Validation of a diagnostic approach to exclude recurrent venous thromboembolism

Summary.  Introduction:  The diagnosis of recurrent venous thromboembolism (VTE) is a challenge in clinical practice. Our objective was to evaluate the safety of a diagnostic strategy utilizing comparison of diagnostic test results with baseline imaging results to rule out suspected recurrent VTE. Methods:  The REVERSE study was a prospective cohort study whose primary aim was to develop a clinical prediction rule for recurrent VTE. We included and followed patients who completed 5–7 months of anticoagulant therapy after a first unprovoked VTE. Suspected cases of recurrent VTE were assessed according to standardized diagnostic criteria based on comparison of diagnostic test results with those obtained at the time of anticoagulant treatment withdrawal. Results:  Out of the 398 suspected events, a recurrent VTE was diagnosed in 106 cases (26.6%) and excluded in 292 cases. In 76 cases (19%), the diagnosis of recurrent VTE was excluded on the basis of the fact that no significant change on diagnostic imaging was detected when compared to baseline imaging. During the ensuing 3 months, six patients received anticoagulant therapy after recurrent VTE was excluded, and two were lost to follow-up. Eight of 284 remaining patients in whom recurrent VTE had been excluded, who were not treated and who were not lost to follow-up were diagnosed with subsequent VTE (3-month risk, 2.8%; 95% confidence interval, 1.4–5.5%). Six of these eight patients with subsequent recurrent VTE had a known superficial or distal thrombosis at the time of initial suspected recurrent VTE. Conclusion:  A diagnostic strategy comparing diagnostic test results obtained at the time of the suspected recurrent event with those obtained at baseline can safely and effectively rule out recurrent VTE in a significant proportion of patients. Registered at http://www.clinicaltrials.gov identifier: NCT00261014.     

Diagnosis and management of venous thromboembolism

Venous thromboembolic disease is a common disease associated with significant morbidity and mortality. Accurate and timely diagnosis should be guided by the use of validated clinical prediction rules. The mainstay of therapy is anticoagulation, although alternative approaches, such as use of concurrent thrombolysis or placement of vena caval filters, may be appropriate in selected patients. Determination of duration of anticoagulation requires a detailed assessment of the risk factors associated with the event allowing estimation of recurrence risk, and careful assessment of bleeding risk. Although extremely effective, anticoagulants have a narrow therapeutic window; systems should be in place to reduce risk of adverse events associated with these agents.     

Cancer and venous thromboembolism: a multidisciplinary approach

In this paper, we briefly review the relation between cancer and venous thromboembolism (VTE), an association that has been recognized for more than a century. In particular we focus on VTE as predictor and prognostic factor for cancer and the antineoplastic potential of antithrombotic treatment. Cancer may cause disturbances in the haemostatic system by numerous mechanisms that can lead to an increased risk of VTE. Patients with known cancer are at increased risk of VTE; however, VTE may also be a predictor of subsequent cancer in the years afterwards. Furthermore, cancer patients with VTE are more likely to have advanced disease and a worse prognosis than cancer patients without a VTE episode. These findings may have implications for the clinical care of patients with VTE in terms of screening for cancer. However, extensive cancer screening programs are not recommended in general for patients with VTE. A wide range of antithrombotic drugs including heparin, oral anticoagulants, and platelet inhibitors have been examined in order to study the effect on the prevention and treatment of various cancers. These efforts have resulted in a considerable amount of useful data from animal models and a number of promising reports from retrospective analyses and small-scale trials linking antithrombotic treatment with an increased survival in cancer patients and even a lower risk of primary cancer. However, the clinical implications of these findings must await properly designed and conducted randomized clinical trials.     

Diagnosis and treatment of recurrent venous thromboembolism

The diagnosis of recurrent venous thromboembolism includes an evaluation of the patient for inherited or acquired disorders, associated with an increased risk of thromboembolism. Treatment depends, in part, on the underlying disease and, in part, on an adequate understanding of the principles of anticoagulant therapy.     

A need for a simplified approach to venous thromboembolism prophylaxis in acute medical inpatients

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the UK. Studies have shown that pulmonary embolism causes or contributes to approximately 1 in 10 hospital deaths of medical patients admitted to general hospitals in the UK (Lindblad B, Sternby NH, Bergqvist D. BMJ 1991; 302: 709-11), with pulmonary embolus being the most common preventable cause of hospital death. Thromboprophylaxis is safe, highly effective and cost effective, but despite various current clinical guidelines, physicians fail to prescribe prophylaxis for the majority of medical inpatients at risk of VTE. This article outlines the current evidence for VTE prophylaxis in medical patients and discusses the reasons behind the insufficient use of prophylaxis in the acute medical setting.     

Familial segregation of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is postulated as a complex disease, but the heritability and mode of inheritance are uncertain. OBJECTIVE: To determine if VTE (i) segregates in families; (ii) is attributable to inheritance, shared environment, or both; and (iii) the possible mode of inheritance. PATIENTS AND METHODS: In a family-based study of relatives from 751 probands (60% female) with objectively diagnosed VTE (without cancer), we performed complex segregation analyses corrected for mode of ascertainment, considering age-specific, non-gender- and gender-specific liability classes under Mendelian and non-Mendelian assumptions. We tested 12 models categorized into four model sets: (i) sporadic (assumes no genetic effect); (ii) Mendelian inheritance of a major gene (including dominant, additive, recessive or codominant classes); (iii) mixed model (Mendelian inheritance including the same four classes plus the effect of polygenes); and (iv) non-Mendelian. RESULTS: Among the 16 650 relatives, 753 (48% female) were affected with VTE, of whom 62% were first-degree relatives. The sporadic model was rejected in both non-gender- and gender-specific liability class analyses. Among the remaining gender-specific models, the unrestricted (non-Mendelian) inheritance model was favored with an estimated heritability of 0.52. Among the Mendelian models, the dominant mixed model was preferred, with an estimated heritability and major disease allele frequency of 0.62 and 0.25, respectively, suggesting an effect of several minor genes. CONCLUSION: A multifactorial non-Mendelian inheritance model was favored as the cause for VTE, while a model postulating a purely environmental cause was rejected. VTE is probably a result of multigenic action as well as environmental exposures.     

The influence of venous thromboembolism on quality of life and severity of chronic venous disease.

BACKGROUND: It is not known whether burden-of-illness differs in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. OBJECTIVE: To compare severity of disease and quality of life in chronic venous disease patients with and without prior venous thromboembolism. PATIENTS and METHODS: The VEINES Study population is an international cohort of 1531 outpatients with chronic venous disease in Belgium, France, Italy and Canada. Clinical severity of chronic venous disease graded using the seven-category 'CEAP' scale, and quality of life using standardized generic (SF-36) and venous disease-specific (VEINES-QOL/Sym) questionnaires were compared in patients with and without venous thromboembolism. Multivariable analyses with adjustment for known confounders were used to examine associations between venous thromboembolism and quality of life. RESULTS: One hundred and fifty-one (10%) patients had prior venous thromboembolism. These patients had more severe chronic venous disease than those without venous thromboembolism (P <0.0001), including a higher frequency of healed or active ulcers (29% vs. 7%, respectively). Multivariable analyses controlling for age, sex, country, education, body mass index, years of chronic venous disease and comorbid conditions demonstrated that prior venous thromboembolism was an independent predictor of poorer generic quality of life (SF-36 Mental Component Summary score, P=0.047; SF-36 Physical Component Summary score, P=0.012) and venous disease-specific quality of life (VEINES-QOL, P = 0.0002; VEINES-Sym, P=0.009). CONCLUSIONS: Disease severity is worse and quality of life poorer in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. Our findings support the need for further research of interventions to prevent and treat the long-term complications of venous thromboembolism.     

Perioperative cardiovascular evaluation. Step-by-step approach to risk assessment and follow-up care

One of the integral responsibilities in primary care medicine is medical consultation, especially when a surgical procedure is contemplated. A good grasp of the elements of multiple specialties and an understanding of the complexity of a proposed operation are essential for an appropriate preoperative evaluation. This article covers the steps in assessing cardiovascular risk in candidates for noncardiac surgery, including consideration of patient-specific and surgery-specific factors. The authors also recommend close postoperative follow-up to reduce morbidity and mortality.     

Prophylaxis and therapy of venous thromboembolism.

Heparin is an anticoagulant drug which is used for the prophylaxis and treatment of venous thromboembolism and for the treatment of some cases of arterial thromboembolism. Venous thromboembolism is the commonest preventable cause of death in hospitalized patients, and the best approach to reduce its morbidity and mortality is the use of safe, effective, prophylaxis in patients at high risk. The use of low doses of heparin given s.c. (5000 units, 8 hourly)) has been shown in prospective clinical trials to be effective prophylaxis against venous thrombosis and nonfatal and fatal pulmonary embolism in patients undergoing general abdominothoracic surgery, without producing dangerous bleeding. Low-dose heparin, however, is not totally effective in patients undergoing hip surgery and suprapubic prostatectomy. The lack of benefit in these patients may be related to the intensity of the provocation to thrombosis. The use of heparin in large doses to treat thrombosis is associated with hemorrhagic complications in up to 30% of patients. There is evidence that continuous i.v. heparin is associated with fewer hemorrhagic complications than intermittent i.v. heparin, but the frequency is not related to the dose or to the use of laboratory monitoring. Hemorrhagic complications occur more frequently in elderly patients and in females and is more common following surgical operations. The frequency of recurrent venous thromboembolism is low in patients on therapeutic doses of heparin, and there is no difference in the frequency of recurrence in patients receiving heparin by continuous i.v. or intermittent i.v. administration.     

Action to reduce incidence of venous thromboembolism

Despite the availability of well-known and effective prophylactic measures, between 25,000 and 32,000 people in England each year contract a fatal venous thromboembolism while in hospital. This article highlights concerns raised by the House of Commons inquiry into this problem and outlines the Departments of Health's response.