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PubMed2002

Pharmacological thromboembolic prophylaxis in a medical ward: room for improvement.

To evaluate the adequacy of pharmacological thromboembolic prevention in the medical ward of a university hospital, we performed a retrospective study in 227 consecutive inpatients. The presence of risk factors, and type, length, and dose of pharmacological prevention were documented by chart review. Only 22% of the 153 risk patients received adequate prevention, whereas 38% of the patients at low risk were given pharmacological prophylaxis. The high prevalence of over- and undertreatment is an indicator of less than optimal care. Quality of care interventions, such as the development of local guidelines, might improve the appropriateness of pharmacological thromboembolic prophylaxis in medical inpatients.

Aged↗
PubMed2003

Venous thromboembolism, oral contraceptives and high prothrombin levels.

The G20210A prothrombin mutation, associated with elevated prothrombin levels, is a risk factor for venous thromboembolism (VTE) and displays a strong interaction with oral contraceptives (OC). No data are available on VTE risk of OC use in women with high prothrombin levels, either associated or not with the mutation. The aim of this study was to evaluate the risk of VTE in OC users with high prothrombin levels, either including or excluding carriers of the prothrombin mutation. Prothrombin levels were measured by a chromogenic assay in 152 women who suffered from VTE in reproductive age and in 296 healthy women. Subjects carrying thrombophilic alterations other than the G20210A prothrombin mutation were excluded. Prothrombin levels were stratified into quartiles. The OR of subjects in the upper quartile were 3.10 [95% confidence interval (CI) 1.73-5.55] and 2.07 (95% CI 1.11-3.85) in all women and in those not carrying the prothrombin mutation, respectively. Among the 152 patients, 88 had experienced VTE during OC; in the control group we considered as OC users the women who had used OC for at least 6 months in the 2 years before presentation but had stopped the treatment at least 3 months before the time of blood sampling (n = 127). For the interaction between OC and prothrombin levels only the two extreme strata of prothrombin were considered. Women with the lowest prothrombin levels and who did not use OC were used as reference category. The VTE risk of using OC in subjects with prothrombin levels in the upper quartile was increased 5.4-fold (95% CI 2.38-12.3) and 3.5-fold (95% CI 1.48-8.22) in all women and in those not carrying the prothrombin mutation, respectively. We conclude that elevated prothrombin levels, even in women without the G20210A prothrombin mutation, are associated with an increased risk for venous thromboembolism and that oral contraceptive use potentiates such association.

Adolescent↗
PubMed2003

The risk of recurrent venous thromboembolism among patients with high factor IX levels.

High factor IX (FIX) is a risk factor of deep vein thrombosis. The impact of high FIX on the risk of recurrent venous thrombosis is unknown. We prospectively followed 546 patients after anticoagulation for a first spontaneous venous thromboembolism. Patients with a natural coagulation inhibitor deficiency, lupus anticoagulant or cancer were excluded. At 3 years, the likelihood of recurrence was 23% among patients with high FIX (exceeding the 75th percentile) compared with 11% among patients with lower levels. Among patients with high FIX, the relative risk of recurrence was 2.2 (95% CI: 1.3-3.6) before and was 1.6 (95% CI: 1.0-2.8) after adjustment for age, gender, duration of anticoagulation, FV Leiden, FII G20210A, high FVIII and hyperhomocysteinemia. Compared with patients with low factor IX (< 138 IU dL(-1)) and low FVIII (</= 234 IU dL(-1)), the relative risk of recurrence was 1.5 among patients with high FIX and low FVIII, 2.7 among patients with low FIX and high FVIII and 6.6 among patients with high FIX and high FVIII. High levels of FIX confer an increased risk of recurrent venous thromboembolism and enhance the risk of recurrence among patients with high FVIII.

Adult↗
PubMed2003

Prevalence and risk factors of non-fatal venous thromboembolism in the active population of the VITA Project.

Cost-effective strategies for the identification of subjects at risk of venous thromboembolism (VTE) in the active population are still lacking. Our objectives were to identify risk factors for venous thromboembolism in active subjects. We analyzed data from a population-based sample of 15055 Caucasians aged 18-65 years randomly selected from the census list of the township of Vicenza, Italy. A validated methodology was used to retrospectively identify subjects with previous VTE. Body mass index (BMI), smoking, oral contraceptive use, previous superficial vein thrombophlebitis (SVT) and familial history of VTE, all at the age of first thrombosis, were ascertained by direct interview and by review of available medical records. Ninety-two deep vein thromboses [prevalence: 61.1/10000, 95% confidence interval (CI) 49.2-74.9], three upper deep vein thrombosis (prevalence: 1.9/10000, 95% CI 0.4-5.8) and 21 pulmonary embolism (prevalence: 13.9/10000, 95% CI 8.6-21.3) were identified. After age and sex adjustment, clinically identifiable risk factors were: history of SVT [odds ratio (OR) = 6.8], oral contraceptive use (OR = 4.7), family history of VTE (OR = 4.5), smoking (OR = 1.7) and BMI above the third tertile (OR vs. mid-tertile 2.9). While previous SVT and BMI were associated with VTE in all circumstantial situations (surgery/trauma, pregnancy or idiopathic VTE), for oral contraceptive use, positive family history and smoking the degree of association varied significantly depending on the situation. Non-fatal VTE affects 0.7% of the subjects belonging to an active population, 56% of cases being potentially preventable. In 30% of VTE cases, at least two easily recognizable risk factors are present. Clinical assessment of risk factors remains the mainstay of VTE prevention.

Adolescent↗
PubMed2003

The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopedic surgery.

BACKGROUND: The selective antithrombotic fondaparinux is more effective than the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism (deep-vein thrombosis [DVT] or pulmonary embolism) in patients undergoing major orthopedic surgery, but its cost-effectiveness is undetermined. OBJECTIVES: To evaluate the cost-effectiveness of fondaparinux relative to enoxaparin as prophylaxis against venous thromboembolism (VTE) for patients undergoing total hip replacement, total knee replacement or hip fracture surgery in the UK. PATIENTS/METHODS: A decision analysis model was created simulating the impact of fondaparinux and enoxaparin on patient outcomes and costs over various time points up to 5 years following surgery. The main outcome measures were treatment costs per patient and the incidence of clinical VTE and VTE-related deaths. A weighted (combined) cohort reflects the proportion of patients undergoing these procedures in 2000/2001. RESULTS: In the combined cohort, compared with enoxaparin, fondaparinux is expected to produce 20 fewer clinical VTE events and 3.2 fewer VTE-related deaths per 1000 procedures at 5 years. Cost savings at 5 years are pound 27 per patient with fondaparinux (discounted at 6% per year). In each of the three surgical groups, fondaparinux leads to lower expected costs per patient and to a smaller number of VTE events and VTE-related deaths. RESULTS are sensitive to the price difference between fondaparinux and enoxaparin and variation in the rate of late DVT. The analysis is robust to variations in all other key parameters. CONCLUSIONS: Compared with enoxaparin, fondaparinux is more effective and reduces costs to the healthcare system. At current prices, fondaparinux is the recommended strategy in the UK for prophylaxis following major orthopedic surgery.

Anticoagulants↗
PubMed2001

Thromboembolic risk in atrial flutter. The FLASIEC (FLutter Atriale Società Italiana di Ecografia Cardiovascolare) multicentre study.

AIMS: Patients with atrial flutter are believed to be at lower risk of thromboembolism than patients with atrial fibrillation. However, the incidence of atrial thrombi and the need for anticoagulation in patients with atrial flutter is not well established. METHODS AND RESULTS: A prospective observational multicentre study was undertaken to assess the frequency of atrial thrombi and spontaneous echocontrast and the prevalence for aortic complex atherosclerotic lesions in a cohort of unselected patients with atrial flutter. We evaluated 134 patients (102 male, aged 70+/-9 years); exclusion criteria were history of atrial fibrillation, rheumatic mitral valve disease and mitral mechanical prosthesis. The median of atrial flutter duration was 33 days. Twelve patients had been taking warfarin for more than 7 days. One hundred and twenty-four patients (94%) underwent a transoesophageal echocardiogram, which revealed left atrial appendage thrombi in two patients (1.6%) and right atrial thrombi in one patient (1%). At least moderate left atrial echocontrast was found in 16/124 patients (13%). Complex atherosclerotic aortic plaques were detected in 10 patients (8%). Atrial flutter conversion was attempted in 93/134 patients (69%). At the 1-month follow-up, two patients experienced a thromboembolic event following restoration of sinus rhythm. CONCLUSIONS: Atrial thrombi and echocontrast, and complex aortic atherosclerotic plaques are relatively uncommon in patients with atrial flutter. Post-cardioversion embolism was observed in two patients in our study population.

Aged↗
PubMed2000

Venous thromboembolic disease: an observational study in medical-surgical intensive care unit patients.

PURPOSE: Acute and chronic illness, immobility, and procedural and pharmacologic interventions may predispose patients in the intensive care unit (ICU) to venous thromboembolic (VTE) disease. The purpose of this study was to observe potential risk factors and diagnostic tests for VTE, and prophylaxis against VTE in medical-surgical ICU patients. MATERIALS AND METHODS: In a prospective observational study, 93 consecutive patients admitted to a mixed medical-surgical ICU were followed. We recorded demographics, admitting diagnoses, APACHE II score, VTE risk factors, antithrombotic, anticoagulant and thrombolytic agents, diagnostic tests for deep venous thrombosis (DVT) and pulmonary embolus (PE), and clinical outcomes. RESULTS: Patients were 65.5 (15.5) years old with an APACHE II score of 21.1 (9.0); 44 (47.3%) were female. Admission diagnoses were medical (58, 67.4%) and surgical (35, 37.6%). The duration of ICU stay was 3 days (interquartile range: 1, 8.5 days) and the ICU mortality rate was 20.4% (19 of 93). We observed 8 VTE events among 5 of 93 patients (incidence 5.4% [0.8 to 10.0]); 2 patients had DVT and PE before admission, 1 had DVT as an admitting diagnosis, 1 had DVT on day 2 and PE on day 3, and 1 had PE on day 2. Over 804 ICU patient-days, 2 of 5 ultrasound examinations diagnosed DVT and 2 of 3 ventilation-perfusion lung scans diagnosed PE. Of 64 patients in whom heparin was not contraindicated and who were not anticoagulated, subcutaneous heparin prophylaxis was prescribed for 40 (62.5%) patients. ICU-acquired VTE risk factors were mechanical ventilation (odds ratio [OR] 1.56), immobility (OR 2.14), femoral venous catheter (OR 2.24), sedatives (OR 1.52), and paralytic drugs (OR 4.81), whereas VTE heparin prophylaxis (OR 0.08), aspirin (OR 0.42), and thromboembolic disease stockings (OR 0.63) were associated with a lower risk. Only warfarin (OR 0.07, P =.01) and intravenous heparin (OR 0.04, P<.01) were associated with a significantly decreased risk of VTE. CONCLUSIONS: Several ICU-acquired risk factors for VTE were documented in this medical-surgical ICU. VTE prophylaxis was underprescribed, and VTE diagnostic tests were infrequent. Further research is required to determine the incidence, predisposing factors, attributable morbidity, mortality, and costs of VTE in medical-surgical ICU patients, the optimal diagnostic test strategies, and the most cost-effective approaches of prophylaxis.

APACHE↗
PubMed2003

Surgical thrombectomy: current role in thromboembolic occlusions.

Thromboembolic disease occurs in a heterogeneous group of patients with significant co-morbidities and variable presentations, resulting in high morbidity and mortality rates. To decrease these complications, multiple different endovascular modalities have been developed and used to treat this challenging problem. Physicians are now left with a broad array of endovascular and surgical options. Unfortunately, there are little data that accurately compare these modalities. Therefore, an individual approach to each patient with acute ischemia from thromboembolic disease must be employed. In order to tailor the treatment to the needs of each patient, the physician must be familiar with the techniques, complications, technology, and relative strengths and weaknesses of each treatment modality. This article will first outline the main technical considerations for performing surgical thromboembolectomy. The complications of operative thromboembolectomy will then be discussed followed by the data comparing operative and nonoperative therapy. Finally, clinical scenarios that are best treated by surgical intervention will be described.

Blood Loss, Surgical↗
PubMed2002

Treatment of symptomatic venous thromboembolism: improving outcomes.

Antithrombotic therapy with unfractionated heparin (UFH) and warfarin for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) became widely accepted in the early 1960s. Subsequent clinical trials have focused on the importance of early intravenous UFH in the treatment of venous thromboembolic events, the method of heparin administration, the importance of rapid anticoagulation to prevent recurrent venous thromboembolism (VTE), and the optimal duration of UFH administration. Low-molecular-weight heparin (LMWH) represents a significant advance over UFH therapy for VTE. Developed in the late 1980s, LMWH has become an excellent alternative to UFH because it offers superior efficacy and safety, improved pharmacokinetics, longer half-life, and once- or twice-daily subcutaneous administration without the need for laboratory monitoring. Fondaparinux is the first of a new class of antithrombotic agents that targets factor Xa. Based on studies of the heparin binding site of antithrombin, this novel pentasaccharide has superior pharmacokinetics and bioavailability when compared with LMWH and can be administered once daily. Studies in patients undergoing major orthopedic surgery and in those with proximal DVT indicate that the efficacy and safety of fondaparinux may represent an improvement over those of LMWH.

Double-Blind Method↗
PubMed2002

Unresolved issues in the prevention and treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a major health problem. Anticoagulation can significantly decrease the morbidity and mortality associated with VTE. Heparin and coumarin derivatives have been the standard of care for the last 50 years, and the development of low-molecular-weight heparin preparations has significantly improved the prevention and treatment of venous thromboembolic disease. With these advances, investigators are now able to address some of the unresolved issues in antithrombotic therapy, including the search for the optimal antithrombotic agent in high-risk patients, the optimal timing of thromboprophylaxis initiation in the surgical population, and the duration of prophylaxis for the prevention of initial and recurrent VTE events. Clinical trials have begun to investigate many of these issues, and the resulting data have already contributed to improving the management of patients with a high risk of VTE.

Clinical Trials as Topic↗
PubMed2002

Thromboembolic disease in surgery for malignancy-rationale for prolonged thromboprophylaxis.

Patients undergoing surgery for malignancy are at increased risk of initial and recurrent venous thromboembolism (VTE). Several factors have been found to increase the risk of deep vein thrombosis (DVT) in cancer patients both during the first days after the operation and after discharge from hospital. Although, in general, thromboprophylaxis is provided to cancer patients after surgery, the length of time these patients require prophylaxis has not yet been established. Autopsy series, clinical series, and clinical trials indicate that up to about 40% of VTE occurs post discharge. General surgical patients undergoing major abdominal surgery require VTE prophylaxis, and prolonged thromboprophylaxis should be considered in the post-discharge period in high-risk patients, particularly those with cancer. Evidence from studies in general and orthopedic surgery show that prolonged prophylaxis reduces the number of thromboembolic events after discharge from hospital. Prophylaxis should be simple, safe, and effective and should be administered easily to allow continuation of therapy after discharge. Low-molecular-weight heparins are potentially the most suitable agents for long-term thromboprophylaxis in cancer patients.

Heparin, Low-Molecular-Weight↗
PubMed2002

Venous thromboembolic risk and its prevention in hospitalized medical patients.

In medical patients, the risk of venous thromboembolism (VTE) is substantially underestimated and prophylaxis is used far less than in surgical patients, reflecting the scarcity of evidence supporting antithrombotic therapy in nonsurgical settings. However, current consensus documents recommend assessment of all medical, as well as surgical, patients for thromboembolic risk and provide prophylaxis recommendations according to the risk level, determined by the presence of different clinical and molecular risk factors. Although long-term, underlying clinical and molecular risk factors also have a major impact on overall risk in medical patients; risk clearly varies with the type of medical condition. Myocardial infarction, stroke, and malignant disease are linked to a high rate of VTE; recent evidence highlights patients with cardiopulmonary disease as a distinct risk group. Despite skepticism in some quarters, high-quality evidence confirms the efficacy of unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) in reducing asymptomatic deep vein thrombosis (DVT) in a broad spectrum of medical patients; further studies are required to clarify the effect on fatal pulmonary embolism (PE). Emerging data from the recent PRINCE and MEDENOX studies demonstrate that the LMWH enoxaparin provides effective and well-tolerated VTE prevention in patients with severe cardiopulmonary disease. Emerging evidence has led to a grade 1A recommendation for the use of thromboprophylaxis in these patients in the most recent consensus conference on thromboprophylaxis. Further studies, however, are required to clarify the optimal duration of prophylaxis in medical patients and to evaluate the potential role of outpatient prophylaxis. Accurate risk assessment and prompt implementation of appropriate prophylaxis, selected on the basis of evidence from well-designed controlled clinical trials, may reduce the future morbidity and mortality due to VTE in medical patients.

Clinical Trials as Topic↗
PubMed2003

Rheological abnormalities and thromboembolic complications in heart disease: spontaneous echo contrast and red cell aggregation.

The role of abnormal rheological changes in the pathogenesis of thromboembolism has received much attention in recent years, especially in the field of cardiology. Such changes are sometimes seen in an echocardiogram as a smokelike haze known as spontaneous echo contrast (SEC). The presence and severity of SEC correlate with dilated cardiac chambers and the incidence of thromboembolic complications. It is caused by increased red cell aggregation and increased fibrinogen levels, both of which are known risk factors for thrombosis. Although not used clinically, measurements of red cell aggregation can be made in research settings. This can provide findings that give insight into factors causing increased red cell aggregation. A small series of patients with angina pectoris was studied with the Myrenne aggregometer for red cell aggregation. The results, which show correlation between the plasma fibrinogen and triglyceride levels, are presented. As yet, there are only a few therapeutic guidelines for the correction of abnormally high fibrinogen levels in patients at risk.

Blood Viscosity↗
PubMed2003

Venous thromboembolism in medical patients--the scope of the problem.

The risk of venous thromboembolism (VTE) in medical patients has been substantially underestimated and prophylaxis is used far less than it is in surgical patients, reflecting the scarcity of evidence supporting antithrombotic therapy in nonsurgical settings. Reports of the frequency of deep venous thrombosis (DVT) in general medical patients in the absence of prophylaxis vary from 10 to 26%, depending on the methods used for diagnosis of DVT and the patient population studied. The risk in specific groups may be higher and may exceed that reported in low- or moderate-risk surgical patients. Data from several studies show that DVT developed in approximately 55% of patients with stroke, 24% of patients with myocardial infarction, and, in general medical populations, congestive heart failure, respiratory distress and/or underlying chest infections appeared to increase the risk of VTE. The frequency of VTE in patients with congestive heart failure has been reported to be as high as 40%. In a study among patients in a medical intensive care unit, it was found that 33% had VTE, of which 48% were proximal leg thromboses. Many other medical conditions increase the risk of thromboembolic events. These include malignant disease, which is commonly associated with a hypercoagulable state; inflammatory conditions such as systemic lupus erythematosus and inflammatory bowel disease; coma; and nephrotic syndrome. Accurate risk assessment and prompt implementation of appropriate prophylaxis, selected on the basis of evidence from well-designed, controlled clinical trials, may reduce future morbidity and mortality due to VTE in medical patients.

Adult↗
PubMed2006

Prevention of venous thromboembolism.

Patients with clinical conditions such as surgery, trauma, and acute medical illness have a transiently increased risk of venous thromboembolism and merit consideration for adequate thromboprophylaxis. The choice of an appropriate pharmacologic or physical means of prophylaxis should be made taking into account both the thrombotic and bleeding risk associated with patient-related factors and the type of surgery or other disease state involved. A large number of randomized clinical trials, meta-analyses, and guidelines developed by scientific societies worldwide have addressed this issue and have provided information and recommendations that should be considered carefully. The aim of this review is to provide the practicing physician with a brief updated summary of the subject, stratifying those patients at low thrombotic risk who do not require specific thromboprophylaxis apart from early ambulation, from those at moderate or higher thrombotic risk. Patients at moderate thrombotic risk face a 10 to 20% risk of deep vein thrombosis (DVT) and require prophylaxis with low-dose unfractionated heparin or low molecular weight heparins (LMWHs) at a dosage < 3400 U once daily, or with graduated elastic stockings if their bleeding risk is high. Patients with an expected 20 to 40% DVT rate without prophylaxis are considered at high thrombotic risk and should be treated preferentially with LMWHs at high prophylactic dosage (> 3400 U). Patients undergoing major orthopedic surgery face a DVT rate > 40%, are considered at very high risk of venous thromboembolism, and should be given either LMWHs at high prophylactic dosage, fondaparinux, or vitamin K antagonists--either alone or in association with intermittent pneumatic compression devices.

Anticoagulants↗
PubMed2006

Management of oral anticoagulant treatment in patients with venous thromboembolism.

Oral anticoagulants (OAs) are the drugs of choice for the prevention of recurrence and death in patients with venous thromboembolism (VTE). Oral anticoagulant treatment (OAT) aims to retard blood coagulation to obtain maximum protection against thromboembolic events with the lowest risk of bleeding. The intensity of OAT is ascertained by measuring the prothrombin time (PT), which is expressed as the international normalized ratio (INR). The efficacy and safety of these drugs depends on the ability to maintain the level of anticoagulation as close as possible to the therapeutic target (INR = 2.5) or inside the therapeutic range (INR = 2.0 to 3.0). Given that dosage of oral anticoagulants varies from patient to patient and within the single patient, clinical and laboratory (biological effect of the drug) check-ups must be performed periodically. The management of patients with VTE, as well as that of other patients receiving OAT, includes medical controls and expertise that are better available in specialized centers (anticoagulation clinics).

Administration, Oral↗
PubMed1991

Prevention of thromboembolism after spinal cord injury.

Thromboembolism is a major cause of morbidity and mortality in patients with spinal cord injury. The prevalence of DVT approaches 100%, and 1 to 2% will die of PE. Following injury, there is hypercoagulability as reflected by an increase in von Willebrand factor activity and antigen, and increased platelet reactivity to collagen. Thrombosis usually occurs 1 to 3 weeks after injury, with a peak between days 7 and 9. Intermittent calf compression boots reduce the frequency of thrombosis to 40%, and the addition of aspirin, 300 mg twice daily, and dipyridamole, 75 mg thrice daily, decrease this further to 25%. In an attempt to provide more effective prophylaxis, a further trial was conducted using heparin. Twenty-nine patients were randomized to receive 5000 U subcutaneously every 12 hours and compared with an equal number of patients treated with doses of heparin adjusted to prolong the APTT to 1.5 times control values; the mean dose was 13,200 U every 12 hours. Thromboembolism occurred in 9 (31%) of those on the fixed dose (6 DVT and 3 PE) and only 2 (7%) on the adjusted dose (p less than 0.05); however, 7 (24%) of the patients receiving the higher doses of heparin had bleeding compared with none of those on the fixed dose (p less than 0.02). Most recently, we have compared the safety and effectiveness of a low molecular weight heparin (Logiparin, Novo) with standard heparin. The former was given once daily in a dose of 3500 anti-Xa units, and the latter was 5000 U every 8 hours, both given subcutaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticoagulants↗
PubMed1995

Aortic bioprosthesis without early anticoagulation--risk of thromboembolism.

Anticoagulation after implantation of a bioprosthetic heart valve has been suggested during a high-risk period of 3 months following surgery. There is little information available concerning the risk of thromboembolism during this period if anticoagulation is not carried out. However, this is of interest since 60-80% of all bleeding complications due to anticoagulation occur during the first year of treatment. Between 1983 and 1993, 57 of our patients did not receive oral anticoagulation after implantation of a bioprothesis in the aortic position (49 Hancock, 7 Mitroflow and one Edwards stentless). All patients were investigated retrospectively. A risk for thromboembolic complications of 1.75% is calculated for the first six months following surgery, being 3.5 per 100 patients/year. There seems to be no advantage in standard anticoagulation (INR 2.5-4) with its risk of serious bleeding complications of about 4% during this period of treatment. Low-dose anticoagulation (INR 2.0-2.3), however, preferably in combination with prothrombin estimation by the patients, seems to offer a relatively safe treatment for these patients.

Administration, Oral↗