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PubMed1998

Venous thromboembolism and cancer.

BACKGROUND: Although cancer has been clearly associated with venous thromboembolism (VTE), many aspects of this relation are poorly understood, including the cancer sites most affected and the cancer risk during long-term follow-up. To clarify these relations, we carried out a large, population-based analysis of VTE and cancer risk. METHODS: Using the Swedish Inpatient Register and linkage to the nationwide Cancer Registry, we assessed cancer incidence during 1989 among 61,998 patients without a previous cancer diagnosis admitted to hospital between 1965 and 1983 for VTE. To measure possible increases in cancer risk, we computed standardised incidence ratios (SIRs) using Swedish national cancer rates for the period of the study. FINDINGS: At the time of thromboembolic admission or during the first year of follow-up, 2509 cancers were diagnosed (SIR 4.4, 95% CI 4.2-4.6) [corrected]. The SIR for polycythaemia vera was 12.9 (8.6-18.7), and the SIRs for cancers of the liver, pancreas, ovary, and brain, and for Hodgkin lymphoma also exceeded 5.0. Patients aged less than 65 years had higher SIRs than those who were older. In subsequent years, 6081 cancers were diagnosed (1.3, 1.3-1.3). Even 10 years or more after admission to hospital with VTE, cancer incidence had increased (1.3, 1.3-1.4). INTERPRETATION: At the time of VTE or in the first year afterwards, we found a large increase in the risk for diagnosis of virtually all cancers. In subsequent years, a persistent 30% increase in risk remains. Either premalignant change promotes thrombosis, or cancer and thrombosis share common risk factors.

Cohort Studies↗

PubMed2001

Experimental thromboembolic stroke in cynomolgus monkey.

To develop an experimental model of thromboembolic stroke without intracranial surgery, an autologous blood clot was delivered to the middle cerebral artery (MCA) via the internal carotid artery in cynomolgus monkeys. Male cynomolgus monkeys, in which a chronic catheter had been earlier implanted in the left internal carotid artery, were used. The clot was flushed into the internal carotid artery under sevofluorane anesthesia. A neurologic deficit score was assigned after MCA embolization. After 24 h, cerebral infarct size and location were determined by the TTC staining method. Cerebral blood flow (CBF) was measured prior to and after MCA embolization, using positron emission tomography (PET). After embolization, long-lasting and profound extensor hypotonia of the contralateral upper and lower limbs, and mild to severe incoordination were observed. Contralateral hemiplegia was observed over the following 24 h. In gross morphologic observation of the brain, the lesions involved mostly the caudate nucleus, putamen, globus pallidus and insular cortex. CBF was maximally reduced in the left MCA territory, but not in the right MCA territory. This model is relevant to thromboembolic stroke in human in neurologic dysfunction and histopathologic brain damage.

Animals↗

PubMed2003

Plasma D-dimer for the diagnosis of thromboembolic disorders in dogs.

D-dimer is formed during thrombus formation when factor XIIIa crosslinks the terminal D-domains of fibrin. The D-dimer epitope is exposed when the thrombus is lysed by plasmin. Thus, D-dimer represents both thrombin and plasmin activation and is specific for fibrinolysis. D-dimer concentrations are increased in dogs with DIC or other thromboembolic disorders, but because D-dimer is an indicator of physiologic or pathologic fibrinolysis, values are elevated in other conditions associated with fibrinolysis, including orthopedic surgery, neoplasia, and internal hemorrhage. It can be used as an ancillary test for the diagnosis of DIC but is not recommended as a sole test for this purpose. D-dimer has the potential to be a useful laboratory test for the detection of pulmonary thromboembolism in dogs. Further studies are needed to determine the appropriate applications for this test in veterinary patients to aid in clinical decision making, treatment, and patient care.

Animals↗

PubMed1993

[Treatment of venous thromboembolic disease in patients with cancer].

Results of classical anticoagulant therapy in cancer patients with venous thromboembolism (VT) are highly discussed. We retrospectively analysed the outcome of 43 patients with VT and cancer: 32% developed specific complications during either i.v. heparin therapy (10 +/- 0.9 days) or treatment by antivitamin K (106 +/- 14.9 days). Recurrence of thromboembolism (16%) and/or hemorrhages (16%) were much more frequent than in patients without cancer, underlying need for alternative therapy in cancer patients with VT.

Female↗

PubMed1997

[Cost of low molecular weight heparin used in the prevention or therapy of thromboembolic disease].

Low-molecular-weight heparin are widely used for prophylaxis or curative treatment of thromboembolic disease. In France, low molecular weight heparin can only be used for the surgical prophylaxis (general and orthopaedic) of thromboembolic disease, for the initial treatment of deep vein thrombosis and in haemodialysis. In an economic approach we try to assess costing information which takes account of drug acquisition costs but also costs of drug administration and costs of drug therapy failure (failed prophylaxis, bleeding and recurrent thrombosis). At least, it has been argued that low molecular weight heparin may take it possible to discharge patients earlier and even to treat patients at home or as out-patients, thus creating further cost savings.

Cost Control↗

PubMed2002

The use of low-molecular-weight heparin for the management of venous thromboembolism in pregnancy.

Thromboembolic disease is a rare, but important, complication of pregnancy that remains a leading non-obstetric cause of maternal death. The prevention and management of venous thromboembolism (VTE) in pregnant women is a complex area of medicine: a balance must be found between protecting the health of the mother and minimizing the risk to the unborn fetus. Until now, unfractionated heparin has been regarded as the drug of choice for the prevention and treatment of VTE during pregnancy. However, because of its significant side effects (osteoporosis and heparin-induced thrombocytopenia), the inconvenient mode of administration and need for monitoring, unfractionated heparin is now being replaced by low-molecular-weight heparin (LMWH). There is a convincing body of clinical evidence from well-designed studies and prospective case series that supports the efficacy and safety of LMWH in pregnant women. There are also encouraging observations on the efficacy of LMWH in the prevention of severe obstetric complications, which are frequently associated with inherited or acquired thrombophilias. The recently-published guidelines of The American College of Chest Physicians (ACCP), summarized in this review, allows the development of higher clinical standards. However, there is concern over the greater cost of LMWH compared with unfractionated heparin and oral anticoagulants, and cost-effectiveness studies are needed.

Abortion, Habitual↗

PubMed2002

Cancer and thromboembolic disease: how important is the risk of thrombosis?

The overall incidence of postoperative DVT in patients with cancer is twice as high as in cancer-free patients. Immobilisation and chemotherapy increase the risk of thrombosis as does the insertion of central venous lines. Patients with cancer who have established thrombosis exhibit a remarkably high risk of recurrent thromboembolism, particularly in the first months after the interruption of anticoagulant treatment: the risk is double that of non-cancer patients. Even during anticoagulant treatment, the cumulative incidence of recurrent thromboembolism is 3.5 times higher in patients with malignancy than in cancer-free patients. Conversely, there is a high rate of cancer detection in patients with idiopathic VTE: the risk of concomitant cancer is approximately four times higher in these patients than in those with thrombosis triggered by known factors. Extensive screening for cancer in patients with idiopathic venous thrombosis allows early detection of malignancies and identification of malignancy at an early stage.

Comorbidity↗

PubMed2004

[Therapeutic education of patients receiving anticoagulants for thromboembolic venous disease: description of the Educ'AVK program].

Educ'AVK is an education program designed for patients starting an oral anticoagulant treatment following a thromboembolic event (deep venous thrombosis or pulmonary embolism). Patients enrolled are judged capable of self-management of their drug treatment. The intervention, adapted to a short-term treatment, consists in an 3-step one-on-one teaching session conducted by a trained pharmacist. 1) Identification of the patient's needs--or educational diagnosis. 2) Definition of educational objectives adapted, first, to the patient's cognition: to be able to describe indications for therapy and potential risks factors for anticoagulant bleeding, to interpret INR lab tests and to solve a problematic treatment situation related second, to the patient's behaviour: to be able to anticipate the risk (how to enhance compliance, how to deal with a missed dose.), to take relevant decisions when dealing a therapeutic incident (bleeding, INR outside of the targeted range). 3) Choice of appropriate teaching contents and methods to reach the objectives. We used the "individual guidance" technique associated with original tools: a picture book to describe the pathology and the treatment; a booklet synthesizing all the information given by the educator during the consultation. This booklet presents 3 key-points: the information is specifically targeted to thromboembolic venous disease; the information integrates the risk-level of the patient (3 different booklets according to the patient's level of risk, of bleeding, of thromboemboly, no specific risk); there is a section where the patient writes down his/her INR results in a table specifically adapted to his/her risk level--bleeding, thromboemboly, no specific risk--and giving recommendations for the management of INR out of the targeted range.

Anticoagulants↗

PubMed1998

Venous thromboembolic events in pediatric patients. Diagnosis and management.

Venous thromboembolism is a rapidly increasing secondary complication in children being treated for serious, life-threatening, primary diseases. Most current management guidelines and recommendations for imaging techniques have been extrapolated from the results of trials in adults. This may be less than optimal for children as there are important differences. The purpose of this article is to summarize the information on venous thromboembolism in children, and offer some guidelines for diagnosis, prophylaxis, and therapeutic intervention based on the best available evidence.

Adolescent↗

PubMed2000

Oral contraceptive pills and hormonal replacement therapy and thromboembolic disease.

The risk of thromboembolic complications with the use of second and third generation oral contraceptives is minimal and probably related to underlying congenital or acquired thrombophilic states. Estrogen dose-dependency leads to increased thrombin generation and increased plasmin generation. There is no convincing evidence that the balance between clotting and fibrinolysis is disturbed. The risk of venous thromboembolism with pregnancy is greater than with oral contraceptives. Hormone replacement therapy is safe for healthy women, and the benefits far outweigh the potential risks.

Contraceptives, Oral↗

PubMed2003

Venous thromboembolism and cancer: new issues for an old topic.

Thromboembolic complications represent the second leading cause of death for cancer patients. Even though the correlation between cancer and a hypercoagulable state has been widely recognised, the pathogenesis of thromboembolism during malignancy is not yet entirely understood. The direct or indirect activation of the coagulation cascade favours neoplastic dissemination and metastasis. Disordered coagulation is encountered in up to 90% of cancer patients, although only 15% of them develop a localised acute or chronic deep venous thrombosis or a disseminated intravascular coagulation. This risk is significantly increased by chemotherapy, hormone therapy, surgery and central venous catheters. Therefore, much effort is needed to develop efficient prophylaxis and treatment, to reduce recurrence and bleeding and finally, to improve quality of life. Better knowledge about the biochemical bases of the coagulation process represents a pivotal step in cancer biology comprehension and global therapeutic management.

Antineoplastic Agents↗

PubMed2001

Thromboembolism complicating thrombin injection of femoral artery pseudoaneurysm: management with intraarterial thrombolysis.

Ultrasound (US)-guided compression of pseudoaneurysms is being rapidly replaced by US-guided percutaneous treatment with thrombin injection because of the less intensive nature of this procedure. Thromboembolism after percutaneous treatment with thrombin injection is rare and has been described in brachial artery pseudoaneurysms. These were managed with intravenous administration of heparin and surgical thrombectomy. In this report, the authors describe thromboembolic complication of thrombin injection after treatment of a femoral artery pseudoaneurysm. This was managed by intraarterial thrombolysis with use of recombinant tissue plasminogen activator (rt-PA) with resolution of all major occlusive changes. A lower dose of thrombin injection and frequent postprocedural monitoring of distal pulses is recommended.

Aged↗

PubMed2003

Prevention of venous thromboembolism in pregnancy.

Pulmonary thromboembolism, rising from deep venous thrombosis (DVT), is a major cause of maternal death in the developed World. DVT is a significant source of morbidity in pregnancy and the puerperium with long-term sequelae such as post-thrombotic syndrome. The major risk factors for venous thromboembolism (VTE) are: increasing age, particularly over 35 years; operative vaginal delivery; Caesarean section, especially emergency Caesarean section in labour; high body mass index; previous VTE, especially if idiopathic or thrombophilia-associated; thrombophilia; and a family history of thrombosis suggestive of an underlying thrombophilia. Thromboprophylaxis centres largely on the use of low-molecular-weight heparin (LMWH). LMWHs, such as enoxaparin and dalteparin, have substantial clinical and practical advantages compared with unfractionated heparin, particularly in terms of improved safety with a significantly lower incidence of heparin-induced osteoporosis and thrombocytopenia. Such agents should be used in women with significant risk factors for VTE both antenatally and post-partum.

Female↗

PubMed2003

Arterial thromboembolism in pregnancy.

Arterial occlusion resulting from primary thrombus formation in an artery or due to embolization from a site elsewhere in the circulation is uncommon in women of childbearing age. Myocardial infarction, stroke and peripheral arterial occlusion are rare in pregnant or puerperal women. Although atherosclerosis is the most common cause of arterial thromboembolism in the general population, other mechanisms--for example, prosthetic heart valves and drugs which cause vasospasm--are also important in young and pregnant patients. The clinical sequelae of arterial thromboembolism include sudden death and significant long-term morbidity. The best management must be the recognition of women at risk and, where possible, risk reduction and the introduction of measures to prevent acute events.

Arterial Occlusive Diseases↗

PubMed2005

Influence of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, B vitamins and other factors on plasma homocysteine and risk of thromboembolic disease in Chinese.

BACKGROUND: Thromboembolic disease is a major cause of morbidity and mortality in many countries. Our previous study found that Chinese subjects carried the same polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene as described in Western studies. The aim of the present study was to determine the influence of MTHFR polymorphism, B vitamins and other factors on plasma homocysteine (Hcy) levels and risk of thromboembolic disease in Chinese. METHODS: One hundred and six subjects were enrolled into the study. They were categorized into 4 groups: healthy individuals (n = 42); those with diabetes mellitus (n = 20); those with deep vein thrombosis (DVT) (n = 11); and those with coronary artery disease (CAD) (n = 33). Plasma levels of folic acid, vitamins B6 and B12, Hcy, and fasting blood sugar were measured; total cholesterol, triglycerides, complete blood count, and 677 C-->T mutation in MTHFR were determined. RESULTS: Plasma Hcy was lowest in the healthy subjects, higher in diabetics, followed by patients with DVT, and highest in patients with CAD (p < 0.001, ANOVA). MTHFR C677T polymorphism was the common factor affecting plasma logHcy levels in all 4 groups of subjects. Triglycerides affected plasma logHcy in the CAD patients. For the 4 groups as a whole, MTHFR polymorphism, triglycerides, and vitamin B12 were the most significant factors influencing plasma Hcy. CONCLUSION: We suggest that high plasma Hcy is an important risk factor for CAD. Other factors including MTHFR polymorphism, vitamin B12, triglycerides, total cholesterol, and gender might affect Hcy levels in different diseases and conditions.

Adult↗

PubMed2000

Emerging concepts in the diagnosis and management of venous thromboembolism during pregnancy.

Multiple changes in the coagulation system occur during pregnancy and account for the hypercoagulable state of pregnancy. Consequently, pregnant women are five times more likely to experience venous thromboembolism than non-pregnant women. Although the estimated rates of such events are low, venous thromboembolic disease is a leading cause of maternal death. The administration of intravenous or subcutaneous unfractionated heparin is the treatment and prophylaxis of choice. Warfarin is safe and efficacious following delivery, but should be avoided during pregnancy. LMWH is a promising alternative for treatment and prophylaxis, but further clinical experience is required.

Anticoagulants↗

PubMed2004

Economic evaluation of enoxaparin for the prevention of venous thromboembolism in acutely ill medical patients.

OBJECTIVE: To conduct an economic evaluation of the prevention of venous thromboembolism in acutely ill medical patients. METHOD: We used a previously described economic model created in the context of the UK National Health Service and applied it to St. Thomas' Hospital, London. A clinical review to determine the number of medical admissions that would require thromboprophylaxis at St. Thomas' Hospital, based on the inclusion criteria of a medical thromboprophylaxis trial (MEDENOX), was conducted. Costs and effectiveness were determined, based on the provision of thromboprophylaxis to 2000 medical patients. RESULTS: Comparing treatment with low-molecular-weight heparin (enoxaparin, 40 mg once daily), unfractionated heparin (5000 IU twice daily), or no prophylaxis, the highest cost of thromboprophylaxis was associated with unfractionated heparin (199,000 pounds sterling = 4306,000 Euros), compared with enoxaparin (198,000 pounds sterling = 305,000 Euros) or no prophylaxis (176,000 pounds sterling = 271,000 Euros). The model suggested that enoxaparin thromboprophylaxis would result in fewer thromboembolic-related events. Using sensitivity analysis, incorporating certain St. Thomas'-specific costs showed enoxaparin compared with unfractionated heparin or no thromboprophylaxis was cost saving. The cost savings of 65,000 pounds sterling ( = 100,000 Euros) and 31,000 pounds sterling ( = 48,000 Euros) respectively are based on maximum uptake of thromboprophylaxis. CONCLUSIONS: The graded implementation of enoxaparin thromboprophylaxis over a four-year period would require funding redistribution. The funding Health Authority would save overall but St. Thomas' would require an increase in drug expenditure across the clinical directorates of 35,000 pounds sterling ( = 54,000 Euros) after 4 years.

Acute Disease↗

PubMed2003

The clinical thrombosis center and clinical thrombologist: a new US health systems paradigm for the management of venous thromboembolic disease.

New paradigms for the diagnosis, prophylaxis, acute treatment, and ongoing management of patients with venous thromboembolic disease (VTE), a better understanding of the genotypic and phenotypic mechanisms of thrombophilic states, and the possibility of a greatly expanded armamentarium of antithrombotic therapies are necessitating a more formalized and systematic approach to VTE management. This has required many US healthcare institutions to develop piecemeal approaches in management models for VTE utilizing local champions from a variety of subspecialties. Development of a formalized Clinical Thrombosis Center from an already established Anticoagulant Management Service utilizing a clinical thrombologist, a new role for a physician who has developed expertise in anticoagulation and VTE management, presents a new paradigm in which this disease may be approached at a formalized, institutional level. Thus the clinical thrombologist working through a Clinical Thrombosis Center can develop a system-of-care approach to link the rapid advances in the field of thromboembolism to clinical applications, formulate evidence-based disease management guidelines, and conduct patient-oriented translational clinical research in VTE.

Cardiology↗