Semin Thromb Hemost 2015; 41(03): 287-293
DOI: 10.1055/s-0035-1549092
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

International Survey on D-Dimer Test Reporting: A Call for Standardization

Giuseppe Lippi
1   Department of Clinical Chemistry and Hematology, Academic Hospital of Parma, Parma, Italy
,
Armando Tripodi
2   Department of Clinical Sciences and Community Health, University of Milano, Italy
3   IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
,
Ana-Maria Simundic
4   University Department of Chemistry, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia
,
Emmanuel J. Favaloro
5   Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, NSW Health Pathology, Westmead, New South Wales, Australia
› Author Affiliations
Further Information

Publication History

Publication Date:
03 April 2015 (online)

Abstract

D-dimer is the biochemical gold standard for diagnosing a variety of thrombotic disorders, but result reporting is heterogeneous in clinical laboratories. A specific five-item questionnaire was developed to gain a clear picture of the current standardization of D-dimer test results. The questionnaire was opened online (December 24, 2014–February 10, 2015) on the platform “Google Drive (Google Inc., Mountain View; CA),” and widely disseminated worldwide by newsletters and alerts. A total of 409 responses were obtained during the period of data capture, the largest of which were from Italy (136; 33%), Australia (55; 22%), Croatia (29; 7%), Serbia (26; 6%), and the United States (21; 5%). Most respondents belonged to laboratories in general hospitals (208; 51%), followed by laboratories in university hospitals (104; 26%), and the private sector (94; 23%). The majority of respondents (i.e., 246; 60%) indicated the use of fibrinogen equivalent unit for expressing D-dimer results, with significant heterogeneities across countries and health care settings. The highest prevalence of laboratories indicated they were using “ng/mL” (139; 34%), followed by “mg/L” (136; 33%), and “µg/L” (73; 18%), with significant heterogeneity across countries but not among different health care settings. Expectedly, the vast majority of laboratories (379; 93%) declared to be using a fixed cutoff rather than an age-adjusted threshold, with no significant heterogeneity across countries and health care settings. The results of this survey attest that at least 28 different combinations of measurement units are currently used to report D-dimer results worldwide, and this evidence underscores the urgent need for more effective international joined efforts aimed to promote a worldwide standardization of D-dimer results reporting.

 
  • References

  • 1 Lippi G, Cervellin G, Franchini M, Favaloro EJ. Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future. J Thromb Thrombolysis 2010; 30 (4) 459-471
  • 2 Bates SM. D-dimer assays in diagnosis and management of thrombotic and bleeding disorders. Semin Thromb Hemost 2012; 38 (7) 673-682
  • 3 Lippi G, Franchini M, Targher G, Favaloro EJ. Help me, Doctor! My D-dimer is raised. Ann Med 2008; 40 (8) 594-605
  • 4 Lippi G, Favaloro EJ. D-dimer measurement and laboratory feedback. J Emerg Med 2009; 37 (1) 82-83 , author reply 83
  • 5 Favaloro EJ, Franchini M, Lippi G. Aging hemostasis: changes to laboratory markers of hemostasis as we age - a narrative review. Semin Thromb Hemost 2014; 40 (6) 621-633
  • 6 Lippi G, Favaloro EJ, Cervellin G. A review of the value of D-dimer testing for prediction of recurrent venous thromboembolism with increasing age. Semin Thromb Hemost 2014; 40 (6) 634-639
  • 7 Lippi G, Montagnana M. D-dimer testing in pregnancy: clinically useful, but at what cost?. Ann Intern Med 2008; 148 (6) 484 , author reply 484–485
  • 8 Bates SM, Jaeschke R, Stevens SM , et al; American College of Chest Physicians. Diagnosis of DVT: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (2 Suppl) e351S-418S
  • 9 Bogavac-Stanojević N, Dopsaj V, Jelić-Ivanović Z, Lakić D, Vasić D, Petrova G. Economic evaluation of different screening alternatives for patients with clinically suspected acute deep vein thrombosis. Biochem Med (Zagreb) 2013; 23 (1) 96-106
  • 10 Lippi G, Cervellin G, Casagranda I, Morelli B, Testa S, Tripodi A. D-dimer testing for suspected venous thromboembolism in the emergency department. Consensus document of AcEMC, CISMEL, SIBioC, and SIMeL. Clin Chem Lab Med 2014; 52 (5) 621-628
  • 11 Lippi G, Plebani M. False myths and legends in laboratory diagnostics. Clin Chem Lab Med 2013; 51 (11) 2087-2097
  • 12 Hogg K, Wells PS, Gandara E. The diagnosis of venous thromboembolism. Semin Thromb Hemost 2012; 38 (7) 691-701
  • 13 Levi M, van der Poll T. A short contemporary history of disseminated intravascular coagulation. Semin Thromb Hemost 2014; 40 (8) 874-880
  • 14 Dentali F, Squizzato A, Marchesi C, Bonzini M, Ferro JM, Ageno W. D-dimer testing in the diagnosis of cerebral vein thrombosis: a systematic review and a meta-analysis of the literature. J Thromb Haemost 2012; 10 (4) 582-589
  • 15 Karska-Basta I, Kubicka-Trzaska A, Pogrzebielski A, Romanowska-Dixon B. A new insight into retinal vein occlusion pathogenesis. Klin Oczna 2013; 115 (4) 269-274
  • 16 Cervellin G, Lippi G. Of MIs and men—a historical perspective on the diagnostics of acute myocardial infarction. Semin Thromb Hemost 2014; 40 (5) 535-543
  • 17 Wiseman S, Marlborough F, Doubal F, Webb DJ, Wardlaw J. Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis. Cerebrovasc Dis 2014; 37 (1) 64-75
  • 18 McDermott MM, Liu K, Ferrucci L , et al. Circulating blood markers and functional impairment in peripheral arterial disease. J Am Geriatr Soc 2008; 56 (8) 1504-1510
  • 19 Salvagno GL, Targher G, Franchini M, Lippi G. Plasma D-dimer in the diagnosis of acute aortic dissection. Eur Heart J 2008; 29 (9) 1207 , author reply 1207–1208
  • 20 Oshiro A, Yanagida Y, Gando S, Henzan N, Takahashi I, Makise H. Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation. Crit Care 2014; 18 (2) R61
  • 21 Lippi G, Veraldi GF, Fraccaroli M, Manzato F, Cordiano C, Guidi G. Variation of plasma D-dimer following surgery: implications for prediction of postoperative venous thromboembolism. Clin Exp Med 2001; 1 (3) 161-164
  • 22 Rodelo JR, De la Rosa G, Valencia ML , et al. D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. Am J Emerg Med 2012; 30 (9) 1991-1999
  • 23 Gomes M, Khorana AA. Risk assessment for thrombosis in cancer. Semin Thromb Hemost 2014; 40 (3) 319-324
  • 24 Danese E, Montagnana M, Cervellin G, Lippi G. Hypercoagulability, D-dimer and atrial fibrillation: an overview of biological and clinical evidence. Ann Med 2014; 46 (6) 364-371
  • 25 Dempfle CE. D-dimer: standardization versus harmonization. Thromb Haemost 2006; 95 (3) 399-400
  • 26 Madoiwa S, Kitajima I, Ohmori T, Sakata Y, Mimuro J. Distinct reactivity of the commercially available monoclonal antibodies of D-dimer and plasma FDP testing to the molecular variants of fibrin degradation products. Thromb Res 2013; 132 (4) 457-464
  • 27 Crowther MA, Bates SM, Keeney M, Raby A, Flynn G. Human-derived D-dimer for external quality assessment: results of four surveys in Ontario. Am J Clin Pathol 2008; 130 (5) 805-810
  • 28 Olson JD, Cunningham MT, Higgins RA, Eby CS, Brandt JT. D-dimer: simple test, tough problems. Arch Pathol Lab Med 2013; 137 (8) 1030-1038
  • 29 Plebani M, Favaloro EJ, Lippi G. Patient safety and quality in laboratory and hemostasis testing: a renewed loop?. Semin Thromb Hemost 2012; 38 (6) 553-558
  • 30 Favaloro EJ, Lippi G. Laboratory reporting of hemostasis assays: the final post-analytical opportunity to reduce errors of clinical diagnosis in hemostasis?. Clin Chem Lab Med 2010; 48 (3) 309-321
  • 31 Raskob GE, Angchaisuksiri P, Blanco AN , et al; ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to global disease burden. Semin Thromb Hemost 2014; 40 (7) 724-735
  • 32 Schouten HJ, Geersing GJ, Koek HL , et al. 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 2013; 346: f2492
  • 33 Bonar R, Favaloro EJ, Adcock DM. Quality in coagulation and haemostasis testing. Biochem Med 2010; 20 (2) 184-199
  • 34 Reber G, de Moerloose P, Standardization of D-dimer Testing. In: Quality in Laboratory Hemostasis and Thrombosis, 2nd ed. Kitchen S, Olson JD, Preston FE , eds. Oxford, United Kingdm: John Wiley & Sons; 2013
  • 35 Medved L, Weisel JW ; Fibrinogen and Factor XIII Subcommittee of Scientific Standardization Committee of International Society on Thrombosis and Haemostasis. Recommendations for nomenclature on fibrinogen and fibrin. J Thromb Haemost 2009; 7 (2) 355-359
  • 36 Favaloro EJ, Plebani M, Lippi G. Regulation in hemostasis and thrombosis: part I-in vitro diagnostics. Semin Thromb Hemost 2013; 39 (3) 235-249