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1. A technique is described for the separation of fibrinogen by paper electrophoresis and the effects of various anticoagulants are compared: the best results were obtained with a veronal buffer and with heparin as anticoagulant. 2. Numerous difficulties, including that of avoiding denaturation of the fibrinogen and the incomplete separation of fibrinogen from the neighboring fractions, render quantitative estimation unsatisfactory and inferior to the standard methods. [ABSTRACT FROM AUTHOR]

The article discusses the benefits of anticoagulants in the treatment of pulmonary embolism. The effects of heparin, the mainstay of treatment, and its hazards in treating pulmonary embolism are discussed. It was found that anticoagulants such as warfarin prevents the recurrence of pulmonary embolism but with consideration on the hazards of treatment.

The article presents abstracts on several Phlebological topics including endovenous laser ablation of insufficient performing veins, usefulness of thrombophilia testing and therapeutic use of simvastatin for venous ulcers.

Lambl's excrescence (LE), a rare thin linear fibrous thread of collagen and elastic fibrous tissue originating at closure margins of heart valve leaflets is considered a rare cause of thromboembolism, causing ischemic stroke, transient ischemic attack (TIA), acute coronary syndrome, or peripheral thromboembolism. The gold standard for diagnosing LE is transesophageal echocardiography (TEE). Due to the rarity of the disease and lack of significant research, no guidelines exist about the management of LE. Twenty-two papers about LE were reviewed, focusing on the management aspect aiming to assist in guideline publication. Articles were retrieved using PubMed database using "Lambl's excrescences" as a keyword. All free full text papers up to 2023 were retrieved. In this report, we present the first publication of a case of a TIA secondary to LE in the United Arab Emirates. A 53-year-old male presented with transient attacks of left monocular blindness with complete recovery 2 days later. Extensive stroke work-up was negative, except for TEE, which showed an echo-dense linear mobile structure attached to the aortic surface of the aortic valve closure margin, suggesting LE. As no guidelines exist on the management of LE, the patient was started on Clopidogrel 75 mg daily and remained asymptomatic for 2 years. After reviewing the literature, we suggest the use of Aspirin for patients with ⩾1 embolic event attributed to LE while not on antiplatelets or anticoagulants, as it is the most used and recommended treatment option and is effective in preventing recurrent thromboembolic events. [ABSTRACT FROM AUTHOR]

Tissue necrosis is a serious but rare complication of sclerotherapy. Early detection and targeted management are essential to prevent progression and minimise serious complications. In the first instalment of this paper, we reviewed the pathogenic mechanisms of post-sclerotherapy necrosis. Here, we describe risk minimisation and management strategies. Risk factors must be addressed to reduce the chance of necrosis following sclerotherapy. These may be treatment-related including poor choice of sclerosant type, concentration, volume or format, poor injection technique, suboptimal ultrasound visualisation and treatment of vessels in high-risk anatomical areas. Risk factors specific to individual patients should be identified and optimised pre-operatively. Tissue necrosis is more likely to occur with extravasation of irritant sclerosants such as absolute alcohol, sodium iodide, bleomycin and hypertonic saline, whereas extravasation of foam detergent sclerosants rarely results in tissue loss. Proposed treatments for extravasation of irritant sclerosants include infiltration of an isotonic fluid and hyaluronidase. Management of inadvertent intra-arterial injections may require admission for neurovascular observation and monitoring for ischaemia, intravenous systemic steroids, anticoagulation, thrombolysis and prostanoids infusion when required. Treatment of veno-arteriolar reflex vasospasm (VAR-VAS) necrosis follows the same protocol involving systemic steroids but rarely requires hospital admission and may not require anticoagulation. In general, treatment of post-sclerotherapy necrosis is challenging and most proposed treatment measures are not evidence-based and only supported by anecdotal personal experience of clinicians. Despite all measures, once the necrosis has set in, it is very difficult to reverse the process and all measures described here may only be useful in prevention of progression and extension of the ulceration. Mid to long-term measures include addressing exacerbating factors, management of medical and psychosocial comorbidities, treatment of secondary infections and referrals to relevant specialists. All ulcers should be managed with compression and prescribed dressing regimes in line with the healing stage of the ulcer. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 associated VTE is a new disease entity with high morbidity and mortality. The aim of this paper is to review contemporary emerging literature on the incidence, pathophysiology, predictive prognostic indicators, and management consensus for Covid-19 related thrombotic complications, in particular DVT and PE. Methods: A literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All searches were done via PubMed. References of review articles were further screened according to the exclusion criteria. Results: In total, 154 records were identified and 20 duplicates were removed. A final 68 articles were included in the qualitative analysis. COVID-19 related thrombosis can affect multiple organs of the body, presenting in the form of arterial or venous thrombosis such as ischemic stroke, myocardial infarction, mesenteric ischemia, limb ischemia, DVT, or PE. DVT and PE has an overall incidence of 6–26%, and severely ill COVID-19 patients have even higher incidence of thromboembolism. On the other hand, incidence of arterial thromboembolism is much lower with incidence of 0.7%–3.7%. D-dimer is found to be an independent risk factor, and IMPROVE score, Caprini score, and Padua score have all been used as predictors. International guidelines suggest the use of low molecular weight heparin (LMWH) or fondaparinux for prophylaxis of VTE, and therapeutic dosage of weight adjusted LMWH for treatment if confirmed diagnosis. Conclusions: Contemporary rapidly evolving evidence shows that COVID-19 associated thrombosis was a novel clinical entity, especially in severely ill COVID-19 patients. There are multiple society-driven guidelines only, but without any level 1 evidence for management regimen. The ideal dose for prophylaxis is not established and may vary depending on balance of bleeding and thrombosis risk. The risk of bleeding may be increased in patients in intensive care unit. [ABSTRACT FROM AUTHOR]

Objective: Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature. Method: We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status. Results: The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein. Conclusion: Future pharmacokinetic studies are warranted to better understand the interaction. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this paper were to identify and compare clinical prediction models used to assess the risk of venous thromboembolism (VTE) in ambulatory patients with cancer, as well as review the rationale and implementation of a pharmacist-led VTE screening program using the Khorana Risk Score model in an ambulatory oncology centre in Sault Ste. Marie, Ontario, Canada. Data Sources: PubMed was used to identify clinical practice guidelines and review articles discussing risk prediction models used to assess VTE risk in ambulatory patients with cancer. Data Summary: Three commonly used VTE risk prediction models in ambulatory patients with cancer: the Khorana Risk Score, Vienna Cancer and Thrombosis Study (CATS) and Protecht Score, were identified via literature review. After considering guideline recommendations, site-specific factors (i.e. laboratory costs, time pharmacists spent calculating VTE risk) and evidence from the CASSINI and AVERT trials, a novel pharmacist-led VTE risk assessment program using the Khorana Risk Score was developed during a fourth-year PharmD clinical rotation at the Algoma District Cancer Program (ADCP) [ambulatory cancer care centre]. ADCP patients with a Khorana Risk Score of ≥ 2 were referred to the hematologist for a full VTE workup. Considering limitations, inclusion and exclusion criteria of the CASSINI and AVERT trials, the hematologist and pharmacy team decided on appropriate initiation of thromboprophylaxis with a direct oral anticoagulant (DOAC). Conclusions: The Khorana Risk Score was the chosen model used for the pharmacist-led VTE risk assessment program due to its user-friendly scoring algorithm, evidence from validation studies and clinical trials, as well as ease of integration into pharmacy workflow. More research is needed to determine if pharmacist-led VTE risk assessment programs will impact patient outcomes, such as morbidity and mortality, secondary to cancer-associated thrombosis. [ABSTRACT FROM AUTHOR]

Approximately 1–2 per 1000 pregnancies are complicated by venous thromboembolism (VTE). VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE) and the diagnostic management of pregnancy-related VTE is challenging. Current guidelines vary greatly in their approach to diagnosing PE in pregnancy as they base their recommendations on scarce and weak evidence. The pregnancy-adapted YEARS diagnostic algorithm is well tolerated and is the most efficient diagnostic algorithm for pregnant women with suspected PE, with 39% of women not requiring computed tomographic pulmonary angiography. Low-molecular-weight heparin is the first-choice anticoagulant treatment in pregnancy and should be continued until 6 weeks postpartum and for a minimum of 3 months. Direct oral anticoagulants should be avoided in women who want to breastfeed. Management of delivery needs a multidisciplinary approach in order to decide on an optimal delivery plan. Neuraxial analgesia can be given in most patients, provided time windows since last low-molecular-weight heparin dose are respected. Women with a history of VTE are at risk of recurrence during pregnancy and in the postpartum period. Therefore, in most women with a history of VTE, thromboprophylaxis in subsequent pregnancies is indicated. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

Introduction: NVAF is estimated to affect between 6.4 and 7.4 million Americans in 2018, and increases the risk of stroke 5-fold. To mitigate this risk, guidelines recommend anticoagulating AF patients unless their stroke risk is very low. Despite these recommendations, 30.0-60.0% of NVAF patients do not receive indicated anticoagulation. To better understand why this may be, we surveyed PCPs and cardiologists nationwide on their attitudes, knowledge and practices toward managing NVAF with warfarin and direct-acting oral anticoagulants (DOACs). Methods: We surveyed 1,000 PCPs and 500 cardiologists selected randomly from a master list of the American Medical Association, using a paper based, anonymous, self-administered, mailed scannable survey. The survey contained questions on key demographics and data concerning attitudes, knowledge and practices related to prescribing DOACs. The surveys went out in the fall/winter of 2017-8 with a $10 incentive gift card. Survey responses were scanned into an Excel database and analyzed using SAS 9.3 (Cary, NC) for descriptive and inferential statistics. Results: Two hundred and forty-nine providers (167 PCPs, 82 cardiologists) participated in the study with a response rate of 18.8% (249/1320). Respondent mean years ±SD of experience since completing residency was 23.2 ± 13.8. Relative to cardiologists, less PCPs use CHADsVASC (36.8% vs. 74.4%) (p < 0.0001); more have never used HAS-BLED, HEMORR2HAGES, or ATRIA (38.5% vs. 9.8%) (p <.0001); more felt that their lack of knowledge/experience with DOACs was a barrier to prescribing the agents (p = 0.005); and more reported that they could use additional education on DOACs (87.0% vs. 47.0%) (p < 0.0001). Overall, cardiologists were more concerned about ischemic stroke outcomes, while PCPs were more concerned with GI bleeding. Cardiologists also felt that clinical trial data were most helpful in choosing the most appropriate DOAC for their patients, while PCPs felt that Real World Data was most useful. Conclusions: Cardiologists were more concerned with ischemic stroke while anticoagulating patients and utilized screening instruments like CHADsVASC in a majority of their patients. PCPs were concerned with GI bleeds when anticoagulating but nearly 40.0% utilized no screening tools to assess bleeding risk. Our findings show that future education about DOACs would be warranted especially with PCPs. [ABSTRACT FROM AUTHOR]

Data on characteristics and outcomes of coronavirus (COVID)-19 patients complicated with arterial thrombosis (AT) are scarce. Therefore, we carried out a systematic review (PRISMA, PROSPERO statements; PubMed, Scopus, and Web of Science) to identify risk factors, clinical presentation, treatment, and outcomes. We included publications from December 2019 to October 2020. Groups: (a) ischemic stroke, (b) thrombotic storm, (c) peripheral vascular thrombosis, (d) myocardial infarction, and (e) left cardiac thrombus or in-transit thrombus (venous system thrombus floating or attaching to the right heart). We considered 131 studies. The most frequent cardiovascular risk factors were: hypertension, diabetes, and dyslipidemia. A high proportion presented with asymptomatic, mild, or moderate COVID-19 (n = 91, 41.4%). We identified a high percentage of isolated ischemic stroke and thrombotic storm. Groups with higher mortality rate: intracardiac thrombus (1/2, 50.0%), thrombotic storm (18/49, 36.7%), and ischemic stroke (48/131, 36.6%). A small number received thromboprophylaxis. Most patients received antithrombotic treatment. The most frequent bleeding complication was intracranial hemorrhage, primarily with isolated stroke. Overall mortality was 33.6% (74/220). Despite a wide range of COVID-19 severity, a high proportion had AT as a complication of non-severe disease. AT can affect different vascular territories; mortality is associated with stroke, intensive care unit stay, and severe COVID-19. [ABSTRACT FROM AUTHOR]

Background Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value. Methods A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed. Results Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents. Conclusions The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer. [ABSTRACT FROM AUTHOR]

This article focuses on several tests for deterring mucopolysaccharides (MPS) in urine have been developed. The screening tests include the toluidine blue spot lest, the albumin turbidimetric test, the gross albumin turbidity test and the cetyltrimethyl-ammonium bromide test. The spot-test technic with toluidine blue of researchers, currently in wide use, lacks both specificity and is not sufficiently sensitive for the detection of MPS at the low concentrations found in normal human urine. The procedure presented herein lessens the time requirement and provides for identification of normal and abnormal levels of MPS in urine. The classification of some disorders involving MPS depends upon the separation and identification of several of the acid MPS: chondroitin sulfate A, chondroitin sulfate B (ChS B), chondroitin sulfate, heparin and hyaluronic acid. Modification of a previously published, technic permits the MPS identification of ChS B and other MPS components in urine of patients diagnosed as having one of the mucopolysaccharidoses.

Objectives: Determine indication specific 4-Factor prothrombin complex concentrate (4FPCC) dosing strategies within a hospital system and subsequent effectiveness. Background: 4FPCC is FDA approved for reversal of vitamin K antagonists (VKA) for acute major bleeding or need for urgent surgery/invasive procedure. Since its approval, off label use has expanded to include direct oral anticoagulant reversal and perioperative hemostasis. Optimal dosing strategies remain controversial, and recent studies have evaluated fixed-dose regimens with lower doses than those recommended in product labeling. Methods/Materials: Retrospective cohort with manual chart review for patients who received 4FPCC spanning 2 years. Primary outcome was to characterize dosing. Secondary outcomes were INR normalization, hemostatic efficacy, in-hospital mortality, and renal function change. Results: Of the 300 patients evaluated, 80% received 4FPCC for anticoagulant reversal, with 66% of those for VKA and 34% for DOAC. The remaining 20% received 4FPCC for a non-reversal indication. Of the patients requiring anticoagulation reversal, 25% received doses lower than recommended and 6% received higher. 71% of patients received 4FPCC for life-threatening bleed, and 45% of them had intracranial hemorrhage. Higher mortality with higher than recommended doses was the only statistically significant secondary outcome (P =.018). Conclusion: We found that lower doses than recommended were used in a significant number of patients. The higher than recommended doses group constituted a small proportion of patients and the higher mortality was attributed to patient acuity on presentation. Additional studies evaluating dosing approach are required to determine lowest effective dosing for various indications. [ABSTRACT FROM AUTHOR]

Objectives. Venous thromboembolism (VTE) occurs more frequently in cancer patients than in non-cancer patients and outcomes are poor in patients with both cancer and thrombosis. Patients with cancer who develop thrombosis are more likely to experience a recurrence of VTE and have increased bleeding complications while receiving oral anticoagulant treatment. The purpose of this paper is to discuss the causes and outcomes of thrombosis in cancer patients, the limitations of warfarin therapy, the guidelines and data for the use of low-molecular-weight heparins (LMWHs) in the treatment and secondary prevention of thrombosis in cancer patients, and emerging data regarding survival with the use of LMWH in cancer patients. Methods. Literature for this paper has been collected using multiple sources, including primary, secondary, and tertiary references. Online searches have been conducted utilizing the PubMed and OVID databases, and abstracts from the Proceedings of the American Society of Clinical Oncology and the American Society of Hematology Annual Meeting and Exhibition. The following key terms were used in the search: cancer, deep vein thrombosis, pulmonary embolism, anticoagulation, LMWHs, guidelines, survival, cost. Results. The long-term use of LMWHs in the settings of cancer and thrombosis are supported by recent clinical trial evidence that demonstrate their equivalent safety and improved efficacy when compared to oral anticoagulants resulting in their inclusion in current guidelines. Finally, newer studies offer further evidence of improved outcomes with dalteparin and nadroparin, including possible survival benefits. Conclusions. Treatment with LMWHs has been shown to be more effective than warfarin in the extended treatment of VTE in patients with cancer and is safe in this setting. Use of a LMWH for at least the first 3–6 months of long-term treatment is now considered the standard of care for patients with cancer and is recommended in numerous guidelines. Additionally, further evaluation of the survival benefits of LMWH in cancer patients is warranted. [ABSTRACT FROM AUTHOR]

The DOAC Dipstick test has potential for aiding in patient care as the rapid, near-patient result reporting, classifying type of DOAC and above/below threshold levels, can assist clinical decision making in multiple settings. The use of direct acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban has changed the management and prevention of ischemic stroke in patients with atrial fibrillation, treatment of venous thromboembolism (VTE), prophylaxis for prevention of VTE following elective surgery, and management of acute coronary syndrome.[1] DOACs are inhibitors of either thrombin or coagulation factor Xa. [Extracted from the article]

All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from cancer-associated VTE. However, there is still a debate about whether the new oral anticoagulant, rivaroxaban, can bring better efficacy and safety outcomes globally. Thus, this systematic review and meta-analysis was conducted to evaluate the efficacy and safety of rivaroxaban. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure for relevant published papers before 1 September 2019, with no language restrictions. The primary outcomes are defined as the recurrence of VTE. The secondary outcomes are defined as clinically relevant non-major bleeding, adverse major bleeding events, and all-cause of death. The data were analyzed by Stata with risk ratio (RR) and 95% confidence interval (CI). Four trials encompassing 1996 patients were included. Rivaroxaban reduced recurrent VTE with no significant difference (RR = 0.68, 95% CI = 0.43–1.07). Similarly, there were no significant differences in adverse major bleeding events (RR = 0.86, 95% CI = 0.37–2.00), clinically relevant non-major bleeding (RR = 1.24, 95% CI = 0.73–2.12) and all-cause mortality (RR = 0.76, 95% CI = 0.40–1.44). In a selected study population of cancer patients with VTE, rivaroxaban is as good as other anticoagulants. Further, carefully designed randomized controlled trials should be performed to confirm these results. [ABSTRACT FROM AUTHOR]

Catheter-directed thrombolysis for deep venous thrombosis is considered the basic treatment modality for intrathrombus removal. This method is preferably used in patients with iliofemoral deep venous thrombosis due to poor spontaneous recanalization in this segment, especially on the left side. The method was published almost 25 years ago and has gained ground in the treatment because of poor results from systemic thrombolysis and because of the possibility of stenting any underlying iliac obstruction during the procedure. However, the publications of catheter-directed thrombolysis reveal a great heterogeneity concerning catheter-directed thrombolysis technique and the lack of high quality evidence about monitoring as a tool to minimize the risk of bleeding and pulmonary embolism. Strict inclusion and exclusion criteria, correct composition and infusion of thrombolysis agent, imaging thrombus clearance during catheter-directed thrombolysis, ensuring flow enhancement during the bedridden situation, careful evaluation of indication for stenting based on imaging, and sufficient conversion to anticoagulation treatment following catheter-directed thrombolysis are essential. The aim of this paper is to discuss different treatment aspects of catheter-directed thrombolysis for iliofemoral thrombosis and to suggest a monitoring model for future treatment. [ABSTRACT FROM AUTHOR]

Objective The objective of this paper is to determine which kinds of assays for antiphospholipid antibodies (aPL) should be tested for clinical practice for patients with recurrent pregnancy loss (RPL). Materials and methods We studied 560 patients with a history of RPL prospectively. We determined the obstetric significance of 11 commercially available tested assays for lupus anticoagulant (LA)-aPTT StaClot, phosphatidylserine-dependent antiprothrombin (aPS/PT) IgG, IgM, classical cardiolipin (CL) IgG, IgM, CL IgG, IgM, IgA, and β2glycoprotein I (β2GPI) IgG, IgM, IgA Phadia. Obstetric significance was defined as the potential for anticoagulant therapy to improve the subsequent live birth rate, or a difference in the live birth rate between positive and negative untreated cases. Results The LA-aPTT StaClot assay and aPS/PT IgG assay, but not CL IgG, were found to have obstetric significance. Our conventional tests covered positive cases with the aPS/PT IgM and classical CL IgG assays. The results of the LA-aPTT StaClot, LA-aPTT and LA-RVVT assays showed different distributions, although strong or moderate correlation was observed. Conclusion LA-aPTT StaClot and aPS/PT IgG might be suitable for use in routine practice for patients with RPL. Each test for aPL should be ascertained for obstetric significance, because similar assays may have different outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To examine the longitudinal prevalence and recovery of olfactory, gustatory, and oral chemesthetic deficits in a sizable cohort of SARS-CoV-2 infected persons using quantitative testing. To determine whether demographic and clinical factors, mainly the medications used after the COVID-19 diagnosis, influence the test measures. Methods: Prospective cohort in a hospital with primary, secondary, tertiary, and quaternary care. Patients with confirmed COVID-19 were tested during the acute infection phase (within 15 days of initial symptom, n = 187) and one (n = 113) and 3 months later (n = 73). The University of Pennsylvania Smell Identification Test, the Global Gustatory Test, and a novel test for chemesthesis were administered at all visits. Results: During the acute phase, 93% were anosmic or microsmic and 29.4% were hypogeusic. No one was ageusic. A deficit in oral chemesthesis was present in 13.4%. By 3 months, taste and chemesthesis had largely recovered, however, some degree of olfactory dysfunction remained in 54.8%. Remarkably, patients who had been treated with anticoagulants tended to have more olfactory improvement. Recovery was greater in men than in women, but was unrelated to disease severity, smoking behavior, or the use of various medications prior to, or during, COVID-19 infection. Conclusions: When using quantitative testing, olfactory disturbances were found in nearly all SARS-CoV-2 infected patients during the acute infection phase. Taste or chemesthetic deficits were low. Olfactory impairment persisted to some degree in over half of the patients at the 3-month follow-up evaluation, being more common in women and less common in those who had been treated earlier with anticoagulants. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]

Introduction: There is no consensus among surgeons with regard to prevention of venous thromboembolism (VTE) in patients undergoing surgical treatment of varicose veins. We performed a systematic review of the available literature. Methods: We systematically searched the online database from PubMed for studies about the incidence of VTE and thromboprophylaxis in varicose vein surgery. We included 13 papers for review. Results: The incidence of VTE after varicose vein surgery remains unclear.Most retrospective case series report an incidence of deep venous thrombosis (DVT) of approximately 1%, based on a clinical diagnosis. However, three prospective studies have systematically detected DVT by means of duplex ultrasound and showed that the true incidence might be 5-10 times higher than expected on a clinical basis. Discussion: More data on the incidence of VTE, and the need for postoperative thromboprophylaxis are necessary to formulate evidence-based clinical guidelines. Therefore, high-quality randomised clinical trials, with high numbers of included patients, and ideally comparing prophylaxis to placebo are warranted. [ABSTRACT FROM AUTHOR]

The relationship between cancer and venothromboembolic events is a complex, multifactorial process which is still not fully understood and therefore the use of current generic guidelines may be inadequate. Current management of cancer-related VTE may be suboptimal because of the lack of cancer-specific studies into the role of primary prophylaxis in both ambulant and non-ambulant cancer patients. Further research into developing cancer-specific risk assessment tools and the choice, dose and duration of prophylaxis is required. The management of confirmed symptomatic VTE in cancer patients is outlined but certain controversies remain. Areas for further research include the management of asymptomatic unsuspected VTE events, recurrent VTE events on treatment and the role of IVC filters and other treatment options are required. This paper attempts to cover some of the recent developments and areas of uncertainty surrounding the management of cancer-related VTE. [ABSTRACT FROM AUTHOR]

Oral anticoagulant-associated intracerebral hemorrhage is increasing in incidence and is the most feared complication of therapy with vitamin K1 antagonists. Anticoagulant-associated intracerebral hemorrhage has a high risk of ongoing bleeding, death, or disability. The most important aspect of clinical management of anticoagulant-associated intracerebral hemorrhage is represented by urgent reversal of coagulopathy, decreasing as quickly as possible the international normalized ratio to values ≤1·4, preferably ≤1·2, together with life support and surgical therapy, when indicated. Protocols for anticoagulant-associated intracerebral hemorrhage emphasize the immediate discontinuation of anticoagulant medication and the immediate intravenous administration of vitamin K1 (mean dose: 10-20 mg), and the use of prothrombin complex concentrates (variable doses calculated estimate circulating functional prothrombin complex) or fresh-frozen plasma (15-30 ml/kg) or recombinant activated factor VII (15-120 μg/kg). Because of cost and availability, there is limited randomized evidence comparing different reversal strategies that support a specific treatment regimen. In this paper, we emphasize the growing importance of anticoagulant-associated intracerebral hemorrhage and describe options for acute coagulopathy reversal in this setting. Additionally, emphasis is placed on understanding current consensus-based guidelines for coagulopathy reversal and the challenges of determining best evidence for these treatments. On the basis of the available knowledge, inappropriate adherence to current consensus-based guidelines for coagulopathy reversal may expose the physician to medico-legal implications. [ABSTRACT FROM AUTHOR]

Symptomatic venous thromboembolism (VTE) occurs in 15% of patients with advanced malignancy. Primary thromboprophylaxis using low-molecular-weight heparin (LMWH) is supported by Level 1A evidence but is under-utilized in the palliative setting. A systematic search was performed of Medline, Cochrane Library, EMBASE, AMED, and Web of Science for papers published between 1960 and January 2010 using search terms: 'palliative', 'thromboprophylaxis', 'thromboembolism', 'heparin', and 'advanced cancer'. Forty-two citations were obtained, of which 34 were excluded as they dealt with treatment of VTE, novel anticoagulants, or LMWH as a cancer treatment. Eight original articles were reviewed independently by two authors. Data was extracted according to a predetermined questionnaire. Studies examined practice in specialist palliative care (SPC) units, and attitudes held by a total of 32 physicians and 198 patients. Patients find LMWH acceptable, particularly patients who experienced a sudden decline in performance status. Reluctance to prescribe LMWH is based on physicians' concerns regarding negative impact on quality of life, and lack of evidence specific to the palliative care setting. In conclusion, LMWH prophylaxis should be implemented in patients with a previously good performance status who have a transiently increased risk of VTE and no contraindications. Further research is required using outcome measures specific to palliative care. [ABSTRACT FROM AUTHOR]

In the current paper, we provide recommendations for the assessment of deep vein thromboses for the purpose of therapeutic trials evaluating antithrombotic drugs in the prevention of deep venous thrombosis. We have reviewed recently published articles on diagnostic and therapeutic studies, and we have evaluated methods of assessments. Ascending venography has been considered as the reference test for the confirmation of DVT. A roentgenographic image is subsequently available for review and allows classification by blinded, objective observers. However, venography poses substantial clinical and methodological limitations, particularly in the setting of systematic screening for all patients enrolled in a randomized clinical trial. Compression ultrasonography may replace venography for systematic screening of DVT in clinical trials, provided that specific methodological details are specified in the protocol and are fulfilled to ensure high and comparable sensitivity and specificity from all participating centers. This non-invasive technique has virtually no contraindications, and therefore more patients can be enrolled and evaluated. Furthermore, the compression ultrasonograph can be videotaped for central reading, Compression ultrasonography has already been adopted as the principal method for evaluating DVT in several ongoing large scale prevention trials with the approval of major drug agencies. [ABSTRACT FROM AUTHOR]

Antiaggregant and anticoagulant drugs are essential in the management of the manifestations due to antiphospholipid syndrome (APS) in patients with primary Hughes' syndrome or systemic lupus erythematosus. Coumadin derivatives (warfarin and acenocumarol), heparin and aspirin are used for secondary thromboprophylaxis and treatment of recurrent miscarriage. The available evidence for each indication is reviewed in this paper. There is still debate regarding the optimal intensity of oral anticoagulation, the best drug combination for pregnancy failure in APS and the management of asymptomatic patients with antiphospholipid antibodies. [ABSTRACT FROM AUTHOR]

Warfarin is the most commonly prescribed anti-coagulant medication. Warfarin's pharmacokinetics (PK) in its enantiomeric form have been reported to be highly variable. Five population pharmacokinetic model studies for warfarin were identified in this systematic review. This review summarized these studies and reported on various factors affecting warfarin PK. Most studies reported a one-compartment model with first-order absorption and elimination for both S-warfarin and R-warfarin. Warfarin disposition has been reported to be influenced by various factors, including gender, age, genetic variation, body surface area (BSA), concurrent drug, weight, and ethnicity. So, all of these factors must be considered when addressing this pharmacokinetic variability. These models should undergo an external evaluation to confirm their generalizability and to support model-informed dosing in clinical settings. [ABSTRACT FROM AUTHOR]

We report an unusual case of a 40-year-old male patient who experienced painful swelling of the left lower limb that persisted for 1 week. Imaging modalities not only confirmed the diagnosis of acute iliofemoral venous thrombosis and pulmonary embolism (PE), but also an incidental finding of interrupted inferior vena cava (IVC). This congenital anomaly is uncommon but rarely associated with venous thromboembolism (VTE). The azygos continuation was compressed by the descending aorta against the 11th thoracic vertebrae, which was identified as the cause of VTE. He was treated successfully with anticoagulation and compression therapy. The patient was discharged with lifelong oral Rivaroxaban and remained asymptomatic. In the literature, only 9 cases of interrupted IVC-associated PE were identified but none was due to significant venous compression. [ABSTRACT FROM AUTHOR]

All of the circumstances influencing any of the elements of Virchow's Triad can increase the risk of venous thromboembolism. Assessing prothrombotic factors can sometimes be difficult. One of the examples of such a condition is nephrotic syndrome. In this condition at least two elements of Virchow's triad are affected: physiological blood composition and the venous blood flow which is slowed down by the edema. Except for the cases mentioned in KDIGO (Kidney Disease: Improving Global Outcomes), the use of anticoagulant drugs in the prophylaxis of VTE (Venous Thromboembolism) in nephrotic syndrome seems unclear. Nevertheless, due to the increased risk of VTE, it is worth implementing mechanical anticoagulant prophylaxis, which can also improve the quality of life of patients by reducing swelling. The article analyzes the current knowledge on the field and gives some proposals with low bleeding risk. [ABSTRACT FROM AUTHOR]

Background: Adequate antithrombotic therapy is essential to prevent thrombus formation during percutaneous endovascular interventions (PVI). We hypothesize that interventions for non-complex lesions of iliac arteries do not need procedural anticoagulation if patients are under dual antiplatelet therapy (DAPT). Methods: Iliac PVIs performed without procedural anticoagulation were retrospectively screened between 2017 and 2021. Baseline characteristics of patients, in-hospital events and 30-day follow-ups were obtained from hospital records. Each PVI was reviewed for procedural details. Primary safety outcome was thromboembolic events during intervention. Secondary safety outcome was adverse vascular events at 30-day follow-up. Procedure times of iliac interventions were compared to peripheral angiography procedures of patients with similar demographic characteristics. Results: We identified 108 iliac interventions without procedural anticoagulation, median age of 62 (interquartile range 56-68) years, 9 (8.3%) females. Median lesion length was 30 (19-50) mm. We observed a thrombotic finding in 4 (3.7%) procedures. Visible luminal thrombus was observed in 2 (1.9%) and introducer sheath thrombosis in 2 procedures (1.9%), all of which were in patients with in-stent lesions. No distal embolization was observed in final angiography of these procedures. At 30-day follow-up, acute limb ischemia was not observed and clinically driven target vessel revascularization was not required in any of the patients. Procedure time of iliac interventions was similar to that of lower extremity diagnostic procedures [18 (11-24) vs 18 (14-24) min, respectively, P =.364]. No major bleeding event was observed after iliac interventions. Conclusion: Non-complex lesions of iliac arteries can be managed within a time frame similar to that of lower extremity diagnostic procedures. These interventions can be performed safely without procedural anticoagulation, provided patient receives DAPT. Intervention of in-stent lesions should ideally be avoided without procedural anticoagulation. [ABSTRACT FROM AUTHOR]

In spite of a 10–13 fold increased risk of bleeding, standard doses of coumarin with a target prothrombin time of 2.7–4.5 INR (International Normalized Ratio) are chronically used in the Netherlands by 4–5% of the adult population forty to eighty years old, mainly for the secondary prevention of myocardial infarction. The Dutch Thrombosis Services, who monitor these patients, use less rigorous criteria than the standard studies do. It would not, therefore, be too much of a surprise if the numbers of bleeding complications in practice would be much higher than expected from the standard papers so far. To answer this question the authors studied emergency intestinal bleedings in a population-based cohort study of chronic acenocoumarin users (813 person years) and their age-matched and population-based controls (17,620 person years). Of 142 first bleedings serious enough to require immediate sigmoidoscopy, 35 were connected with acenocoumarin (25%). The overall incidences in the acenocoumarin cohort and the age-matched controls were, respectively, 4.3 and 0.6 bleedings/100 person years, RR (relative risk) 7.09, p < 0.0001. Relative Risk (RR) = Incidence Among Exposed⁄Incidence Among Nonexposed The acenocoumarin bleeders and their controls had symmetric clinical diagnoses and levels of hemoglobin. However, acenocoumarin bleeders were significantly older and more frequently males. The sex- and age-adjusted RRs were, however, only slightly different from the crude data, suggesting no major influence of these asymmetries on the overall results. Prothrombin times in the acenocoumarin bleeders were frequently higher than the target range. In the subjects initially excluded from the controls because they used alternative compounds that enhance bleedings, incidences of bleedings were calculated as well. The incidences were 0.6 bleeding/100 person years (RR 1.01, ns) for the patients receiving NSAIDS (nonsteroidal antiinflammatory drugs); 1.5 (RR 2.50, p < 0.05) for aspirin; and 1.6 (RR 2.67, 0.05 < p < 0.1) for dipyridamole. The authors conclude that in an adult population of 5% acenocoumarin users, about 25% of the emergency intestinal bleedings are connected with coumarin. The numbers of coumarin bleedings are 4–6 times higher than reported so far. They also demonstrate that the risk of bleeding from coumarin far exceeds the risks from alternative oral antithrombotic agents, such as aspirin and dipyridamole. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to discuss the controversies surrounding the use and dosing of direct-acting oral anticoagulants (DOACs) in obese patients recognizing the limitations of the existing evidence base that preclude strong recommendations. Data Sources: A literature search of MEDLINE was performed (2020 to end August 2022) subsequent to recent guidelines using the following search terms: direct acting anticoagulants, obesity, rivaroxaban, apixaban, edoxaban, dabigatran, dabigatran etexilate, and clinical practice guidelines. English-language studies and those conducted in adults were selected. Data Synthesis: The available randomized studies evaluating DOACs had relatively small numbers of patients with more extreme forms of obesity (body mass index [BMI] > 40 kg/m2) and none of the larger studies had a specific focus on dosing DOACs in obese patients. Recent guidelines by the International Society on Thrombosis and Haemostasis (ISTH) have specific recommendations for dosing DOACs in obesity. There are pharmacokinetic/pharmacodynamic and observational studies published before and after the ISTH guidelines with a focus on DOAC dosing in obese patients that generally support the recommendations in the guidelines, but most involved small numbers of patients usually with BMIs <45 kg/m2. Relevance to Patient Care and Clinical Practice: This review discusses DOAC dosing in obesity with important considerations for clinicians related to DOAC choice and dosing. Conclusions: Dosing alterations of DOACs do not appear to be necessary when used for either prophylaxis or treatment in patients with BMIs up to approximately 45 to 50 kg/m2, but research is needed for BMIs >50 kg/m2. [ABSTRACT FROM AUTHOR]

Purpose: To present stent-graft treatment of floating thrombus in the abdominal aorta. A review of the literature about aortic floating thrombus (AFT) was also performed. Case report: A 56-year-old female with no risk factors for vascular disease but with history of a mild COVID-19 infection in the previous month, for which she had started anticoagulant therapy at a prophylactic dosage, developed an acute ischemia of the lower limbs and was diagnosed with floating thrombosis of the abdominal aorta. The thrombus was excluded from the aortic blood flow by deployment of a stent-graft in the abdominal aorta. At 12 months, the patient was well, and the thrombus in the abdominal aorta appears to be completely excluded by the stent-graft. A review of the available literature from 1980 to 2022 showed 74 cases of AFT located in the aortic arch, in the descending thoracic and in the abdominal aorta. In most cases the AFT involved the aortic arch (38/74, 51.3%) and/or the descending thoracic aorta (30/74, 40.5%), while the abdominal aorta was involved in 6 cases. In 2 of these 6 cases, the patients had a COVID-19 infection. The AFT was mostly approached either medically with anticoagulation/systemic thrombolysis (32/74, 43.2%) or with surgical removal (31/74, 41.9%), while endovascular coverage of the thrombus with an endograft was performed in 6 cases of AFT located in the aortic arch and in the descending thoracic aorta (3 cases each). Conclusion: There is no consensus about the optimal treatment of AFT. In selected cases, abdominal stent-grafts may be used for stabilization and exclusion of symptomatic abdominal aorta floating thrombosis to prevent progression and recurrent embolization. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the effectiveness and safety of rivaroxaban in patients with isolated distal deep vein thrombosis (IDDVT). Methods: Symptomatic venous thromboembolism (VTE) and major bleeding were assessed. Results: Of 1016 patients with acute symptomatic/asymptomatic DVT and/or pulmonary embolism treated with rivaroxaban, 288 had IDDVT and 294 had proximal DVT (pDVT). The IDDVT group had fewer patients on the higher rivaroxaban dose (30 mg/day) (42.7% vs. 66.0%) and a shorter treatment duration (135.5 vs 369.5 days) than the pDVT group. VTE recurrence occurred in 14 and 11 patients with IDDVT and pDVT, respectively (2.89% vs. 2.29% per patient-year; p = 0.534). Major bleeding was less frequent in the IDDVT group (1.55% vs. 4.53% per patient-year; p = 0.044). Comparable effectiveness and safety were observed with 15 and 30 mg/day rivaroxaban in the IDDVT group. Conclusions: Short-term, low-dose rivaroxaban seems safe and effective for IDDVT treatment. [ABSTRACT FROM AUTHOR]

Splanchnic vein thrombosis (SVT) is not rare in patients with acute pancreatitis. It remains unclear about whether anticoagulation should be given for acute pancreatitis-associated SVT. The PubMed, EMBASE, and Cochrane Library databases were searched. Rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were pooled and compared between patients with acute pancreatitis-associated SVT who received and did not receive therapeutic anticoagulation. Pooled rates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity among studies was evaluated. Overall, 16 studies including 698 patients with acute pancreatitis-associated SVT were eligible. After therapeutic anticoagulation, the pooled rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were 44.3% (95%CI = 32.3%-56.6%), 10.7% (95%CI = 4.9%-18.5%), 13.3% (95%CI = 6.9%-21.4%), 16.8% (95%CI = 6.9%-29.9%), 21.2% (95%CI = 7.5%-39.5%), and 29.1% (95%CI = 16.1%-44.1%), respectively. Anticoagulation therapy significantly increased the rate of SVT recanalization (RR = 1.69; 95%CI = 1.29-2.19; P<.01), and marginally increased the risk of bleeding (RR = 1.98; 95%CI = 0.93-4.22; P = .07). The rates of death (RR = 1.42; 95%CI = 0.62-3.25; P = .40), intestinal ischemia (RR = 2.55; 95%CI = 0.23-28.16; P = .45), portal cavernoma (RR = 0.51; 95%CI = 0.21-1.22; P = .13), and gastroesophageal varices (RR = 0.71; 95%CI = 0.38-1.32; P = .28) were not significantly different between patients who received and did not receive anticoagulation therapy. Heterogeneity was statistically significant in the meta-analysis of intestinal ischemia, but not in those of SVT recanalization, any bleeding, death, portal cavernoma, or gastroesophageal varices. Anticoagulation may be effective for recanalization of acute pancreatitis-associated SVT, but cannot improve the survival. Randomized controlled trials are warranted to further investigate the clinical significance of anticoagulation therapy in such patients. [ABSTRACT FROM AUTHOR]

The Management of Anticoagulation in the Periprocedural Period (MAPPP) app is a free tool providing up-to-date guidelines on the periprocedural management of patients on long-term anticoagulants. After validating its effectiveness in the post-procedural period, we aimed to study its overall cost-effectiveness. SF-12 surveys were sent to eligible patients, converted into SF-6D forms, and subsequently into quality-adjusted life years (QALYs) to calculate the incremental cost-effectiveness ratio (ICER). The number of 30-day readmissions was used to calculate hospitalization costs, utilizing publicly available data. From 1/1/2018 to 1/31/2019, 642 patients were screened for enrollment, with an overall response rate of 94% (164/175) among the consented and 49% (164/336) among all eligible patients. The average QALY score was 0.7134 (95% CI [0.6836, 0.7431]) for the patients whose treatment plan followed the MAPPP app recommendations (acceptance group) and 0.7104 (95% CI [0.6760, 0.7448]) for those who did not (rejection group), without statistically significant differences. The difference in ICER scores was - $429 866.67, with the negative sign demonstrating that acceptance was the dominant strategy. By utilizing QALYs and ICER scores we have shown that the acceptance of MAPPP app recommendations is the dominant strategy for the periprocedural management of patients on long-term anticoagulation. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine which type of prophylaxis was effective for postoperative symptomatic venous throm- boembolism (VTE) in patients with gynecological malignancies. A total of 1756 consecutive patients undergoing laparotomy as first-line treatment were included. In Period 1 (2004-2009), low-molecular weight heparin (LMWH) was not available for post- operative VTE prophylaxis, but available in after Period 2 (2009-2013). In Period 3 (2013-2020), patients with pretreatment VTE could switch from LMWH to direct oral anticoagulant (DOAC) as of 2015. Preoperative VTE was screened by measuring D-dimer, followed by venous ultrasound imaging, and computed tomography and/or perfusion lung scintigraphy. Postoperative symptomatic VTE occurred with an incidence of 2.8% by the measures without prophylactic LMWH administration in Period 1. The incidence of postoperative symptomatic VTE was 0.6% in Period 2 and 0.3% in Period 3, being significantly reduced com- pared with Period 1 (P < .01 and < .0001). The incidences were not significantly different between Periods 2 and 3, but no patient switching to DOAC in Period 3 (n = 79) developed symptomatic VTE. Our preoperative VTE screening and postoperative selec- tive LMWH administration were significantly preventive against postoperative symptomatic VTE. [ABSTRACT FROM AUTHOR]

Even though routine screening of the general hospital population is discouraged, medical laboratories may use a "lupus sensitive" activated partial thromboplastin time test (aPTT) with phospholipid concentrations that are susceptible to inhibition by lupus anticoagulant (LA), to screen for the presence of LA. If deemed necessary, follow-up testing according to ISTH guidelines may be performed. However, LA testing is a laborious and time-consuming effort that is often not readily available due to a lack of automation and/or temporary unavailability of experienced staff. In contrast, the aPTT is a fully automated test that is available 24/7 in almost all medical laboratories and is easily interpreted with the use of reference ranges. In addition to clinical signs, the result of an LA sensitive aPTT may thus be used to lower the suspicion of the presence of LA and reduce costly follow-up testing. In this study, we show that a normal LA sensitive aPTT result may be safely used to refrain from LA testing in the absence of strong clinical suspicion. [ABSTRACT FROM AUTHOR]

Identifying adherence to direct oral anticoagulants (DOACs) plays a major role in treatment efficacy and safety. The DOAC Dipstick can detect DOACs in urine samples of acutely diseased patients at plasma thresholds of about 30 ng/mL. A prospective observational consecutive cohort study was performed on outpatients taking DOACs. The presence of direct oral factor Xa inhibitors (DXIs) in patient urine samples were independently evaluated by visual interpretation of the DOAC Dipstick pad colors. DOAC plasma con- centration was assessed using STA®-Liquid Anti-Xa and STA®-Liquid Anti-IIa chromogenic substrate assays. Positive DOAC Dipstick results were compared with a threshold plasma of DOAC concentration ≥30 ng/mL. Of 120 patients (age 55.4 + 16.1 years, female n = 63), 77 were on rivaroxaban and 43 on apixaban. Plasma concentrations were 129 ± 118 ng/mL for rivaroxaban, and 163 ± 130 ng/mL for apixaban, DOAC Dipstick test has a sensitivity of 97.2% and a positive predictive value of 89.5% at 30 ng/mL. No differences occurred between DXIs. Specificity and negative predictive value could not be determined due to the low number of true negative values. There were no differences in the interpretation of rivaroxaban and apixaban pad colors between observers (Kappa 1.0). Results show that DOAC Dipstick may be a useful tool for identifying DXIs in urine samples in an outpatient setting at a plasma threshold ≥ 30 ng/mL. Further studies should include patients treated with dabigatran, vitamin K antagonists, or other anticoagulants. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) demonstrated similar efficacy and lower risk of intracranial hemorrhage than warfarin in patients with atrial fibrillation and venous thromboembolism. Given the lack of data identifying risk factors in patients who bled while on a DOAC, we sought to investigate these characteristics. Materials and Methods: This retrospective chart review was approved by the Mass General Brigham Institutional Review Board and assessed patients who experienced bleeding events while on DOAC therapy from 6/1/2015 to 7/1/2020. Patient characteristics were evaluated, including age, sex, body mass index (BMI), renal function, concomitant therapies, and baseline comorbidities. Results: Eighty-seven patients were included for analysis, with a median age of 75.8 years. Most patients were female (51.7%) and 24 (27.6%) had a BMI >30. At time-of-event, 21 patients (24.1%) had acute kidney injury. Thirty-three patients (37.9%) were on concomitant antiplatelet therapy (APT), with 31 (35.6%) on single APT and 2 on dual APT. Pertinent comorbidities included hypertension (74.7%), ischemic cerebrovascular accident (28.7%), thyroid abnormality (23.0%), active cancer (14.9%), and anemia (13.8%). Eleven patients (12.6%) had a prior bleeding event. Most patients were on apixaban (69.0%) for the indication of stroke prevention in nonvalvular atrial fibrillation/flutter (72.4%). FDA-approved dosing was used in most patients (92.0%), and all deviations reflected underdosing. Most bleeding events were defined as major (95.4%), occurred at a critical organ site (72.4%), and developed spontaneously (58.6%). Conclusions: These data provide insight into characteristics of patients who experience bleeding events while on DOAC therapy. Understanding these potential risk factors may optimize the safe use of these agents. [ABSTRACT FROM AUTHOR]

The prevalence of venous thromboembolism is high in patients with COVID-19, despite prophylactic anticoagulation. The evidence that supports the preferred thromboprophylaxis regimen in non-critically ill patients with mild to moderate COVID-19 is still limited. Therefore, this systematic review andmeta-analysis aimed to compare the clinical outcomes of hospitalized patients with mild to moderate COVID-19 who received standard thromboprophylaxis anticoagulation with intermediate to high prophylaxis regimens. We systematically searched MEDLINE and Embase databases for published studies until August 17th, 2022. We included studies on patients with mild to moderate COVID-19 who received thromboprophylaxis during their hospital stay. Patients who received standard prophylaxis dose "control group" were compared to patients who received intermediate to high prophylaxis "intervention group". Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes. A comprehensive analysis was conducted, encompassing seven studies involving a total of 1931 patients. The risk of all-cause thrombosis was not statistically different between the two groups (risk ratio [RR] 1.48, 95% confidence interval [CI] [0.11, 20.21]). The risk of minor bleeding was reported to be lower in patients who received intermediate to high prophylaxis (RR 0.64, 95% CI 0.21, 1.97), while had a higher risk of major bleeding compared with the standard prophylaxis (RR 1.40, 95% CI 0.43, 4.61); however, did not reach the statistical significance. The overall risk for all hospital mortality favored the utilization of intermediate to high doses over the standard thromboprophylaxis dosing (RR 0.47, 95%CI 0.29, 0.75). In medically ill patients with COVID-19, there is no difference between standard and intermediate to high prophylaxis dosing regarding thrombosis and bleeding. However, it appears that intermediate to high prophylaxis regimens are linked to additional survival benefits. [ABSTRACT FROM AUTHOR]

Cancer-associated venous thromboembolism (CAT) guidelines recommend direct oral anticoagulants as alternatives to low-molecular- weight heparin (LMWH) in most patients. This study compared the effectiveness and safety of rivaroxaban versus LMWH for a broad CAT cohort. The cohort study used electronic health data from January 2012 to December 2020 to evaluate patients with active cancer experiencing acute venous thromboembolism (VTE) and treated with rivaroxaban or LMWH. Propensity score-overlap weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE, bleeding-related hospitalization, and all-cause mortality were calculated. In total, 4935 patients were identified (27.9% on rivaroxaban and 72.1% on LMWH). The cancer types included gastrointestinal (29.4%), genitourinary (26.2%), lung (24.0%), breast (19.7%), and hematologic (14.4%). Rivaroxaban was associated with a reduction in recurrent VTE versus LMWH among all patients with cancer (HR=0.78; 95%CI=0.61-0.99) at 3 months. No differences in bleeding-related hospitalization or all-cause mortality were observed. Directionally similar results to those at 3 months were observed at 6 months for all outcomes. In conclusion, we observed fewer recurrent VTE cases and no increase in bleeding-related hospitalizations with rivaroxaban versus LMWH at 3 months in this patient cohort with various cancer types. [ABSTRACT FROM AUTHOR]

Objectives: To discuss the differential diagnosis of a case with leg swelling and pain with special emphasis on soft-tissue malignancy. Methods: Symptomatic deep vein thrombosis (DVT) of lower limb was treated with standard anticoagulants. In view of persistent symptoms for three months, repeat duplex venography, magnetic resonance imaging (MRI) and biopsy were undertaken to uncover the underlying pathology. Results: Imaging and biopsy revealed a 5 × 11 cm myxoid liposarcoma, adherent to the vein, that was the cause of her persistent symptoms despite anticoagulation, possibly by its local mass effect and also by its potential to create a thrombogenic milieu. Excision of the tumour led to symptom relief. A Medline search of English language papers was undertaken to review related literature. Conclusion: The report highlights the importance of considering neo-plastic masses as differential in painful leg swelling. Diagnosis is made by a high index of suspicion in atypical cases and confirmed by follow-up duplex or MRI. Treatment involves surgical excision that provides symptom relief as well as avoids potential tumour extension. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome (APS). Methods: We performed a literature search using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. We also performed a meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness and safety of DOACs versus warfarin in patients with APS. Results: Five RCTs involving 648 patients with APS (330 in DOAC-treated and 318 in control groups) were included in the meta-analysis. Among the patients included in the analysis, 29 (8.8%) patients experienced recurrent thrombosis in the DOAC treatment group, and 10 patients (3.1%) had thrombosis recurrence in the warfarin treatment group, resulting in a higher incidence in DOAC-treated than in the warfarin-treated groups [odds ratio (OR) = 2.163, 95% CI = 0.985–4.748, p = 0.055]. Incidence of arterial thrombosis was significantly higher in DOAC-treated patients than in warfarin-treated patients (OR = 5.168, 95% CI = 1.567–17.04, p = 0.007). Stroke and thrombosis occurrences were significantly higher in the triple positivity group than in the warfarin therapy group (OR = 12.03, 95% CI = 2.249–64.36, p = 0.004; OR = 2.940, 95% CI = 1.016–8.504, p = 0.047). However, venous thrombosis occurrences did not differ significantly between the DOAC-treated and warfarin-treated groups. There were no significant differences between the DOAC and warfarin groups in terms of any bleeding, major bleeding, minor bleeding, and all-cause mortality. Conclusion: DOACs were associated with higher rates of arterial thrombosis than warfarin in patients with APS, especially in the triple-positive group. However, a higher risk of recurrent venous thrombosis was not found in APS patients treated with DOACs compared to those treated with warfarin. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation (AC) management of the Impella varies considerably among treatment centers. Published data regarding the management of complications including heparin-induced thrombocytopenia, bleeding and thrombosis are limited. Objective: A multidisciplinary team was assembled to 1) identify baseline knowledge of nurses and pharmacists involved in Impella anticoagulation management; 2) develop an educational tool specific to Impella anticoagulation; 3) reassess knowledge following implementation of the tool. Methods: A team consisting of pharmacists, nurses and a physician developed surveys that were subsequently distributed to 28 nurses and 17 pharmacists. Survey questions measured knowledge in 4 areas of anticoagulation management: product selection, administration, monitoring and therapeutic recommendation. A pocket card containing flow diagrams for Impella anticoagulation management was developed. Following distribution of the card and education on its application, surveys were redistributed to measure the change in knowledge. Results: The frequency (%) of correct answers for all survey questions for both pharmacists and nurses significantly increased from 38% to 84% (p < 0.00001) and 63% to 93% (p < 0.00001), respectively. Substantial increases in the frequency of correct answers in the majority of question categories were observed for both pharmacists and nurses postintervention. Conclusion and Relevance: Using a multidisciplinary approach, an institution-specific pocket card addressing the complexities of Impella anticoagulation was developed. Following dissemination of the card and education on its application, improved knowledge across the scope of Impella anticoagulation management was observed in both pharmacists and nurses. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease (COVID-19) has spread rapidly to more than 200 countries and regions worldwide. Although several options have been implemented in attempts to control the rate of COVID-19 infection, the mortality rates remain high. The aim of this study is to evaluate whether patients with severe COVID-19 will benefit from the combination of anticoagulant and glucocorticoid therapy. Methods: A single-center retrospective cohort study of patients with COVID-19 was performed. Several factors influencing patients with COVID-19 have been analyzed retrospectively, including basic conditions, inflammatory factors, coagulation parameters, medications, and outcomes. Continuous and categorical variables have been evaluated via binary logistic regression analysis to predict mortality. The association between anticoagulant treatment and outcomes has also been evaluated, stratifying patients according to glucocorticoid treatment. Results: 61 patients with severe COVID-19, including 23 critically ill patients have been enrolled in the study. In those with severe and critical illness COVID-19, mortality rate was lower in those who received combined anticoagulant and glucocorticoid with odds ratio of 0.003 (p = 0.042) and 0.031 (p = 0.046), respectively. In cases of severe COVID-19, those who were treated with both anticoagulant and glucocorticoid had lower mortality (17.6%) than those treated with glucocorticoid alone (31.8%), although this did not reach statistical significance (p = 0.321). In the critically ill COVID-19 patients who received both anticoagulant and glucocorticoid, there was significantly lower mortality (30%) than those who received glucocorticoid alone (77.8%) (p = 0.047). Seventy-five percent of non-survivors of COVID-19 met the International Society on Thrombosis and Haemostasis criteria of disseminated intravascular coagulation (total points ≥5). Conclusion: Patients with severe COVID-19 or critically ill patients with COVID-19 may benefit from the combination therapy of anticoagulant and glucocorticoid. As the disease getting severe, more benefits may be obtained from the combination therapy. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to investigate the management of patients who were admitted to hospital with an acute haemarthrosis whilst taking oral anticoagulants, and highlight the outcomes of different management strategies. Methods: A retrospective review was performed of all orthopaedic admissions over a 42-month period (January 2015–July 2018) to the Orthopaedic Department of a London District General Hospital. All patients admitted with a spontaneous joint haemarthrosis and concomitant use of oral anticoagulants was identified. Anonymised data was placed on a secure trust database. Findings: A total of 31 patients were included. 22 patients (71%) had their anticoagulant temporarily held during admission. 9 patients (32%) had their anticoagulation reversed with 10 mg of vitamin K. 5 patients had their haemarthrosis aspirated either on admission or during their hospital stay. The overall mean length of stay in patients with a haemarthrosis was 7.0 days. The mean length of stay in patients who had their anticoagulation held was 8.6 days. In contrast, patients who continued taking their anticoagulation were found to have an average length of stay of 2.3 days. No patients suffered a thrombotic event in the 60 days following discharge. No adverse events were recorded following joint aspiration. Conclusion: There is currently no consensus on the management of haemarthrosis in patients on oral anticoagulants. Continuing the anticoagulants did not increase length of hospital stay. Further research may focus on assessing the effect of management adjuncts on patient outcomes and their cost effectiveness to aid the development of local and/or national guidelines. [ABSTRACT FROM AUTHOR]

Background: Clopidogrel is the most commonly prescribed P2Y12 inhibitor for acute coronary syndrome (ACS) or stent placement, though ticagrelor or prasugrel may be preferred. Medication-related factors may influence selection of therapy. Objectives: To determine which factors most greatly influence cardiology-provider and patient selection of P2Y12 inhibitor to guide shared-decision making (SDM). Methods: Single-center study assessed survey responses from 32 cardiology-providers who prescribed and 105 patients who received clopidogrel, prasugrel, or ticagrelor for ACS or stent placement. Respondents ranked factors influencing P2Y12 inhibitor selection and reported preference of therapy. Patients reported experience with shared decision-making process. Results: Cardiology-providers ranked risk of bleeding, comfort/experience, and cost as most influential. Patients ranked risk of drug interaction, adverse effects, and reduction in myocardial infarction as most influential. Significant differences between cardiology-providers and patients were found for 5 of 8 factors. Cardiology-providers ranked once daily administration (p = 0.01), risk of bleeding (p = 0.002), and cost (p < 0.001) as more important than patients. Patients ranked risk of adverse effects (p = 0.007) and drug interactions (p = 0.005) as more important than cardiology-providers. Cardiology-providers prescribed ticagrelor 42.3% of the time following ACS, though 78.1% ranked it as their preferred agent. Patients were prescribed ticagrelor 9.3% of the time, though 55.7% ranked it as their preferred agent. Use of SDM was reported by 21.6% of patients and 88.5% were unaware that multiple P2Y12 inhibitors existed. Conclusion: Significant differences exist between cardiology-providers and patients regarding factors influencing P2Y12 inhibitor selection, specifically safety-related factors, once daily administration, and cost. Most patients were not involved in SDM. [ABSTRACT FROM AUTHOR]