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Bedeutung von Biomarkern bei der Lungenarterienembolie

Importance of biomarkers in pulmonary embolism

  • Schwerpunkt: Biomarker in der Akutmedizin
  • Published:
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Zusammenfassung

Die Lungenarterienembolie (LAE) ist als dritthäufigste kardiovaskuläre Erkrankung eine Hauptursache für Hospitalisierung, Morbidität und Mortalität in den westlichen Industrienationen. Aufgrund vieler unterschiedlicher klinischer Erscheinungsformen sowie unspezifischer Krankheitszeichen ist eine schnelle Diagnosefindung häufig schwierig. Die D‑Dimere entstehen nach Aktivierung des Gerinnungssystems mit Produktion sowie Abbau von Fibrin. Sie sind aktuell der einzige allgemeine Laborparameter, der die Aktivität der Gerinnungskaskade widerspiegelt. Die vorliegende Übersicht befasst sich damit, welchen Nutzen die D‑Dimere im Rahmen der LAE-Diagnostik haben, welche Besonderheiten zu beachten sind und wo die Grenzen und Probleme dieses Biomarkers liegen. In Zusammenschau ist zu sagen, dass die D‑Dimere in Kombination mit der klinischen Vortestwahrscheinlichkeit ein verlässlicher Biomarker zum Ausschluss einer LAE sind. Hierbei sollten jedoch testspezifische Grenzwerte berücksichtigt werden. Bei Patienten über 50 Jahre sollte ein altersadjustierter Grenzwert verwendet werden. Im Rahmen von Erkrankungen oder Situationen, die auch ohne Vorliegen einer LAE mit erhöhten D‑Dimeren einhergehen, wie Malignomen, Operationen, Infektionen oder Schwangerschaft, wird die Verwendung der D‑Dimere nicht empfohlen.

Abstract

Pulmonary embolism (PE) is the third most prevalent cardiovascular disease and a major cause for hospitalization, morbidity and mortality in western industrialized countries. The patients’ clinical presentation varies greatly with often unspecific symptoms. These circumstances render a quick diagnosis and treatment initiation important but both remain clinical challenges. The D‑dimers become detectable after activation of the coagulation system with production and subsequent degradation of fibrin. They currently represent the only general biomarker that reflects the activity of the coagulation cascade. This review describes the role of D‑dimers in the diagnostics of PE as well as important points to be considered and the limits of this biomarker. In conclusion, D‑dimers are a reliable biomarker for excluding PE if used in combination with the clinical pretest probability. Test-specific thresholds must be used. In patients aged 50 years or above, age-adjusted cut-offs should be used. The use of D‑dimers is not recommended in patients with certain diseases or in situations that are accompanied by increased D‑dimers without the presence of PE. Such situations include malignancies, major surgery, infections and pregnancy.

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Literatur

  1. Carrier M, Lee AY, Bates SM et al (2008) Accuracy and usefulness of a clinical prediction rule and D‑dimer testing in excluding deep vein thrombosis in cancer patients. Thromb Res 123:177–183

    Article  CAS  Google Scholar 

  2. Carrier M, Righini M, Djurabi RK et al (2009) VIDAS D‑dimer in combination with clinical pre-test probability to rule out pulmonary embolism. A systematic review of management outcome studies. Thromb Haemost 101:886–892

    Article  CAS  Google Scholar 

  3. Christersson C, Wallentin L, Andersson U et al (2014) D‑dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation−observations from the ARISTOTLE trial. J Thromb Haemost 12:1401–1412

    Article  CAS  Google Scholar 

  4. Dahlback B (2000) Blood coagulation. Lancet 355:1627–1632

    Article  CAS  Google Scholar 

  5. Davie EW, Ratnoff OD (1964) Waterfall sequence for intrinsic blood clotting. Science 145:1310–1312

    Article  CAS  Google Scholar 

  6. Dempfle CE (2005) Bestimmung des D‑Dimers in der klinischen Routine. Dtsch Arztebl 102:A428–A432

    Google Scholar 

  7. Dempfle CE (2005) Validation, calibration, and specificity of quantitative D‑dimer assays. Semin Vasc Med 5:315–320

    Article  Google Scholar 

  8. Deutsche Gesellschaft für Kardiologie – Herz-und Kreislaufforschung e. V. (2015) ESC Pocket Guidelines. Management der akuten Lungenembolie, Version 2014. Börm Bruckmeier Verlag, Grünwald

    Google Scholar 

  9. Douma RA, le Gal G, Sohne M et al (2010) Potential of an age adjusted D‑dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. BMJ 340:c1475

    Article  Google Scholar 

  10. Le Gal G, Righini M, Roy PM et al (2006) Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 144:165–171

    Article  Google Scholar 

  11. Geersing GJ, Janssen KJ, Oudega R et al (2009) Excluding venous thromboembolism using point of care D‑dimer tests in outpatients: a diagnostic meta-analysis. BMJ 339:b2990

    Article  CAS  Google Scholar 

  12. Geersing GJ, Toll DB, Janssen KJ et al (2010) Diagnostic accuracy and user-friendliness of 5 point-of-care D‑dimer tests for the exclusion of deep vein thrombosis. Clin Chem 56:1758–1766

    Article  CAS  Google Scholar 

  13. Geersing GJ, Zuithoff NP, Kearon C et al (2014) Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis. BMJ 348:g1340

    Article  CAS  Google Scholar 

  14. Giannitsis E, Mair J, Christersson C et al (2017) How to use D‑dimer in acute cardiovascular care. Eur Heart J Acute Cardiovasc Care 6:69–80

    Article  Google Scholar 

  15. Hellenkamp K, Pruszczyk P, Jimenez D et al (2018) Prognostic impact of copeptin in pulmonary embolism: a multicentre validation study. Eur Respir J 51(4):pii:1702037. https://doi.org/10.1183/13993003.02037-2017

    Article  CAS  Google Scholar 

  16. Kline JA, Williams GW, Hernandez-Nino J (2005) D‑dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem 51:825–829

    Article  CAS  Google Scholar 

  17. Klok FA, Mos IC, Nijkeuter M et al (2008) Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Arch Intern Med 168:2131–2136

    Article  Google Scholar 

  18. Konstantinides SV, Torbicki A, Agnelli G et al (2014) 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 35:3033–3069, 3069a–3069k

    Article  CAS  Google Scholar 

  19. Kostrubiec M, Labyk A, Pedowska-Wloszek J et al (2010) Assessment of renal dysfunction improves troponin-based short-term prognosis in patients with acute symptomatic pulmonary embolism. J Thromb Haemost 8:651–658

    Article  CAS  Google Scholar 

  20. Kostrubiec M, Labyk A, Pedowska-Wloszek J et al (2012) Neutrophil gelatinase-associated lipocalin, cystatin C and eGFR indicate acute kidney injury and predict prognosis of patients with acute pulmonary embolism. Heart 98:1221–1228

    Article  CAS  Google Scholar 

  21. Lankheit MHL, Konstantinides S (2018) Akute Lungenembolie – Update 2018. Kardio Up2date 14(01):67–81

    Article  Google Scholar 

  22. Lee AY, Julian JA, Levine MN et al (1999) Clinical utility of a rapid whole-blood D‑dimer assay in patients with cancer who present with suspected acute deep venous thrombosis. Ann Intern Med 131:417–423

    Article  CAS  Google Scholar 

  23. Luxembourg B, Krause M, Lindhoff-Last E (2007) Basiswissen Gerinnungslabor. Dtsch Arztebl 104(21):A1489–A1498

    Google Scholar 

  24. Macfarlane RG (1964) An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 202:498–499

    Article  CAS  Google Scholar 

  25. Marill KA (2008) Serum D‑dimer is a sensitive test for the detection of acute aortic dissection: a pooled meta-analysis. J Emerg Med 34:367–376

    Article  Google Scholar 

  26. Perrier A, Desmarais S, Miron MJ et al (1999) Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 353:190–195

    Article  CAS  Google Scholar 

  27. Pöss J, Freund A (2018) Lungenarterienembolie: Prozessorientierte und standardisierte Umsetzung der nationalen und internationalen Leitlinien. Kardiologe 12:68–82

    Article  Google Scholar 

  28. Righini M, Goehring C, Bounameaux H et al (2000) Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med 109:357–361

    Article  CAS  Google Scholar 

  29. Righini M, Van Es J, Den Exter PL et al (2014) Age-adjusted D‑dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 311:1117–1124

    Article  CAS  Google Scholar 

  30. Rumley A, Emberson JR, Wannamethee SG et al (2006) Effects of older age on fibrin D‑dimer, C‑reactive protein, and other hemostatic and inflammatory variables in men aged 60–79 years. J Thromb Haemost 4:982–987

    Article  CAS  Google Scholar 

  31. Schouten HJ, Geersing GJ, Koek HL et al (2013) Diagnostic accuracy of conventional or age adjusted D‑dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ 346:f2492

    Article  Google Scholar 

  32. Schrecengost JE, LeGallo RD, Boyd JC et al (2003) Comparison of diagnostic accuracies in outpatients and hospitalized patients of D‑dimer testing for the evaluation of suspected pulmonary embolism. Clin Chem 49:1483–1490

    Article  CAS  Google Scholar 

  33. Shimony A, Filion KB, Mottillo S et al (2011) Meta-analysis of usefulness of d‑dimer to diagnose acute aortic dissection. Am J Cardiol 107:1227–1234

    Article  CAS  Google Scholar 

  34. Sodeck G, Domanovits H, Schillinger M et al (2007) D‑dimer in ruling out acute aortic dissection: a systematic review and prospective cohort study. Eur Heart J 28:3067–3075

    Article  Google Scholar 

  35. Wayne PA (2011) Quantitative D‑dimer for the exclusion of venous thromboembolic disease: approved guideline. CLSI document H59-A

    Google Scholar 

  36. Wells PS, Hirsh J, Anderson DR et al (1995) Accuracy of clinical assessment of deep-vein thrombosis. Lancet 345:1326–1330

    Article  CAS  Google Scholar 

  37. Wells PS, Anderson DR, Rodger M et al (2003) Evaluation of D‑dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 349:1227–1235

    Article  CAS  Google Scholar 

  38. Wicki J, Perneger TV, Junod AF et al (2001) Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 161:92–97

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Universitäres Herzzentrum Lübeck, Medizinische Klinik II (Kardiologie, Angiologie, Intensivmedizin), Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    S. Kupp &  J. Pöss

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S. Kupp und J. Pöss geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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G. Hasenfuß, Göttingen

S. von Haehling, Göttingen

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Kupp, S., Pöss, J. Bedeutung von Biomarkern bei der Lungenarterienembolie. Internist 60, 571–577 (2019). https://doi.org/10.1007/s00108-019-0607-6

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