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Acute venous thromboembolism.

OBJECTIVE: To review the recent advances in management of acute venous thromboembolism. DATA SOURCES: Articles and published reviews on venous thromboembolism, pulmonary embolism and deep vein thrombosis. SUMMARY OF REVIEW: Acute venous thromboembolism describes a group of disorders that include venous thrombosis (usually deep vein thrombosis) and pulmonary thromboembolism. Ultrasound supplemented by Doppler flow detection imaging has become the investigation of choice in the diagnosis of deep vein thrombosis and spiral volumetric computed tomography or ventilation perfusion scan (if the patient is haemodynamically stable) or bedside echocardiography (if the patient is hypotensive) are often the initial investigations in a patient who has a suspected pulmonary thromboembolism. Magnetic resonance venography has only recently been evaluated and may prove in future to be a valuable diagnostic test for both deep vein thrombosis and pulmonary thromboembolism. Treatment requires immediate anticoagulation using either subcutaneous low molecular weight heparin (e.g. enoxaparin 1 mg/kg 12-hourly or dalteparin 100 IU anti Xa/kg twice daily) or intravenous unfractionated heparin (80 U/kg as a bolus then 18 U/kg/hr and adjusted to keep the APTT 1.5-2x the control value). Oral anticoagulation using warfarin is started simultaneously with heparin. Fibrinolytic therapy is considered in all patients with pulmonary thromboembolism in whom there are no contraindications, as the improvement in right ventricular function is greater and the pulmonary artery perfusion defect is less compared with patients treated by anticoagulation alone. Fibrinolytic therapy is usually only considered in patients with deep vein thrombosis if severe limb oedema is present. While streptokinase, urokinase and alteplase have been recommended, alteplase (100 mg over two hours with heparinisation) may be the treatment of choice as alteplase has a shorter half life, has a more rapid effect and may be more effective in lysing older clots, when compared with streptokinase or urokinase. Reteplase (10 U over 2 minutes followed by 10 U 30 minutes later) may be as effective as alteplase. CONCLUSIONS: Acute venous thromboembolism is a disorder that carries a high morbidity and mortality. Anticoagulation with or without fibrinolysis is the treatment of choice.

Journal Article↗

[Fatal pulmonary thromboembolism: is its incidence increasing or diminishing? Analysis of 178 cases from 1971 to 1988].

A retrospective study was undertaken on 178 cases (6.9% out of 2569 autopsies) of fatal pulmonary thromboembolism, 86 males and 92 females, aged 28-87 years (mean age = 71 +/- 13), in whom pulmonary emboli were found at autopsies, performed from 1971 to 1988. Fatal pulmonary thromboemboli means that no other cause of death was found at autopsy, and emboli occluded at least 2 lobar arteries. In 43 cases (24.2%) the fatal pulmonary thromboembolism developed after surgery. Considering the percentage of the cases of fatal pulmonary thromboembolism on the number of autopsies performed every year, the incidence of this disease increased throughout the period under study. There is a significant difference in incidence of fatal pulmonary thromboembolism in the autopsies in years 1971-79 in comparison with the years 1980-88. In fact the fatal pulmonary thromboembolism cases are 5.1% from 1340 autopsies in the period 1971-79, and 8.9% from 1229 autopsies in the period 1980-88. This increase in incidence is due mainly to the fatal pulmonary thromboembolism in the medical patients (from 3.2% to 7.5%) while the postoperative cases show a slight decrease, from 1.9% to 1.4%. The mean age of patients with fatal pulmonary thromboembolism increases in the second period considered. Age and medical treatment are the most important risk factors. In spite of the increasing age of the population and the increased use of major surgery, there is a tendency to constant or decreased incidence of fatal pulmonary thromboembolism, at least in surgical patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Risk of venous thromboembolism after SARS-CoV-2 vaccination-Evidence from genome-wide association study and population-based observational study.

AIM: We aimed to investigate whether genetic variation is associated with venous thromboembolism after immunization with SARS-CoV-2 vaccines. METHODS: We conducted a genome-wide association study (GWAS) on cases of venous thromboembolism within 42 days after SARS-CoV-2 vaccination, recruited from reports of adverse drug reactions sent to the Swedish Medical Products Agency. Two hundred one cases (43% women, 91% Swedish) were compared with 4891 Swedish population controls. Analyses were performed on two candidate variants in coagulation factor II (rs1799963) and coagulation factor V (rs6025), on 14 prespecified candidate genes and across the whole genome. To support the findings, we conducted an observational register study of the Swedish general population with/without a diagnosis of thrombophilia and the risks of venous thromboembolism after SARS-CoV-2 vaccination. RESULTS: In the GWAS, the main findings were that the candidate variants of coagulation factors II rs1799963 and V rs6025 were significantly associated with venous thromboembolism (odds ratio [OR] 2.4 [95% confidence interval (CI) 1.2-4.8], p = .015 and OR 1.8 [95% CI 1.3-2.6], p = .0022). No genetic marker passed the significance threshold in the candidate gene analysis or the full genome-wide analysis. In the register study, people with a thrombophilia diagnosis had a five-fold elevated risk of venous thromboembolism within 42 days after vaccination, adjusted for potential confounders, OR 5.06 [95% CI 3.98-6.44]. CONCLUSION: Well-characterized genetic variants in the genes of coagulation factors II and V were associated with thromboembolism after SARS-CoV-2 immunization. Further research is recommended to elucidate their potential role in vaccine-related thromboembolic events.

Adult↗

Genetic Downregulation of Interleukin-6 Signaling, Coagulation Function, and Risk of Thromboembolic Disease.

BACKGROUND: Although genetic evidence supports IL-6 (interleukin-6) signaling inhibition as protective against atherosclerotic disease, its potential effects on thromboembolic outcomes are not well established. We conducted a Mendelian randomization analysis to investigate the association of genetically proxied IL-6 signaling inhibition with venous thromboembolism, cardioembolic stroke, and coagulation cascade protein levels. METHODS: IL-6 signaling inhibition was proxied using the rs2228145 IL6R missense variant, which impairs classical IL-6 signaling and lowers CRP (C-reactive protein) levels. Genetic associations with thromboembolic disease outcomes were obtained from genome-wide association studies of venous thromboembolism (81 190 cases) and cardioembolic stroke (10 804 cases). As atherosclerotic comparator traits, we included coronary artery disease (181 522 cases) and large-artery atherosclerotic stroke (6399 cases). Genetic associations with 35 coagulation cascade protein levels were obtained from the UK Biobank (n=6218) and deCODE cohorts (n=35 559). Mendelian randomization estimates were derived using the Wald ratio method, scaled per 1-unit decrease in natural log-transformed CRP levels. RESULTS: Genetically proxied IL-6 signaling inhibition was associated with increased risk of venous thromboembolism (odds ratio [OR], 1.31 [95% CI, 1.16-1.47], P=6.5×10-6) but not with cardioembolic stroke (OR, 1.25 [95% CI, 0.73-2.14], P=0.42). Conversely, protective associations were observed for both coronary artery disease and large-artery atherosclerotic stroke. Proteomic analyses demonstrated significant reductions in levels of 5 procoagulant and 7 anticoagulant or antifibrinolytic proteins. CONCLUSIONS: These findings suggest that IL-6 signaling inhibition dysregulates coagulation homeostasis and increases venous thromboembolism risk. Further experimental, translational, and epidemiologic studies are warranted to delineate underlying mechanisms and to evaluate thromboembolic safety in pharmacologic IL-6 signaling inhibition.

Humans↗

Incident thromboembolism in the aorta and the renal, mesenteric, pelvic, and extremity arteries after discharge from the hospital with a diagnosis of atrial fibrillation.

BACKGROUND: The impact of atrial fibrillation (AF) on risk of peripheral arterial thromboembolism is unknown. METHODS: We analyzed the risk of thromboembolism (embolus and/or thrombosis) in the aorta and the renal, mesenteric, pelvic, and extremity arteries in a cohort of patients discharged from the hospital with an incident diagnosis of AF relative to the risk of thromboembolism in these vessels in the Danish population. In a random sample of half of the Danish population, 14 917 men and 14 945 women aged 50 to 89 years were identified in the Danish National Hospital Discharge Register with a diagnosis of AF from January 1, 1980, through December 31, 1993. Patients were followed up from diagnosis of AF in the Danish National Hospital Discharge Register and the Causes of Death Register until the first diagnosis of a thromboembolic event, death, or the end of 1993. Risk of a thromboembolic event relative to the risk in the Danish population was analyzed by means of Poisson regression modeling. RESULTS: Patients with a hospital diagnosis of AF had an increased risk of thromboembolic events in the aorta and the renal, mesenteric, pelvic, and extremity arteries (relative risk, 4.0 [95% confidence interval, 3.5-4.6] in men; and relative risk, 5.7 [95% confidence interval, 5.1-6.3] in women) compared with the Danish population. CONCLUSION: A hospital diagnosis of AF is an important risk factor for peripheral arterial thromboembolic complications.

Aged↗

Short-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of prospective studies investigating symptomatic outcomes.

BACKGROUND: The prevalence of asymptomatic deep vein thrombosis diagnosed by venography after hip or knee replacement remains high despite 7 to 10 days of anticoagulant prophylaxis. However, the risk of symptomatic events in such patients is unclear. We performed a meta-analysis to provide reliable estimates of the risk of symptomatic venous thromboembolism occurring within 3 months of hip or knee replacement in patients who received short-duration (7-10 days) anticoagulant prophylaxis. METHODS: The MEDLINE, EMBASE, and Cochrane databases were searched from January 1993 to March 2001, supplemented by a manual search of bibliographies and conference abstracts, to identify prospective studies of patients undergoing hip or knee replacement who received short-duration prophylaxis (ie, 7-10 days of fixed-dose low-molecular-weight heparin or adjusted-dose warfarin, with a target international normalized ratio of 2.0-3.0). Studies were classified as clinical outcome studies if the outcome was symptomatic venous thromboembolism or as venographic outcome studies if the outcome was asymptomatic deep vein thrombosis diagnosed after bilateral venography. RESULTS: There were 4 clinical outcome studies with 6089 patients who had 3 months of follow-up, and 13 venographic outcome studies with 7080 patients who had venography 7 to 10 days after surgery. In clinical outcome studies, the 3-month incidence of nonfatal venous thromboembolism was 3.2% (95% confidence interval [CI], 2.0%-4.4%), and the 3-month incidence of fatal pulmonary embolism was 0.10% (95% CI, 0.02%-0.20%). The postprophylaxis incidence of nonfatal venous thromboembolism was 2.2% (95% CI, 1.4%-3.0%), and the incidence of fatal pulmonary embolism was 0.05% (95% CI, 0%-0.12%). The postprophylaxis incidence of symptomatic venous thromboembolism was higher after hip than after knee replacement (2.5% vs 1.4%; P=.02). In venographic outcome studies, the prevalence of deep vein thrombosis (total and proximal) was higher after knee than after hip replacement (total: 38.8% vs 16.4%; P<.001; proximal: 7.6% vs 3.8%; P<.001). CONCLUSIONS: In patients who undergo hip or knee replacement and receive short-duration anticoagulant prophylaxis, symptomatic nonfatal venous thromboembolism will occur in about 1 of 32 patients and fatal pulmonary embolism will occur in about 1 of 1000 patients within 3 months of the surgery. Although the prevalence of asymptomatic deep vein thrombosis is more than 2-fold higher after knee replacement than after hip replacement 7 to 10 days after surgery, in the subsequent 3 months, symptomatic venous thromboembolism is more likely to occur after hip replacement.

Anticoagulants↗

Thromboembolic adverse events after use of recombinant human coagulation factor VIIa.

CONTEXT: The US Food and Drug Administration (FDA) licensed recombinant human coagulation factor VIIa (rFVIIa) on March 25, 1999, for bleeding in patients with hemophilia A or B and inhibitors to factors VIII or IX. Use in patients without hemophilia has been increasing since licensure. OBJECTIVE: To review serious thromboembolic adverse events (AEs) reported to the FDA's Adverse Event Reporting System (AERS). DESIGN, SETTING, AND PATIENTS: The AERS database was reviewed from March 25, 1999, through December 31, 2004, for thromboembolic AE reports with rFVIIa. The AERS database includes US and non-US spontaneous AE reports from both approved (specific indications for patients with hemophilia) and unlabeled uses. It also includes serious AEs in patients enrolled in postlicensure clinical trials who received rFVIIa. Manufacturer reporting to FDA is mandatory, but primary notification from clinicians and others to FDA or manufacturers is voluntary for spontaneous reports; therefore, AERS underrepresents actual event occurrences. MAIN OUTCOME MEASURE: Reported thromboembolic events occurring in patients administered rFVIIa. RESULTS: A total of 431 AE reports for rFVIIa were found, of which 168 reports described 185 thromboembolic events. Seventeen events occurred in patients with hemophilia and 59 occurred in patients enrolled in postlicensure trials. Unlabeled indications accounted for 151 of the reports, most with active bleeding (n = 115). Reported AEs were thromboembolic cerebrovascular accident (n = 39), acute myocardial infarction (n = 34), other arterial thromboses (n = 26), pulmonary embolism (n = 32), other venous thromboses (including deep vein thrombosis) (n = 42), and clotted devices (n = 10). In 36 (72%) of 50 reported deaths, the probable cause of death was the thromboembolic event. In 144 patients with timing information, 73 events (52%) occurred in the first 24 hours after the last dose (30 events within 2 hours). Sixty-four reports (38%) noted concomitant use of hemostatic agents. Most reports lacked sufficient information to evaluate potential dosage associations. CONCLUSIONS: Most reported thromboembolic AEs followed the use of rFVIIa for unlabeled indications and occurred in arterial and venous systems, often resulting in serious morbidity and mortality. Analysis of the relationship between AEs and rFVIIa is hindered by concomitant medications, preexisting medical conditions, confounding by indication, and inherent limitations of passive surveillance. Randomized controlled trials are needed to establish the safety and efficacy of rFVIIa in patients without hemophilia.

Adolescent↗

Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism.

BACKGROUND: Currently, the most frequently used secondary treatment for patients with venous thromboembolism is vitamin K antagonists targeted at an INR of 2.5 (range 2.0 to 3.0). However, based on the continuing risk of bleeding and uncertainty regarding the risk of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with vitamin K antagonists for these patients. Recently, several studies were published in which the risk and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism. OBJECTIVES: The objective of this review was to evaluate efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005). The Specialised Register is constructed from electronic searches of MEDLINE (from inception to October 2005) and EMBASE (inception to October 2005) and through handsearching relevant journals. In addition, we also contacted colleagues for details of trials. The last searches were carried out on 11 October 2005. SELECTION CRITERIA: Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two reviewers (BH and MP) extracted the data and assessed the quality of the trials independently. MAIN RESULTS: Eight studies with a total of 2994 patients were included. A consistent reduction in the risk of recurrent events was observed during prolonged treatment with vitamin K antagonists (OR 0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91 to 1.69). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61). AUTHORS' CONCLUSIONS: In conclusion, this meta-analysis shows that treatment with vitamin K antagonists reduces the risk of recurrent venous thromboembolism for as long as it is used. However, the absolute risk of recurrent venous thromboembolism declines over time, while the risk for major bleeding remains. Thus, the efficacy of vitamin K antagonist administration decreases over time since the index event.

Anticoagulants↗

Thromboembolism prophylaxis during laparoscopic cholecystectomy.

BACKGROUND: The aim of this study was to determine current UK practice with regard to thromboembolism prophylaxis during laparoscopic cholecystectomy. METHODS: Postal questionnaires were sent to 800 members of the Association of Surgeons; replies were received from 551 surgeons (69 per cent) of whom 417 practised laparoscopic cholecystectomy. RESULTS: Heparin was prescribed to all patients by 74 per cent, and selectively by 20 per cent, of respondents. Surgeons who performed fewer than ten laparoscopic cholecystectomies per annum were significantly less likely to use heparin (P < 0.001) and more likely to believe that heparin produces significant adverse bleeding (P < 0.01). Thirty per cent of respondents used low molecular weight heparin. Stocking to deter thromboembolism were used by 74 per cent, and pneumatic compression by 37 per cent. Indications for heparin varied considerably and were not influenced by Thromboembolic Risk Factors (THRIFT) guidelines. Only 20 per cent of respondents considered that thromboembolism was a problem; 91 per cent reported that they had never experienced a thromboembolic complication following laparoscopic cholecystectomy. CONCLUSION: The rate of thromboembolism after laparoscopic cholecystectomy is unknown but most surgeons believe the risk is very low. Surgeons' attitudes towards thromboembolism prophylaxis are variable, but most experienced surgeons use low-dose heparin.

Adult↗

An overview of venous thromboembolism prophylaxis.

This symposium reviewed the risk factors and problems associated with venous thromboembolism in surgical patients, especially those patients having total hip replacement. The importance of venous thromboembolism prophylaxis was emphasized by a theoretical analysis indicating that venous thromboembolism in patients having hip replacement not only saves lives but is also effective. A discussion of the pharmacology of low-molecular-weight heparin (LMWH) included a review of its role, clinically and experimentally, in venous thromboembolism prophylaxis. Three of the discussants presented their favorable experiences with LMWH in reducing the incidence of venous thromboembolism in patients having hip replacement. It can be concluded that LMWH does reduce the incidence of venous thromboembolism in patients having hip replacement without causing an increase in blood loss. If its effectiveness and safety remain substantiated, LMWH may soon become the preferred agent for venous thromboembolism prophylaxis.

Humans↗

Thromboembolism in patients undergoing thoracotomy.

To determine the incidence of thromboembolism in relation to thoracotomy, 77 patients undergoing pulmonary resection were prospectively studied up to 30 days postoperatively for deep venous thrombosis and pulmonary embolism. Overall, 20 of 77 patients (26%) had thromboembolic events during their hospitalization. Four deep venous thromboses and 1 pulmonary embolism were detected in 5 of 77 patients preoperatively for an incidence of 6%. Postoperative thromboembolism was detected in 15 of 77 (19%): deep venous thrombosis in 11 (14%) and pulmonary embolism in 4 (5%). No postoperative thromboembolisms occurred in the 17 patients receiving preoperative aspirin or ibuprofen, whereas they did occur in 25% of the remainder (15/60). Thromboembolism after pulmonary resection was more frequent with bronchogenic carcinoma than with metastatic cancer or benign disease (15/59 [25%] versus 0/18 [0%]; p < 0.01), adenocarcinoma compared with other types of carcinoma (11/25 [44%] versus 4/34 [12%]; p < 0.0004), large primary lung cancer (> 3 cm in diameter) compared with smaller lesions (9/19 [47%] versus 6/40 [15%]; p < 0.0001), stage II compared with stage I (7/14 [50%] versus 7/34 [21%]; p < 0.04), and pneumonectomy or lobectomy compared with segmentectomy and wedge resection (14/49 [29%] versus 1/28 [4%]; p < 0.005). Three of 4 patients with thromboembolism detected preoperatively had operation within the previous year. Postoperative pulmonary embolism was fatal in 1 of 4 (25%) and accounted for the one death. These results suggest patients undergoing thoracotomy for lung cancer, especially adenocarcinoma, should be considered for thromboembolic prophylaxis.

Adenocarcinoma↗

Atrial flutter and the risk of thromboembolism: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis of observational studies to assess the risk of thromboembolism associated with atrial flutter. METHODS: MEDLINE, EMBASE, bibliographies, and consultation with clinical experts were used to identify studies that report the risk of thromboembolism associated with attempted cardioversion and longer-term risk in chronic atrial flutter. The review process and data extraction were performed by two reviewers. Study event rates were assessed graphically, and a chi-squared test was used to assess heterogeneity across studies. Meta-regression with weighted logistic regression was used to assess the association between study-level clinical factors and reported thromboembolic event rates. RESULTS: We found 13 studies that reported the risk of thromboembolism associated with cardioversion of atrial flutter. Short-term event rates ranged from 0% to 7.3%. A chi-squared test for heterogeneity was significant (P < 0.001), so results were not pooled. Instead, a meta-regression analysis was performed, which partly explained the heterogeneity across studies. Studies were more likely to report high event rates when they included patients with a prior history of thromboembolism, and to report lower event rates when at least some patients were anticoagulated or if patients underwent echocardiography before cardioversion. Four studies reported the longer-term risk of thromboembolism, and these suggest a yearly event rate of approximately 3% with sustained atrial flutter. CONCLUSION: These findings suggest that atrial flutter is indeed associated with an increased risk of thromboembolism, and that clinical factors account for the low event rates reported in some studies.

Atrial Flutter↗

Incidence of venous thromboembolism in patients hospitalized with cancer.

BACKGROUND: There are sparse data on the frequency of venous thromboembolism in patients with various types of cancer. We sought to determine the incidence and relative risk of venous thromboembolism, pulmonary embolism, and deep venous thrombosis in patients with malignancies. SUBJECTS AND METHODS: The number of patients discharged with a diagnostic code for 19 types of malignancies, pulmonary embolism or deep venous thrombosis from 1979 through 1999 was obtained from the National Hospital Discharge Survey. Patients studied were men and women of all ages and races. RESULTS: In patients with any of the 19 malignancies studied, 827,000 of 40,787,000 (2.0%) had venous thromboembolism, which was twice the incidence in patients without these malignancies, 6,854,000 of 662,309,000 (1.0 %). The highest incidence of venous thromboembolism was in patients with carcinoma of the pancreas, 51,000 of 1,176,000 (4.3%), and the lowest incidences were in patients with carcinoma of the bladder and carcinoma of the lip, oral cavity or pharynx. The overall incidences of pulmonary embolism and deep venous thrombosis were also twice the rates in noncancer patients. Incidences with cancer were not age dependent. The incidence of venous thromboembolism in patients with cancer began to increase in the late 1980s. CONCLUSION: Patients with cancer had twice the incidence of venous thromboembolism, pulmonary embolism and deep venous thrombosis as patients without cancer. The incidence of venous thromboembolism, pulmonary embolism and deep venous thrombosis associated with cancer differed according to the type of cancer, was comparable in elderly and younger patients, and increased in the late 1980s and 1990s.

Adult↗

Derivation and validation of a Bayesian network to predict pretest probability of venous thromboembolism.

STUDY OBJECTIVE: A Bayesian network can estimate a numeric pretest probability of venous thromboembolism on the basis of values of clinical variables. We determine the accuracy with which a Bayesian network can identify patients with a low pretest probability of venous thromboembolism, defined as less than or equal to 2%. METHODS: Using commercial software, we derived a population of Bayesian networks from 25 input variables collected on 3,145 emergency department (ED) patients with suspected venous thromboembolism who underwent standardized testing, including pulmonary vascular imaging, and 90-day follow-up (11.0% of patients were venous thromboembolism positive). The best-fit Bayesian network was selected using a genetic algorithm. The selected Bayesian network was tested in a validation population of 1,423 ED patients prospectively evaluated for venous thromboembolism, including 90-day follow-up (8.0% were venous thromboembolism positive). The Bayesian network probability estimate was normalized to a score of 0% to 100%. RESULTS: Of 1,423 patients in the validation cohort, 711 (50%; 95% confidence interval [CI] 47% to 52%) had a score less than or equal to 2% that predicted a low pretest probability. Of these 711 patients, 700 (98.5%; 95% CI 97.2% to 99.2%) had no venous thromboembolism at follow-up. CONCLUSION: A Bayesian network, derived and independently validated in ED populations, identified half of the validation cohort as having a low pretest probability (< or =2%); 98.5% of these patients were correctly classified by the network.

Adult↗

Thrombophilic abnormalities and recurrence of venous thromboembolism in patients treated with standardized anticoagulant treatment.

INTRODUCTION: Whether patients with hereditary or acquired thrombophilia have an increased risk for recurrence of venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) is still controversial. The aim of this study was to evaluate the incidence of recurrence of venous thromboembolism in patients with and without thrombophilic abnormalities treated with standardized anticoagulant treatment. MATERIAL AND METHODS: Database was from a prospective multicenter randomized study aimed at evaluating the long-term clinical benefit of extending to 1 year the 3-month oral anticoagulant treatment after a first episode of idiopathic proximal deep vein thrombosis. The screening for thrombophilia included antithrombin, protein C, protein S deficiencies, resistance to activated protein C and/or factor V R506Q mutation, the mutation 20210GA of the prothrombin gene, hyperhomocysteinemia and antiphospholipid antibodies. The diagnosis of venous thromboembolism recurrence was done by objective tests and adjudicated by a panel unaware of the results of the thrombophilia screening. RESULTS: A screening for thrombophilic abnormalities was performed in 195 patients. Twenty of 57 (35.1%) thrombophilic patients experienced a recurrence of venous thromboembolism as compared with 29 of 138 (21.0%) patients without thrombophilia (HR=1.78, 95% CI 1.002-3.140, p=0.046). The difference in VTE recurrence between patients with and without thrombophilia was accounted for by those who received 3 months of oral anticoagulation (HR=3.21, 95% CI 1.349-7.616, p=0.008). No difference between thrombophilic and non-thrombophilic patients was observed in the time interval from the index episode to recurrent venous thromboembolism (29.1+/-23.9 and 30.6+/-19.8 months, respectively). CONCLUSIONS: Thrombophilic abnormalities are associated with an increased risk of venous thromboembolism recurrence. The role of thrombophilia in the long-term management of venous thromboembolism should be addressed in prospective management studies.

Aged↗

Extended outpatient therapy with low molecular weight heparin for the treatment of recurrent venous thromboembolism despite warfarin therapy.

PURPOSE: The optimal management of patients who have recurrent thromboembolism while being treated with oral anticoagulation therapy is unknown. This study reports managing such patients with extended duration low molecular weight heparin therapy. SUBJECTS AND METHODS: This study was a retrospective review of the prospective databases of three tertiary care teaching hospitals over a 27-month period. All patients who had recurrent symptomatic thromboembolism while being treated with warfarin were identified. All patients were treated with low molecular weight heparin (dalteparin), 200 U/kg daily. Data were collected for recurrent venous thromboembolism, bleeding, and survival. RESULTS: Eight hundred eighty-seven patients were managed for acute thromboembolism. In 32 patients, symptomatic, objectively documented thromboembolism recurred while they were taking warfarin; 63% of the patients with recurrence had cancer, compared with 30% of patients without recurrence. All recurrences were treated with dalteparin. In 3 patients (9% [95% confidence interval: 2% to 25%]), symptomatic recurrence developed while they were being treated with low molecular weight heparin. Nineteen patients (59%) died while receiving anticoagulation therapy; all deaths but 1 were due to malignancy, and none was due to pulmonary embolism or bleeding. CONCLUSIONS: These results suggest that recurrent venous thromboembolism is more likely to develop in cancer patients while being treated with warfarin and that long-term therapy with low molecular weight heparin may be effective in managing warfarin-failure thromboembolic disease.

Adolescent↗

Venous thromboembolism in pregnant Chinese women.

OBJECTIVE: To evaluate the incidence, disease pattern, and risk factors for thromboembolism in pregnant Chinese women. METHODS: We conducted a study from January 1998 to December 2000. Women with thromboembolic diseases were identified and their case records retrieved and reviewed. Demographic characteristics were compared between women with and without thromboembolism. RESULTS: Thirty-two women were diagnosed as having thromboembolic disease during the study period. The total number of deliveries over the study period was 16,993, giving an incidence of 1.88 per 1000 deliveries. There were two cases of pulmonary embolism and one resulted in a maternal death. The others had deep vein thrombosis of which over 80% were limited to calf veins only. The ultrasound examinations requested for suspected deep venous thrombosis before and after the event of maternal death were 1.62 and 10.7 per 1000 deliveries (P <.001); and the corresponding cases of deep venous thrombosis diagnosed were 0.29 and 2.94 per 1000 deliveries, respectively (P <.001). The majority (75%) of cases were diagnosed in the postpartum period, mainly after cesarean delivery. Women with venous thromboembolism were older, had higher body mass index, and a higher incidence of preeclampsia. CONCLUSION: Thromboembolic disease is not uncommon among pregnant Chinese women. The incidence was similar to that of the white population, although the sites of vascular occlusion were different. The long-standing belief that thromboembolism is rare among Chinese is at least partly because of underdiagnosis.

Asian People↗

The factor V leiden mutation and the risk of venous thromboembolism in gynecologic oncology patients1.

OBJECTIVE: To measure the strength of the association between the factor V Leiden mutation and venous thromboembolism in gynecologic oncology patients. METHODS: We conducted a case-control study of gynecologic cancer patients in a referral center who were group matched for demographics, tumor type, and treatment. The prevalence of the factor V Leiden mutation was determined in both cases and controls, and an odds ratio was calculated. The factor V Leiden mutation was detected using polymerase chain reaction amplification and nucleic acid restriction digest of deoxyribonucleic acid extracted from leukocytes. RESULTS: Seventy-five patients were enrolled in the study. Seventy-four samples were available for analysis. There were no differences between the cases and controls with respect to age, race, body mass index, smoking, cancer type, high stage (III or IV) of cancer, or treatment modality. The odds ratio for having the factor V Leiden mutation in patients with venous thromboembolism was 0.3 (95% confidence interval 0.1, 1.7). CONCLUSION: This study suggests that the factor V Leiden mutation is not associated with an increased risk of venous thromboembolism in gynecologic oncology patients. This contrasts with other studies showing a strong association between the factor V Leiden mutation and venous thromboembolism in cases of previously unexplained venous thromboembolism, and venous thromboembolism associated with other hypercoagulable states, such as pregnancy and oral contraceptive use. The risk of venous thromboembolism due to cancer outweighs the contribution of the factor V Leiden mutation.

Adult↗