Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted.
Background and Aims To investigate the behaviour of miR-19a and miR-20a, two microRNAs involved in posttranscriptional modulation of TF expression in peripheral blood mononuclear cells (PBMCs) exposed to high glucose (HG) and lipopolysaccharide (LPS), and to evaluate the involvement of angiotensin II in that process. Methods TF Procoagulant Activity (PCA, one-stage clotting assay), antigen (Ag, ELISA), and miR-19a and miR-20a levels (specific TaqMan® MicroRNA Assays) were evaluated in PBMCs exposed to high glucose (HG, 50 mM), LPS (100 ng/mL), and Olmesartan (OLM, 10−6 M), an angiotensin II type 1 receptor antagonist. Results HG increased TF expression and decreased both miRs as compared to control glucose conditions (11.1 mM). In HG-activated PBMCs, LPS stimulated TF expression and downregulated miR-20a, an effect reverted by OLM (10−6 M); miR-19a expression was unchanged by LPS in both CG and HG conditions. Conclusions miR-19a and miR-20a are inhibited by inflammatory stimuli active on TF expression and their response differs by the stimulus under investigation; angiotensin II may participate in that mechanism.
Introduction. The purpose of this study is to assess referral patterns and the yield of ventilation-perfusion (V/Q) scintigraphy in patients referred for acute pulmonary embolism (PE). Methods. We retrospectively reviewed the charts of all patients who underwent V/Q studies between April 1, 2008, and March 31, 2010. Patients were subdivided into 4 groups based on their referral source: emergency department (ED), hospital inpatient ward, outpatient thrombosis clinic, and all other outpatient sources. Results. A total of 1008 patients underwent V/Q scintigraphy to exclude acute PE. The number of ED, inpatient, thrombosis clinic, and outpatient studies was 43 (4.3%), 288 (28.6%), 351 (34.8%), and 326 (32.3%). Proportion of patients with contrast contraindication varied significantly among the different groups. Of the 1,008 studies, 331 (32.8%) were interpreted as normal, 408 (40.5%) as low, 158 (15.7%) as intermediate, and 111 (11.0%) as high probability for PE. 68 (6.7%) patients underwent CTPA within 2 weeks following V/Q. Conclusion. The rate of nondiagnostic studies is lower than that reported in previously published data, with a relatively low rate of intermediate probability studies. Only a small fraction of patients undergoing a V/Q scan will require a CTPA.
Insertion of an IVC filter can be a safe and effective way to avoid PE in thrombosis patients who cannot be anticoagulated. If temporary filters are not promptly removed they can become difficult to remove, causing avoidable complications and often requiring lifelong warfarin. In this study, two sequential audits of retrieval of temporary IVC filters were conducted before and after the implementation of a coordinated management strategy for IVC filter follow-up. 33 filter placements were examined over a 15-month period (Group A). Following implementation of the strategy a comparable 15-month period in which 33 IVC filters were placed was audited (Group B). Following implementation, failed retrievals dropped from 15% to 9%. The number successfully retrieved did not change at 45%. The number made permanent from the outset following expert discussion increased from 12% to 39%. The number of filters with no attempted retrieval and no consultation about retrieval decreased from 27% to 9% (these patients were lost to follow-up with multiple contact attempts made). In Group B 100% of placed IVC filters were followed up appropriately. The proposed model is an easily implemented plan to avoid patient morbidity caused by temporary IVC filters made unintentionally permanent by loss to follow-up.
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.
Coronary atherothrombotic diseases such as coronary artery disease, peripheral vascular disease, cerebrovascular disease, and heart failure are the serious concerns of the thrombus formed in blood vessels. Anticoagulant and antiplatelet drugs are the cornerstones of the management of these diseases. To prevent the recurrence of these diseases, double antiplatelet drugs such as aspirin and clopidogrel has been the standard management in most hospitals. However, aspirin resistance and clopidogrel inefficient effects due to noncompliance with double drugs regimen can cause a sinister effect on patients. Medicinal plants serve as a greater resource for new medication and their potential currently became a topic of interest to the researchers all over the world. Traditionally, certain herbs have been used as a treatment for heart diseases but have been investigated for their antiplatelet properties. This current review explained few traditional antithrombotic herbals and their antiplatelet properties in vitro and in vivo and this is to be deeply discussed in further research.
Background. Central venous catheters and peripherally inserted central catheters are well established risk factors for upper limb deep vein thrombosis. There is limited literature on the thrombosis rates in patients with peripheral catheters. A prospective observational study was conducted to determine the incidence of peripheral catheter-related thrombosis in surgical patients. Methods. Patients deemed high risk for venous thrombosis with a peripheral catheter were considered eligible for the study. An ultrasound was performed on enrolment into the study and at discharge from hospital. Participants were reviewed twice a day for clinical features of upper limb deep vein thrombosis during their admission and followed up at 30 days. Results. 54 patients were included in the study. The incidence of deep vein thrombosis and superficial venous thrombosis was 1.8% and 9.2%, respectively. All cases of venous thrombosis were asymptomatic. Risk factor analysis was limited by the low incidence of thrombosis. Conclusion. This study revealed a low incidence of deep vein thrombosis in surgical patients with peripheral catheters (1.8%). The study was underpowered; therefore the association between peripheral catheters and thrombosis is unable to be established. Future studies with larger sample sizes are required to determine the association between peripheral catheters and thrombosis.
Background. The Pulmonary Embolism Severity Index (PESI) score can risk-stratify patients with PE but its widespread use is uncertain. With the PESI, we compared length of hospital stay between low, moderate, and high risk PE patients and determined the number of low risk PE patients who were discharged early. Methods. PE patients admitted to St. Joseph Mercy Oakland Hospital from January 2005 to August 2010 were screened. PESI score stratified acute PE patients into low (<85), moderate (86–105), and high (>105) risk categories and their length of hospital stay was compared. Patients with low risk PE discharged early (≤3 days) were calculated. Results. Among 315 PE patients, 51.7% were at low risk. No significant difference in hospital stay between low (7.11 ± 3 d) and moderate (6.88 ± 2.9 d) risk, p > 0.05, as well as low and high risk (7.28 ± 3.0 d), p > 0.05, was found. 9% of low risk patients were discharged ≤ 3 days. Conclusions. There was no significant difference in length of hospital stay between low and high risk groups and only a small number of low risk patients were discharged from the hospital early suggesting that risk tools like PESI may not have a widespread use.
Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis.
Background. Thromboembolic events are major causes of morbidity, and prevention is important. We aimed to compare chemical prophylaxis (CP) and mechanical prophylaxis (MP) as methods of prevention in nonsurgical patients on mechanical ventilation. Methods. We performed a retrospective study of adult patients admitted to the Cooper University Hospital ICU between 2002 and 2010. Patients on one modality of prophylaxis throughout their stay were included. The CP group comprised 329 patients and the MP group 419 patients. The primary outcome was incidence of thromboembolic events. Results. Acuity measured by APACHE II score was comparable between the two groups (p = 0.215). Univariate analysis showed 1 DVT/no PEs in the CP group and 12 DVTs/1 PE in the MP group (p = 0.005). Overall mortality was 34.3% and 50.6%, respectively. ICU LOS was similar. Hospital LOS was shorter in the MP group. Multivariate analysis showed a significantly higher incidence of events in the MP prophylaxis group (odds ratio 9.9). After excluding patients admitted for bleeding in both groups, repeat analysis showed again increased events in the MP group (odds ratio 2.9) but this result did not reach statistical significance. Conclusion. Chemical methods for DVT/PE prophylaxis seem superior to mechanical prophylaxis in nonsurgical patients on mechanical ventilation and should be used when possible.
Background. Trials have shown that novel oral anticoagulants may decrease length of stay versus warfarin. A comparison of length of stay in the treatment of pulmonary embolism (PE) has not been performed outside post hoc analysis of a large clinical trial. Objective. To evaluate if rivaroxaban decreases length of stay compared to warfarin plus enoxaparin in the treatment of PE. Methods. This was a multicenter, retrospective, observational cohort study. Patients were identified based on discharge diagnosis of PE and were excluded if they received anticoagulants prior to admission and had additional indications for anticoagulation or reduced creatinine clearance. The primary endpoint was length of stay. Secondary endpoints included time from initial dose of oral anticoagulant to discharge and length of stay comparison between subgroups. Results. Inclusion criterion was met by 158 patients (82 warfarin, 76 rivaroxaban). The median length of stay was 4.5 days (interquartile range [IQR], 2.7, 5.9) in the warfarin group and 1.8 days (IQR, 1.2, 3.7) in the rivaroxaban group (P < 0.001). Time interval from first dose of oral anticoagulant to discharge was shorter with rivaroxaban (P < 0.001). Conclusions. Patients given rivaroxaban had decreased length of stay versus those given warfarin plus enoxaparin for the treatment of PE.
Background. Venous thromboembolism (VTE) is the third leading cause of cardiovascular death in patients undergoing surgery. However, VTE prophylaxis practices in cardiac surgery are based on noncardiac surgical literature. The objective of our study was to extract current patterns of VTE prophylaxis practices in cardiac surgery patients. We also aimed to identify health care professionals knowledge of available evidence supporting VTE prophylaxis in adult cardiac surgery patients. Methods. A web-based survey was developed and sent to all Canadian cardiac surgery centers with the intent to have the survey distributed to all personnel involved in the perioperative care of adult cardiac surgery patients. Participation in the questionnaire was voluntary and anonymized. Results. Thirty-five responses were obtained. Sixty-nine percent reported having an established protocol for VTE prophylaxis. However, 83% reported using VTE prophylaxis in their daily practice despite lack of protocol. The majority (60%) believed that the class of recommendation was high despite the lack of evidence. Conclusions. Our survey demonstrated the following. (a) Majority of Canadian centers employ VTE prophylaxis, with considerable variability. (b) There is a misconception among health care professionals about the strength of evidence supporting VTE prophylaxis in cardiac surgery. Our findings highlight the need for appropriately designed studies to fill this knowledge gap.
Introduction. Low molecular weight heparin (LMWH) is preferred for malignancy-associated venous thromboembolism (VTE). Many providers monitor LMWH with anti-Xa levels, despite little validation on correspondence with patient outcome. Methods. This is a retrospective, single institution study of anti-Xa measurement in malignancy-associated thrombosis. Cases were identified using the Electronic Data Warehouse, and inclusion was confirmed by two independent reviewers. Malignancy type, thrombotic history, measurement rationale and accuracy, clinical context, and management changes were evaluated. Results. 167 cases met inclusion criteria. There was no clear rationale for anti-Xa testing in 56%. Impaired renal function (10%), documented or suspected recurrent thrombosis despite anticoagulation (9%), and bleeding (6%) were the most common reasons for testing. Incorrect measurement occurred in 44%. Renal impairment was not a significant impetus for testing, as 70% had a GFR > 60. BMI > 30 was present in 40%, and 28% had a BMI < 25. Clinical impact was low, as only 11% of patients had management changes. Conclusions. Provider education in accuracy and rationale for anti-Xa testing is needed. Our study illustrates uncertainty of interpretation and clinical impact of routine anti-Xa testing, as management was affected in few patients. It is not yet clear in which clinical context providers should send anti-Xa levels.
Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and there has been ongoing research to find a drug that can promote vessel recanalisation more completely and with less side effects. In this review article, the major studies which have validated the use and safety of tPA are discussed. The safety and efficacy of other thrombolytic and anticoagulative agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab, eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are both plasminogen activators with higher fibrin affinity and longer half-life compared to alteplase. They have shown greater reperfusion rates and improved functional outcomes in preliminary studies. Argatroban is a direct thrombin inhibitor used as an adjunct to intravenous tPA and showed higher rates of complete recanalisation in the ARTTS study with further studies which are now ongoing. Adjuvant thrombolysis techniques using transcranial ultrasound are also being investigated and have shown higher rates of complete recanalisation, for example, in the CLOTBUST study. Overall, development in medical therapies for stroke is important due to the ease of administration compared to endovascular treatments, and the new treatments such as tenecteplase, desmoteplase, and adjuvant sonothrombolysis are showing promising results and await further large-scale clinical trials.
Introduction. This study aimed to compare management patterns of patients with SVT among healthcare practitioners based in North America versus those in the global community. Methods. A 17-question, multiple choice survey with questions regarding SVT diagnosis and management strategies was provided to practitioners who attended the American Venous Forum (AVF) meeting in 2011. Results. There were 487 practitioners surveyed with 365 classified as North American (US or Canada) and 122 (56 Europe, 25 Asia, 11 South America, and 7 Africa) representing the global community. The key difference seen between the groups was in the initial imaging study used in patients presenting with SVT (P = 0.046) and physicians in the US ordered fewer bilateral duplex ultrasounds and more unilateral duplex ultrasounds (49.6% versus 58.2%, 39.7% versus 34.4%). In the US cohort, phlebologists and vascular surgeons constituted 82% (n = 300) of the specialties surveyed. In the global community, SVT was managed by phlebologists or vascular surgeons 44% (n = 54) of the time. Surgical management was highly variable between groups. Conclusion. There is currently no consensus between or among practitioners in North America or globally as to the surgical management of SVT, duration of follow-up, and anticoagulation parameters.
Background. Heightened levels of Factor VIII (FVIII) have been associated with both arterial and venous thrombosis. While elevated FVIII is common during acute ischemic stroke (AIS), whether elevated FVIII confers an increased risk for recurrent thrombotic events (RTEs) following AIS has not been previously explored. Methods. Consecutive AIS patients who presented to our center between July 2008 and September 2013 and had FVIII measured during admission were identified from our stroke registry. Baseline characteristics and the occurrence of RTE (recurrent or progressive ischemic stroke, DVT/PE, and MI) were compared in patients with and without elevated FVIII levels. Results. Of the 298 patients included, 203 (68.1%) had elevated FVIII levels. Patients with elevated FVIII had higher rates of any in-hospital RTE (18.7% versus 8.4%, P=0.0218). This association remained after adjustment for baseline stroke severity and etiology (OR 1.01, 95% CI 1.00–1.01, P=0.0013). Rates of major disability were also higher in patients who experienced a RTE (17.8% versus 3.2%, P<0.0001). Conclusion. A significantly higher frequency of in-hospital RTEs occurred in AIS patients with elevated FVIII. The occurrence of such events was associated with higher morbidity. Further study is indicated to evaluate whether FVIII is a candidate biomarker for increased risk of RTEs following AIS.
Background . Hypercoagulable disorders can lead to deep vein thrombosis (DVT), arterial thrombosis or embolization, and early or recurrent bypass graft failure. The purpose of this study was to identify whether diabetes increased the likelihood of heparin-induced platelet factor 4 antibodies in at risk vascular patients. Methods . We reviewed clinical data on 300 consecutive patients. A hypercoagulable workup was performed if patients presented with (1) early bypass/graft thrombosis (<30 days), (2) multiple bypass/graft thrombosis, and (3) a history of DVT, pulmonary embolus (PE), or native vessel thrombosis. Relevant clinical variables were analyzed and compared between patients with diabetes (DM) and without diabetes (nDM). Results . 85 patients (47 women; age 53 ± 16 years, range 16–82 years) had one of the defined conditions and underwent a hypercoagulable evaluation. Screening was done in 4.7% of patients with early bypass graft thrombosis, 60% of patients were screened because of multiple bypass or graft thrombosis, and 35.3% had a previous history of DVT, PE, or native vessel thrombosis. Of the 43 patients with DM and 42 nDM evaluated, 59 patients (69%) had an abnormal hypercoagulable profile. An elevated heparin antibody level was present in 30% of DM and 12% of nDM patients (chi-squared test P<0.04). Additionally, DM was associated with a higher likelihood of arterial complications while nDM was associated with a higher rate of venous adverse events (chi-squared test P<0.003). Conclusions . Diabetes is associated with a higher likelihood of developing heparin-induced antibodies and an increased combined incidence of arterial complications that include early or multiple bypass/graft thrombosis. This finding may influence the choice of anticoagulation in diabetic patients at risk with vascular disease.
The genetic variants linked with the susceptibility of individuals to VTE are well known; however, the studies explaining the ethnicity based difference in susceptibility to VTE are limited. Present study assesses mutations in six candidate genes contributing to the etiology of VTE in Indian subjects. The study comprised 93 VTE patients and 102 healthy controls. A PCR-RFLP based analysis was performed for nine mutations in the following genes associated with VTE: favtor V Leiden (FVL), prothrombin, tissue factor pathway inhibitor (TFPI), fibrinogen-beta, plasminogen activator inhibitor 1 (PAI-1), and methylene tetrahydrofolatereductase (MTHFR). All the subjects were found to be monomorphic for FVL 1691G/A, prothrombin 20210G/A and TFPI −536C/T mutations. The mutation in the MTHFR gene (677C/T) was observed only in patients. Contrarily, higher frequency of mutation in the PAI-1 −844G/A and the fibrinogen-β−455G/A was observed in controls in comparison to the patients. This study suggests that the PAI-1 −844G/A and fibrinogen-β−455G/A could be protective variants against VTE in Indians. While MTHFR 677C/T mutation was found to be associated, in contrast to other populations, the established genetic variants FVL 1691G/A, prothrombin 20210G/A, and TFPI −536C/T may not be associated with VTE in Indians thus revealing the basis of ethnicity related differences in susceptibility of Indians to VTE.
Background. Stroke is a leading cause of mortality and disability in Brazil and around the world. Cardioembolism is responsible for nearly 30% of the origins of ischemic stroke. Methods. We analyzed data of 256 patients with cardioembolic ischemic stroke (according to TOAST classification) who were admitted into the Hospital São Lucas-PUCRS from October 2011 to January 2014. The cardioembolic subtype was divided into six subgroups: arrhythmias, valvular heart disease, coronary artery disease, cardiomyopathy, septal abnormalities, and intracardiac injuries. The prevalence of the most important cardiovascular risk factors and medications in use for prevention of systemic embolism by the time of hospital admission was analyzed in each patient. Results. Among 256 patients aged 60.2 +/− 6.9 years, 132 males, arrhythmias were the most common cause of cardioembolism corresponding to 50.7%, followed by valvular heart disease (17.5%) and coronary artery disease (16%). Hypertension (61.7%) and dyslipidemia (43.7%) were the most common risk factors. Less than 50% of patients with arrhythmias were using oral anticoagulants. Conclusions. Identifying the prevalence of cardioembolic stroke sources subgroups has become an increasingly important role since the introduction of new oral anticoagulants. In this study, arrhythmias (especially atrial fibrillation) were the main cause of cardioembolism.
Atrial fibrillation (AF) is an independent risk factor for stroke. Anticoagulation therapy has a risk of intracerebral hemorrhage. The use of percutaneous left atrial appendage (LAA) closure devices is an alternative to anticoagulation therapy. Echocardiography has a leading role in LAA closure procedure in patient selection, during the procedure and during followup. A comprehensive echocardiography study is necessary preprocedural in order to identify all the lobes of the LAA, evaluate the size of the LAA ostium, look for thrombus or spontaneous echo contrast, and evaluate atrial anatomy, including atrial septal defect and patent foramen ovale. Echocardiography is used to identify potential cardiac sources of embolism, such as atrial septal aneurysm, mitral valve disease, and aortic debris. During the LAA occlusion procedure transeosophageal echocardiography provides guidance for the transeptal puncture and monitoring during the release of the closure device. Procedure-related complications can be evaluated and acceptable device release criteria such as proper position and seating of the occluder in the LAA, compression, and stability can be assessed. Postprocedural echocardiography is used for followup to assess the closure of the LAA ostium. This overview paper describes the emerging role of LAA occlusion procedure with transeosophageal echocardiography guidance as an alternative to anticoagulation therapy in patients with AF.
