CASE RECORDS of the Massachusetts General Hospital: case 43181.
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Protein C and protein S deficiencies increase the risk of venous thrombosis and pulmonary embolism, but their role in arterial thrombosis or embolism is controversial. We describe cerebral ischemia in two young women in a family with inherited deficiencies of both proteins C and S and provide evidence that a combined deficiency of proteins C and S may be a high risk factor for ischemic stroke in young adults.
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Anticoagulation is an essential component of the care of patients with venous thromboembolism (VTE). Traditional anticoagulants for the treatment of VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the oral vitamin K antagonist, warfarin. A variety of anticoagulant agents with improved pharmacologic and clinical profiles are emerging and offer benefits over the traditional therapies. One of the most recent advances has been the development of new agents, such as oral direct thrombin inhibitors and factor Xa inhibitors, that have a more selective and targeted effect on the coagulation cascade. Recent clinical trials have evaluated fondaparinux, the first commercially available factor Xa inhibitor, in the treatment of patients with deep vein thrombosis and pulmonary embolism and indicate efficacy and safety as compared with traditional options such as UFH and LMWH. Fondaparinux is a welcomed addition to the available antithrombotic options.
Aspirin and the nonsteroidal anti-inflammatory drugs (NSAIDs) have been commercially available for decades, and their ability to reduce pain and inflammation are well known. The ability of these agents to cause adverse effects are also known, and the search for newer NSAIDs with less side effects accelerated after the two isoforms of cyclooxygenase (COX) (COX-1 and COX-2) were discovered. The selective COX-2 inhibitors seem to have equivalent efficacy, but potentially less gastrointestinal adverse effects than the traditional NSAIDs. Recent concern that the selective COX-2 inhibitors could increase cardiovascular events requires more investigation. In the meantime, aspirin continues to receive attention as a potential primary cardiovascular agent because of its antiplatelet effects and past and current clinical trials. Several trials have demonstrated that low-dose aspirin may significantly reduce the risk of myocardial infarction and other cardiovascular events. However, the benefits of aspirin need to be weighed against its primary side effect in these situations (hemorrhagic stroke). Patients at low risk for future cardiovascular events are probably not good candidates for this therapy; however, those individuals with a high risk of a future cardiovascular event may qualify for this therapy. Aspirin has also demonstrated a potential ability to reduce the risk of deep venous thrombosis and pulmonary embolism. A recent large trial of low-dose aspirin after major surgery revealed that this agent could also have some activity in the venous component of the human body. Aspirin may also have some applicability for reducing side effects of oral estrogens in men with advanced prostate cancer. Thus, it seems as if aspirin, NSAIDS, and even the selective COX-2 inhibitors may have therapeutic potential far beyond reducing pain and general inflammation. These overall observations and effects provided some of the impetus to investigate their potential ability to reduce the risk and possibly progression of a number of cancers. A few already available over-the-counter products and prescriptions seem to be receiving attention as possible anticancer agents.
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