Recurrent Thromboembolism Research Articles

MASSIVE STROKE ON ANTICOAGULATION; A CASE OF NONBACTERIAL THROMBOTIC ENDOCARDITIS IN A PATIENT WITH LUNG ADENOCARCINOMA

SESSION TITLE: Lung Cancer 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Non Bacterial Thrombotic Endocarditis (NBTE) is a rare condition that refers to noninfectious lesions of the heart valves. 80% of the cases are associated with advanced malignancy. When compared to other malignancies, higher rates are observed in patients with adenocarcinoma. (1) We present a case of massive stroke in a patient with NBTE secondary to Stage IV Lung Adenocarcinoma (LA) while on Apixaban. CASE PRESENTATION: 56y.o. male with no significant past medical history presented with abdominal pain and worsening shortness of breath. On further evaluation, he was noted to have splinter hemorrhages as well. Additional workup revealed multiple pulmonary nodules, hilar and mediastinal lymphadenopathy. A biopsy was obtained which was consistent with Lung Adenocarcinoma. PET Scan revealed metastatic activity in the neck and mediastinum. He was also found to have bilateral extensive Deep Vein Thrombosis in the lower extremities. Transesophageal Echocardiogram demonstrated a 3x4 mm mass on the anterior leaflet of the mitral valve. All infectious workup was negative and a diagnosis of NBTE was made. Treatment with low molecular weight heparin was discussed but patient refused, and consequently was sent home on Apixaban. Two weeks later, he was found down at his residence. Upon arrival to Emergency Department, he was noted to have complete left sided hemi neglect. Brain imaging revealed non-reversible ischemia in right Middle Cerebral Artery Territory. Mitral valve vegetation was the likely culprit. Computed Tomography (CT) of the head revealed hemorrhagic transformation. No further neurologic or cardiac intervention was performed. The patient was eventually discharged on Rivaroxaban and was instructed to follow up with his oncologist for initiation of chemotherapy. DISCUSSION: It's well known that low molecular weight heparin (LMWH) is the first choice for anticoagulation in NBTE secondary to malignancy, (1) nevertheless the patient refused it so he was placed on Apixaban instead, proving unfortunately to be ineffective. Anticoagulation with this medication has yet to be evaluated in patients with NBTE. Recent studies point out that Rivaroxaban and Edoxaban are comparable to (LMWH) in preventing Venous Thromboembolism and further embolic episodes caused by NBTE (2,3). CONCLUSIONS: Vegetations in NBTE vary in size from microscopic to large and exuberant. They can easily dislodge and cause embolic phenomena. LMWH, Rivaroxaban or Edoxaban should always be considered in these type of patients. Further investigation is required regarding other oral anticoagulants. We hope that clinicians can take our case as reference as properly managing these patients will have a dramatic impact on quality of live and even life expectancy. Reference #1: Mazokopakis EE, Syros PK, Starakis IK. Nonbacterial thrombotic endocarditis (marantic endocarditis) in cancer patients. Cardiovasc Hematol Disord Drug Targets 2010; 10:84. Reference #2: Gary E. et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med 2018; 378:615-624 Reference #3: Young A. et al Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism: Results of the Select-D Pilot Trial. Thromb Res. 2016 Apr;140 Suppl 1:S172-3. DISCLOSURES: No relevant relationships by Girish Balachandran Nair, source=Web Response No relevant relationships by Fernando Figueroa Rodriguez, source=Web Response no disclosure on file for Hira Iftikhar

Measurement of coagulation factors during rivaroxaban and apixaban treatment: Results from two crossover trials

BackgroundPrediction models for venous thromboembolism recurrence will likely be improved by adding levels of coagulation factors. Risk assessment is ideally performed during anticoagulant treatment, however, the influence of direct oral anticoagulants on coagulation factors is uncertain. ObjectiveTo assess the influence of rivaroxaban and apixaban on several coagulation factor levels. MethodsIn two crossover trials we assessed the influence of rivaroxaban and apixaban intake on factor (F)VIII, FXI and FXII‐activity and fibrinogen, von Willebrand factor (VWF:Ag), and d‐dimer levels. At three sessions with a washout period in between, blood was taken from 12 healthy male individuals immediately before intake of rivaroxaban 15 mg twice daily (n = 6) or apixaban 10 mg twice daily (n = 6) and three hours after the last intake. ResultsOverall, measured levels were lower after rivaroxaban/apixaban intake. The paired mean difference after rivaroxaban intake was −38 IU/dL (95% CI −43; −33) for FVIII:C, −29 U/dL (95% CI −45; −12) for FXI:C, −22 IU/dL (95% CI −43; −1) for FXII:C, −0.11 g/L (95% CI −0.25; 0.03) for fibrinogen, −7 IU/dL (95% CI −18; 3) for VWF:Ag, −27 ng/mL (95% CI −50; −4) for d‐dimer and −0.36 (95% CI −0.57; −0.15) for Ln d‐dimer. After apixaban intake this was −29 IU/dL (95% CI −38; −21) for FVIII:C, −29 IU/dL (95% CI −36; −22) for FXI:C, −19 IU/dL (95% CI −24; −15) for FXII:C, −0.18 g/L (95% CI −0.33; 0.03) for fibrinogen, −52 ng/mL (95% CI −100; −4) for d‐dimer, 0.25 (−0.60; 0.09) for Ln d‐dimer and 1 IU/dL (95% CI −7; 9) for VWF:Ag. ConclusionFVIII:C, FXI:C, FXII:C, and d‐dimer measurements were influenced by rivaroxaban/apixaban intake, while fibrinogen and VWF:Ag were not.

Pathomorphological changes in lungs of deceased with obesity: review of literature and analysis of own observations.

Background. Obesity is a disease that is characterized by excessive significant harmful effects on the functioning of almost all major systems of the human body. Pathological transformations of the lungs deserve particular attention, given the controversy of literary data relating to pathogenesis and morphological manifestations. The analysis of modern literature shows insufficient quantity and proof of the conducted researches. Objective. To find the morphological changes of the lungs and to establish the dependence of their genesis with the overall obesity by means of a retrospective analysis of protocols of autopsies and necropsy of deceased persons with obesity with the definition of pathomorphological changes of the pulmonary tissue. Methods. The authors analyzed 993 autopsy cases during the year of 2017 on the basis of the Lviv Regional Pathology Bureau. Obesity was detected in 67 death cases, of which 25 cases were randomly selected in order to objectify the detected changes in the lungs. The purposeful study of histological changes in lungs of 25 deceased with obesity has been carried out. Pulmonary tissue has been studied using standard histological techniques – hematoxylin-eosin staining. Results. Among the deceased patients there were 16 (64%) women and 9 (36%) men. The age of the patients ranged from 29 to 90 years. The average age of men was 60.88 ± 5.90; the average age of women was 67.31 ± 3.68. In 5 cases of the general investigation group no pulmonary pathology was detected. Among the 20 cases, the most commonly encountered pathology was pneumosclerosis (17 cases, 68% ). The second, most frequently detected pathology, was chronic bronchitis in the stage of exacerbation or remission (12 cases, 48%). Three cases (12%) were diagnosed with pulmonary thromboembolism: acute - 2 cases and one diagnosed case of recurrent pulmonary thromboembolism. Among other cases, there were pneumonias (3 cases), idiomatic pulmonary fibrosis and squamous cell carcinoma of the lungs. Conclusion. In investigation group of obese deceased, lung diseases were found in 80% of cases. Typical pathomorphological changes of the lungs in obese deceased were diffuse pneumosclerosis (whose correlation with sex and age is not detected) of varying degrees of generalization and chronic bronchitis.

Vascular Thoracic Outlet Syndrome: Experiences at the National Institute of Cardiovascular Diseases, Dhaka

Background: To analyze our recent experiences at the National Institute of Cardiovascular Diseases (NICVD) with the management of vascular Thoracic Outlet Syndrome (TOS).Methods: Retrospective review identified 51 patients (age range 23 to 67 years) with vascular TOS, among them 47 patients with arterial type TOS underwent surgical treatment from January 2012 to December 2015. Evaluation included clinical assessment plus duplex ultrasonography and contrast arteriography and outcome of treatment.Results: In 44 (94%) patients, surgery was successful in relieving the ischemic symptoms. Major amputations could be avoided in 21 of the 28 patients presenting with gangrene. Recurrent thrombo-embolism of the distal arterial tree was found in 5 patients requiring repeat embolectomy. At one year follow-up, 73% of the patients remained free from ischemic upper limb symptoms.Conclusions: Though relatively uncommon, arterial TOS is a potentially limb threatening condition. Early detection of the anatomical abnormality with its surgical correction is required to avoid major complications.Cardiovasc. j. 2018; 11(1): 50-52

Thirty-day outcomes in patients with acute pulmonary embolism who discontinued anticoagulant therapy before 90 days

The contemporary natural history of patients with acute pulmonary embolism (PE) not receiving (or early discontinuing) anticoagulant therapy has not been consistently evaluated. To assess the rate of the composite outcome of PE-related death, sudden death, or recurrent thromboembolism (VTE) within 30 days in all PE patients in whom anticoagulation was not administered or discontinued prematurely (<90 days of anticoagulation). We used the RIETE database to assess the incidence rates (per 100 person-days) of the composite outcome within the subsequent 30 days. The risk of these events was compared to PE patients who were anticoagulated for ≥90 days. Of 34,447 PE recruited from 2001 to 2017, 47 (0.14%) did not receive anticoagulants and 1348 (3.91%) discontinued it before 90 days. Fatal PE developed in 25 (53%) of those without any anticoagulation and in 45 (3.33%) with premature discontinuations. Sudden death or non-fatal recurrent VTE occurred in 6 (0.45%) and 24 (1.48%) patients, respectively. The incidence of the primary outcome declined logarithmically from 6.36 per 100 patient-days in untreated patients to 0.32-0.13 in those treated for 8-90 days. During the first week of follow-up, the incidence rate was 13.9 and 0.60-0.31 per 100 patient-days, respectively. The adjusted odds of the primary outcome was 27 fold higher in untreated than in treated patients, and progressively decreased to 2.5-7 fold higher in patients treated for at least 7 days. The incidence of the composite outcome was highest during the first week, and inversely and logarithmically correlated with the duration of anticoagulant therapy.

Ability of the Khorana score to predict recurrent thromboembolism in cancer patients with ischemic stroke

Cancer patients with acute ischemic stroke (AIS) are high-risk for recurrent thromboembolic events (RTE). Currently, no risk stratification model exists to predict RTE in this population. We tested the hypothesis that the Khorana score, a validated risk model for predicting venous thromboembolism in cancer patients, can effectively classify RTE risk in cancer patients with AIS. We retrospectively identified adults with active solid or hematological cancer diagnosed with AIS at a tertiary-care cancer center from 2005 to 2010. The Khorana score at the time of index stroke was calculated. The primary outcome was arterial or venous RTE. Cox regression was used to evaluate the association of the Khorana score and its individual components with RTE. Harrell’s c-statistic was used to calculate the score’s discriminatory ability. Among 263 AIS patients, median survival was 84 days (IQR 24–149 days) and 90 (34%) had RTE. The median Khorana score was 2 (IQR 1–2, range 0–5). Cumulative rate of RTE was 28% among patients who scored 0, 36% with scores of 1–2, and 32% with scores of 3–6. The overall Khorana score was marginally associated with RTE (HR, 1.14; 95% CI, 1.02–1.28). Of its individual components, only leukocytosis was associated with RTE (HR adjusted for other components, 1.45; 95% CI 1.11–1.90). The score’s c-statistic for predicting RTE was 0.57. In this study, the Khorana score had poor discriminatory ability for predicting RTE in cancer patients with AIS. Future research is needed to identify better methods for predicting RTE in this high-risk population.

A case series of outcomes in isolated subsegmental pulmonary embolism on ventilation-perfusion imaging.

The risk of recurrent venous thromboembolic disease and the management of patients with isolated subsegmental pulmonary embolism (SSPE) remain unclear. We sought to assess the long-term clinical outcome of patients with isolated SSPE demonstrated by isolated subsegmental mismatch found on ventilation/perfusion (V/Q) scans. We performed a retrospective observational study of 1300 consecutive patients with suspected pulmonary embolism who underwent index V/Q single-photon emission computed tomography between 2012 and 2013. Forty (3%) patients were found to have isolated SSPE identified on V/Q scan. Of the 40 patients with isolated SSPE on V/Q scan, 19 underwent further investigation with computed tomography pulmonary angiogram (CTPA) within 48 h. Among 19 patients who had corroborating CTPA performed concurrently, 94.7% of the SSPEs identified on V/Q were not detectable on CTPA. Of the 40 patients, 10 (25%) were anticoagulated. In a median follow-up of 3.28±0.55 years, all-cause mortality occurred in two patients, recurrence of suspected venous thromboembolism (VTE) occurred in 12 (30%) of 40 patients, but none had confirmed recurrent thromboembolism on further imaging. In the 40 patients with SSPE on V/Q, there was no difference in the risk of recurrence of suspected VTE or mortality between patients treated with anticoagulation and not treated (hazard ratio: 2.04, 95% confidence interval: 0.75-7.28). In this case series, a large proportion of patients with isolated SSPE on V/Q imaging were not identified on corroborating CTPA performed within 48 h. In patients with isolated SSPE (identified by isolated subsegmental mismatch on V/Q single-photon emission computed tomography), we found no difference in risk of recurrent suspected VTE or all-cause mortality in those treated with anticoagulation and those not treated.

Progress of recurrence of venous thromboembolism in cancer patients

Cancer patients complicated with venous thromboembolism (VTE) face treatment problems, very high recurrence rate and bleeding rate. Cancer itself and the antitumor treatment plan are the important factors causing the recurrence. After the relapse, the prognosis of the patients is extremely bad, and more than 50% of the patients died within 1 year. Until now, there is no unified effective treatment plan for the relapse. This paper reviews the recurrence of VTE and the related research progress. Key words: Venous thromboembolism; Recurrence; Low molecular weight heparins; Anticoagulants

Thromboprophylaxis in pregnant women with thrombophilia and a history of thrombosis.

Background Despite intensive research, thromboembolism still accounts for significant maternal morbidity and mortality. We examined thrombophilia in patients with thromboembolism during pregnancy and evaluated the efficiency of antithrombotic prophylaxis in patients with thrombophilia for the prevention of recurrent thromboembolism. Materials and methods Sixty-eight women with a history of thromboembolism were managed during pregnancy, in light of their thrombotic history and the result of thrombophilia assessment. Group I (n=50) received prophylaxis with low molecular weight heparin (LMWH)±aspirin (50-100 mg/day) in preconception period or from the 1st trimester, during pregnancy and at least 6 weeks postpartum. Group II (n=18) received LMWH±aspirin from the II to III trimester. Results Thromboses were associated with pregnancy in 27 patients (39.7%), with systemic diseases - in nine (13.2%), oral contraceptives use - 22 (32.3%), immobilization due to surgery and/or trauma, long flight - six (8.9%), septic complications - two (2.9%). Nevertheless, 24.5% of patients had no apparent provoking factor for the development of thrombotic complications. Thirty-seven (54%) patients with venous thromboembolism (VTE) had familial history of VTE, and 25 (36.7%) had personal history of pregnancy complications (fetal loss syndrome, preeclampsia and placental abruption) (P<0.05 vs. control). Thrombophilia was detected in 58 (85.3%). Usual thrombogenic polymorphisms [factor V (FV) Leiden and prothrombin G20210A, heterozygous forms] were revealed in 16 (23.5%) and eight (11.7%) patients, respectively. Antiphospholipid antibodies (aPL) circulation was found in 34 (50%) patients. Non-usual thrombogenic polymorphisms were identified in 44 (64.7%) of the women and hyperhomocysteinemia - in 30 (44.2%). In group I no one had severe obstetric complications. All the patients were delivered at term and all the babies were alive. In group II moderate-to-severe obstetric complications were noted: preeclampsia - in 11 (16.2%), severe preeclampsia - seven (10.3%), preterm delivery - in 18 (26.4%) patients from subgroup II (P<0.05). Conclusions Women with a personal or a family history of thromboembolism and obstetric complications should be screened for thrombophilia. Beginning anticoagulant therapy early in such patients is effective not only for preventing recurring thrombosis but also preventing obstetric complications. Late prophylaxis after the completion of the trophoblast invasion therapy is much less effective.

Efficacy and safety of rivaroxaban compared to enoxaparin in treatment of cancer-associated venous thromboembolism.

Low molecular weight heparin (LMWH) is the guideline-endorsed treatment for cancer-associated venous thromboembolism (cVTE). Study objectives were to compare the efficacy and safety of rivaroxaban and enoxaparin in cVTE. Using a cohort study design, consecutive patients with cVTE (3/1/2013-7/31/2016), enrolled in the Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry, were compared to contemporary cancer patients receiving enoxaparin. The cumulative incidence of venous thromboembolism (VTE) recurrence, major and clinically relevant non-major bleeding, and survival were assessed at 3 and 12months. Ninety-eight patients received rivaroxaban (51% female, mean age 63±12years) and 168 enoxaparin (34.5% female, mean age 62±15years). The most common cancers included gastrointestinal/pancreatic, genitourinary and hematologic cancers. More than half of patients had pulmonary emboli at presentation. More than half had metastases, and two-thirds were receiving chemotherapy. At 3months, there were no differences in VTE recurrence (rivaroxaban 1.0% vs enoxaparin 4.2%; P=.15), major bleeding (rivaroxaban 5.1% vs enoxaparin 3.6%; P=.55), or all-cause mortality (rivaroxaban 4.1% vs enoxaparin 8.9%; P=.14). At 12months, these outcomes did not differ by treatment strategy. The results of this "real-world" experience with cVTE suggest that rivaroxaban may offer a safe and effective alternative to LMWH.

Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism

BackgroundVenous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism also has been established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined. MethodsThe current study analyzed clinical characteristics, time course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism). ResultsDuring the anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 and 36 days, respectively) than venous thromboembolism recurrences (median 97 days). Thirty-day mortality rates after each event were: 20% after recurrent pulmonary embolism, 13% after recurrent deep vein thrombosis, 41% after major bleeding, 40% after myocardial infarction, 64% after ischemic stroke, and 83% after lower limb amputation. Bleeding was the leading cause of death (67 fatal bleeds), whereas cumulative mortality due to arterial ischemic events (n = 27) was similar to that related to pulmonary embolism recurrences (n = 26). ConclusionsIn this study, arterial ischemic events and major bleeding appeared early after venous thromboembolism in patients with active cancer and were among frequent causes of their deaths. The risk and severity of arterial events need to be considered in this clinical setting.

Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation

Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation.

Treatment of high- and intermediate-risk pulmonary embolism using the AngioJet percutaneous mechanical thrombectomy system in patients with contraindications for thrombolytic treatment - a pilot study.

IntroductionIntravenous thrombolysis is the treatment of choice in patients presenting with high- and intermediate-risk pulmonary embolism. The role of percutaneous mechanical pulmonary thrombectomy (PMPT) is not fully established, although selected patients can be managed with this method.AimThis open-label single-centre prospective pilot study was aimed at assessing the feasibility of PMPT for the treatment of severe pulmonary embolism in a Polish hospital. We also evaluated the safety and efficacy of such management.Material and methodsWe managed 7 patients, aged 52.7 ±16.6 years, presenting with high- and intermediate-risk pulmonary embolism (4 patients with class 5 and one patient with class 4 of the Pulmonary Embolism Severity Index), with occlusion of at least 2 lobar arteries and contraindications for thrombolysis. Percutaneous mechanical pulmonary thrombectomy was performed using the AngioJet system.ResultsIt was possible to introduce the thrombectomy system to the pulmonary arteries in all patients. The procedure was successful in 6 patients (technical success rate: 85.7%). Two (28.6%) patients died during the hospital stay, one patient with unsuccessful thrombectomy and the other due to pneumonia. In all survivors control echocardiography demonstrated normalised function of the right ventricle. Also, dyspnoea disappeared and blood gas parameters normalised. There was no recurrent thromboembolism during 3–14 months of follow-up.ConclusionsIn the Polish setting, in selected patients, management of high- and intermediate-risk pulmonary embolism with PMPT is technically feasible. Such treatment is relatively safe and effective. It can be an alternative to standard management, especially in patients with contraindications for fibrinolysis or surgical embolectomy.

Systematic Review and Meta-analysis of Outcomes of Patients With Subsegmental Pulmonary Embolism With and Without Anticoagulation Treatment.

This systematic review addresses the controversy over the decision to anticoagulate patients with subsegmental pulmonary embolism (SSPE). We searched Ovid MEDLINE, PubMed, Embase, the Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, Google Scholar, and bibliographies in March 2017. Two authors reviewed and retained papers with symptomatic patients who underwent computerized tomographic pulmonary angiography and had sufficient information to determine SSPE; decision to treat (or not) with systemic anticoagulation; and outcomes of bleeding, venous thromboembolism (VTE) recurrence, and death. Papers were assessed for selection and publication bias and heterogeneity, with Eggers and the inconsistency indexes (I2 ). From 1,512 papers screened, we included 14 studies comprising 15,563 patients for full-length review and analysis. Pooled data demonstrated I2 =99% with an Eggers p<0.001, suggesting significant publication bias. The pooled prevalence of SSPE was 4.6% (95% confidence interval [CI]=1.8%-8.5%). The frequency of bleeding in SSPE patients treated with anticoagulation (n=589) was 8.1% (95% CI=2.8%-15.8%), with no available bleeding data in untreated patients (n=126). The frequency of VTE recurrence within 90 days was 5.3% (95% CI=1.6%-10.9%) for treated versus 3.9% (95% CI=4.8%-13.4%) for untreated, while the frequency of death was 2.1% (95% CI=3.4%-5.2%) for treated versus 3.0% (95% CI=2.8%-8.6%) for untreated. This systematic review highlights the lack of any clinical trial to make a clear inference about harm or benefit of anticoagulation for SSPE. Comparison of pooled data from uncontrolled outcome studies shows no increase in VTE recurrence or death rates for patients who were not anticoagulated. These data suggest clinical equipoise for decision to anticoagulate or not anticoagulate patients with SSPE. However, this inference is limited by small numbers, imprecision, and the lack of a controlled clinical trial.

Early discharge of patients with pulmonary embolism in daily clinical practice: A prospective observational study comparing clinical gestalt and clinical rules

ObjectivesTo estimate the efficiency and safety of clinicians' gestalt in the identification of patients with pulmonary embolism (PE) candidates for early discharge and to compare the efficiency and safety of clinical gestalt with that of the Pulmonary Embolism Severity Index (PESI), the simplified PESI (sPESI) and the Hestia criteria (HC). MethodsConsecutive adult patients presenting to the emergency department of four Italian hospitals with confirmed diagnosis of PE were included. Data for PESI, sPESI and HC assessment were prospectively collected. Patients were managed according to the clinical gestalt of the attending physician, independent of the results of PESI, sPESI and HC. Efficiency was defined as the prevalence of candidates to early discharge. The primary safety measure was the incidence of a composite of venous thromboembolic recurrence, major haemorrhage or all-cause mortality within 30 days. ResultsOut of 547 included patients, 178 (32.5%) were judged to be at low risk and discharged within 48 h from presentation. HC identified a higher proportion (41.7%) whereas both PESI (24.1%) and sPESI (18.3%) identified a lower proportion of candidates for early discharge when compared to clinical gestalt (P < 0.01 for all). The incidence of the safety outcome was 2.8% in early-discharged patients according to clinical gestalt and 2.3%, 3.0% and 2.6% in candidates to early discharge according to PESI, sPESI and HC, without differences between strategies. ConclusionsIn our cohort, clinical gestalt identified one-third of PE patients for early discharge. Among different strategies HC showed the highest efficiency sharing similar safety with the other strategies.

Reduced plasma fibrin clot permeability is associated with recurrent thromboembolic events in patients with antiphospholipid syndrome.

APS is associated with arterial and venous thrombosis. The unfavourable fibrin clot phenotype, including formation of dense and poorly lysable clots, has been reported in thrombotic APS. We investigated whether abnormal plasma clot properties are predictive of recurrent thromboembolism in APS. We followed 126 consecutive patients with thrombotic APS and 105 control subjects, without APS, matched for thrombotic events. Plasma fibrin clot permeability (Ks), turbidity measurements and clot lysis time were evaluated ⩾5 months after a thrombotic event. The primary composite end point was symptomatic recurrent venous thromboembolism, ischaemic stroke and/or myocardial infarction. During follow-up (median, 62 months; range 46-74 months; 1183.2 patient-years), the primary outcome was observed in 33 (26.2%) APS patients and 16 (15.2%) controls, including 25 (19.8%) and 14 (13.3%) subjects with recurrent venous thromboembolism, respectively. Reduced Ks and prolonged clot lysis time predicted recurrent thromboembolic events in APS patients [per 1 × 10-9 cm2: hazard ratio (HR) = 0.37; 95% CI: 0.24, 0.56; and per 10 min: HR = 1.20; 95% CI: 1.01, 1.40, respectively] and in controls (per 1×10-9 cm2: HR = 0.23; 95% CI: 0.11, 0.42; and per 10 min: HR = 1.51; 95% CI: 1.08, 2.16, respectively). A multivariate analysis showed that positive IgG and IgM anti-β2 glycoprotein I antibodies, withdrawal of anticoagulation, lower platelet count and reduced Ks predicted thromboembolic events in APS patients. Formation of denser fibrin networks could be a novel risk factor for recurrent thromboembolism in APS, which highlights the importance of fibrin phenotype in thrombotic disorders.

Recurrence of venous thromboembolism among non small cell lung cancer patients treated with EGFR inhibitors

Recurrence of venous thromboembolism among non small cell lung cancer patients treated with EGFR inhibitors

Anticoagulation Therapy in SELECTeD Cancer Patients at Risk of Recurrence of Venous Thromboembolism: Results of the ‘select-d’ Pilot Trial

Anticoagulation Therapy in SELECTeD Cancer Patients at Risk of Recurrence of Venous Thromboembolism: Results of the ‘select-d’ Pilot Trial

Risk factors for recurrence in deep vein thrombosis patients following a tailored anticoagulant treatment incorporating residual vein obstruction

BackgroundFinding the optimal duration of anticoagulant treatment following an acute event of deep vein thrombosis (DVT) is challenging. Residual venous obstruction (RVO) has been identified as a risk factor for recurrence, but data on management strategies incorporating the presence of RVO and associated recurrence rates in defined clinical care pathways (CCP) are lacking. ObjectivesWe aimed to investigate the long‐term clinical outcomes and predictors of venous thromboembolism (VTE) recurrence in a contemporary cohort of patients with proximal DVT and managed in a CCP incorporating the presence of RVO. PatientsAll patients treated at the Maastricht University Medical Center within an established clinical care pathway from June 2003 through June 2013 were prospectively followed for up to 11 years in a prospective management study. ResultsOf 479 patients diagnosed with proximal DVT, 474 completed the two‐year CCP (99%), and 457 (94.7%) the extended follow‐up (2231.2 patient‐years; median follow‐up 4.6 years). Overall VTE recurrence was 2.9 per 100 patient‐years, 1.3 if provoked by surgery, 2.1 if a non‐surgical transient risk factor was present and 4.0 if unprovoked. Predictors of recurrent events were unprovoked VTE (adjusted hazard ratio [HR] 4.6; 95% CI 1.7, 11.9), elevated D‐dimer one month after treatment was stopped (HR 3.3; 1.8, 6.1), male sex (HR 2.8; 1.5, 5.1), high factor VIII (HR 2.2; 1.2, 4.0) and use of contraceptives (HR 0.1; 0.0, 0.9). ConclusionsPatients with DVT managed within an established clinical care pathway incorporating the presence of RVO had relatively low incidences of VTE recurrence.

Outcomes during anticoagulation in patients with symptomatic vs. incidental splanchnic vein thrombosis

IntroductionCurrent guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. MethodsWe used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. ResultsIn March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71–5.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47–2.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14–8.17) and anaemia (HR: 4.11; 95%CI: 1.45–11.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68–10.1) were associated with at increased risk for major bleeding. ConclusionsThe rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy.