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PubMed1997

Venous thromboembolism in the cancer patient.

Patients with malignancies are at increased risk of developing venous thromboembolic disease. Diagnosis and treatment of deep venous thromboembolism and pulmonary embolism in this group of patients poses some unique challenges, but generally should parallel that of patients without malignancy. Prophylaxis with low-dose warfarin should be considered in patients with indwelling central venous catheters and in some patients receiving chemotherapy for cancer. Although patients who present with idiopathic deep venous thromboembolism or pulmonary embolism may be at increased risk of developing clinically apparent malignancy, there is no data to suggest that an aggressive search for cancer in these patients is more appropriate than routine physical exam and laboratory testing.

Heparin↗

PubMed2003

Pulmonary thromboembolism after long car travel (Tromboembolismo pulmonar tras viaje prolongado en automóvil).

Prolonged immobility, especially bed rest for medical or surgical processes, constitutes one of the main risk factors for developing pulmonary thromboembolism. Immobility during extended plane or coach journeys (economy class syndrome) is not a frequent cause of serious pulmonary thromboembolism in healthy travellers. We report a case of serious pulmonary thromboembolism after a prolonged journey by car.

Automobiles↗

PubMed2005

Venous thromboembolic prophylaxis after elective total hip arthroplasty.

Elective total hip arthroplasty is a common orthopaedic procedure that has been proven to relieve pain and reliably improves the quality of life of its patients. However, patients having a total hip arthroplasty are among those at greatest risk for venous thromboembolic disease. Therefore, most orthopaedic surgeons use routine prophylaxis. Although several agents have been shown to reduce the risk of thromboembolic disease, there is no clear preference for a particular agent in elective total hip arthroplasty. This evidence-based review focuses on the efficacy and safety of the agents that currently are used for prophylaxis against deep venous thrombosis. These agents include warfarin, low-molecular-weight heparin, fondaparinux, aspirin, and mechanical devices. Furthermore, the influence of shorter hospital stays on duration of prophylaxis and screening will be discussed. The most effective prophylactic agents for patients after total hip arthroplasty include low-molecular-weight heparin, warfarin, and fondaparinux. Pneumatic compression devices have been proven to reduce distal thromboembolic events but multi-center, randomized studies need to be done to determine the efficacy of mechanical prophylaxis with short hospital stays. The selection of a prophylaxis regimen is a balance between efficacy and safety, and individual patient factors can influence the prophylaxis regimen that is used.

Arthroplasty, Replacement, Hip↗

PubMed2005

The John Charnley Award: prevention of readmission for venous thromboembolic disease after total hip arthroplasty.

UNLABELLED: Venous thromboembolic disease remains the most common reason for readmission after total hip arthroplasty. Prospective analysis of screening contrast venography was done from 1984 to 2003 in 1972 patients having elective total hip arthroplasty. Patients with deep venous thrombosis or pulmonary embolism received warfarin therapy; those with negative venograms received no further anticoagulation. From 1984 to 1992, patients not completing venography were discharged without warfarin; since 1993, patients without venography received warfarin for 6 weeks. Readmission for deep venous thrombosis, pulmonary embolism, or bleeding was tracked for 6 months. Venograms were completed in 1032 patients; 175 (16.9%) had deep venous thrombosis. Deep venous thrombosis was reduced by a clinical pathway that included continuous epidural anesthesia (14.2% versus 22.5%). The overall readmission rate for venous thromboembolic disease was 1.62%, including 14 pulmonary emboli (three fatal) and 18 femoral deep venous thrombosis. Readmission occurred in 0.27% (1 of 360) patients on continued warfarin, compared with 2.2% (19 of 880) with negative venograms discharged without further anticoagulation. Three patients (0.15%) suffered fatal pulmonary emboli; all had negative venograms and received no outpatient prophylaxis. Extended outpatient warfarin therapy provided effective protection against venous thromboembolic disease readmission. Surveillance venography was a poor predictor of need for continued prophylaxis; all patients should have extended anticoagulation after total hip arthroplasty. LEVEL OF EVIDENCE: Therapeutic study, Level I-1 (high-quality randomized trial with statistically significant difference or no statistically significant difference but narrow confidence intervals). See the Guidelines for Authors for a complete description of levels of evidence.

Anticoagulants↗

PubMed2005

Recruitment maneuver and high positive end-expiratory pressure improve hypoxemia in patients after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism.

OBJECTIVES: To investigate the effects of a recruitment maneuver and high positive end-expiratory pressure (PEEP) on oxygenation and hemodynamics in hypoxemic patients with pulmonary hypertension after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. DESIGN: Prospective, observational, clinical study. SETTING: A surgical intensive care unit in a national heart institute. PATIENTS: Fourteen consecutively admitted patients who developed acute lung injury (Pa(O2) <300 torr at F(IO2) 1.0) and pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. INTERVENTIONS: The recruitment maneuver was an increase of PEEP to 30 cm H2O in one step for 1 min at F(IO2) 1.0. The level of pressure control ventilation during the recruitment maneuver was the same as before the maneuver. Subsequently, PEEP was decreased in 15-min intervals from 15 to 10, 5, and 0 cm H2O. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and respiratory variables were analyzed before and during the recruitment maneuver and at each PEEP level. At F(IO2) 1.0, Pa(O2) increased from 240 +/- 62 torr to 470 +/- 83 torr at 15 cm H2O of PEEP and 469 +/- 75 torr at 10 cm H2O of PEEP after the recruitment maneuver (p < .001). At 15 cm H2O of PEEP, cardiac index decreased (from 2.7 +/- 0.6 at baseline to 2.2 +/- 0.3 L.min(-1).m(-2), p < .01) and mean blood pressure decreased (from 86 +/- 8 at baseline to 74 +/- 11 mm Hg, p < .05), but they returned to the baseline levels at 10 cm H2O of PEEP (2.5 +/- 0.4 L.min(-1).m(-2) and 83 +/- 9 mm Hg). There were no differences in mean pulmonary artery pressure at different levels of PEEP. CONCLUSIONS: In hypoxemic patients with pulmonary hypertension after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism, oxygenation was improved by the recruitment maneuver followed by high PEEP. However, hemodynamics were transiently suppressed and overall oxygen delivery did not change.

Adult↗

PubMed2004

Prevention of venous thromboembolism in the plastic surgery patient.

The term venous thromboembolism refers to a spectrum of disease that includes deep venous thrombosis and pulmonary embolism. Both deep venous thrombosis and pulmonary embolism are often clinically silent and thus difficult to diagnose, which leads to a substantial delay in treatment that results in high rates of morbidity and mortality. The purposes of this article are to help physicians determine the proper venous thromboembolism prophylaxis and to simplify the complex problem of treating venous thromboembolism. The tools provided in this article will help expedite and clarify the decision-making process.

Adult↗

PubMed2004

Tumor thromboembolism masquerading as bland pulmonary embolism.

Catheter-based interventions provide an important alternative to medical surgical management of massive central pulmonary thromboembolism. Because this option is increasingly being used, it is important to recognize that not all pulmonary thromboemboli are bland. The authors describe two cases in which tumor masqueraded as bland thromboembolism. Identification of tumor thromboembolism may help to alter future work-ups, provide useful prognostic information for a patient, and affect future treatment options.

Carcinoma, Bronchogenic↗

PubMed1993

The effect of defibrotide on thromboembolism in the pulmonary vasculature of mice and rabbits and in the cerebral vasculature of rabbits.

1. Administration of bovine thrombin (100 u kg-1) into the carotid artery of rabbits induces a sustained accumulation of 111 Indium-labelled platelets within the cranial vasculature over the subsequent 3 h. 2. Intracarotid (i.c.) administration of defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h) prior to i.c. thrombin (100 u kg-1) significantly reduces the ability of thrombin to induce cranial thromboembolism in rabbits. 3. Intravenous (i.v.) administration of thrombin (20 u kg-1) in rabbits induces a reversible accumulation of radiolabelled platelets into the thoracic circulation which is significantly reduced by i.v. administration of defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h) prior to i.v. thrombin. In contrast, platelet accumulation in response to adenosine diphosphate (ADP; 20 micrograms kg-1, i.v.) or platelet activating factor (PAF; 50 ng kg-1, i.v.) is not significantly affected by this treatment. 4. Intravenous administration of the nitric oxide (NO)-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg kg-1) potentiates platelet accumulation induced by low dose thrombin (10 u kg-1, i.v.) within the pulmonary vasculature of rabbits. The potentiated response is significantly abrogated following pretreatment with defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h, i.v.). 5. Intravenous injection of human thrombin (1250 u kg-1) to mice induces death within the majority of animals which is significantly reduced by pretreatment with defibrotide (150-175 mg kg-1, i.v.). In contrast, death induced by i.v. collagen (1.25 mg kg-1) plus adrenaline (75 microg kg-1) is not significantly affected by defibrotide pretreatment.6. The inhibitory effect of defibrotide in mice is abolished following concomitant treatment with the inhibitor of fribrinolysis, tranexamic acid (100 mg kg-1, i.v.), but is unaffected following treatment with the cyclo-oxygenase inhibitor, aspirin (300 mg kg-1, i.p.).7. The protective effect of defibrotide against thrombin-induced thromboembolism in the mouse is potentiated by recombinant tissue-plasminogen activator (rt-PA; 1 mg kg-1, i.v.) or unfractionated heparin (10 u kg-1, i.v.) administration.8. The results suggest that defibrotide may possess antithrombotic activity on thrombin-induced thromboembolism which, at least in the mouse, may be partially mediated via induction of the fibrinolytic pathway.

Animals↗

PubMed1983

Occult pulmonary thromboembolism presenting as diffuse interstitial pneumonitis in cancer patients.

The prompt and accurate recognition of non-malignant complications is of critical importance in the care of cancer patients. Pulmonary thromboembolism is particularly important because it is common, treatable and frequently difficult to diagnose. Two patients are presented who died of recurrent pulmonary thromboemboli which were unrecognized because open lung biopsies showed diffused interstitial pneumonitis. The association of pulmonary thromboembolism and interstitial inflammation has been recognized at autopsy, and there are a number of plausible mechanisms which could link these processes. Interstitial pneumonitis should be added to the numerous protean manifestations with which pulmonary thromboembolism is associated.

Adult↗

PubMed1997

Low-molecular-weight heparin: prophylaxis and treatment of venous thromboembolism.

Intravenous heparin followed by warfarin has been the classical anticoagulant therapy of acute venous thromboembolism for the last 30 years. Furthermore, low-dose unfractionated heparin given two to three times daily has been the most popular form of prophylaxis for venous thrombosis. In recent years, a number of low-molecular-weight heparins have become available for clinical trials. These agents have many advantages over unfractionated heparin and are now being used widely internationally for the prevention and treatment of venous thromboembolism. Indeed, low-molecular-weight heparin will undoubtedly replace intravenous unfractionated heparin not only in the treatment of venous thromboembolism, but in other conditions where heparin therapy is indicated. Whether or not the low-molecular-weight heparins can decrease or eliminate some of the complications of unfractionated heparin will depend on the outcome of future clinical trials.

Fibrinolytic Agents↗

PubMed1992

Chronic major-vessel thromboembolic pulmonary artery obstruction: appearance at angiography.

The pulmonary angiograms of 250 patients evaluated for chronic thromboembolic pulmonary hypertension were reviewed. Pulmonary thromboendarterectomy was performed in each of these individuals, and the surgical findings were correlated with abnormal angiographic patterns. The pulmonary angiographic findings suggestive of chronic thromboembolic disease included "pouching" defects, webs or bands, intimal irregularities, abrupt vascular narrowing, and complete vascular obstruction. Pouching is reported by the authors to be a previously undescribed angiographic feature of this disease. Carefully obtained and properly interpreted pulmonary angiograms are necessary to confirm the diagnosis of operable chronic thromboembolic disease. Differential diagnostic possibilities should be considered prior to a decision to perform surgical correction.

Adolescent↗

PubMed1994

Chronic pulmonary thromboembolism: detection of regional hypoperfusion with CT.

PURPOSE: To study the relationship of regional hypoperfusion and areas of decreased lung attenuation on computed tomographic (CT) scans of patients with chronic pulmonary thromboembolism. MATERIALS AND METHODS: Preoperative CT scans of five patients (four men and one woman, aged 29-72 years) with chronic pulmonary thromboembolism were reviewed and compared with axial single photon emission CT (SPECT) perfusion scans obtained at similar levels. Regions of varying attenuation and perfusion were scored on a three-point scale. RESULTS: In the five patients, 198 regions were identified. Of 176 abnormal regions at SPECT, 133 were abnormal at CT (sensitivity, 75.6%). Eleven of 22 regions interpreted as normal at SPECT were judged to have normal attenuation at CT (specificity, 50%). The overall accuracy of CT for detecting areas of hypoperfusion was 72.7% (P = .011). CONCLUSION: A mosaic pattern of lung attenuation at CT is a sign of variable regional perfusion and may suggest chronic pulmonary thromboembolism as a cause for pulmonary hypertension.

Chronic Disease↗

PubMedDate not supplied

Surgical treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: There are only limited treatment options for patients with chronic thromboembolic pulmonary hypertension in Canada. OBJECTIVE: To conduct a case-series study to assess the effectiveness of surgical endarterectomy of the pulmonary artery. DESIGN AND SETTING: Twenty-one patients with chronic thromboembolic pulmonary hypertension were admitted for surgery between July 1995 and October 1999. Clinical, laboratory and radiological data were collected for all patients who then underwent pulmonary thromboendarterectomy. MAIN RESULTS: Thirteen men and eight women between 22 and 71 years of age underwent surgery. The main presenting complaint was dyspnea on exertion. Pulmonary vascular resistance ranged from 382 to 1694 dynes s cm-5 with a mean of 765+/-372 dynes s cm-5 (normal is less than 180 dynes s cm-5) with a mean cardiac index of 2.2+/-0.9 L/min/m2. Two patients had concomitant tricuspid valve replacement and one patient had coronary bypass grafting. In three cases, the surgery involved a repeat sternotomy. After surgery, there was a significant drop in the pulmonary vascular resistance (208+/-92 dynes s cm-5, P<0.05) and a concomitant rise in the cardiac index to a mean of 3.1+/-0.6 L/min/m2 (P<0.05). There was one death in a patient who also had severe chronic obstructive pulmonary disease. Of the remaining patients, all but two showed significant clinical improvement. Spiral computed tomography postsurgery demonstrated improvement in pulmonary perfusion with either complete clearing or significant improvement in the mosaic perfusion pattern. Right ventricular function and pressure on echocardiogram improved in all but two patients. CONCLUSIONS: Pulmonary thromboendarterectomy provides effective treatment for chronic thromboembolic pulmonary hypertension.

Adult↗

PubMed1998

The special case of venous thromboembolism in pregnancy.

Pulmonary thromboembolism remains a major cause of maternal death in the Western world. The frequency of antepartum deaths, including deaths in the first and second trimester, which can be associated with early pregnancy problems such as hyperemesis, is similar in number to the deaths occurring following delivery. Risk factors for deep vein thrombosis have been identified and include age > 35 years, operative delivery (particularly emergency Caesarean section), obesity and a personal or family history of thrombosis or thrombophilia. These risk factors should be used to guide administration of thromboprophylaxis during both pregnancy and the post-partum period, particularly after Caesarean section. Specific consideration towards thromboprophylactic agents is required. Warfarin crosses the placenta, is a known teratogen when used in early pregnancy and can also be associated with bleeding problems in the foetus, particularly at the time of delivery. Thus, warfarin has a limited use in the antenatal period and is usually only employed in patients such as those with artificial heart valves who require long-term anticoagulation. However, as warfarin does not cross the breast in any significant amount, it is suitable during breast feeding. In contrast, heparin does not cross the placenta or the breast therefore foetal problems are not associated with this treatment. However, heparin can be associated with problems such as heparin-induced osteoporosis, allergy and heparin-induced thrombocytopenia. The risk of some of these complications can be reduced by the use of low-molecular-weight heparins. When venous thromboembolism is suspected in pregnancy, it is critically important to obtain an objective diagnosis. This will include real-time or duplex ultrasound scan of the legs to elaborate the venous system, ventilation perfusion lung scan and, occasionally, venography. Treatment of established venous thromboembolism is similar to that in the non-pregnant patient and it is likely that low-molecular-weight heparins will play a major role in thromboprophylaxis in the future.

Adult↗

PubMedDate not supplied

Assessment of the risk and prophylactic treatment of venous thromboembolism in the elderly.

Numerous large randomized controlled trials have assessed the benefit of prophylactic anticoagulation for venous thromboembolism in selected patients. However, few trials were conducted in elderly patients, as this issue was not addressed in this specific population,or as elderly patients were excluded of these studies. Therefore, as the risk of a first episode of venous thromboembolism (in surgical and in medical setting) and the risk of a major anticoagulant-related bleeding are both increased in elderly subjects, the results of the main available studies can not be extrapolated to this population. Consequently, in practice, the balance between expected benefit and risk of prophylactic anticoagulation should be carefully assessed for each individual elderly patient taking in account the specific risk of venous thromboembolism in elderly in the absence of anticoagulation, the risk of anticoagulant related bleeding according to the type of anticoagulant treatment and the intrinsic risk of bleeding of elderly subjects and, lastly, the available guideline recommendations. In order to improve such evaluation, it is anticipated that further prophylactic studies are needed in elderly patients. In addition, the development of anticoagulation clinics and new oral anticoagulants should help to reduce anticoagulant related bleeding for an equivalent, or an increased, benefit.

Aged↗

PubMedDate not supplied

Cerebral thromboembolism among young women and men in Denmark 1977-1982.

In the period 1977-1982, the Danish National Patient Register recorded 1000 cases of cerebral thromboembolic attacks among women 15-44 years of age, and 971 cases among men of the same age. Cerebral infarction accounted for 70% of cases and transient ischemic attacks (TIA) for the remaining 30%. By analysing this material we found an average age-adjusted incidence rate of cerebral thromboembolism of 14.4/100.000 among men and 15.5/100.000 among women. The incidence rates rose rapidly with increasing age. Women aged 15-34 had significantly higher incidence rates of brain infarction and TIA compared to those of men of the same age. This was reversed in the age group 35-44. The magnitude of the ratio between the female and the male mean incidence rates by increasing age corresponded exactly to the age distribution of the use of oral contraceptives in Denmark. The relative risk for developing cerebral thromboembolism among users of oral contraceptives was estimated to be 3.2-6.5. The mortality in male patients with brain infarction was 3.3% and in females 1.7%. The mean duration of stay in hospital was 8.8 days for TIA and about 26 days for cerebral infarction. Sixteen percent of men and 13.6% of women had hypertension during their stay.

Adolescent↗

PubMed2001

Hemorrhagic transformation after fibrinolysis with tissue plasminogen activator: evaluation of role of hypertension with rat thromboembolic stroke model.

BACKGROUND AND PURPOSE: We used a rat model of thromboembolic stroke to evaluate whether hypertension increases the incidence of hemorrhage after fibrinolysis with tissue plasminogen activator (tPA). METHODS: In this model, a microclot suspension was injected into the middle cerebral artery territory to induce focal ischemia. Reperfusion was induced in spontaneously hypertensive rats (SHR) by administering tPA (10 mg/kg) intravenously at 2 hours or 6 hours after the onset of thromboembolic focal ischemia. In untreated control rats, saline was administered at 2 hours after ischemia. RESULTS: Hemorrhagic transformation was observed only in rats that received tPA at 6 hours (6 of 8 rats [75%]). Reduction of mean arterial blood pressure from 122+/-3 to 99+/-2 mm Hg with hydralazine, given to SHR for 1 week before ischemia, significantly decreased the incidence of hemorrhage in 2 of 11 rats (18%). tPA reduced infarct volumes, but cotreatment with hydralazine did not result in further protection. CONCLUSIONS: This study demonstrates that in this rat thromboembolic model of stroke, tPA-induced hemorrhage is dependent on blood pressure and that pharmacological reduction of hypertension during fibrinolysis can reduce the risk of hemorrhagic transformation.

Animals↗

PubMed2001

Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement.

BACKGROUND: With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement. METHODS AND RESULTS: This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7+/-2) and confirmed symptomatic venous thromboembolism recorded </=48 hours after the last dose of rNAPc2. Primary safety outcome was major bleeding </=72 hours after the last dose. An independent, blinded Central Adjudication Committee assessed all outcome events. Of 293 patients studied, 251 (86%) could be evaluated for primary efficacy analysis. A dosage of 3.0 microgram/kg administered within 1 hour after surgery provided the best observed results, with an overall deep vein thrombosis rate of 12.2%, a proximal deep vein thrombosis rate of 1.3%, and a major bleeding rate of 2.3%. CONCLUSIONS: A randomized, double-blind trial that compared rNAPc2 with current best prophylactics is warranted based on encouraging, first-reported clinical results for a factor VIIa/tissue factor inhibitor evaluated for thrombosis prophylaxis.

Aged↗