Effect

Blood coagulation, medically known as hemostasis, is a highly complex cascade-like reaction that occurs in the blood vessel in which the mutually activating blood coagulation factors ultimately activate an enzyme called thrombin, which splits off small fragments from the giant protein fibrinogen (also known as blood coagulation factor II), which cross-link the blood platelets (medically known as thrombocytes) to form a stable blood clot. The formation of the main coagulation enzyme thrombin is either triggered from the outside (“extrinsic”) in the case of vascular damage that leads to the exposure of connective tissue fibers (collagen) by toxins produced by bacteria (“endotoxins”), or the activation is triggered by substances released into the blood vessel from the inside (“intrinsic”).In any case, the blood clotting factors only work optimally when various accompanying substances, membrane lipids and electrically positively charged calcium are also present. The latter is needed so that the coagulation factors can attach themselves to the electrically negatively charged surfaces of the blood platelets and cross-link them stably. Therapeutically, the necessary presence of calcium is used to make blood uncoagulable by withdrawing calcium (e.g. so that blood does not immediately coagulate when it is drawn, molecules called citrate or EDTA are added to bind the calcium present in the blood so that it is no longer available for blood coagulation).

Metabolization of the coumarins

What happens to coumarins in the body (medical: pharmacokinetics)? The two most important coumarins used are phenprocoumon (better known under its trade name Marcumar®), which is effective for 7 to 10 days longer, and warfarin (better known as coumadin), which inhibits clotting for up to 6 days. Coumarins are the first anticoagulant drugs that can be taken as tablets, i.e. orally, because they are almost completely absorbed into the blood from the intestine like other nutrients (medically: resorbed) and are not destroyed by the hydrochloric acid of the stomach.

It should be noted that the maximum effect of CumarineMarcumar® does not occur immediately, but only after 24 to 36 hours, since only the new formation of coagulation factors is inhibited, but not the factors still present in the blood are broken down. At the beginning of a therapy, therefore, immediately effective anticoagulant anticoagulants must first be administered. As a rule, heparin is used, which directly inhibits the main enzyme of blood coagulation, thrombin (as well as blood coagulation factor X). On the contrary, the administration of coumarin initially even leads to increased blood clotting, which makes the additional administration of heparin necessary: coumarins also inhibit the formation of anticoagulant proteins called “Protein C” and “Protein S”. If these “natural thrombosis protective substances” are no longer sufficiently formed, the undesirable effect – namely, increased clot formation – is imminent.