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In patients with deep vein thrombosis (DVT), the factors which predispose to concomitant symptomatic pulmonary embolism (PE) have remained uncertain. From a prospective cohort of 5,451 consecutive patients with ultrasound-confirmed DVT, we analyzed 4,211 patients with a known status for presence (n=639) or absence (n=3572) of symptomatic PE. Age and gender were similar in DVT plus PE (63.7+/-15.6 years; 49% men) and DVT patients (63.4+/-17.3 years; 46% men). Body mass index (BMI) was higher in patients with DVT plus PE (median 29.0, range 15.4-67.0 kg/m2) than in patients with DVT (median 26.8, range 9.7-64.4 kg/m2; p<0.001). Chronic lung disease (17% vs. 12%; p<0.001), a personal history of PE (11% vs. 6%; p<0.001), and a family history of DVT or PE (8% vs. 4%; p<0.001) were more frequent in DVT plus PE patients. Twenty-seven percent of DVT plus PE patients received prophylaxis prior to the thromboembolic event compared with 32% of DVT patients (p=0.002). Proximal DVT (OR 1.84, 95% CI 1.39-2.43), prior PE (OR 1.68, 95% CI 1.20-2.35), obesity (BMI >30 kg/m2) (OR 1.65, 95% CI 1.33-2.04), chronic lung disease (OR 1.51, 95% CI 1.13-2.01), as well as omission of prophylaxis (OR 1.30, 95% CI 1.04-1.64) emerged as independent predictors of concomitant symptomatic PE.
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PMID:Risk factors associated with symptomatic pulmonary embolism in a large cohort of deep vein thrombosis patients. 1573

Previous publications have highlighted seasonal variations in the incidence of thrombosis and pulmonary embolism, and that weather patterns can influence these. While medical risk factors for pulmonary thrombo-embolism such as age, obesity, hypercoagulable states, cancer, previous thrombo-embolism, immobility, limb paralysis, surgery, major illness, trauma, hypotension, tachypnoea and right ventricular hypokinesis are not directly implicated regarding environmental factors such as weather, they could be influenced indirectly by these. This would be especially relevant in polluted areas that are associated with a higher pulmonary embolism risk. Routine nuclear medicine lung ventilation/perfusion studies (V/Q scans) of 2071 adult patients referred to the nuclear medicine department of the Royal Surrey County Hospital in Guildford, UK, between January 1998 and October 2002 were reviewed and 316 of these patients were classified as positive for pulmonary embolism with high probability scan on PIOPED criteria. The occurrence of positive scans was compared to environmental factors such as temperature, humidity, vapour pressure, air pressure and rainfall. Multiple linear regression was used to establish the significance of these relations. The incidence of pulmonary embolism was positively related to vapour pressure and rainfall. The most significant relation was to vapour pressure (p=0.010) while rainfall was less significant (p=0.017). There was no significant relation between pulmonary embolism and air pressure, humidity or temperature. It is postulated that rainfall and water vapour may be contributary factors in thrombosis and pulmonary embolism by way of pollutants that are carried as condensation nuclei in micro-droplets of water. In particular, fossil fuel pollutants are implicated as these condensation nuclei. Pollutants may be inhaled by populations exposed to windborne vapour droplets in cities or airports. Polluted vapour droplets may be absorbed by the lung to hasten coagulation cascades in the blood. This may lead to thrombosis and increased pulmonary embolism under high vapour pressure conditions. With combined factors such as pre-existing ill health or immobility on long flights, the risk of thrombosis and consequent embolism might increase substantially.
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PMID:The influence of weather and environment on pulmonary embolism: pollutants and fossil fuels. 1582 16

Thrombosis is a rare complication in patients with congenital clotting factor deficiencies. In most cases, it is related to inherited procoagulant factors, use of central venous catheters or administration of coagulation factor concentrates. There are only a few case reports about thrombotic events during treatment with fresh frozen plasma (FFP). We report the case of a patient with homozygous inherited factor V deficiency, who developed a pulmonary embolism at a time of treatment with methylene blue treated FFP (MBFFP). The patient had only two other factors predisposing to thrombosis and both were acquired: obesity and bed rest. He started anticoagulant treatment with low molecular weight heparin (LMWH) while the deficient factors were replaced with MBFFP. After 8 days of treatment the patient developed a severe respiratory insufficiency. Pulmonary haemorrhage was considered among the differential diagnosis and LMWH was stopped. An inferior vena cava filter was placed without any further thrombotic complications. To our knowledge, there are no reports about patients with clotting factor deficiencies who developed a thrombotic event during treatment with MBFFP.
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PMID:Pulmonary embolism in a patient with severe congenital deficiency for factor V during treatment with fresh frozen plasma. 1587 74

Optimal safety for a donor is an essential condition for living-related liver transplantation (LRLT). Severe pulmonary embolism may be a rare complication for the donors, but it is potentially fatal. Various risk factors and prophylactic methods for thromboembolic complications have been described. We report here a case of severe pulmonary embolism in a living-related liver transplantation donor who underwent right liver lobectomy, although the patient had no apparent risk factor for thromboembolism except for slight obesity (body mass index = 27). In addition, the donor received prophylactic use of graduated compression stockings and intermittent pneumatic compression by use of a special device from the start of anesthesia until the patient was able to ambulate. Fortunately, the patient was successfully treated with urokinase and heparin infusion followed by warfarin administration.
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PMID:A case of suspected severe pulmonary embolism in a living-related liver transplantation donor. 1589 92

Patients with Prader-Willi syndrome (PWS) are recognized to have a tendency of sudden, unexpected death (SED), but its exact cause is unknown because of paucity of such case reports. Since growth hormone (GH) treatment was applied to PWS patients worldwide, several cases of death have been reported. However, whether the therapy is directly related to their SED remains unknown, too. We collected 13 deceased PWS patients (Group A, aged 9 months to 34 years) who had never received GH therapy, and seven deceased patients (Group B, all boys aged 0.7-15 years) having received the therapy from the registration in PWS-patient-support associations and from the literature, respectively. We then compared the cause of SED between the two groups. Irrespective of GH therapy, SED of infants under age 1 year was associated with milk aspiration or hypothalamic dysregulation of respiration, while SED of patients in early childhood or adolescence occurred at sleeping in association with preceding viral infections. In contrast, SED of four adult (>20 years of age) patients who never received GH therapy was associated with complications, such as leg cellulites and pulmonary embolism, secondary to massive obesity and diabetes mellitus (DM). Two Group-B patients (aged 14 and 20 years) without any obesity-related or diabetes-related complications died of drowning in a bath tub, and their drowning death could be related to poor respiratory control. These findings indicated that the cause of SED is not essentially different between PWS patients with and without GH treatment. Deceased PWS patients may have had underlying respiratory dysregulation and hypothalamic dysfunction, and GH therapy might have led to certain obstructive respiratory disturbances that exacerbated the respiratory conditions. This will call clinicians' attention when using GH in PWS patients, for example, careful determination of the dose of GH and careful monitoring of patient's respiratory conditions, especially in male obese patients with respiratory problems.
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PMID:Cause of sudden, unexpected death of Prader-Willi syndrome patients with or without growth hormone treatment. 1593 39

Thrombotic events are an increasingly recognized complication of treatment with intravenous immunoglobulins (IVIg). We aimed to define clinical characteristics, risk factors and outcome for venous thrombosis as opposed to arterial thrombosis following administration of IVIg. Six patients with post-IVIg venous thrombosis were identified at our institution. In addition, a review of the literature revealed 65 reported cases. Arterial thrombosis (stroke and myocardial infarction) was four times more common than venous thrombosis (deep vein thrombosis and pulmonary embolism). The incidence rate was estimated at 0.15-1.2% per treatment course, but the large increase in reported cases in 2003 suggests that the true incidence may be significantly greater. The following differences were found between arterial and venous events: arterial thrombosis occurred early after IVIg administration (49% within 4 h, 77% within 24 h) and was associated with advanced age and atherosclerotic vascular disease; venous thrombosis occurred later (54% more than 24 h after IVIg administration) and was associated with factors contributing to venous stasis (obesity and immobility). Thirteen patients died (mortality 20%), 11 of whom had arterial thrombosis. In conclusion, IVIg-associated thrombosis is more common than previously recognized, and is associated with significant mortality. The different characteristics of arterial and venous events may reflect different pathophysiological mechanisms. A better understanding of these mechanisms should aid in defining a risk-benefit ratio for the individual patient.
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PMID:Venous and arterial thrombosis following administration of intravenous immunoglobulins. 1660 87

Japanese women are unaccustomed to taking hormone therapies such as oral contraceptives (OCs) and hormone replacement therapy (HRT); therefore, there are few studies associated with hormone treatment in Japan. This study focused on evaluating thromboembolism during hormone therapy in Japanese women. In February 2002, we mailed questionnaires regarding the monthly average number of patients who had received prescriptions for OCs and HRT, and the incidence of arterial and venous thromboemboli during hormone therapy for the last 10 years. The mailings were sent to hospitals and clinics that are registered as monitoring institutions with the Japan Association of Obstetricians and Gynecologists. Of 1083 institutes, 771 responded (71% response rate). In July 2002, to obtain additional information on hormone therapy, patient history, and outcomes, we sent follow-up questionnaires to 39 institutions that responded as having experienced cases of thromboembolism. Thirty-nine institutions (5.1% of institutions responding to survey) experienced 53 cases of thromboembolism during hormone therapy. The 53 patients included 29 who received OCs (OC patients), 13 who received HRT (HRT patients), and 11 who received other hormone treatment. Among the 29 OC patients, eight had been diagnosed as having arterial thromboembolism (ATE), including two patients with myocardial infarction (MI) and six with ischemic stroke, whereas 20 had venous thromboembolism (VTE), including two with pulmonary embolism (PE) The remaining patient had an unknown thromboembolic event. Of the OC patients, 75.9% had a thromboembolism within the first year, and 58.6% patients were in their 40s. In 13 HRT patients, seven had ATE, including two MI patients and three with ischemic brain stroke, whereas six had VTE, including one PE patient. The duration of HRT varied widely from less than 1 year to more than 3 years; moreover, the HRT type did not affect thromboembolism occurrence. More than 70% of ATE patients and less than one third of VTE patients had to be hospitalized for the treatment of thromboembolism, and more than 75% of VTE patients recovered completely. However, one third of the ATE patients recovered with mild sequelae, one OC patient had severe sequelae due to stroke, and another OC patient died due to an ischemic event. The estimated incidence of thromboembolism in OC patients and HRT patients was 3.6 to 14.4 and 1.7 to 3.4 per 100,000 woman-years, respectively. The risk factors of thromboembolism, which were found consistently in this study, included obesity, smoking, lifestyle, and aging. Approximately 95% of institutions had not experienced thromboembolism in their hormone therapy patients, suggesting the incidence of thromboembolism during hormone therapy might be low. However, according to an analysis of risk factors, screening users of hormone supplements may be essential for providing safe hormone therapy. Moreover, because of the early occurrence of thromboembolism during hormone therapy, especially with OCs, it is important to monitor and instruct patients with caution from immediately after therapy initiation.
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PMID:Thromboembolism during hormone therapy in Japanese women. 1605 96

Patients undergoing major lower-extremity orthopedic surgery such as total hip replacement (THR) and total knee replacement (TKR) are at an increased risk of venous thromboembolism (VTE). Routine prophylaxis is necessary to reduce the risk of deep vein thrombosis (DVT), which may progress to potentially fatal pulmonary embolism and secondary complications such as postthrombotic syndrome, recurrent DVT, and chronic pulmonary hypertension. Prophylaxis in patients undergoing TKR, THR, and hip fracture surgery is now standard practice and generally involves anticoagulant treatment with either low-molecular-weight heparin (LMWH) or warfarin for a period of 7 to 10 days, with extended prophylaxis in those with ongoing risk factors such as obesity, cancer, or previous VTE. Data from clinical practice suggest that there is a general trend toward longer postsurgical prophylaxis and shorter hospital stays, making practicality of treatment an important consideration. LMWH is effective for the prophylaxis of VTE, but the parenteral route of administration is not convenient for use in the outpatient setting. Warfarin, on the other hand, can be administered orally but requires the infrastructure for careful patient monitoring and dose adjustments because of its unpredictable dose-response relationship. The development of new anticoagulants has been pursued with the aim of improving efficacy, predictability, consistency of response, safety, and convenience. A recently approved anticoagulant, fondaparinux, has been proven to provide superior efficacy for the prevention of VTE compared with LMWH, but this agent requires parenteral administration and does not overcome the convenience issue. Ximelagatran is the oral form of the direct thrombin inhibitor melagatran, which is available for subcutaneous administration. Ximelagatran has a consistent anticoagulant response allowing fixed oral dosing without the need for coagulation monitoring. The efficacy and safety profile of melagatran/ximelagatran prophylaxis for VTE following THR and TKR has compared favorably with standard LMWH prophylaxis, as seen in the European METHRO II and III trials and EXPRESS trial, and with warfarin prophylaxis, as seen in the North American EXULT A and B trials. Several prophylactic treatment regimens have been evaluated in the European trials to determine the optimal dosing and timing of first dose of melagatran to achieve the best balance of efficacy and safety. Preoperative initiation of melagatran was more effective than when prophylactic treatment was initiated postoperatively, and the lowest rates of bleeding were associated with a postoperative initiation of prophylaxis. Early administration of the first postoperative melagatran dose (4 to 8 hours) was also associated with better prophylactic efficacy relative to a later postoperative start (8 to 12 hours). The results of the comprehensive international clinical trial program and in particular the optimal balance of efficacy/safety data provided by the METHRO III study have led to approval of melagatran/ximelagatran in 2004 in the European Union for the prevention of VTE in patients undergoing elective hip or knee replacement surgery. Ximelagatran has the potential to maximize the use of anticoagulation in patients discharged following major lower-extremity orthopedic surgery.
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PMID:Ximelagatran for the prevention of venous thromboembolism following elective hip or knee replacement surgery. 1612 14

Acutely ill general medical patients are at moderate-to-high risk of venous thromboembolism (VTE); approximately 10-30% may develop deep vein thrombosis or pulmonary embolism, the latter being a leading contributor to deaths in hospital. Medical conditions associated with a high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious disease. Predisposing risk factors for VTE in medical patients include history of VTE, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility, and obesity. Unfractionated heparin (UFH), low-molecular weight heparin (LMWH), and fondaparinux sodium have been shown to be effective agents in the prevention of VTE in medical patients. In this setting, UFH has a higher rate of bleeding complications than LMWH. There is no evidence supporting the use of aspirin, warfarin, or mechanical methods to prevent VTE in medical patients. We recommend either LMWH or fondaparinux sodium as well tolerated and effective thromboprophylactic agents in medical patients.
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PMID:Pharmacological prevention of venous thromboembolism in medical patients at risk. 1625 29

Hospitalized patients with acute medical conditions are at significant risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Despite consensus-group recommendations that at-risk medical patients should receive thromboprophylaxis, there is currently no consensus as to which patients are at risk, and many patients may not receive appropriate thromboprophylaxis. This paper reviews evidence for the risk of VTE associated with different medical conditions and risk factors, and presents a risk-assessment model for risk stratification in medical patients. Medical conditions associated with a moderate to high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Importantly, analyses of data from the MEDENOX study show that thromboprophylaxis significantly reduces the risk of VTE in these patient subgroups. Risk factors in medical patients include a history of VTE, history of malignancy, increasing age, thrombophilia, prolonged immobility, and obesity. These medical conditions and risk factors are included in a risk-assessment model which is hoped will provide a simple means of assisting clinicians in deciding whether thromboprophylaxis should be used in an individual patient.
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PMID:Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. 1627 Jun 26


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