Download PDF
Adipositas - Ursachen, Folgeerkrankungen, Therapie 2015; 09(02): 64-72
DOI: 10.1055/s-0037-1618922
Thrombose & Embolie
Schattauer GmbH

Besonderheiten der Antikoagulation bei adipösen Patienten

Anticoagulation in obesity
K. Chobanyan-Jürgens
1   Institut für Klinische Pharmakologie, Medizinische Hochschule Hannover
,
M. May
2   Clinical Research Center Hannover, Medizinische Hochschule Hannover
› Author Affiliations
Further Information

Publication History

Publication Date:
22 December 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Antikoagulanzien dienen der Prophylaxe und Therapie thromboembolischer Ereignisse. Indikationen wie stationäre und post-operative Prophylaxe bei bariatrischen Patienten sowie die wirksamen Dosierungen bei stark adipösen Patienten sind durch Zulassungsdaten nicht abgedeckt, die offiziellen Fachinformationen daher nur wenig hilfreich. Eine Unterdosierung von Antikoagulanzien kann das Thromboembolierisiko erhöhen oder die Wirksamkeit der Therapie reduzieren, eine Überdosierung das Risiko für Blutungen erhöhen. Standarddosierungen praktisch aller Antikoagulanzien führen bei stark adipösen Patienten zu einer reduzierten Medikamentenexposition. Dosierungen für Heparine und Fondaparinux sollten unter Beachtung substanzspezifischer Strategien erhöht werden. Die ohnehin notwendige INR-Kontrolle von Phenprocoumon/Warfarin macht spezifische Dosisempfehlungen unnötig. Für Dabigatran, Rivaroxaban und Apixaban liegen Daten zur Sicherheit und Wirksamkeit bei moderat adipösen Patienten vor, eine Dosisanpassung erscheint nicht notwendig. Stark adipöse Patienten wurden bislang nicht untersucht, der Einsatz der neuen Antikoagulanzien im Bereich malabsorptiver chirurgischer Eingriffe wird derzeit nicht empfohlen.

Summary

Thromboembolic events are prevented and treated by anticoagulants. Specific indications like pre- and post-surgery prevention in bariatric patients as well as choice of efficacious doses in massively obese patients are not covered by data submitted for approval. Thus, regularly official summaries of product characteristics information are not helpful. Underdosing of anticoagulants may increase the risk for thromboembolic events and decrease the efficacy of thrombosis treatment whereas overdosing might increase the bleeding risk. Administration of standard doses of nearly all anticoagulants results in decreased drug exposure. Heparin and fondaparinux doses therefore should be increased by substance-specific strategies. Phenprocoumon/warfarin require regular INR measurements in any case, specific dose recommendations are therefore not necessary. The safe and efficacious use of standard doses of dabigatran, rivaroxaban and apixaban in moderately obese patients is covered by clinical data, whereas massively obese patients were not studied. These new anticoagulants should not currently be used in patients undergoing malabsorptive bariatric surgery.

Schlüsselwörter

Heparin - niedermolekulares Heparin (NMH) - Fondaparinux - Phenprocoumon - Dabigatran - Rivaroxaban - Apixaban - Adipositas - bariatrische Chirurgie

Keywords

Heparin - low molecular weight heparin (LMWH) - fondaparinux - phenprocoumon - dabigatran - rivaroxaban - apixaban - obesity - bariatric surgery
 

  • Literatur

  • 1 Darvall KA, Sam RC, Silverman SH. et al. Obesity and thrombosis. Eur J Vasc Endovasc Surg 2007; 33: 223-233.
    CrossrefPubMedGoogle Scholar
  • 2 Eichinger S, Hron G, Bialonczyk C. et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med 2008; 168: 1678-1683.
    CrossrefPubMedGoogle Scholar
  • 3 Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med 2005; 118: 978-980.
    CrossrefPubMedGoogle Scholar
  • 4 Geerts WH, Bergqvist D, Pineo GF. et al. American College of Chest Physicians. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice thtuation kann nur durch kontrollierte ran-Gründen sinnvoll sein, gibt aber keine Guidelines. 8th. edition 381S-453S.
    Google Scholar
  • 5 Cook LM, Kahn SR, Goodwin J, Kovacs MJ. Frequency of renal impairment, advanced age, obesity and cancer in venous thromboembolism patients in clinical practice. J Thromb Haemost 2007; 05: 937-941.
    CrossrefPubMedGoogle Scholar
  • 6 Patel JP, Roberts LN, Arya R. Anticoagulating obese patients in the modern era. Br J Haematol 2011; 155: 137-149.
    CrossrefPubMedGoogle Scholar
  • 7 Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med 1993; 119: 874-881.
    PubMedGoogle Scholar
  • 8 Myzienski AE, Lutz MF, Smythe MA. Unfractionated heparin dosing for venous thromboembolism in morbidly obese patients: case report and review of the literature. Pharmacotherapy 2010; 30: 324.
    CrossrefPubMedGoogle Scholar
  • 9 Steuernagel C. Blutgerinnung und Antikoagulation. Lewandowski K, Bein T. (Hrsg). Adipositas-Management. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft; 2012
    Google Scholar
  • 10 Rowan BO, Kuhl DA, Lee MD. et al. Anti-Xa levels in bariatric surgery patients receiving prophylactic enoxaparin. Obes Surg 2008; 18: 162-166.
    CrossrefPubMedGoogle Scholar
  • 11 Freeman A, Horner T, Pendleton RC, Rondina MT. Prospective comparison of three enoxaparin dosing regimens to achieve target anti-factor Xa levels in hospitalized, medically ill patients with extreme obesity. Am J Hematol 2012; 87: 740-743.
    CrossrefPubMedGoogle Scholar
  • 12 Spinler SA, Ou FS, Roe MT. et al. Weight-based dosing of enoxaparin in obese patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE initiative. Pharmacotherapy 2009; 29: 631-638.
    CrossrefPubMedGoogle Scholar
  • 13 Walden A, Levison R, Singh S, Keeling D. A case of fatal pulmonary embolism raising questions about the dosing regimen for dalteparin in the very obese. Br J Haematol 2008; 142: 487-489.
    CrossrefPubMedGoogle Scholar
  • 14 Wilson SJ, Wilbur K, Burton E, Anderson DR. Effect of patient weight on the anticoagulant response to adjusted therapeutic dosage of low-molecularweight heparin for the treatment of venous thromboembolism. Haemostasis 2001; 31: 42-48.
    PubMedGoogle Scholar
  • 15 Al-Yaseen E, Wells PS, Anderson J, Martin J, Kovacs MJ. The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients. J Thromb Haemost 2005; 03: 100-102.
    CrossrefPubMedGoogle Scholar
  • 16 Nagler M, Haslauer M, Wuillemin WA. Fondaparinux - data on efficacy and safety in special situations. Thromb Res 2012; 129: 407-417.
    CrossrefPubMedGoogle Scholar
  • 17 Büller HR, Davidson BL, Decousus H. et al. Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003; 349: 1695-1702.
    CrossrefPubMedGoogle Scholar
  • 18 Büller HR, Davidson BL, Decousus H. et al. Matisse Investigators. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med 2004; 140: 867-873.
    CrossrefPubMedGoogle Scholar
  • 19 Diepstraten J, Hackeng CM, van Kralingen S. et al. Anti-Xa levels 4 h after subcutaneous administration of 5700 IU nadroparin strongly correlate with lean body weight in morbidly obese patients. Obes Surg 2012; 22: 791-796.
    CrossrefPubMedGoogle Scholar
  • 20 Egan G, Ensom MH. Measuring anti-factor xa activity to monitor low-molecular-weight heparin in obesity: a critical review. Can J Hosp Pharm 2015; 68: 33-47.
    PubMedGoogle Scholar
  • 21 Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 2009; 43: 1064-1083.
    CrossrefPubMedGoogle Scholar
  • 22 Meyer Czu Schwabedissen, Mevissen V, Schmitz F, Woodruff S, Langebartels G, Rau T, Zerres K, Hoffmann R, Ortlepp JR. Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not. Eur J Clin Pharmacol 2006; 62: 713-720.
    CrossrefPubMedGoogle Scholar
  • 23 van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 2014; 12: 320-328.
    CrossrefPubMedGoogle Scholar
  • 24 Moore TJ, Cohen MR, Mattison DR. Dabigatran, bleeding, and the regulators. BMJ 2014; 349: g4517.
    CrossrefPubMedGoogle Scholar
  • 25 Kubitza D, Becka M, Zuehlsdorf M, Mueck W. Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol 2007; 47: 218-226.
    CrossrefPubMedGoogle Scholar
  • 26 Upreti VV, Wang J, Barrett YC, Byon W, Boyd RA, Pursley J, LaCreta FP, Frost CE. Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects. Br J Clin Pharmacol 2013; 76: 908-916.
    CrossrefPubMedGoogle Scholar
  • 27 Di Minno MN, Lupoli R, Di Minno A, Ambrosino P, Scalera A, Dentali F. Effect of body weight on efficacy and safety of direct oral anticoagulants in the treatment of patients with acute venous thromboembolism: A meta-analysis of randomized controlled trials. Ann Med 2015; 47: 61-88.
    CrossrefPubMedGoogle Scholar
  • 28 May M, Engeli S. Pharmakokinetische Besonderheiten bei adipösen Patienten. Adipositas 2014; 08: 89-94.
    PubMedGoogle Scholar