Accuracy and safety of pretest probability assessment of deep vein thrombosis by physicians in training using the explicit Wells clinical model.
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Biomedical subjects
Publications and source records attributed to J C Wautrecht.
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Testing for laboratory evidence of thrombophilia is now common but it has limited predictive value for the majority of unselected symptomatic patients. So when is testing indicated ? And which one? The term "thrombophilia" describes disorders of the haemostatic mechanisms which are likely to predispose to thrombosis. Thrombophilia may be heritable, acquired or mixed, resulting of the environment interacting with genetic background. To date, a limited number of genetic variants and other defects are proven to be independent risk factors for venous thromboembolism. These include antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden, the prothrombin gene mutation, hyperhomocysteinemia and antiphospholipid antibodies. There is no good evidence currently available to support the hypothesis that heritable thrombophilias increase the risk of arterial disease. But acquired or mixed thrombophilias such as hyperhomocysteinemia and antiphospholipid antibodies have been found in association with both venous and arterial thrombotic disorders. When testing for thrombophilia is indicated, especially in case of venous thromboembolism, it should include assays for heritable, mixed or acquired defects: deficiency of antithrombin, protein C or protein S, factor V Leiden and prothrombin G20210A mutations, elevated factor VIII, hyperhomocysteinemia and for antiphospholipid antibodies. Depending on the site of venous thrombosis, laboratory testing to exclude myeloproliferative disorders should be performed.
Atherothrombosis is a common physiopathologic process resulting in morbid or fatal ischemic events affecting the cerebral, coronary, or peripheral arterial circulation. Antiplatelet agents are effective in preventing recurrence of vascular events among patients with established vascular disease or with multiple risk factors. Aspirin was the most widely studied antiplatelet drug but the optimal dose remains difficult to define. This article summarizes new data on antiplatelet agents including aspirin, clopidogrel, dipyridamole and glycoprotein IIb/IIIa antagonists with the aim of giving practical recommendations in this very moving field of therapy.
Anticoagulants used in daily practice include low molecular weight heparins (LMWHs) and vitamin K antagonists. LMWHs are easy to use by means of adjusted subcutaneous injection, weight-adjusted in case of therapeutic indications. LMWHs are cleared principally by the renal route and are contra-indicated in case of renal insufficiency. The LMWHs are indicated in the prevention and treatment of venous thromboembolism. They can be safely administered in pregnancy and during breast-feeding. Oral anticoagulant therapy is the treatment of choice for long term management. Vitamin K antagonists are contra-indicated in pregnancy, especially between the 6th and the 12th week of gestation (risk of embryopathy); they can be given during breast-feeding subject to some precaution. Main indications for vitamin K antagonists are long term treatment of venous thromboembolism, prevention of both arterial and venous thrombo-embolic events associated with the antiphospholipid--antibody syndrome, prevention of systemic embolism associated with heart valves and, rheumatic mitral valve disease and, atrial fibrillation and, acute myocardial infarction.
The antiphospholipid syndrome (APS) defines the clinical association between antiphospholipid antibodies and a syndrome of hypercoagulability or thrombophilia (the term of "sticky blood" is sometimes used in APS). Antiphospholipid antibodies comprise a broad family of antibodies including both lupus anticoagulants and anticardiolipin antibodies. The pathogenesis of APS remains unclear. Nevertheless, an understanding of the biology, clinical and laboratory diagnosis, and clinical manifestations of APS are important to the neurologist because the brain is commonly affected by the disease. These points are addressed herein focusing on neurological manifestations of APS. Treatment of APS of which anticoagulation is the cornerstone is also discussed.
The Department of Vascular Diseases can be defined as a multidisciplinary integrated clinical entity involving internists and surgeons interested in patient care, education and research in the field of arterial, venous and lymphatic diseases. Because of the increasing medical complexity with the proliferation of treatment options available, the combined expertise of specialists from different training background is required to provide the optimal patient management. The truly integrated entity with interactions on daily basis between internists and surgeons also provides opportunities for improvement in the training of fellows in vascular medicine. Basic and clinical research is focused on thrombosis and atherosclerosis. The main topics that have been developed include: the pathophysiology of thrombosis, atherogenesis and the diagnosis and treatment of venous thromboembolic disease. The successful development of our Department demonstrates that the combined expertise of internists and surgeons has resulted in marked improvement in the efficiency of patient management.
OBJECTIVE: To determine the nature of and to compare the inflammatory responses induced by (1) endovascular and (2) conventional abdominal aortic aneurysm (AAA) repair. MATERIAL AND METHODS: Twelve consecutive patients undergoing elective infrarenal AAA repair were prospectively studied. Seven patients were selected for endovascular procedures (the EAAA group); five patients underwent open surgery (the OAAA group). Three control patients undergoing carotid thromboendarterectomy were also included. Serial peripheral venous blood samples were collected preoperatively, immediately after declamping or placement of the endograft, and at hours 1, 3, 6, 12, 24, 48, and 72. Acute phase response expression of peripheral T lymphocyte and monocyte activation markers and adhesion molecules (flow cytometry), soluble levels of cell adhesion molecules (enzyme-linked immunosorbent assay), cytokine (tumor necrosis factor alpha, interleukin-6, and interleukin-8) release (enzyme-linked immunosorbent assay), and liberation of complement products (nephelometry) were measured. RESULTS: Regarding acute phase response, the EAAA and OAAA groups showed significant increases in C-reactive protein (P <.001 and P =.001), body temperature (P =.035 and P =.048), and leukocyte count (P <.001 and P <.001). Similar time course patterns were observed with respect to body temperature (P =.372). Statistically significant different patterns were demonstrated for C-reactive protein (P =.032) and leukocyte count (P =.002). Regarding leukocyte activation, a significant upregulation of peripheral T lymphocyte CD38 expression was observed in the OAAA group only (P =.001). Analysis of markers such as CD69, CD40L, CD25, and CD54 revealed no perioperative fluctuations in any group. Regarding circulating cell adhesion molecules, the EAAA and OAAA groups displayed significant increases in soluble intercellular adhesion molecule-1 (P =.003 and P =.001); there was no intergroup difference (P =.193). All groups demonstrated high soluble von Willebrand factor levels (P =.018, P =. 007, and P =.027), there being no differences in the patterns (P =. 772). Otherwise, soluble vascular cell adhesion molecule-1, soluble E-selectin, and soluble P-selectin did not appear to vary in any group. Regarding cytokine release, although a tendency toward high tumor necrosis factor alpha and interleukin-8 levels was noticed in the EAAA group, global time course effects failed to reach statistical significance (P =.543 and P =.080). In contrast, interleukin-6 showed elevations in all groups (P =.058, P <.001, and P =.004). Time course patterns did not differ between the EAAA and OAAA groups (P =.840). Regarding complement activation, the C3d/C3 ratio disclosed significant postoperative elevations in the EAAA and OAAA groups (P =.013 and P =.009). This complement product release was reduced in the EAAA group (P <.001). CONCLUSIONS: The current study indicated that both endovascular and coventional AAA repair induced significant inflammatory responses. Our findings showed that there were no large differences between the procedures with respect to circulating cell adhesion molecule and cytokine release. Moreover, the endoluminal approach produced a limited response in terms of acute phase reaction, T lymphocyte activation, and complement product liberation. This might support the concept that endovascular AAA repair represents an attractive alternative to open surgery. Given the relatively small sample size, further larger studies are required for confirmation of our observations.
BACKGROUND: Total plasma homocysteine (tHcy) is an independent risk factor for cardiovascular disease in adults. Data for children and adolescents are lacking. OBJECTIVE: The aim of this study was to provide a reference range for tHcy and to explore the relation between tHcy and nutritional indexes in a Belgian pediatric population. DESIGN: tHcy, folate, and vitamin B-12 were measured in 647 healthy children (353 girls and 294 boys) aged 5-19 y. RESULTS: The tHcy distribution was, as in adults, skewed to the right [geometric mean (-1 SD, +1 SD): 7.41 micromol/L (5.51, 9.96)]. Concentrations were lowest in younger children and increased with age. After the tHcy distribution was examined according to age, 3 age ranges were distinguished: 5-9 y [6.21 micromol/L (5.14, 7.50)], 10-14 y [7.09 micromol/L (5.69, 8.84)], and 15-19 y [8.84 micromol/L (6.36, 12.29)]. We observed no significant differences in tHcy values between girls and boys in children aged < 15 y; in postpubertal children, however, concentrations were higher in boys than in girls. In the 3 age groups, folate was inversely correlated with tHcy; the negative relation between tHcy and vitamin B-12 was less strong. Familial cardiovascular disease was more frequent in children who had hyperhomocysteinemia. CONCLUSIONS: These observations suggest that in children, as in adults, genetic, nutritional, and endocrine factors are determinants of the metabolism of homocysteine. The significance of tHcy values in childhood and young adulthood in terms of predicting cardiovascular risk in adulthood should be investigated.
Effort-linked intermittent claudication of arterial origin in sportsmen is often attributed to endofibrosis of the external iliac artery. Some knowledge of possible differential diagnoses, in particular the fibrodysplasia, is of importance regarding the therapy involved. Angioplasty treatment of external iliac endofibrosis may be controversial. However, the same does not apply to fibrodysplasia angioplasty, particularly if the latter is accomplished by inserting an endoprothesis. A case of fibromuscular dysplasia of external iliac artery in a 37 year old woman, treated with endoluminal angioplasty and stent, is reported.
PURPOSE: To describe an exclusion endoluminal technique for management of abdominal aortic aneurysms among high-risk patients with complex anatomic features. METHODS: From January 1995 to December 1996, among 143 patients with infrarenal abdominal aortic aneurysm treated by means of endograft placement, 9 (6.3%) had complex aortic or aortoiliac morphologic features. For these patients, the endograft was delivered through a femoral cutdown in an occluding aortoiliac configuration. The contralateral iliac artery was occluded with an iliac endograft. Axillofemoral bypass grafting was performed. Computed tomographic scans were obtained regularly. RESULTS: There was 1 postoperative death of severe arrhythmia. All aneurysms were found to be affected by thrombosis on immediately postoperative computed tomographic scans, except in 1 patient with a proximal leak, which was managed successfully with angiographic embolization. The mean follow-up time was 12 months. Aortic aneurysm diameter decreased from 2 mm at 6 months (2 patients) to 6 mm at 12 months (6 patients). All axillofemoral bypass grafts are patent. CONCLUSIONS: Placement of an occluding endograft associated with axillofemoral bypass grafting is a good alternative for patients at high risk with complex anatomic features. Longer-term follow-up study is needed to evaluate this endoluminal technique.
We describe the case of a patient with adventitial cystic disease of the popliteal artery in which a direct anatomic communication between the cysts and the nearby knee joint was demonstrated by magnetic resonance imaging and confirmed by surgery. This unusual observation could shed some light on the much debated question of the cause, the pathogenesis, and the management of the affection. Moreover, it emphasizes the importance and the role of magnetic resonance imaging in the diagnosis of adventitial cystic disease of the popliteal artery.
A qualitative (Instantia) and a quantitative (VIDAS D-Dimer) D-Dimer test have been evaluated and compared with an ELISA method (Asserachrom D-D) in a population of 74 patients suspected of presenting a deep vein thrombosis. Among the thirty-two patients presenting a deep vein thrombosis on phlebography, there were 16 (50%) proximal vein thrombosis and 16 (50%) distal vein thrombosis. Sensitivity and negative predictive value for proximal thrombosis were 100% in all three tests. For distal vein thrombosis, sensitivity and negative predictive value were respectively 81% and 81% for Asserachrom D-DI 75% and 76% for VIDAS D-Dimer and 63% and 82% for Instantia. In conclusion, this study shows that these D-Di assays are a useful tool to exclude proximal vein thrombosis, at least for patients who are not under anticoagulant therapy.
Cerebral venous thrombosis is a polymorphic clinical entity for which diagnosis has become more frequent with the advent of neuroradiology. The superior sagittal and transverse sinuses are frequently involved, whereas cavernous sinus thrombosis is much less frequent. Inherited resistance to the anticoagulant action of activated protein C (APC resistance), antithrombin deficiency, protein C and S deficiencies, and hyperhomocysteinemia seem to represent major causes of thrombophilia when unusual thromboembolic events (ie, before the age of 45 years) are observed. The authors present the combined occurrence of protein C and protein S deficiencies in a 32-year-old woman, manifested by extensive cerebral venous thrombosis.
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INTRODUCTION: The question of the role of season as a predisposing factor for development of venous thromboembolic disease still remains a matter of debate. Actually, most reports described a higher incidence of thrombotic disorders in winter, while a recent study showed no seasonal variation in the incidence of deep vein thrombosis (DVT). These data led us to study the seasonal distribution of all outpatients with DVT admitted to our Department over a period of 14 years. METHODS: Retrospective review of the files of all outpatients with confirmed (venography or ultrasound) DVT of the legs admitted from Jan. 1st 1982 to Dec. 31st 1995 (n = 512; mean age 59.4 years; 49.4% women). RESULTS: DVT occurred in spring in 135 (26.4%), in summer in 104 (20.3%), in autumn in 142 (27.7%) and in winter in 131 (25.6%) patients. This distribution appears to be similar to an expected uniform distribution [chi 2(3) df = 6.48; p = 0.090 (NS)]. CONCLUSIONS: In our study, by investigating retrospectively 512 outpatients with confirmed DVT, no correlation was found between season and development of thrombosis, suggesting that cold seasons do not represent a predisposing factor for DVT. Further large prospective studies are needed in order to validate our data and to investigate the clinical implications and the precise role of the season in the risk of occurrence of venous thrombosis.
Any surgical procedure is followed by an inflammatory reaction, associated with arteriolar dilatation and increased capillary permeability. The normal evolution is in most cases a progressive decrease of the inflammatory signs. Some patients however, particularly after orthopedic trauma affecting the extremities, develop algodystrophy, initially characterized by arterial vasodilatation and low capillary flow. In an effort to better understand the normal phenomena seen after uncomplicated hand surgery, the authors have evaluated the postoperative arterial blood flow using the Duplex flowmetry ultrasound technique in 13 patients operated for carpal tunnel syndrome, who did not subsequently develop algodystrophy. After measurement of the transverse section of the ulnar and radial arteries, and longitudinal measurement of the mean velocimetry, the arterial blood flow was calculated. The measurements were done 1, 2 and 4 weeks after the operative procedure. The study demonstrated a moderate (15%-30%) but significant increase in the arterial blood flow to the hand, related to arterial dilatation of the vessels and to an increase in blood velocimetry.
CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. DESIGN: Case-control study. SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. RESULTS: The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.
Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown etiology, often associated with various systemic disorders such as inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis, diabetes mellitus and hematologic malignancies. The ulcers are characterized by their undermined violaceous borders. The disease remains a therapeutic challenge. Corticosteroids are the mainstay of therapy; however, side effects from this treatment and recalcitrant pyoderma gangrenosum require therapeutic alternatives. We report the case of a large subacute pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and successfully treated by an autograft. This observation supports the opinion that the risk of pathergy of a graft can be avoided by the stabilization of the disease.