Idiopathic Deep Venous Thrombosis Research Articles

Absence of Infrarenal Portion of the Inferior Vena Cava With Acute Lower Extremities Venous Thrombosis: A Case Report

A lack of congenital Inferior Vena Cava (IVC) is an uncommon malformation that has been identified in combination with idiopathic Deep Venous Thrombosis (DVT), exclusively. It may not even be revealed during the lifetime. A 63-year-old female was accepted with three months of abdominal and pelvic pain and localized edema on the right flank. During this admission, she was examined and recognized for deep vein thrombosis (DVT). Ct scan images showed a lack of the Inferior Vena Cava with enormous thrombosis collaterals of the superficial vein in the abdomen. In this case report, we report a woman with side pain who has an absence of the IVC.

Recurrent PROC and novel PROS1 mutations in Vietnamese patients diagnosed with idiopathic deep venous thrombosis.

Genetic mutations of PROC and PROS1 are well-known risk factors for deep venous thrombosis (DVT) in the Asian population. However, the genetic profile of Vietnamese patients with DVT remains elusive. This study aimed to investigate the spectrum of genetic mutations of these two genes in Vietnamese patients diagnosed with idiopathic DVT. A total of 50 Vietnamese patients diagnosed with idiopathic DVT were recruited in this study. The entire coding regions of the protein C and protein S genes were amplified and directly sequenced to determine genetic alterations. Four and six genetic mutations were detected in protein C and protein S genes, respectively, in 24 Vietnamese DVT patients. PROC c.565C>T (p.R189W) was the most common mutation found in 13 out of 50 patients, while the mutations of PROS1 comprised three missense and three nonsense variants which diffuse along the gene. This study shows that mutations of protein C and protein S genes are prevalent in Vietnamese patients diagnosed with idiopathic DVT, and PROC c.565C>T (p.R189W) was the most common genetic alteration.

Facing Deep Venous Thrombosis (DVT) in University Tertiary Hospital: Role of Conventional Thrombophilia Testing in Idiopathic DVT Treatment

INTRODUCTION: Deep venous thrombosis (DVT) is a frequent cause or morbidity and mortality, and multiple genetic and environmental factors are involved in its etiopathogenesis. According to it, besides investigating about personal and familiar DVT history, thrombophilia testing is often asked by physicians in order to diagnose patients, even if current validated markers can't predict the risk of recurrence of the disease. METHODS: We developed an observational and prospective study between January 2017 and December 2017, in order to register the patients with DVT that were treated in our DVT unit. As secondary objectives, we wanted to know how many had an idiopathic DVT, if we tested all of them for thrombophilia, which of them stopped treatment and the results after one year of follow up. RESULTS: We included 172 patients with DVT, 56.9% were men, and the average age was 66.4 years old with an increased incidence above the 50 years old. In our study group we found 43.6% (75) of patients without major risk factors for DVT, classified as idiopathic DVT and we will refer to them in this abstract from now on. Just 36.7% of them had a positive personal history of DVT and 36.7% had familiar history. Almost all were localized in the lower limbs (98.7%) and 17.3% presented in association with pulmonary embolism (PE) at diagnosis. All of them started treatment with LMWH, and after the first clinical visit, 26.7% continued with it, while 51.2% changed to VKA and 22.1% to DOACs. Only 45 (60%) of idiopathic DTVs were tested for thrombophilia (patients younger than 60 years old, with extensive DVT, or personal or familiar history of DVT): 31 had a negative study, 11 had a positive study for hereditary thrombophilia (4 S protein deficiency, 3 C protein deficiency, 2 V Leiden factor mutation + prothrombin mutation, 1 V Leiden factor mutation, 1 prothrombin mutation), and 3 were diagnosed of antiphospholipid syndrome. All these patients with positive study or antiphospholipid syndrome received indefinite anticoagulation. From all the patients with idiopathic DVT, 77.3% received indefinite anticoagulation, 17.3% were treated for 3-6 months, 4% for >6-12 months and 1,3% for 15 months. Only one patient who stopped treatment after 3 months had a recurrent DVT and had to restart it. CONCLUSIONS: DVT is the most frequent indication for thrombophilia testing and regarding its multifactorial etiology, it must be performed specially in incidental cases. In our incidental DVT study group (with PE associated or not), we found a 31.1% of positive studies, consistent with what is expected in general DVT population, but in contrast with it is described in the literature, we found more cases of S and C deficiency than V Leiden factor and prothrombin mutations. We also had only one patient with recurrence DVT after few months of stopping anticoagulation, no thrombophilia was found. This low rate of recurrence that differs from the latest data published, might be explained by the short time of follow up that we have, so it would be interesting to increase it, as well as the number of patients in the cohort studied. There is a need for investigating new clinical and genetic scores in order to improve the poor predictive role in recurrent disease with the current thrombophilia markers. Disclosures Bosch: F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

The incidence of FVL and PT G20210A mutations in patients with idiopathic deep venous thrombosis

Background: Factor V Leiden (FVL), prothrombin gene (PT G20210A), and methylenetetrahydrofolate reductase (MTHFR) C677T mutations are known as molecular biomarkers to evaluate the predisposition of deep venous thrombosis (DVT). These hereditary risk factors affect the natural anticoagulant mechanisms and activate the coagulation mechanisms because of an imbalance between procoagulant and anticoagulant factors. Our study aimed to determine the prevalence of these mutations in Turkish patients presenting with idiopathic DVT. Methods: A total of 135 patients with idiopathic DVT admitted to our clinic were investigated for FVL, PT G20210A, and MTHFR (C677T, A1298C) gene mutations. Screening of polymorphisms was carried out by using SNaPshot® multiplex system (Applied Biosystems Inc.). Wild, heterozygous and homozygous genotypic distributions of these mutations were defined as number and percentage frequency. Results: There were 74 male and 61 female patients ranging in age from 18 to 85 years. FVL mutation was found in 66 (41.47%) patients (12 homozygotes 8.88%, 44 heterozygotes 32.59%), PT G20210A was found in 14 (10.36%) patients (1 homozygous 0.74%, 13 heterozygotes 9.62%). MTHFR C677T was found in 53 (39.25%) patients (10 homozygotes 7.40%, 43 heterozygotes 31.85%), and MTHFR A1298C was found in 84 (62.22%) patients (16 homozygotes 11.85%, 68 heterozygotes 50.37%).

Venous thromboembolism — recommendations on the prevention, diagnostic approach and management. The 2017 Polish Consensus Statement

The 2017 Polish Consensus Statement (PCS 2017) includes updated recommendations on the prevention, diagnostic approach, and management of venous thromboembolism (VTE). For VTE without cancer, the authors of PCS 2017 recommend apixaban, edoxaban, rivaroxaban, and dabigatran over vitamin K antagonists (VKA) as long-term anticoagulant therapy. For VTE with cancer, the authors of PCS 2017 recommend low molecular weight heparins (LMWH) over VKA, apixaban, edoxaban, rivaroxaban and dabigatran. For extended secondary prevention of deep venous thrombosis (DVT), PCS 2017 recommends apixaban, edoxaban, rivaroxaban, dabigatran, VKA, and sulodexide. For extended secondary prevention of pulmonary embolism (PE), PCS 2017 recommends apixaban, edoxaban, rivaroxaban, dabigatran and VKA. For extended secondary prevention in patients with idiopathic DVT and a high risk of bleeding complications, the authors of PCS 2017 recommend NOT to stop anticoagulation and use sulodexide. For extended secondary prevention in patients with idiopathic PE and a high risk of bleeding, the authors of PCS 2017 recommend NOT to stop anticoagulation and suggest treatment with apixaban, edoxaban, rivaroxaban, and dabigatran in reduced doses adjusted to the risk of bleeding. For VTE treated with anticoagulants, PCS 2017 recommends against insertion of a vena cava filter. For patients with DVT, PCS 2017 suggests USING compression stockings routinely to prevent postthrombotic syndrome. For subsegmental PE without proximal DVT, PCS 2017 suggests clinical surveillance over anticoagulation with a low risk of recurrent VTE, and anticoagulation over clinical surveillance with a high risk of recurrent VTE. The 2017 Polish Consensus Statement suggests thrombolytic therapy for PE with hypotension, and systemic therapy over catheter-directed thrombolysis. For recurrent VTE on a non-LMWH anticoagulant, PCS 2017 suggests LMWH, and for recurrent DVT and/or PE on LMWH, PCS 2017 suggests increasing the dose of LMWH.

Patients With a History of Idiopathic Deep Venous Thrombosis Have Long-Term Increased Levels of Inflammatory Markers and Markers of Endothelial Damage.

Although the role of inflammation in DVT has been investigated in different studies, there is no definite answer as to whether increased systemic inflammation is the cause or the consequence of DVT. To follow inflammatory parameters in a cohort of patients with idiopathic DVT. Out of 49 patients with an acute idiopathic DVT, which were investigated four months after an acute episode (DEVTA 1), 43 patients were included in the follow-up study investigating inflammatory markers and hemostatic markers of endothelial damage five years after an acute DVT (DEVTA 2). A control group consisted of 43 sex and age matched healthy subjects (CONTROLS). The levels of inflammatory markers were significantly higher in DEVTA 2 in comparison to CONTROLS: tumor necrosis factor alpha 2.0 pg/mL (1.1-2.3) vs 1.3 pg/mL (0.8-1.9), p < .001, high sensitivity C-reactive protein 3.2 mg/L (1.5-5.2) vs 1.7 mg/L (0.9-3.0), p = .008, interleukin-6 (IL-6) 2.7 pg/mL (2.0-3.5) vs 2.1 pg/mL (1.5-2.6), p = .025, IL-8 5.0 pg/mL (3.6-7.3) vs 2.4 pg/mL (1.8-2.8), p < .001. IL-10 was significantly decreased (0.9 pg/mL (0.7-1.8) vs 1.8 (1.5-2.2), p < .001. Most of the proinflammatory markers remained elevated in the DEVTA 2 in comparison to DEVTA 1. Markers of endothelial damage were higher in DEVTA 2 in comparison to CONTROLS and higher than in DEVTA 1. Patients with idiopathic DVT have long-term increased inflammatory markers and markers of endothelial damage. These findings favor the hypothesis that inflammation is a cause and not merely a consequence of acute DVT.

Time taken to the maximum increase in the oxygenated hemoglobin level in calf muscle as a predictor of mild and moderate post-thrombotic syndrome.

Near-infrared spectroscopy (NIRS) allows continuous noninvasive monitoring of changes in the tissue levels of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) and can identify the severity of chronic venous diseases. Here we investigated the predictors of post-thrombotic syndrome (PTS) using NIRS in patients with a first episode of deep venous thrombosis (DVT). The study enrolled 129 patients with DVT. Risk factors in each patient were assessed at presentation. Venous abnormalities confirmed by ultrasound and parameters derived from NIRS were evaluated at 6 months after DVT. On standing, increases in O2Hb and HHb (ΔO2Hbst and ΔHHbst) and the times taken for each concentration to become maximal (TO2Hbst, and THHbst) were measured. During 10 tiptoe movements, O2Hb showed a continuous decrease (ΔO2Hbex), whereas venous expulsion (ΔHHbEex) and subsequent retention (ΔHHbRex) were observed. The oxygenation index (HbD; HbD= O2Hb- HHb) was also calculated at the end of standing and at the end of 10 tiptoe movements (ΔHbDst and ΔHbDex). Final clinical manifestations were evaluated at 6 years, and PTS was considered to be present if the Villalta score was ≥5. Thirteen patients were excluded and 116 patients were finally included. Of these, 19 (16%) developed PTS. Among various NIRS-derived parameters, TO2Hbst had the highest area under the curve (0.88; 95% confidence interval [CI], 0.80-0.93; P< .01) with the best cutoff value (TO2Hbst ≤48 seconds). On univariate analysis, variables associated with greater risk for development of PTS were stroke (odds ratio [OR], 5.59; 95% CI, 0.74-42.41; P= .06), idiopathic DVT (OR, 4.13; 95% CI, 1.36-12.55; P< .01) and iliofemoral DVT (OR, 4.31; 95% CI, 1.48-12.60; P< .01) at initial presentation, venous occlusion combined with reflux (OR, 4.24; 95% CI, 1.50-12.00; P< .01), and NIRS-derived TO2Hbst ≤48 seconds (OR, 43.03; 95% CI, 9.04-204.81; P<.01) at 6 months. Multivariate logistic regression analysis finally revealed venous occlusion combined with reflux (OR, 4.80; 95% CI, 1.03-22.36; P< .05) and NIRS-derived TO2Hbst ≤48 seconds (OR, 53.73; 95% CI, 8.43-342.41; P< .01) to be independently associated with PTS progression. NIRS-derived TO2Hbst ≤48 seconds is a promising time-course predictor of PTS progression.

The Typical Presentation Spectrum of Deep Vein Thrombosis Associated with Inferior Vena Cava Malformations.

Congenital malformations of the inferior vena cava (IVC) are rare and underreported. They can be a risk factor for deep venous thrombosis (DVT) as a result of inadequate venous drainage of the lower extremities through collateral circulation. The significant number of cases reported in the literature highlights their importance, warranting investigating their existence in younger individuals with idiopathic DVT of the lower extremities and pelvic veins. In this systematic review, we depict the typical presentation of IVC malformations, their management, and the management of their associated DVT.

Current Practice Patterns of Phamacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Hospitalized Children: A Survey of Pediatric Hemostasis and Thrombosis Experts in North America

Background:The prevalence of venous thromboembolism (VTE) is on the rise in critically sick hospitalized children. It is one of the most common hospital acquired complications (HAC) and Joint Commission for Accreditation for Hospitals (JCAHO) has mandated to develop institutional guidelines to prevent VTE. It is recommended to use pharmacologic thromboprophylaxis (PTP), the most effective intervention for VTE prevention, for eligible adult population. Unfortunately this strategy is not systematically evaluated in children due to sample size and recruitment issues. Therefore the risks and benefits of universal PTP in critically sick children are unclear specifically in the context of exposure to acquired risk factors including central venous lines (CVLs), age, cancer, infection and trauma/surgery. We sought to understand expert clinical decision-making.Aims:To understand the current practice patterns of pharmacological thromboprophylaxis and the perceived risks of VTE in hospitalized children.Methods:This cross-sectional self-administered multiple-choice survey questionnaire was administered to pediatric hematologists who are members of Hemostasis Thrombosis Research Society (HTRS) with at least 5 years of experience. The survey designed to collect physicians’ demographics, thromboprophylaxis policies and opinions about the use of PTP using 13 multiple choice questionnaire and 4 clinical scenarios.Results:The response rate was 47.3% [53/112]. Majority practiced at University affiliated hospitals (73%). Only 44% of respondents were in favor of adoption of universal PTP policy for children and 65% of them didn’t support thromboprophylaxis for CVL. Only one third of the participants had established policy for PTP mainly for intensive care unit, orthopedic and trauma patients.Almost all respondents (98 %) used PTP for a select patient population based on following risk factors: known inherited thrombophilia, morbid obesity, chronic inflammatory condition, history of idiopathic deep venous thrombosis (DVT), CVL related DVT, detected antiphospholipid antibody and teenagers with DVT risk factors. The factors that were not important for thromboprophylaxis included: underlying malignancy, positive blood culture, diabetic ketoacidosis, immobilization and CVLs, whether being critically sick newborns or not. Four different adolescent, child, and infant scenarios were answered by 94 % of respondents.Case (1) A newborn on mechanical ventilation with sepsis, thrombocytopenia and femoral line dysfunction without CVL-thrombosis. About 72% of respondents didn’t consider AC, 68% of them didn’t consider mechanical thromboprophylaxis. If developed MRSA sepsis and right hip osteomyelitis later on, only 42% of all respondents would not consider AC. So, in the newborns, PTP may not benefit for CVL malfunction but may be beneficial in the setting of osteomyelitis. LMWH was the preferred choice of PTP.Case (2): A 10 years old boy with a fracture femur with 4 weeks immobilization, 66 % of respondents were not in favor of AC, 69 % of them would consider mechanical thromboprophylaxis. So, Mechanical thromboprophylaxis was preferred over PTP in orthopedic patients.Case (3): An overweight teenager girl with Down syndrome on mechanical ventilation for pneumonia and receiving mechanical thromboprophylaxis, 46% of all respondents considered AC and only 34% of them would continue AC post-discharge. If she has been on oral contraceptive pills (OCPs), 68% would prescribe TPT. So, PTP in critically ill teenagers is equipoise even with overweight and immobilization. OCPs were perceived as important risk factor for VTE.Case (4): A child with ALL who had an acute stroke following induction chemotherapy including Asparginase, 82% of all respondents would consider AC for re-induction regimen containing Asparginase. So, PTP is recommended in children with ALL and Asparginase related strokes if re-exposed.Conclusions:The results of survey revealed that despite concerns about rising VTE prevalence, there is equipoise about the adoption of a universal PTP policy for children. Experts take into consideration multiple risk factors when deciding about primary thromboprophylaxis. The variability in clinical thromboprophylaxis practices highlights the need for rigorous prospective randomized trials so as to develop evidence-based VTE prevention strategies for children. DisclosuresNo relevant conflicts of interest to declare.

Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: a retrospective cohort study.

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, β2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (β-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and β2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and β2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.

Epicardial adipose tissue and idiopathic deep venous thrombosis: An association study

ObjectiveEpicardial fat (EpiF) reflects abdominal visceral adiposity and visceral fat plays an important role in the development of an unfavorable metabolic and atherosclerosis risk profile. An increased cardiovascular risk has been evidenced in patients with deep venous thrombosis (DVT). Advancing age is characterized by alterations of body fat mass and function In this study we studied the association between EpiF, DVT, age, obesity and other atherosclerosis risk factors. Methods and results77 patients were recruited: 44 men and 33 women, 38 without DVT (65.9 ± 16.3 years, range 26–92 years) and 39 with DVT (65.4 ± 17.2 years, range 28–90 years). The study design was balanced for established atherosclerosis risk factors (gender, obesity, smoking habits, dyslipidemia, diabetes mellitus, arterial hypertension), for previous cardiovascular events, for use of statins and platelet anti-aggregating agents. Multivariate regression model and RECPAM regression tree were used to study the association between EpiF thickness and the other potential risk factors. Patients with DVT showed a thicker EpiF with respect to those without DVT (12 ± 2 mm vs. 9 ± 2 mm respectively, p < 0.001). Multivariate linear regression model showed that DVT, obesity and age were positively associated with EpiF thickness after adjusting for the established atherosclerosis risk factors. Furthermore, the RECPAM analysis was performed to evaluate interactions between DVT, age and obesity: four main distinct and homogeneous subgroups of patients in terms of EpiF thickness were identified. The most important variable in partitioning patients was represented, as expected, by DVT (p < 0.001) followed by age (p = 0.004), while obesity did not contribute to the model as well as the other atherosclerosis risk factors. Patients with DVT and older than 41 years of age had higher EpiF thickness in respect of patients with DVT and younger than 41 years of age. In patients without DVT the estimated cut-off age was 50 years, and older patients had thicker EpiF in respect of patients younger than 50 years of age. Conclusion: DVT should be considered as strongly associated with EpiF thickness. Advancing age (with or without spontaneous DVT) is significantly associated with an increased EpiF thickness. The measurement of EpiF thickness, a valuable marker of cardio-metabolic risk, may represent a useful and reliable method to evaluate cardiovascular risk in patients with idiopathic deep phlebothrombosis.

Tratamiento de la trombosis venosa profunda asociada a agenesia de vena cava inferior. Revisión de las anomalías de vena cava inferior

The development of the inferior vena cava is a complex embryological process, with numerous anastomoses among pairs of veins, which may result in many anatomic variants. In the general population, the absence of inferior vena cava is a rare anomaly (0.07%), but this represents 5-9.5% of idiopathic deep venous thrombosis in patients under 30 years-old and its treatment options remain controversial.

Idiopathic deep venous thrombosis and epicardial fat thickness: The age, gender and obesity connection

Background Epicardial fat (EF) reflects abdominal visceral adiposity and visceral fat plays an important role in the development of an unfavorable cardiometabolic risk profile. Echocardiographic assessment of EF is considered a valuable method to assess visceral adipose tissue. An increased cardiovascular risk has been evidenced in patients with deep venous thrombosis (DVT). In this study we have evaluated the amount of EF in patients with DVT. Patients and methods We have analyzed the EF on a population of 77 subjects with the same atherosclerosis risk factors, 38 without idiopathic DVT (mean age 65.95 ± 16.29 years) and 39 with idiopathic DVT (mean age 65.49 ± 17.22 years). Results Subjects with DVT showed a statistically significant increase of EF thickness (12.32 ± 1.73 mm vs. 9.07 ± 1.89 mm, p < 0.0001). Univariate linear regression analyses evidenced that EF correlated positively with venous thombosis ( p < 0.001), age ( p < 0.001), obesity ( p = 0.003), dyslipidemia ( p = 0.01), arterial hypertension ( p =0.047) and multivariate linear regression models showed that EF correlated positively with venous thrombosis ( p < 0.001), age ( p < 0.001), male gender ( p = 0.025) and obesity ( p < 0.001). Conclusion The data presented indicate that subjects with spontaneous DVT have an increased amount of EF, a reliable indicator of abdominal visceral adiposity and a marker of unfavorable metabolic and cardiovascular risk profile.

Idiopathic deep venous thrombosis and arterial endothelial dysfunction in the elderly

Arterial and venous thrombosis have always been regarded as different pathologies and epidemiological studies have examined the association between venous thrombosis and indicators of atherosclerosis and/or arterial thromboembolic events. We measured the flow-mediated dilation (FMD), a well-known marker of arterial endothelial dysfunction, in young-middle-aged and old-aged patients with and without unprovoked deep venous thrombosis (DVT). The aim of this study was to investigate whether DVT was a significant predictor for impaired FMD, considering all the patients and young-middle-aged (age < 65 years) and old-aged (age ≥ 65 years) patients separately. FMD was measured in the brachial artery on a population of 120 subjects with the same atherosclerosis risk factors, 68 male and 52 female, 70 young-middle-aged subjects (mean age ± SD 49.5 ± 10.5 years) and 50 old-aged subjects (76.2 ± 7.7 years). Patients with DVT showed a significant decrease of FMD compared to patients without DVT (6.8 ± 5.5% vs. 10.9 ± 3.5%, p < 0.001). Moreover, old-aged patients showed a significant decrease of FMD compared to the young-middle-aged subjects (7.4 ± 4.1% vs. 9.8 ± 5.3%, p = 0.005). In the whole study population, DVT was strongly associated with FMD (risk factors adjusted β = -4.14, p < 0.001). A significant interaction between age and the presence of DVT on predicting FMD was found (p = 0.003) suggesting a differential behavior of DVT as predictor of FMD. In young-middle-aged group, multivariate model confirmed that DVT was the most significant predictor of continuous FMD (β = -6.06, p < 0.001). On the contrary, DVT was no more a predictor of FMD in the old age group (β = -0.73, p = 0.556). Furthermore, old-aged patients without DVT showed a statistically significant decrease of FMD compared to the young-middle-aged subjects without DVT (8.2 ± 2.1% vs. 12.6 ± 2.7%, p<0.001) and old-aged patients with DVT showed a not statistically significant decrease of the FMD compared to the young-middle-aged patients with DVT (6.7 ± 5.3% vs. 6.8 ± 5.7%, p = 0.932). In conclusion, young-middle-aged patients with spontaneous DVT show an impaired FMD, whereas this impairment in old-aged subjects is evident independently from the presence or absence of DVT. Aging per se may be associated with physiologic abnormalities in the systemic arteries and with endothelial dysfunction.

Economic Burden and Cost Determinants of Deep Venous Thrombosis During the Two Years Following Diagnosis: a Prospective Evaluation

AbstractAbstract 566 Background and objectives:Deep venous thrombosis (DVT) is a common and serious vascular condition that is frequently complicated by the chronic post-thrombotic syndrome. Costs of DVT may occur over a long period and may be medical and non-medical in nature. During a Canadian multicenter cohort study of the long-term outcomes after DVT (The Venous Thrombosis Outcomes [VETO] Study), we prospectively quantified resource use and costs related to DVT during two years after DVT diagnosis, and identified clinical determinants of costs. Methods:The study population consisted of 355 consecutive patients diagnosed with objectively confirmed acute DVT at one of 7 participating hospitals in the province of Quebec, Canada. Using a societal perspective, we tracked total medical resource use (hospitalizations, physician visits, other health professional visits, medications, ambulance services, stockings, assistive devices) and non-medical resource use (loss of productivity, home care, transportation) incurred by DVT during the 2 years after diagnosis. Data sources included weekly patient-completed cost diaries, nurse-completed case report forms (baseline, 1, 4, 8, 12, 24 months and at any DVT-related clinical event) and the Quebec provincial administrative healthcare database (“RAMQ”). Resources for each patient were valued using individual patient level information obtained from RAMQ and patient diaries. Statistics Canada data, provincial health professionals associations and local suppliers were used to estimate resource costs if individual information was not available. The value of lost productivity was estimated using a friction-cost approach. Multivariate regression modeling for predictors of medical costs during 2 years included baseline demographic and clinical characteristics as well as the development of post-thrombotic syndrome (PTS) during study follow-up. Results:At study entry, mean age was 56.5 years, 50.1% were male, 2/3 were out-patients and 58.0% had proximal DVT. The mean duration of heparin and warfarin treatment was 7.6 days (SD 6.0) and 21.6 weeks (SD 10.0), respectively. During 2 years follow-up, the rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% CI 2.2, 4.9). Patients reported, on average, 15.0 (SD 14.5) physician visits and 0.7 (SD 1.2) non-physician visits. Patients required 12.7 (SD 9.2) transportations, 38.6 (SD 138.0) hours of assistance and missed 12.1 (SD 39.8) workdays. The average per-patient total cost over 2 years was Can$4109 (95% CI $3658, $4561) with 63.7% of costs attributable to non-medical resource use. The two largest medical cost components were hospitalizations (Can$502; 95% CI $261, $744) and physician visits (Can$356; 95% CI $320, $392). More than two-thirds of all resource consumption occurred during the first 4 months after diagnosis. In multivariate analysis focusing on determinants of medical costs, concomitant pulmonary embolism (p = 0.002), idiopathic DVT (p= 0.003), and development of post-thrombotic syndrome during follow-up (p= 0.002) were independently associated with increased costs. Conclusion:The economic burden of DVT over the two years following initial diagnosis is substantial with almost two-thirds of costs attributable to non-medical resource use. Concomitant pulmonary embolism, idiopathic DVT, and development of PTS are important predictors of medical costs after DVT. Better adherence to thromboprophylaxis strategies and use of measures to prevent occurrence of PTS have the potential to diminish costs and resource utilization related to DVT. Disclosures:No relevant conflicts of interest to declare.

What is the optimum duration of anticoagulation for the management of patients with idiopathic deep venous thrombosis and pulmonary embolism?

Anticoagulant therapy is highly effective in preventing recurrent events in patients with venous thrombo-embolism (VTE). For patients with ‘secondary’ or ‘provoked’ VTE affecting isolated calf veins or upper limb, there is general agreement that six weeks to three months of anticoagulation is adequate. Those with ‘provoked’ iliofemoral deep vein thrombosis (DVT) or pulmonary embolism (PE) are usually treated for three or six months. The duration of treatment in patients with idiopathic VTE, however, is controversial. Some experts recommend long-term anticoagulation after the first episode of VTE, whereas others, including ourselves, advocate only three months of anticoagulation.

What is the Optimal Duration of Treatment for DVT? An Update on Evidence-Based Medicine of Treatment for DVT

Venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary embolism, represent a major source of morbidity and mortality today. Incidence of DVT is estimated to be 56 to 160/100,000 population per year. Systemic anticoagulation with low molecular weight heparin or unfractionated heparin with initiation of oral vitamin K antagonist therapy has been shown to be beneficial in preventing pulmonary embolism and reducing extension and recurrence of DVT. The duration of anticoagulation following an episode of DVT is determined by the greatest predictors of recurrence. These include the presence of reversible risk factors, nonreversible risk factors, and no risk factors (idiopathic or unprovoked DVT). Short durations of anticoagulation are only appropriate for calf DVTs in patients with reversible risk factors. Patients with nonreversible risk factors, such as malignancy and certain inherited thrombophilias with a strong family history of venous thromboembolism will require lifelong anticoagulation. Those with proximal DVT due to reversible risk factors require 3 to 6 months of anticoagulation. Patients with idiopathic DVT require reassessment of risk-to-benefit ratio of hemorrhage from oral vitamin K antagonist therapy compared to reducing risk of recurrence and frequently require prolonged oral anticoagulant therapy. Monitoring with d-dimer and serial ultrasounds may offer an individualized approach to therapy.

P44 Tumor markers in the diagnosis of idiopathic deep venous thrombosis associated cancer in aged patients

P44 Tumor markers in the diagnosis of idiopathic deep venous thrombosis associated cancer in aged patients

The development of persistent thrombotic masses in patients with deep venous thrombosis randomized to long-term anticoagulation treatment

The aim of the study was to assess the regression rate of persistent echogenic masses in patients with idiopathic deep venous thrombosis (DVT) who were after initial 6 months randomized to long-term anticoagulation treatment or to discontinuation of anticoagulation. We followed 168 patients with idiopathic DVT for two years since diagnosis. After 6 months of standard therapy (heparin/LMWH, warfarin with target INR 2-3) we randomized patients with persistent echogenic masses of over 20% of venous diameter to either discontinuation of warfarin or to continuation of warfarin for another 6 months. We evaluated the size of thrombotic masses with duplex ultrasound. After 6 months of standard therapy complete regression was observed in 69 patients while in 99 patients echogenic masses persisted, with 71 patients maintaining an obstruction of at least 20% of venous cross-sectional area. 52 patients were randomized. 27 patients continued warfarin therapy and in 25 patients warfarin was discontinued. After discontinuation of warfarin a further trend to regression was seen in both groups. A significant difference in regression of thrombotic masses between the 6th and 12th month of follow up was seen in patients continuing to receive warfarin, both within the popliteal vein (2.81 +/- 1.56 vs. 2.10 +/- 1.67 mm, p < 0.05) and the femoral vein (3.95 +/- 2.74 vs. 2.30 +/- 1.34 mm, p < 0.05). After 6 months of DVT treatment persistent echogenic masses can be found in almost two thirds of patients. Even after discontinuation of anticoagulation treatment echogenic masses further regress. However, the rate of regression in patients with deep venous thrombosis between the 6th and 12th month was greater in patients randomized to continue warfarin during this period than in patients without anticoagulation.

D-dimer and Factor VIII are Independent Risk Factors for Recurrence After Anticoagulation Withdrawal for a First Idiopathic Deep Vein Thrombosis

Conclusion: Elevated levels of D-dimer and factor VIII at 30 ± 10 days after cessation of vitamin K antagonist (VKA) therapy for a first episode of idiopathic proximal deep venous thrombosis (DVT) are independent risk factors for recurrent venous thromboembolism (VTE). Summary: The optimal duration of VKA therapy after a first episode of VTE is unknown. It appears VKA extension after unprovoked VTE can reduce the risk of recurrent VTE but at the potential price of increased bleeding. There is therefore intense interest in stratifying patients with idiopathic VTE with respect to risk factors that may increase rates of recurrence. The specific objective of this study was to assess the risk of recurrence of VTE associated with elevated D-dimer levels and factor VIII levels after withdrawal of VKA therapy for symptomatic idiopathic proximal VTE. Consecutive outpatients with the first episode of idiopathic proximal DVT were enrolled into the study after cessation of VKA therapy. At 30 ± 10 days after cessation of VKA therapy, levels of D-dimer (cutoff value, 500 ng/mL) and chromogenic factor VIII, as well as inherited thrombophilias were determined. Follow-up extended for 2 years. Overall recurrence rate of VTE was 16.4% (55 of 336; 95% confidence interval [CI], 13%-21%). The multivariate hazard ratio for recurrence was 2.45 (95% CI, 1.24-4.99) for abnormal D-dimer and 2.76 (95% CI, 1.57-4.85) for factor VIII >75th percentile (2.42 μ/mL). The values were adjusted for age, sex, and thrombophilia. Compared with normal levels of D-dimer and factor VIII, the multivariate hazard ratio was 4.5 (95% CI, 1.7-12.2) for normal D-dimer levels with factor VIII >2.42 U/mL, and 2.7 (95% CI, 1.2-6.6) and 7.1 (95% CI, 2.8-17.6) for abnormal D-dimer with factor VIII, respectively, below and above 2.42 U/mL. Comment: The appropriate length of treatment with VKA therapy for patients with idiopathic VTE is unknown. The data suggest the longer the treatment period with VKA, the less the recurrence rates of VTE. Of course, VKAs are associated with increased risk of bleeding and are inconvenient for the patient. There is therefore intense interest in stratifying risk among those patients with idiopathic VTE. This is another study that attempts to do just that. The percentage of patients with both normal D-dimer and factor VIII <75th percentile was 37%. This implies that at least a third of patients with idiopathic VTE have a low risk of VTE recurrence. Larger studies are warranted to determine if the combination of factor VIII and D-dimer analysis can be used to tailor duration of VKA therapy after idiopathic VTE.