[News on venous thromboembolic disease]. / Novedades en la enfermedad tromboembólica venosa.

This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery.

Prognosis of venous thromboembolism in orthopaedic surgery or trauma patients and use of thromboprophylaxis. / Pronóstico de la enfermedad tromboembólica venosa en cirugía ortopédica o pacientes traumatológicos y uso de tromboprofilaxis.

BACKGROUND: There is scarce evidence about the prognosis of venous thromboembolism in patients undergoing orthopedic surgery and in patients suffering non-surgical trauma. METHODS: We used the RIETE database (Registro Informatizado de pacientes con Enfermedad Trombo Embólica) to compare the prognosis of venous thromboembolism and the use of thromboprophylaxis in patients undergoing different orthopedic procedures and in trauma patients not requiring surgery. RESULTS: From March 2001 to March 2015, a total of 61,789 patients were enrolled in RIETE database. Of these, 943 (1.52%) developed venous thromboembolism after elective arthroplasty, 445 (0.72%) after hip fracture, 1,045 (1.69%) after non-major orthopedic surgery and 2,136 (3.46%) after non-surgical trauma. Overall, 2,283 patients (50%) initially presented with pulmonary embolism. Within the first 90 days of therapy, 30 patients (0.66%; 95% CI 0.45-0.93) died from pulmonary embolism. The rate of fatal pulmonary embolism was significantly higher after hip fracture surgery (n = 9 [2.02%]) than after elective arthroplasty (n = 5 [0.53%]), non-major orthopedic surgery (n = 5 [0.48%]) or non surgical trauma (n = 11 [0.48%]). Thromboprophylaxis was more commonly used for hip fracture (93%) or elective arthroplasty (94%) than for non-major orthopedic surgery (71%) or non-surgical trauma (32%). Major bleeding was significantly higher after hip fracture surgery (4%) than that observed after elective arthroplasty (1.6%), non-major orthopedic surgery (1.5%) or non-surgical trauma (1.4%). CONCLUSIONS: Thromboprophylaxis was less frequently used in lower risk procedures despite the absolute number of fatal pulmonary embolism after non-major orthopedic surgery or non-surgical trauma, exceeded that observed after high risk procedures.

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.

Matching risk with treatment strategies in deep vein thrombosis management.

Successful and cost-effective prophylaxis against venous thromboembolism (VTE) depends on the availability of safe and effective antithrombotic methods, and the ability to match these to patients according to their level of thromboembolic risk. The last 20 years have seen significant developments in methods of thromboprophylaxis but, despite use of the best available methods, VTE still occurs in a significant proportion of patients. Efforts are now focused both on developing more effective pharmacological and physical methods, and improving assessment of thromboembolic risk in clinical practice, with the goal of avoiding unnecessary prophylaxis in low-risk patients and providing enhanced protection to high-risk patients. Factors known to exert a direct effect on thromboembolic risk include previous VTE, advancing age, surgery, malignancy, immobility, and the presence of thrombophilic states. Other less well-defined risk factors include obesity, pregnancy, and leg varicosities. Various risk assessment models (RAMs) have been devised based on these factors, but most of the resulting risk assessment formulae, some of them based on laboratory test results, have been too complicated to gain acceptance in routine clinical practice. Reflecting the need to refine the use of thromboprophylaxis in clinical practice, a number of RAMs have been developed recently, based on epidemiological evidence. Some models include specific recommendations for prophylaxis, based on evidence from randomized, controlled trials.

Risk factor assessment in the management of patients with suspected deep venous thrombosis.

BACKGROUND: To evaluate the prevalence of thrombosis risk factors in a group of patients undergoing venous duplex scanning (VDS) and to design a risk factor stratification model with the ability to improve the diagnostic yield of VDS. METHODS: Risk factor assessment and VDS were performed on 1,000 patients with clinically suspected lower extremity deep vein thrombosis (DVT) and patients were divided into two groups based upon the outcome of their scan: those with and those without confirmed DVT. Univariate and multivariate logistic regression analyses were performed in order to determine the significance of each risk factor in relation to having a confirmed DVT. RESULTS: There were 181 patients (18.1%) with confirmed DVT. A prior history of DVT/pulmonary embolism, malignancy, prior immobilization, and age over 70 were the most important risk factors associated with having a DVT confirmed on VDS. A novel risk factor stratification model was created utilizing the odds ratios of those factors found to be significant and the prevalence of DVT was found to be 92.4% in the high risk category, 11.5% in the moderate risk category, and 3.2% in the low risk category using this model. CONCLUSIONS: Venous duplex scanning is established as the screening test of choice when one suspects the diagnosis of DVT despite the significant cost of performing and interpreting the test. We suggest that a better clinical model utilizing risk factor assessment may be the key to increasing the yield rate and cost-effectiveness of VDS by excluding low-risk patients from undergoing unnecessary testing.

A side-to-end choledochoduodenostomy between the common bile duct and the stump of the transected duodenum.

A technique for treating patients with benign pyloric stenosis and associated choledocholithiasis upon a dilated common bile duct is described. The procedure consists in the performance of a Billroth II partial gastrectomy with the Hofmeinster-Finsterer modification and truncal vagotomy and a simultaneous side-to-end choledochoduodenostomy between the common bile duct and the duodenal stump. We have operated two cases in this way up to now without complications and with good postoperative results.

Finding the right fit: effective thrombosis risk stratification in orthopedic patients.

Patients undergoing orthopedic surgery are at increased risk of venous thromboembolic events. Proven prophylactic measures are available but are generally underused. However, even one of the most effective therapies available, low-molecular-weight heparin, fails to prevent deep vein thrombosis in approximately 15% of patients undergoing total hip replacement. Clinical outcomes and cost-effectiveness of venous thromboembolism prophylaxis may be optimized by tailoring the treatment to the level of risk of each patient. Overall thromboembolic risk depends on the interactions among multiple factors, such as those that relate to the current clinical status and underlying susceptibility of the patient. Presently, risk assessment models that consider these factors may be of practical assistance in stratifying patients. Improving identification of patients with additional risk factors is a goal of future models. Novel therapies, such as the recombinant hirudin desirudin, or strategies, such as prolonged postoperative prophylaxis, may provide improved protection in these patients and should be considered in the future.

Prevention of postoperative venous thromboembolism following laparoscopic cholecystectomy.

Advantages of laparoscopic cholecystectomy are less patient discomfort and shorter hospital stay than with the traditional open approach. Nevertheless, this operation is performed under general anesthesia, using muscle relaxants and pneumoperitoneum, with most patients in the reverse Trendelenburg position. It has been shown that this procedure is associated with significant hypercoagulability and dilation of the veins of the leg. We review the role of these factors as potential risk factors for the development of postoperative venous thromboembolism and also report the rate of thromboembolic complications following laparoscopic cholecystectomy. Based on the available evidence, it is concluded that laparoscopic cholecystectomy, despite being a "minimally invasive procedure," may be associated with a definite risk of developing postoperative venous thromboembolism that could extend beyond hospital discharge. Accordingly, thrombosis prophylaxis should be considered for these patients.

Venous thromboembolism after hospital discharge.

Several methods of prophylaxis have significantly reduced the risk of developing VTE during hospital admission. There is a current tendency toward a reduction in the hospital stay, which does not necessarily mean that patients are protected from experiencing thrombotic complications after leaving the hospital. A number of patients will develop DVT and PE after hospital discharge if prophylaxis is prematurely discontinued while they persist at risk. Further studies are necessary to establish whether extending prophylaxis beyond discharge will reduce the rate of late-onset thromboses and which are the best prophylactic alternatives for the different patient groups at risk. Meanwhile, it is our standard of practice to utilize a combination of GES and either low-dose heparin or warfarin, at least for 3 or 4 weeks after discharge in high-risk patients. In countries where low molecular weight heparins are available, these agents represent an attractive alternative to unfractionated heparin because of their better dosage schedule and safety profile.

Perspectives on thromboelastography.

The knowledge of these sources of error together with strict methodology assure reliable results and avoid what some authors consider limitations of the test. These so-called limitations are actually due to incomplete information or insufficient experience. It is our opinion that the key for success when using TEG is to use the test in those cases for which it has been indicated. Also, the fact that TEG is a global test of coagulation should be kept in mind and therefore the need for additional hemostatic tests should be evaluated when applicable (Fig.3). According to this review, the established applications of TEG are as follows: (1) detection of hypercoagulable states, particularly in the postoperative period and for patients with malignancies; (2) management of patients who are administered intravenous heparin; (3) monitoring the coagulation state during liver transplantation; (4) monitoring the coagulation state and management of patients during cardiopulmonary bypass; and (5) diagnosis and treatment of hematologic dysfunctions, particularly hemophilia. Management of patients under warfarin administration, as well as monitoring of the adjustment of subcutaneous heparin prophylaxis in several surgical procedures, should probably belong to this list, but further studies are needed to confirm these roles. Used by experienced hands, TEG is a valuable hemostatic test, the future of which is already present.

Clinical assessment of venous thromboembolic risk in surgical patients.

Prophylaxis against postoperative venous thromboembolism should be tailored according to the patient's level of risk. However, risk assessment is not yet in widespread use in surgical practice. In this study, 538 general surgical patients were prospectively assessed based on a scoring system containing 20 risk factors. Depending on the total risk factor score, the patients were grouped into low (0 to 1, 34.5%), moderate (2 to 4, 48.5%), or high risk (more than 4, 17.2%) categories. Statistically significant (p less than 0.0001) correlation was found between our results and those of three existing risk assessment systems. Overall, of the 538 patients, 37.2% received prophylaxis; 10%, 42.1%, and 76% received prophylaxis in the low-, moderate-, and high-risk categories, respectively. Mechanical prophylactic modalities (graduated elastic compression and sequential intermittent compression) were preferred over pharmacologic modalities. These results suggest that implementation of prophylaxis remains underutilized despite published reports, including NIH guidelines. Our results indicate that the majority of surgical patients seen in this suburban hospital have two or more risk factors for developing venous thromboembolism.

Home use of impulse compression of the foot and compression stockings in the treatment of chronic venous insufficiency.

PURPOSE: The use of intermittent pneumatic compression, in addition to elastic bandages or stockings, accelerates the healing of leg ulcers in patients with severe chronic venous insufficiency (CVI). There is recent evidence that impulse compression of the plantar venous plexus reduces post-traumatic ankle swelling and prevents postoperative venous thromboembolism. The purpose of this study was to evaluate the clinical and hemodynamic responses after home use of impulse foot compression for 3 months in patients already using therapeutic compression stockings for the management of CVI. METHODS: Twelve extremities from 9 patients with documented CVI, class 4 to 5 according to the Clinical, Etiology, Anatomy, Pathophysiology classification system, were included in this prospective cohort study. All patients were instructed to use a foot pump device at home for 2 hours a day for 3 months in addition to therapeutic compression stockings (30-40 mm Hg) worn during the day. The device was set to three cycles (3 seconds) of compression (120 mm Hg) per minute. A clinical scoring system was completed before foot compression and 1, 2, and 3 months thereafter. In addition, all patients underwent air plethysmography studies at the same time intervals, including venous volume, venous filling index, ejection fraction, and residual volume fraction. RESULTS: Patients reported significant improvement in their scores for swelling (P <.05) and pain (P <.04). Air plethysmography showed a reduction in venous volume and venous filling index, although these differences were not significant. Ejection fraction remained unchanged and residual volume fraction was significantly reduced (P <.05) compared with baseline. The foot compression devices were well tolerated by all the patients in the study. CONCLUSIONS: The use of home foot impulse compression plus elastic stockings significantly reduced the residual volume fraction as measured by air-plethysmography in a group of patients with severe CVI. This favorable hemodynamic response could, in part, explain the clinical improvement achieved by this combined treatment. However, this represents a preliminary pilot study that needs to be confirmed in future randomized controlled studies with more patients included.

Laboratory assays and duplex scanning outcomes after symptomatic deep vein thrombosis: preliminary results.

PURPOSE: The purpose of this article was to assess a number of hematologic and fibrinolytic assays at the time of diagnosis of deep vein thrombosis (DVT) and at several intervals over a period of 6 months afterward and to correlate these results with the results of serial duplex scanning. METHODS: Thirty-five patients (average age 61, range 18 to 82) with acute symptomatic DVT confirmed by duplex scanning were included. On diagnosis, blood was drawn, and plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), D-dimer (DD), and tissue factor pathway inhibitor (TFPI) were determined. Duplex scanning and all laboratory assays were repeated 1 week, 1 month, 3 months, and 6 months thereafter. RESULTS: The rate of DVT complete resolution 6 months after diagnosis was 57%. Whereas plasma levels of PAI were similar throughout the 6-month follow-up period, t-PA increased significantly 1 week after diagnosis and decreased thereafter. Both DD and TFPI levels decreased significantly after diagnosis compared with presentation values. Comparing these assay levels between patients with complete resolution versus partial or no resolution, PAI levels were significantly higher during the first week in patients with poor outcome. Plasma levels of t-PA were higher in cases with good outcome, and DD levels were higher in patients with poor outcome. TFPI levels were similar in both outcome groups. CONCLUSIONS: Patients with complete DVT resolution on duplex scanning at 6 months had significantly lower levels of PAI on presentation and after 1 week than did those with incomplete lysis. Although differences were not significant, t-PA levels were higher and DD lower in patients with good outcome. Our results suggest that certain plasma fibrinolytic assays might correlate with the outcome of DVT, as assessed by duplex ultrasonography.

Modifications of plasma levels of tissue factor pathway inhibitor and endothelin-1 induced by a reverse Trendelenburg position: influence of elastic compression--preliminary results.

PURPOSE: The purpose of this study was to assess the effects of the passive 45-degree reverse Trendelenburg position and graduated compression stockings (GCS) on plasma tissue factor pathway inhibitor (TFPI) and endothelin-1 levels in a group of volunteers. METHODS: Ten healthy subjects lay on an examining table for 30 minutes while baseline measurements were made. The table was then tilted to a 45-degree upright position for 60 minutes, and measurements were repeated. On a different day, subjects were tilted again, but on this occasion they wore thigh-length GCS. Blood was drawn before and 60 minutes after tilting during both sessions, and plasma TFPI and endothelin-1 were obtained. Cross-sectional areas of the calf medial gastrocnemius vein, before and after tilting, were measured by a duplex scanner. RESULTS: Upright tilting induced a significant dilation of the medial gastrocnemius veins that was partially corrected by the use of elastic stockings. Similarly, endothelin-1 levels significantly increased after tilting. The use of GCS did not modify these differences. On the other hand, although TFPI levels were not affected by tilting without stockings, they were significantly elevated after tilting when GCS were used. CONCLUSIONS: Upright passive tilting induces significant dilation of the deep calf veins and is associated with a significant increase in plasma levels of endothelin-1, whereas TFPI levels remain unchanged. The use of elastic stockings reduces the degree of calf distention but does not prevent an increase in endothelin-1. TFPI levels are significantly increased after tilting when GCS are used. This might represent a previously unknown mechanism of action of elastic stockings with interesting potential for deep vein thrombosis prophylaxis. More studies are warranted in a larger series to confirm these results.

Venous thromboembolism prophylaxis and risk assessment in medical patients.

In summary we have developed a VTE risk assessment system for medical patients based on our prior experience in surgical patients. In this model we divide individuals into low, moderate, and high-risk categories. We realize that our system needs further validation with appropriate diagnostic endpoints to correlate the actual occurrence of venous thromboembolism with the predicted risk on the basis of our score system. Nevertheless, the proposed model reflects one approach to achieving a prophylaxis tailored to the patients' risk.

Evaluation of therapeutic compression stockings in the treatment of chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) affects a significant portion of the world's population, causing substantial morbidity and medical expenditure. Its pathophysiology is based on venous hypertension in the lower extremities, with vascular compression therapy remaining the foundation of its medical management. OBJECTIVE: To evaluate the effectiveness of therapeutic compression stockings in the treatment of lower extremity CVI. METHODS: A group of 112 patients with CVI received graduated-compression stockings and rated the severity of their symptoms on a five-point scale before wearing the stockings, and then again after 1 and 16 months of treatment. Patient complaints associated with stocking use and patient compliance rates were also recorded at 1 and 16 months. RESULTS: A statistically significant improvement (p < 0.001) was reported in patient severity scores for lower extremity swelling, pain, skin discoloration, activity tolerance, depression and sleeping problems after 1 and 16 months of treatment with compression stockings. CONCLUSION: Therapeutic graduated-compression stockings are an effective treatment for CVI of the lower extremities.

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 post-operative 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.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of oral anticoagulation therapy on deep vein thrombosis rates four weeks after total hip replacement.

PURPOSE: The purpose of this study was to assess the rate of postoperative deep vein thrombosis (DVT) as a function of oral anticoagulation therapy after total hip replacement surgery. METHODS: A total of 125 patients completed the study. All the patients received sequential gradient pneumatic compression over elastic stockings until hospital discharge. In addition, all the patients underwent postoperative heparin therapy followed by oral warfarin therapy, adjusted in dose to maintain a goal international normalized ratio (INR) level of 2.0 to 3.0. Warfarin therapy and compression stockings were continued for 1 month after surgery. Bilateral duplex scanning was performed 1 and 4 weeks after surgery to assess the rate of DVT. RESULTS: Nineteen of the 125 patients had DVT develop (15.2%). Of those thromboses, six (31.6%) and 13 (68%) were detected 1 week and 1 month after surgery, respectively. The rate of proximal DVT was 2.4% (3 of 125) 1 week after surgery and rose to 8.2% (10 of 122) 1 month after surgery. Most DVT cases (64%; 12 of 19) were asymptomatic. The patients in whom DVT developed had significantly lower INR values during the second to fourth postoperative weeks than did those patients without thrombosis, and no differences in INR values were found during the first postoperative week. CONCLUSION: The risk of the development of DVT extends beyond hospital discharge in patients who undergo total hip replacement, despite a regimen of prolonged oral anticoagulation therapy. This is particularly true in patients whose INR values did not reach therapeutic range during the first postoperative month. Therefore, thrombosis prophylaxis regimens on the basis of the administration of warfarin should try to maintain INR values within therapeutic range during the entire first postoperative month to minimize the incidence of DVT.