Heparin-a unique blood anticoagulant
There are many types of blood anticoagulants. Among them, heparin anticoagulants are much higher in cost than other anticoagulants, and they are unique and irreplaceable. The anticoagulation principle of heparin is based on the natural blood anticoagulation mechanism in the animal's body, so it can be used for anticoagulation drugs in the body as well as anticoagulation in vitro.
Molecular structure of heparin
Principle of heparin anticoagulation:
Heparin sodium or heparin lithium are commonly used heparin salts, and the effective anticoagulant ingredient is heparin, which is a kind of mucopolysaccharide sulfate. Heparin can enhance the activity of the natural anticoagulant component antithrombin III (ATIII) in plasma by more than one hundred times. By combining with ATIII, it can enhance the activity of ATIII on the coagulation factor II (FIIa or thrombin) and the activity of two important factors in plasma. Inhibition of coagulation factor X (FXa) to achieve the function of anticoagulation. Short-chain heparin (such as low molecular weight heparin) can also block coagulation to achieve antithrombotic effect by inhibiting FXa, but there is a difference between medicinal heparin and in vitro anticoagulant heparin.
Source of heparin:
Both in vitro anticoagulant heparin and medicinal heparin need to be prepared from crude heparin extracted from animals. At first, heparin was derived from bovine lungs and then from bovine intestinal mucosal heparin. Later, due to the outbreak of mad cow disease in Europe, bovine heparin was no longer used. Relevant agencies stipulate that crude heparin is derived from pigs and cannot be mixed with heparin derived from ruminants.
In 2015, the United States restarted the use of bovine heparin due to market resources. It should be noted that the structure of bovine heparin and porcine heparin is significantly different (the former has a higher degree of N-sulfation), and the anticoagulant activity of bovine heparin It is about 160 U/mg, which is much lower than porcine heparin (usually it can reach more than 200 U/mg). Moreover, the incidence of HIT caused by bovine heparin in medicine is higher than that of porcine heparin.
Synthesis of heparin:
Heparin cannot be artificially synthesized at present, and can only be biosynthesized and stored in mammalian mast cells, requiring a total of 6 steps of enzymatic reactions. For example, the synthesis of nucleic acids, peptides, and proteins all have templates available, and heparin is a polysaccharide, the product of a series of enzymatic reactions, and it is difficult to synthesize.
At present, part of the structural skeleton of heparin has been synthesized in the laboratory, and the artificial synthesis of heparin will eventually be overcome in the future. Desheng is a blood collection reagent company, and the heparin provided is an in vitro anticoagulant purified by porcine heparin.
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