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[Thromboembolic risks and surgery for varicose veins].

The authors carried out a study on 53 patients operated on for varices with the object of determining the risk of postoperative thromboembolism. They tried to answer three questions : 1) What is the magnitude of the risk of thromboembolism after this kind of surgery? 2) What is the value of the different methods of detection available? 3) What attitude should be adopted towards therapy, not of thromboembolism as a complication, but of the threat of thromboembolism?

Anticoagulants↗

Methionine synthase polymorphism A2756G is associated with susceptibility for thromboembolic events and altered B vitamin/thiol metabolism.

BACKGROUND AND OBJECTIVES: Vitamin B12 dependent methionine synthase (MS) regulates de novo production of methionine from homocysteine (Hcy). Since moderate elevations in Hcy are considered vasculotoxic, we examined a common variant (A2756G-MS) of the gene coding for this enzyme as a risk for thromboembolism. DESIGN AND METHODS: We investigated A2756G-MS and folate/thiol status in 51 individuals who had experienced a thromboembolic event (TE) and 95 subjects being treated for non-thromboembolic (NTE) vascular problems. RESULTS: The prevalence of the mutant G allele was lower in TE subjects than in controls, indicating a protective role for this base substitution (OR 0.39; 95%CI 0.20-0.78; p=0.010). Consistent with an advantage conferred by this allele, heterozygotes had generally lower levels of Hcy and glutathione (GSH), and higher levels of B-vitamins than wildtypes. The OR for the wildtype having an increased risk for TE was 2.32 (95%CI 1.06-5.08). Additionally, as might be predicted, TE-wildtypes had elevated GSH levels compared to corresponding NTE-wildtypes (p=0.004) - a likely response to oxidative stress. NTE subjects showed a dramatic reduction in Hcy between wildtype and heterozygote (p=0.017), and again between recessive and heterozygote genotypes (p=0.002). The same pattern, although not significant, occurred in TE subjects. The similarity in Hcy between clinical groups for each genotype raises questions on the etiological role of Hcy in TE. The functional relationship between enzyme variant and its B12-cofactor may be of more interest, since the polymorphic site occurs near the B12-binding domain, and our results indicate wildtype-TE subjects have a much lower level of vitamin B12 than heterozygote-TE subjects (p=0.0019). This effect is attenuated in NTE subjects. INTERPRETATION AND CONCLUSIONS: . A2756G-MS may protect against a thromboembolic event. The role of Hcy remains unclear.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

[Short- and mean results of mitral and aortic valve replacement with a Björk-Shiley disc prosthesis. Thromboembolic and hemorrhagic complications].

96 patients with a Björk aortic valve and 112 patients with a Björk mitral valve were followed up for four and a half years and five years after operation respectively. The actuarial survival rate was 82.5% in the aortic and 73% in the mitral patients. Late death was observed in 7.3% of mitral patients with thromboembolic complications and 4.2% of mitral patients with left ventricular dysfunction, compared to 2.6% of aortic patients with thromboembolism and 3.6% with left ventricular dysfunction. The incidence of thrombolic complications was three times as great with the prosthesis in the mitral position. The probability of absence of thromboembolic complications, studied by actuarial methods, was 93% at 4 1/2 years in aortic prostheses compared to 82% at 5 years in the mitral prostheses. 12 haemorrhagic complications (5.7%), with one fatality, were observed. Aortic valve replacement with a Björk prosthesis is a very satisfactory operation and the results compare favourably with other prostheses. However, the risk of thromboembolic complications should be seriously considered in the surgical indications when this prosthesis is to be used for mitral valve replacement.

Adolescent↗

Lack of association between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene and venous thromboembolism in Northwestern Greece.

BACKGROUND: Hyperhomocysteinemia has been associated with venous thrombosis. Under known and unknown conditions the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is accompanied by elevated levels of homocysteine. However, the relationship of this mutation with venous thromboembolism (VTE) remains controversial. The purpose of this study was to evaluate the association of the MTHFR mutation with VTE. METHODS: The presence of the C677T mutation in the MTHFR gene was investigated in a population of 176 consecutive patients with a history of venous thromboembolism and in a control group of 300 healthy subjects, using DNA analysis. RESULTS: The prevalence of homozygosity in the patient group was 13.6% and in healthy subjects 10%. The odds ratio for venous thromboembolism in the presence of the homozygous genotype (677TT) was 1.4 (95% confidence interval (C.I.), 0.8 to 2.5), which was not statistically significant. CONCLUSIONS: Homozygosity for the T677 allele of the MTHFR gene, although slightly more prevalent in patients compared to controls, has not been found in association with venous thromboembolism.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Low molecular weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancy.

OBJECTIVE: To evaluate the effect and dose of dalteparin given to pregnant women with acute venous thromboembolism. DESIGN: An observational study of pregnant women in Norway. SETTING: Delivery and haematological departments in Norway. POPULATION: Twenty women, aged 22-41 years, with acute venous thromboembolism verified by objective means. METHODS: Patients were treated with dalteparin from diagnosis until delivery. Treatment was monitored with anti-activated factor Xa (anti-Xa) activity, and the dose was adjusted to achieve target 0.5-1.0 U/mL 2-3 hours post-injection. MAIN OUTCOME MEASURES: Anti-Xa activity and side effects. RESULT: None of the patients suffered recurrent venous thromboembolism or major bleeding complications. In 9 of 13 women starting with conventional dose of dalteparin (100 iu/kg bd), dose escalation was necessary to reach target anti-Xa activity. None of the six women who started with 105-118 iu/kg bd required dose escalation. One woman who started with 133 iu/kg bd required dose reduction. Bioaccumulation of dalteparin was not observed. CONCLUSION: Our study suggests that dalteparin may be used for the treatment of acute venous thromboembolism in pregnancy. Approximately 10-20% higher doses of dalteparin may be needed as compared with non-pregnant individuals.

Acute Disease↗

Travel and the risk of symptomatic venous thromboembolism.

Whether long-distance travel and symptomatic venous thromboembolism (VTE) are associated is debated. On the basis of the available literature a fair risk estimate cannot be obtained. We estimated an accurate odds ratio for the relationship between recent travelling and symptomatic VTE. From three case-control studies consisting of 788 and 170 patients with clinically suspected deep vein thrombosis (DVT) and 989 patients with clinically suspected pulmonary embolism (PE) referred for diagnostic work-up, a pooled odds ratio for the relation between travel and symptomatic VTE was calculated. Cases were patients in whom the diagnosis was confirmed according to a diagnostic management strategy, whereas controls were patients in whom the diagnosis was excluded and who had an uneventful clinical follow-up. Patients were seen in the period April 1997 to September 2000. Travel history was recorded prior to diagnostic work-up. The pooled odds ratio for the association between any travel and symptomatic venous thromboembolism was 0.9 (95% CI: 0.6-1.4). The median travel time was 7 h (quartile range 4 to 10 h). Separate analyses performed for different types of transport (plane, car, bus or train) yielded comparable odds ratios. The analysis for duration of travelling showed an increased odds ratio of 2.5 (95% CI: 1.0-6.2) in the category of 10-15 h of travelling. This study shows that the average traveller does not have an increased risk for symptomatic venous thromboembolism. Only very long travelling (more than 10 h) may be associated with venous thromboembolic disease.

Adolescent↗

Thrombopoietin serum levels in patients with inflammatory bowel disease with and without previous thromboembolic events.

BACKGROUND/AIMS: Patients affected by inflammatory bowel disease frequently suffer from thromboembolic complications and mesenteric microvascular occlusion could be involved in the pathogenesis of inflammatory bowel disease. Increased platelet counts and abnormal platelet function seem to play a crucial role in determining the hypercoagulable state observed in inflammatory bowel disease. Thrombopoietin is considered the primary regulator of thrombopoiesis and recent studies have investigated the role of thrombopoietin in inflammatory bowel disease. However, the available data are not conclusive. The aim of this study was to assess thrombopoietin serum levels in inflammatory bowel disease patients according to platelet counts, disease activity and previous thrombotic events. METHODOLOGY: Seventy-one patients with inflammatory bowel disease [41 with ulcerative colitis and 30 with Crohn's disease] and 30 healthy controls were investigated. Eight (11%) inflammatory bowel disease patients had suffered previous thromboembolic complications, none had active thrombosis. Thrombopoietin serum levels were measured by ELISA. RESULTS: Mean thrombopoietin levels were significantly increased in inflammatory bowel disease patients with active disease compared to both healthy controls and patients with inactive disease. Platelet counts were significantly higher only in patients with active disease with respect to healthy subjects. No correlation was found between thrombopoietin levels and platelet counts in either controls or inflammatory bowel disease patients. No differences were found either in thrombopoietin levels or in platelet counts comparing inflammatory bowel disease patients with and without thromboembolic complications. CONCLUSIONS: Our data show elevated thrombopoietin levels in active inflammatory bowel disease. However, no correlation was found between platelet counts and thrombopoietin levels, supporting the hypothesis that other circulating factors than thrombopoietin interact in determining reactive thrombocytosis. Furthermore, thrombopoietin levels did not differ in inflammatory bowel disease patients with or without previous thromboembolic events. This finding could be probably explained by the lack of patients with active thrombosis at the moment of inclusion in the study.

Adult↗

[Thromboembolism in lung cancer patients].

We reviewed 649 primary lung cancer patients with special reference to the occurrence of thromboembolism. Thirteen episodes of thromboembolism were detected in 12 (1.8%) of the 649. Eight of the 12 were men, and their mean age was 63. Adenocarcinoma was the predominant cell type. Most patients had an advanced stage of the disease, but in some in the cancer was at an early stage. In 5 cases, the finding of thromboembolisms led to diagnosis of the lung cancer (38.5%). Anticoagulant therapy was performed in 9 cases, of which 8 responded without serious complication. We emphasize the importance of anticoagulant therapy as a therapy indicated for thromboembolism in patients with lung cancer.

Adenocarcinoma↗

High plasma concentration of factor VIII coagulant is also a risk factor for venous thromboembolism in the elderly.

BACKGROUND AND OBJECTIVES: A high level of coagulant factor VIII is a well known risk factor for venous thromboembolism, but most studies have enrolled patients under 70 years old. This study aimed to test the hypothesis that an association also exists in the elderly. DESIGN AND METHODS: This hospital-based case-referent study took place at the Department of Internal Medicine and Chest Diseases, University Hospital, Brest, France. We enrolled 161 patients with a first episode of venous thrombosis and 239 subjects, referred for a clinical suspicion of venous thromboembolism which was subsequently ruled out. Factor VIII coagulant activity and plasma fibrinogen concentration were measured. RESULTS: High factor VIII coagulant activity was significantly associated with venous thromboembolism, irrespective of the age group. Patients over 70 years with factor VIII coagulant activity above 225% had a 2.4-fold increased risk of venous thromboembolism compared to those patients with levels below 130% (age- and fibrinogen-adjusted odds ratio: 2.6, 95% CI 1.1 to 6.1). INTERPRETATION AND CONCLUSIONS: Our results show that high levels of factor VIII coagulant, a determinant of venous thrombosis in adulthood, is also a risk factor in the elderly.

Age Factors↗

Venous thromboembolic risk and prevention in acute medical illness.

We describe a case in which an elderly woman is hospitalised for acute medical illness and ask how this patient's risk of venous thromboembolism should be assessed and managed. Venous thromboembolism was previously regarded as a surgical problem, but occurs at least as frequently among medical patients. The risk of venous thromboembolism varies, but recent studies have provided detailed data on the risk in patients with acute medical illness, in particular those patients with acute heart failure, respiratory failure and acute infectious disease. As the evidence has accumulated, specific guidelines recommend provision of thromboprophylaxis to patients at risk. An approach to venous thromboembolic risk assessment and prevention in acutely ill medical patients is presented.

Acute Disease↗

[Therapeutic indications for acute venous thromboembolism. Current status and future perspectives].

Except for selected patients requiring aggressive therapies, the large majority of patients with acute venous thromboembolism are currently treated with full doses of unfractionated or low-molecular-weight heparins (LMWH) followed by oral anticoagulants for variable periods of time. LMWHs present a number of potential advantages over unfractionated heparin: a longer plasma half-life, improved subcutaneous bioavailability, and a more predictable dose-response relationship. As a result of these pharmacokinetic properties, these compounds have the potential to greatly simplify the initial treatment of venous thromboembolism, making the treatment of suitable patients feasible in an outpatient setting with considerable saving in costs and improvement in patients' quality of life. The use of unfractionated heparin is still desirable in the initial treatment of acute pulmonary embolism in non-critically ill patients. The use of heparin protocols assures that virtually all patients will promptly achieve the therapeutic range for the activated partial thromboplastin time. Although the optimal duration of anticoagulation in patients suffering an episode of venous thromboembolism is presently unknown, it seems reasonable to administer a short-term course of coumarin drugs to patients with thrombosis associated with transient risk factors, while a longer course should be considered in patients with idiopathic thrombosis and in those with permanent risk factors. At present, indefinite anticoagulant therapy remains a clinical judgment in the individual patient. The efficacy and safety of emerging drugs (pentasaccharide, ximelagatran) in the treatment and secondary prevention of venous thromboembolic disorders is currently under investigation.

Acute Disease↗

Symptomatic venous thromboembolism in Hong Kong Chinese children.

OBJECTIVE: To determine the incidence of venous thromboembolic disease in children of Chinese origin, and associated predisposing factors. DESIGN. Retrospective case series. SETTING: A general, public hospital serving a population of approximately 181,000 children in Hong Kong. PATIENTS AND METHODS: Hong Kong Chinese children under the age of 15 years who were diagnosed with a symptomatic venous thromboembolic event between 1995 and 2000 were included. Data on clinical features, predisposing factors, treatment, and outcome were obtained from review of hospital medical records. RESULTS: Eight children (five girls and three boys) of mean age 11.5 years (range, 0-14.7 years) were included in the study. They presented with deep vein thrombosis (n=4, with pulmonary embolism in one), superior vena cava thrombosis (n=1), and cerebral venous sinus thrombosis (n=3). Predisposing factors included hereditary protein C deficiency (n=3), protein S deficiency (n=2), anticardiolipin antibodies (n=1), malignancy (n=3), recent neurosurgery (n=2), infection (n=1), with multiple predisposing factors seen in three patients. Anticoagulant therapy was prescribed in five patients, and long-term warfarin therapy was required in two cases. Venous thromboembolic disease resolved in all children, but one patient had a recurrence after cessation of warfarin therapy, and one patient had post-thrombotic syndrome. CONCLUSION: The rate of venous thromboembolic disease in Hong Kong Chinese children was comparable to that seen in Caucasian children, with an annual incidence of 0.74 per 100,000 children. Predisposing factors, including hereditary prothrombotic conditions, were common.

Adolescent↗

Factor V Leiden and prothrombin gene 20210A variant in neonatal thromboembolism and in healthy neonates and adults: a study in a single center.

This study was conducted to identify the prevalence of FV1691A and PT20210A mutations in neonates with symptomatic thromboembolism and in healthy neonates and adults. A review of 137 healthy neonates, 368 healthy adults, and 9 neonates with clinical thrombosis was done to investigate for hereditary prothrombotic mutations. For the neonates with thromboembolism, data were collected to reveal the underlying diagnosis, site of thrombosis, and associated risk factors. Investigations included screening for factor V 1691A and prothrombin 20210A. Seven of 9 neonates had one or more risk factors at the time of thromboembolism. Seventy percent (5/7) had underlying congenital thrombophilia (4/7 FV Leiden, 1/7 homozygote protein C deficiency). Among the healthy population, 11.9% of the neonates and 9% of the adults had FV1691A mutation, 4.8% of the neonates and 2.7% of the adults had PT 20210A mutation. Incidence of FV1691A mutation in the neonates with symptomatic thromboembolism was very high. The prevalence of both FV1691A and PT20210A mutations were remarkably higher than previously reported.

Adult↗

[Thromboembolic diseases from the hematologic viewpoint: 13 case examples].

Numerous patients with a thromboembolic history are referred to our Central Haematology Laboratory for a complete investigation of thrombophilia. Among them, patients with idiopathic thromboembolism represent the largest group. In collaboration with the obstetrician we control pregnant women at increased risk for thromboembolic complications. Individuals with myeloproliferative disorders often suffer from thromboembolism and are investigated at our Laboratory as well. Thirteen illustrative cases are presented, which are of diagnostic and/or therapeutic interest for the practitioner.

Adult↗

[Indications and monitoring of antithrombotic prophylaxis for venous thromboembolism during pregnancy and post-partum].

Pregnancy and puerperium are well-known risk factors for venous thromboembolism, but the actual incidence of the disease is low (about 1/1,500 pregnancies). Pregnancy-associated venous thromboembolism is rare, though it is still the second cause of maternal death in France. Several types of prophylaxis are available, mainly clinical vigilance and aggressive investigation of women with symptoms of venous thromboembolism, or antithrombotic prophylaxis. Given the low incidence of the pathology, it seems desirable to select high-risk groups of women for such strategies. The most studied and identified risk factors are prior episodes of venous thromboembolism and biological thrombophilias. Prophylaxis through low molecular weight heparin during pregnancy and the puerperium should be considered mainly in these two groups. Noteworthy, no prospective and randomized study is available, and treatment recommendations are grade C.

Drug Monitoring↗

[Thromboembolic accident after mitral valve replacement].

Between January 1981 and December 2000, we report 112 cases of mitral valvular replacement with bileaflet prothesis. Saint Jude prosthesis was implanted in 71% of cases. With a mean follow-up of 110 months we report a thromboembolic accident in 7 cases (6.2%). The linear rate of thromboembolic accident is 0.69% A/P. This complication was concerned 5 women and 5 men. The mean age is 54 years (43-65 years). An embolic accident without prosthesis thrombosis is noted in 6 cases. We report only one case of prosthesis occlusive thrombosis with urgent chirurgical intervention. Par rapport au RVM, l'ATE est survenue dans uns délai moyen de 129 months (86-168 months). Left atrium size, embolic antecedent, and bad anticoagulation are the predicted factors of thromboembolic accidents in our study. Patient age and sex, atrial fibrillation, type of bileaflet prosthesis don't influence the occurrence of thromboembolic accident.

Adult↗

Intraoperative adjusted-dose heparin thromboembolic prophylaxis in primary total hip arthroplasty.

Intraoperative, fixed, intermittent, low-dose intravenous heparin prophylaxis has been reported to significantly reduce the incidence of thromboembolic disease from 24.3% to 8.3% after primary total hip arthroplasty (THA). This study examined the potential efficacy of adjusted-dose intraoperative heparin administration, keeping the activated clotting time at 30%-50% greater than normal. It was hypothesized that prolongation of clotting parameters in a uniform manner would further decrease the incidence of thromboembolic disease postoperatively. Sixty-one patients completed the protocol. The overall incidence of thromboembolic disease was 9.8%. Five patients had a positive postoperative venogram: four in the calf and one in the proximal deep thigh vein. One patient had a symptomatic nonfatal pulmonary embolus diagnosed by ventilation-perfusion scan. There were no complications related to heparin administration. This approach was therefore equally as effective as the fixed-dose regimen, and it further confirmed the efficacy and safety of an intraoperative heparin prophylaxis regimen. The extra efforts required to maintain a constant intraoperative level of anticoagulation did not prove advantageous over the simpler, fixed-dose regimen in reducing the incidence of thromboembolic disease after primary THA.

Adult↗

Epoprostenol in chronic thromboembolic pulmonary hypertension with distal lesions.

BACKGROUND: Although patients with primary pulmonary hypertension and patients with chronic thromboembolic pulmonary hypertension with distal lesions may share similar pathophysiological characteristics, scarce information is available on the usefulness of epoprostenol in this form of secondary pulmonary hypertension. The aim of this study was to evaluate the feasibility, safety and efficacy of epoprostenol therapy in surgically untreatable patients with chronic thromboembolic pulmonary hypertension. METHODS: Continuous infusive therapy with epoprostenol was undertaken in 16 patients with primary pulmonary hypertension and in 11 surgically untreatable thromboembolic pulmonary hypertension patients. The median follow-up was 12.4 months (range 6-23 months). Patients underwent clinical, echocardiographic and hemodynamic evaluation at baseline and a 6-min walk test every 3 months after beginning epoprostenol; ultrasound evaluations were repeated in a subgroup of patients. RESULTS: Epoprostenol therapy improved the clinical status, exercise tolerance and NYHA functional class. A greater left ventricular end-diastolic volume was recorded at echocardiography in both groups. CONCLUSIONS: Epoprostenol therapy may be feasible, safe and clinically effective in patients with surgically untreatable chronic thromboembolic pulmonary hypertension.

Antihypertensive Agents↗