D-dimer: old dogmas, new (COVID-19) tricks.
COVID-19
D-dimer
SARS-CoV-2
thrombosis
venous thromboembolism
Journal
Clinical chemistry and laboratory medicine
ISSN: 1437-4331
Titre abrégé: Clin Chem Lab Med
Pays: Germany
ID NLM: 9806306
Informations de publication
Date de publication:
25 04 2023
25 04 2023
Historique:
received:
04
07
2022
accepted:
04
07
2022
medline:
3
4
2023
pubmed:
19
7
2022
entrez:
18
7
2022
Statut:
epublish
Résumé
D-dimer is a fibrin degradation product encompassing multiple cross-linked D domains and/or E domains present in the original fibrinogen molecule, whose generation is only theoretically possible when hemostasis and fibrinolysis pathways are concomitantly activated. D-dimer measurement has now become a pillar in the diagnosis/exclusion and prognostication of venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC), when incorporated into validated clinical algorithms and especially using age-adjusted diagnostic thresholds. Although emerging evidence is also supporting its use for predicting the duration of anticoagulant therapy in certain categories of patients, the spectrum of clinical applications is constantly expanding beyond traditional thrombotic pathologies to the diagnosis of acute aortic dissection, acute intestinal ischemia and cerebral venous thrombosis among others, embracing also clinical management of coronavirus disease 2019 (COVID-19). Recent findings attest that D-dimer elevations are commonplace in patients with severe acute respiratory syndrome (SARS-CoV-2) infection (especially in those with thrombosis), its value predicts the clinical severity (up to death) of COVID-19 and remains more frequently increased in COVID-19 patients with post-discharge clinical sequelae. Further, D-dimer-based anticoagulant escalation may be associated with a lower risk of death in patients with severe SARS-CoV-2 infection and, finally, D-dimer elevation post-COVID-19 vaccination mirrors an increased risk of developing vaccine-induced thrombocytopenia and thrombosis (VITT).
Identifiants
pubmed: 35849562
pii: cclm-2022-0633
doi: 10.1515/cclm-2022-0633
doi:
Substances chimiques
fibrin fragment D
0
Fibrin Fibrinogen Degradation Products
0
COVID-19 Vaccines
0
Anticoagulants
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
841-850Informations de copyright
© 2022 Walter de Gruyter GmbH, Berlin/Boston.
Références
Lippi, G, Adcock, D, Favaloro, EJ. Understanding the “philosophy” of laboratory hemostasis. Diagnosis 2019;6:223–6. https://doi.org/10.1515/dx-2018-0099 .
doi: 10.1515/dx-2018-0099
Lippi, G, Favaloro, EJ. Laboratory hemostasis: from biology to the bench. Clin Chem Lab Med 2018;56:1035–45. https://doi.org/10.1515/cclm-2017-1205 .
doi: 10.1515/cclm-2017-1205
Dickneite, G, Herwald, H, Korte, W, Allanore, Y, Denton, CP, Matucci Cerinic, M. Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions. Thromb Haemostasis 2015;113:686–97. https://doi.org/10.1160/th14-07-0625 .
doi: 10.1160/th14-07-0625
Thachil, J, Lippi, G, Favaloro, EJ. D-dimer testing: laboratory aspects and current issues. Methods Mol Biol 2017;1646:91–104.
Kearon, C, de Wit, K, Parpia, S, Schulman, S, Afilalo, M, Hirsch, A, et al.. Diagnosis of pulmonary embolism with d-dimer adjusted to clinical probability. N Engl J Med 2019;381:2125–34. https://doi.org/10.1056/nejmoa1909159 .
doi: 10.1056/nejmoa1909159
Lippi, G, Franchini, M, Targher, G, Favaloro, EJ. Help me, doctor! my D-dimer is raised. Ann Med 2008;40:594–605. https://doi.org/10.1080/07853890802161015 .
doi: 10.1080/07853890802161015
Lippi, G, Bonfanti, L, Saccenti, C, Cervellin, G. Causes of elevated D-dimer in patients admitted to a large urban emergency department. Eur J Intern Med 2014;25:45–8. https://doi.org/10.1016/j.ejim.2013.07.012 .
doi: 10.1016/j.ejim.2013.07.012
Ageno, W, Squizzato, A, Wells, PS, Büller, HR, Johnson, G. The diagnosis of symptomatic recurrent pulmonary embolism and deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemostasis 2013;11:1597–602. https://doi.org/10.1111/jth.12301 .
doi: 10.1111/jth.12301
Konstantinides, SV, Meyer, G, Becattini, C, Bueno, H, Geersing, GJ, Harjola, VP, et al.. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS): the task force for the diagnosis and management of acute pulmonary embolism of the European society of cardiology (ESC). Eur Respir J 2019;54:1901647. https://doi.org/10.1183/13993003.01647-2019 .
doi: 10.1183/13993003.01647-2019
Lim, W, Le Gal, G, Bates, SM, Righini, M, Haramati, LB, Lang, E, et al.. American society of hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv 2018;2:3226–56. https://doi.org/10.1182/bloodadvances.2018024828 .
doi: 10.1182/bloodadvances.2018024828
Raja, AS, Greenberg, JO, Qaseem, A, Denberg, TD, Fitterman, N, Schuur, JD. Evaluation of patients with suspected acute pulmonary embolism: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med 2015;163:701–11. https://doi.org/10.7326/m14-1772 .
doi: 10.7326/m14-1772
Bates, SM, Jaeschke, R, Stevens, SM, Goodacre, S, Wells, PS, Stevenson, MD, et al.. 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. https://doi.org/10.1378/chest.11-2299 .
doi: 10.1378/chest.11-2299
National Institute for Health Care and Excellence . Venous thromboembolic diseases: diagnosis, management and thrombophilia testing – NICE guideline [NG158] ; Published: 26 March 2020 [Accessed 30 Jun 2022].
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;52:621–8. https://doi.org/10.1515/cclm-2013-0706 .
doi: 10.1515/cclm-2013-0706
Stevens, SM, Woller, SC, Kreuziger, LB, Bounameaux, H, Doerschug, K, Geersing, GJ, et al.. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest 2021;160:e545–608. https://doi.org/10.1016/j.chest.2021.07.055 .
doi: 10.1016/j.chest.2021.07.055
Rodger, MA, Kahn, SR, Wells, PS, Anderson, DA, Chagnon, I, Le Gal, G, et al.. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ (Can Med Assoc J) 2008;179:417–26. https://doi.org/10.1503/cmaj.080493 .
doi: 10.1503/cmaj.080493
Legnani, C, Palareti, G, Cosmi, B, Cini, M, Tosetto, A, Tripodi, A, PROLONG Investigators (FCSA and Italian Federation of Thrombosis Centers) . Different cut-off values of quantitative D-dimer methods to predict the risk of venous thromboembolism recurrence: a post-hoc analysis of the PROLONG study. Haematologica 2008;93:900–7. https://doi.org/10.3324/haematol.12320 .
doi: 10.3324/haematol.12320
Legnani, C, Cini, M, Cosmi, B, Carraro, P, Tripodi, A, Erba, N, et al.. Age and gender specific cut-off values to improve the performance of D-dimer assays to predict the risk of venous thromboembolism recurrence. Intern Emerg Med 2013;8:229–36. https://doi.org/10.1007/s11739-011-0608-5 .
doi: 10.1007/s11739-011-0608-5
Rodger, MA, Le Gal, G, Langlois, NJ, Gin, B, Mallick, R, Giulivi, A, et al.. HERDOO2 clinical decision rule to guide duration of anticoagulation in women with unprovoked venous thromboembolism. Can I use any D-dimer? Thromb Res 2018;169:82–6. https://doi.org/10.1016/j.thromres.2018.07.020 .
doi: 10.1016/j.thromres.2018.07.020
Eichinger, S, Heinze, G, Kyrle, PA. D-dimer levels over time and the risk of recurrent venous thromboembolism: an update of the Vienna prediction model. J Am Heart Assoc 2014;3:e000467. https://doi.org/10.1161/jaha.113.000467 .
doi: 10.1161/jaha.113.000467
de Winter, MA, van Es, N, Büller, HR, Visseren, FLJ, Nijkeuter, M. Prediction models for recurrence and bleeding in patients with venous thromboembolism: a systematic review and critical appraisal. Thromb Res 2021;199:85–96. https://doi.org/10.1016/j.thromres.2020.12.031 .
doi: 10.1016/j.thromres.2020.12.031
Iba, T, Levi, M, Levy, JH. Sepsis-induced coagulopathy and disseminated intravascular coagulation. Semin Thromb Hemost 2020;46:89–95. https://doi.org/10.1055/s-0039-1694995 .
doi: 10.1055/s-0039-1694995
Favaloro, EJ. Laboratory testing in disseminated intravascular coagulation. Semin Thromb Hemost 2010;36:458–67. https://doi.org/10.1055/s-0030-1254055 .
doi: 10.1055/s-0030-1254055
Toh, CH, Hoots, WK, SSC on Disseminated Intravascular Coagulation of the ISTH . The scoring system of the scientific and standardisation committee on disseminated intravascular coagulation of the international society on thrombosis and haemostasis: a 5-year overview. J Thromb Haemostasis 2007;5:604–6. https://doi.org/10.1111/j.1538-7836.2007.02313.x .
doi: 10.1111/j.1538-7836.2007.02313.x
Levi, M, Toh, CH, Thachil, J, Watson, HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British committee for standards in haematology. Br J Haematol 2009;145:24–33. https://doi.org/10.1111/j.1365-2141.2009.07600.x .
doi: 10.1111/j.1365-2141.2009.07600.x
Wada, H, Thachil, J, Di Nisio, M, Mathew, P, Kurosawa, S, Gando, S, et al.. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemostasis 2013;4. https://doi.org/10.1111/jth.12155 [Epub ahead of print].
doi: 10.1111/jth.12155
Takemitsu, T, Wada, H, Hatada, T, Ohmori, Y, Ishikura, K, Takeda, T, et al.. Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation. Thromb Haemostasis 2011;105:40–4. https://doi.org/10.1160/th10-05-0293 .
doi: 10.1160/th10-05-0293
Suzuki, K, Wada, H, Imai, H, Iba, T, Thachil, J, Toh, CH, et al.. A re-evaluation of the D-dimer cut-off value for making a diagnosis according to the ISTH overt-DIC diagnostic criteria: communication from the SSC of the ISTH. J Thromb Haemostasis 2018;16:1442–4. https://doi.org/10.1111/jth.14134 .
doi: 10.1111/jth.14134
Liu, Y, Cai, J, Wang, C, Jin, J, Qu, L. A systematic review and meta-analysis of incidence, prognosis, and laboratory indicators of venous thromboembolism in hospitalized patients with coronavirus disease 2019. J Vasc Surg Venous Lymphat Disord 2021;9:1099–111. https://doi.org/10.1016/j.jvsv.2021.01.012 .
doi: 10.1016/j.jvsv.2021.01.012
Xiao, D, Tang, F, Chen, L, Gao, H, Li, X. Cumulative evidence for the association of thrombosis and the prognosis of COVID-19: systematic review and meta-analysis. Front Cardiovasc Med 2022;8:819318. https://doi.org/10.3389/fcvm.2021.819318 .
doi: 10.3389/fcvm.2021.819318
Vitaliti, G, Giacchi, V, Sciacca, M, Ruggieri, M, Falsaperla, R. Thrombotic events in children and adolescent patients with SARS-Cov-2 infection: a systematic review with meta-analysis on incidence and management. Expet Rev Hematol 2022;27. https://doi.org/10.1080/17474086.2022.2094758 [Epub ahead of print].
doi: 10.1080/17474086.2022.2094758
Lippi, G, Favaloro, EJ. D-Dimer is associated with severity of coronavirus disease 2019: a pooled analysis. Thromb Haemostasis 2020;120:876–8. https://doi.org/10.1055/s-0040-1709650 .
doi: 10.1055/s-0040-1709650
Varikasuvu, SR, Varshney, S, Dutt, N, Munikumar, M, Asfahan, S, Kulkarni, PP, et al.. D-dimer, disease severity, and deaths (3D-study) in patients with COVID-19: a systematic review and meta-analysis of 100 studies. Sci Rep 2021;11:21888. https://doi.org/10.1038/s41598-021-01462-5 .
doi: 10.1038/s41598-021-01462-5
Whyte, CS, Simpson, M, Morrow, GB, Wallace, CA, Mentzer, AJ, Knight, JC, et al.. The suboptimal fibrinolytic response in COVID-19 is dictated by high PAI-1. J Thromb Haemostasis 2022;3. https://doi.org/10.1111/jth.15806 [Epub ahead of print].
doi: 10.1111/jth.15806
Galland, J, Thoreau, B, Delrue, M, Neuwirth, M, Stepanian, A, Chauvin, A, et al.. White blood count, D-dimers, and ferritin levels as predictive factors of pulmonary embolism suspected upon admission in noncritically ill COVID-19 patients: the French multicenter CLOTVID retrospective study. Eur J Haematol 2021;107:190–201. https://doi.org/10.1111/ejh.13638 .
doi: 10.1111/ejh.13638
Riyahi, S, Hectors, SJ, Prince, MR, Sweeney, EM, Lane, EG, Honya, R, et al.. Predictors of acute deep venous thrombosis in patients hospitalized for COVID-19. Medicine (Baltim) 2021;100:e27216. https://doi.org/10.1097/md.0000000000027216 .
doi: 10.1097/md.0000000000027216
Maatman, TK, Jalali, F, Feizpour, C, Douglas, A2nd, McGuire, SP, Kinnaman, G, et al.. Routine venous thromboembolism prophylaxis may Be inadequate in the hypercoagulable state of severe coronavirus disease 2019. Crit Care Med 2020;48:e783–90. https://doi.org/10.1097/ccm.0000000000004466 .
doi: 10.1097/ccm.0000000000004466
Naymagon, L, Zubizarreta, N, Feld, J, van Gerwen, M, Alsen, M, Thibaud, S, et al.. Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19. Thromb Res 2020;196:99–105. https://doi.org/10.1016/j.thromres.2020.08.032 .
doi: 10.1016/j.thromres.2020.08.032
Lippi, G, Favaloro, EJ. Cerebral venous thrombosis developing after COVID-19 vaccination: VITT, VATT, TTS, and more. Semin Thromb Hemost 2022;48:8–14. https://doi.org/10.1055/s-0041-1736168 .
doi: 10.1055/s-0041-1736168
Fazio, S, Tufano, A, de Simone, G. Sustained high D-dimer in outpatients who have recovered from mild to moderate coronavirus disease 2019 (COVID-19). Semin Thromb Hemost 2022;48:115–7. https://doi.org/10.1055/s-0041-1729857 .
doi: 10.1055/s-0041-1729857
Engelen, MM, Vandenbriele, C, Balthazar, T, Claeys, E, Gunst, J, Guler, I, et al.. Venous thromboembolism in patients discharged after COVID-19 hospitalization. Semin Thromb Hemost 2021;47:362–71. https://doi.org/10.1055/s-0041-1727284 .
doi: 10.1055/s-0041-1727284
Atalay, B, Cesur, A, Agirbasli, M. The Discrepancy between biomarkers of lung injury and 1-year mortality in COVID-19. Eur J Clin Invest 2022;26:e13827. https://doi.org/10.1111/eci.13827 .
doi: 10.1111/eci.13827
Lehmann, A, Prosch, H, Zehetmayer, S, Gysan, MR, Bernitzky, D, Vonbank, K, et al.. Impact of persistent D-dimer elevation following recovery from COVID-19. PLoS One 2021;16:e0258351. https://doi.org/10.1371/journal.pone.0258351 .
doi: 10.1371/journal.pone.0258351
Li, P, Zhao, W, Kaatz, S, Latack, K, Schultz, L, Poisson, L. Factors associated with risk of postdischarge thrombosis in patients with COVID-19. JAMA Netw Open 2021;4:e2135397. https://doi.org/10.1001/jamanetworkopen.2021.35397 .
doi: 10.1001/jamanetworkopen.2021.35397
Tassiopoulos, AK, Mofakham, S, Rubano, JA, Labropoulos, N, Bannazadeh, M, Drakos, P, et al.. D-dimer-driven anticoagulation reduces mortality in intubated COVID-19 patients: a cohort study with a propensity-matched analysis. Front Med 2021;8:631335. https://doi.org/10.3389/fmed.2021.631335 .
doi: 10.3389/fmed.2021.631335
Arachchillage, DRJ, Shi, C, Saliu, D, Kozman, P, Mi, E, Buti, N, et al.. Efficacy and safety of D-dimer, weight, and renal function-adjusted thromboprophylaxis in patients with coronavirus disease 2019 (COVID-19). Semin Thromb Hemost 2021;47:436–41.
Barnes, GD, Burnett, A, Allen, A, Ansell, J, Blumenstein, M, Clark, NP, et al.. Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 2022;17:1–14. https://doi.org/10.1007/s11239-022-02643-3 .
doi: 10.1007/s11239-022-02643-3
García-Cervera, C, Giner-Galvañ, V, Wikman-Jorgensen, P, Laureiro, J, Rubio-Rivas, M, Gurjian Arena, A, et al.. Estimation of admission D-dimer cut-off value to predict venous thrombotic events in hospitalized COVID-19 patients: analysis of the SEMI-COVID-19 registry. J Gen Intern Med 2021;36:3478–86. https://doi.org/10.1007/s11606-021-07017-8 .
doi: 10.1007/s11606-021-07017-8
Thachil, J, Longstaff, C, Favaloro, EJ, Lippi, G, Urano, T, Kim, PY. The need for accurate D-dimer reporting in COVID-19: communication from the ISTH SSC on fibrinolysis. J Thromb Haemostasis 2020;18:2408–11. https://doi.org/10.1111/jth.14956 .
doi: 10.1111/jth.14956
Favaloro, EJ, Thachil, J. Reporting of D-dimer data in COVID-19: some confusion and potential for misinformation. Clin Chem Lab Med 2020;58:1191–9. https://doi.org/10.1515/cclm-2020-0573 .
doi: 10.1515/cclm-2020-0573
de Guadiana-Romualdo, LG, Morell-García, D, Favaloro, EJ, Vílchez, JA, Bauça, JM, Martín, MJA, et al.. Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: results from a Spanish multicenter registry (BIOCOVID-Spain study). J Thromb Thrombolysis 2022;53:103–12. https://doi.org/10.1007/s11239-021-02527-y .
doi: 10.1007/s11239-021-02527-y
Favaloro, EJ, Lippi, G. Recommendations for minimal laboratory testing panels in patients with COVID-19: potential for prognostic monitoring. Semin Thromb Hemost 2020;46:379–82. https://doi.org/10.1055/s-0040-1709498 .
doi: 10.1055/s-0040-1709498
Hardy, M, Lecompte, T, Douxfils, J, Lessire, S, Dogné, JM, Chatelain, B, et al.. Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory. Thromb J 2020;18:17. https://doi.org/10.1186/s12959-020-00230-1 .
doi: 10.1186/s12959-020-00230-1
Spyropoulos, AC, Levy, JH, Ageno, W, Connors, JM, Hunt, BJ, Iba, T, et al.. Scientific and standardization committee communication: clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemostasis 2020;18:1859–65. https://doi.org/10.1111/jth.14929 .
doi: 10.1111/jth.14929
Ortel, TL, Neumann, I, Ageno, W, Beyth, R, Clark, NP, Cuker, A, et al.. American society of hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020;4:4693–738. https://doi.org/10.1182/bloodadvances.2020001830 .
doi: 10.1182/bloodadvances.2020001830
Orsi, FA, De Paula, EV, Santos, FO, Teruchkin, MM, Campêlo, DHC, Mello, TT, et al.. Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian society of thrombosis and hemostasis and the thrombosis and hemostasis committee of the Brazilian association of hematology, hemotherapy and cellular therapy. Hematol Transfus Cell Ther 2020;42:300–8. https://doi.org/10.1016/j.htct.2020.06.001 .
doi: 10.1016/j.htct.2020.06.001
National Institute for Health Care and Excellence . COVID-19 rapid guideline: managing COVID-19 – last updated: 15 June 2022 . Available from: https://www.nice.org.uk/guidance/ng191 [Accessed 30 Jun 2022].
Task Force for the Management of COVID-19 of the European Society of Cardiology , Baigent, C, Windecker, S, Andreini, D, Arbelo, E, Barbato, E, Bartorelli, AL, et al.. European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis. Cardiovasc Res 2022;118:1385–412. https://doi.org/10.1093/cvr/cvab342 .
doi: 10.1093/cvr/cvab342
Gorog, DA, Storey, RF, Gurbel, PA, Tantry, US, Berger, JS, Chan, MY, et al.. Current and novel biomarkers of thrombotic risk in COVID-19: a consensus statement from the international COVID-19 thrombosis biomarkers colloquium. Nat Rev Cardiol 2022;19:475–95. https://doi.org/10.1038/s41569-021-00665-7 .
doi: 10.1038/s41569-021-00665-7
Favresse, J, Lippi, G, Roy, PM, Chatelain, B, Jacqmin, H, Ten Cate, H, et al.. D-dimer: preanalytical, analytical, postanalytical variables, and clinical applications. Crit Rev Clin Lab Sci 2018;55:548–77. https://doi.org/10.1080/10408363.2018.1529734 .
doi: 10.1080/10408363.2018.1529734