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Cost-effectiveness of fondaparinux vs. enoxaparin as venous thromboembolism prophylaxis in Sweden.

Deep-vein thrombosis and pulmonary embolism are important causes of morbidity and mortality among patients undergoing major surgery. Fondaparinux is a new antithrombotic agent for use in prophylaxis, and this study compared its cost and effect vs. enoxaparin as prophylactic treatment in patients undergoing total knee replacement, total hip replacement, or hip-fracture surgery in Sweden. The analyses were based on a simulation model. Swedish data on cost for deep-vein thrombosis and pulmonary embolism were obtained from a large sample of patients undergoing major orthopedic surgery. The relative risk reduction for treatment with fondaparinux was estimated from results of four recently published clinical trials. The base case analyses showed that fondaparinux was cost saving and more effective than enoxaparin after total knee replacement and hip-fracture surgery and had costs per prevented venous thromboembolism of about 239 after total hip replacement. Fondaparinux is thus more cost-effective than enoxaparin as prophylactic treatment in patients undergoing major surgery in Sweden.

Journal Article↗

Venous thromboembolism after brain tumor surgery: a retrospective review.

We retrospectively reviewed the incidence rate of clinical postoperative deep vein thrombosis and/or pulmonary embolism in 1703 patients undergoing initial craniotomy for meningioma, glioma, or cerebral metastasis. The incidence rate of clinical thromboembolic complications was 1.59% for all tumor groups within the first 4 weeks of surgery. Patients undergoing surgery for meningiomas had a statistically significant increased risk of thromboembolism despite fewer overall perioperative risk factors, when compared with the other tumor groups. The tumor-specific incidence rates of deep vein thrombosis and/or pulmonary embolism for meningioma, glioma, and metastasis were 3.09%, 0.97%, and 1.03%, respectively. Whether this difference was a result of increased surgical time or an inherent property of meningiomas could not be ascertained.

Adult↗

Bilateral deep venous thrombosis in protein S deficiency. Detection by radionuclide venography.

Patients with primary hypercoagulopathies often present with recurrent, spontaneous deep venous thrombosis and pulmonary embolism. An adolescent eventually diagnosed with protein S deficiency presented with unilateral deep venous thrombosis documented ultrasonographically. Scintigraphic studies showed no evidence of pulmonary embolism but revealed a complete absence of deep venous flow in both lower extremities, the pelvis, and the abdomen. Subsequent ultrasonography and CT scanning documented this marked thrombotic extension. Radionuclide scintigraphy may play an important role in the serial evaluation of primary hypercoagulable states, particularly when pulmonary scintigraphy is combined with bilateral, lower extremity venography.

Adolescent↗

Pulmonary embolism: even your patient is at risk.

The American Society of Plastic Surgeons' Clinical Guidelines specifically focuses on reducing complications from deep vein thrombosis and pulmonary embolism (PE). The incidence of these problems in plastic surgery is low. A 1998 survey of plastic surgeons found the incidence of deep vein thrombosis and PE in facelift patients to be 0.39% and 0.16% respectively (McDevitt, 1999). Despite the low occurrence of these complications in plastic surgical patients, PE is the third leading cause of death in the United States. PE is evasive and often deadly and therefore requires respect and understanding by all members of the health care team.

Humans↗

Measurement of fibrinopeptide A in human blood.

Since thrombin cleaves fibrinopeptides A (FPA) and B from the NH(2)-terminal end of the fibrinogen molecule, measurement of fibrinopeptide levels in plasma may provide a direct index of thrombin action. Recently a radioimmunoassay for FPA has been developed, and in the present paper, we describe the application of this assay to the measurement of FPA levels in clinical blood samples. Since fibrinogen cross-reacts with antibodies to FPA, dialysis was used to extract the peptide from plasma. In vitro generation of FPA was prevented by removing the fibrinogen from the plasma by precipitation with ethanol before dialysis. The processing technique permitted recovery of 75% of FPA added to blood in vitro. Evidence that the immunoreactivity measured in plasma is due to FPA was provided by the results of experiments in which two antisera to FPA with different specificities showed comparable results and addition of thrombin caused no change in immunoreactivity. In contrast, extracts of streptokinasetreated plasma showed a five-fold increase in activity when treated with thrombin and markedly different immunoreactivity with the two antisera. Plasma FPA levels in 30 normal men were below 2 ng/ml, with a mean of 0.5 ng/ml. FPA levels in 12 patients with reduced fibrinogen levels or reduced platelet counts or both ranged between 4 and 289 ng/ml. FPA levels in 13 patients with normal or elevated fibrinogen levels, including 6 patients with clinical evidence of venous thrombosis or pulmonary embolism or both, ranged between 5 and 23 ng/ml. FPA and fibrinogen degradation product levels did not correlate, and in several patients, elevated FPA levels were found in the presence of normal fibrinogen degradation product levels. After infusion of FPA-containing solutions in four normal individuals, FPA showed a disappearance rate from the plasma consistent with a t((1/2)) of 3-5 min. Heparin infusions in six patients with venous thrombosis or pulmonary embolism or both and elevated FPA levels were followed by a prompt decline in FPA level at a mean rate equivalent to a 3-5 min t((1/2)).

Anticoagulants↗

[Clinical manifestations and prevalence of hypercoagulable states in patients with venous thromboembolic disease].

BACKGROUND: Blood flow stasis, an alteration in the coagulation process or endothelium injury the most common mechanisms involved in venous thromboembolic diseases (TED) and constitute the so-called hypercoagulable states (HS). The HS have been classified into two groups: primary and secondary and several of them can be measured. Our purpose was to investigate the prevalence in Spain of measurable HS in patients with venous TED and to know the clinical picture of pulmonary embolism in these patients. PATIENTS AND METHOD: Sixty of 175 consecutive patients diagnosed with deep venous thrombosis and pulmonary embolism fulfilled criteria to study a HS. The study was performed 1 month after anticoagulant therapy was finished. RESULTS: Seventeen (28%) of the 60 patients had one HS that was a primary disorder in 14 and a secondary one in 3. The increase of PAI-1 level was the most common; recurrence of thrombotic events and familial history were frequent in these selected patients. CONCLUSIONS: The prevalence of hypercoagulable states in venous thromboembolic disease was high in this series. The clinical picture was similar to those to be expected and PAI-1 was the most frequent marker of hypercoagulable states.

Adult↗

Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study. A randomized, controlled trial.

BACKGROUND: The clinical significance of asymptomatic deep venous thrombosis that develops after joint arthroplasty and the value of screening tests to detect thrombi are uncertain. OBJECTIVES: To determine 1) the rate of symptomatic deep venous thrombosis or pulmonary embolism occurring after hospitalization for joint arthroplasty and 2) the value of screening compression ultrasonography. DESIGN: Double-blind, randomized, controlled trial. SETTING: Tertiary care hospital. PATIENTS: 1024 patients undergoing elective total hip or knee arthroplasty who received warfarin prophylaxis. INTERVENTION: Patients were randomly assigned to undergo either bilateral compression ultrasonography or a sham procedure before hospital discharge. Patients with a diagnosis of asymptomatic deep venous thrombosis were treated after discharge with standard anticoagulant therapy; other patients had warfarin therapy discontinued at discharge. All patients were followed for 90 days. RESULTS: In the screening group, asymptomatic proximal deep venous thrombosis was detected in 13 of 518 patients (2.5%). Another 4 patients subsequently developed symptomatic proximal deep venous thrombosis, and 1 patient treated for asymptomatic deep venous thrombosis developed major bleeding, for a total outcome event rate of 1.0% (5 of 518 patients). In the placebo group, 3 patients developed symptomatic proximal deep venous thrombosis and 2 had nonfatal pulmonary embolism, for a total event rate of 1.0% (5 of 506 patients) (difference, 0 percentage points [95% CI, -1.2 to 1.2 percentage points]). CONCLUSIONS: In patients undergoing total hip or knee arthroplasty, the use of warfarin prophylaxis during hospitalization results in a very low rate of symptomatic deep venous thrombosis or pulmonary embolism after hospital discharge. The use of screening compression ultrasonography at hospital discharge does not seem to be justified in this setting.

Algorithms↗

Prediction of pulmonary embolism extent by clinical findings, D-dimer level and deep vein thrombosis shown by ultrasound.

Pulmonary embolism (PE) may encompass a wide spectrum of severity. To determine whether clinical findings, D-dimer (DD) concentration, and deep vein thrombosis (DVT) shown by lower-limb venous compression ultrasonography (US) might predict the scintigraphic extent of PE, we studied 104 hemodynamically stable consecutive outpatients with acute PE diagnosed by a high-probability ventilation-perfusion lung scan. Scintigraphic extent of PE was classified into three categories: perfusion defects corresponding to <30%, 30-50%, or >50% of the total lung area. Median respiratory and heart rates were found to be significantly related to the extent of PE. Higher median alveolar-arterial oxygen difference values were observed as the proportion of lung perfusion defects increased (>50% vs. <30%, 6.3 vs. 3.6 kPa, P <.0001). Median plasma DD concentration was 7950 microg/L in patients with >50% perfusion defects compared to 2731 microg/L in those with <30% defects (P = .0001). DD levels above 4000 microg/L were associated to more extensive perfusion defects (>50% vs. <30% defects, OR 30; 95% CI 5.8-155). Finally, a proximal DVT was more likely among patients with larger perfusion defects (>50% vs. <30% defects, OR 4.5; 95% CI 1.5-13.6). In conclusion, clinical signs such as tachypnea and tachycardia, alveolar-arterial oxygen difference, plasma DD concentration, and presence of DVT on US are predictors of a larger PE, as assessed by the extent of perfusion defects on high probability lung scans.

Adult↗

Alternatives in the management of penetrating injuries to the iliac vessels.

BACKGROUND: The high mortality and morbidity rates after iliac vessel injuries remain a challenging problem for trauma surgeons. Several controversial issues surround the management of iliac vessel injuries, including the value of abbreviated laparotomy, the role of extra-anatomic bypass reconstruction (EABR), the use of vascular prostheses in the presence of contamination, and the need and timing for fasciotomy. METHODS: Retrospective review of the records of patients who sustained an injury to the iliac vessel between 1987 and 1996. RESULTS: A total of 64 patients were treated, including 23 with isolated iliac vein injuries, 17 with arterial injuries, and 24 with combined arteriovenous injuries. Vascular prostheses were placed in 17 patients with arterial injuries, including 12 with associated intestinal wounds. Graft infection did not occur. Of the 24 patients with combined injuries, 11 underwent abbreviated laparotomy and 1 died. Five deaths, however, occurred in 13 patients in whom no attempts were made for damage control laparotomy. Significant differences between survivors and nonsurvivors included final arterial pH, final prothrombin time, length of hypotension, and number of transfusions. Arterial ligation with EABR was performed in five patients and failed in two. Deep venous thrombosis and pulmonary embolism occurred in four patients, in three of them after venous injuries were ligated. The overall mortality rate was 23%. CONCLUSION: Our findings show that (1) abbreviated laparotomy reduces mortality in iliac injuries; (2) EABR should be performed early after stabilization to prevent limb ischemia; (3) the use of vascular prostheses with associated intestinal injuries did not appear to increase the incidence of graft infection; and (4) after vein ligation, early fasciotomy and prophylaxis against extremity swelling, deep venous thrombosis, and pulmonary embolism should be considered.

Adolescent↗

[Diagnosis and therapy of leg and pelvic deep vein thrombosis in pregnancy].

OBJECTIVE: To establish differences in the management of acute thrombosis in the deep venous system associated with pregnancy in patients undergoing thrombectomy and in patients receiving heparin therapy. MATERIALS AND METHODS: From 1984 to 1995 the course of pregnancy was assessed retrospectively in 26 patients with acute deep vein thrombosis. Thirteen patients underwent thrombectomy with establishment of an arteriovenous fistula and 13 patients received conservative treatment with heparin therapy. In addition to the assessment of clinical symptoms, signs of thrombosis, diagnoses established with imaging techniques and of laboratory parameters, early complications and obstetric data obtained in surgically and conservatively treated patients were compared. RESULTS: The incidence of deep vein thrombosis in the 26 patients (median age 28 years) was 0.21%. In 53.8% of the cases the occurrence of thrombosis was observed in the second trimester (median: 27.5 weeks of gestation). The presence of risk factors was demonstrated in 58% of cases. The most frequently reported symptoms were swelling of the affected leg (88.5%) and pain (61.5%). A marked predilection for the left leg was recorded in 88% of cases. In contrast to phlebography, twice the number of sonographic studies were performed. The comparison of both therapeutic regimes showed a three-fold increase in the rate of early complications in patients after thrombectomy. The rate of recurrent thrombosis in these patients was 58.3% compared to a recurrence rate of 15.4% in patients undergoing heparin therapy. CONCLUSIONS: Recurrent thrombosis and pulmonary embolism represent the most frequent complications associated with thrombosis in the deep venous system during pregnancy. Although currently there is a lack of conclusive data on the development of postthrombotic syndrome, heparin therapy appears to be associated with fewer maternal risks. Interdisciplinary cooperation is urgently needed.

Adult↗

Paradoxical cerebral emboli associated with pulmonary arteriovenous shunts: report of three cases.

Paradoxical embolism to the cerebral circulation is rarely diagnosed in life; however, three such cases have recently been observed: two with multiple congenital pulmonary arteriovenous malformations and one with an acquired arteriovenous fistula. In each case the pulmonary lesion(s) were treated by percutaneous balloon embolizations. Paradoxical embolism should be included in the differential diagnosis of cerebral arterial embolism for which there is no obvious source, especially when there is also evidence of concurrent peripheral venous thrombosis and/or pulmonary embolism.

Adult↗

Cost effectiveness of low-molecular weight heparin versus warfarin following hip replacement surgery.

Little information is available on the efficacy of low-molecular-weight heparin (enoxaparin) versus warfarin for treatment of deep vein thrombosis and pulmonary embolism following hip replacement surgery. Still less is known of the comparative cost effectiveness of these two therapies. A retrospective study was done on 56 patients who underwent elective hip surgery at an urban medical center between 1991 and 1996. All patients received enoxaparin or warfarin for purposes of thromboprophylaxis. An analysis of medication cost, therapy, laboratory monitoring, and bleeding events of the two antithrombolytic agents was undertaken. Total savings with enoxaparin averaged $1253 per patient, or $137,886 over the study period. The incidence of deep vein thrombosis or pulmonary embolism was 0% with enoxaparin and 3% with warfarin. These data indicate that enoxaparin is a more cost-effective and efficacious regimen for thromboprophylaxis following hip replacement surgery than warfarin.

Black or African American↗

Enoxaparin: in the prevention of venous thromboembolism in medical patients.

Enoxaparin (enoxaparin sodium) is a low-molecular-weight heparin that binds to and increases the activity of antithrombin III. The resulting complex inhibits prothrombinase-mediated thrombin generation and direct thrombin generation by binding to factor Xa and thrombin factor IIa. Enoxaparin, used as prophylaxis in medically ill patients at increased risk for thromboembolism, has shown significantly increased efficacy compared with placebo in reducing the incidence of deep vein thrombosis and pulmonary embolism. Indeed, 291 patients receiving subcutaneous enoxaparin 40 mg/day had a frequency of venous thromboembolism of 5.5% during 14 days of treatment, whereas 14.9% of the 288 placebo recipients experienced thromboemboli (p < 0.001). There was no reduction in the incidence of thromboembolism in the 287 recipients of enoxaparin 20 mg/day (15%). In other studies, prophylactic treatment for 7 days with subcutaneous enoxaparin 40 mg/day was at least as effective as unfractionated heparin in reducing the frequency of venous thromboembolism in 959 nonsurgical patients at increased risk for deep vein thrombosis and pulmonary embolism (total incidence = 0.2 and 1.4%, respectively). Moreover, enoxaparin recipients experienced fewer adverse events than did heparin recipients. The most frequent adverse events reported in medically ill and surgical patients receiving enoxaparin 40 mg/day were hemorrhage (17.4 vs 14.3% for placebo), hematoma at injection site, anemia, fever, peripheral edema, nausea, ecchymosis and edema (unspecified site).

Anticoagulants↗

Postoperative thromboembolism and the use of oral contraceptives.

We have previously reported the results of a retrospective study of the relationship between oral contraceptives and deep vein thrombosis and pulmonary embolism occurring in the absence of an evident predisposing cause. The present paper describes a similar investigation of the relationship between oral contraceptives and thromboembolism following certain surgical procedures.Of 30 patients with thromboembolism, 12 (40%) had been using oral contraceptives during the month preceding surgery, while only 9 of 60 matched controls (15%) had been doing so. From these data it is estimated that the risk of postoperative thromboembolism is increased threefold to fourfold by the use of contraceptive steroids.It is recognized that few of the episodes of deep vein thrombosis and pulmonary embolism that occur postoperatively are detectable clinically, and that not all of these are recorded in discharge summaries or diagnostic indexes. Despite these considerations, we have been unable to detect any important bias in the data which could account for the observed association between oral contraceptives and the development of postoperative thromboembolism.

Adolescent↗

Pentasaccharides in the prophylaxis and treatment of venous thromboembolism: a systematic review.

PURPOSE OF REVIEW: The aim of this review is to perform a critical analysis of all completed studies evaluating pentasaccharides-synthetically derived, selective inhibitors of activated factor X-in prophylaxis in major orthopedic surgery and the treatment of venous thromboembolism. RECENT FINDINGS: Venous thromboembolism is a disorder with considerable morbidity when left untreated. New antithrombotic agents have been developed that selectively inhibit components of the coagulation system, thereby avoiding the difficulties associated with current anticoagulants. The pentasaccharides fondaparinux and idraparinux are the first of a new class of synthetic selective inhibitors of activated factor X. Fondaparinux has been extensively investigated in two areas: orthopedic surgery and venous thromboembolism. It is clear from four thromboprophylaxis studies in major orthopedic surgery that fondaparinux is 50% more effective in reducing venous thromboembolism than enoxaparin. This superior efficacy led to an overall increase in major bleeding, which was however primarily due to more fondaparinux-treated patients with bleeding indexes of 2 or greater. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two groups. In the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, fondaparinux was equally effective as low molecular weight heparins and unfractionated heparin, respectively, without a different incidence in major bleeding in fondaparinux and comparator heparin groups. SUMMARY: Fondaparinux, one of the first of a new class of synthetic selective factor Xa inhibitors, is overall 50% more effective in reducing venous thromboembolism than enoxaparin in major orthopedic surgery, with an overall 1% increased rate of major bleeding, when compared with enoxaparin. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two treatment groups. Fondaparinux is equally effective as low molecular weight heparins and unfractionated heparin in the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, respectively. Finally, as with any new drug, fondaparinux should be used cautiously and only in patients who reflect the population of the clinical trials in which the drug was evaluated.

Clinical Trials as Topic↗

Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy.

OBJECTIVE: To estimate the incidence, timing, and associated clinical characteristics of objectively diagnosed pregnancy-associated venous thromboembolism. METHODS: We retrospectively reviewed venous thromboembolism cases (deep venous thrombosis and pulmonary embolism) that occurred between 1978 and 1996. Study inclusion criteria required the objective diagnosis with either Doppler ultrasound, venography, impedance plethysmography, pulmonary angiography, ventilation-perfusion scanning, or computed tomography or magnetic resonance imaging. RESULTS: Among 268,525 deliveries there were 165 (0.06%) episodes of venous thromboembolism (one per 1627 births). There were 127 cases of deep venous thrombosis and 38 cases of pulmonary embolism. Only 14% (23 of 165 patients) had a history of venous thromboembolism. Most cases of deep venous thrombosis were in the left leg (104 of 127, 81.9%), with nearly three quarters of them (94 of 127, 74.8%) occurring during the antepartum period. Among cases of antepartum deep venous thrombosis, half were detected before 15 weeks' gestation (47 of 95, 49.5%), and only 28 cases occurred after 20 weeks (P < .001). Most of the pulmonary embolisms occurred in the postpartum period (23 of 38, 60.5%) and were strongly associated with cesarean delivery (19 of 36,470 compared with four of 232,032, P < .001). CONCLUSION: The incidence of venous thromboembolism during pregnancy is lower than has been previously described. Most cases occurred in the antepartum period, with the risk of deep venous thrombosis appearing to begin even before the second trimester.

Adolescent↗