الفهرس 
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Abstract
Warfarin, also known by the brand names Coumadin among others, is an anticoagulant normally used in the prevention of thrombosis and thrombo-embolism, the formation of blood clots in the blood vessels and their migration elsewhere in the body, respectively. It was initially introduced in 1948 as a pesticide against rats and mice, and is still used for this purpose, although more potent poisons such as brodifacoum have since been developed. In the early 1950s, warfarin was found to be effective and relatively safe for preventing thrombosis and thrombo-embolism in many disorders. It was approved for use as a medication in 1954, and has remained popular ever since. Warfarin is the most widely prescribed oral anticoagulant drug in North America.1
Despite its effectiveness, treatment with warfarin has several shortcomings. Many commonly used medications interact with warfarin, as do some foods (particularly leaf vegetable foods or ”greens,” since these typically contain large amounts of vitamin K1) and its activity has to be monitored by blood testing for the international normalized ratio (INR) to ensure an adequate yet safe dose is taken. A high INR predisposes patients to an increased risk of bleeding, while an INR below the therapeutic target indicates the dose of warfarin is insufficient to protect against thrombo-embolic events.
Warfarin and related 44-hydroxycoumarin-containing molecules decrease blood coagulation by inhibiting vitamin-K epi-oxide -reductase, an enzyme that recycles oxidized vitamin K1 to its reduced form after it has participated in the carboxylation of several blood coagulation proteins, mainly prothrombin and factor VII. Despite being labeled a vitamin K antagonist, warfarin does not antagonize the action of vitamin K1, but rather antagonizes vitamin K1recycling, depleting active vitamin K1. Thus, the pharmacologic action may always be reversed by fresh vitamin K1. When administered, these drugs do not anti-coagulate blood immediately. Instead, onset of their effect requires about two to three days before remaining active clotting factors have had time to naturally disappear in metabolism, and the duration of action of a single dose of warfarin is 2 to 5 days. Reversal of warfarin’s effect by discontinuing its use, or by administering vitamin K1, requires a similar period of time1.
Warfarin is a synthetic derivative of dicoumarol, a 4-hydroxycoumarin-derived myco-toxin anticoagulant originally discovered in spoiled sweet clover-based animal feeds. Dicoumarol, in turn, is derived from coumarin, a sweet-smelling but coagulation-inactive chemical found naturally in ”sweet” clover (to which it gives its odor and name), tonka beans (also known as ”cumaru” from which coumarin’s name derives), and many other plants. The name ’warfarin’ stems from its discovery at the University of Wisconsin, incorporating the acronym for the organization that funded the key research, ”WARF” for the Wisconsin Alumni Research Foundation and the ending ”-arin”, indicating its link with coumarin2.
Warfarin is used to decrease the tendency for thrombosis or as secondary prophylaxis (prevention of further episodes) in those individuals who have already formed a blood clot (thrombus). Warfarin treatment can help prevent formation of future blood clots and help reduce the risk of embolism (migration of a thrombus to a spot where it blocks blood supply to a vital organ2.
Warfarin is best suited for anticoagulation (clot formation inhibition) in areas of slowly running blood (such as in veins and the pooled blood behind artificial and natural valves) and in blood pooled in dysfunctional cardiac atria. Thus, common clinical indications for warfarin use are atrial fibrillation, the presence of artificial heart valves, deep venous thrombosis, and pulmonary embolism (where the embolized clots first form in veins). Warfarin is also used in antiphospholipid syndrome. It has been used occasionally after heart attacks (myocardial infarctions), but is far less effective at preventing new thrombosis in coronary arteries. Prevention of clotting in arteries is usually undertaken with antiplatelet drugs, which act by a different mechanism from warfarin (which normally has no effect on platelet function)2
In the past years, therapies for children and young adults with heart disease have improved dramatically. These improvements have led to a growing number of women of childbearing age with valvular heart disease as more patients survive to adulthood.1 The first successful term pregnancy in a woman with a prosthetic heart valve was reported in 1966.1 However, the therapeutic management of this population remains challenging; in particular, no clear consensus exists on the optimal prosthetic heart valve (when repair is not feasible) or the most suitable anticoagulation strategy for patients who become pregnant. The association between mechanical valve prosthesis and adverse pregnancy outcomes has been recognized and incorporated into a risk score for adverse cardiac complications. The presence of a mechanical heart valve confers a high risk of adverse outcomes and necessitates close monitoring by cardiac and obstetric care teams during pregnancy. Oral anticoagulation therapy (with warfarin or other vitamin K antagonists) is the most effective strategy for preventing thromboembolic complications in pregnant women. However, the use of oral anticoagulants during pregnancy is associated with increased fetal morbidity and mortality. The risk of embryopathy can be reduced by changing to unfractionated or low-molecular-weight heparin, either specifically during fetal organogenesis or for longer periods during pregnancy. However, the risk of potentially life-threatening maternal thromboembolic complications is increased with heparin compared with oral anticoagulants. No data on the efficacy of novel anticoagulants (such as dabigatran and rivaroxaban) in patients with mechanical prosthetic heart valves are available, and the safety of these drugs in pregnancy has not been studied3,4.
Physicians should consider the hemodynamic, hemostatic, and metabolic alterations that are characteristic of pregnancy when choosing anticoagulant strategies for pregnant women with prosthetic heart valves. During pregnancy, the concentrations of several coagulation factors, including fibrinogen, increase, whereas stasis, vitamin-K-dependent activity, protein S activity, and fibrinolysis decrease, resulting in a hypercoagulable state and an increased risk of thromboembolism. Drug pharmacokinetics can also be affected by pregnancy-related physiological changes, such as increases in glomerular filtration rate (in the second semester) and plasma volume (which can affect volume of distribution of drugs). These physiological changes have implications for the absorption, bioavailability, and clearance of anticoagulant medications3.
Therapeutic decision-making for individual patients should be evidence-based, and physicians should consider the risks and benefits of the various anticoagulation treatments. In this Review, we discuss the controversies surrounding the choice of prosthetic heart valve in women of childbearing age and the advantages and disadvantages of various anticoagulation strategies during pregnancy. We suggest a framework for multidisciplinary decision-making that draws on the best available evidence and takes into account the need to consider the preferences of individual patients4.
as such the main aim of this study is to collect all possible information and studies practically done on Warfarin as an Anticoagulant usage during pregnancy in post operative valvular prosthesis or pre-operative regardless to the pathology of the initial disease. We may not bring in our intension or a decision over the chemical formula, we may not also show the usage of coumarine as a non-medical substance taking its route to be an accumulated chemical product to women blood during pregnancy in passive (as in food and drinks). Teratogenicity and thromboembolism due to warfarine usage as an anticoagulant to be considered the main argument of our research