When must Marcumar® not be given?
In general, coumarins must not be administered during pregnancy, as they can cause severe damage both in the early stages of child development (“embryopathies”, third to eighth week of pregnancy) and in the later, usually less sensitive developmental stages (“fetopathies”, from the ninth week of pregnancy onwards).
Alternatives to Marcumar®
The most frequently used anticoagulants, in addition to CoumarinsMarcumar®, are heparin, which can only be administered intravenously, and a mini protein originally derived from leeches (scientific name: Hirudo medicinalis), hirudin. disaccharide of a glucosamine and a glucosuronic acid). The anticoagulant effect of heparin consists in the 1000-fold increase (or acceleration) in the effectiveness of a blood-clotting inhibitor, antithrombin (often referred to in the literature as AT for short).
Antithrombin itself inhibits the enzyme thrombin, which is essential for blood coagulation and cross-links the blood platelets by means of fibrin for wound closure, by forming inactive complexes with it. Heparin itself is not a uniformly structured molecule, but occurs in different sizes, so that two subgroups with different properties and applications can be distinguished: On the one hand, there are the “unfractionated” heparins consisting of larger building blocks (a molecule is between 6,000 and 30,000 times heavier than a single hydrogen atom), which are administered intravenously for treatment of pulmonary embolism, leg vein thrombosis and for anticoagulation in cases of angina pectoris (see above).On the other hand, there are “fractionated” heparins, also called “low molecular weight” because of their smaller molecular size (these are always lighter than 6000 hydrogen atoms). The different chemical properties compared to the high-molecular heparins are the reason for the increasingly frequent use of this group of drugs: they only have to be injected under the skin (medically: subcutaneously) once a day, which is why they are also regularly used in the outpatient sector (e.g. by the family doctor).
In addition, undesirable side effects occur much less frequently: In addition to the bleeding that can occur with all anticoagulants, there is an increased risk of osteoporosis (bone loss) and allergic reactions. Osteoporosis is a systemic disease of the skeleton characterized by reduced bone mass and disruption of the microarchitecture. It is characterized, for example, by spontaneously occurring bone fractures without a previous trauma accident being able to explain the fracture.
The best protection against this disease, which mainly affects the female sex, is an adequate dietary intake of calcium (which is mainly contained in milk) and an adequate supply of vitamin D (it is recommended to eat sea fish twice a week). In addition, sufficient physical activity should be ensured, as this promotes mineralization of the bones. Prolonged periods of sex hormone deficiency should be avoided; if necessary, the estrogens required for bone metabolism can be substituted within the framework of hormone replacement therapy, e.g. in post-menopausal women.
Heparin-induced thrombocytopenia, or HITs for short, are two diseases in which platelets are destroyed due to a malfunction of the immune system. In the less severe, reversible type 1 HITs, up to 30% of the platelets are usually lost early on in the start of heparin therapy. Type 2, on the other hand, is more severe, often life-threatening, and occurs in about 0.5 to 3 % of cases after the fifth to eleventh day after the start of therapy.
The fatal effect (in up to 30 % of patients) is not so much the severe loss of platelets (the number of platelets contained in a microliter often drops from around 300,000 to less than 50,000), but the massive release of coagulation-promoting substances from the walls of the blood vessels. This is the reason why HIT 2 is called “White Clot Syndrome”: vascular occlusion of the arteries in blood depleted of red blood platelets as well as the formation of clots in leg veins and pulmonary embolisms can be life-threatening. To avoid these complications, therapy must be stopped immediately at the first warning signs of HIT and continued with another anticoagulant.
Hirudin, which used to be obtained from leeches, has proven its worth and can now also be produced by genetic engineering (the substances obtained in this way were analogously called “lepirudin” and “desirudin”). The up to 15 cm large, olive-green colored annelids use the hirudin to liquefy the blood of their host animals. Particularly in the medicine of the 19th century, the use of leeches for the treatment of the most different illnesses was widespread; today, however, the leech stands under nature conservation in Europe and may be collected after the Washingtoner Artenschutzabkommen only with special permission.
An advantage of hirudin over heparins, apart from the possibility of application in patients with HIT 2, is its rapid onset of action and generally good tolerability, so that undesirable side effects are very rare. The disadvantage, however, is the poorer controllability: unlike heparins, there is no antidote that would enable the premature termination of anticoagulation (the heparin effect can be neutralized by injecting the protein protamine, which is obtained from salmon).
