Endogenous Heparin

Abstract

Since the drug, heparin, is prepared from mammalian tissue, there is a widespread assumption that its presence in tissue (as endogenous heparin) normally plays an important role in the prevention of coagulation and thrombosis [24,101] This assumption in turn is based on the further assumptions that significant amounts of heparin are present normally in primate tissue and that mast cells and heparin are synonymous. Such conclusions are derived from evidence that defines heparin as an anticoagulant, a releaser of lipoprotein lipase, a metachromatic mucopolysaccharide, or as the metachromatic component of mast cells and basophilic leukocytes. DEFINITIONS USED FOR HEPARIN IN BLOOD OR TISSUESListed below are operational definitions for endogenous heparin which are widely used. Other substances satisfying each definition are given in parentheses.(1) Anticoagulant activity which (a) appears in plasma (fibrinogen split products, antibodies to coagulation factors, etc); (b) is heat stable (inorganic salts, organic acids, amino acids and polyaminoacids, lipid inhibitors, other mucopolysaccharides); (c) occurs in tissues (lipids, other mucopolysaccharides, peptones, peptides, inorganic salts); (d) inhibited by protamine or toluidine blue (fibrinogen, fibrin split products, nucleic acids, chondroitins [sulfate] A,B,C,D & E,heparitins [sulfate] A,B,C,D).(2) Activity in releasing lipoprotein lipase, etc., which is blocked by protamine, etc. (other sulfated mucopolysaccharides).(3) Mucopolysaccharide characterized by (a)carbazole color reaction (chondroitins, heparitins, uronic acids [detoxication products]); (b)not eluted from adsorbents by <M NaCl (multisulfated chondroitins); (c) metachromasia with toluidine blue, etc. (given by heparinoids, mucopolysaccharides, polyelectrolytes; however, electrolytes can be used to suppress color differentially from mucopolysaccharides); (d) electrophoretic migration (heparinoids, chondroitins A,B,C,D,E, polyelectrolytes: These can be distinguished by position and color); (e) destruction by adapted enzymes of Flavobacterium heparinum (heparitins; chondroitins A,B and C are destroyed by constitutive enzymes of Flavobacterium heparinum).(4) The metachromatic component of mast cells and basophilic leukocytes (chondroitins and heparitins).It is evident, then, that all these operational definitions are equally applicable to other biologic substances in blood and tissues which occur more frequently and in larger quantities. Hence, their use to identify heparin requires rigid exclusion of the similarly acting substances occurring in blood or tissue fluids, something which is difficult to accomplish. The presence of thromboplastin, platelet factor 4 or other basic proteins and the thromboplastic activity of hyaluronic acid [1] present many traps in using simple tests for anticoagulant activity with a mixture of crude mucopolysaccharides. The problems involved with coagulation test systems used to test for heparin [46] were recently demonstrated by the WHO international study of the assay of heparin...

Determination of Plasma Heparin Level Improves Identification of Systemic Mast Cell Activation Disease

“…In human tissues, MCs (of both the connective tissue and mucosal varieties; [ 17 , 18 ]) are the main source of heparin [ 19 , 20 ]. Human MCs have been estimated to contain 2.4 to 7.8 μg heparin per 10 6 cells [ 21 ].…”

Protein–polyelectrolyte interactions

“…265 GAGs exhibit polyelectrolyte behavior in solution, as unambiguous observation by Jacques, subsequently ignored. 266 Key polyelectrolyte parameters are its high linear charge density, salt dependent chain stiffness, and characteristic dependences of chain dimensions on MW and ionic strength. The exceptionally high linear charge density arises from extensive posttranslational sulfation.…”

Effects of Primary Mast Cell Disease on Hemostasis and Erythropoiesis

“…The presence of hemorrhagic disorders in patients with MC disease is mainly explained by the anticoagulant activity of MC degranulation products like heparin, histamine and tryptase [24] and by hyperfibrinolysis [17]. In human tissues, MCs are the main source of heparin [25,26]. Increased release of heparin from MCs can reach circulating concentrations similar to heparin levels achieved during thrombo prophylaxis by subcuta-neously applied heparin [17,27] and, thereby, could contribute to the bleeding diathesis.…”