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  • Title: [-Anticoagulant drugs-].
    Author: Gulba DC.
    Journal: Herz; 1996 Feb; 21(1):12-27. PubMed ID: 8647576.
    Abstract:
    In todays medicine, anticoagulant drugs like heparin and coumadin derivatives have become indispensable for the treatment of thrombo-embolic diseases. Heparin, consisting of long poly-sulfated polysaccharide chains of variable length and sequences is mostly derived from porcine mucosa. Its bioavailability by other than the parenteral way of administration is almost negligible. Therefore, with only few exceptions, it is almost exclusively applied in hospitalized patients (short-term therapy) or to bridge 2 phases of treatment with oral anticoagulant drugs. Today, besides the conventional high-molecular weight heparins, new fractionated heparins are gaining more and more attention. They offer the advantage of a more reliable resorption from the subcutaneous tissue and thus warrant reliable plasma levels. In many recent randomized trials of deep vein thrombosis and pulmonary embolism, those fractionated heparins have proven to successfully substitute for intravenously applied, aPTT-controlled unfractionated heparin. It remains however open, whether this also translates into the prevention of arterial thrombo-embolic diseases. Heparin may not pass through the placental barrier nor into the milk and is regarded non-teratogenic. Therefore, it may be regarded the ideal anticoagulant for pregnant women and lactating mothers. Those women, however, still carry the heparin-associated risk of bleeding and osteoporosis. In comparison: Coumadin derivatives interfere with the carboxylation of the clotting factors II, VII, IX, and X as well as proteins C and S. By inhibiting the synthesis of these proteins they shift the haemostatic balance to a lower level. In addition, they are almost completely bioavailable by the enteral pathway. They are, therefore, regarded the drugs of choice for long-term anticoagulant therapy in patients at particular thromboembolic risk. For their therapeutic range, being extremely narrow, meticulous drug monitoring by repeated INR-measurements as well as a reliable compliance of the patient to drug intake and dietary restrictions are mandatory to exclude phases with over- or under-anticoagulation. Above all, coumadin therapy is characterized by numerous drug interactions. Thus, whenever the basal medication is changed, for whatever reason, more intense care must be laid to drug monitoring, and the intervals for INR determinations must transiently be shortened. Coumadin derivatives do pass through the placental barrier and in minor amounts also into the milk of breast feeding mothers. Furthermore, they are highly teratogenic. If taken during pregnancy, malformations of the central nervous system are reported to occur in some 10% to 30% of the infants. Thus during pregnancy and in the lactation period, coumadin therapy should be avoided. Bleeding episodes of different severity are the most frequent adverse effects of anticoagulant therapy, no matter whether heparin or coumadin is given. There is a direct relation between the intensity of anticoagulant therapy and the frequency of bleeds. Luckily, most bleeding episodes do not create major therapeutic problems. In case of severe bleeds, however, the anticoagulant therapy must immediately be suspended. In case of coumadin therapy the immediate administration of 4 packs of PPSB (prothrombin-complex-concentrates) or FFP (fresh-frozen-plasma) with concomitant low doses of heparin is additionally advised. Allopecia diffusa, urticartia and allergic reactions are known side effects of anticoagulant therapy. Patients on long-term heparin may also suffer from severe osteoporosis. On the other hand, heparin treatment raises the hazzards of a HAT-Syndrome (heparin-associated thrombocytopenia) (estimated frequency 0.01% to 0.1% of treated patients), giving rise to severe and life-threatening thrombo-embolic side effects predominantly in the arterial tree. In these cases, heparin must be suspended despite those severe thrombo-embolic episodes.
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