Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Jan 2000
ReviewVitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements.
Epidemiological studies have shown that higher blood homocysteine levels appear to be associated with higher risks of coronary, cerebral, and peripheral vascular disease and are inversely related to blood levels of folate and of vitamin B12 and vitamin B6. However, observational studies cannot exclude the possibility that elevated homocysteine levels may be associated with some other factor, rather than being causally related to vascular disease. Large-scale clinical trials of sufficient dose and duration of treatment are required to test this hypothesis, but there was substantial uncertainty about the optimal vitamin regimen to test in such trials. ⋯ Vitamin B12 (mean 0.5 mg) produced an additional reduction in blood homocysteine of 7%, whereas vitamin B6 (mean 16.5 mg) did not have any significant effect. Hence, in typical populations, daily supplementation with both 0.5 to 5 mg folic acid and about 0.5 mg vitamin B12 would be expected to reduce homocysteine levels by one quarter to one third (from about 12 micromol/L to about 8 to 9 micromol/L). Large-scale randomized trials of such regimens are now required to determine whether lowering homocysteine levels by folic acid and vitamin B12, with or without added vitamin B6, reduces the risk of vascular disease.
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Hyperhomocysteinemia refers to an elevated circulating level of the sulfur-containing amino acid homocysteine and has been shown to be a risk factor for vascular disease in the general population. In patients with renal failure, hyperhomocysteinemia is a common feature. The underlying pathophysiological mechanism for this phenomenon is unknown. ⋯ The effects of vitamin B12 or vitamin B6 are unclear. Large intervention trials are now needed to establish whether homocysteine-lowering therapy will reduce atherothrombotic events in patients with renal failure. These studies are now planned or are ongoing.
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Semin. Thromb. Hemost. · Jan 2000
ReviewStrategies for the safe and effective exclusion and diagnosis of deep vein thrombosis by the sequential use of clinical score, D-dimer testing, and compression ultrasonography.
Patients with suspected deep vein thrombosis (DVT) are subjected to leg vein compression ultrasonography (CUS) that confirms DVT in only 20 to 30% of patients. A positive CUS is consistent with DVT irrespective of clinical score. The sequential use of a simple clinical score assessment, a rapid sensitive enzyme-linked immunosorbent assay (ELISA) D-dimer test and CUS to safely exclude DVT is promising. ⋯ A negative CUS, a low clinical score, and a positive ELISA D-dimer, even less than 1000 ng/mL exclude DVT with a nega tive predictive value of more than 99%. Patients with a negative CUS, but a positive ELISA D-dimer, and a moderate or high clinical score have a probability of DVT of 3 to 5% and 20 to 30%, respectively, and are thus candidates for repeated CUS testing. The proposed sequential use of the clinical score assessment, a rapid ELISA D-dimer test, and CUS will be the most cost-effective diagnostic strategy for DVT because of a significant reduction of CUS examinations and gain of time for the patient and physician in charge.
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Semin. Thromb. Hemost. · Jan 2000
ReviewInhibitor antibodies to factor VIII and factor IX: management.
Inhibitor antibodies directed against factor VIII or factor IX present challenges to the clinician. Fortunately, several management options are available, although each has disadvantages as well as advantages. Alloantibodies against factor VIII (which develop in 25 to 50% of children with severe hemophilia A, as well as in a small percentage of children with mild or moderate hemophilia A) may be low titer and transient or may be high titer. ⋯ Corticosteroids and cyclophosphamide are generally recommended. For treatment of bleeding, therapeutic options include (human) factor VIII concentrates, porcine factor VIII, APCC, and rFVIIa. The choice of product is generally determined by the consulting hematologist's familiarity with the product, product availability and cost, as well as response to treatment.
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Semin. Thromb. Hemost. · Jan 2000
Comparative StudyComparative efficacy of different low-molecular-weight heparins (LMWHs) and drug interactions with LMWH: implications for management of vascular disorders.
The low-molecular-weight heparins (LMWHs) are more efficacious and safer than unfractionated heparin (UFH) in the prevention and treatment of venous thrombosis and to a certain extent in the treatment of acute ischemic syndromes. Because of their predictable pharmacokinetics and bioavailability after subcutaneous administration, LMWHs can be more convenient for outpatient use than UFH. Differences in the manufacturing process of LMWHs result in significant structural and molecular weight differences; thus, LMWHs have individual biochemical and pharmacological profiles and are not interchangeable on the basis of either mass or anti-Xa activity. ⋯ Abciximab and roxifiban further inhibited clot strength by affecting the transmission of platelet contractile force to fibrin by platelet GPIIb/IIIa receptors. Subtherapeutic doses of tinzaparin combined with abciximab or roxifiban resulted in a distinct synergy that improved anticoagulant and antiplatelet efficacy mediated by TF, fXa, or thrombin. As these data suggest, the combination of low-dose tinzaparin with low-dose GPIIb/IIIa antagonists (abciximab, roxifiban) may be efficacious in the prevention and treatment of various thromboembolic disorders.