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PubMed1999

Assessment of the risk for venous thromboembolism among users of hormone replacement therapy.

Although hormone replacement therapy (HRT) provides health benefits, concerns about harmful effects have been raised, including an increased risk of venous thromboembolism. The purpose of this review is to assess the risk for venous thromboembolism associated with HRT. Data searches involved the MEDLINE database from January 1982 to December 1997, and bibliographies of retrieved articles. Seven case-control studies and 1 prospective cohort study considering venous thromboembolism as the outcome of interest were selected and rated according to methodological criteria. Results of case-controls studies were pooled to determine an overall estimate. The pooled risk ratio (95% confidence interval) for venous thromboembolism among current users of HRT compared with non-users (never-users and past-users combined) was 2.1 (1.4 to 3.0) in the case-control studies (n = 7). Based on one prospective cohort study, the risk of primary pulmonary embolism associated with HRT was 2.1 (1.2 to 3.8). No association was found with past use of HRT. The risk of venous thromboembolism was higher within the first year of treatment. There was no strong evidence for a dose-response relationship with estrogen. No striking difference in risk of venous thromboembolism was observed between unopposed and opposed regimens. The small number of women using transdermal estrogen therapy precluded any firm conclusions about the impact of the route of estrogen administration. Current use of oral estrogen as HRT is associated with a 2- to 3-fold increased risk of venous thromboembolism. However, the absolute risk remains low, and these findings need to be weighed against the potential benefits of treatment. Whether transdermal estrogen therapy is safe with respect to venous thromboembolism has yet to be adequately investigated.

Dose-Response Relationship, Drug↗

PubMed1996

Compression sonography in patients with indeterminate or low-probability lung scans: lack of usefulness in the absence of both symptoms of deep-vein thrombosis and thromboembolic risk factors.

OBJECTIVE: We sought to determine whether compression sonography could be eliminated in the evaluation of patients who lacked both thromboembolic risk factors and symptoms of deep-vein thrombosis and who had an indeterminate or low-probability lung scan. MATERIALS AND METHODS: The medical records of 155 consecutive patients who underwent bilateral lower-extremity sonography after an indeterminate or low-probability lung scan were reviewed. The presence of thromboembolic risk factors and deep-vein thrombosis symptoms and the result of sonography were recorded. Patients were divided into two groups: group 1 consisted of patients with either thromboembolic risk factors or deep-vein thrombosis symptoms, and group 2 consisted of patients without thromboembolic risk factors and without deep-vein thrombosis symptoms. The incidences of deep-vein thrombosis in groups 1 and 2 were compared by use of a two-tailed Fisher's exact test. RESULTS: Thromboembolic risk factors or deep-vein thrombosis symptoms were found in 109 of 155 patients (70%) (group 1). Deep-vein thrombosis was found in nine of 108 patients (8%) in group 1. Both thromboembolic risk factors and deep-vein thrombosis symptoms were absent in 47 of 155 patients (30%) (group 2). Deep-vein thrombosis was found in none of 47 patients (95% confidence interval, 0-8%) in group 2. The difference in the incidences of deep-vein thrombosis in groups 1 and 2 approached statistical significance (p = .0579). The negative predictive value of the absence of both thromboembolic risk factors and deep-vein thrombosis symptoms in excluding deep-vein thrombosis was 100% (95% confidence interval, 93-100%). CONCLUSION: If both symptoms of deep-vein thrombosis and thromboembolic risk factors are absent, the usefulness of lower-extremity sonography in detecting deep-vein thrombosis in patients with an indeterminate or low-probability lung scan is low. The manner in which these findings may be used to modify individual practice patterns will undoubtedly depend on the rate of detection of deep-vein thrombosis at a given institution.

Algorithms↗

PubMed2006

Our inability to predict thromboembolic events after prosthetic valve surgery.

BACKGROUND AND AIM OF THE STUDY: Thromboembolic and bleeding complications detract from outcome for patients with prosthetic heart valves. The study aim was to investigate whether measurement of coagulation activation markers and transcranial Doppler ultrasound microembolic signals (MES) could identify patients at subsequent higher risk of thromboembolism or bleeding events. METHODS: A total of 526 patients (mean age 66 years; 266 males, 260 females) who underwent elective valve replacement surgery was enrolled between April 1999 and October 2002. Clinical assessment and blood sampling for coagulation activation markers was performed preoperatively and at three and 12 months postoperatively. Transcranial Doppler MES were recorded in the first 144 patients. Status was reviewed between 21st April and 9th June 2005, with 99.4% follow up. RESULTS: Among patients, 62% had an aortic valve replaced, and mechanical valves constituted 60% of all implants. The mean follow up was 3.61 years; total follow up was 1,899.2 patient-years (pt-yr). In total, 115 patients died, while 61 experienced a total of 80 thromboembolic events: linearized event rates were 3.94% (mechanical valves) and 4.4% (bioprostheses). There was no difference between mitral and aortic implants, or among bileaflet, tilting-disc mechanical and porcine valves. Atrial fibrillation was not influential. Coagulation activation markers were not associated with thromboembolic events, except for an elevated von Willebrand factor (vWF), which was associated with a five-fold increase in embolic event rate. Fifty-one patients experienced 59 bleeding events; eight patients experienced multiple events. Linearized event rates were 3.37% (mechanical valves) and 2.49% (bioprostheses). The INR was suboptimal in 44-58% of patients. Transcranial Doppler MES were not associated with blood coagulation markers or thromboembolic events. CONCLUSION: Coagulation activation markers (except vWF) and MES did not predict thromboembolic events in valve replacement patients. Thromboembolic and bleeding event rates for West of Scotland patients generally exceeded reported rates: suboptimal anticoagulation appeared common and most likely influenced thromboembolic and bleeding event rates more than any other factor.

Aged↗

PubMed1988

[Mortality and morbidity of thromboembolism in drug prevention--5-year analysis].

In a period of five years a general medical prevention of postoperative venous thromboembolic disease was tested in major gynaecological operations, in patients undergoing radium insertions for gynaecological cancer and in patients with caesarean section. Preoperatively was the beginning of the daily therapy with Dihydroergotamine (DHE) and every four days the therapy with Acetylsalicylic acid (ASS). The results of 2,346 therapy-cycles with medical prevention of thromboembolic disease in 2,280 patients are reported. Risks of thromboembolic disease were in 63% of the gynaecologic patients (mean age 52.4 +/- 8.9 years) and in 34% of the obstetrical patients (mean age 24.6 +/- 5.1 years). Postoperative bleeding complications occurred in 12 cases (0.5%) and the number of reoperations was lower than 1 0/00). Postoperative thromboembolic complications were found clinically and radiologically in 0.3% of the patients. Letal embolism of the lung happened in 2 patients (0.9 0/00). A general medical prevention of thromboembolic disease with DHE and ASS can be recommended because of the low rate of postoperative bleeding complications and of the reduced rate of postoperative thromboembolic disease. A prevention of thromboembolic disease by individual dosage of heparin must be considered in patients at high risk for thromboembolic disease.

Adenocarcinoma↗

PubMed1995

Cardiac and vascular sources of peripheral thromboembolism in patients with atrial fibrillation. A combined transesophageal and vascular ultrasonographic study.

Atrial fibrillation is associated with an increased risk of peripheral thromboembolism. Although emboli arising from the left atrium are the most probable causes of peripheral ischemic events, coexistent vascular mechanisms may play a role in the genesis of thromboembolism. To assess the prevalence and the relative role of cardiac and vascular sources of thromboembolism in patients with atrial fibrillation 101 consecutive patients with (group 1: 47 patients) and without (group 2: 54 patients) recent thromboembolism were studied by transesophageal echocardiography and ultrasound duplex scanning of carotid arteries. Left atrial thrombosis was found in 19 (40%) group 1 patients and in 3 (5%) group 2 patients. Left atrial thrombosis and/or spontaneous echocardiographic contrast were significantly more frequent in group 1 patients than in group 2 (70% vs 20%, p < 0.001). Stepwise regression analysis revealed that they were the only independent predictors of thromboembolism (p = 0.018, p = 0.0003 respectively). Among clinical and transthoracic echocardiographic variables, left atrial diameter (p = 0.022), rheumatic mitral stenosis (p = 0.0058) and absence of significant mitral regurgitation (p = 0.027) emerged as independent predictors of left atrial thrombosis and/or spontaneous echocardiographic contrast. When transesophageal parameters were also entered into the analysis, the only independent predictor was low blood flow velocity within the left atrial appendage (p = 0.0001). Vascular sources (obstructive carotid arteries plaques, non-obstructive ulcerated carotid plaques and thoracic aortic atherosclerotic debris) were found in 30.6% of patients. Their prevalence was not significantly different in the two groups (34% in group 1, 27% in group 2). Vascular and cardiac sources coexisted in 23% of patients with thromboembolism. Seven of the 10 patients with more severe vascular lesions (i.e., obstructive carotid artery lesions or pedunculated mobile aortic debris) were from group 1 and 5 of them had negative cardiac results. In conclusion, these results indicate that a cardioembolic mechanism due to blood stasis within the left atrium is involved in most of the atrial fibrillation-related thromboembolic events. In patients with atrial fibrillation vascular sources are not infrequent and may be involved in the genesis of ischemic events in some patients. Transesophageal echocardiography may be useful in identifying subgroups of patients with atrial fibrillation who are at high thromboembolic risk.

Adult↗

PubMed1998

Venous thromboembolism associated with air travel: a report of 33 patients.

BACKGROUND: The medical literature suggests long distance travel, particularly air travel, may be a risk factor for venous thromboembolism, but the risk is poorly quantified. METHODS: We reviewed 134 records of patients hospitalized with venous thromboembolism for comments regarding recent travel. Patients who had traveled within 31 d prior to venous thromboembolism were defined as recent travelers. RESULTS: Of 134 patients records, 66 (49%) had documented inquiries regarding travel and 33 (50%) were recent air travelers. Data regarding demographics, mode of travel, day of onset of symptoms in relation to travel, and other risk factors for venous thromboembolism were abstracted from the records of the recent travelers. There were 12 (36%) travelers who had no other predisposition for venous thromboembolism. All had traveled non-stop by aircraft for 4 or more hours; none was identified as a crew-member. The median day of onset of venous thromboembolism was on travel day 4 (range: day 1-31). There were 8 (24%) patients who had onset during air travel or on the day of arrival, and 27 (82%) had onset by travel day 15. Air travel for 4 or more hours within the preceding 31 d was the most common risk factor for venous thromboembolism in our study patients and was present in 50%. This incidence is much higher than previously described, perhaps due to limiting the study population to those in which the presence or absence of travel was documented. CONCLUSION: Prospective studies are needed to better define the risk factors for venous thromboembolism among long distance air passengers and crew-members, and to determine effective preventive measures.

Adult↗

PubMed1976

Thromboembolism following total hip-replacement arthroplasty. The efficicy of dextran-aspirin and dextran-warfarin in prophylaxis.

The efficacy of two antithrombotic regimens, combined dextran and aspirin and combined dextran and warfarin, was analyzed by comparing the incidence of thromboembolism following total hip replacement in two groups of similar patients. Of the 427 who received dextran and aspirin, 7 per cent had thromboembolic complications, including one case of fatal pulmonary embolus and one case of recurrent emboli that required vena caval ligation, and 15 per cent had wound-healing complications. Of the 197 patients who received dextran and warfarin, 5 per cent had thromboembolism and 24 per cent had wound healing complications. Although both prophylactic regimens seemed effective, dextran and aspirin appeared less effective in reducing thromboembolic complications than dextran and warfarin, but there were fewer wound complications in that group. One-fourth of the patients on dextran-warfarin were not adequately anticoagulated despite close supervision. In forty-five patients with a history of thromboembolism who were excluded from the study and analyzed separately, warfarin alone and the two described regimens were equally ineffective in preventing thromboembolism, and the incidence of thromboembolic complications was high. Dextran-aspirin and dextran-warfarin appear to be satisfactory and relatively simple methods of thromboembolic prophylaxis.

Arthroplasty↗

PubMed1998

[Prevention of thromboembolism with low-molecular-weight heparin in ambulatory surgery and unoperated surgical and orthopedic patients].

Prophylaxis of thromboembolism is now well established in orthopaedic outpatients with plaster cast and after elective hip surgery. The present study was undertaken to evaluate the safety of out-of-hospital prevention of venous thromboembolism and to determine the incidence of thromboembolic complications in orthopaedic and surgical patients with or without surgical intervention on an out-patient basis during prophylaxis of thromboembolism with low-molecular-weight heparin and to study the feasibility of this treatment regimen. The treatment period was 1-4 weeks (mean 17 days). Main indications for prophylaxis of thromboembolism were arthroscopy and surgical or non-surgical intervention of bone fractures of the lower leg. The incidence of clinically diagnosed venous thromboembolism was 11/1604 (0.7%) in operated and 8/1017 (0.8%) in non-operated patients. Pulmonary embolism occurred twice in operated patients (0.1%) and in none of the non-operated patients. Minor bleeding complications were rare and major bleeding complications did not occur. Haematomas at the injection site occurred in only 4% of patients. Thrombocytopenia did not occur in any patient. The present study demonstrates the feasibility and safety to prophylaxis of thromboembolism with low-molecular-weight heparin in orthopaedic operated and non-operated out-patients with various orthopaedic or surgical diseases leading to immobilization. The incidence of clinically apparent thromboembolic complications is low and similar to medical bedridden inpatients.

Adult↗

PubMed2001

A latex D-dimer reliably excludes venous thromboembolism.

BACKGROUND: D-Dimer, a cross-linked fibrin degradation product, has a high sensitivity in patients with suspected venous thrombosis. Traditional latex D-dimer assays, however, have not been sufficiently sensitive to exclude venous thromboembolism. METHODS: To determine the clinical utility of a latex D-dimer assay (MDA D-Dimer; Organon Teknika Corporation, Durham, NC) in patients with suspected venous thromboembolism, we conducted a retrospective cohort study involving 595 unselected patients at 4 tertiary care hospitals. Patients had blood drawn for performance of the D-dimer assay and underwent objective testing for venous thromboembolism. Pretest probability was determined using validated models in 571 patients. Patients were classified as venous thromboembolism positive or negative according to results of objective tests and 3-month follow-up. The sensitivities, specificities, predictive values, and negative likelihood ratios of the assay were calculated for all patients and for subgroups of patients with known cancer or a low, moderate, or high pretest probability of venous thromboembolism. RESULTS: The prevalence of venous thromboembolism was 19.0% (113/595). Of those who had a pretest probability assessment, 35.9% had a low pretest probability, 49.7% a moderate pretest probability, and 14.4% a high pretest probability. Using a discriminant value of 0.50 microg fibrinogen equivalent units per milliliter, the assay showed an overall sensitivity of 96%, a negative predictive value of 98%, a specificity of 45%, and a negative likelihood ratio of 0.09. In patients with a low or moderate pretest probability, the sensitivity, negative predictive value, and negative likelihood ratio were 97%, 99%, and 0.07, respectively. CONCLUSIONS: The MDA D-Dimer assay is the first latex agglutination assay with sufficient sensitivity to be clinically useful in the exclusion of venous thromboembolism. A negative result has the potential to be used as the sole test to exclude venous thromboembolism in patients with a low or moderate pretest probability of disease.

Female↗

PubMed2003

Doppler microembolic load predicts risk of thromboembolic complications in Novacor patients.

OBJECTIVE: Left ventricular assist devices have become an established method to bridge patients with end-stage cardiac failure to heart transplantation. Besides infection and bleeding, thromboembolism represents one of the most serious complications. We evaluated the value of microembolic signals in predicting thromboembolic events for individual patients and distinctive left ventricular assist device periods. METHODS: Twenty patients (14 male) aged 23-57 years supported with the Novacor N100 left ventricular assist device were enrolled in this study. All patients were on effective anticoagulation, 12 patients additionally received antiplatelet therapy. Unilateral detection of microembolic signals was performed once weekly by insonation of the middle cerebral artery using transcranial Doppler sonography for 30 minutes duration. Evidence of clinically manifest thromboembolic events was based on regular questionnaires, clinical examinations, and results of diagnostic procedures. RESULTS: During a cumulative follow-up of 3876 left ventricular assist device days, 44 thromboembolic complications occurred (incidence, 1.1%) in 15 out of 20 patients. A total of 360 transcranial Doppler sonography monitorings (range, 5-34 per patient) were performed with an overall microembolic signals prevalence of 35.3% and a microembolic signal mean of 2.3 +/- 9.2 per examination. There was a highly significant correlation between the individual microembolic signal activity and the respective incidence of clinical thromboembolism (r = 0.61-0.9; P <.01). Patients with additional antiplatelet treatment had significantly less thromboembolic complications (0.7%) and lower microembolic signal prevalence (18.3%) than those without (2.8% and 65.4%, respectively). Individual patients and left ventricular assist device months with clinical thromboembolization could be identified using the microembolic signal activity with moderate positive (0.37-0.7) and high negative predictive values (0.82-1.0). CONCLUSIONS: The amount of microembolic signals, serially detected in patients with the Novacor left ventricular assist device, is significantly associated with their incidence of embolic complications. The high negative predictive value of microembolic signals enables to identify those patients and left ventricular assist device periods with particularly low risk of clinical thromboembolization.

Adult↗

PubMed2002

Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study.

BACKGROUND: Moderate hyperhomocysteinaemia is a risk factor for venous thromboembolism. We do not know whether this risk depends on homocysteine itself or on components of the homocysteine remethylation pathway, such as methylfolate. We did a case-control study to analyse the relation between the major components of the homocysteine remethylation pathway and risk of venous thromboembolism. METHODS: We measured concentrations of homocysteine, methionine, and folate in plasma, total folate and methylfolate in red-blood cells, and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotype and other known risk factors for venous thromboembolic disease in 243 patients with deep vein thrombosis or pulmonary embolism and controls matched for sex and age. FINDINGS: Concentrations in plasma of homocysteine differed significantly between cases and controls. We noted a strong concentration-dependent association between concentrations of methylfolate in red-blood cells and risk of venous thromboembolism. The adjusted conditional odds ratio ranged from 1.0 for methylfolate 249 microg/L or greater to 7.1 (3.2-15.8) for methylfolate 141 microg/L or less. Methionine concentrations below the median were also independently associated with raised risk of venous thromboembolic disease, as were established risk factors such as high body-mass index, history of cancer, family history of thromboembolism, oral contraceptive use, and factor V Leiden mutation. Furthermore, the association between concentrations of methylfolate in red-blood cells and risk of thromboembolism varied according to MTHFR C677T genotype. INTERPRETATION: Measurement of methylfolate concentrations in red-blood cells might help to identify people at risk of venous thromboembolism.

Adult↗

PubMed2003

ACE DD genotype: an independent predisposition factor to venous thromboembolism.

BACKGROUND: The renin angiotensin system affects haemostasis through different mechanisms; data on the possible role of angiotensin-converting enzyme I/D polymorphism in the pathogenesis of deep venous thrombosis are conflicting, and no information is available regarding the A1166C polymorphism of the angiotensin type 1 receptor gene. In order to investigate this issue, angiotensin-converting enzyme and AT1R polymorphisms were genotyped in 336 consecutive venous thromboembolism patients and 378 controls. MATERIALS AND METHODS: Haemostasis-related risk factors have been evaluated by routine tests. Factor V Leiden, Factor II (G20210A), angiotensin-converting enzyme (I/D), and angiotensin type 1 receptor (A1166C) polymorphisms have been identified by molecular analysis. RESULTS: We documented a significant association between angiotensin-converting enzyme DD genotype and venous thromboembolism (OR=2.19 95%CI 1.51-3.17 adjusted for acquired and haemostasis-related risk factors, P<0.0001); in patients with haemostasis-related risk factors, angiotensin-converting enzyme DD genotype modified the risk of venous thromboembolism in hyperhomocysteinaemic and Factor V Leiden patients and was associated with the risk of recurrent venous thromboembolism (OR=1.83 95%CI 1.06-3.17 P=0.03). In patients without haemostasis-related risk factors the angiotensin-converting enzyme DD genotype was still an independent predictor of venous thromboembolism (OR=3.29 95%CI 2.17-4.98 adjusted for acquired risk factors, P<0.0001). No significant association between the angiotensin type 1 receptor CC genotype and venous thromboembolism was found. CONCLUSIONS: This study shows that angiotensin-converting enzyme DD genotype represents a susceptibility marker of thrombosis in subjects apparently without predisposing factors and traditional thrombophilic alterations, and increases the risk of venous thromboembolism in subjects in whom a thrombogenic condition occurs. Moreover, angiotensin-converting enzyme DD genotype may be considered a new predisposing factor to venous thromboembolism recurrence.

Adolescent↗

PubMed2002

Operative classification of thromboembolic disease determines outcome after pulmonary endarterectomy.

OBJECTIVE: We sought to determine whether type and location of thromboembolic disease in the pulmonary vascular tree predicts the hemodynamic result and clinical outcome in patients undergoing pulmonary endarterectomy. METHODS: From 1998 to 2000, 202 patients with pulmonary hypertension and pulmonary vascular resistance ranging from 194 to 2950 dynes-s-cm(-5) underwent pulmonary endarterectomy. Preoperative and postoperative tricuspid valve function, pulmonary artery pressure, and pulmonary vascular resistance were determined by means of transthoracic echocardiography and measurements with a Swan-Ganz catheter (Edwards Lifesciences, Irvine, Calif), respectively. Patients underwent intraoperative classification of thromboembolism as follows: type 1 (76 patients), fresh thrombus in the main-lobar pulmonary arteries; type 2 (81 patients), intimal thickening and fibrosis proximal to the segmental arteries; type 3 (38 patients), disease within distal segmental arteries only; and type 4 (7 patients), distal arteriolar vasculopathy without visible thromboembolic disease. RESULTS: Overall perioperative mortality was 4.5% (9/202 patients). By means of univariate analysis, patients with type 3 or 4 disease (distal pulmonary vasculopathy) had more residual postoperative tricuspid regurgitation (P <.0001), higher postoperative pulmonary artery systolic pressure (P <.0001), and greater postoperative pulmonary vascular resistance (P <.0001) compared with that seen in patients with type 1 or 2 disease, in whom thromboembolic disease was more surgically accessible. Factors such as severity of preoperative tricuspid regurgitation, patient age, and circulatory arrest time had no correlation with postoperative hemodynamic improvement. Patients with distal thromboembolic disease (type 3-4) had higher perioperative mortality, required longer inotropic support, and had longer hospital stays compared with patients with type 1 or 2 thromboembolic disease. CONCLUSION: The degree of improvement in pulmonary hypertension and tricuspid regurgitation after pulmonary endarterectomy is determined by the type and location of pulmonary thromboembolic disease. Classification of thromboembolism is useful for predicting patient outcome after pulmonary endarterectomy.

Endarterectomy↗

PubMed1998

Autopsy-verified venous thromboembolism within a defined urban population--the city of Malmö, Sweden.

OBJECTIVE: To analyse the frequency of autopsy-proven venous thromboembolism within a defined region and evaluate if certain risk groups not earlier recognized could be found. The incidence of objectively diagnosed venous thromboembolism was also calculated. SETTING: The city of Malmö, Sweden, with 230,000 inhabitants. MAIN OUTCOME MEASURE: Analysis of 2,356 autopsies for the year 1987 of deceased inhabitants from the city of Malmö (2,981 deceased, autopsy frequency 79.0%) regarding venous thromboembolism. RESULTS: 25% of autopsies revealed venous thromboembolism. At the acute-care hospital 31%, at the chronic hospital 37%, but in forensic autopsies of non-hospital deaths only 5% (p<0.001) revealed venous thromboembolism. Major pulmonary embolism was seen in 13% and was more frequent in in-hospital deaths (p<0.001). Two in-hospital and two non-hospital deaths due to pulmonary embolism and fractures were found: two patients with knee fractures, one hip fracture and one ankle fracture patient. The incidence of objectively diagnosed venous thromboembolism (autopsy, phlebography, perfusion scintigraphy) was calculated and an incidence of 42.5/10,000 inhabitants/year was found, (strongly age-dependent). CONCLUSION: Venous thromboembolism is a common finding in autopsies of hospitalized patients. Patients with fractures other than hip fractures are less well studied as regards venous thromboembolic complications. Further studies on these fracture patients are warranted.

Adult↗

PubMed1995

Incidence of pulmonary thromboembolism, infarction and haemorrhage in disseminated intravascular coagulation: a necroscopic analysis.

BACKGROUND: The pathological features of the lung in disseminated intravascular coagulation (DIC) have not been established. This study was carried out on lungs taken at necropsy to examine the incidence and extent of thromboembolism, infarction, and haemorrhage. METHODS: The subjects were 87 patients whose illnesses were complicated by DIC and 64 patients who showed no abnormalities of blood coagulation in their terminal illness. The lungs were fixed by intrabronchial infusion of 10% formalin, cut into 5 mm thick slices, and each cut surface was carefully examined for macroscopic thromboembolism, infarction, and haemorrhage. Five tissue blocks per case were taken for quantitative analysis of microscopic thromboembolism. RESULTS: In the control group macroscopic thromboembolism was identified in 20 cases (31.3%), infarction in one, and haemorrhage also in one. Moreover, fibrin thrombosis was seen in 13 cases (20.3%) and microthromboembolism in 24 (37.5%). Of the 87 patients with DIC, thromboembolism was found in 51 cases (58.6%), infarction in six, haemorrhage in 14, microscopic fibrin thrombosis in 43 (49.4%), and microthromboembolism in 45 (51.7%). Macroscopic thromboembolism, haemorrhage, and fibrin thrombosis were found more often in the patients with DIC. CONCLUSIONS: In addition to fibrin thrombosis, macroscopic thromboembolism and haemorrhage were the main pathological findings in the lungs of patients dying with DIC. The frequency of pulmonary infarction increased in proportion to the frequency of thromboembolism.

Aged↗

PubMed1997

Age-specific incidence rates of venous thromboembolism among heterozygous carriers of factor V Leiden mutation.

BACKGROUND: Previous reports suggest that younger carriers of the factor V Leiden mutation are at greater risk for venous thromboembolism than are older carriers. However, available data on thromboembolic risk are limited. OBJECTIVE: To determine age-specific incidence rates of venous thromboembolism associated with the factor V Leiden mutation. DESIGN: Prospective cohort study. PATIENTS: 14,916 initially healthy men participating in the Physicians' Health Study who were followed from 1982 to August 1994 for the occurrence of deep venous thrombosis or pulmonary embolism. MEASUREMENTS: Polymerase chain reaction was used to determine factor V Leiden mutation status in 156 study participants who developed venous thromboembolism during follow-up and in 2406 study participants who remained free of vascular disease. RESULTS: Risks for venous thromboembolism in heterozygous carriers of factor V Leiden mutation increased with age at a rate significantly greater than that in noncarriers. Whereas incidence rates of venous thromboembolism were similar in men with and men without the factor V Leiden mutation who were younger than 50 years of age, incidence rate differences (per 1000 person-years of observation) between affected and unaffected men increased significantly from 1.23 (95% CI, -0.4 to 2.9) for those aged 50 to 59 years to 1.61 (CI, -0.5 to 3.7) for those aged 60 to 69 years of age to 5.97 (CI, 0.6 to 11.3) for those aged 70 years or older (P for trend = 0.008). For idiopathic venous thromboembolism, age-specific incidence rate differences between men with and without the factor V Leiden mutation increased significantly with age (P = 0.017). However, no significant relation was found for secondary events (P > 0.2). CONCLUSIONS: The findings support the hypothesis that the pathogenesis of venous thromboembolism involves acquired as well as genetic risk factors and indicate that determination of factor V Leiden mutation status should not be limited to young patients.

Adult↗

PubMed2004

Factor V Leiden and the risk for venous thromboembolism in the adult Danish population.

BACKGROUND: Odds ratios for venous thromboembolism (deep venous thrombosis and pulmonary embolism) derived from case-control studies range from 3 to 16 for heterozygotes compared with noncarriers and up to 79 for homozygotes compared with noncarriers. OBJECTIVE: To estimate risks for venous thromboembolism in the adult Danish population according to factor V Leiden genotype. DESIGN: Cohort study with 23 years of follow-up. SETTING: Adult Danish population. PARTICIPANTS: 9253 randomly selected individuals. MEASUREMENTS: Hospitalization and death from venous thromboembolism, factor V Leiden genotype, and additional thromboembolic risk factors. RESULTS: Adjusted hazard ratios in heterozygotes and homozygotes compared with noncarriers were 2.7 (95% CI, 1.8 to 3.8) and 18 (CI, 4.1 to 41) for venous thromboembolism overall, 2.4 (CI, 1.3 to 3.8) and 22 (CI, 0 to 60) for deep venous thrombosis, and 3.0 (CI, 1.7 to 4.9) and 11 (CI, 0 to 33) for pulmonary embolism. The lowest absolute 10-year risks for venous thromboembolism in factor V Leiden heterozygotes and homozygotes--0.7% (CI, 0.5% to 1.0%) and 3% (CI, 1% to 8%)--were found in nonsmokers younger than 40 years of age with a body mass index below 25 kg/m2; the corresponding highest risks--10% (CI, 7% to 14%) and 51% (CI, 13% to 100%)--were found in smokers older than 60 years of age with a body mass index above 30 kg/m2. CONCLUSIONS: Hazard ratios for venous thromboembolism in factor V Leiden heterozygotes and homozygotes compared with noncarriers in the adult Danish population were approximately 3 and 18, respectively. The simultaneous presence of smoking, obesity, and old age resulted in absolute 10-year thromboembolic risks of 10% in heterozygotes and 51% in homozygotes.

Adult↗

PubMed2000

High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism.

BACKGROUND: Established risk factors, including deficiencies of protein C, protein S or antithrombin and the factor V Leiden and prothrombin mutation, are present in about one third of unselected patients with venous thromboembolism. In addition to these inherited thrombophilic defects, elevated plasma levels of factor VIIIc have been suggested to be important in the pathogenesis of (recurrent) venous thromboembolism. The objective of this study was to assess the relevance of factor VIIIc plasma concentration in consecutive patients with venous thromboembolism. METHOD: We studied the prevalence of elevated plasma levels of factor VIIIc in 65 patients with a proven single episode and in 60 matched patients with documented recurrent venous thromboembolism. The reference group consisted of 60 age- and sex-matched patients who were referred for suspected venous thromboembolism, which was refuted by objective testing and long-term clinical follow-up. To minimalize the influence of the acute phase, blood was obtained at least 6 months after the thromboembolic event and results were adjusted for fibrinogen and C-reactive protein. Factor VIIIc was re-determined several years after the first measurement in a subset of patients to evaluate the variability over time. To study a possible genetic cause, a family study was done. FINDINGS: In the control, single and recurrent episode group, the prevalences of plasma levels of factor VIIIc above 175 IU/dl (90th percentile of controls) were 10% (95% CI: 4 to 21%), 19% (95% CI: 10 to 30%) and 33% (95% CI: 22 to 47%), respectively. For each 10 IU/dl increment of factor VIIIc, the risk for a single and recurrent episode of venous thrombosis increased by 10% (95% CI: 0.9 to 21%) and 24% (95% CI: 11 to 38%), respectively. Both low and high plasma levels of factor VIIIc were consistent over time (R = 0.80, p = 0.01). A family study indicated a high concordance for elevated factor VIIIc plasma concentrations among first degree family members. Adjustment for fibrinogen, C-reactive protein and known thrombophilic risk factors did not change the observed association of elevated factor VIIIc with thrombosis. INTERPRETATION: Elevated plasma levels of factor VIIIc are a significant, prevalent, independent and dose-dependent risk factor for venous thromboembolism. It also predisposes to recurrent venous thromboembolism.

Adult↗