Zusammenfassung
Heparin besteht aus einem Gemisch von Polysacchariden unterschiedlicher Kettenlänge. Die Substanz wurde von McLEAN (1) als gerinnungshemmend erkannt und von HOWELL (2) nach dem Ursprungsort benannt. In kommerziellen Heparinpräparationen mit einem Molekulargewicht von etwa 12.000 Dalton liegen dementsprechend im Mittel 35 Saccharide oder 8–9 Tetrasaccharide vor (3). Die Molekulargewichtsverteilung dieser Präparationen reicht von 3.000 bis 30.000 Dalton. Die gerinnungshemmende Aktivität dieser Heparinfraktionen ist in vitro für Faktor Xa 2,5mal höher als für unfraktionierte Heparine, während die Inhibierung von aPTT etwa gleich ist (4, 5, 6). Die-Faktor-Xa/aPTT-Ratio beträgt, entsprechend für niedermolekulares Heparin, das 2,5fache im Vergleich zu unfraktioniertem Heparin (7).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Literatur
McLean J: The thromboplastic action of cephalin. Am J Physiol (1916) 41: 250
Howell WH, Holt E: Two new fractions in blood coagulation. Heparin and proantithrom- bin. Amer J Physiol (1918) 47: 328–341
Harenberg J, de Vries JX: Characterization of heparins by high performance size exclu- sion liquid chromatography. J Chromatogr (1983) 261: 287–292
Barrowcliffe TW, Johnson A, Eggleton CA, Kemball-Cook G, Thomas DP: Anticoagu- lant activities of high and low-molecular-weight heparin fractions. Brit J Haematol (1979) 41: 573–582
Eggleton CA, Barrowcliffe TW, Merton RE, Thomas DP: In vitro and in vivo studies of the anti Xa activity of heparin. Thromb Res (1981) 24: 319–328
Lane DA, Mac Gregor IR, Michalski R, Kakkar VV: Anticoagulant activities of four unfractionated and fractionated heparins. Thromb Res (1978) 12: 237–246
Barrowcliffe TW, Curtis AD, Johnson EA, Thomas DP: An International Standard for Low Molecular Weight Heparin. Thromb Hemostas (1988) 60: 1–7
Holmer E: Anticoagulant properties of heparin and heparin fractions. Scand J Haematol (1980b) 24, Suppl 35, 25–34
Casu B, Oreste P, Torri G, Zopetti G, Choay J, Lormeau JC, Petitou M: The structure of heparin oligosaccharide fragments with high antifactor Xa activity containing the minimal antithrombin III-binding sequence. Biochem J (1981) 197: 599–609
Choay J, Petitou M, Lormeau JC, Sinay P, Casu B, Gatti G: Structure activity relationship in heparin: A synthetic pentasaccharide with high affinity for antithrombin III. Biochem Biophys Res Commun (1983) 116: 492–499
Walenga JM, Petitou M, Lormeau JC, Samama M, Fareed J, Choay J: Antithrombotic activity of a synthetic heparin pentasaccharide in a rabbit stasis thrombosis model using different thrombogenic challenges. Thromb Res (1987) 46: 187–198
Lam LH, Silbert JE, Rosenberg RD: The separation of active and inactive forms of heparin. Biochem Biophys Res Comm (1976) 69: 570–577
Estes JW, Pelikan EW, Krüger-Thiemer E: A retrospective study of the pharmcokinetics of heparin Clin. Pharma Therap (1969) 10: 329–337
Harenberg J, Stehle G, Augustin J, Zimmermann R: Comparative Human Pharmacology of Low Molecular Weight Heparins. Sem Thromb Hemostas (1989) 15: 414–423
Whitehead MI, MacCarthy TGH: A comparative trial of subcutaneous dodium and calcium heparin as assessed by local haematoma formation and pain. In: Kakkar VV, Thomas DP (eds) Heparin. Chemistry and Clinical Usage. Academic Press, London, New York, San Francisco. (1976) p. 361–366
Cade JF, Andrews JT, Stubbs AE: Comparison of sodium and calcium heparin in prevention of venous thromboembolism. Aust N Z J Med (1982) 12: 501–504
Thomas DP, Sagar S, Stamatakis JD, Mafei FHA, Erdi A, Kakkar VV: Plasma heparin levels after administration of calcium and sodium salts of heparin. Thromb Res (1976) 9: 241–248
Johnson EA, Kirwood TBL, Stirling Y, Perezu-Requejo JL, Ingram GIC, Bangham DR, Brozovic M: Four Heparin Preparations: Anti-Xa potentiating effect of Heparin after subcutaneous injection. Thrombos Haemostas (1976) 35: 586–591
Harenberg J, Giese Ch, Knödler A, Zimmermann R: Antifactor Xa clotting method for heparin and low molecular weight heparins. Ärztl Lab (1986) 32: 181–184
Harenberg J, Giese Ch, Knödler A, Zimmermann R: Comparative study on a new one-stage clotting assay for heparin and its low molecular weight derivatives. Haemostasis (1989) 19: 13–20
Harenberg J: Pharmacology of Low Molecular Weight Heparins. Sem Thromb Hemostas (1990) 16 Suppl: 12–18
Harenberg J, Gnasso A, de Vries JX, Zimmermann R, Augustin J: Anticoagulant and lipolytic effects of a low-molecular-weight heparin fraction. Thromb Res (1985) 39: 683–692
Merton RE, Thomas DP: Experimental studies on the relative efficacy of dermatan sulphate and heparin as antithrombotic agents. Thrombos Haemostas (1987) 58: 839–846
Harenberg J, Würzner B, Zimmermann R, Schettler G: Bioavailability and antagonization of the low-molecular-weight heparin CY 216 in man. Thromb Res (1986) 44: 549–555
Rostin M, Montastruc JL, Houin G, D’Azemar P, Bayrou B, Boneu B: Pharmacodynamics of CY 216 in healthy volunteers: inter-individual variations. Fundam Clin Phar ma-col (1990) 4: 17–23
Hobbelen PM, Vogel GM, Meuleman DG: Time courses of the antithrombotic effects, bleeding enhancing effects and interactions with factors Xa and thrombin after administration of low molecular weight heparinoid Org 10172 or heparin to rats. Thromb Res (1987) 48: 549–558
Hoppensteadt D, Walenga JM, Fareed J.:Comparative antithrombotic and hemorrhagic effects of dermatan sulfate, heparian sulfate and heparin. Thromb Res (1990) 60: 191–200
Bang CJ, Berstad A, Talstad I: Gastric mucosal bleeding after unfractionated and low molecular weight heparin in rats. Scand J Gastroenterol (1990) 25: 379–382
Harenberg J, Giese C, Dempfle CE, Stehle G, Heene DL: Biological activity and safety of the subcutaneous administration of high doses of low molecular weight heprin for 8 days in human volunteers. Thromb Haemost (1989) 61: 357–362
Frydman AM, Bara L, Le Roux Y, Woler M, Chauliac F, Samama MM: The antithrombotic activity and pharmacokinetics of enoxaparine, a low molecular weight heparin, in humans given single subcutaneous doses of 20 to 80 mg. J Clin Pharmacol (1988) 28: 609–618
Mombelli G, Schaedelin J, Beck EA Pharmakokinetik von Heparin nach einmaliger in-travenöser oder subkutaner Injektion Schweiz Med Wschr (1977) 107: 810–815
Esquerre, JP Boneu B, Guiraud R: Kinetics of technetium-labeled heparin in thrombo- embolism: Preliminary report Int J Nucl Med Biol (1979) 6: 215–220
Teien AN, Bjornson J: Heparin elimination in uraemic patients on haemo-dialysis Scand J Haemat (1976) 17, 19–25
Andrassy K, Salzmann W, Saggau W, Storch H, Ritz E: Is more heparin necessary for low-dose heparin prophylaxis in uremic patients? Thrombos Haemostas (1981) 46: 740–742
Teien AN: Heparin elimination in patients with liver cirrhosis Thromb Haemostas (1977) 38: 701–705
Hirsh J, van Aken WG, Gallus AS, Dollery CT, Cade JF, Yung WL: Heparin Kinetics in Venous Thrombosis and Pulmonary Embolism Circulation, (1976) 53: 691–695
Simon TL, Hyers TM, Gaston JP, Harker: LA Heparin pharmacokinetics: increased re- quirements in pulmonary embolism Brit J Haem (1978) 39: 111–120
Mungall D, Raskob G, Coleman R, Rosenbloom D, Ludden T, Hull R: Pharmacokinetics and dynamics of heparin in patients with proximal vein thrombosis. J Clin Pharmacol (1989) 29: 896–900
Ostergaard PB, Nilsson B, Bergqvist D, Hedner U, Pedersen PC: The effect of low mole-cular weight heparin on experimental thrombosis and haemostasis–the influence of production method. Thromb Res (1987) 45: 739–749
Psuja P: Kinetics of radiolabelled (99mTc) heparin and low molecular weight heparin fraction CY 216, CY 222 in patients with uncomplicated myocardial infarction. Folia Haematol Leipz (1988) 115: 661–668
Andrew M, Cade J, Buchanan MR, Cerskus AL, Jefferis A, Towell M, Hirsh J: Low mo-lecular weight heparin does not cross the placenta. Thrombos Haemostas (1983) 50: 225
Forestier F, Daffos F, Rainaut M, Toulemonde F: Low Molecular Weight Heparin (CY 216) Does Not Cross the Placenta During the Thrid Trimester of Pregnancy. Thromb Haemostas (1987) 57: 234
Harenberg J, Leber G, Augustin J, Raedsch R, Schwarz F, Stiehl A, Zimmermann R: Ambulante Langzeitprophylaxe der Thromboembolie mit niedermolekularem Heparin. Klin Wschr (1987) 65: 331–337
Harenberg J, Schwarz F, Dietz R, Leber G, Zimmermann R, Kübler W: Antikoagulation mit niedermolekularem Heparin bei Patienten mit prothetischem Herzklappenersatz. Z Kardiol (1987) 76: 284–28
Harenberg J, Leber G, Zimmermann R, Schmidt W: Thromboembolieprophylaxe mit niedermolekularem Heparin in der Schwangerschaft. Geburtsh u Frauenheilk (1987) 47: 15–18
Doutremepuich D, Deharo E, Doutremepuich F, Lalanne MC, Toulemonde F: Kinetic study of tPA release induced by heparin and heparin fragment. Thromb Res (1989) 53: 615–621
Sorensen JV, Bonis LC, Lassen MR, Christiansen HM, Schott P, Olsen AD, Neerstrand HS: Association between plasma levels of tissue plasminogen activator and postoperative deep vein thrombosis–influence of prophylaxis with a low molecular weight heparin. Thromb Res (1990) 59: 131–138
Eriksson E, Wollter IM, Christenson B, Stigendal L, Risberg B: Heparin and fibrinolysis–comparison of subcutaneous administration of unfractionated and low molecular weight heparin. Thromb Haemost (1988) 59: 284–288
Grimaudo V, Omri A, Kruithof EK, Hauert J, Bachmann F: Fibrinolytic and anticoagulant activity after a single subcutaneous administration of a low dose of heparin or a low molecular weight heparin-dihydroergotamine combination. Thromb Haemost (1988) 59: 388–391
Agnelli G, Levi M, Cosmi B, ten Cate JW, Nenci GG: Additive effect of dDAVP and standard heparin in increasing plasma t-PA. Thromb Haemost (1989) 61: 507–510
Rapaport RS, Ronchetti-Blume M, Vogel RL, Hung PP: Heparin potentiates endothelial cell growth factor stimulation of plasminogen activator synthesis by diploid human lung fibroblasts. Thromb Haemost (1988) 59: 514–522
Fry ET, Sobel BE: Lack of interference by heparin with thrombolysis or binding of tissue-type plasminogen activator to thrombi. Blood (1988) 71: 1347–1352
Millot F, Etienne J, Aiach M, Meyniel D, Brault D, Pieron R, Laruelle P: Effet d’un dérivé de l’héparine de faible poids moléculaire sur la libération d’une activité lipolytique dans la circulation sanguine. C R Acad Sc (1982) 295: 771–776
Harenberg J, Stehle G, Dempfle CE, von Hodenberg E, Heene DL: Beeinflussung der Blutgerinnung and der Lipasen durch das niedermolekulare Heparin CY 216. Ärztl Lab (1989) 35: 73–79
Broze GJ, Miletich JP: Characterization of the inhibition of tissue factor in serum. Blood (1987 a) 69: 150–155
Schmidt M, Barrowcliffe TW, Gray E, Watton J, Harenberg J: Anti-Xa clotting activities in different hepatic-triglyceride lipase preparations from post-heparin plasma. Thromb Res (1991) 63: 503–508
Lindahl AK, Abildgaard U, Stokke G: Release of extrinsic pathway inhibitor after heparin injection: increased response in cancer patients. Thromb Res (1990) 59: 651–656
Harenberg J, Schäfer M, Stehle G, Schmidt M, Dempfle CE, Heene DL: Release of the extrinsic inhibitor, hepatic lipase and anti-factor Xa activity into post-heparin plasma. Thromb Haemost (1991) 65: 915
Harenberg J, Giese Ch, Knödler A, Zimmermann R, Schettler G: Neutralization of a Low Molecular Weight Heparin Kabi 2165 by Protamine Chloride. Klin Wochenschr (1986) 64: 1171–1175.
Harenberg J, Gnasso A, de Vries JX, Zimmermann R, Augustin J: Inhibition of lowmolecular-weight heparin by protamine chloride in vivo. Thromb Res (1985) 38: 11–20
Hubbard AR, Jennings CA: Neutralization of heparan sulphate and low-molecularweight heparin by protamine. Thrombos Haemostas (1985) 13: 86–90
Massonnet-Castel S, Pelissier E, Bara L, Terrier E, Abry B, Guibourt P, Swanson J, Jaulmes B, Carpentier A, Samama M: Partial reversal of low-molecular-weight heparin (PK 10169) Anti-Xa activity by protamine sulfate: In vitro and in vivo study during cardiac surgery with extracorporal circulation. Haemostasis (1986) 16: 139–145
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1993 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Harenberg, J. (1993). Pharmakologie der Heparine in der Thromboseprophylaxe. In: Husfeldt, K.J., Raschke, R. (eds) Thrombosen und Embolien: Arzthaftung. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78297-8_4
Download citation
DOI: https://doi.org/10.1007/978-3-642-78297-8_4
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-56826-1
Online ISBN: 978-3-642-78297-8
eBook Packages: Springer Book Archive