Evaluation of Once Weekly Subcutaneous Idraparinux Versus Standard Therapy with Heparin and Vitamin K Antagonists in the Treatment of Deep-Vein Thrombosis or Pulmonary Embolism - The Van Gogh Investigators.

Abstract Background Venous thromboembolism is treated with heparins, followed by a vitamin K antagonist. It would be desirable to replace this complex approach with one simple anticoagulant regimen. Methods We conducted two randomized, open-label trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare efficacy and safety of idraparinux alone versus standard therapy, and document non-inferiority for efficacy. Patients received either idraparinux (2.5 mg once-weekly, subcutaneously), or low-molecular-weight heparin/unfractionated heparin with adjusted-dose vitamin K antagonists, for three or six months. The primary efficacy outcome was the three-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal). Results In the deep-vein thrombosis study the incidence of recurrence at day 92 was 2.9 percent with idraparinux and 3.0 percent in controls (odds ratio 0.98, 95 percent confidence interval 0.63 to 1.50), satisfying the pre-specified non-inferiority requirement. The six-month hazard ratio was 1.01. The incidence of clinically relevant bleeding at day 92 was 4.5 percent and 7.0 percent , respectively (P<0.01). By six months bleeding rates were similar. In the pulmonary embolism study the incidence of recurrence at day 92 was 3.4 percent with idraparinux and 1.6 percent in controls (odds ratio 2.14, 95 percent confidence interval 1.21 to 3.78), excluding non-inferiority. Conclusion In patients with deep-vein thrombosis, once-weekly subcutaneous idraparinux for three or six months had similar efficacy and safety as heparins and vitamin K antagonists, while, in pulmonary embolism, this regimen was less efficacious than standard anticoagulant therapy which had an unexpectedly low recurrence rate.

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Should Patients with Deep Vein Thrombosis Alone be Treated as Those with Concomitant Asymptomatic Pulmonary Embolism? A Prospective Study

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613337 ◽

2002 ◽

Vol 88 (12) ◽

pp. 938-942 ◽

Cited By ~ 15

Author(s):

Harry Büller ◽

Anthonie Lensing ◽

Montserrat Bonet ◽

Javier Roncales ◽

Jordi Muchart ◽

...

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Major Bleeding ◽

Odds Ratio ◽

Vitamin K Antagonists ◽

Fixed Dose ◽

Once Daily ◽

Bleeding Rate ◽

Vein Thrombosis ◽

Deep Vein

SummaryThe established initial treatment of patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) consists of the administration of subcutaneous, weight adjusted, low-molecular weight heparin (LMWH). However, the use of the same LMWH dosages for patients with either DVT or PE is not supported by data from comparative studies.1,000 consecutive patients with acute, proximal DVT were prospectively evaluated. All patients underwent a ventilation-perfusion lung scan on admission, and remained in hospital for at least 7 days. Patients with silent PE received once daily 10,000 to 15,000 IU subcutaneous LMWH dalteparin according to body weight for 7 days, and then vitamin K antagonists. Patients with DVT alone received LMWH in a fixed dose of 10,000 IU once daily for at least 5 days, and then vitamin K antagonists. The rate of both, major bleeding and symptomatic PE episodes during the 7-day study period was evaluated.Thirteen patients (1.3%) developed recurrent PE (1 died) and 16 patients (1.6%) had major bleeding (7 died). Recurrent PE was significantly more common in patients with silent PE (9 of 258 patients, 3.5%) than in those with DVT alone (4 of 742 patients, 0.5%. Odds ratio: 6.5; p <0.001). There were no significant differences in bleeding rate between patients with silent PE and those with DVT alone. However, the use of a fixed 10,000 IU dose in patients with DVT alone led to a significantly lower bleeding rate in patients weighing over 70 kg: 1 of 349 patients (0.3%) as compared to 9 of 393 patients (2.3%) in those weighing less than 70 kg (odds ratio: 0.12; p = 0.018).Fixed-dose 10,000 IU of LMWH dalteparin once daily proved to be both effective and safe in patients with DVT alone. The observed recurrence rate of 0.5% in these patients compares favourably with the 3.5% rate in patients with silent PE. Furthermore, this fixed-dosage was also safe. Patients weighing over 70 kg had a significant decrease in the rate of major bleeding, and no compensatory increase in the rate of recurrent PE.

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Vitamin K Antagonists (Coumarins), Drugs Used in the Prevention and Treatment of Cardioembolism, Deep Vein Thrombosis, and Pulmonary Embolism

Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease ◽

10.1016/b978-0-12-411462-3.00040-0 ◽

2015 ◽

pp. 395-398 ◽

Cited By ~ 2

Author(s):

Francesco Marongiu ◽

Doris Barcellona

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Vein Thrombosis ◽

Prevention And Treatment ◽

Deep Vein

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Is the Prevalence of the Factor V Leiden Mutation in Patients with Pulmonary Embolism and Deep Vein Thrombosis Really Different?

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614474 ◽

1999 ◽

Vol 81 (03) ◽

pp. 345-348 ◽

Cited By ~ 22

Author(s):

Rosa Karemaker ◽

Philomeen Kuijer ◽

Martin Prins ◽

Harry Büller ◽

Franktien Turkstra

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Odds Ratio ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Vein Thrombosis ◽

Common Odds Ratio ◽

Deep Vein

Summary Introduction. Previous investigations have suggested a lower prevalence of the factor V Leiden mutation in patients with pulmonary embolism, as compared to patients with deep leg vein thrombosis. Methods. We studied unselected patients with pulmonary embolism, in whom we also assessed the presence of deep vein thrombosis by ultra-sonography. We assessed the prevalence of heterozygosity for the factor V Leiden mutation and compared the outcome of patients with a normal ultrasound (primary pulmonary embolism) to those with an abnormal ultrasound (combined form of venous thromboembolism). Furthermore, we performed a literature search to identify all articles regarding the prevalence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and a combined form of venous thromboembolism. We calculated a (common) odds ratio for these 3 manifestations of venous thromboembolism, including the current findings. Results. In 92 patients with proven pulmonary embolism, 25 (27%) had also an abnormal ultrasound. In these patients, the prevalence of the factor V Leiden mutation was 24% (95% CI 9%-45%), whereas the mutation was present in 5 of 67 patients with primary pulmonary embolism (7%; 95% CI 2%-16%). The literature analysis indicated the common odds ratio for the presence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and the combined form of venous thromboembolism to be 7.9 (95% CI 5-12), 3.5 (95% CI 2-6) and 6.8 (95% CI 3-14), respectively. Conclusion. In patients with primary pulmonary embolism the prevalence of the factor V Leiden mutation appears to be half of that reported in patients with primary deep vein thrombosis. The mechanism remains unclear.

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Incidence of venous thromboembolism among patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000980 ◽

2020 ◽

Vol 30 (4) ◽

pp. 491-497 ◽

Cited By ~ 3

Author(s):

Julia Rose Salinaro ◽

Kourtnie McQuillen ◽

Megan Stemple ◽

Robert Boccaccio ◽

Jessie Ehrisman ◽

...

Keyword(s):

Ovarian Cancer ◽

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Primary Outcome ◽

Vein Thrombosis ◽

Deep Vein

ObjectivesNeoadjuvant chemotherapy may be considered for women with epithelial ovarian cancer who have poor performance status or a disease burden not amenable to primary cytoreductive surgery. Overlap exists between indications for neoadjuvant chemotherapy and known risk factors for venous thromboembolism, including impaired mobility, increasing age, and advanced malignancy. The objective of this study was to determine the rate of venous thromboembolism among women receiving neoadjuvant chemotherapy for epithelial ovarian cancer.MethodsA multi-institutional, observational study of patients receiving neoadjuvant chemotherapy for primary epithelial ovarian, fallopian tube, or peritoneal cancer was conducted. Primary outcome was rate of venous thromboembolism during neoadjuvant chemotherapy. Secondary outcomes included rates of venous thromboembolism at other stages of treatment (diagnosis, following interval debulking surgery, during adjuvant chemotherapy, or during treatment for recurrence) and associations between occurrence of venous thromboembolism during neoadjuvant chemotherapy, subject characteristics, and interval debulking outcomes. Venous thromboembolism was defined as deep vein thrombosis in the upper or lower extremities or in association with peripherally inserted central catheters or ports, pulmonary embolism, or concurrent deep vein thrombosis and pulmonary embolism. Both symptomatic and asymptomatic venous thromboembolism were reported.ResultsA total of 230 patients receiving neoadjuvant chemotherapy were included; 63 (27%) patients overall experienced a venous thromboembolism. The primary outcome of venous thromboembolism during neoadjuvant chemotherapy occurred in 16 (7.7%) patients. Of the remaining venous thromboembolism events, 22 were at diagnosis (9.6%), six post-operatively (3%), five during adjuvant chemotherapy (3%), and 14 during treatment for recurrence (12%). Patients experiencing a venous thromboembolism during neoadjuvant chemotherapy had a longer mean time to interval debulking and were less likely to undergo optimal cytoreduction (50% vs 80.2%, p=0.02).ConclusionsPatients with advanced ovarian cancer are at high risk for venous thromboembolism while receiving neoadjuvant chemotherapy. Consideration of thromboprophylaxis may be warranted.

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Venous Thromboembolism

10.2310/vasc.2101 ◽

2017 ◽

Author(s):

Guillermo A. Escobar ◽

Peter K. Henke ◽

Thomas W. Wakefield

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Lower Extremity ◽

The United States ◽

Laboratory Evaluation ◽

Individual Risk ◽

Vein Thrombosis ◽

Clinical Scenarios ◽

Deep Vein

Deep vein thrombosis (DVT) and pulmonary embolism (PE) comprise venous thromboembolism (VTE). Together, they comprise a serious health problem as there are over 275,000 new VTE cases per year in the United States, resulting in a prevalence of one to two per 1,000 individuals, with some studies suggesting that the incidence may even be double that. This review covers assessment of a VTE event, initial evaluation of a patient suspected of having VTE, medical history, clinical presentation of VTE, physical examination, laboratory evaluation, imaging, prophylaxis against perioperative VTE, indications for immediate intervention (threat to life or limb), indications for urgent intervention, and management of nonemergent VTE. Figures show a modified Caprini score questionnaire used at the University of Michigan to determine individual risk of VTE and the indicated prophylaxis regimen; Wells criteria for DVT and PE; phlegmasia cerulea dolens secondary to acute left iliofemoral DVT after thigh trauma; compression duplex ultrasonography of lower extremity veins; computed tomographic angiogram of the chest demonstrating a thrombus in the pulmonary artery, with extension into the right main pulmonary; management of PE according to Wells criteria findings; management of PE with right heart strain in cases of massive or submassive PE; treatment of DVT according to clinical scenario; a lower extremity venogram of a patient with May-Thurner syndrome and its subsequent endovascular treatment; and various examples of retrievable vena cava filters (not drawn to scale). Tables list initial clinical assessment for VTE, clinical scenarios possibly benefiting from prolonged anticoagulation after VTE, indications for laboratory investigation of secondary thrombophilia, venous thromboembolic risk accorded to hypercoagulable states, and Pulmonary Embolism Rule-out Criteria Score to avoid the need for D-dimer in patients suspected of having PE. This review contains 11 highly rendered figures, 5 tables, and 167 references. Key words: anticoagulation; deep vein thrombosis; postthrombotic syndrome; pulmonary embolism; recurrent venous thromboembolism; thrombophilia; venous thromboembolism; PE; VTE; DVT

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Inferior Vena Cava Agenesis and Deep Vein Thrombosis: A Pharmacological Alternative to Vitamin K Antagonists

European Journal of Case Reports in Internal Medicine ◽

10.12890/2019_001310 ◽

2019 ◽

Author(s):

Inês Esteves Cruz ◽

Pedro Ferreira ◽

Raquel Silva ◽

Francisco Silva ◽

Isabel Madruga

Keyword(s):

Deep Vein Thrombosis ◽

Inferior Vena Cava ◽

Vitamin K ◽

Oral Anticoagulation ◽

Inferior Vena ◽

Vitamin K Antagonists ◽

Anticoagulation Therapy ◽

Vena Cava ◽

Vein Thrombosis ◽

Deep Vein

Inferior vena cava (IVC) agenesis is a rare congenital abnormality affecting the infrarenal segment, the suprarenal or the whole of the IVC. It has an estimated prevalence of up to 1% in the general population that can rise to 8.7% when abnormalities of the left renal vein are considered. Most IVC malformations are asymptomatic but may be associated with nonspecific symptoms or present as deep vein thrombosis (DVT). Up to 5% of young individuals under 30 years of age with unprovoked DVT are found to have this condition. Regarding the treatment of IVC agenesis-associated DVT, there are no standard guidelines. Treatment is directed towards preventing thrombosis or its recurrence. Low molecular weight heparin and oral anticoagulation medication, in particular vitamin K antagonists (VKAs) are the mainstay of therapy. Given the high risk of DVT recurrence in these patients, oral anticoagulation therapy is suggested to be pursued indefinitely. As far as we know, this is the first case reporting the use of a direct factor Xa inhibitor in IVC agenesis-associated DVT. Given VKA monitoring limitations, the use of a direct Xa inhibitor could be an alternative in young individuals with anatomical defects without thrombophilia, but further studies will be needed to confirm its efficacy and safety.

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Venous Thromboembolism in Denmark: Seasonality in Occurrence and Mortality

TH Open ◽

10.1055/s-0039-1692399 ◽

2019 ◽

Vol 03 (02) ◽

pp. e171-e179 ◽

Cited By ~ 2

Author(s):

Nils Skajaa ◽

Erzsébet Horváth-Puhó ◽

Kasper Adelborg ◽

Paolo Prandoni ◽

Kenneth J. Rothman ◽

...

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Seasonal Pattern ◽

Cerebral Vein ◽

Cerebral Vein Thrombosis ◽

Splanchnic Vein Thrombosis ◽

Vein Thrombosis ◽

Winter Peak ◽

Deep Vein

Background Many cardiovascular conditions exhibit seasonality in occurrence and mortality, but little is known about the seasonality of venous thromboembolism. Methods Using Danish registries, we identified all patients with deep vein thrombosis, pulmonary embolism, splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis during 1977–2016. We tallied monthly deaths occurring within 90 days of the venous thromboembolism diagnosis. We estimated peak-to-trough ratios and timing of the peak of both diagnoses and deaths summed over all years of the study period. The departure from 1.0 of the peak-to-trough ratio measures the intensity of any seasonal pattern. Results We estimated a peak-to-trough ratio of 1.09 (95% confidence interval: 1.07–1.11) for deep vein thrombosis and 1.22 (1.19–1.24) for pulmonary embolism occurrence. The peak-to-trough ratios for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence were 1.10 (1.01–1.20), 1.19 (1.00–1.40), and 1.12 (1.07–1.17), respectively. The occurrence of all conditions peaked during winter or fall. In time trend analyses, the peak-to-trough ratio increased considerably for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence. In associated mortality, the peak-to-trough ratio for deep vein thrombosis was larger (1.15, 1.07–1.23) than that for pulmonary embolism (1.04, 1.01–1.08). Discussion Excess winter risks were modest, but more marked for pulmonary embolism occurrence than for deep vein thrombosis occurrence. The seasonal pattern intensified throughout the study period for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis. The winter peak in mortality following pulmonary embolism was smaller than that for deep vein thrombosis.

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Risk of recurrent venous thromboembolism among deep vein thrombosis and pulmonary embolism patients treated with warfarin

Current Medical Research and Opinion ◽

10.1185/03007995.2014.998814 ◽

2014 ◽

Vol 31 (3) ◽

pp. 439-447 ◽

Cited By ~ 10

Author(s):

Beth L. Nordstrom ◽

Michael A. Evans ◽

Brian R. Murphy ◽

Edith A. Nutescu ◽

Jeff R. Schein ◽

...

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Vein Thrombosis ◽

Recurrent Venous Thromboembolism ◽

Deep Vein

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More than one in two venous thromboembolism treated in French hospitals occurs during the hospital stays

Phlebology The Journal of Venous Disease ◽

10.1177/0268355515575592 ◽

2015 ◽

Vol 31 (6) ◽

pp. 390-396 ◽

Cited By ~ 2

Author(s):

Francois-André Allaert ◽

Eric Benzenine ◽

Catherine Quantin

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Hospital Stay ◽

Principal Diagnosis ◽

Vein Thrombosis ◽

Icd 10 ◽

Hospital Stays ◽

Deep Vein

Objective The objective was to describe the prevalence of venous thromboembolism, pulmonary embolism, and deep vein thrombosis among hospitalized patients and the percentages of those occurring during the hospital stays. Methods French DRG gave now the opportunity to investigate the frequency of venous thromboembolism occurring during the hospital stay. Statistics are issued from the national PMSI MCO databases encoded using the CIM10. Since 2010–2011 it is possible to differentiate the reason for hospital admission from the pathologies which secondly occurred. Any stay with the ICD-10 codes selected was considered as a hospital-occurred thrombosis unless it was the principal diagnosis of the first medical unit summary. To eliminate outpatient consultations or in day care, stays of <48 h were excluded. Results The results pertain to the 78,838,983 hospitalizations in France from 2005 to 2011 and on the 18,683,603 hospital stays in 2010–2011. The incidence of hospital stays came to 860,343 (1.09%) for venous thromboembolism, with 428,261 (0.543%) for deep vein thrombosis without pulmonary embolism and 432,082 (0.548%) for pulmonary embolism. It corresponds to an incidence of 189 per 100,000 inhabitants. Out of 100 hospital stays involving venous thromboembolism, for 40.3% venous thromboembolism was the cause of hospitalization whereas 59.7% can be considered to have occurred during hospital stay. These distributions are of 25.6 and 74.4% for deep vein thrombosis, respectively, 53.8 and 46.2% for pulmonary embolism. Conclusion The high proportion of hospital-occurred venous thromboembolism is an alarming situation that should question the quality of prevention and/or its effectiveness.

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