Juan I. Arcelus

Venous thromboembolism (VTE) in Europe - The number of VTE events and associated morbidity and mortality

Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations. These factors are thought to result in marked underestimates ofVTE incidence. The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of nonfatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries. The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE. Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE. VTE is a major health problem in the EU, with over one million VTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented. These results have important implications for the allocation of healthcare resources.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014

PURPOSE To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts. RESULTS Of the 53 publications identified and reviewed, none prompted a change in the 2013 recommendations. RECOMMENDATIONS Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND VTE is a common cause of preventable death in surgical patients. METHODS We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (∼1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (∼3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (∼6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations. CONCLUSIONS Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients.

Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease.

Effective and safe methods of preventing venous thromboembolism (VTE) are now widely available, but a significant proportion of patients develop VTE either because thromboprophylaxis has not been used or because the intensity of thromboprophylaxis is not matched to the level of risk. Thromboembolic risk varies widely according to the clinical setting and presence of underlying risk factors, but VTE may not be suspected even in high-risk patients. Clinical risk factors for VTE include recent surgery, cancer, stroke, previous VTE, immobilization, and advanced age. Recent attention has focused on the role of inherited and acquired molecular factors in determining overall thromboembolic risk. These factors include the classic thrombophilias-deficiencies of antithrombin III, protein C, and protein S-and several newly described molecular risk factors: factor V Leiden, the prothrombin 20210A gene mutation, and hyperhomocysteinemia. Based on emerging knowledge of risk factors, several risk assessment models (RAMs) have been devised that stratify patients according to overall VTE risk, allowing thromboprophylaxis to be tailored appropriately. Compared with older risk assessment formulas, current RAMs are simpler and include specific recommendations for thromboprophylaxis based on the available scientific evidence. Consensus documents on VTE prevention classify patients into low-, moderate-, and high-risk categories. More recently, a new risk group, very high risk, has been described. Very-high-risk patients are especially prone to thromboembolic complications and need intensive and in some cases prolonged thromboprophylaxis.

Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients.

Hospitalized patients with acute medical conditions are at significant risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Despite consensus-group recommendations that at-risk medical patients should receive thromboprophylaxis, there is currently no consensus as to which patients are at risk, and many patients may not receive appropriate thromboprophylaxis. This paper reviews evidence for the risk of VTE associated with different medical conditions and risk factors, and presents a risk-assessment model for risk stratification in medical patients. Medical conditions associated with a moderate to high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Importantly, analyses of data from the MEDENOX study show that thromboprophylaxis significantly reduces the risk of VTE in these patient subgroups. Risk factors in medical patients include a history of VTE, history of malignancy, increasing age, thrombophilia, prolonged immobility, and obesity. These medical conditions and risk factors are included in a risk-assessment model which is hoped will provide a simple means of assisting clinicians in deciding whether thromboprophylaxis should be used in an individual patient.

Prevention of VTE in nonorthopedic surgical patients. Antithrombotic therapy and prevention of thrombosis, 9th ed

BACKGROUND VTE is a common cause of preventable death in surgical patients. METHODS We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (∼1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (∼3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (∼6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations. CONCLUSIONS Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients.

The management and outcome of acute venous thromboembolism: a prospective registry including 4011 patients.

OBJECTIVE To obtain a realistic overview of management and clinical outcomes of patients with venous thromboembolism (VTE) in Spain on the basis of data from a national multicenter registry. METHODS A prospective registry was initiated in Spain in March 2001. Data were collected from patients with objectively confirmed deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and entered into the online registry by physicians who were responsible for the management of these patients. RESULTS As of August 2002, 4011 patients with confirmed VTE were included in the registry: 60% with DVT, 23% with PE, and 17% with both DVT and PE. Diagnostic methods for VTE included compression ultrasonography (86%), venography (10%), V/Q lung scans (42%), computed tomography scan (28%), and pulmonary angiography (0.9%). D-dimer testing was performed in 61% of cases and was positive in 92% of patients with confirmed VTE. The majority of DVT (95%) were located in the lower extremities (82% proximal and 4% bilateral), while 4.8% were located in the upper extremities or neck veins. Most patients (90.5%) were admitted to hospital. In the acute phase, treatment consisted of low molecular weight heparin (LMWH) in 88%, unfractionated heparin (UFH) in 11%, and fibrinolysis in 0.8%. Cava filters were inserted in 2% of patients, mainly because of active bleeding (13%), increased hemorrhagic risk (38%), or recurrent VTE (29%). Absolute bed rest was recommended to 63% of patients. Secondary prevention of VTE included oral anticoagulants (75%) and LMWH (24.5%). Therapeutic compression stockings were prescribed to 53% of patients at the time of hospital discharge. Regarding the main clinical outcomes during an average (+/-SD) follow-up period of 156 +/- 95 days, 19% had adverse events: 12.5% of patients died, 5.5% had clinically confirmed VTE recurrence, and 9.8% suffered bleeding complications (44% with major bleeding). CONCLUSIONS This prospective observational multicenter registry provides a large database reflecting the actual day-to-day clinical practice regarding VTE management in a European country. The most important findings were the increasing use of spiral computed tomography for PE diagnosis, the unexpectedly high proportion of patients admitted to hospital despite the use of LMWH in almost 90% of cases in the acute phase, and the utilization of LMWH for secondary prevention in almost 25% of cases. On the other hand, this large-scale prospective registry permits on-line consultation of high-risk situations to assess how difficult cases were treated and what their outcomes were. This will provide a most useful tool for the practicing physician responsible for the management of VTE patients.

Postoperative hypercoagulability and deep-vein thrombosis after laparoscopic cholecystectomy

Patients who undergo laparoscopic cholecystectomy (LC) are operated on under general anesthesia, in a reverse Trendelenburg position, with 12–15-mmHg pneumoperitoneum. All of these factors can induce venous stasis of the legs, which may lead to postoperative deep-vein thrombosis (DVT). The objectives of this study were to assess the degree of hypercoagulability and to determine the rate of postoperative DVT in a group of 100 patients in whom LC was completed. Whole-blood thrombelastography (TEG) and plasma-activated partial thromboplastin time (PTT) determination were carried out preoperatively and on the 1st postoperative day. All patients received pre-, intra-, and postoperative graduated compression stockings and sequential pneumatic compression devices until fully ambulatory. Twenty-six percent of the patients with a risk score >4, or a postoperative TEG index >+5.0, received subcutaneous heparin (5,000 units b.i.d.), beginning in the postoperative period and continuing for 4 weeks as an outpatient. A complete venous duplex scan of both legs was performed on the 7th postoperative day, at the time of their office visit.Our results revealed significant postoperative hypercoagulability for the TEG index (P<0.005) and for PTT (P<0.05). One patient had an asymptomatic DVT (1%), and no side effects from the mechanical or pharmacological prophylaxis occurred in this series.These data suggest that the low incidence of thrombosis in the face of theoretical and laboratory evidence of postoperative hypercoagulability may reflect an effective prophylactic regime. Alternatively, the incidence of these thrombotic problems may be very low, or the sensitivity and timing of duplex scanning may be inadequate to identify asymptomatic venous thrombosis. Until further studies are done to resolve these issues, we feel that mechanical prophylaxis combined with selective low-dose heparin therapy is safe and effective in patients having laparoscopic cholecystectomy.

A guide to venous thromboembolism risk factor assessment

Venous thromboembolism (VTE) remains a widespread clinical problem associated with signi~cant morbidity and mortality. It is estimated that VTE results in 300,000 to 600,000 hospitalizations each year in the United States [1]. Of these patients, 50,000 to 100,000 will die of a pulmonary embolism, which is presently the leading cause of preventable death in hospitalized patients [1,2]. Untreated deep vein thrombosis (DVT) predisposes patients to episodes of recurrent VTE and the development of the postphlebitic syndrome (PTS), which can involve a constellation of symptoms ranging from leg edema, pain, aching and tiredness, to the development of skin discoloration, scarring, and even open ulceration [3–7]. VTE and its post-thrombotic sequelae have a staggering impact on healthcare expenses, costing the United States over one billion dollars annually [8,9]. Surgical patients in particular are at a high risk for DVT since the surgical procedure itself is very traumatic and often accompanied by bed rest that increases venous stasis. Without appropriate prophylaxis, DVT rates range from 45–70% and 15–30% in orthopedic and general surgery patients respectively [2]. For this reason, surgeons should be aware of current guidelines that detail how to appropriately protect their patients from the development of DVT. The rationale for VTE prophylaxis is based on the fact that two-thirds of DVT cases are asymptomatic, and PE is most often clinically silent [3]. In addition, the clinical diagnosis of a DVT or PE is insensitive and unreliable since few of their signs and symptoms are speci~c. Implementation of treatment must be done before the complete clinical picture has developed, since the ~rst manifestation of the disease may be a fatal PE. Unrecognized and untreated DVT may also lead to long-term morbidity related to the development of the post-thrombotic syndrome and future episodes of recurrent VTE. Consequently, prevention is the key to reducing death and morbidity from VTE, and the key to appropriate prophylaxis is risk factor analysis (RFA). Even though the importance of preventing the development of VTE has been emphasized by a number of consensus conference guidelines over the past 20 years, the speci~c recommendations in the guidelines have not been universally adopted into clinical practice [1,10–13]. Various surveys over the past few years have reported wide practice variations in the prevention of VTE, including an under-utilization of prophylaxis and a lack of awareness among physicians of VTE as a problem. In a recent 1998 survey of 1,145 Fellows of the American College of Surgeons, Caprini showed that only 47% and 31% of the responding surgeons were familiar with the 1986 NIH Consensus Conference and the American College of Chest Physicians guidelines respectively [14]. An alarming 90% of the surgeons were not familiar with the 1992 THRIFT Conference or the 1992 European Consensus Conference Guidelines [14]. Some investigators feel that the availability and reinforcement of written protocols, particularly in non-teaching hospitals where VTE prophylaxis is signi~cantly underutilized, may improve the utilization of VTE prophylaxis [15]. It has already been shown that continual medical education (CME) programs and protocol implementation can signi~cantly increase the frequency with which physicians prescribe appropriate methods of VTE prophylaxis [16]. The 1998 Chest Consensus Guidelines emphasized the need for continuing educational programs to increase the use of appropriate prophylactic measures and the importance of risk factor assessment in diagnosing and treating DVT [17]. RFA is essential in surgical patients because prophylaxis is encumbered with risks (e.g., bleeding com-

Clinical presentation and time-course of postoperative venous thromboembolism: Results from the RIETE Registry

There is little literature about the clinical presentation and time-course of postoperative venous thromboembolism (VTE) in different surgical procedures. RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we analysed the baseline characteristics, thromboprophylaxis and therapeutic patterns, time-course, and three-month outcome of all patients with postoperative VTE. As of January 2006, there were 1,602 patients with postoperative VTE in RIETE: 393 (25%) after major orthopaedic surgery (145 elective hip arthroplasty, 126 knee arthroplasty, 122 hip fracture); 207 (13%) after cancer surgery; 1,002 (63%) after other procedures. The percentage of patients presenting with clinically overt pulmonary embolism (PE) (48%, 48%, and 50% respectively), the average time elapsed from surgery to VTE (22 +/- 16, 24 +/- 16, and 21 +/- 15 days, respectively), and the three-month incidence of fatal PE (1.3%, 1.4%, and 0.8%, respectively), fatal bleeding (0.8%, 1.0%, and 0.2%, respectively), or major bleeding (2.3%, 2.9%, and 2.8%, respectively) were similar in the three groups. However, the percentage of patients who had received thromboprophylaxis (96%, 76% and 52%, respectively), the duration of prophylaxis (17 +/- 9.6, 13 +/- 8.9, and 12 +/- 11 days, respectively) and the mean daily doses of low-molecular-weight heparin (4,252 +/- 1,016, 3,260 +/- 1,141, and 3,769 +/- 1,650 IU, respectively), were significantly lower in those undergoing cancer surgery or other procedures. In conclusion, the clinical presentation, time-course, and three-month outcome of VTE was similar among the different subgroups of patients, but the use of prophylaxis in patients undergoing cancer surgery or other procedures was suboptimal.