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16 pages, 1652 KiB

Open AccessArticle

Telemedicine-Based Specialized Care Improves the Outcome of Anticoagulated Individuals with Venous Thromboembolism—Results from the thrombEVAL Study

by Karsten Keller, Sebastian Göbel, Vincent ten Cate, Marina Panova-Noeva, Lisa Eggebrecht, Markus Nagler, Meike Coldewey, Maike Foebel, Christoph Bickel, Michael Lauterbach, Christine Espinola-Klein, Karl J. Lackner, Hugo ten Cate, Thomas Münzel, Philipp S. Wild and Jürgen H. Prochaska

J. Clin. Med. 2020, 9(10), 3281; https://doi.org/10.3390/jcm9103281 - 13 Oct 2020

Cited by 4 | Viewed by 2296

Abstract

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to [...] Read more.

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011–March 2013). Patients were evaluated using clinical visits, computer-assisted personal interviews, self-reported data and laboratory measurements according to standard operating procedures. Overall, 360 patients with VTE from RMC and 254 from CS were included. Time in therapeutic range (TTR) was higher in CS compared to RMC (76.9% (interquartile range [IQR] 63.2–87.1%) vs. 69.5% (52.3–85.6%), p < 0.001). Crude rate of thromboembolic events (rate ratio [RR] 11.33 (95% confidence interval [CI] 1.85–465.26), p = 0.0015), clinically relevant bleeding (RR 6.80 (2.52–25.76), p < 0.001), hospitalizations (RR 2.54 (1.94–3.39), p < 0.001) and mortality under OAC (RR 5.89 (2.40–18.75), p < 0.001) were consistently higher in RMC compared with CS. Patients in RMC had higher risk for primary outcome (clinically relevant bleedings, thromboembolic events and mortality, hazard ratio [HR] 5.39 (95%CI 2.81–10.33), p < 0.0001), mortality (HR 5.54 (2.22–13.84), p = 0.00025), thromboembolic events (HR 6.41 (1.51–27.24), p = 0.012), clinically relevant bleeding (HR 5.31 (1.89–14.89), p = 0.0015) and hospitalization (HR 1.84 (1.34–2.55), p = 0.0002). Benefits of CS care were still observed after adjusting for comorbidities and TTR. In conclusion, anticoagulation quality and outcome of VTE patients undergoing VKA treatment was significantly better in CS than in RMC. Patients treated in CS had lower rates of adverse events, hospitalizations and lower mortality. CS was prognostically relevant, beyond providing advantages of improved international ratio (INR) monitoring. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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17 pages, 851 KiB

Open AccessArticle

Venous Thromboembolism among Hospitalized Patients with COVID-19 Undergoing Thromboprophylaxis: A Systematic Review and Meta-Analysis

by Gerald Chi, Jane J. Lee, Adeel Jamil, Vamsikrishna Gunnam, Homa Najafi, Sahar Memar Montazerin, Fahimehalsadat Shojaei and Jolanta Marszalek

J. Clin. Med. 2020, 9(8), 2489; https://doi.org/10.3390/jcm9082489 - 3 Aug 2020

Cited by 85 | Viewed by 8380

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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17 pages, 1511 KiB

Open AccessArticle

Delayed Thrombin Generation Is Associated with Minor Bleedings in Venous Thromboembolism Patients on Rivaroxaban: Usefulness of Calibrated Automated Thrombography

by Jaroslaw Zalewski, Konrad Stepien, Karol Nowak, Sandi Caus, Saulius Butenas and Anetta Undas

J. Clin. Med. 2020, 9(7), 2018; https://doi.org/10.3390/jcm9072018 - 27 Jun 2020

Cited by 12 | Viewed by 2468

Abstract

Bleeding is the most feared and difficult to predict adverse event of anticoagulation. We sought to investigate whether calibrated automated thrombography (CAT) parameters are associated with minor bleeding (MB) in anticoagulated patients following venous thromboembolism (VTE). Enrolled were 132 patients on rivaroxaban, 145 [...] Read more.

Bleeding is the most feared and difficult to predict adverse event of anticoagulation. We sought to investigate whether calibrated automated thrombography (CAT) parameters are associated with minor bleeding (MB) in anticoagulated patients following venous thromboembolism (VTE). Enrolled were 132 patients on rivaroxaban, 145 on vitamin K antagonists (VKA) and 31 controls who stopped anticoagulation. Prior to the next dose of the anticoagulant, we measured CAT parameters, along with rivaroxaban concentration and INR. During a median follow-up of 10 months, we recorded minor and major bleedings. On rivaroxaban, 27 (20.5%) patients with MB had longer time to start thrombin generation, lower peak thrombin generation and lower endogenous thrombin potential compared with subjects without MB (all p < 0.001). All CAT parameters, except for peak thrombin generation (p = 0.049), were similar in VKA patients with (n = 25, 17.2%) vs. without MBs. By logistic regression, time to start thrombin generation (p = 0.007) and unprovoked VTE (p = 0.041) independently predicted MBs on rivaroxaban. Major bleedings were more frequent in patients with MBs (17.3% vs. 1.8%, p < 0.001). Abnormal CAT parameters characterize VTE patients prone to MBs on rivaroxaban, but not on VKA. Time to start thrombin generation measured about 24 h since the last rivaroxaban dose might help predict MBs. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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12 pages, 1067 KiB

Open AccessArticle

Outpatient Pulmonary Rehabilitation in Patients with Persisting Symptoms after Pulmonary Embolism

by Stephan Nopp, Frederikus A. Klok, Florian Moik, Milos Petrovic, Irmgard Derka, Cihan Ay and Ralf Harun Zwick

J. Clin. Med. 2020, 9(6), 1811; https://doi.org/10.3390/jcm9061811 - 10 Jun 2020

Cited by 24 | Viewed by 3226

Abstract

Background: Patients with pulmonary embolism (PE) may suffer from long-term consequences, including decreased functional capacity. Data on pulmonary rehabilitation (PR) in patients with PE are scarce, and no data on outpatient PR are available so far. Methods: We analyzed data of 22 PE [...] Read more.

Background: Patients with pulmonary embolism (PE) may suffer from long-term consequences, including decreased functional capacity. Data on pulmonary rehabilitation (PR) in patients with PE are scarce, and no data on outpatient PR are available so far. Methods: We analyzed data of 22 PE patients who attended outpatient PR due to exertional dyspnea. Patients underwent a multi-professional 6-week PR program. The primary outcome was change in 6-min walk test (6MWT). Secondary outcomes included changes in strength and endurance tests. To assess long-term benefits, follow-up was performed a median of 39 months after PR. Results: Patients started PR a median of 19 weeks after the acute PE event. Their median age was 47.5 years, 33% were women and all presented with NYHA (New York Heart Association) class II and higher. After PR, patients showed significant and clinically relevant improvements in 6MWT (mean difference: 49.4 m [95% CI 32.0−66.8]). Similarly, patients increased performance in maximum strength, endurance and inspiratory muscle strength. At long-term follow-up, 78% of patients reported improved health. Conclusion: We observed significant improvements in exercise capacity in PE patients undergoing outpatient PR. The majority of patients also reported a long-term improvement in health status. Prospective studies are needed to identify patients who would benefit most from structured PR. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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11 pages, 696 KiB

Open AccessArticle

Elevated Lactate Levels in Acute Pulmonary Embolism Are Associated with Prothrombotic Fibrin Clot Properties: Contribution of NETs Formation

by Michał Ząbczyk, Joanna Natorska, Agnieszka Janion-Sadowska, Krzysztof P. Malinowski, Marianna Janion and Anetta Undas

J. Clin. Med. 2020, 9(4), 953; https://doi.org/10.3390/jcm9040953 - 30 Mar 2020

Cited by 24 | Viewed by 3798

Abstract

Background: Elevated plasma lactate levels correlate with high mortality rate in acute pulmonary embolism (PE) patients. We hypothesized that elevated lactate levels correlate with prothrombotic fibrin clot properties and enhanced neutrophil extracellular trap (NET) formation in acute PE. Methods: As many as 126 [...] Read more.

Background: Elevated plasma lactate levels correlate with high mortality rate in acute pulmonary embolism (PE) patients. We hypothesized that elevated lactate levels correlate with prothrombotic fibrin clot properties and enhanced neutrophil extracellular trap (NET) formation in acute PE. Methods: As many as 126 normotensive acute PE patients (aged 58 ± 14 years) were enrolled. Plasma fibrin clot permeability (K_s), clot lysis time (CLT), endogenous thrombin potential (ETP), citrullinated histone H3 (citH3), and plasminogen activator inhibitor-1 antigen (PAI-1), together with plasma L-lactate levels were evaluated on admission. Results: Lactate levels ≥2 mM were found in 70 (55.6%) patients in whom we observed 29% higher neutrophil count and 45% elevated plasma citH3 levels. Elevated lactate levels were associated with more prothrombotic fibrin properties as reflected by 11% reduced K_s, 13% longer CLT, along with 11% increased ETP. Lactate levels were positively associated with plasma citH3 concentrations, ETP, CLT, and PAI-1 (p < 0.05). An increase of lactate levels by 1 mM leading to the prolongation of CLT by 8.82 min was shown in the linear regression. Conclusions: Our findings suggest a new mechanism contributing to a negative impact of elevated lactate levels on prognosis in acute PE patients, in particular hypofibrinolysis, associated with enhanced NET formation. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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Review

Jump to: Research

13 pages, 278 KiB

Open AccessReview

Current Challenges in Diagnosis of Venous Thromboembolism

by Zachary Liederman, Noel Chan and Vinai Bhagirath

J. Clin. Med. 2020, 9(11), 3509; https://doi.org/10.3390/jcm9113509 - 29 Oct 2020

Cited by 12 | Viewed by 3901

Abstract

In patients with suspected venous thromboembolism, the goal is to accurately and rapidly identify those with and without thrombosis. Failure to diagnose venous thromboembolism (VTE) can lead to fatal pulmonary embolism (PE), and unnecessary anticoagulation can cause avoidable bleeding. The adoption of a [...] Read more.

In patients with suspected venous thromboembolism, the goal is to accurately and rapidly identify those with and without thrombosis. Failure to diagnose venous thromboembolism (VTE) can lead to fatal pulmonary embolism (PE), and unnecessary anticoagulation can cause avoidable bleeding. The adoption of a structured approach to VTE diagnosis, that includes clinical prediction rules, D-dimer testing and non-invasive imaging modalities, has enabled rapid, cost-effective and accurate VTE diagnosis, but problems still persist. First, with increased reliance on imaging and widespread use of sensitive multidetector computed tomography (CT) scanners, there is a potential for overdiagnosis of VTE. Second, the optimal strategy for diagnosing recurrent leg deep venous thrombosis remains unclear as is that for venous thrombosis at unusual sites. Third, the conventional diagnostic approach is inefficient in that it is unable to exclude VTE in high-risk patients. In this review, we outline pragmatic approaches for the clinician faced with difficult VTE diagnostic cases. In addition to discussing the principles of the current diagnostic framework, we explore the diagnostic approach to recurrent VTE, isolated distal deep-vein thrombosis (DVT), pregnancy associated VTE, subsegmental PE, and VTE diagnosis in complex medical patients (including those with impaired renal function). Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

27 pages, 733 KiB

Open AccessReview

Prevention of Venous Thromboembolism in 2020 and Beyond

by Matthew Nicholson, Noel Chan, Vinai Bhagirath and Jeffrey Ginsberg

J. Clin. Med. 2020, 9(8), 2467; https://doi.org/10.3390/jcm9082467 - 1 Aug 2020

Cited by 108 | Viewed by 20571

Abstract

Venous thromboembolism (VTE) is the third most common cause of vascular mortality worldwide and comprises deep-vein thrombosis (DVT) and pulmonary embolism (PE). In this review, we discuss how an understanding of VTE epidemiology and the results of thromboprophylaxis trials have shaped the current [...] Read more.

Venous thromboembolism (VTE) is the third most common cause of vascular mortality worldwide and comprises deep-vein thrombosis (DVT) and pulmonary embolism (PE). In this review, we discuss how an understanding of VTE epidemiology and the results of thromboprophylaxis trials have shaped the current approach to VTE prevention. We will discuss modern thromboprophylaxis as it pertains to genetic risk factors, exogenous hormonal therapies, pregnancy, surgery, medical hospitalization, cancer, and what is known thus far about VTE in COVID-19 infection. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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9 pages, 213 KiB

Open AccessReview

Screening for Occult Cancer in Patients with Venous Thromboembolism

by Julien D’Astous and Marc Carrier

J. Clin. Med. 2020, 9(8), 2389; https://doi.org/10.3390/jcm9082389 - 27 Jul 2020

Cited by 9 | Viewed by 4399

Abstract

Unprovoked venous thromboembolism (VTE) can be the first sign of an occult cancer. The rate of occult cancer detection within 12 months of a newly diagnosed unprovoked VTE is approximately 5%. Therefore, it is appealing for clinicians to screen patients with unprovoked VTE [...] Read more.

Unprovoked venous thromboembolism (VTE) can be the first sign of an occult cancer. The rate of occult cancer detection within 12 months of a newly diagnosed unprovoked VTE is approximately 5%. Therefore, it is appealing for clinicians to screen patients with unprovoked VTE for occult cancer, as it could potentially decrease cancer-related mortality and morbidity and improve quality of life. However, several randomized controlled trials have failed to report that an extensive occult cancer screening strategy (e.g., computed tomography of the abdomen/pelvis) is improving these patient-important outcomes. Therefore, clinical guidance documents suggest that patients should only undergo a limited screening strategy including a thorough medical history, physical examination, basic laboratory investigations (i.e., complete blood count and liver function tests), chest X-ray, as well as age- and gender-specific cancer screening (breast, cervical, colon and prostate). More intensive occult cancer screening including additional investigations is not routinely recommended. This narrative review will focus on the epidemiology, timing, and evidence regarding occult cancer detection in patients with unprovoked VTE. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

14 pages, 756 KiB

Open AccessReview

Diagnostic and Therapeutic Management of Upper Extremity Deep Vein Thrombosis

by Floris T. M. Bosch, Marcello Di Nisio, Harry R. Büller and Nick van Es

J. Clin. Med. 2020, 9(7), 2069; https://doi.org/10.3390/jcm9072069 - 1 Jul 2020

Cited by 35 | Viewed by 12651

Abstract

Upper extremity deep vein thrombosis (UEDVT) accounts for 5% of all deep vein thromboses (DVTs). UEDVT may be complicated by post thrombotic syndrome and pulmonary embolism, and early recognition and prompt start of anticoagulant treatment are key. Primary UEDVT, also known as Paget-von [...] Read more.

Upper extremity deep vein thrombosis (UEDVT) accounts for 5% of all deep vein thromboses (DVTs). UEDVT may be complicated by post thrombotic syndrome and pulmonary embolism, and early recognition and prompt start of anticoagulant treatment are key. Primary UEDVT, also known as Paget-von Schrötter syndrome, is associated with repeated or sudden physical activity of the upper arm and venous outflow obstruction due to anatomical variations. Secondary UEDVT is often associated with malignancy or use of intravenous devices, such as central venous catheters or pacemaker leads. Although the diagnosis and treatment of UEDVT have many similarities with DVT of the lower extremities, knowledge of specific aspects regarding UEDVT is important to guide optimal management. In this review, we will discuss the epidemiology, diagnosis, and treatment of UEDVT based on the current literature. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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21 pages, 351 KiB

Open AccessReview

Predicting the Risk of Recurrent Venous Thromboembolism: Current Challenges and Future Opportunities

by Hannah Stevens, Karlheinz Peter, Huyen Tran and James McFadyen

J. Clin. Med. 2020, 9(5), 1582; https://doi.org/10.3390/jcm9051582 - 22 May 2020

Cited by 10 | Viewed by 4512

Abstract

Acute venous thromboembolism (VTE) is a commonly diagnosed condition and requires treatment with anticoagulation to reduce the risk of embolisation as well as recurrent venous thrombotic events. In many cases, cessation of anticoagulation is associated with an unacceptably high risk of recurrent VTE, [...] Read more.

Acute venous thromboembolism (VTE) is a commonly diagnosed condition and requires treatment with anticoagulation to reduce the risk of embolisation as well as recurrent venous thrombotic events. In many cases, cessation of anticoagulation is associated with an unacceptably high risk of recurrent VTE, precipitating the use of indefinite anticoagulation. In contrast, however, continuing anticoagulation is associated with increased major bleeding events. As a consequence, it is essential to accurately predict the subgroup of patients who have the highest probability of experiencing recurrent VTE, so that treatment can be appropriately tailored to each individual. To this end, the development of clinical prediction models has aided in calculating the risk of recurrent thrombotic events; however, there are several limitations with regards to routine use for all patients with acute VTE. More recently, focus has shifted towards the utility of novel biomarkers in the understanding of disease pathogenesis as well as their application in predicting recurrent VTE. Below, we review the current strategies used to predict the development of recurrent VTE, with emphasis on the application of several promising novel biomarkers in this field. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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15 pages, 304 KiB

Open AccessReview

Catheter-Based Therapies and Other Management Strategies for Deep Vein Thrombosis and Post-Thrombotic Syndrome

by Siddhant Thukral and Suresh Vedantham

J. Clin. Med. 2020, 9(5), 1439; https://doi.org/10.3390/jcm9051439 - 12 May 2020

Cited by 17 | Viewed by 3537

Abstract

Acute deep vein thrombosis (DVT) causes substantial short-term and long-term patient morbidity. Medical, lifestyle, and compressive therapies have been investigated for the prevention of pulmonary embolism (PE) and recurrence of venous thromboembolism (VTE). However, patient-centered outcomes such as resolution of presenting DVT symptoms [...] Read more.

Acute deep vein thrombosis (DVT) causes substantial short-term and long-term patient morbidity. Medical, lifestyle, and compressive therapies have been investigated for the prevention of pulmonary embolism (PE) and recurrence of venous thromboembolism (VTE). However, patient-centered outcomes such as resolution of presenting DVT symptoms and late occurrence of post-thrombotic syndrome (PTS) have not been prioritized to the same degree. Imaging-guided, catheter-based endovascular therapy has been used in selected patients to alleviate these sequelae, but important questions remain about their optimal use. In this article, we review the available evidence and summarize the rationale for use of catheter-based therapy in specific patient groups. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

10 pages, 827 KiB

Open AccessReview

New Paradigms of Extended Thromboprophylaxis in Medically Ill Patients

by Kira MacDougall and Alex C Spyropoulos

J. Clin. Med. 2020, 9(4), 1002; https://doi.org/10.3390/jcm9041002 - 2 Apr 2020

Cited by 14 | Viewed by 4452

Abstract

Extended thromboprophylaxis given to medically ill patients for up to 45 days following an acute hospitalization remains an emerging topic among many hospital-based health care providers. Recent advancements in the field of extended thromboprophylaxis using risk stratification and careful patient selection criteria have [...] Read more.

Extended thromboprophylaxis given to medically ill patients for up to 45 days following an acute hospitalization remains an emerging topic among many hospital-based health care providers. Recent advancements in the field of extended thromboprophylaxis using risk stratification and careful patient selection criteria have led to an improved safety profile of direct oral anticoagulants (DOACs) and established net clinical benefit when given to key patient subgroups at high risk of venous thromboembolism (VTE) and low risk of bleeding. The Food and Drug Administration (FDA) has now approved the DOACs betrixaban and rivaroxaban for both in-hospital and extended thromboprophylaxis in medically ill patients in these key subgroups, which represents more than one-quarter of hospitalized medically ill patients. This has potential to significantly reduce VTE-related morbidity and mortality for these patients. Emerging data also supports reductions in the risk of arterial thromboembolism in medically ill patients with extended thromboprophylaxis post-hospital discharge using DOACs. This article aims to review the most recent concepts of predicting and preventing VTE and to discuss emerging paradigms of extended thromboprophylaxis in hospitalized medically ill patients utilizing an individualized, risk-adapted approach. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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20 pages, 9605 KiB

Open AccessReview

Prevention and Management of the Post-Thrombotic Syndrome

by Ilia Makedonov, Susan R. Kahn and Jean-Philippe Galanaud

J. Clin. Med. 2020, 9(4), 923; https://doi.org/10.3390/jcm9040923 - 27 Mar 2020

Cited by 60 | Viewed by 14955

Abstract

The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency secondary to prior deep vein thrombosis (DVT). It affects up to 50% of patients after proximal DVT. There is no effective treatment of established PTS and its management lies in its prevention [...] Read more.

The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency secondary to prior deep vein thrombosis (DVT). It affects up to 50% of patients after proximal DVT. There is no effective treatment of established PTS and its management lies in its prevention after DVT. Optimal anticoagulation is key for PTS prevention. Among anticoagulants, low-molecular-weight heparins have anti-inflammatory properties, and have a particularly attractive profile. Elastic compression stockings (ECS) may be helpful for treating acute DVT symptoms but their benefits for PTS prevention are debated. Catheter-directed techniques reduce acute DVT symptoms and might reduce the risk of moderate–severe PTS in the long term in patients with ilio-femoral DVT at low risk of bleeding. Statins may decrease the risk of PTS, but current evidence is lacking. Treatment of PTS is based on the use of ECS and lifestyle measures such as leg elevation, weight loss and exercise. Venoactive medications may be helpful and research is ongoing. Interventional techniques to treat PTS should be reserved for highly selected patients with chronic iliac obstruction or greater saphenous vein reflux, but have not yet been assessed by robust clinical trials. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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20 pages, 347 KiB

Open AccessReview

Cerebral and Splanchnic Vein Thrombosis: Advances, Challenges, and Unanswered Questions

by Nicoletta Riva and Walter Ageno

J. Clin. Med. 2020, 9(3), 743; https://doi.org/10.3390/jcm9030743 - 10 Mar 2020

Cited by 22 | Viewed by 3862

Abstract

Cerebral vein thrombosis (CVT) and splanchnic vein thrombosis (SVT) are two manifestations of venous thromboembolism (VTE) at unusual sites. They have an incidence at least 25–50 times lower than usual site VTE, but represent true clinical challenges. Recent evidence on the epidemiology, risk [...] Read more.

Cerebral vein thrombosis (CVT) and splanchnic vein thrombosis (SVT) are two manifestations of venous thromboembolism (VTE) at unusual sites. They have an incidence at least 25–50 times lower than usual site VTE, but represent true clinical challenges. Recent evidence on the epidemiology, risk factors, prognosis, and treatment of CVT and SVT has been published in the last two decades, thus contributing to a better understanding of these diseases. The improvement in imaging techniques and a higher degree of clinical suspicion may have led to the observed increased frequency, whereas a better knowledge of provoking mechanisms could have contributed to reducing the proportion of events classified as unprovoked or idiopathic (13–21% of CVT, 15–27% of SVT). Few small randomized clinical trials and a number of observational studies, although hampered by heterogeneous therapeutic approaches, shed light on the safety and effectiveness of anticoagulant therapy in these populations. However, there are still some grey areas that warrant future research. In this narrative review, we discuss recent advances and therapeutic challenges in CVT and SVT. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

16 pages, 1097 KiB

Open AccessReview

Low Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis

by Ruben J. Eck, Wouter Bult, Jørn Wetterslev, Reinold O. B. Gans, Karina Meijer, Iwan C.C. van der Horst and Frederik Keus

J. Clin. Med. 2019, 8(12), 2039; https://doi.org/10.3390/jcm8122039 - 21 Nov 2019

Cited by 13 | Viewed by 3530

Abstract

International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many patient categories. Guidance on the optimal prophylactic dose is lacking. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized [...] Read more.

International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many patient categories. Guidance on the optimal prophylactic dose is lacking. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials to assess benefits and harms of low-dose LMWH versus placebo or no treatment for thrombosis prophylaxis in patients at risk of VTE. PubMed, Cochrane Library, Web of Science, and Embase were searched up to June 2019. Results were presented as relative risk (RR) with conventional and TSA-adjusted confidence intervals (CI). Forty-four trials with a total of 22,579 participants were included. Six (14%) had overall low risk of bias. Low-dose LMWH was not statistically significantly associated with all-cause mortality (RR 0.99; 95%CI 0.85–1.14; TSA-adjusted CI 0.89–1.16) but did reduce symptomatic VTE (RR 0.62; 95%CI 0.48–0.81; TSA-adjusted CI 0.44–0.89) and any VTE (RR 0.61; 95%CI 0.50–0.75; TSA-adjusted CI 0.49–0.82). Analyses on major bleeding (RR 1.07; 95%CI 0.72–1.59), as well as serious adverse events (SAE) and clinically relevant non-major bleeding were inconclusive. There was very low to moderate-quality evidence that low-dose LMWH for thrombosis prophylaxis did not decrease all-cause mortality but reduced the incidence of symptomatic and asymptomatic VTE, while the analysis of the effects on bleeding and adverse events remained inconclusive. Full article

(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)

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