Original Article
A Comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Acute Pulmonary Embolism
N Engl J Med 1997; 337:663-669September 4, 1997
- Abstract
Background
Low-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism.
Methods
We randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death.
Results
In the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P = 0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study.
Conclusions
Under the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism.
Media in This Article
Figure 1
Time-to-Event Analysis of the Occurrence of Recurrent Thromboembolism, Major Bleeding, or Death, Studied as a Combined Outcome.Table 1
Base-Line Characteristics of the Study Patients.Article Activity
- Article
Low-molecular-weight heparins are an important new class of antithrombotic agents. They differ from standard, unfractionated heparin in having a higher ratio of anti–factor Xa to anti–factor IIa activity, greater bioavailability, a longer half-life, and a more predictable anticoagulant response when administered subcutaneously in fixed doses.1,2
The efficacy and safety of low-molecular-weight heparin for the initial treatment of deep-vein thrombosis are well established.3-5 However, in most clinical trials comparing low-molecular-weight heparin with unfractionated heparin to treat acute deep-vein thrombosis, associated symptomatic pulmonary embolism either was a criterion for exclusion from the study or occurred in only a minority of the patients. Consequently, although deep-vein thrombosis and pulmonary embolism are generally considered to be different expressions of the same disease, there is limited information on the efficacy and safety of low-molecular-weight heparin for the initial treatment of symptomatic pulmonary embolism.6,7 Therefore, the role of low-molecular-weight heparin in patients with acute pulmonary embolism must be determined before this therapeutic approach is extended to the overall spectrum of venous thromboembolism.
Because the low-molecular-weight heparins are distinct compounds with different pharmacologic profiles and different dose regimens, it is uncertain whether the results obtained with one preparation can be extended to another. In 1992, Hull et al. reported that a once-daily subcutaneous injection of tinzaparin was at least as effective and safe as continuous intravenous heparin in patients with proximal-vein thrombosis.8
We therefore conducted a randomized trial in which patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or pulmonary embolectomy were given either continuous, intravenous unfractionated heparin or a single daily subcutaneous injection of tinzaparin. Considering the trend toward better efficacy and safety with low-molecular-weight heparin as compared with unfractionated heparin,3-5 we sought to determine whether tinzaparin was clinically superior to unfractionated heparin with regard to the combined outcome of symptomatic recurrent thromboembolism, major bleeding, and death. A secondary aim was to compare the two treatments with respect to changes in scores for scintigraphically detected pulmonary vascular obstruction from day 1 to day 8.
Methods
Study Design
This study was a multicenter, randomized, unblinded trial comparing continuous, adjusted-dose, intravenous unfractionated heparin with once-daily subcutaneous low-molecular-weight heparin (tinzaparin) in patients with acute, symptomatic pulmonary embolism. The study was conducted in 57 centers in France, Belgium, and Switzerland. The study protocol was approved by the institutional review boards of all the participating centers.
Patients
Consecutive patients over 18 years of age with clinically suspected acute pulmonary embolism were considered for enrollment in the study. Before their inclusion, pulmonary embolism had to be objectively documented by pulmonary angiography, by ventilation–perfusion lung scanning indicating a high probability of pulmonary embolism,9 or by scanning with indeterminate results that was accompanied by deep-vein thrombosis confirmed by venography or compression ultrasonography.
Patients were excluded from the study if, in the opinion of the physician in charge, they had massive pulmonary embolism requiring thrombolytic therapy or pulmonary embolectomy; if they had active bleeding or disorders contraindicating anticoagulant therapy; if they had received anticoagulant therapy at a therapeutic dose for more than 24 hours before entering the study (the receipt of such therapy for 24 hours or less before randomization was permitted); if their life expectancy was less than three months; if they had severe hepatic or renal failure; if noncompliance was likely; or if they were pregnant. After the patients gave written informed consent, central randomization was performed with the use of a 24-hour computer service.
Treatment Regimens
The patients assigned to therapy with low-molecular-weight heparin were given a fixed dose of 175 international anti–factor Xa units of tinzaparin (Innohep, Leo Pharmaceutical Products, Ballerup, Denmark) per kilogram of body weight subcutaneously once daily. The patients assigned to therapy with unfractionated heparin (Leo Pharmaceutical Products) received an initial bolus dose of 50 IU per kilogram, followed by a continuous intravenous infusion at an initial rate of 500 IU per kilogram per day. The dose was subsequently adjusted so that the activated partial-thromboplastin time would be two to three times the control value in normal subjects. The tests were performed six hours after the start of treatment, whenever a subtherapeutic activated partial-thromboplastin time had been measured after a dose adjustment, and otherwise daily.
In each patient, oral anticoagulant therapy was begun between the first and third days of the initial heparin therapy and was continued for at least three months on an open-label basis. The dose was adjusted to achieve an international normalized ratio of 2.0 to 3.0. Treatment with either unfractionated heparin or low-molecular-weight heparin was given until the international normalized ratio was 2.0 or above on two measurements made 24 hours apart after at least five days of treatment with heparin. The use of antiplatelet and antiinflammatory drugs was prohibited during the study.
Surveillance and Follow-up
All the patients were examined daily during the initial therapy; symptoms and signs of recurrent venous thromboembolism or bleeding were sought. When pulmonary embolism was documented by angiography alone, a perfusion lung scan was required within 48 hours of enrollment. For all patients, compression ultrasonography of the lower limbs was strongly encouraged at enrollment.
Patients in whom recurrent pulmonary embolism was suspected on the basis of clinical signs or symptoms underwent ventilation–perfusion scanning or angiography. Recurrent pulmonary embolism was diagnosed if there was a new perfusion defect, segmental or larger, on the lung scan. If the lung scan was inconclusive, pulmonary angiography was performed; a recurrence was defined as a new intraluminal filling defect or a new sudden cutoff in an arterial branch that was not present on the first angiogram. If no previous pulmonary angiogram was available for comparison, a recurrence was diagnosed when the angiogram showed an intraluminal defect or a sudden cutoff in an area where the initial perfusion lung scan showed normal perfusion.
Patients with suspected new or recurrent deep-vein thrombosis on the basis of the clinical findings underwent ultrasonography or venography, whichever test had been previously performed and had results available for comparison. The criterion for deep-vein thrombosis was either a constant intraluminal filling defect on venography or a lack of compressibility on ultrasonography when that finding represented a change from the results of the base-line test. All the angiograms and venograms were reviewed by three readers who were unaware of the treatment assignments. In addition, perfusion lung scans were systematically repeated in all patients between day 8 and day 11.
Complete blood counts were obtained twice weekly during the initial treatment period (from day 1 to day 8) and whenever there was any bleeding. Severe thrombocytopenia was defined as present if the platelet count fell below 50,000 per cubic millimeter or if it was between 50,000 and 100,000 per cubic millimeter and accompanied by clinical signs of bleeding or thrombosis.
Bleeding was defined as major if it was overt and associated either with a decrease in the hemoglobin concentration by at least 2.0 g per deciliter or with the need for the transfusion of 2 or more units of blood, or if the bleeding was intracranial or retroperitoneal.
Deaths were classified as due to pulmonary embolism (when there was strong clinical evidence or evidence at autopsy), hemorrhage, cancer, or other causes (including unknown causes).
Outcome Measures
The primary end point was a combined outcome event, defined as death, symptomatic recurrent thromboembolism, or major bleeding within the first eight days of the study. This combined end point was also assessed at day 90. Data on all potential outcome events were submitted to an independent adjudication committee whose members were unaware of the treatment assignments.
A secondary end point was the change from day 1 to day 8 in the extent of scintigraphically detectable pulmonary vascular obstruction, expressed as a percentage. The method used to calculate this percentage has been previously described.10 Each lobe was assigned a weight based on the regional distribution of blood flow, as follows: right upper lobe, 0.18; right middle lobe, 0.12; right lower lobe, 0.25; left upper lobe, 0.13; lingula, 0.12; left lower lobe, 0.2. The perfusion of each lobe was estimated visually on the basis of the film density and was scored on a scale from 0 (not perfused) to 1 (normally perfused), with use of a semiquantitative method of evaluation (0, 0.25, 0.50, 0.75, and 1). Each lobar-perfusion score was then calculated by multiplying the weight assigned to the lobe by the estimated perfusion of that lobe and totaling the six separate lobar-perfusion scores. The percentage of vascular obstruction was calculated as: (1 - overall perfusion score) × 100. All the scans were reviewed independently and scored according to this method by two readers, each unaware of the patient's treatment assignment. Cases in which there were disputes (that is, any absolute differences in scoring by more than 10 percent between the two readers) were reevaluated by both readers, and a consensus was reached.
Statistical Analysis
The primary analysis was performed on an intention-to-treat basis. The results in the two treatment groups were compared by Fisher's exact test. Ninety-five percent confidence intervals for the difference between the two groups in the incidence of outcome events were calculated with the normal approximation to the binomial distribution. The log-rank test was used to assess differences in the cumulative incidence of events.
Results
Patients
The recruitment of patients began in July 1995 and was completed in July 1996. Of 1482 consecutive patients who met the criteria for enrollment, 766 (52 percent) were excluded from the study for the following reasons: massive pulmonary embolism requiring thrombolytic therapy (177 patients) or interruption of the inferior vena cava (55), contraindications to anticoagulant therapy or concomitant use of an unauthorized drug (81), previous treatment with an anticoagulant drug for more than 24 hours (266), short life expectancy (51), any reason that rendered follow-up impracticable (101), and various other reasons (35). Among the 716 eligible patients, 104 (15 percent) declined to participate. Of the remaining 612 patients, 308 were randomly assigned to receive intravenous unfractionated heparin and 304 to receive low-molecular-weight heparin. Four patients (one assigned to unfractionated heparin and three assigned to low-molecular-weight heparin) did not receive the study drug but were included in the follow-up and in the study analysis. The base-line characteristics of the treatment groups were similar (Table 1Table 1
Base-Line Characteristics of the Study Patients. and Table 2Table 2
Selected Characteristics of Pulmonary Embolism in the Study Patients at Enrollment.).Anticoagulant Therapy
Among the 612 patients included in the study, 423 (69 percent) — 201 assigned to unfractionated heparin and 222 assigned to low-molecular-weight heparin — received therapeutic doses of unfractionated heparin before randomization. The mean (±SD) duration of anticoagulant treatment at a therapeutic dose before randomization was 18±6 hours in the patients assigned to unfractionated heparin and 18±7 hours in the patients assigned to low-molecular-weight heparin. The doses and duration of the study treatments and of oral anticoagulant agents are shown in Table 3Table 3
Anticoagulant Therapy Provided to the Study Patients According to Treatment Group..Primary End Points
During the eight days after randomization, nine patients assigned to receive unfractionated heparin (2.9 percent) died or had symptomatic recurrent venous thromboembolism or major bleeding, as compared with nine patients assigned to receive low-molecular-weight heparin (3.0 percent) (Table 4Table 4
Outcome Events in the Study Patients According to Treatment Group.). There was an absolute difference of 0.1 percentage point between the two groups (95 percent confidence interval, -2.7 to 2.6).From day 1 through day 90, 22 patients (7.1 percent) assigned to unfractionated heparin and 18 patients (5.9 percent) assigned to low-molecular-weight heparin reached at least one of the clinical end points. There was an absolute difference of 1.2 percentage points (95 percent confidence interval, -2.7 to 5.1), and there was no significant difference between the treatment groups.
Analysis by the log-rank test, which takes into account the length of time to the first clinical event, did not show any significant difference between groups (P = 0.55) in the frequency of the combined end point (Figure 1Figure 1
Time-to-Event Analysis of the Occurrence of Recurrent Thromboembolism, Major Bleeding, or Death, Studied as a Combined Outcome.).Mortality
During the initial treatment (from day 1 to day 8), three patients receiving unfractionated heparin died (1.0 percent), as compared with four patients receiving low-molecular-weight heparin (1.3 percent). During the three-month study period, 14 patients assigned to unfractionated heparin died (4.5 percent), as compared with 12 patients assigned to low-molecular-weight heparin (3.9 percent) (Table 4). The causes of death are shown in Table 5Table 5
Causes of Death in the Two Treatment Groups..Recurrent Venous Thromboembolism
Among the 308 patients treated with unfractionated heparin, 30 had at least one episode of clinically suspected recurrent thromboembolism during the three months of the study. Of these patients, six (1.9 percent of the entire treatment group) met the criteria established by the adjudication committee for documented recurrent thromboembolism. Among the 304 patients treated with low-molecular-weight heparin, 32 had suspected recurrences, 5 of whom (1.6 percent) met the committee's criteria. Overall, 5 of the 612 patients had pulmonary embolism, 3 had only deep-vein thrombosis, and 3 had both pulmonary embolism and deep-vein thrombosis.
Bleeding Complications
During the initial treatment (from day 1 to day 8), five patients receiving unfractionated heparin (1.6 percent) had major bleeding, as compared with three patients receiving low-molecular-weight heparin (1.0 percent). The activated partial-thromboplastin time was above the therapeutic level in two of the five patients receiving unfractionated heparin. The international normalized ratio was above the therapeutic level in one patient in each group. One patient in the unfractionated-heparin group who had retroperitoneal bleeding on day 6 died on day 7. There were no episodes of fatal bleeding among the patients receiving low-molecular-weight heparin. During the initial treatment, minor bleeding was noted in 8 patients receiving unfractionated heparin and 17 patients receiving low-molecular-weight heparin (P = 0.10).
From day 9 through day 90, 10 patients had major bleeding (Table 4) and 22 had minor bleeding (9 patients receiving unfractionated heparin and 13 patients receiving low-molecular-weight heparin). One patient assigned to unfractionated heparin died of a hemorrhagic stroke on day 36, and one patient assigned to low-molecular-weight heparin died with massive hemoptysis on day 68 (Table 5).
Overall, during the three-month study period, there was major bleeding in eight patients assigned to unfractionated heparin (2.6 percent) and six patients assigned to low-molecular-weight heparin (2.0 percent) (Table 4).
Perfusion Lung Scans
For 65 patients (34 treated with unfractionated heparin and 31 treated with low-molecular-weight heparin), the percentage of scintigraphically detectable vascular obstruction could not be accurately assessed at enrollment, and these patients were therefore excluded from the analysis of vascular obstruction. For the 547 remaining patients, the mean vascular obstruction at enrollment was 46±21 percent in 274 patients assigned to unfractionated heparin and 47±20 percent in 273 patients assigned to low-molecular-weight heparin. Overall, the base-line extent of scintigraphically detectable vascular obstruction exceeded 50 percent in 47 percent of patients (Table 2).
Twenty-nine additional patients could not be studied at day 8. From day 1 to day 8, the absolute decrease in pulmonary vascular obstruction was 19.0±13.9 percent in 260 patients assigned to unfractionated heparin and 18.4±13.5 percent in 258 patients assigned to low-molecular-weight heparin.
Among the patients assigned to unfractionated heparin, the perfusion lung scans improved in 81 percent, remained unchanged in 17 percent, worsened in 0.3 percent, and could not be properly compared from day 1 to day 8 in 1.7 percent. Among the patients assigned to low-molecular-weight heparin, the scans improved in 80 percent, remained unchanged in 17 percent, worsened in 0.7 percent, and could not be properly compared from day 1 to day 8 in 2.1 percent.
Other Findings
Heparin-induced thrombocytopenia developed on day 7 in one patient receiving unfractionated heparin (platelet count, 29,000 per cubic millimeter) and in no patient receiving low-molecular-weight heparin. On day 2, one patient treated with low-molecular-weight heparin had an ischemic stroke associated with pulmonary hypertension and a patent foramen ovale, suggesting a paradoxical embolism.
Discussion
Pulmonary embolism is a potentially fatal disease in which anticoagulant therapy has been shown to improve outcomes dramatically.11 Unfractionated heparin is considered the treatment of choice for most patients with pulmonary embolism, except those with hemodynamic instability, who may need thrombolytic therapy.2,12
Our study indicates that tinzaparin, a low-molecular-weight heparin, can be used safely and effectively when given once daily to treat patients with acute, symptomatic pulmonary embolism. Indeed, in both the group receiving unfractionated heparin and the group receiving low-molecular-weight heparin, rates of recurrence, major bleeding, and death were both similar and low. During the initial eight days of treatment, the overall incidence of severe critical events was similar in both groups (roughly 3 percent). During the three months of follow-up, there was a nonsignificant trend favoring low-molecular-weight heparin as compared with unfractionated heparin, with overall rates of recurrence, major bleeding, and death of 5.9 percent and 7.1 percent, respectively.
Our study was unblinded, but we took special care to minimize potential biases. For this purpose, consecutive patients were included, all suspected recurrences of thromboembolism had to be confirmed by objective tests, and all the critical events were assessed by an independent adjudication committee.
Our findings are consistent with those of recent studies of the treatment of deep-vein thrombosis with low-molecular-weight heparins.3-5 In one study, among patients treated with tinzaparin for proximal deep-vein thrombosis, after three months the reported incidence of recurrence was 2.8 percent, that of major bleeding was 2.8 percent, and that of death was 4.7 percent.8 Using the same regimen of tinzaparin to treat acute pulmonary embolism, we observed similar rates of recurrent thromboembolism (1.6 percent), major bleeding (2.0 percent), and death (3.9 percent).
In patients with pulmonary embolism receiving unfractionated heparin, rates of recurrence, major bleeding, and death in the first three months of treatment have been reported to be markedly higher than in our study — about 5 to 10 percent higher for each end point.13-15 However, these data were derived from small trials performed 5 to 20 years ago. At that time, the diagnosis of pulmonary embolism was generally based on pulmonary angiography, which is associated with an increased incidence of severe hemorrhagic complications.16
The selection criteria we used probably caused some patients who were at high risk of death, recurrence, or major bleeding to be excluded from the study. Indeed, among the 1482 patients who met the criteria for enrollment, 12 percent were excluded because they required thrombolytic therapy, 3.7 percent because they needed interruption of the vena cava, 3.4 percent because of a short life expectancy, and 5.5 percent because of a contraindication to anticoagulant therapy. However, all the patients included in our study presented with clinical symptoms due to pulmonary embolism, and 28 percent had clinical features compatible with major pulmonary embolism, including cyanosis, syncope, acute right ventricular failure, and even shock (in 2.0 percent). Also, 47 percent of our patients had evidence on perfusion scanning of vascular obstruction exceeding 50 percent. In that subgroup, the event rate was slightly higher (8.7 percent) than it was in the subgroup of patients whose perfusion scans showed less than 50 percent obstruction (5.8 percent). In the subgroup with more severe obstruction, the trend continued to favor low-molecular-weight heparin over unfractionated heparin.
Nevertheless, the unexpectedly low event rate in the overall study population markedly reduced the statistical power of the study to detect a significant difference between the treatment groups. However, the general trend suggests that low-molecular-weight heparin is as effective and safe as intravenous unfractionated heparin under the conditions of the study. Had the trend favoring low-molecular-weight heparin continued, almost 10,000 patients would have been required for the study to show a statistically significant difference.
Among patients with deep-vein thrombosis, a major advantage of low-molecular-weight heparin over continuous intravenous unfractionated heparin is that the therapeutic regimen is greatly simplified, increasing convenience to patients and allowing the possibility of outpatient treatment that could substantially reduce costs.17,18 Our study suggests that the use of low-molecular-weight heparin may be extended to patients with acute symptomatic pulmonary embolism after those with hemodynamic instability are excluded.
Supported by Leo Pharmaceuticals, France.
We are indebted to John Stinson, M.D. (Dublin, Ireland), for reviewing the manuscript.
Source Information
From Hôpital Antoine Béclère, Clamart (G.S.); Hôpital Laennec, Paris (H.S.); Hôpital Trousseau, Tours (B.C.); Hôpital Bellevue, St. Etienne (Y.P.); Hôpital Hôtel Dieu, Paris (J.-P.L.); Hôpital André Mignot, Versailles (R.A.); Hôpital Hôtel Dieu, Rennes (M.L.); Hôpital Henri Duffaut, Avignon (J.-L.H.); Hôpital Pasteur, Nice (E.F.); Hôpital Universitaire, Grenoble (J.-L.B.); Hôpital de la Cavale Blanche, Brest (D.M.); and Leo Pharmaceuticals, St. Quentin en Yvelines (B.B.) — all in France.
Address reprint requests to Dr. Simonneau at the Service de Pneumologie et Réanimation, Hôpital Antoine Béclère, 157 rue de la Porte de Trivaux, 92141 Clamart, France.
The centers and investigators participating in the Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire (THÉSÉE) study are listed in the Appendix.
Appendix
The following investigators, all in France except as otherwise noted, also participated in this study. Study Centers: Hôpital Laennec, Paris — G. Meyer; Hôpital Antoine Béclère, Clamart — F. Parent; Hôpital Trousseau, Tours — G. Pacouret; Hôpital Bellevue, St. Etienne — H. Decousus and B. Tardy; Hôpital Hôtel Dieu, Paris — A. Achkar; Hôpital André Mignot, Versailles — J. Schwob and J.P. Normand; Hôpital Hôtel Dieu, Rennes — C. Almange; Hôpital Robert Debré, Reims — J. Elaerts and D. Maes; Centre Hospitalier Schaffner, Lens — P. Pignon; Centre Hospitalier, Pau — N. Delarche and M. Le Blay; Centre Hospitalier Général, Narbonne — P. Battistella; Hôpital Bichat, Paris — P.G. Steg and D. Czitrom; Hôpital Gabriel Montpied, Clermont Ferrand — B. Citron; Centre Hospitalier Lyon Sud, Lyon — D. Vital Durand and C. Grange; Hôpital Bon Secours, Metz — K. Khalife; Centre Hospitalier Général, Angoulême — M. Waynberger; Centre Hospitalier Général Lucien Hussel, Vienne — M. Madignier; Hôpital Sud, Amiens — J.C. Quiret and G. Jarry; Hôpital Edouard Herriot, Lyons — J. Ninet; Hôpital Broussais, Paris — J.N. Fiessinger and J. Emmerich; Hôpital Boucicaut, Paris — J. Labrousse and J.L. Diehl; Centre Hospitalier Général, Firminy — P. Sagnol; Hôpital d'Instruction des Armées Sainte Anne, Toulon — G.V. Dussarat; Centre Hospitalo-Universitaire, Lille — G. Ducloux and O. Nugue; Clinique des Franciscaines, Nîmes — E. Bosc; Gasthuisberg Hospital, Leuven, Belgium — R. Verhaeghe; Centre Hospitalier, Blois — M. Lang; Hôpital Victor Provo, Roubaix — P. Quandalle and X. Demarcq; Centre Hospitalo-Universitaire Dupuytren, Limoges — C. Cassat and G. Rambaud; Hôpital Central, Nancy — M.C. Laprevote and G. Thibaut; Hôpital Victor Dupouy, Argenteuil — J.P. Sollet; Centre Hospitalier Général Robert Ballanger, Aulnay-sous-Bois — O. Sitbon; Hôpital du Bocage, Dijon — B. Lorcerie and B. Bonnotte; Centre Hospitalo-Universitaire, Caen — G. Grollier; Centre Hospitalier, Martigues — A. Ebagosti; Hôpital Saint Jacques, Besançon — J.P. Bassand; Hôpital Cantonal Universitaire, Geneva — A. Perrier; Hôpital Beaujon, Clichy — R. Pariente, A. Cohen-Solal, and G. Jebrak; Centre Hospitalo-Universitaire, Rouen — H. Levesque; Hôpital de la Timone, Marseilles — M. Bory; Centre Hospitalo-Universitaire la Miletrie, Poitiers — R. Barraine; Centre Hospitalier Gustave Dron, Tourcoing — E. Decoulx; Hôpital Hôtel Dieu, Angers — P. Geslin and P. Tron; Hôpital de Rangueil, Toulouse — A. Elias; Hôpital Louis Mourrier, Colombes — D. Dreyfuss; Centre Hospitalo-Universitaire, Le Krémlin-Bicêtre — O. Taravella; Hôpital Saint Eloi, Montpellier — C. Janbon; Centre Hospitalier, Le Mans — D. Fagart; Centre Hospitalier de la Côte Basque, Bayonne — A. Blanc; Hôpital du Val de Grâce, Paris — J.P. Ollivier; Hôpital Arnaud de Villeneuve, Montpellier — J.M. Davy; Hôpital Louis Pradel, Lyons — J.F. Cordier. Central Data Management Office and Biostatistics: Leo Pharmaceuticals France, St. Quentin en Yvelines — A. Rakotomanga, J.J. Heilmann, L. Nguyen Trong, C. El Rawadi, J.C. Dhuin, and L. Goncalves. Adjudication Committee: P. Girard (Paris), B. Jarrousse (Bobigny), and M. Stern (Suresnes). Independent Supervision Committee: H. Bounameaux (Geneva), M. Dechavanne (Lyons), and A. Leizorovicz (Lyons). Central reading of lung scans: M.A. Collignon (Paris) and M. Wartski (Le Plessis-Robinson).
- References
References
1
Hirsh J ,Levine MN . Low molecular weight heparin. Blood 1992;79:1-17
Web of Science | Medline2
Ginsberg JS . Management of venous thromboembolism. N Engl J Med 1996;335:1816-1828
Full Text | Web of Science | Medline3
Leizorovicz A ,Simonneau G ,Decousus H ,Boissel JP . Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ 1994;309:299-304
CrossRef | Web of Science | Medline4
Lensing AWA ,Prins MH ,Davidson BL ,Hirsh J . Treatment of deep venous thrombosis with low-molecular-weight heparins: a meta-analysis. Arch Intern Med 1995;155:601-607
CrossRef | Web of Science | Medline5
Siragusa S ,Cosmi B ,Piovella F ,Hirsh J ,Ginsberg JS . Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 1996;100:269-277
CrossRef | Web of Science | Medline6
Thery C ,Simonneau G ,Meyer G , et al. Randomized trial of subcutaneous low-molecular-weight heparin CY 216 (Fraxiparine) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism: a dose-ranging study. Circulation 1992;85:1380-1389
Web of Science | Medline7
Meyer G ,Brenot F ,Pacouret G , et al. Subcutaneous low-molecular-weight heparin Fragmin versus intravenous unfractionated heparin in the treatment of acute non massive pulmonary embolism: an open randomized pilot study. Thromb Haemost 1995;74:1432-1435
Web of Science | Medline8
Hull RD ,Raskob GE ,Pineo GF , et al. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992;326:975-982
Full Text | Web of Science | Medline9
The PIOPED Investigators
CrossRef | Web of Science10
Meyer G ,Collignon MA ,Guinet F ,Jeffrey AA ,Barritault L ,Sors H . Comparison of perfusion lung scanning and angiography in the estimation of vascular obstruction in acute pulmonary embolism. Eur J Nucl Med 1990;17:315-319
CrossRef | Medline11
Barritt DW ,Jordan SC . Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960;1:1309-1312
CrossRef | Web of Science | Medline12
Hyers TM ,Hull RD ,Weg JG . Antithrombotic therapy for venous thromboembolic disease. Chest 1995;108:Suppl:335S-351S
CrossRef | Web of Science | Medline13
The Urokinase Pulmonary Embolism Trial: a national cooperative studyCirculation 1973;47:Suppl II:II-1
14
Monreal M ,Ruiz J ,Salvador R ,Morera J ,Arias A . Recurrent pulmonary embolism: a prospective study. Chest 1989;95:976-979
CrossRef | Web of Science | Medline15
Goldhaber SZ ,Haire WD ,Feldstein ML , et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993;341:507-511
CrossRef | Web of Science | Medline16
Stein PD ,Hull RD ,Raskob G . Risks for major bleeding from thrombolytic therapy in patients with acute pulmonary embolism: consideration of noninvasive management. Ann Intern Med 1994;121:313-317
Web of Science | Medline17
Levine M ,Gent M ,Hirsh J , et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996;334:677-681
Full Text | Web of Science | Medline18
Koopman MMW ,Prandoni P ,Piovella F , et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996;334:682-687
Full Text | Web of Science | Medline
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Jason A. Stamm. (2011) Risk Stratification for Acute Pulmonary Embolism. Critical Care Clinics
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Elie A Akl, Nawman Labedi, Irene Terrenato, Maddalena Barba, Francesca Sperati, Elena V Sempos, Paola Muti, Deborah Cook, Holger Schünemann, Elie A Akl. 2011. Low molecular weight heparin versus unfractionated heparin for perioperative thromboprophylaxis in patients with cancer. .
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James M. Hunt, Todd M. Bull. (2011) Clinical Review of Pulmonary Embolism: Diagnosis, Prognosis, and Treatment. Medical Clinics of North America 95:6, 1203-1222
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Paul D. Stein, Fadi Matta. (2011) Epidemiology and Incidence: The Scope of the Problem and Risk Factors for Development of Venous Thromboembolism. Critical Care Clinics 27:4, 907-932
CrossRef6
N. FALVO, C. BONITHON-KOPP, K. RIVRON GUILLOT, J. A. TODOLI, M. JIMéNEZ-GIL, P. DI MICCO, M. MONREAL, . (2011) Heparin-associated thrombocytopenia in 24 401 patients with venous thromboembolism: findings from the RIETE Registry1. Journal of Thrombosis and Haemostasis 9:9, 1761-1768
CrossRef7
Catherine Nelson-Piercy, Raymond Powrie, Jean-Yvonne Borg, Marc Rodger, David J. Talbot, John Stinson, Ian A. Greer. (2011) Tinzaparin use in pregnancy: an international, retrospective study of the safety and efficacy profile. European Journal of Obstetrics & Gynecology and Reproductive Biology
CrossRef8
W. ZONDAG, I. C. M. MOS, D. CREEMERS-SCHILD, A. D. M. HOOGERBRUGGE, O. M. DEKKERS, J. DOLSMA, M. EIJSVOGEL, L. M. FABER, H. M. A. HOFSTEE, M. M. C. HOVENS, G. J. P. M. JONKERS, K. W. van KRALINGEN, M. J. H. A. KRUIP, T. VLASVELD, M. J. M. DE VREEDE, M. V. HUISMAN, . (2011) Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. Journal of Thrombosis and Haemostasis 9:8, 1500-1507
CrossRef9
Mariette J. Agterof, Roger E.G. Schutgens, Noureddine Moumli, M.J.C. Eijkemans, René van der Griend, Ellen A.M. Tromp, Douwe H. Biesma. (2011) A prognostic model for short term adverse events in normotensive patients with pulmonary embolism. American Journal of Hematology 86:8, 646-649
CrossRef10
Alain Leizorovicz, Virginie Siguret, Dominique Mottier. (2011) Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: The Innohep® in Renal Insufficiency Study (IRIS). Thrombosis Research 128:1, 27-34
CrossRef11
M.J. Agterof, R.E.G. Schutgens, J.F. Verzijlbergen, M.M.C. van Buul, E.A.M. Tromp, M.J.C. Eijkemans, R. van der Griend, D.H. Biesma. (2011) No firm association between N-terminal pro-brain natriuretic peptide and percentage of pulmonary vascular obstruction in patients with acute pulmonary embolism. Thrombosis Research 127:6, 547-550
CrossRef12
Elie A Akl, Srinivasa Rao Vasireddi, Sameer Gunukula, Maddalena Barba, Francesca Sperati, Irene Terrenato, Paola Muti, Holger Schünemann, Elie A Akl. 2011. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. .
CrossRef13
Pietro Roversi, Mauro Campanini. (2011) BPCO e tromboembolismo venoso. Italian Journal of Medicine 5:1, 57-66
CrossRef14
Jawed Fareed, Cafer Adiguzel, Indermohan Thethi. (2011) Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism. Thrombosis Journal 9:1, 5
CrossRef15
G. Palareti. (2011) Bleeding with anticoagulant treatments. Hämostaseologie 31:4, 237-242
CrossRef16
Paul D. Stein, Fadi Matta. (2010) Epidemiology and Incidence: The Scope of the Problem and Risk Factors for Development of Venous Thromboembolism. Clinics in Chest Medicine 31:4, 611-628
CrossRef17
M. J. KOVACS, J. D. HAWEL, J. F. REKMAN, A. LAZO-LANGNER. (2010) Ambulatory management of pulmonary embolism: a pragmatic evaluation. Journal of Thrombosis and Haemostasis 8:11, 2406-2411
CrossRef18
Petra MG Erkens, Martin H Prins, Martin H Prins. 2010. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. .
CrossRef19
H. Bounameaux. (2010) Contemporary management of pulmonary embolism: the answers to ten questions. Journal of Internal Medicine 268:3, 218-231
CrossRef20
Luis A Pérez-de-Llano, Virginia Leiro-Fernández, Rafael Golpe, Jose M Núñez-Delgado, Ana Palacios-Bartolomé, Lidia Méndez-Marote, Esteve Colomé-Nafria. (2010) Comparison of tinzaparin and acenocoumarol for the secondary prevention of venous thromboembolism: a multicentre, randomized study. Blood Coagulation & Fibrinolysis1
CrossRef21
Edmundas Kadusevicius, Gabriele Kildonaviciute, Birute Varanaviciene, Danguole Jankauskiene. (2010) Low-molecular-weight heparins: Pharmacoeconomic decision modeling based on meta-analysis data. International Journal of Technology Assessment in Health Care 26:03, 272-279
CrossRef22
Remedios Otero, Fernando Uresandi, David Jiménez, Miguel Ángel Cabezudo, Mikel Oribe, Dolores Nauffal, Francisco Conget, Consolación Rodríguez, Aurelio Cayuela. (2010) Home treatment in pulmonary embolism. Thrombosis Research 126:1, e1-e5
CrossRef23
Adam Torbicki. (2010) Enfermedad tromboembólica pulmonar. Manejo clínico de la enfermedad aguda y crónica. Revista Española de Cardiología 63:7, 832-849
CrossRef24
Sheridan M. Hoy, Lesley J. Scott, Greg L. Plosker. (2010) Tinzaparin Sodium. Drugs 70:10, 1319-1347
CrossRef25
M. Moia, S. Braham. (2010) Nuovi farmaci antitrombotici in chirurgia ortopedica: dagli studi clinici all’uso nella pratica quotidiana. Archivio di Ortopedia e Reumatologia 121:1, 32-35
CrossRef26
Paul D. Stein, Fadi Matta. (2010) Acute Pulmonary Embolism. Current Problems in Cardiology 35:7, 314-376
CrossRef27
Saina Attaran, Pavlo Somov, Wael I. Awad. (2010) Randomised high- and low-dose heparin prophylaxis in patients undergoing thoracotomy for benign and malignant disease: effect on thrombo-elastography. European Journal of Cardio-Thoracic Surgery 37:6, 1384-1390
CrossRef28
M. J. AGTEROF, R. E. G. SCHUTGENS, R. J. SNIJDER, G. EPPING, H. G. PELTENBURG, E. F. M. POSTHUMA, J. A. HARDEMAN, R. VAN DER GRIEND, T. KOSTER, M. H. PRINS, D. H. BIESMA. (2010) Out of hospital treatment of acute pulmonary embolism in patients with a low NT-proBNP level. Journal of Thrombosis and Haemostasis 8:6, 1235-1241
CrossRef29
C. JAKOBSSON, D. JIM
NEZ, V. G
CrossRef30
Wendy Lim. (2010) Using low molecular weight heparin in special patient populations. Journal of Thrombosis and Thrombolysis 29:2, 233-240
CrossRef31
Vibhu Sharma, Charles Koczka, Conrad Fischer. (2010) Underutilization of evidence-based strategies in the diagnosis and treatment of venous thromboembolism among trainees. Journal of Hospital Medicine 5:1, E26-E30
CrossRef32
Stephen M. Pastores, Louis P. Voigt. (2010) Acute Respiratory Failure in the Patient with Cancer: Diagnostic and Management Strategies. Critical Care Clinics 26:1, 21-40
CrossRef33
R. Tomasi, M. Burgau. (2009) Sekundäre erfolgreiche Thrombolyse einer massiven Lungenembolie am 15. postoperativen Tag nach Versagen von konservativen Therapiemaßnahmen. Intensivmedizin und Notfallmedizin 46:8, 577-583
CrossRef34
L.-C. Linke. (2009) Therapie der postoperativen Thrombose. Der Orthopäde 38:9, 812-817
CrossRef35
Yuquan Zou, Eugene Khor. (2009) Preparation of sulfated-chitins under homogeneous conditions. Carbohydrate Polymers 77:3, 516-525
CrossRef36
Stephen M. Pastores. (2009) Management of venous thromboembolism in the intensive care unit. Journal of Critical Care 24:2, 185-191
CrossRef37
Shaker A. Mousa. 2009. Emerging Links Between Thrombosis, Inflammation, and Angiogenesis: Key Role of Heparin and Low-Molecular-Weight Heparins. , 289-306.
CrossRef38
Won-Ho Choi, Sung Uk Kwon, Yoon Jung Jwa, Jung A Kim, Yun-Ho Choi, Je Ho Chang, Hoon Jung, Joon Hyung Doh, June Namgung, Sung Yun Lee, Won Ro Lee. (2009) The Pulmonary Embolism Severity Index in Predicting the Prognosis of Patients With Pulmonary Embolism. The Korean Journal of Internal Medicine 24:2, 123
CrossRef39
Sang Tae Kim. (2009) Perioperative pulmonary embolism. Korean Journal of Anesthesiology 56:3, 245
CrossRef40
Isaac E. Hall, Martin S. Andersen, Harlan M. Krumholz, Cary P. Gross. (2009) Predictors of Venous Thromboembolism in Patients with Advanced Common Solid Cancers. Journal of Cancer Epidemiology 2009, 1-9
CrossRef41
Kenneth E. Wood. (2009) A History of Pulmonary Embolism and Deep Venous Thrombosis. Critical Care Clinics 25:1, 115-131
CrossRef42
(2008) Guías de práctica clínica sobre diagnóstico y manejo del tromboembolismo pulmonar agudo. Revista Española de Cardiología 61:12, 1330.e1-1330.e52
CrossRef43
Wendy Lim. (2008) Low-molecular-weight heparin in patients with chronic renal insufficiency. Internal and Emergency Medicine 3:4, 319-323
CrossRef44
Elie A. Akl, Sandeep Rohilla, Maddalena Barba, Francesca Sperati, Irene Terrenato, Paola Muti, Fadi Bdair, Holger J. Schünemann. (2008) Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. Cancer 113:7, 1685-1694
CrossRef45
Guy Meyer, Benjamin Planquette, Olivier Sanchez. (2008) Long-term outcome of pulmonary embolism. Current Opinion in Hematology 15:5, 499-503
CrossRef46
Andrew Walden, Richard Levison, Sudir Singh, David Keeling. (2008) A case of fatal pulmonary embolism raising questions about the dosing regimen for dalteparin in the very obese. British Journal of Haematology 142:3, 487-489
CrossRef47
M. A. Crowther, T. E. Warkentin. (2008) Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents. Blood 111:10, 4871-4879
CrossRef48
Elie A Akl, Maddalena Barba, Sandeep Rohilla, Irene Terrenato, Francesca Sperati, Paola Muti, Holger Schünemann, Elie A Akl. 2008. Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer. .
CrossRef49
A.J. Burge, K.D. Freeman, P.J. Klapper, L.B. Haramati. (2008) Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clinical Radiology 63:4, 381-386
CrossRef50
, A. Torbicki, A. Perrier, S. Konstantinides, G. Agnelli, N. Galie, P. Pruszczyk, F. Bengel, A. J.B. Brady, D. Ferreira, U. Janssens, W. Klepetko, E. Mayer, M. Remy-Jardin, J.-P. Bassand, , A. Vahanian, J. Camm, R. De Caterina, V. Dean, K. Dickstein, G. Filippatos, C. Funck-Brentano, I. Hellemans, S. D. Kristensen, K. McGregor, U. Sechtem, S. Silber, M. Tendera, P. Widimsky, J. L. Zamorano, , J.-L. Zamorano, F. Andreotti, M. Ascherman, G. Athanassopoulos, J. De Sutter, D. Fitzmaurice, T. Forster, M. Heras, G. Jondeau, K. Kjeldsen, J. Knuuti, I. Lang, M. Lenzen, J. Lopez-Sendon, P. Nihoyannopoulos, L. Perez Isla, U. Schwehr, L. Torraca, J.-L. Vachiery. (2008) Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). European Heart Journal 29:18, 2276-2315
CrossRef51
Tapson, Victor F., . (2008) Acute Pulmonary Embolism. New England Journal of Medicine 358:10, 1037-1052
Full Text52
Guy Meyer, Benjamin Planquette, Olivier Sanchez. (2008) Long-term outcome of pulmonary embolism. Therapy 5:2, 159-167
CrossRef53
Marieke JHA Kruip, Frank WG Leebeek. (2008) Advances in the detection of pulmonary embolism. Expert Opinion on Medical Diagnostics 2:2, 171-181
CrossRef54
Elie A Akl, Sandeep Rohilla, Maddalena Barba, Francesca Sperati, Irene Terrenato, Paola Muti, Holger Schünemann, Elie A Akl. 2008. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. .
CrossRef55
Mark Crowther, Wendy Lim. (2007) Low molecular weight heparin and bleeding in patients with chronic renal failure. Current Opinion in Internal Medicine 6:6, 648-652
CrossRef56
Amanda J. Ghanim, Constantine Daskalakis, David J. Eschelman, Walter K. Kraft. (2007) A five-year, retrospective, comparison review of survival in neurosurgical patients diagnosed with venous thromboembolism and treated with either inferior vena cava filters or anticoagulants. Journal of Thrombosis and Thrombolysis 24:3, 247-254
CrossRef57
Keiichi Ishida, Masahisa Masuda. (2007) Review of Acute Pulmonary Embolism in a General Hospital. Surgery Today 37:9, 740-744
CrossRef58
C. Becattini, G. Agnelli. (2007) Acute pulmonary embolism: risk stratification in the emergency department. Internal and Emergency Medicine 2:2, 119-129
CrossRef59
Vicky Tagalakis, Mark Blostein, Cassianne Robinson-Cohen, Susan R. Kahn. (2007) The effect of anticoagulants on cancer risk and survival: Systematic review. Cancer Treatment Reviews 33:4, 358-368
CrossRef60
David H. Lee, Theodore E. Warkentin. 2007. Frequency of Heparin-Induced Thrombocytopenia. , 67-116.
CrossRef61
I. A. NÆSS, S. C. CHRISTIANSEN, P. ROMUNDSTAD, S. C. CANNEGIETER, F. R. ROSENDAAL, J. HAMMERSTRØM. (2007) Incidence and mortality of venous thrombosis: a population-based study. Journal of Thrombosis and Haemostasis 5:4, 692-699
CrossRef62
Thomas C. Krivak, Kristin K. Zorn. (2007) Venous Thromboembolism in Obstetrics and Gynecology. Obstetrics & Gynecology 109:3, 761-777
CrossRef63
Takahiro Yasui, Nobuhiro Tanabe, Jiro Terada, Noriyuki Yanagawa, Hidefumi Shimizu, Hiroshi Matsubara, Susumu Hoshino, Ayako Fujikawa, Satoko Mizuno, Mari Yatomi, Seiichiro Sakao, Takahiro Uruma, Yasunori Kasahara, Yuichi Takiguchi, Koichiro Tatsumi, Takayuki Kuriyama. (2007) Multidetector-Row Computed Tomography Management of Acute Pulmonary Embolism. Circulation Journal 71:12, 1948-1954
CrossRef64
Matthew T. Rondina, Robert C. Pendleton, Michelle Wheeler, George M. Rodgers. (2007) The treatment of venous thromboembolism in special populations. Thrombosis Research 119:4, 391-402
CrossRef65
Samuel Z. Goldhaber. 2007. Deep Vein Thrombosis and Pulmonary Embolism. , 245-256.
CrossRef66
Gregory Piazza, Samuel Z. Goldhaber. (2006) Venous Thromboembolism Guidebook. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 5:4, 211-227
CrossRef67
Patrick Y. Wen, David Schiff, Santosh Kesari, Jan Drappatz, Debra C. Gigas, Lisa Doherty. (2006) Medical management of patients with brain tumors. Journal of Neuro-Oncology 80:3, 313-332
CrossRef68
Gilles L. Fraser, Richard R. Riker. (2006) Unfractionated- versus low-molecular-weight-heparin-associated HIT in hospitalized medical patients. Journal of Hospital Medicine 1:6, 380-381
CrossRef69
Massimo Miniati, Simonetta Monti, Matteo Bottai, Elvio Scoscia, Carolina Bauleo, Lucia Tonelli, Alba Dainelli, Carlo Giuntini. (2006) Survival and Restoration of Pulmonary Perfusion in a Long-Term Follow-Up of Patients After Acute Pulmonary Embolism. Medicine 85:5, 253-262
CrossRef70
Philippe de Moerloose, Charles Marc Samama, Serge Motte. (2006) Management of venous thromboembolism. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 53:S2, S80-S88
CrossRef71
Juan Ruiz Manzano. (2006) Tratamiento ambulatorio de la tromboembolia pulmonar. Medicina Clínica 127:1, 11-12
CrossRef72
David Keeling. (2006) Duration of anticoagulation: decision making based on absolute risk. Blood Reviews 20:3, 173-178
CrossRef73
Paul G. Kluetz, Charles S. White. (2006) Acute Pulmonary Embolism: Imaging in the Emergency Department. Radiologic Clinics of North America 44:2, 259-271
CrossRef74
KLAS NORRBY. (2006) Low-molecular-weight heparins and angiogenesis.. APMIS 114:2, 79-102
CrossRef75
Dorothy S. Lo, Christian G. Rabbat, Catherine M. Clase. (2006) Thromboembolism and anticoagulant management in hemodialysis patients: A practical guide to clinical management. Thrombosis Research 118:3, 385-395
CrossRef76
A. T. Cohen, C. Hirst, B. Sherrill, P. Holmes, D. Fidan. (2005) Meta-analysis of trials comparing ximelagatran with low molecular weight heparin for prevention of venous thromboembolism after major orthopaedic surgery. British Journal of Surgery 92:11, 1335-1344
CrossRef77
Marc Meysman, Patrick Haentjens. (2005) Pulmonary embolism: Current treatment options. Current Treatment Options in Cardiovascular Medicine 7:6, 483-490
CrossRef78
, , , , , , , , , , , , , , , , . (2005) Interdisziplinäre S2-Leitlinie. Diagnostik und Therapie der Bein- und Beckenvenenthrombose und der Lungenembolie. Intensivmedizin und Notfallmedizin 42:7, 552-565
CrossRef79
Joseph A. Caprini, Victor F. Tapson, Thomas M. Hyers, Albert L. Waldo, Ann K. Wittkowsky, Richard Friedman, Kevin J. Colgan, Alicia C. Shillington. (2005) Treatment of venous thromboembolism: Adherence to guidelines and impact of physician knowledge, attitudes, and beliefs. Journal of Vascular Surgery 42:4, 726-733
CrossRef80
Carlo J van Dongen, Melvin R Mac Gillavry, Martin H Prins, Carlo J van Dongen. 2005. Once versus twice daily low molecular weight heparin for the initial treatment of venous thromboembolism. .
CrossRef81
M.E. Daskalopoulos, S.S. Daskalopoulou, E. Tzortzis, P. Sfiridis, A. Nikolaou, D. Dimitroulis, I. Kakissis, C.D. Liapis. (2005) Long-term Treatment of Deep Venous Thrombosis with a Low Molecular Weight Heparin (Tinzaparin): A Prospective Randomized Trial. European Journal of Vascular and Endovascular Surgery 29:6, 638-650
CrossRef82
Shaker A Mousa. (2005) Anti-thrombotics in thrombosis and cancer. Future Oncology 1:3, 395-403
CrossRef83
&NA;. (2005) Tinzaparin is effective in the prophylaxis and treatment of thromboembolic disease. Drugs & Therapy Perspectives 21:6, 1-3
CrossRef84
Paolo Prandoni. (2005) Emerging strategies for treatment of venous thromboembolism. Expert Opinion on Emerging Drugs 10:1, 87-94
CrossRef85
Nathan I. Shapiro, Jeffrey Spear, Susan Sheehy, Jeremy Brown, Jonathan A. Edlow. (2005) Barriers to the use of outpatient enoxaparin therapy in patients with deep venous thrombosis. The American Journal of Emergency Medicine 23:1, 30-34
CrossRef86
Isabelle Gouin-Thibault, Eric Pautas, Virginie Siguret. (2005) Safety Profile of Different Low-Molecular Weight Heparins Used at Therapeutic Dose. Drug Safety 28:4, 333-349
CrossRef87
Timothy A. Morris, Alan Jacobson, James J. Marsh, James R. Lane. (2005) Pharmacokinetics of UH and LMWH are similar with respect to antithrombin activity. Thrombosis Research 115:1-2, 45-51
CrossRef88
Mark A. Crowther, Finn Wisloff. (2005) Evidence based treatment of the antiphospholipid syndrome. Thrombosis Research 115:1-2, 3-8
CrossRef89
Darlene J. Elias. (2004) Pulmonary Embolism in Orthopaedic Patients: Diagnosis and Treatment. Techniques in Orthopaedics 19:4, 317-326
CrossRef90
H. Lévesque, C. Belizna, P. Michel, C. Pfister. (2004) Traitement de la maladie thromboembolique veineuse chez les patients souffrant de cancers. La Revue de Médecine Interne 25:12, 906-914
CrossRef91
Stephen Trzeciak, R Phillip Dellinger. (2004) Other supportive therapies in sepsis: An evidence-based review. Critical Care Medicine 32:Supplement, S571-S577
CrossRef92
Carlo J van Dongen, Angelique GM van den Belt, Martin H Prins, AWA Lensing, Martin H Prins. 2004. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. .
CrossRef93
David Bergqvist. (2004) Bleeding profiles of anticoagulants, including the novel oral direct thrombin inhibitor ximelagatran: definitions, incidence and management. European Journal of Haematology 73:4, 227-242
CrossRef94
Peter A. Heppner, Stephen J. Monteith, Andrew J. J. Law. (2004) Spontaneous spinal hematomas and low-molecular-weight heparin. Journal of Neurosurgery: Spine 1:2, 232-236
CrossRef95
Virginie Siguret, Eric Pautas, Isabelle Gouin. (2004) Low molecular weight heparin treatment in elderly subjects with or without renal insufficiency: new insights between June 2002 and March 2004. Current Opinion in Pulmonary Medicine 10:5, 366-370
CrossRef96
Mehmet Kurtoglu, Hakan Yanar, Yilmaz Bilsel, Recep Guloglu, Sevda Kizilirmak, Dincay Buyukkurt, Volkan Granit. (2004) Venous Thromboembolism Prophylaxis after Head and Spinal Trauma: Intermittent Pneumatic Compression Devices Versus Low Molecular Weight Heparin. World Journal of Surgery 28:8, 807-811
CrossRef97
Edith A. Nutescu, Cathy M. Helgason. (2004) Evolving Concepts in the Treatment of Venous Thromboembolism: The Role of Factor Xa Inhibitors. Pharmacotherapy 24:7 Part 2, 82S-87S
CrossRef98
Marios E. Daskalopoulos, Stella S. Daskalopoulou, Christos D. Liapis. (2004) Low molecular weight heparins: the optimal treatment for venous thromboembolism. Current Medical Research and Opinion 20:7, 1001-1005
CrossRef99
S SRIVASTAVA. (2004) Diagnosis of pulmonary embolism with various imaging modalities. Seminars in Vascular Surgery 17:2, 173-180
CrossRef100
Daniel Farray, Teresa L Carman, Bernardo B Fernandez. (2004) The treatment and prevention of deep vein thrombosis in the preoperative management of patients who have neurologic diseases. Neurologic Clinics 22:2, 423-439
CrossRef101
J.A Krishnan, J.B Segal, M.B Streiff, D.T Bolger, J Eng, M.W Jenckes, L.J Tamariz, E.B Bass. (2004) Treatment of venous thromboembolism with low-molecular-weight heparin: a synthesis of the evidence published in systematic literature reviews. Respiratory Medicine 98:5, 376-386
CrossRef102
Samuel Z Goldhaber. (2004) Pulmonary embolism. The Lancet 363:9417, 1295-1305
CrossRef103
Shuwei Gao, Carmen Escalante. (2004) Venous thromboembolism and malignancy. Expert Review of Anticancer Therapy 4:2, 303-320
CrossRef104
Thomas B. Kinney. (2004) Case Presentation: Post Op Day 3, Chest Pain and Dsypnea. Journal of Vascular and Interventional Radiology 15:2, P44-P50
CrossRef105
Susan M Cheer, Christopher J Dunn, Rachel Foster. (2004) Tinzaparin Sodium. Drugs 64:13, 1479-1502
CrossRef106
Graham F Pineo, Russell D Hull. (2003) Tinzaparin in the treatment of venous thromboembolism. Expert Opinion on Pharmacotherapy 4:12, 2355-2362
CrossRef107
Edwin J.R. van Beek, Jim M. Wild, Christian Fink, Alan R. Moody, Hans-Ulrich Kauczor, Matthijs Oudkerk. (2003) MRI for the diagnosis of pulmonary embolism. Journal of Magnetic Resonance Imaging 18:6, 627-640
CrossRef108
Daniel J Brotman, Scott Kaatz. (2003) Should patients on warfarin for 3 months for idiopathic proximal deep venous thrombosis receive bridging therapy precolonoscopy (with expected biopsy)?. Medical Clinics of North America 87:6, 1205-1214
CrossRef109
The Matisse Investigators. (2003) Subcutaneous Fondaparinux versus Intravenous Unfractionated Heparin in the Initial Treatment of Pulmonary Embolism. New England Journal of Medicine 349:18, 1695-1702
Full Text110
Shaker A Mousa. (2003) Antithrombotics in thrombosis and cancer. Expert Review of Cardiovascular Therapy 1:2, 283-291
CrossRef111
M. N. Levine, A. Y. Lee, A. K. Kakkar. (2003) From Trousseau to targeted therapy: new insights and innovations in thrombosis and cancer. Journal of Thrombosis and Haemostasis 1:7, 1456-1463
CrossRef112
S. Schulman. (2003) Unresolved issues in anticoagulant therapy. Journal of Thrombosis and Haemostasis 1:7, 1464-1470
CrossRef113
Gregory Piazza, Samuel Z. Goldhaber. (2003) Periprocedural Management of the Chronically Anticoagulated Patient. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 2:2, 96-103
CrossRef114
U. Priglinger, G. Delle Karth, A. Geppert, C. Joukhadar, S. Graf, R. Berger, M. Hülsmann, S. Spitzauer, I. Pabinger, G. Heinz. (2003) Prophylactic anticoagulation with enoxaparin: Is the subcutaneous route appropriate in the critically ill?*. Critical Care Medicine 31:5, 1405-1409
CrossRef115
Janet A Rowan, Claire McLintock, Rennae S Taylor, Robyn A North. (2003) Prophylactic and therapeutic enoxaparin during pregnancy: Indications, outcomes and monitoring. The Australian and New Zealand Journal of Obstetrics and Gynaecology 43:2, 123-128
CrossRef116
Ian A Greer. (2003) Prevention and management of venous thromboembolism in pregnancy. Clinics in Chest Medicine 24:1, 123-137
CrossRef117
H. Bounameaux, A. Perrier. (2003) LMWH contra LMWH: superior, equivalent or non-inferior?. Journal of Thrombosis and Haemostasis 1:3, 414-415
CrossRef118
Roger D Yusen, Brian F Gage. (2003) Outpatient treatment of acute venous thromboembolic disease. Clinics in Chest Medicine 24:1, 49-61
CrossRef119
Selim M Arcasoy, Anil Vachani. (2003) Local and systemic thrombolytic therapy for acute venous thromboembolism. Clinics in Chest Medicine 24:1, 73-91
CrossRef120
Rodger L Bick, Sylvia Haas. (2003) Thromboprophylaxis and thrombosis in medical, surgical, trauma, and obstetric/gynecologic patients. Hematology/Oncology Clinics of North America 17:1, 217-258
CrossRef121
Philippe Cestac, Haleh Bagheri, Maryse Lapeyre-Mestre, Pierre Si??, Atoussa Fouladi, Eric Maupas, Philippe L??ger, Bernard Fontan, Patrice Massip, Jean-Louis Montastruc. (2003) Utilisation and Safety of Low Molecular Weight Heparins. Drug Safety 26:3, 197-207
CrossRef122
(2003) Retroperitoneal haematoma and tinzaparin. Current Medical Research and Opinion 19:3, 238-239
CrossRef123
Geno J Merli. (2003) Current pharmacotherapeutic options for treating deep vein thrombosis. Expert Opinion on Pharmacotherapy 4:1, 55-65
CrossRef124
Mizuhiro Arima, Tatsuji Kanoh, Atsutoshi Takagi, Kosei Tanimoto, Tetsuya Oigawa, Shigeru Matsuda. (2003) Clinical Features of Acute Pulmonary Thromboembolism in Younger Patients. Circulation Journal 67:4, 330-333
CrossRef125
Enrico Bernardi, Paolo Prandoni. (2003) Safety of low molecular weight heparins in the treatment of venous thromboembolism. Expert Opinion on Drug Safety 2:1, 87-94
CrossRef126
Tze Foon Lai, Johnny Wu, Tim Henderson, Wilfred Winlaw. (2002) Septic superior ophthalmic vein thrombosis: to coagulate or not to coagulate?. Clinical and Experimental Ophthalmology 30:6, 447-449
CrossRef127
(2002) Pharmacotherapy of pulmonary embolism. Expert Opinion on Pharmacotherapy 3:12, 1719-1725
CrossRef128
CJ van Dongen, Gillavry MR Mac, MH Prins. 2002. Once versus twice daily LMWH for the initial treatment of venous thromboembolism. .
CrossRef129
K. T. Tan, E. J. R. van Beek. (2002) Diagnosis and Treatment of Pulmonary Embolism: An Overview. Imaging Decisions MRI 6:3, 3-10
CrossRef130
Shaker A. Mousa. (2002) The Low Molecular Weight Heparin, Tinzaparin, in Thrombosis and Beyond. Cardiovascular Drug Reviews 20:3, 199-216
CrossRef131
Hugo Partsch. (2002) Bed rest versus ambulation in the initial treatment of patients with proximal deep vein thrombosis. Current Opinion in Pulmonary Medicine 8:5, 389-393
CrossRef132
RODERICK NAZARIO, LAWRENCE J. DELORENZO, GEORGE P. MAGUIRE. (2002) Treatment of Venous Thromboembolism. Cardiology in Review 10:4, 249-259
CrossRef133
Mark N Levine. (2002) Managing thromboembolic disease in the cancer patient: efficacy and safety of antithrombotic treatment options in patients with cancer. Cancer Treatment Reviews 28:3, 145-149
CrossRef134
Steven R. Deitcher, Teresa L. Carman. (2002) Deep venous thrombosis and pulmonary embolism. Current Treatment Options in Cardiovascular Medicine 4:3, 223-238
CrossRef135
Doris Moser, Michael Rasse, Christian Schopper, Georgios Lagogiannis, Michael Frass, Rolf Ewers, Alan D. Kaye, Roland Hofbauer. (2002) A scanning electron microscopic study on thrombogenicity of intraarterial catheters for chemotherapeutic treatment in head and neck cancer. Head & Neck 24:6, 566-574
CrossRef136
Patrick Y. Wen, Peter W. Marks. (2002) Medical management of patients with brain tumors. Current Opinion in Oncology 14:3, 299-307
CrossRef137
Shaker A Mousa. (2002) Anticoagulants in thrombosis and cancer: the missing link. Expert Review of Anticancer Therapy 2:2, 227-233
CrossRef138
Jean-Pierre Cambus, Sylvie Saivin, Jean-Jacques Heilmann, Henri Caplain, Bernard Boneu, Georges Houin. (2002) The pharmacodynamics of tinzaparin in healthy volunteers. British Journal of Haematology 116:3, 649-652
CrossRef139
M DEGREGORIO, M GIMENO, A MAINAR, M HERRERA, R TOBIO, R ALFONSO, J MEDRANO, M FAVA. (2002) Mechanical and Enzymatic Thrombolysis for Massive Pulmonary Embolism. Journal of Vascular and Interventional Radiology 13:2, 163-169
CrossRef140
Eric Pautas, Isabelle Gouin, Oliver Bellot, Jean-Paul Andreux, Virginie Siguret. (2002) Safety Profile of Tinzaparin Administered Once Daily at a Standard Curative Dose in Two Hundred Very Elderly Patients. Drug Safety 25:10, 725-733
CrossRef141
N. Meneveau, J.P. Bassand. (2002) Quand suspecter une embolie pulmonaire chez un malade ayant une thrombose veineuse profonde ?. Annales de Cardiologie et d'Angéiologie 51:3, 139-145
CrossRef142
C. Schmidt. (2002) Traitement ambulatoire des thromboses veineuses profondes des membres inférieurs à la phase aiguë. Annales de Cardiologie et d'Angéiologie 51:3, 152-157
CrossRef143
J. Jaime Caro, Denis Getsios, Ingrid Caro, Judith A. O??Brien. (2002) Cost Effectiveness of Tinzaparin Sodium Versus Unfractionated Heparin in the Treatment of Proximal Deep Vein Thrombosis. PharmacoEconomics 20:9, 593-602
CrossRef144
Pierre Laurent, Guy-Vincent Dussarat, Jacques Bonal, Christophe Jego, Philippe Talard, Christian Bouchiat, Gilles Cellarier. (2002) Low Molecular Weight Heparins. Drugs 62:3, 463-477
CrossRef145
Ian A. Greer. (2001) The acute management of venous thromboembolism in pregnancy. Current Opinion in Obstetrics and Gynecology 13:6, 569-575
CrossRef146
P GIBSON, K ROSENEMONTELLA. (2001) Anticoagulants. Best Practice & Research Clinical Obstetrics & Gynaecology 15:6, 847-861
CrossRef147
DK Cundiff, J Manyemba, David Cundiff. 2001. Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism.. .
CrossRef148
E VANBEEK, E BROUWERS, B SONG, P STEIN, M OUDKERK. (2001) Clinical Validity of a Normal Pulmonary Angiogram in Patients with Suspected Pulmonary Embolism?A Critical Review. Clinical Radiology 56:10, 838-842
CrossRef149
Philip MW Bath, Ewa Lindenstrom, Gudrun Boysen, Peter De Deyn, Pal Friis, Didier Leys, Reijo Marttila, Jan-Edwin Olsson, Desmond O'Neill, Jean-Marc Orgogozo, Bernd Ringelstein, Jan-Jacob van der Sande, Alexander GG Turpie. (2001) Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial. The Lancet 358:9283, 702-710
CrossRef150
James D. Douketis. (2001) Prognosis in pulmonary embolism. Current Opinion in Pulmonary Medicine 7:5, 354-359
CrossRef151
Samuel Z Goldhaber. (2001) Unsolved Issues in the Treatment of Pulmonary Embolism. Thrombosis Research 103:6, V245-V255
CrossRef152
Philip S. Wells. (2001) Outpatient treatment of patients with deep-vein thrombosis or pulmonary embolism. Current Opinion in Pulmonary Medicine 7:5, 360-364
CrossRef153
Mark LH Tie, Bogda Koczwara. (2001) Radiology interventions in patients receiving low molecular weight heparin: Timing is critical. Australasian Radiology 45:3, 313-317
CrossRef154
I GREER, A THOMSON. (2001) Management of venous thromboembolism in pregnancy. Best Practice & Research Clinical Obstetrics & Gynaecology 15:4, 583-603
CrossRef155
M DESANCHO, J RAND. (2001) BLEEDING AND THROMBOTIC COMPLICATIONS IN CRITICALLY ILL PATIENTS WITH CANCER. Critical Care Clinics 17:3, 599-622
CrossRef156
S PASTORES. (2001) ACUTE RESPIRATORY FAILURE IN CRITICALLY ILL PATIENTS WITH CANCERDiagnosis and Management. Critical Care Clinics 17:3, 623-646
CrossRef157
Larry M. Lopez. (2001) Low-Molecular-Weight Heparins Are Essentially the Same for Treatment and Prevention of Venous Thromboembolism. Pharmacotherapy 21:6 Part 2, 56S-61S
CrossRef158
Christopher R May. (2001) Management of venous thromboembolic disease in the lower limb. Emergency Medicine Australasia 13:2, 211-223
CrossRef159
Graham F. Pineo. (2001) New Developments in the Prevention and Treatment of Venous Thromboembolism. Pharmacotherapy 21:6 Part 2, 51S-55S
CrossRef160
Eric Racine. (2001) Differentiation of the Low-Molecular-Weight Heparins. Pharmacotherapy 21:6 Part 2, 62S-70S
CrossRef161
Wee S. Chan, Sanjeev D. Chunilal, Jeffrey S. Ginsberg. (2001) Antithrombotic therapy during pregnancy. Seminars in Perinatology 25:3, 165-169
CrossRef162
Agnes Y.Y Lee. (2001) Treatment of Venous Thromboembolism in Cancer Patients. Thrombosis Research 102:6, V195-V208
CrossRef163
Alexander G.G Turpie. (2001) Looking forward in the treatment of deep-vein thrombosis. Seminars in Hematology 38, 49-57
CrossRef164
Peter F. Fedullo, Douglas M. Humber. (2001) Acute and chronic pulmonary emboli. Current Treatment Options in Cardiovascular Medicine 3:2, 139-150
CrossRef165
Breddin, Hans Klaus, Hach-Wunderle, Viola, Nakov, Roumen, Kakkar, Vijay V., . (2001) Effects of a Low-Molecular-Weight Heparin on Thrombus Regression and Recurrent Thromboembolism in Patients with Deep-Vein Thrombosis. New England Journal of Medicine 344:9, 626-631
Full Text166
Beth A. Duplaga, Christina W. Rivers, Edith Nutescu. (2001) Dosing and Monitoring of Low-Molecular-Weight Heparins in Special Populations. Pharmacotherapy 21:2, 218-234
CrossRef167
E Pautas, V Siguret, M d’Urso, M Laurent, P Gaussem, M Février, B Durand-Gasselin. (2001) Surveillance d’un traitement par la tinzaparine à dose curative pendant dix jours chez le sujet âgé. La Revue de Médecine Interne 22:2, 120-126
CrossRef168
Jeffrey S. Barrett, James W. Hainer, David M. Kornhauser, James L. Gaskill, Tsushung A. Hua, Per Sprogel, Kristen Johansen, J.J. van Lier, William Knebel, Henry J. Pieniaszek. (2001) Anticoagulant Pharmacodynamics of Tinzaparin Following 175 IU/kg Subcutaneous Administration to Healthy Volunteers. Thrombosis Research 101:4, 243-254
CrossRef169
Ermanno Attanasio, Pierluigi Russo, Gabriella Carunchio, Luciano Caprino. (2001) Dermatan Sulfate versus Unfractionated Heparin for the Prevention of Venous Thromboembolism in Patients Undergoing Surgery for Cancer. PharmacoEconomics 19:1, 57-68
CrossRef170
John A. Heit. (2001) Current Management of Acute Symptomatic Deep Vein Thrombosis. American Journal of Cardiovascular Drugs 1:1, 45-50
CrossRef171
Ian D. Timms. (2001) Low-Molecular-Weight Heparins: Overview and Potential Uses in Interventional Radiology. Journal of Vascular and Interventional Radiology 12:1, P33-P39
CrossRef172
Timothy A Morris, James J Marsh, Ronald Konopka, Craig A Pedersen, Peter G Chiles. (2000) Anti-thrombotic Efficacies of Enoxaparin, Dalteparin, and Unfractionated Heparin in Venous Thrombo-embolism. Thrombosis Research 100:3, 185-194
CrossRef173
J. Weimann, W. Zink, M. M. Gebhard, A. Gries, E. Martin, J. Motsch. (2000) Effects of oxygen and nitric oxide inhalation in a porcine model of recurrent microembolism. Acta Anaesthesiologica Scandinavica 44:9, 1109-1115
CrossRef174
John R Toomey, Michael N Blackburn, Barbara L Storer, Richard E Valocik, Paul F Koster, Giora Z Feuerstein. (2000) Comparing the Antithrombotic Efficacy of a Humanized Anti-factor IX(a) Monoclonal Antibody (SB 249417) to the Low Molecular Weight Heparin Enoxaparin In a Rat Model of Arterial Thrombosis. Thrombosis Research 100:1, 73-79
CrossRef175
Jeroen F van der Heijden, Martin H Prins, Harry R Büller. (2000) For the Initial Treatment of Venous Thromboembolism. Thrombosis Research 100:2, 121-130
CrossRef176
Rodger L. Bick. (2000) Proficient and Cost-Effective Approaches for the Prevention and Treatment of Venous Thrombosis and Thromboembolism. Drugs 60:3, 575-595
CrossRef177
V. J. Martlew. (2000) Peri-operative management of patients with coagulation disorders. British Journal of Anaesthesia 85:3, 446-455
CrossRef178
F López-Jiménez. (2000) Update in Internal Medicine. Archives of Medical Research 31:4, 329-352
CrossRef179
P. de Moerloose, G. Reber, A. Perrier, T. Perneger, H. Bounameaux. (2000) Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism. British Journal of Haematology 110:1, 125-129
CrossRef180
Manuel Monreal. (2000) Long-term treatment of venous thromboembolism with low-molecular-weight heparin. Current Opinion in Pulmonary Medicine 6:4, 326-329
CrossRef181
Spiros G Frangos, Alan H Chen, Bauer Sumpio. (2000) Vascular drugs in the new millennium11No competing interests declared.. Journal of the American College of Surgeons 191:1, 76-92
CrossRef182
Graham F. Pineo, Russell D. Hull. (2000) Disorders of pulmonary circulation: pulmonary vascular disease. Current Opinion in Pulmonary Medicine 6:4, 293-295
CrossRef183
Thomas W Wakefield. (2000) Treatment options for venous thrombosis. Journal of Vascular Surgery 31:3, 613-620
CrossRef184
Carlos A. Estrada, Christopher J. Mansfield, Gustavo R. Heudebert. (2000) Cost-effectiveness of Low-Molecular-Weight Heparin in the Treatment of Proximal Deep Vein Thrombosis. Journal of General Internal Medicine 15:2, 108-115
CrossRef185
A THOMSON, I GREER. (2000) Non-haemorrhagic obstetric shock. Best Practice & Research Clinical Obstetrics & Gynaecology 14:1, 19-41
CrossRef186
Samuel Z. Goldhaber. (2000) Medical Management of Venous Thromboembolic Disease. Journal of Vascular and Interventional Radiology 11:2, 160-162
CrossRef187
Ian D. Timms. (2000) Low-Molecular-Weight Heparins. Journal of Vascular and Interventional Radiology 11:2, 392-396
CrossRef188
Walter Ageno. (2000) Treatment of Venous Thromboembolism. Thrombosis Research 97:1, V63-V72
CrossRef189
William E. Wade, Bradley C. Martin, Jeffrey A. Kotzan, William J. Spruill, Marie A. Chisoholm, Matthew Perri. (2000) Formulary Management of Low Molecular Weight Heparins. PharmacoEconomics 17:1, 1-12
CrossRef190
AGM van den Belt, MH Prins, AWA Lensing, AA Castro, OAC Clark, AN Atallah, E Burihan. 1999. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. .
CrossRef191
Roland Hofbauer, Doris Moser, Michael Frass, Rainer Oberbauer, Alan D. Kaye, O. Wagner, Stylianos Kapiotis, Wilfred Druml. (1999) Effect of anticoagulation on blood membrane interactions during hemodialysis. Kidney International 56:4, 1578-1583
CrossRef192
Wee Shian Chan, Joel G. Ray. (1999) Low Molecular Weight Heparin Use During Pregnancy: Issues of Safety and Practicality. Obstetrical & Gynecological Survey 54:10, 649-654
CrossRef193
Stavros Konstantinides. (1999) Aktuelle Diagnostik und Therapie der akuten Lungenembolie. Herz 24:6, 411-420
CrossRef194
David M. Spiegel, Robert J. Anderson. (1999) Is low-molecular-weight heparin useful for venovenous hemofiltration in the intensive care unit?. Critical Care Medicine 27:10, 2316-2317
CrossRef195
Paolo Prandoni, Pier Mannuccio Mannucci. (1999) Deep-vein thrombosis of the lower limbs: diagnosis and management. Best Practice & Research Clinical Haematology 12:3, 533-554
CrossRef196
Graham F. Pineo, Russell D. Hull. (1999) Disorders of pulmonary circulation. Current Opinion in Pulmonary Medicine 5:4, 209
CrossRef197
Gary E. Raskob. (1999) Heparin and low molecular weight heparin for treatment of acute pulmonary embolism. Current Opinion in Pulmonary Medicine 5:4, 216
CrossRef198
Brian M. Legere, Raed A. Dweik, Alejandro C. Arroliga. (1999) VENOUS THROMBOEMBOLISM IN THE INTENSIVE CARE UNIT. Clinics in Chest Medicine 20:2, 367-384
CrossRef199
Jack Hirsh, Shannon M Bates. (1999) Prognosis in acute pulmonary embolism. The Lancet 353:9162, 1375-1376
CrossRef200
Edward C. Grendys, James V. Fiorica. (1999) Advances in the prevention and treatment of deep vein thrombosis and pulmonary embolism. Current Opinion in Obstetrics and Gynaecology 11:1, 71-79
CrossRef201
Gregory A. Schmidt. (1999) Pulmonary embolism. Current Opinion in Critical Care 5:1, 61
CrossRef202
Anthonie WA Lensing, Paolo Prandoni, Martin H Prins, HR Büller. (1999) Deep-vein thrombosis. The Lancet 353:9151, 479-485
CrossRef203
Max P. Rosen. (1999) Spiral CT angiography for suspected pulmonary embolism: A cost-effectiveness analysis. Academic Radiology 6:1, 72-74
CrossRef204
Arian R. van Erkel, Peter M.T. Pattynama. (1999) Authors' response. Academic Radiology 6:1, 74-75
CrossRef205
James N. Huang, Akiko Shimamura. (1998) LOW-MOLECULAR-WEIGHT HEPARINS. Hematology/Oncology Clinics of North America 12:6, 1251-1281
CrossRef206
Andrew J Thomson, Isobel D Walker, Ian A Greer. (1998) Low-molecular-weight heparin for immediate management of thromboembolic disease in pregnancy. The Lancet 352:9144, 1904
CrossRef207
Mohammed A Quader, Lisa S Stump, Bauer E Sumpio. (1998) Low molecular weight heparins: current use and indications. Journal of the American College of Surgeons 187:6, 641-658
CrossRef208
(1998) Pulmonary Embolism. New England Journal of Medicine 339:21, 1555-1557
Full Text209
Philip MW Bath. (1998) Low molecular weight heparin in acute stroke. Expert Opinion on Investigational Drugs 7:8, 1323-1330
CrossRef210
N. Curzen, R. Haque, A. Timmis. (1998) Applications of thrombolytic therapy. Intensive Care Medicine 24:8, 756-768
CrossRef211
Goldhaber, Samuel Z., . (1998) Pulmonary Embolism. New England Journal of Medicine 339:2, 93-104
Full Text212
David Bergqvist. (1998) MODERN ASPECTS OF PROPHYLAXIS AND THERAPY FOR VENOUS THROMBO-EMBOLIC DISEASE. ANZ Journal of Surgery 68:7, 463-468
CrossRef213
Yu, David R., Miller, Redonda, Bray, Paul F., . (1998) Through Thick and Thin. New England Journal of Medicine 338:23, 1684-1687
Full Text214
P.E. Rose, D. Fitzmaurice. (1998) New approaches to the delivery of anticoagulant services. Blood Reviews 12:2, 84-90
CrossRef215
S C Litin, J A Heit, K A Mees. (1998) Use of low-molecular-weight heparin in the treatment of venous thromboembolic disease: answers to frequently asked questions. The Thrombophilia Center Investigators.. Mayo Clinic Proceedings 73:6, 545-550
CrossRef216
Sylvia K. Haas. (1998) TREATMENT OF DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM. Medical Clinics of North America 82:3, 495-510
CrossRef217
. (1997) Behandeling van diepe veneuze trombose met laagmoleculaire heparines. Medisch-Farmaceutische Mededelingen 35:10, 210-210
CrossRef218
Wood, Alastair J.J., , Weitz, Jeffrey I., . (1997) Low-Molecular-Weight Heparins. New England Journal of Medicine 337:10, 688-699
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