism (VTE) is a frequent cause of preventable harm among hospitalized patients. Many prescribed prophylaxis doses are not administered despite supporting evidence. We previously demonstrated a patient-centered education bundle improved VTE prophylaxis administration broadly; however, patient-specific factors driving nonadministration are unclear. We examine the effects of the education bundle on missed doses of VTE prophylaxis by sex. METHODS: We performed a post-hoc analysis of a nonrandomized controlled trial to evaluate the differences in missed doses by sex. Pre-intervention and intervention periods for patients admitted to 16 surgical and medical floors between 10/2014-03/2015 (pre-intervention) and 04/2015-12/2015 (intervention) were compared. We examined the conditional odds of (1) overall missed doses, (2) missed doses due to patient refusal, and (3) missed doses for other reasons. RESULTS: Overall, 16,865 patients were included (pre-intervention 6853, intervention 10,012), with 2350 male and 2460 female patients (intervention), and 6373 male and 5682 female patients (control). Any missed dose significantly reduced on the intervention floors among male (odds ratio OR 0.55; 95% confidence interval CI, 0.44-0.70, P < 0.001) and female (OR 0.59; 95% CI, 0.47-0.73, P < 0.001) patients. Similar significant reductions ensued for missed doses due to patient refusal (P < 0.001). Overall, there were no sex-specific differences (P-interaction >0.05). CONCLUSIONS: Our intervention increased VTE prophylaxis administration for both female and male patients, driven by decreased patient refusal. Patient education should be applicable to a wide range of patient demographics representative of the target group. To improve future interventions, quality improvement efforts should be evaluated based on patient demographics and drivers of differences in care.

Update on Guidelines for the Management of Cancer-Associated Thrombosis.

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer. Over the past 2 decades, enormous advances have been made in the management of CAT. The growing evidence base informing practice has led to the publication of a number of guidelines and guidance documents on the diagnosis and treatment of CAT. The goal of this review is to examine the latest versions of evidence-based guidelines, highlighting the differences and similarities in their methodology, their disease-specific content, and recommendations for management. Our analysis shows that for most clinical topics, the different guidelines provide roughly similar management advice. However, there are a number of important clinical topics in CAT that are not currently covered by the existing guidelines. We think inclusion of these topics in future versions of the guidelines will facilitate ongoing efforts to optimize the care of patients with CAT. IMPLICATIONS FOR PRACTICE: Cancer-associated thrombosis (CAT) is a common complication in patients with cancer. This review examines the differences and similarities of the current CAT guidelines methods and recommendations. Current guidelines largely agree on many aspects of CAT management. However, there are a number of topics in CAT that are not currently included in guidelines where evidence-based guidance would be very helpful for clinicians. Coverage of these topics in future guidelines is encouraged to optimize clinical practice.

Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors.

With timely and effective treatment, most patients with thrombotic thrombocytopenic purpura (TTP) survive the acute TTP episode. In addition to the risk of relapse, TTP survivors have higher all-cause mortality than the general population and increased rates of chronic morbidities, including hypertension, depression, and mild cognitive impairment. We conducted this retrospective-prospective cohort study to determine the incidence and prevalence of stroke after recovery from acute TTP and to test the hypothesis that lower ADAMTS13 activity after recovery from TTP is associated with an increased risk of stroke during remission. Of 170 consecutive patients treated for TTP at The Johns Hopkins Hospital from 1995 through 2018, 14 (8.2%) died during the index episode and 19 were observed for less than 1 month after recovery. Of the remaining 137 patients, 18 (13.1%) developed stroke unrelated to an acute TTP episode over a median observation period of 3.08 years, which is fivefold higher than the expected prevalence of 2.6% from an age- and sex-matched reference population (P = .002). ADAMTS13 activity during remission was measured in 52 patients and was >70% in 44.2%, 40% to 70% in 23.1%, 10% to 39% in 25%, and <10% in 7.7%. Stroke after recovery from acute TTP occurred in 0% (0 of 22) of patients with normal remission ADAMTS13 activity (>70%) and in 27.6% (8 of 29) of patients with low ADAMTS13 activity (≤70%; P = .007). In conclusion, stroke is common after recovery from TTP and is associated with reduced ADAMTS13 activity during remission.

How to Choose An Appropriate Anticoagulant for Cancer-Associated Thrombosis.

Venous thromboembolic disease can be a fatal complication of cancer. Despite advances in prevention, thousands of patients require treatment of cancer-associated thrombosis (CAT) each year. Guidelines have advocated low-molecular-weight heparin (LMWH) as the preferred anticoagulant for CAT for years, based on clinical trial data showing LMWH to be associated with a lower risk of recurrent thrombosis when compared with vitamin K antagonists. However, the potentially painful, subcutaneously administered LMWH injections can be expensive, and clinical practice has not been consistent with guideline recommendations. Recently, studies have compared LMWH to the direct oral anticoagulants (DOACs) for the management of CAT. Based on promising trial results outlined in this review, DOACs are now preferred anticoagulants for CAT occurring in patients without gastric or gastroesophageal lesions. For patients with gastrointestinal cancers, who may be at higher risk of hemorrhage with the DOACs, LMWH remains the anticoagulant of choice. Applying the latest data from this rapidly evolving field to care for diverse patient groups can be challenging. This article provides an evidence-based review of outpatient anticoagulant selection for lower-extremity deep vein thrombosis or pulmonary embolism in the setting of cancer, and takes into account special populations with cancer.

Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.

Nonadministration of pharmacologic venous thromboembolism prophylaxis is less common in hospitalized patients with COVID-19.

INTRODUCTION: The incidence of venous thromboembolism (VTE) in patients hospitalized with COVID-19 is higher than most other hospitalized patients. Nonadministration of pharmacologic VTE prophylaxis is common and is associated with VTE events. Our objective was to determine whether nonadministration of pharmacologic VTE prophylaxis is more common in patients with COVID-19 versus other hospitalized patients. MATERIALS AND METHODS: In this retrospective cohort analysis of all adult patients discharged from the Johns hopkins hospital between Mar 1 and May 12, 2020, we compared demographic, clinical characteristics, VTE outcomes, prescription and administration of VTE prophylaxis between COVID-19 positive, negative, and not tested groups. RESULTS: Patients tested positive for COVID-19 were significantly older, and more likely to be Hispanic, have a higher median body mass index, have longer hospital length of stay, require mechanical ventilation, develop pulmonary embolism and die (all p < 0.001). COVID-19 patients were more likely to be prescribed (aOR 1.51, 95% CI 1.38-1.66) and receive all doses of prescribed pharmacologic VTE prophylaxis (aOR 1.48, 95% CI 1.36-1.62). The number of patients who missed at least one dose of VTE prophylaxis and developed VTE was similar between the three groups (p = 0.31). CONCLUSIONS: It is unlikely that high rates of VTE in COVID-19 are due to nonadministration of doses of pharmacologic prophylaxis. Hence, we should prioritize research into alternative approaches to optimizing VTE prevention in patients with COVID-19.

US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021.

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures: Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

What Does Venous Thromboembolism Mean in the National Surgical Quality Improvement Program?

BACKGROUND: Venous thromboembolism (VTE) affects an estimated 350,000 to 600,000 individuals and causes approximately 100,000 deaths annually in the United States. Postoperative VTE is a core measure reported by The American College of Surgeons' National Surgical Quality Improvement Program (NSQIP). The objective of this research was to assess the validity of VTE events reported by NSQIP. MATERIALS AND METHODS: This is a retrospective analysis using NSQIP data from January 2006 through December 2018 and the electronic health record system data from five adult hospitals in the Johns Hopkins Health System. We included patients aged 18 years and older with a VTE event identified in our NSQIP data set. The main outcome measure was the proportion of valid VTE events, defined as concordant between the NSQIP data set and medical chart review for clinical documentation. RESULTS: Of 474 patients identified in our NSQIP database with a VTE, 26 (5.5%) did not meet the strict NSQIP definition of VTE. Nine had a preoperative history of DVT and no new postoperative event, seven had a negative workup for VTE, six had a peripheral arterial thrombus, two did not receive or refused therapy, one had an aortic thrombus, and one had a venous thrombosis in a surgical flap. CONCLUSIONS: We identified a considerable number of surgical patients misclassified as having a VTE in NSQIP, when did not truly. This highlights the need to improve definition specificity and standardize processes involved in data extraction, validation, and reporting to provide unbiased data for use in quality improvement.

Therapeutic Plasma Exchange: A potential Management Strategy for Critically Ill COVID-19 Patients.

In the 5 months since initial reports of COVID-19 came to light, the death toll due to SARS-CoV-2 has rapidly increased. The morbidity and mortality of the infection varies based upon patient age, comorbid conditions, viral load, and the availability of effective treatments. Findings from limited autopsies, clinical observations, and laboratory data suggest that high cytokine levels and a procoagulant state can precipitate acute respiratory distress syndrome and multi-organ dysfunction syndrome in critically ill patients. To complicate matters, comorbidities may affect the response to medical treatments currently in use, all of which are still in trial phase. Therapeutic plasma exchange (TPE) merits consideration in the treatment of critically ill COVID-19 patients and is an avenue for clinical trials to pursue. If efficacious, faster recovery of patients may lead to shorter intensive care unit stays and less time on mechanical ventilation. Herein, we briefly discuss some of the various approaches currently being investigated for the treatment of SARS-CoV-2 with a focus on potential benefits of TPE for selected critically ill patients.

Venous Thromboembolism Quality Measures Fail to Accurately Measure Quality.

Venous thromboembolism (VTE) is 1 of the most common causes of preventable harm for patients in hospitals. Consequently, the Joint Commission, the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, the United Kingdom Care Quality Commission, the Australian Commission on Safety and Quality in Health Care, the Maryland Health Services Cost Review Commission, and the American College of Surgeons have prioritized measuring and reporting VTE outcomes with the goal of reducing the incidence of and preventable harm from VTE. We developed a rubric for defect-free VTE prevention, graded each organizational VTE quality measure, and found that none of the current VTE-related quality measures adequately characterizes VTE prevention efforts or outcomes in hospitalized patients. Effective VTE prevention is multifactorial: clinicians must assess patients' risk for VTE and prescribe therapy appropriate for each patient's risk profile, patients must accept the prescribed therapy, and nurses must administer the therapy as prescribed. First, an ideal, defect-free VTE prevention process measure requires: (1) documentation of a standardized VTE risk assessment; (2) prescription of optimal, risk-appropriate VTE prophylaxis; and (3) administration of all risk-appropriate VTE prophylaxis as prescribed. Second, an ideal VTE outcome measure should define potentially preventable VTE as VTE that developed in patients who experienced any VTE prevention process failures.

Ultrasound for Lower Extremity Deep Venous Thrombosis: Multidisciplinary Recommendations From the Society of Radiologists in Ultrasound Consensus Conference.

Venous ultrasound is the standard imaging test for patients suspected of having acute deep venous thrombosis (DVT). There is variability and disagreement among authoritative groups regarding the necessary components of the test. Some protocols include scanning the entire lower extremity, whereas others recommend scans limited to the thigh and knee supplemented with serial testing. Some protocols use gray-scale ultrasound alone, whereas others include Doppler interrogation. Point-of-care ultrasound is recommended in some settings, and there is heterogeneity of these protocols as well. Heterogeneity of recommendations can lead to errors including incorrect application of guidelines, confusion among requesting physicians, and incorrect follow-up. In October 2016, the Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts to evaluate the current evidence to develop recommendations regarding ultrasound protocols for DVT and the terminology used to communicate results to clinicians. Recommendations were made after open discussion and by unanimous consensus.The panel recommends a comprehensive duplex ultrasound protocol from thigh to ankle with Doppler at selected sites rather than a limited or complete compression-only examination. This protocol is currently performed in many facilities and is achievable with standard ultrasound equipment and personnel. The use of these recommendations will increase the diagnosis of calf DVT and provide better data to explain the presenting symptoms. The panel recommends a single point-of-care protocol that minimizes underdiagnoses of proximal DVT.The panel recommends the term chronic postthrombotic change to describe the residual material that persists after the acute presentation of DVT to avoid potential overtreatment of prior thrombus.Adoption of a single standardized comprehensive duplex ultrasound and a single point-of-care examination will enhance patient safety and clinicians' confidence.

How I treat central venous access device-related upper extremity deep vein thrombosis.

Central venous access device (CVAD)-related thrombosis (CRT) is a common complication among patients requiring central venous access as part of their medical care. Complications of CRT include pulmonary embolism, recurrent deep venous thrombosis, loss of central venous access, and postthrombotic syndrome. Patient-, device-, and treatment-related factors can influence the risk of CRT. Despite numerous randomized controlled trials, the clinical benefit of pharmacologic thromboprophylaxis for the prevention of CRT remains to be established. Therefore, minimizing patient exposure to known risk factors is the best available approach to prevent CRT. Venous duplex is recommended for the diagnosis of CRT. Anticoagulation for at least 3 months or the duration of the indwelling CVAD is recommended for treatment of CRT. Thrombolysis should be considered for patients at low risk for bleeding who have limb-threatening thrombosis or whose symptoms fail to resolve with adequate anticoagulation. CVAD removal should be consider for patients with bacteremia, persistent symptoms despite anticoagulation, and if the CVAD is no longer needed. Superior vena cava filters should be avoided. Prospective studies are needed to define the optimal management of patients with or at risk for CRT.

Etiology and Management of Upper-Extremity Catheter-Related Thrombosis in Cancer Patients.

Central venous access devices are a critical instrument in the treatment and supportive care delivery for oncology patients. Catheter-related thrombosis (CRT) is a common complication of central venous access devices in oncology patients. Risk factors for CRT include patient-, device-, and treatment-related risk factors. Treatment of CRT is indicated to reduce symptoms, prevent catheter malfunction, prevent recurrent DVT or thromboembolic pulmonary embolism, and minimize the risk of post-thrombotic syndrome. Minimal prospective data exist on the prevention and treatment of catheter-related thromboses in cancer patients. As such recommendations largely are derived from data in the lower-extremity DVT and PE studies in cancer and non-cancer patients. Based on the available literature, primary pharmacologic prophylaxis against CRT is not recommended in cancer patients. Treatment options for CRT include catheter removal, anticoagulation, catheter-directed thrombolysis, or surgical thrombectomy. Current evidence-based guidelines recommend LMWH as the anticoagulant of choice. However, recent data showing efficacy and safety of DOACs in cancer-related VTE may be extrapolated to treatment of CRT in cancer patients. In patients with CRT, catheter removal should be pursued if continued vascular access is no longer needed, the catheter is dysfunctional, a catheter-associated infection is present, or if CRT symptoms do not resolve with anticoagulation alone. Catheter-directed thrombolysis is reserved for rare severe cases of CRT. Herein we discuss the pathophysiology, clinical presentation, diagnosis, and general management of CRT in cancer patients.