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Anti-Xa effect of a low molecular weight heparin (dalteparin) does not accumulate in extended duration therapy for venous thromboembolism in cancer patients.

Many patients with venous thromboembolism are being treated with low molecular weight heparin for extended periods of time. It is not certain if it is necessary to assess anti-Xa levels for extended treatment periods. This study is a prospective assessment of anti-Xa levels in patients on long-term therapy for acute venous thromboembolism who have active cancer. Consecutive consenting patients from one center in a multicenter trial that compared 6 months of low molecular weight heparin with oral anticoagulant therapy were treated with therapeutic doses of dalteparin (200 IU per kilogram) subcutaneously daily. Anti-Xa levels were assessed at the end of weeks 1 and 4,4-6 hours after injection of dalteparin. Patients were followed for bleeding and recurrent venous thromboembolism. There were 24 patients who had anti-Xa levels measured at weeks 1 and 4. Two other patients had week 1 measurements performed but died before the week 4 sample was collected due to their underlying cancer. The mean anti-Xa levels at weeks 1 and 4 were 1.11 and 1.03 anti-Xa units/ml respectively (P=0.13). These results suggest that for patients with active cancer receiving extended duration therapy with low molecular weight heparin (dalteparin) there is no accumulation of anti-Xa effect over the first month of therapy. Monitoring of anti-Xa levels in this situation is usually not required.

Adult↗

Preeclampsia and pregnancy loss in women with a history of venous thromboembolism and prophylactic low-molecular-weight heparin (LMWH) during pregnancy.

Limited data are available regarding complications of pregnancy and pregnancy outcome under prophylaxis with low-molecular-weight heparin (LMWH) in women with a history of thromboembolism (TE). We retrospectively evaluated pregnancy complications in a cohort of 80 women. All had a history of TE (76 venous, two arterial and two venous and arterial) and received prophylactic LMWH during 86 pregnancies. The rate of preeclampsia and stillbirth in these women was compared to that of a control group of 313 women without a history of TE and LMWH. Prophylaxis was started at a median of 10 weeks of gestation and usually continued until six weeks post partum. In 94% of the cases the outcome of pregnancy was favourable with a live birth. Four pregnancies (4.7%) ended in miscarriage. Two (2.3%) pregnancies were complicated by a thromboembolic event (one deep leg vein thrombosis and PRIND, respectively). One patient developed HELLP-syndrome. Severe preeclampsia occurred in three (3.8%) and stillbirth in one (1.3%) of the patients (n = 80), whereas this was the case in four (1.3%, odds ratio 3.01; 95% confidence interval (CI) 0.66-13.73, p = 0.15) and 10 (3.2%, OR = 0.38; 95% CI 0.05-3.04, p = 0.72) control women. Mean birth weight and standard deviation of infants was 3,160 +/- 930 g in patients and 3,300 +/- 540 g in controls (p = 0.11). We conclude that a favourable pregnancy outcome in women with a history of thromboembolism who use prophylactic LMWH during pregnancy can be expected. There was a trend towards a higher risk of preeclampsia, and these women should be carefully monitored for this complication.

Abortion, Spontaneous↗

Hypercholesterolemia enhances thromboembolism in arterioles but not venules: complete reversal by L-arginine.

We investigated in vivo the effect of cholesterol diet-induced hypercholesterolemia (HC) on thromboembolism in nonatherosclerotic rabbit mesenteric arterioles and venules (diameter 21 to 45 micrometer). After mechanical vessel wall injury, the ensuing thromboembolic reaction was studied by intravital videomicroscopy. A dramatic prolongation of embolization duration (median >600 seconds) was observed in the arterioles of the HC group compared with the arterioles of a normal chow-fed (NC) control group (142 seconds, P<0.0001); concomitantly, relative thrombus height increased (thrombus height/vessel diameter was 68% for the HC group and 58% for the NC group; P<0.05). By contrast, in venules, cholesterol did not affect embolization duration (42 seconds for HC group, 34 seconds for NC group) and thrombus height (66% for HC group, 64% for NC group). Furthermore, the role of endothelial NO synthesis was studied. In arterioles, stimulation of endogenous NO synthesis through mesenteric superfusion of L-arginine (1 mmol/L) completely reversed cholesterol-enhanced embolization (152 seconds) but did not influence thrombus height (63%). L-Arginine had no effect in venules of the HC group (51 seconds) and nor in the arterioles and venules of the NC group (177 seconds for arterioles, 43 seconds for venules). This study indicates that hypercholesterolemia selectively enhances thrombus formation and embolization in arterioles but not in venules and that stimulation of endogenous NO production antagonizes this enhancement of arteriolar thromboembolism.

Animals↗

Cardioversion of nonrheumatic atrial fibrillation. Reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution.

BACKGROUND: The use of warfarin anticoagulation for several weeks before cardioversion results in a 90% reduction in the incidence of cardioversion-related thromboembolism. The mechanism of this benefit, however, is unknown; it has been widely attributed to organization and adherence of atrial thrombi, a finding observed among pathological studies of patients with rheumatic valvular disease. METHODS AND RESULTS: Serial transesophageal echocardiography was performed in 14 patients with nonrheumatic atrial fibrillation after identification of atrial thrombi on initial transesophageal study. All patients received warfarin anticoagulation and were followed clinically for signs of thromboembolism. Eighteen atrial thrombi were identified on initial transesophageal study, including 14 thrombi confined to the left atrial appendage, 2 in the body of the left atrium, 1 in the right atrial appendage, and 1 in the body of the right atrium. Thrombus size varied from 5 to 20 mm, and 6 were considered mobile. After a median of 4 weeks of warfarin, 16 of 18 atrial thrombi (89%; 95% CI, 73% to 100%) had completely resolved on transesophageal echocardiographic study. In addition, no new thrombi were identified on follow-up study, and no patient had a clinical thromboembolic event between studies. CONCLUSIONS: These data strongly support the hypothesis that among patients with nonrheumatic atrial fibrillation, the mechanism of clinical benefit with 3 to 4 weeks of warfarin before cardioversion is related to thrombus resolution and prevention of new thrombus formation rather than thrombus organization.

Aged↗

Low-molecular-weight heparinoid orgaran is more effective than aspirin in the prevention of venous thromboembolism after surgery for hip fracture.

BACKGROUND: The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid (Orgaran) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips. A double-blind, randomized, controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals. METHODS AND RESULTS: Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti-Factor Xa units or aspirin 100 mg orally twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. All patients had postoperative 125I-fibrinogen leg scanning and impedance plethysmography. If the results of one or both tests were positive, then venography was performed. Otherwise, venography was done at day 14, or sooner if the patient was ready for discharge. Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan, a positive angiogram, or a clinically significant embolism detected at autopsy. Evaluable venograms were obtained in 90 of the 125 patients randomly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin. Venous thromboembolism was detected in 25 (27.8%) patients in the Orgaran group and in 39 (44.3%) patients in the aspirin group. Thus, there was a relative risk reduction of 37% with Orgaran (P=.028; 95% confidence interval, 3.7% to 59.7%). Six (6.8%) of 88 patients in the Orgaran group and 12 (14.3%) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism, a relative risk reduction of 52% with Orgaran (P=.137; 95% confidence interval, -30.7% to 84.6%). Hemorrhagic complications occurred in 2 (1.6%) patients given Orgaran and 8 (6.4%) patients given aspirin (P=.10). There was one major bleed in the Orgaran group compared with four in the aspirin group. CONCLUSIONS: This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.

Administration, Oral↗

Hemodynamic effects of nonionic contrast bolus injection and oxygen inhalation during pulmonary angiography in patients with chronic major-vessel thromboembolic pulmonary hypertension.

BACKGROUND: Pulmonary angiography is the gold standard for the diagnosis of chronic thromboembolic pulmonary hypertension; however, major complications have been reported. This study evaluates the hemodynamic effects of direct pulmonary nonionic contrast bolus injection and oxygen inhalation in patients with chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: In 33 patients, hemodynamic parameters were measured after oxygen inhalation and during bolus injection of nonionic contrast medium in a control group (group 1. n = 11), in a group of patients with moderately severe pulmonary hypertension (group 2, n = 9), and in a group with severe pulmonary hypertension (group 3, n = 13). Oxygen inhalation significantly improved oxygen supply. Pulmonary artery pressure and heart rate were reduced, but pulmonary vascular resistance and total pulmonary resistance were not significantly affected. One hundred ninety-eight angiograms were performed selectively on both pulmonary arteries in the posterior-anterior, oblique, and lateral views. Before contrast bolus injection, RAP and PAP significantly increased because of initial inspiration. Contrast bolus injection caused only a minor pressure increase (delta PA systolic, 2.3 +/- 1.4, 2.5 +/- 1.8, and 5.0 +/- 5.2 mm Hg, groups 1, 2, and 3, respectively) without significance between the groups. After the angiography, pulmonary artery pressure was moderately increased, predominantly in group 3, but pulmonary vascular resistance was not significantly changed. Systemic vascular resistance was decreased. Cardiac index increased in groups 1 and 2 but was unchanged in group 3. Systemic pressure therefore decreased in group 3. CONCLUSIONS: We concluded that bolus injection of nonionic contrast medium causes no major hemodynamic effects even in patients with severe chronic thromboembolic pulmonary hypertension. Oxygen contributes to safety during the procedure.

Administration, Inhalation↗

Intravenous administration of acetylsalicylic acid during endovascular treatment of cerebral aneurysms reduces the rate of thromboembolic events.

BACKGROUND AND PURPOSE: The purpose of this study is to analyze the effect of a modified intraoperative anticoagulation strategy including acetylsalicylic acid (ASA) on complication rates during endovascular coil embolization. METHODS: Two hundred and sixty-one cerebral aneurysms were treated in 247 patients by endovascular coil embolization from January 2001 to September 2004. Additional intravenous administration of 250 mg ASA was applied since January 2003. Patients treated before (-ASA; n=102 aneurysms) and after that date (+ASA; n=159 aneurysms) were compared. End points were rates of thromboembolism and severity of hemorrhages after intraoperative aneurysm rupture. RESULTS: Thromboembolic events during the procedure were observed more often in the -ASA group (18/102 aneurysms, 17.6%) in comparison with the +ASA group (14/159 aneurysms, 8.8%; P=0.028; Fisher exact test). Aneurysm perforation events occurring during or immediately after the procedure were observed equally often in the -ASA group (7/102 aneurysms, 6.9%) in comparison with the +ASA group (10/159 aneurysms, 6.3%). CONCLUSIONS: Intravenous application of ASA is feasible and safe during interventional aneurysm embolization. ASA seems to be associated with a significant reduction in the rate of thromboembolic events without increase in the rate or severity of intraoperative bleedings.

Adult↗

Three-dimensional gadolinium-enhanced magnetic resonance angiography used as a "one-stop shop'' imaging procedure for venous thromboembolism: a pilot study.

Pulmonary embolism and deep venous thrombosis are individual manifestations of a single entity, venous thromboembolic disease. This study aimed to assess the feasibility of 3-dimensional gadolinium-enhanced magnetic resonance angiography used as an "one-stop shop'' imaging procedure visualizing both the pulmonary arteries and the deep lower venous system within a single investigation. The inclusion criterion was a proven or excluded venous thromboembolism. Diagnosis was based on an imaging work-up for pulmonary embolism including either perfusion lung scan or contrast-enhanced spiral computed tomography, or both, and an imaging work-up for deep venous thrombosis including either venous color-coded duplex sonography or ascending phlebography, or both. A gadolinium-enhanced "one-stop shop'' magnetic resonance angiography was performed within 24 hours of completed diagnostic imaging work-up for pulmonary embolism and deep venous thrombosis in 20 patients. Results of pulmonary magnetic resonance angiography were concordant with perfusion lung scan and/or computed tomography in 90% of patients. Magnetic resonance angiography results of the deep lower venous system were concordant with venous duplex sonography and/or phlebography in 75% of patients and seemed to be more precise in 25% of patients. The "one-stop shop'' imaging procedure using gadolinium-enhanced magnetic resonance angiography was feasible and proved to offer a reliable and rapid diagnostic approach in thromboembolic disease, sparing patients' exposure to ionizing radiation and iodinated contrast media.

Adult↗

Effects of giant left atrium on thromboembolism after mitral valve replacement.

The aim of this study was to evaluate the incidence of thromboembolic events in patients with giant left atrium ( > 6.5 cm) after mitral valve replacement. From January 2000 to September 2002, a total of 126 patients who had undergone mitral valve replacement were divided into two groups according to the presence or absence of giant left atrium. Group A comprised 34 patients with left atrium over 6.5 cm without compression symptoms and Group B comprised 92 patients. The preoperative variables did not distinguish the patients in each group, except for atrial fibrillation; Group A 85.2% and Group B 61.9% ( p < 0.01). After mitral valve replacement, left atrium mean diameter was significantly decreased in Group A from 8.1 +/- 1.3 mm to 6.2 +/- 1.6 mm ( p < 0.01). There were no significant differences in thrombosis, hemorrhage and thromboembolism rates in both groups. Postoperative clinical and hemodynamic parameters demonstrated a positive clinical response to mitral valve replacement in patients with giant left atrium. During follow-up no direct relationship between thromboembolism and giant left atrium was evident.

Adolescent↗

Idiopathic thromboembolism associated with triphasic oral contraceptives.

Oral contraceptives are one of the most effective and widely used of the reversible contraceptive methods. Thromboembolic disease associated with the use of oral contraceptives has been widely reported. In recent years, attempts to understand the pathogenesis of oral contraceptive-induced thromboembolic disease have found a correlation between larger estrogen doses and increased risk for a thrombotic event. Because the newer triphasic oral contraceptives provide effective contraception with a method of administration that mimics normal hormonal fluctuations during the menstrual cycle, some prescribers may infer that these products are associated with a decreased incidence of adverse effects over alternative oral contraceptives. We present two cases of idiopathic thromboembolism associated with the use of a triphasic oral contraceptive with a discussion of the proposed pathogenic mechanisms for these events.

Adult↗

Thromboembolic disease and present oral contraception.

Since their introduction, oral contraceptives have been linked to an increased incidence of thromboembolic events. Epidemiologic studies have shown that women who use third-generation oral contraceptives containing desogestrel, gestodene, or norgestimate have a higher risk of venous thrombosis than women who use second-generation oral contraceptives containing levonorgestrel. Women who use oral contraceptives are significantly less sensitive to activated protein C. From January 1996 to December 2001, 17,577 patients were hospitalized in our department, 177 of them (1%) had confirmed diagnosis of venous thromboembolism and 15 of those (177) were women on oral contraceptive therapy. Oral contraceptives were taken from 28 days to 18 months. No other potential congenital or acquired causes of thrombosis were present before thromboembolic events occurred in these women. The discontinuation of the pill combined with usual heparin (in one patient thrombolysis) and coumarin therapy was effective in all cases. After the discontinuation of coumarin (3-6 months), every patient was screened for hereditary thrombophilia. All women on oral contraceptive therapy had confirmed hereditary risk factors for venous thrombosis. Acquired resistance to activated protein C may explain the epidemiologic observation of increased risk of venous thrombosis in oral contraceptive users, especially in women using third-generation oral contraceptives who had other risk factors (hereditary or acquired) for venous thrombosis.

Contraceptives, Oral↗

Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period.

This study evaluated enoxaparin alone versus initial enoxaparin followed by warfarin in secondary prevention of venous thromboembolic events in adults with active malignancy. Cancer patients (n = 122) with acute symptomatic venous thromboembolic events were randomly allocated to receive subcutaneous enoxaparin 1.0 mg/kg every 12 hours for 5 days, followed by 1.0 mg/kg daily (group 1a) or 1.5 mg/kg daily (group 1b) for 175 days, or subcutaneous enoxaparin 1.0 mg/kg every 12 hours for at least 5 days and until a stable international normalized ratio of 2 to 3 was achieved on oral warfarin begun on day 2 and continued to day 180 (group 2). There were no significant differences in major and minor bleeding rates between treatment groups. No bleeding events were intracranial or fatal. Enoxaparin treatment was feasible, generally well tolerated, and effective for a 180-day period in the secondary prevention of venous thromboembolic events in patients with active malignancy.

Adult↗

Postdischarge prophylaxis for venous thromboembolism among high-risk surgery patients.

The role of pharmacological prophylaxis against venous thromboembolism in high-risk surgical patients is straightforward during hospitalization but controversial after hospital discharge. Clinical trials based upon venography-detected deep vein thrombosis (DVT), yield high DVT rates which may not be clinically relevant, since most cases are asymptomatic. On the other hand, clinical surveys based upon clinically overt venous thromboembolism yield low DVT rates that underestimate the problem. If postdischarge prophylaxis is used, oral anticoagulants may be more cost-effective than low-molecular-weight heparins. However, optimal strategies for venous thromboembolism prophylaxis after hospital discharge will not be definitively provided until large studies are performed with sufficient power to detect clinically relevant endpoints such as symptomatic DVT or pulmonary embolism.

Anticoagulants↗

Thromboembolic complications after endovascular aortic aneurysm repair.

PURPOSE: To evaluate the frequency and significance of thromboembolic complications following endovascular treatment of aortic aneurysms. METHODS: One hundred seventy-four patients (153 men; mean 71.4 years, range 26-90) underwent endovascular repair of aneurysms of the thoracic (n = 38) or abdominal (n = 136) aorta using a variety of endografts. All patients were examined preprocedurally using 3-phase helical computed tomography (CT) to determine appropriate endograft size. To exclude the occurrence of infarction in parenchymal organs, the first postprocedural CT scan was compared with preoperative findings. Newly recognized perfusion deficits were taken as evidence of procedure-related infarction. RESULTS: Infarctions were detected in 16 (9.2%) patients: 13 in the kidneys, 2 in the spleen, with 1 in the mesentery; only the mesenteric infarction was clinically symptomatic. Both splenic infarctions were associated with deployment of stent-grafts in the thoracic aorta (5.3% of the 38 patients), while the mesenteric and 13 renal infarctions were seen in patients with infrarenal abdominal aortic aneurysms (0.7% and 9.6%, respectively, of 136 patients). One patient experienced complete thromboembolic occlusion of a renal artery, which was partially recanalized with intraoperative lysis. CONCLUSIONS: Thromboembolic complications of endovascular aortic aneurysm repairs are not uncommon, and although usually asymptomatic, these sequelae have the potential to be life threatening. Perfusion abnormalities may respond to immediate lytic therapy with complete dissolution of the thrombus in certain isolated cases.

Aged↗

Malaysian orthopaedic surgeons' approach to venous thromboembolic disease prophylaxis: attitudes and practice.

PURPOSE: To survey Malaysian orthopaedic surgeons' attitudes to and use of venous thromboembolic disease prophylaxis. METHODS: A total of 144 orthopaedic surgeons from various governmental and private institutions responded to a questionnaire. RESULTS: Only slightly more than half of these surgeons considered venous thromboembolic disease as common a problem in Malaysia as in western countries. The majority of surgeons (91.0%) reported using prophylaxis selectively for patients based on various indicators such as risk grading of surgery, obesity, and malignancy etc. Bleeding tendencies were cited as the greatest fear against the use of pharmacological prophylaxis. Low-molecular-weight heparin appeared to be the most commonly used pharmacological prophylaxis, used either singly or in combination with other forms of prophylaxis. The majority of surgeons employed prophylaxis until their patients were mobile. CONCLUSION: There should be greater awareness among surgeons in Malaysia of the need for protection against venous thromboembolic disease. Current practice needs to be reviewed and further recommendations made for existing protocols.

Anticoagulants↗

eThrombosis: the 21st century variant of venous thromboembolism associated with immobility.

The association between immobility with prolonged sitting and venous thromboembolism has been recognised for > 60 yrs, most recently with long distance air travel. The case of a 32-yr-old male, in whom immobility associated with sitting for long periods at a computer represented the major provoking risk factor for his life-threatening venous thromboembolism, is presented. The authors propose the term "eThrombosis" to describe this 21st Century variant of venous thromboembolism associated with immobility from prolonged sitting. In view of the widespread use of computers in relation to work, recreation and personal communication, the potential burden of eThrombosis may be considerable.

Adult↗

Venous thromboembolism in patients with cancer. Part I. Survey of oncology nurses' attitudes and treatment practices for ambulatory settings.

Patients with cancer have a higher incidence of venous thromboembolism (VTE). Little information currently exists on VTE and the understanding and beliefs of oncology nurses. Therefore, the attitudes and treatment practices of ambulatory oncology nurses were surveyed to determine the current knowledge base of VTE in patients with cancer. Survey results are presented along with a thorough literature review of thromboembolism and the unique risk factors for this frequent complication in patients with cancer. The causes of VTE in this patient population often are multifactorial and include hypercoagulability, stasis, and vascular endothelial damage from procedures or the neoplastic process itself. In particular, chemotherapy administration can increase the risk of thrombosis considerably. New therapies, including thalidomide, require oncology nurses caring for these patients to have heightened awareness of the potential for thrombogenic complications. This is the first of two articles that address the problem of thromboembolism in patients with cancer, including the survey results. (See part II on page 465.) Oncology nurses are essential in the care of VTE in patients with cancer and can help with patient identification, treatment, and compliance for improved patient outcomes.

Ambulatory Care↗

Venous thromboembolism in patients with cancer. Part II. Current treatment strategies.

Patients with cancer have an increased risk of thromboembolism. This complication is connected to a variety of different factors and is influenced by the conditions described in Virchow's triad: stasis, vascular endothelial damage, and hypercoagulability. Once thromboembolism is diagnosed, treatment in patients with cancer usually involves anticoagulation with unfractionated or low-molecular-weight heparin and progression to oral anticoagulant therapy. Duration of treatment is usually three to six months, with most patients receiving six months of anticoagulation. Patients with cancer may be at risk for recurrent thrombosis as well, despite optimal use of oral anticoagulant therapy, and some of these patients may require lifelong heparin therapy. This article describes the current treatment regimens to provide anticoagulation therapy to patients with cancer, including a discussion of the low-molecular-weight heparins and dosing parameters. Nursing interventions to help provide these treatments safely are discussed. Patients with cancer have a high rate of thromboembolism; oncology nurses should heighten their awareness of this important complication, treatment options, and appropriate nursing interventions.

Anticoagulants↗