Venous thromboembolism, treatment

Fondaparinux, the factor Xa-binding pentasaccharide (Arixtra, MW 1,728 Da), is prepared synthetically, unlike UFH, LMWH and danaparoid, which are obtained from animal sources. Despite only inactivating free factor Xa, clinical trials indicate that fondaparinux is an effective antithrombotic agent, both for venous thromboembolism prophylaxis and treatment, as well as for acute coronary syndrome and ST elevation myocardial infarction [4]. 

FIGURE 7-5. Treatment approach for patients with VTE. INR, International Normalized Ratio IV, intravenous LMWH, low-molecular-weight heparin PO, oral SC, subcutaneous UFH, unfractionated heparin VTE, venous thromboembolism. (Adapted from Nutescu EA. Emerging options in the treatment of venous thromboembolism. Am J Health Syst Pharm 2004 61 (Suppl 7) S16, with permission.)... 

Low-molecular-weight heparins and heparinoids are not recommended in the treatment of acute ischemic stroke.11 A meta-analysis was performed using data from 10 randomized controlled trials.19 A non-significant decrease in combined death and disability and a non-significant increase in case fatality and hemorrhage were seen. A reduction in venous thromboembolic events was observed in acute stroke patients however, there was also an increase in extracranial bleeding. 

CHD is the leading cause of death among women in the United States. Retrospective data indicated that HRT was associated with a decrease in risk of CHD by 30% to 50%.21 However, the results of recent RCTs demonstrate that HRT does not prevent or treat CHD in women and that it actually may cause an increase in CHD events. The HERS, published in 1998, was the first RCT conducted in women with established CHD. This trial demonstrated an increased incidence of CHD events within the first year of treatment with HRT and an increased risk of venous thromboembolism (VTE) and gallbladder disease. There was a trend of decreasing incidence... 

In summary, combined estrogen plus progestin should not be used for the prevention of chronic diseases because it increases the risk of CHD, stroke, breast cancer, and venous thromboembolism. However, colorectal cancer and rates of fracture were reduced with combined hormonal treatment. 

Pineo, G. and Hull, R. 1997. Low molecular weight heparin-prophylaxis and treatment of venous thromboembolism. Annual Review of Medicine 48, 79-91. 

Patients with acute stroke should be monitored intensely for the development of neurologic worsening, complications, and adverse effects from treatments. The most common reasons for clinical deterioration in stroke patients are (1) extension of the original lesion in the brain (2) development of cerebral edema and raised intracranial pressure (3) hypertensive emergency (4) infection (e.g., urinary and respiratory tract) (5) venous thromboembolism (6) electrolyte abnormalities and rhythm disturbances and (7) recurrent stroke. The approach to monitoring stroke patients is summarized in Table 13-3. 

FIGURE 14-2. Treatment of venous thromboembolism (VTE). (LMWH, low-molecular-weight heparin PE, pulmonary embolism SBP, systolic blood pressure UFH, unfractionated heparin.)... 

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. 

Shand et al. (2002) have shown that, compared with placebo-treated subjects, long-term raloxifene treatment in postmenopausal women, at a dose of either 60 or 120 mg/d, was not associated with adverse changes in hemorheological factors (determinants of blood viscosity) that may contribute to venous thromboembolism. 

Cancer is a complicated process consisting of well-coordinated multiple steps. Randomized trials to study the effectiveness of LMW heparins as compared with unfractionated heparin in treating venous thromboembolism in cancer patients led to a surprising observation that treatment with heparin... 

Treatment of postmenopausal women with osteoporosis with raloxifene (60mg/day or 120mg/day for 36 months) was found to significantly increase bone mineral density in the spine and femoral neck and decrease the risk of vertebral fracture compared to the placebo treatment.Treatment with raloxifene increased the risk of venous thromboembolism compared to the placebo group and was also associated with a lower risk of breast cancer and did not cause breast pain or vaginal bleeding. 

Cyproterone acetate in combination with ethinylestra-diol is indicated for the treatment of women with severe acne and moderately severe hirsutism. This product has been associated with a greater risk of venous thromboembolism than oral contraceptives. However, in a rigorous case-control study the risk of venous thromboembolism with cyproterone acetate + ethinylestradiol was not significantly greater than the risk in women who took conventional oral contraceptives (25). 

Table 1 Incidences of venous thromboembolism with and without breast cancer taking various treatments (37) ...

Eichinger S. Treatment of venous thromboembolism. Wien Med Wochenschr. 2005 15 7-10. 

Matsagas MI. Outpatient treatment of venous thromboembolism using low molecular weight heparins. An overview. IntAngiol. 2004 23 305-316. 

McRae SJ, Ginsberg JS. Initial treatment of venous thromboembolism. Circulation. 2004 110(suppl 1) 13-19. 

Nutescu EA. Emerging options in the treatment of venous thromboembolism. Am J Health Syst Pharm. 2004 61(suppl 7) S12—S17. 

Pineo GF, Hull RD. Low-molecular-weight heparin for the treatment of venous thromboembolism in the elderly. Clin Appl Thromb Hemost. 2005 11 ... 

Agnelli G, Clinical potential of oral direct thrombin inhibitors in the prevention and treatment of venous thromboembolism. Drugs 2004 64(suppl I ) 47—52. 

Schulman S. The role of ximelagatran in the treatment of venous thromboembolism. Pathophysiol Haemost Thromb 2005 34(suppl I) 18-24. 

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