Venous thromboembolic events (VTEs) represent a serious complication related to hormonal contraception and hormone replacement therapy (HRT). Evidence on hormonal contraceptive- and HRT-related VTEs is derived almost exclusively from observational studies and points to a 2- to 6-fold increased relative risk of VTEs with either therapy. Oral contraceptive pills that contain third-generation progestins (desogestrel or gestodene) seem to be associated with greater VTE risk than those that contain levonorgestrel. Oral contraceptive pill use and HRT are associated with exponentially higher VTE relative risks when used by women who carry an inherited hypercoagulable state. The indication of a lower or a lack of VTE risk associated with the use of progestin-only contraceptives and with transdermal HRT suggests that these therapies may be safer than combination oral contraceptive pills and oral HRT for women in whom oral estrogen therapy is considered contraindicated. Data that support such safety advantages are limited and should be interpreted with caution.

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BACKGROUNDTamoxifen therapy for patients with breast carcinoma is perceived as an independent risk factor for venous thromboembolic events (VTE), but the risk associated with other adjuvant therapies is less well recognized.METHODSThe authors conducted a computerized PubMed literature search for English‐language articles published between January 1966 and December 2003. Studies were analyzed with regard to trial design, breast carcinoma staging, adjuvant agent, definition of VTE outcomes, method of VTE case ascertainment, and the presence of concomitant VTE risk factors.RESULTSAccurate determination of VTE rates was impaired by the universal lack of routine assessments for asymptomatic VTE. Therefore, only the risk of symptomatic VTE could be derived. The risk of VTE was increased twofold to threefold during tamoxifen or raloxifene use for breast carcinoma chemoprevention. It remains unknown whether the risk is increased further in women with inherited hypercoagulable states. In the setting of early‐stage breast carcinoma, the risk of VTE is increased both with tamoxifen use and anastrozole use. Such risk appeared to be lower, albeit not negligible, with anastrozole. Significant methodologic limitations of all available studies in women with advanced‐stage breast carcinoma precluded determination of the true VTE risk associated with different adjuvant hormonal agents and made it nearly impossible to compare the risk between different drugs.CONCLUSIONSAll agents used for breast carcinoma chemoprevention and adjuvant therapy appear to increase the risk of VTE. Available data were insufficient to support any assumptions that newer hormonal forms of hormone manipulation are safer than tamoxifen in women with advanced breast carcinoma. Cancer 2004. © 2004 American Cancer Society.

Summary. Background: Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated response to unfractionated heparin and, less commonly, low molecular weight heparin. It is associated with a high thrombotic risk and the potential for limb and lifethreatening complications. Argatroban is the only approved and currently available anticoagulant for HIT treatment in the USA. Objectives: To report safety and efficacy outcomes with bivalirudin for HIT treatment. Methods: We retrospectively examined records from our registry of patients with a suspected, confirmed or previous history of HIT and who had received bivalirudin for anticoagulation in a single tertiary-care center over a 9-year period. Results: We identified 461 patients who received bivalirudin: 220 (47.7%) were surgical patients, and 241 (52.3%) were medical patients. Of this population, 107 (23.2%) were critically ill, and 109 (23.6%) were dialysis-dependent. Suspected, confirmed and previous history of HIT were reported in 262, 124 and 75 patients, respectively. Of 386 patients with suspected or confirmed HIT, 223 patients (57.8%) had thrombosis at HIT diagnosis. New thrombosis was identified in 21 patients (4.6%) while they were on treatment with therapeutic doses of bivalirudin. No patient required HIT-related amputation. Major bleeding occurred in 35 patients (7.6%). We found a significant increase in major bleeding risk in the critically ill population (13.1%; odds ratio 2.4, 95% confidence interval 1.2-4.9, P = 0.014). The 30-day allcause mortality rate was 14.5% (67 patients), and eight of 67 (1.7%) deaths were HIT-related. Conclusion: Bivalirudin may be an effective and safe alternative option for the treatment of both suspected and confirmed HIT, and appears to reduce the rate of HITrelated amputation.

We conducted a retrospective review to assess outcomes of therapy in patients with newly diagnosed Wegener granulomatosis (WG) using methotrexate (MTX) for mild to moderate disease and short-term treatment with cyclophosphamide (CYC) followed by MTX for severe disease. Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (immediately life-threatening or involving critical organs) was initially treated with CYC and glucocorticoids. Mild to moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2 mg/dL. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2 mg/dL or had diminished to less than 2 mg/dL. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, as modified for Wegener granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less than monthly.Eighty-two (32%) of 253 patients with WG referred to the Center for Vasculitis Care and Research met eligibility criteria. Ineligible patients did not have new-onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of CYC for remission induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage; rapidly progressive glomerulonephritis, including need for dialysis; or neurologic abnormalities. All patients improved: remission was achieved in 50% (41/82) of patients within 6 months and in 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0 for at least 6 consecutive months) was ultimately achieved in 78% (64/82) of patients. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years following remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-quarters of relapses were mild and promptly responded to treatment. Seventeen percent of patients developed serious infections. CYC-associated cystitis or bladder cancer did not occur in any patients. At least 1 form of permanent morbidity from WG alone was noted in 74.0% of patients. Three patients (3.7%) died over a median follow-up period of 4.5 years; no deaths were due to active disease. Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts of 1000/mm was associated with a hazard ratio for relapse of 3.0, although the latter diffe...