Coagulation mixing studies: utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests.

Coagulation testing underpins the investigation of hemostasis and/or monitoring of anticoagulation therapy for prevention and/or treatment of thrombosis related pathology. Assessment of coagulation results requires comparison against a normal reference […]

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Stroke and thromboembolism prevention in atrial fibrillation.

Abstract: Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for stroke and systemic thromboembolism are currently available. […]

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Secondary stroke prevention: a population-based cohort study on anticoagulation and antiplatelet treatments, and the risk of death or recurrence.

Abstract: Using claims databases of a public healthcare program (Quebec) for the years 2010 – 2013, we conducted a cohort study of acute ischemic stroke (AIS) patients to describe secondary […]

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Impact of Multidisciplinary Pulmonary Embolism Response Team Availability on Management and Outcomes.

Abstract: Treatment strategies for complex patients with pulmonary embolism (PE) are often debated given patient heterogeneity, multitude of available treatment modalities, and lack of consensus guidelines. Although multidisciplinary Pulmonary Embolism […]

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Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis.

Abstract: Antithrombotic (anticoagulant or antiplatelet) therapy is withheld from some patients with cerebral cavernous malformations, because of uncertainty around the safety of these drugs in such patients. We aimed to […]

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Changes in Management Following Detection of Previously Unknown Atrial Fibrillation by an Insertable Cardiac Monitor (from the REVEAL AF Study).

The REVEAL AF study demonstrated a high incidence of previously undetected atrial fibrillation (AF) using insertable cardiac monitors (ICMs) in patients with risk factors for AF and stroke. This analysis evaluated whether ICM monitoring led to changes in clinical management after AF detection. Patients with CHADS2 scores ?3 (or =2 with ?1 additional AF risk factor) but no history of AF received an ICM and were followed 18 to 30 months. Physicians recorded changes in clinical management in response to AF detection at scheduled (every 6 months) and unscheduled follow-up visits. Changes in clinical management included oral anticoagulation, rhythm or rate control pharmacotherapy, cardioversion, ablation, and cardiac subspecialist referral. In 387 patients who met inclusion criteria and received an ICM, AF was found in 115. A change in clinical management was taken in 87 patients with AF (76%). In 80 of these 87, a change was taken at the first visit after AF detection. In total, 31 patients (27%) with AF had ?2 visits at which changes in clinical management were taken. The most common change was initiation of oral anticoagulation (n?=?73, 63% of patients with AF). Patients with a change in clinical management at the first visit after AF detection tended to have longer AF episodes and a higher maximal daily AF burden compared with AF patients for whom no change was taken (longest episode: 52 vs 28 minutes; maximal daily AF burden:112 vs 23 minutes). Changes in management more frequently occurred at visits where patients reported AF-compatible symptoms (65% vs 46% of visits, p?=?0.01). In conclusion, ICM monitoring to identify AF guides both immediate and long-term patient management in a population at high risk for stroke.

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Accuracy of the Ottawa score in risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. A systematic review and meta-analysis.

In patients with cancer-associated venous thromboembolism, knowledge on the estimated rate of recurrent events is important for clinical decision regarding anticoagulant therapy. The Ottawa score is a clinical prediction rule designed for this purpose, stratifying patients according to their risk of recurrent venous thromboembolism during the first 6 months of anticoagulation. We conducted a systematic review and meta-analysis of studies validating either the Ottawa score in its original or modified version. Two investigators independently reviewed the relevant articles published from 06/01/2012 to 12/15/2018 and indexed in MEDLINE and EMBASE. Nine eligible studies were identified including 14,963 patients. The original score classified 49.3% of the patients as high-risk, with a sensitivity of 0.7 (95% confidence interval 0.6-0.8), a 6-month pooled rate of recurrent venous thromboembolism of 18.6% (95% confidence interval 13.9-23.9). In the low-risk group, recurrence rate was 7.3% (95% confidence interval 3.4-12.5). The modified score classified 19.8% of the patients at low-risk, with a sensitivity of 0.9 (95% confidence interval 0.4-1.0) and a 6-month pooled rate of recurrent venous thromboembolism of 2.2% (95% confidence interval 1.6-2.9). In the high-risk group, recurrence rate was 10.1% (95% confidence interval 6.4-14.6). Limitations of our analysis included type and dosing of anticoagulant therapy. We conclude that new therapeutic strategies are needed in patients at high-risk for recurrent cancer-associated venous thromboembolism. Low-risk patients, as per the modified score, could be good candidates to oral anticoagulation (PROSPERO CRD42018099506).

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A Multicenter Trial of Vena Cava Filters in Severely Injured Patients.

Whether early placement of an inferior vena cava filter reduces the risk of pulmonary embolism or death in severely injured patients who have a contraindication to prophylactic anticoagulation is not known.In this multicenter, randomized, controlled trial, we assigned 240 severely injured patients (Injury Severity Score >15 [scores range from 0 to 75, with higher scores indicating more severe injury]) who had a contraindication to anticoagulant agents to have a vena cava filter placed within the first 72 hours after admission for the injury or to have no filter placed. The primary end point was a composite of symptomatic pulmonary embolism or death from any cause at 90 days after enrollment; a secondary end point was symptomatic pulmonary embolism between day 8 and day 90 in the subgroup of patients who survived at least 7 days and did not receive prophylactic anticoagulation within 7 days after injury. All patients underwent ultrasonography of the legs at 2 weeks; patients also underwent mandatory computed tomographic pulmonary angiography when prespecified criteria were met.The median age of the patients was 39 years, and the median Injury Severity Score was 27. Early placement of a vena cava filter did not result in a significantly lower incidence of symptomatic pulmonary embolism or death than no placement of a filter (13.9% in the vena cava filter group and 14.4% in the control group; hazard ratio, 0.99; 95% confidence interval [CI], 0.51 to 1.94; P?=?0.98). Among the 46 patients in the vena cava filter group and the 34 patients in the control group who did not receive prophylactic anticoagulation within 7 days after injury, pulmonary embolism developed in none of those in the vena cava filter group and in 5 (14.7%) in the control group, including 1 patient who died (relative risk of pulmonary embolism, 0; 95% CI, 0.00 to 0.55). An entrapped thrombus was found in the filter in 6 patients.Early prophylactic placement of a vena cava filter after major trauma did not result in a lower incidence of symptomatic pulmonary embolism or death at 90 days than no placement of a filter. (Funded by the Medical Research Foundation of Royal Perth Hospital and others; Australian New Zealand Clinical Trials Registry number, ACTRN12614000963628.).

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Clinical Outcomes with Unfractionated Heparin Monitored by Anti-Factor Xa vs. Activated Partial Thromboplastin Time.

Anti-factor Xa (anti-Xa) monitoring of unfractionated heparin (UFH) is associated with less time to achieve therapeutic anticoagulation compared to the activated partial thromboplastin time (aPTT). However, it is unknown whether clinical outcomes differ between these methods of monitoring. The aim of this research was to compare the rate of venous thrombosis and bleeding events in patients that received UFH monitored by anti-Xa compared to the aPTT. A retrospective review of electronic health records identified adult patients that received UFH given intravenously (IV) for ? 2 days with either anti-Xa or aPTT monitoring at an academic tertiary care hospital. This was a pre/post study design conducted between January 1-December 30, 2014 (aPTT) and January 1-December 30, 2016 (anti-Xa). All UFH adjustments were based on institutional nomograms. The primary outcome was venous thrombosis and the secondary outcome was bleeding, both of which occurred between UFH administration and discharge from the index hospitalization. A total of 2,500 patients were in the anti-Xa group and 2,847 patients aPTT group. Venous thrombosis occurred in 10.2% vs. 10.8% of patients in the anti-Xa and aPTT groups, respectively (p = 0.488). Bleeding occurred in 33.7% vs. 33.6% of patients in the anti-Xa and aPTT groups, respectively (p = 0.94). Anti-Xa monitoring was not an independent predictor of either outcome in multivariate logistic regression analyses. Our study found no difference in clinical outcomes between anti-Xa and aPTT-based monitoring of UFH IV. This article is protected by copyright. All rights reserved.

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Investigation of Direct-Acting Oral Anticoagulants and the Incidence of Venous Thromboembolism in Patients Weighing ?120 kg Compared to Patients Weighing <120 kg.

Direct oral anticoagulants (DOACs) present a favorable alternative to warfarin based on the decreased burden of monitoring and fewer drug and food interactions. Although studied in the general population, limited clinical data justifying efficacy in patients weighing ?120 kg present concern for using DOACs in this specific population.The purpose was to identify if a difference exists in incidence of recurrent thromboembolic events in patients receiving a DOAC for the indication of venous thromboembolism (VTE) weighing ?120 kg compared to patients weighing <120 kg.A retrospective database analysis was conducted with patients on apixaban, dabigatran, or rivaroxaban for treatment of VTE from the Veterans Integrated Service Network 8 between January 2012 and June 2017. The primary outcome was incidence of recurrent VTEs while on anticoagulation. Fisher's exact tests were used to evaluate difference in VTEs between the groups.There were 133 patients weighing ?120 kg and 1063 patients weighing <120 kg identified within the 5-year time frame that met inclusion criteria. Although no statistically significant difference was found in incidence of recurrent VTEs between study groups (0.8% vs 1.1%; odds ratio: 0.66; 95% confidence interval: 0.09-5.14; P = .69) few events occurred limiting the power to be able to detect a difference.This study found no difference in VTE recurrence in patients weighing ?120 kg compared to patients <120 kg with few events in either group. Although promising, additional studies are needed to confirm these findings.

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Alert-based computerized decision support for high-risk hospitalized patients with atrial fibrillation not prescribed anticoagulation: a randomized, controlled trial (AF-ALERT).

Despite widely available risk stratification tools, safe and effective anticoagulant options, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is underprescribed. We created and evaluated an alert-based computerized decision support (CDS) strategy to increase anticoagulation prescription in hospitalized AF patients at high risk for stroke.We enrolled 458 patients (CHA2DS2-VASc score ?1) with AF who were not prescribed anticoagulant therapy and were hospitalized at Brigham and Women’s Hospital. Patients were randomly allocated, according to Attending Physician of record, to intervention (alert-based CDS) vs. control (no notification). The primary efficacy outcome was the frequency of anticoagulant prescription. The CDS tool assigned 248 patients to the alert group and 210 to the control group. Patients in the alert group were more likely to be prescribed anticoagulation during the hospitalization (25.8% vs. 9.5%, P < 0.0001), at discharge (23.8% vs. 12.9%, P = 0.003), and at 90 days (27.7% vs. 17.1%, P = 0.007). The alert reduced the odds of a composite outcome of death, myocardial infarction (MI), cerebrovascular event, and systemic embolic event at 90 days [11.3% vs. 21.9%, P = 0.002; odds ratio (OR) 0.45; 95% confidence interval (CI) 0.27-0.76]. The alert reduced the odds of MI at 90 days by 87% (1.2% vs. 8.6%, P = 0.0002; OR 0.13; 95% CI 0.04-0.45) and cerebrovascular events or systemic embolism at 90 days by 88% (0% vs. 2.4%, P = 0.02; OR 0.12; 95% CI 0.0-0.91).An alert-based CDS strategy increased anticoagulation in high-risk hospitalized AF patients and reduced major adverse cardiovascular events, including MI and stroke.NCT02339493.

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Low-Dose Alteplase for the Treatment of Submassive Pulmonary Embolism: A Case Series.

Pulmonary embolism (PE) can lead to significant morbidity and mortality. Thrombolytics are currently approved for the treatment of massive PE; however, the CHEST guidelines recommend against systemic thrombolytic use in acute PE patients without hypotension, unless these patients deteriorate on anticoagulation alone. Several studies have demonstrated the effectiveness of thrombolysis in submassive PE; however, the full thrombolytic dose resulted in significantly increased risk of non-intracranial bleeding and hemorrhagic stroke. The MOPETT trial demonstrated that low-dose tissue plasminogen activator (tPA) significantly reduced the risk of pulmonary hypertension and recurrent PE compared to anticoagulation alone in submassive PE patients without any bleeding events.This case series highlights 5 patient cases utilizing low-dose tPA for submassive PE. All patients had successful resolution of their symptoms and improvement in vitals and laboratory values. Furthermore, no patient had any bleeding during or after tPA administration. Three patients showed improved right ventricle function and reduced or normal right ventricle size on echocardiogram after tPA administration.The potential for low-dose tPA as a safe and efficacious treatment option for submassive PE is illustrated by this case series. However, larger, randomized controlled trials are needed to establish low-dose tPA as an accepted treatment modality.

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Extended Anticoagulation for VTE: A Systematic Review and Meta-Analysis.

The efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) during extended anticoagulation for a VTE remains largely unknown, especially in terms of potential survival benefit. The goal of this study was to assess the effects of VKAs and DOACs on overall mortality and VTE-related mortality, as well as VTE recurrence and safety.PubMed, EMBASE, and the Cochrane Library were searched from January 1990 through September 2018 for randomized controlled trials evaluating the effect of extended anticoagulants as secondary prevention for VTE compared with placebo. The primary outcome was the specific effects of standard-intensity VKAs and DOACs on overall mortality.Sixteen studies (12,458 patients) were included. DOACs were associated with a reduction in overall (risk ratio [RR], 0.48; 95% CI, 0.27-0.86; P = .01) and VTE-related (RR, 0.36; 95% CI, 0.15-0.89; P = .03) mortality, whereas VKAs were not (P > .50). Although VKAs and DOACs similarly prevented recurrent VTE, only VKAs were associated with an increased risk of major bleeding (RR, 2.67; 95% CI, 1.28-5.60; P < .01), resulting in an improved net clinical benefit for DOACs (RR, 0.25 [95% CI, 0.16-0.39; P < .01] vs 0.46 [95% CI, 0.30-0.72; P < .01]; Pinteraction = .05).DOACs for extended anticoagulation were associated with a significant reduction in overall mortality compared with observation alone.PROSPERO; No.: CRD42018088739; URL: https://www.crd.york.ac.uk/prospero/.

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Thrombophlebitis hiding under a KILT – case report on 40?years long-term follow-up of neonatal renal vein thrombosis.

Neonatal renal vein thrombosis is a recognised cause of renal and inferior caval vein atresia (IVCA). However, the long-term impact of the condition is underrecognized with a high burden of morbidity for the patient, especially in adulthood. IVCA has been shown to be an independent risk factor for deep venous thrombosis (DVT) with a high risk of recurrence. The acronym KILT for kidney and inferior vena cava anomaly with leg thrombosis summarizes the pathological situation.We present the case of a 40-year-old patient with pain in the right lower limb resulting from acute thrombophlebitis. No risk factors could be identified. His history was remarkable with two episodes of deep venous thrombosis first of the left, then the right leg 22?years earlier; at that time also, no risk factor was identified. Because of the idiopathic character of that thrombosis, the patient remained on long-term anticoagulation with phenprocoumon. The present thrombophlebitis occurred while the INR was not therapeutic in the preceding weeks. A CT with contrast showed atresia of the inferior vena cava and of the right kidney, and presence of numerous collaterals. A thorough medical history revealed a renal vein thrombosis as a neonate. Anticoagulation was intensified, and stent placement became necessary after a further 2?years.KILT syndrome is a rare but underrecognized condition. Complications may arise in young adulthood only, and it is of prime importance to instruct parents of the pediatric patient of the possible consequences of renal vein thrombosis and to assure guidance from the treating physicians throughout adulthood. Diagnosis of IVCA is by CT with contrast or by MRI, and lifelong anticoagulation may be necessary. Since the KILT syndrome is widely underdiagnosed, we challenge the clinicians to keep it in mind when confronted with thrombophlebitis or thrombosis of the young, male and with no other identifiable risk factors for deep vein thrombosis.

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