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During the past decade, emergence of direct oral anticoagulants (DOACs) has drastically improved the prevention of thrombosis. However, several unmet needs prevail in the field of thrombosis prevention, even in the DOACs' era. The use of DOACs is still constrained and the drugs cannot be administered in every clinical scenario, such as an increased anticoagulant-associated bleeding risk, particularly in some specific populations (cancer - notably those with gastrointestinal or genitourinary cancer - and frail patients), the impossibility to be used in certain patients (eg, end-stage kidney failure during hemodialysis, pregnancy and breastfeeding), and their lack of efficacy in certain clinical scenarios (eg, mechanical heart valves, triple-positive antiphospholipid syndrome). Efforts to find a factor that upon antagonization prevents thrombosis but spares haemostasis have resulted in the identification of coagulation factor XI (FXI) as a therapeutic target. After briefly recapitulating the role of factor XI in the balance of haemostasis, we propose a narrative review of the key data published to date with compounds targeting factor XI to prevent thrombosis as well as the main ongoing clinical studies, opening up prospects for improving the care of patients requiring thrombosis prevention.

The Caprini risk assessment model (RAM) has been validated in over 250 000 patients in more than 100 clinical trials worldwide. Ultimately, appropriate treatment options are dependent on precise completion of the Caprini RAM. As the numerical score increases, the clinical venous thromboembolism rate rises exponentially in every patient group where it has been properly tested. The 2013 Caprini RAM was completed by specially trained medical students via review of the presurgical assessment history, medical clearances, and medical consults. The Caprini RAM was completed for every participant both preoperatively and predischarge to ensure that any changes in the patient’s postoperative course were captured by the tool. This process led to the development of completion guidelines to ensure consistency and accuracy of scoring. The 2013 Caprini scoring system provides a consistent, thorough, and efficacious method for risk stratification and selection of prophylaxis for the prevention of venous thrombosis.

IntroductionCurrent guidance recommends thromboprophylaxis in COVID-19 patients during hospitalization for the prevention of venous thromboembolism and reduction in mortality risk. These recommendations are derived from small observational studies that usually included only patients with severe COVID-19 who were admitted to intensive care. We emulated a hypothetical clinical trial to estimate the effect of early initiation of thromboprophylaxis compared with no thromboprophylaxis on mortality risk among hospitalised COVID-19 patients managed with ward-based care.MethodsData were obtained from 5 collaborating centres using the NIHR COVID-19 cardiovascular dataset. Eligible patients (≥18 years) were hospitalised for COVID-19 between January and October 2020. We used a window of 24 hours from admission to define the treatment strategy (prophylactic dose versus no dose), taking the first dose assigned within this window. The prophylactic dose for dalteparin, enoxaparin, heparin, and tinzaparin were considered. Those that received invasive ventilation or other anti-coagulant medications or doses were excluded. Propensity scores (PS; patients’ estimated probability of receiving thromboprophylaxis) were derived using multivariable logistic regression; patients with high probabilities of either treatment strategy were excluded. Follow-up started 24 hours following admission. Patients who died within 24 hours of hospital admission without receiving thromboprophylaxis were assigned to a treatment group based on their PS, to mitigate immortal time bias. We estimated mortality hazard ratios comparing a prophylactic dose versus no dose, adjusting for confounders and additionally adjusting for the PS. In a sensitivity analysis, we started treatment at admission with early deaths assigned to treatment based on the PS. We performed subgroup analyses based on comorbidities and age groups.ResultsOf 4262 COVID-19 patients that received ward-based care, 3434 without an extreme PS were included (46% female, median age 64 years (interquartile range (IQR) 50-79)). The median follow-up was 183 days (IQR 114-266). 1780 received a prophylactic dose and 1654 received no dose. 62 participants died within the first 24 hours of their admission. There was an estimated 10% lower mortality risk for patients treated with a prophylactic dose versus those without, although the difference was not significant: hazard ratio 0.90 (95% confidence interval 0.77-1.05)) (Figure 1). The hazard ratio attenuated during sensitivity analysis: 0.99 (0.79-1.25). In subgroup analyses, there was a mortality benefit associated with thromboprophylaxis for COVID-19 patients who had a pneumonia (n=337) (0.42 (0.18-0.96)).ConclusionThere was no strong evidence that initiation of heparin based thromboprophylaxis compared with no thromboprophylaxis within 24 hours of admission was associated with a lower mortality risk in COVID-19 patients receiving ward-based care. However, a mortality benefit was associated with thromboprophylaxis amongst COVID-19 patients who had pneumonia that was mild enough to not require intubation.Abstract 209 Figure 1Kaplan-Meier curves displaying cumulative all-cause mortalityConflict of InterestNo conflicts of interest

IntroductionPatients with a Fontan palliation are at risk of thrombosis, that can be associated with major morbidity and mortality. Studies comparing thromboprophylactic strategies in these patients tend to be retrospective with small numbers of patients. Furthermore, this is a heterogenous population leading to further difficulties when trying to apply published literature to real-world patients. Most studies have investigated aspirin and warfarin, and there is sparse data on the role of Direct Oral Anti Coagulants (DOACs) in this population.1 As a result, there is no consensus on the optimal thromboprophylaxis or anticoagulant in these patients. We set out to establish current UK practice in Adult Congenital Heart Disease units.MethodsAn electronic survey was sent to ACHD consultants working in the NHS. This incorporated some basic demographic data and several clinical scenarios based on antithrombotic strategies of an 18-year-old patient with an Extra Cardiac (EC) Fontan palliation. Users were given a pre-specified checklist of options including ‘aspirin’, ‘DOAC’ or ‘warfarin’ with the option to create an alternative free text answer. Data was analysed using simple descriptive statistics.ResultsThere were 32 respondents, 28 of these were from level 1 centres, 3 from level 2 centres and 1 from a level 3 centre. 97% were consultants. There were varying levels of comfort with regard to DOACs in this population (see Figure 1). All respondents would use a DOAC, 35% being very comfortable with their use, 42% being somewhat comfortable but would still usually pick an alternative, and 23% would only use a DOAC in selected cases. The primary reasons for not using DOACs in these patients (see Table 1) included lack of evidence (58%), concerns regarding thrombotic risk (39%) and concerns regarding bleeding risk (26%).In the primary scenario involving an 18-year-old with an EC Fontan and reassuring echo with no history of thrombosis, arrhythmia, or bleeding (see Figure 2), most respondents would anticoagulate with either a DOAC (32%) or warfarin (29%); just under a quarter (23%) would use aspirin and 16% of respondents answered with some ambiguity or selected ‘other’ with free text options such as ‘dual anti-platelet therapy’ and ‘no medication’. In an 18-year-old with an EC Fontan and a history of atrial arrhythmia, 100% of respondents would anticoagulate with just over half (53%) opting for warfarin. A history of intra-cardiac clot increased the selection of warfarin to 75%. DOACs were more likely to be considered first-line in patients with a severe needle phobia (72%) and an INR that was difficult to control (78%).ConclusionThere is a great deal of variation both within and between centres across the UK. This is likely to persist until there are larger, prospective, randomised controlled trials.Abstract 17 Table 1 Reasons for not using DOACs in adults with a Fontan palliation Number (31) Not applicable as I use them routinely10 (32%)Lack of evidence18 (58%)Lack of licensed indication7 (23%)Experience of adverse events3 (10%)Concerns regarding bleeding risk8 (26%)Concerns regarding thrombotic risk12 (39%)Concerns regarding side effects0Not used in my institute 2 (6%)Abstract 17 Figure 1Level of comfort using DOACs in adults with a Fonton palliationAbstract 17 Figure 2First line anti-thrombotic choice in 18-year-old EC Fonton with reassuring echo and no history of thrombosis, arrhythmia or bleedingConflict of InterestNil

The SARS-CoV-2 pandemic and its specific respiratory pathology has generated extensive research that has highlighted the specific nature of the disease (COVID-19). Thrombotic processes in the macrocirculation and microcirculation were among the first reported, accompanying respiratory (pulmonary) manifestations. Of the COVID-19 complications, thrombosis in the venous system (venous thrombosis and pulmonary embolism) and the atrial system (stroke) are the most numerous and severe in terms of evolution and prognosis. The prophylaxis of thrombotic processes in COVID-19, initially empirical, has gained a scientific basis based on research and experience of clinicians.The current paper presents general data on macro- and microcirculatory thrombosis and the rationale for thromboprophylaxis. Thromboprophylaxis in non-hospitalized COVID-19 patients, “non-critical” and “critical” hospitalized patients and possible post-hospital thromboprophylaxis are presented.Heparins (HGMM and HNF) are the most commonly indicated and used antithrombotic agents. Other antithrombotic agents - antiplatelets and direct anticoagulants (oral - DOAC) have a very limited and possibly negative role in thromboprophylaxis in COVID-19.

BackgroundPreliminary reports have described significant procoagulant events in patients with coronavirus disease-2019 (COVID-19), including life-threatening pulmonary embolism (PE).Main textWe review the current data on the epidemiology, the possible underlying pathophysiologic mechanisms, and the therapeutic implications of PE in relation to COVID-19. The incidence of PE is reported to be around 2.6–8.9% of COVID-19 in hospitalized patients and up to one-third of those requiring intensive care unit (ICU) admission, despite standard prophylactic anticoagulation. This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells.ConclusionThromboprophylaxis should be started in all patients with suspected or confirmed COVID-19 admitted to the hospital. The use of an intermediate therapeutic dose of low molecular weight (LMWH) or unfractionated heparin can be considered on an individual basis in patients with multiple risk factors for venous thromboembolism, including critically ill patients admitted to the ICU. Decisions about extending prophylaxis with LMWH after hospital discharge should be made after balancing the reduced risk of venous thromboembolism (VTE) with the risk of increased bleeding events and should be continued for 7–14 days after hospital discharge or in the pre-hospital phase in case of pre-existing or persisting VTE risk factors. Therapeutic anticoagulation is the cornerstone in the management of patients with PE. Selection of an appropriate agent and correct dosing requires consideration of underlying comorbidities.

Background: Preliminary evidence indicates that prophylactic-dose thromboprophylaxis may be inadequate to control the increased risk of venous thromboembolism (VTE) in patients hospitalized for coronavirus disease 2019 (COVID-19) infection. Additionally, it remains unclear whether the D-dimer measurement is useful for VTE risk stratification among COVID-19 patients. This study aimed to offer benchmark data on the incidence of VTE and to examine the difference in D-dimer levels among anticoagulated COVID-19 patients with and without VTE incident. Methods: A comprehensive literature review of PubMed from inception to May 2020 was performed for original studies that reported the frequency of VTE and death among COVID-19 patients who received thromboprophylaxis on hospitalization. The endpoints included VTE (a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT)), PE, DVT, and mortality. Results: A total of 11 cohort studies were included. Among hospitalized COVID-19 patients, 23.9% (95% confidence interval (CI), 16.2% to 33.7%; I2 = 93%) developed VTE despite anticoagulation. PE and DVT were detected in 11.6% (95% CI, 7.5% to 17.5%; I2 = 92%) and 11.9% (95% CI, 6.3% to 21.3%; I2 = 93%) of patients, respectively. Patients in the intensive care unit (ICU) had a higher risk for VTE (30.4% )95% CI, 19.6% to 43.9%)) than those in the ward (13.0% (95% CI, 5.9% to 26.3%)). The mortality was estimated at 21.3% (95% CI, 17.0% to 26.4%; I2 = 53%). COVID-19 patients who developed VTE had higher D-dimer levels than those who did not develop VTE (mean difference, 2.05 µg/mL; 95% CI, 0.30 to 3.80 µg/mL; P = 0.02). Conclusions: The heightened and heterogeneous risk of VTE in COVID-19 despite prophylactic anticoagulation calls into research on the pathogenesis of thromboembolic complications and strategy of thromboprophylaxis and risk stratification. Prominent elevation of D-dimer may be associated with VTE development and can be used to identify high-risk subsets.

Antiphospholipid syndrome, also known as ‘Hughes Syndrome’, is an autoimmune disease characterised by a set of clinical manifestations, almost all of which are direct or indirect sequelae of a hypercoagulable state involving the venous, and to a lesser extent the arterial vasculature. The incidence and prevalence of antiphospholipid syndrome are estimated at approximately 5 de novo cases per 100 000 per year and 40–50 cases per 100 000 individuals, respectively. The clinical spectrum of antiphospholipid syndrome involves haematological (thrombocytopaenia, venous thrombosis), obstetrical (recurrent pregnancy loss), neurological (stroke, transient ischaemic attack, migraine, seizures, cognitive dysfunction, chorea, transverse myelitis, multiple sclerosis), cardiovascular (cardiac valve disease), dermatological (livedo reticularis and racemosa, skin ulceration and necrosis), renal (glomerulonephritis, renal thrombotic microangiopathy) and orthopaedic (avascular necrosis of bones, non-traumatic fractures) manifestations, among others. In addition to the classical antiphospholipid antibodies, namely anticardiolipin antibodies and lupus anticoagulant, new autoantibodies and antibody complexes of different immunoglobulin subtypes (IgA, IgG, IgM) are now recognised as significant contributors to the pathogenesis of antiphospholipid syndrome. Anticoagulation remains the cornerstone in the management of antiphospholipid syndrome; nevertheless, new drugs and therapeutic strategies are being tested, and some have been found effective for the primary and secondary thromboprophylaxis in antiphospholipid syndrome.

Introduction Available evidence to identify factors independently associated with failed thromboprophylaxis (FT) in medical patients is insufficient. The present study seeks to evaluate in hospitalized patients, which clinical factors are associated with the development of FT. Materials and methods A case-control study nested to a historical cohort, comparing patients who developed failed thromboprophylaxis (cases) with those who did not (controls). Univariate and multivariate regression analysis was performed to define the factors associated with FT. Results We selected 204 cases and 408 controls (52.4% men, median age 63 years). Medical patients were 78.4%. The most frequent thromboprophylaxis scheme was enoxaparin. In the failed thromboprophylaxis group, most of the embolic events corresponded to pulmonary embolism (53.4%). Among cases, BMI was higher (26.3 vs. 25 kg/m2, p < 0.001), as was the proportion of patients with leukocytosis > 13,000 (27% vs. 18.9%, p:0.22), and patients who required intensive care management (48% vs. 24.8%, p < 0.001). Factors independently associated with FT were BMI (OR1.04;95%CI 1.00-1.09, p:0.39), active cancer (OR:1.63;95%IC 1.03–2.57, p:0.04), leukocytosis (OR:1.64;95%CI 1.05–2.57, p:0.03) and ICU requirement (OR:3.67;95%CI 2.31–5.83, p < 0.001). Conclusion Our study suggests that the failed thromboprophylaxis is associated with high BMI, active cancer, leukocytosis, and ICU requirement. Future studies should evaluate whether there is benefit in adjusting the thromboprophylaxis scheme in patients with one or more of these factors.

OBJECTIVES: Patients with traumatic brain injury (TBI) have an increased risk for venous thromboembolism (VTE). The current guidelines recommend pharmacologic prophylaxis, but its timing remains unclear. METHODS: In this retrospective cohort study, patients with moderate-to-severe TBI admitted to a tertiary care intensive care unit between 2016 and 2019 were categorized into two groups according to the timing of pharmacologic prophylaxis: early if prophylaxis was given within 72 h from hospital admission and late if after 72 h. RESULTS: Of the 322 patients in the cohort, 46 (14.3%) did not receive pharmacological prophylaxis, mainly due to early brain death; 152 (47.2%) received early pharmacologic prophylaxis and 124 (38.5%) received late prophylaxis. Predictors of late pharmacologic prophylaxis were lower body mass index, intracerebral hemorrhage (odds ratio [OR], 3.361; 95% confidence interval [CI], 1.269-8.904), hemorrhagic contusion (OR, 3.469; 95% CI, 1.039-11.576), and lower platelet count. VTE was diagnosed in 43 patients on a median of 10 days after trauma (Q1, Q3: 5, 15): 6.6% of the early prophylaxis group and 26.6% of the late group (P < 0.001). On multivariable logistic regression analysis, the predictors of VTE were Acute Physiology and Chronic Health Evaluation II score, subarachnoid hemorrhage, and late versus early pharmacologic prophylaxis (OR, 3.858; 95% CI, 1.687-8.825). The late prophylaxis group had higher rate of tracheostomy, longer duration of mechanical ventilation and stay in the hospital, lower discharge Glasgow coma scale, but similar survival, compared with the early group. CONCLUSIONS: Late prophylaxis (>72 h) was associated with higher VTE rate in patients with moderate-to-severe TBI, but not with higher mortality.