Antithrombotic prophylaxis

Prevention of DVT and PE (antithrombotic prophylaxis) is another common indication for UFH, LMWH or coumarin, especially following surgery or immobilizing trauma. Fondaparinux is approved for prevention of DVT and PE after hip and knee surgery, and following abdominal surgery. 

In preparation for chest discomfort during alcohol injection, prophylactic analgesic medication (eg. fentanyl 25 mm IV) is administered. Antithrombotic prophylaxis with intravenous, weight-adjusted heparin is given to maintain an activated clotting time of 200 to 250 seconds. 

What are the two options in terms of antithrombotic prophylaxis in this patient and what are the potential side-effects of each State which of these is the most appropriate for this patient and why. 

As nearly aU of the risks seem to be dose-related (SEDA-21, 96), there is a good prospect that an even lower daily dose of aspirin may offer advantages in antithrombotic prophylaxis without an increased risk of bleeding, but the results of further such studies are stiU awaited (9). 

The efficacy of antithrombotic prophylaxis with cilostazol for the secondary prevention of cerebral infarction has been studied in a Japanese, placebo-controlled trial in 1095 patients (6). There was a 42% relative risk reduction compared with placebo. As in the trials in patients with peripheral arterial disease, mild to moderate headache and palpitation were the most commonly observed symptomatic adverse events attributed to cilostazol they respectively occurred in 13 and 5.3%. Headache with cilostazol is attributed to cerebral vasodilatation induced by relaxation of vascular smooth muscle. 

Vos SC, Hage JJ, Woerdeman LA, Noordanus RP. Acute renal failure during dextran-40 antithrombotic prophylaxis report of two microsurgical cases. Ann Piast Surg 2002 48(2) 193-6. 

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]. 

The ACCP Conference on Antithrombotic Therapy recommended against the use of aspirin as the primary method of VTE prophylaxis.2 Antiplatelet drugs clearly reduce the risk of coronary artery and cerebrovascular events in patients with arterial disease, but aspirin produces a very modest reduction in VTE following orthopedic surgeries of the lower extremities. The relative contribution of venous stasis in the pathogenesis of venous thrombosis compared with that of platelets in arterial thrombosis likely explains the reason for this difference. 

Prophylaxis should be continued throughout the period of risk. For general surgical procedures and medical conditions, prophylaxis can be discontinued once the patient is able to ambulate regularly and other risk factors are no longer present. Most clinical trials support the use of antithrombotic therapy for 21 to 35 days after total hip replacement and hip fracture repair surgeries. 

From the therapeutic point of view, prophylaxis of thrombosis must be continued after withdrawal of heparin, since even when there is no evidence of thrombosis in association with heparin-induced thrombocytopenia, thrombosis can follow after some days (52). Because of cross-reactivity, low molecular weight heparin should not be used when heparin has been withdrawn because of heparin-induced thrombocytopenia nor should warfarin be used, because of the risk of venous gangrene, at least until the thrombocytopenia has resolved. Patients with life-threatening or limb-threatening thrombosis can be treated with thrombolytic drugs. Current views are that two antithrombotic drugs should be used, for example danaparoid plus lepirudin (58). 

The primary adverse effect associated with fondaparinux therapy is bleeding." " The rate of major bleeding in the VTE prophylaxis trials was approximately 2% to 3%. The risk of major bleeding appears to be related to weight therefore, in patients who weigh less than 50 kg, fondaparinux is contraindicated for VTE prophylaxis, and the treatment dose is only 5 mg every 24 hours. Similar to UFH and the LMWHs, fondaparinux should be used with extreme caution in patients with neuraxial anesthesia or following a spinal puncture owing to the risk for spinal or epidural hematoma formation. Unlike UFH and the LMWHs, fondaparinux does not cause heparin-induced thrombocytopenia and does not produce cross-sensitivity in vitro." A specific antidote to reverse the antithrombotic activity of fondaparinux is not currently available, but several potential products have been evaluated. 

LMW heparin, enoxaparin, for preventing VTE after major orthopedic surgery (30). The results from a meta-analysis show thiat fondaparinux (10) is associated with an overall risk reduction versus enoxaparin for the prevention of venous thromboembolism. Of aiU the LMW heparins, enoxaparin is widely regarded as the treatment standard for VTE prophylaxis. Fondaparinux (10) is an injectable solution for the prevention of DVT and is the only antithrombotic agent approved in the United States for hip fracture surgery. 

Anti thrombin III, an anticoagulant and antithrombotic agent (50 to 100 lU/min IV), is indicated for prophylaxis and adjunct treatment of thromboembolism associated with hereditary antithrombin III deficiency (see also Tables 17 and 18). 

Sulfinpyrazone is a structural derivative of the anti-inflammatory drug phenylbutazone. Unlike phenylbutazone, however, sulfinpyrazone does not have significant anti-inflammatory activity. It does have potent uricosuric effects and frequently is used in the treatment of gout. At least four metabolites of sulfinpyrazone have been identified, including the sulfide, sulfone, p-hydroxysulfide, and p-hydroxysulfinpyrazone derivatives (Fig. 31.16) (24). Only the parent sulfinpyrazone and its reduced sulfide metabolite, however, are active as COX inhibitors (98). Because these compounds are reversible inhibitors, the antithrombotic activity lasts only as long as blood levels of the drug and metabolite persist (half-life, 4-6 hours for parent sulfinpyrazone, 11-14 hours for the sulfide metabolite). Sulfinpyrazone is not yet approved in the United States for use in acute myocardial infarction or for transient ischemic attack prophylaxis. 

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