Anticoagulation therapy

Valve Problems. The primary solution to valve problems has been implantable replacement valves. The introduction of these devices necessitates open-heart surgery. There are two types of valves available tissue (porcine and bovine) and mechanical. The disadvantage of tissue valves is that these have a limited life of about seven years before they calcify, stiffen, and have to be replaced. The mechanical valves can last a lifetime, but require anticoagulant therapy. In some patients, anticoagulants may not be feasible or may be contraindicated. Of the valves which require replacement, 99% are mitral and aortic valves. The valves on the left side of the heart are under much greater pressure because the left ventricle is pumping blood out to the entire body, instead of only to the lungs. Occasionally, two valves are replaced in the same procedure. 

Dicoumarol [66-76-2] (5) was isolated from spoiled sweet clover hay. It is prepared synthetically by reaction of 4-hydroxycoumarin with formaldehyde (85). It is used in anticoagulant therapy often associated with heparin. 

Warfarin [81-81-2] (6) is prepared by the Michael condensation of benzyHdene acetone with 4-hydroxycoumarin (86). It is used as a rodenticide (see Poisons, commercial) and in anticoagulant therapy. 

One drawback of thrombolytic therapy is a high incidence of reocclusion. In a report using a canine model, inclusion of heparin [9005-49-6] (anticoagulant therapy) in the treatment prevented this side effect (158). The combination of aspirin [50-78-2] (antiplatelet therapy) and streptokinase (thrombolytic therapy) has also shown significant therapeutic advantages (78). Although additional work is needed to estabUsh the thrombolytic advantage of various combinations, preliminary results in this area indicate promise in terms of increased efficacy and reduced side effects. 

Anticoagulant therapy was developed with the adventitious discovery of dicoumarol (8). A fuller discussion of the rationale for the use of such compounds is found in the chapter on Five-Mem-bered Heterocycles Fused to One Benzene Ring. The reader s attention is directed, however, at the fact that dicoumarol is a polycarbonyl compound containing a very acidic hydrogen. A series of similarly acidic 1,3-indandiones have been found to constitute an additional class of anticoagulant agents. 

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

Advise your dentist or primary health care provider of anticoagulant therapy before any procedure or surgery. 

Avoid IM injections while receiving anticoagulant therapy. 

While early CEA is considered to be relatively safe, it may not always be necessary. For instance, early surgery can be deferred in patients who are medically unstable or for those whose cardiac or respiratory status requires optimization. In the NASCET study, the rate of ipsUateral stroke at 1 month for medically treated patients with high-grade stenoses was only 3.3% and was even lower (1.7%) in patients with near-occlusions. Even in patients with free-floating intraluminal thrombus, anticoagulant therapy is a well tolerated and reasonable first step, given... 

Initiation of anticoagulant therapy within 24 hours of treatment with intravenously administered rt-PA is not recommended (grade A). 

TABLE 7-6. Risk Factors for Major Bleeding While Taking Anticoagulation Therapy... 

Heparin-induced thrombocytopenia (HIT) is a very serious adverse effect associated with UFH use. Platelet counts should be monitored every 2 to 3 days dining the course of UFH therapy.5 HIT should be suspected if the platelet count drops by more than 50% from baseline or to below 120,000. In patients with contraindications to anticoagulation therapy, UFH should not be administered (Table 7-7). 

Inferior vena cava (IVC) interruption is indicated in patients with PE who have a contraindication to anticoagulation therapy... 

Obtain baseline laboratory tests. These tests must be obtained prior to initiating anticoagulation therapy ... 

Screen the patient s pharmacy profile for potential drug-drug interactions with anticoagulation therapy... 

Arrange for follow-up and long-term anticoagulation therapy management. Communicate with the patient s primary care physician and/or refer to a local antithrombosis service, if available. If the patient is to be treated primarily in the hospital, these arrangements can be made 1 to 2 days prior to hospital discharge. 

Bilateral adrenal hemorrhage or infarction—usually due to anticoagulant therapy, coagulopathy, thromboembolic disease, or meningococcal infection. Causes acute adrenal insufficiency. 

No concurrent anticoagulation therapy (i.e., enoxaparin, heparin, or warfarin)... 

Evaluate the patient for adverse effects, including peripheral neuropathy and deep vein thrombosis. Prophylactic anticoagulation therapy should be considered in thalidomide or lenalidomide based therapy. 

The optimal therapeutic range for oral anticoagulant therapy as determined by prothrombin time is expressed in terms of the international normalized ratio (INR). The INR is the prothrombin time ratio (patient s prothrombin time divided by the mean of the normal prothrombin time) that would have been obtained had a World Health Organization reference thromboplastin preparation been used to determine the prothrombin time. The sensitivity of the various reagents (thromboplastins) used to determine the prothrombin time is related to the international sensitivity... 

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