Download PDF
Hamostaseologie 2009; 29(03): 241-246
DOI: 10.1055/s-0037-1617032
Review
Schattauer GmbH

Established anticoagulants in secondary haemostasis

Vitamin K antagonists, heparinsEtablierte Antikoagulanzien der sekundären HämostaseVitamin-K-Antagonisten, Heparine
E. Langer
1   Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité Universitätsmedizin Berlin
,
S. Ziemer
1   Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité Universitätsmedizin Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
05 February 2018 (online)

Also available at
    Permissions and Reprints

Summary

In respect to the actual discussion of new anticoagulants in secondary haemostasis, we will give a short review on established oral anti -coagulation with vitamin K antagonists and parenteral anticoagulation by use of heparin. The different cumarin derivatives phenprocoumon, warfarin, and acenocoumarol are compared concerning to the management and influence of pharmacogenetic and pharmacokinetic factors. Studies to improve the safety of oral anticoagulation by vitamin K supplementation will be briefly discussed. The therapy with heparins include until now some problems of dose-response control. It is necessary to pay attention to contra-indications even for well known anticoagulants. Examples for that will be given.

Zusammenfassung

Vor dem Hintergrund der Diskussion neuer Antikoagulanzien der sekundären Hämostase soll hier ein kurzer Überblick über die etablierte orale Antikoagulation mit Vitamin-K-Antagonisten und die parenterale Antikoagulation mit Heparin gegeben werden. Die Cumarin -derivate Phenprocoumon, Warfarin und Acenocoumarol werden hinsichtlich ihres Handlings und ihrer Beinflussung durch pharmakogenetische und pharmakinetische Faktoren verglichen. Versuche, durch Vitamin-K-Supplementierung die Sicherheit der Antikoagulation mit Vitamin-K-Antagonisten zu erhöhen, werden kurz vorgestellt. Zu den Aspekten der Heparintherapie gehören Fragen der Dosis/Wirkungskontrolle, die noch nicht abschließend geklärt sind. Die Notwendigkeit, auch bei bewährten Präparaten auf relative und absolute Kontraindikationen zu achten, wird anhand von Beispielen erläutert.

Keywords

Vitamin K - vitamin K antagonists - unfractionated heparin - low-molecular-weight heparins

Schlüsselwörter

Vitamin K - Vitamin-K-Antagonisten - unfraktioniertes Heparin - niedermolekulare - Heparine
 

  • Literatur

  • 1 Alberio L. Die orale Antikoagulation. Ther Umschau 2003; 60: 5-9.
    CrossrefPubMedGoogle Scholar
  • 2 Ansell J, Hirsh J, Hylek E, Jacobson A. et al. American College of Chest Physians. Pharmacology and Management of the Vitamin K Antagonists. American College of Chest Physians Evidence-Based Clinical Practice Guidelines.Chest 2008; 133 (Suppl. 06) 160S-198S.
    PubMedGoogle Scholar
  • 3 Ansell J. Factor Xa or thrombin: is factor Xa a better target?. J Thromb Haemost 2007; 5 Suppl1 60-64.
    CrossrefPubMedGoogle Scholar
  • 4 Aston JL, Lodolce AE, Shapiro NL. Interaction between warfarin and cranberry juice. Pharmacotherapy 2006; 26: 1314-1319.
    CrossrefPubMedGoogle Scholar
  • 5 Becquemont L. Evidence for a pharmakogenetic adapted dose of oral anticoagulant in routine medical practice. Eur J Clin Pharmacol 2008; 64: 953-960.
    CrossrefPubMedGoogle Scholar
  • 6 Calatzis A, Peetz D, Haas S. et al. Prothrombinase-induced clotting time assay for determination of the anticoagulant effects of unfractionated and low-molecular-weight heparins, fondaparinux, and thrombin inhibitors. Am J Clin Pathol 2008; 130: 446-454.
    CrossrefPubMedGoogle Scholar
  • 7 Chow WH, Chow TC, Tse TM. et al. Anticoagulation instability with life-threatening complication after dietary modification. Postgrad Med J 1990; 66: 855-857.
    CrossrefPubMedGoogle Scholar
  • 8 Crary SE, van Orden H, Journeycake JM. Experience with intravenous enoxaparin in critically ill infants and children. Pediatr Crit Care Med 2008; 9: 647-649.
    CrossrefPubMedGoogle Scholar
  • 9 Crowther MA, Ageno W, Garcia D. et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin. Ann Intern Med 2009; 150: 293-300.
    CrossrefPubMedGoogle Scholar
  • 10 Cuker A, Ptashkin B, Konkle BA. Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time. J Thromb Haemost 2009; 7: 80-86.
    CrossrefPubMedGoogle Scholar
  • 11 D’Andrea G, D’Ambrosio R, Margaglione M. Oral anticoagulants: Pharmacogenetics: Relationship between genetic and non-genetic factors. Blood Rev 2008; 22: 127-140.
    CrossrefPubMedGoogle Scholar
  • 12 Dämgen-von Brevern G, Kläffling C, Lindhoff-Last E. Überwachung der Antikoagulanzientherapie mit Fondaparinux. Hämostaseologie 2005; 25: 281-285.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Eikelboom JW, Hirsh J. Monitoring unfractionated heparin with the aPTT: Time for a fresh look. Thromb Haemost 2006; 96: 547-552.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Feng Y, Green B, Duffull SB. Development of a dosage strategy in patients receiving enoxaparin by continuous intravenous infusion using modelling and simulation. Br J Clin Pharmacol 2006; 62: 165-176.
    CrossrefPubMedGoogle Scholar
  • 15 Ford SK, Moll S. Vitamin K supplementation to decrease variability of international normalized ratio patients on vitamin K antagonists: a literature review. Curr Opin Hematol 2008; 15: 504-508.
    CrossrefPubMedGoogle Scholar
  • 16 Gage BF, Eby C, Johnson JA. et al. Use of pharmaco-genetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 2008; 84: 326-331.
    CrossrefPubMedGoogle Scholar
  • 17 Good AC, Henz S. A clinical algorithm to predict the loading dose of phenprocoumon. Thromb Res 2007; 120: 921-925.
    CrossrefPubMedGoogle Scholar
  • 18 Grant P. Warfarin and cranberry juice: An interaction?. J Heart Valve Dis 2004; 13: 25-26.
    PubMedGoogle Scholar
  • 19 Haas S, Bauersachs R. Thromboseprophylaxe bei chirurgischen und nicht chirurgischen Patienten. Hämostaseologie 2009; 29: 91-95.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Harenberg J, Giese C, Hagedorn A. et al. Determination of antithrombin-dependent Factor Xa inhibitors by prothrombin-induced clotting time. Semin Thromb Hemost 2007; 33: 503-507.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Harenberg J. (Hrsg). Thrombose und Antikoagulation. Stuttgart: Georg Thieme; 2003
    Google Scholar
  • 22 Herman D, Peternel P, Stegnar M. et al. The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thromb Haemost 2006; 95: 782-787.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Hirsh J, Bauer KA, Donati MB. et al. Parenteral Anticoagulants America College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2008; 133: 141-159.
    CrossrefPubMedGoogle Scholar
  • 24 Kane-Gill Sl, Feng Y, Bobek MB. et al. Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety. J Clin Pharm Ther 2005; 30: 207-213.
    CrossrefPubMedGoogle Scholar
  • 25 Kemkes-Matthes B, Barthels M. Orale Antikoagulanzien vom Cumarintyp. Hämostaseologie 2004; 24: 279-285.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Kemkes-Matthes B, Matzdorff A, Heidt M. et al. Initialphase der oralen Antikoagulanzienzherapie: Vergleich verschiedener Dosierungen von Warfarin und Phenprocoumon. Hämostaseologie 2002; 22: 87-91.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Kristiansen C, Lassen JF, Dahler-Eriksen BS. et al. Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation. Thromb Res 2000; 98: 157-163.
    CrossrefPubMedGoogle Scholar
  • 28 Lippi G, Favaloro EJ. Activated partial thromboplastin time: New tricks for an old dogma. Semin Thromb Hemost 2008; 34: 604-611.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Oldenburg J, Bevans CG, Müller CR. et al. Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle. Antioxid Redox Signal 2006; 8: 347-353.
    CrossrefPubMedGoogle Scholar
  • 30 Oldenburg J, Seidel H, Pötzsch B. et al. Neue Einsichten in die orale Antikoagulationstherapie mit Cumarinen. Hämostaseologie 2008; 28: 44-50.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Oldenburg J, Watzka M, Rost S. et al. VKORC1: molecular target of coumarins. Antioxid Redox Signal 2006; 8: 347-353.
    CrossrefPubMedGoogle Scholar
  • 32 Owen CA, Edby Nichols WI, Bowie EJW. A history of blood coagulation. Rochester. Mayo Foundation for Medical Education and Research 2001; 245-256.
    PubMedGoogle Scholar
  • 33 Poller L, Keown M, Ibrahim S. et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. Thromb Haemost 2008; 6: 935-943.
    CrossrefPubMedGoogle Scholar
  • 34 Salem DN, O’Gara PT, Madias C. et al. Valvular and structural heart disease. Chest 2008; 133: 593-629.
    CrossrefPubMedGoogle Scholar
  • 35 Schiller G, Hiller K. Arzneidrogen. 4. Auflage 1999, Spektrum Akademischer Verlag.
    PubMedGoogle Scholar
  • 36 Sconce E, Khan T, Mason J. et al. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost 2005; 93: 872-875.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Sconce E, Khan T, Wynne HA. et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 2005; 106: 2329-2333.
    CrossrefPubMedGoogle Scholar
  • 38 Sconce E, Avery P, Wynne H. et al. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood 2007; 109: 2419-2423.
    CrossrefPubMedGoogle Scholar
  • 39 Spinler SA, Wittkowsky AK, Nutescu EA. et al. Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular-weight heparin. Ann Pharmacother 2005; 39: 1275-1285.
    CrossrefPubMedGoogle Scholar
  • 40 Stehle S, Kirchheiner J, Lazar A. et al. Pharmacogenetics of oral anticoagulants. Clin Pharmacokinet 2008; 47: 565-594.
    CrossrefPubMedGoogle Scholar
  • 41 Tripodi A, van den Besselaar A. Laboratory Monitoring of anticoagulation: Where do we stand?. Semin Thromb Hemost 2009; 35: 34-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Ufer M. Comparative pharmacokinetics of vitamin K antagonists. Clin Pharmacokinet 2005; 44: 1227-1246.
    CrossrefPubMedGoogle Scholar
  • 43 Van Leeuwen Y, Rosendaal FR, van der Meer FJM. The relationship between maintenance dosages of three vitamin K antagonists: acenocoumarol, warfarin and phenprocoumon. Thromb Res 2008; 123: 225-230.
    CrossrefPubMedGoogle Scholar
  • 44 Vecsler M, Loebstein R, Almog S. et al. Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin. Throm Haemost 2006; 95: 205-211.
    PubMedGoogle Scholar
  • 45 Weitz JI. Factor Xa or thrombin: Is thrombin a better target?. J Thromb Haemost 2007; 5 (Suppl. 01) 65-67.
    CrossrefPubMedGoogle Scholar
  • 46 Werner D, Werner U, Wuerfel A. et al. Pharmacogenetic characteristics of patients with complicated phenprocoumon dosing. Eur J Clin Pharmacol. DOI 10.1007/s00228–009–0639-2.
    PubMedGoogle Scholar
  • 47 Wilke T, Tesch S, Scholz A. et al. The costs of heparin-induced thrombocytopenia: a patient-based cost of illness analysis. J Thromb Haemost 2009; 7: 766-773.
    CrossrefPubMedGoogle Scholar
  • 48 Yang J, Paredes N, Chan AKC. Antithrombotic therapy in children with venous thrombosis. Hämo -staseologie 2009; 29: 80-87.
    PubMedGoogle Scholar