Venous thromboembolism thrombosis Pulmonary embolism

Women who are lactating or who are or may become pregnant (see Warnings) women with active or a history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis hypersensitivity to raloxifene or other constituents of the drug. 

INR 2.0-3.0 Treatment of deep vein thrombosis pulmonary embolism systemic embolism prevention of venous thromboembolism in myocardial infarction mitral stenosis with embolism transient ischaemic attacks atrial fibrillation. 

Venous thromboembolism (VTE) is one of the most common cardiovascular disorders in the United States. VTE is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE) resulting from thrombus formation in the venous circulation (Fig. 7-1).1 It is often provoked by prolonged immobility and vascular injury and is most frequently seen in patients who have been hospitalized for a serious medical illness, trauma, or major surgery. VTE can also occur with little or no provocation in patients who have an underlying hypercoagulable disorder. 

DVT, deep vein thrombosis HIT, heparin-induced thrombocytopenia PAI-I, plasminogen activator inhibitor PE, pulmonary embolism SERM, selective estrogen receptor modulator VTE, venous thromboembolism. 

The WHI demonstrated an increased risk in venous thromboembolic disease in the HRT group (0.34%) compared with placebo (0.16%) (HR 2.11,95% Cl 1.58-2.82). This translates into an NNTH of approximately 555 and 18 more cases of venous thromboembolic events for every 10,000 women treated per year with HRT.3 The risk for deep vein thrombosis also was increased in the ERT arm of the WHI, but pulmonary embolism was not increased significantly.21... 

Venous thromboembolism (VTE) results from clot formation in the venous circulation and is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE). A DVT is a thrombus composed of cellular material (red and white blood cells, platelets) bound together with fibrin strands. A PE is a thrombus that arises from the systemic circulation and lodges in the pulmonary artery or one of its branches, causing complete or partial obstruction of pulmonary blood flow. 

Tamoxifen users present also a doubling incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) (118 vs. 62 cases). This increase is similar to that seen with HRT. There are some aspects of this side effect that should be commented on to improve the management of women eligible for tamoxifen treatment and at risk for DVT (Goldhaber 2005). In the subanalysis of the Italian study (Decensi et al. 2005), the venous thromboembolism definition included DVT, PE, and superficial phlebitis. Most of the VTE that the authors reported were, in fact, cases of superficial phlebitis, whereas the admitted definition of venous thromboembolism excludes this entity. Such conceptual differences, together with differences in age and background characteristics between the four studies, can explain the diversity in the incidences observed. 

There is other evidence that transdermal estrogen replacement therapy has relatively little effect on hemostasis. In a case control study, 155 consecutive patients with a first documented episode of idiopathic venous thromboembolism, 92 of whom had had a pulmonary embolism and 63 a deep venous thrombosis, were compared with 381 healthy matched controls (88). Overall, 32 (21%) of the cases and 27 (7%) of the controls were current users of oral estrogen replacement therapy, whereas 30 (19%) cases and 93 (24%) controls were current users of transdermal estrogen replacement therapy. After adjustment for potential confounding variables, the odds ratios for venous thromboembolism in current users of oral and transdermal estrogen replacement therapy compared with non-users were 3.5 (95% Cl = 1.8, 6.8) and 0.9 (0.5, 1.6) respectively. Estimated risk for venous thromboembolism in current users of oral estrogen replacement therapy compared with transdermal users was 4.0 (1.9, 8.3). 

Thrombotic (blood clot) events, and subsequent complications, are a leading cause of morbidity and mortality in the general population.1 In 2005, it was estimated that there were more than 900,000 total venous thromboembolism events in the United States,2 two thirds of which were acquired in hospital. More than 600,000 of those were nonfatal venous thromboembolism events. Nearly 300,000 were fatal events, including more than 2,200 cases of deep venous thrombosis and 294,000 cases of pulmonary embolism. The majority deaths (93%) were due to sudden fatal pulmonary embolism, or were a consequence of undiagnosed venous thromboembolism. It was estimated that 340,000 patients developed complications from venous thromboembolism, including 336,000 with postthrombotic syndrome and 3,300 with chronic thromboembolic pulmonary hypertension. 

The risks and benefits of HRT should be carefully assessed on an individual basis. This is particularly important in women with predisposing risk factors, such as a personal or family history of deep vein thrombosis or pulmonary embolism, severe varicose veins, obesity or prolonged bed-rest [2], because HRT increases the risk of venous thromboembolism and stroke. HRT has also been observed to increase the risk of gallbladder disease, breast cancer and endometrial cancer. It is recommended that the minimum effective dose should be used for the shortest period of time, with treatment being reviewed at least once a year [2]. 

The convenience (and cost-effectiveness) of LMW heparin therapy has resulted in widespread changes in practice. Patients with acute venous thromboembolism can be treated safely and effectively with LMW heparin as outpatients. Large-scale studies have demonstrated that outpatient treatment of acute deep vein thrombosis (DVT) with unmonitored body-weight adjusted LMW heparin is as safe and effective as inpatient treatment with adjusted dose intravenous standard heparin. Further trials have confirmed the safety and efficacy of LMW heparin therapy in acute pulmonary embolism and that 80% of imselected patients with acute thromboembolism can be safely treated as outpatients. ... 

A third variety, so-called delayed-onset heparin-induced thrombocytopenia has also been described in several reports. In 12 patients, recruited from secondary and tertiary care hospitals, thrombocytopenia and associated thrombosis occurred at a mean of 9.2 (range 5-19) days after the withdrawal of heparin nine received additional heparin, with further falls in platelet counts (32). In a retrospective case series, 14 patients, seen over a 3-year period, developed thromboembolic complications a median of 14 days after treatment with heparin (33). The emboli were venous (n — 10), or arterial (n — 2), or both (n — 2) of the 12 patients with venous embolism, 7 had pulmonary embolism. Platelet counts were mildly reduced in all but two patients at the time of the second presentation. On readmission, 11 patients received therapeutic heparin, which worsened their clinical condition and further reduced the platelet count. 

Thromboembolic events secondary to HIT produce the same signs and symptoms as those of other etiologies (see "Presentation of Deep Venous Thrombosis and Pulmonary Embolism"). 

Venous thromboembolism, including thrombosis of the deep veins of the legs and embolism to the pulmonary arteries, is uncommon in the general population. The absolute risk of venous thromboembolism in non-hormone therapy users is approximately 1 in 10,000 women. Women taking hormone therapy have a twofold increase in risk for thromboembolic events, with the highest risk occurring in the first... 

Venous thromboembolism (VTE) is a complicating condition responsible for high morbidity and mortality in North America and Europe. This disease commonly is linked to advanced age but has both hereditary and acquired risk factors, such as surgery, any form of trauma, and childbirth, associated with it. It encompasses the conditions of deep vein thrombosis (DVT) and pulmonary embolism. In excess of 60,000 deaths annually are attributed to pulmonary embolism. Preventative therapy consists of the use of two different classes of antithrombotic agents, namely anticoagulants and antiplatelet drugs (1,2). 

As is the case with most invasive procedures, deep venous thrombosis and pulmonary embolus represent rare but potential complications of the uterine artery embolization procedure [53]. Patients taking oral contraception are known to be at increased risk for venous thromboembolic disease and there may be a transient hypercoagulability after embolization [92-94],... 

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