ABSTRACT:

D-dimer, product degradation of fibrin, belongs to the most sensitive and specific markers in the diagnostics of thrombotic disorders, mainly acute PE and DVT. This leads to its measurement because of the high sensitivity in ruling out these conditions, thus reducing unnecessary imaging and improving patient management. The importance of D-dimer has been repeatedly said in various studies, notably during the COVID-19 pandemic, where it has been noted as an essential biomarker in the assessment of thrombotic complications, treatment strategy, and prognostic aspects of the patient. This literature review paper covers basic principles and measurements of D-dimer because of up-to-date knowledge on its clinical applications, limitations, and directions for potential future research.

REFERENCES :

1) Álvarez-Pérez, F. J.., Castelo-Branco, M.., & Álvarez-Sabín, J.. (2011). Usefulness of measurement of fibrinogen, D-dimer, D-dimer/fibrinogen ratio, C reactive protein and erythrocyte sedimentation rate to assess the pathophysiology and mechanism of ischaemic stroke. Journal of Neurology, Neurosurgery & Psychiatry , 82 , 986 – 992.
http://doi.org/10.1136/jnnp.2010.230870 
2) Balla, Evangelia D.., Daniilidis, Vasileios., Karlioti, Georgia., Kalamas, Theocharis., Stefanidou, Myrika., Bikiaris, Nikolaos D.., Vlachopoulos, Antonios., Koumentakou, Ioanna., & Bikiaris, D.. (2021). Poly(lactic Acid): A Versatile Biobased Polymer for the Future with Multifunctional Properties—From Monomer Synthesis, Polymerization Techniques and Molecular Weight Increase to PLA Applications. Polymers , 13 . http://doi.org/10.3390/polym13111822
3) Bates, S.., Jaeschke, Roman., Stevens, S.., Goodacre, S.., Wells, P.., Stevenson, M.., Kearon, C.., Schunemann, H.., Crowther, M.., Pauker, S.., Makdissi, R.., & Guyatt, G.. (2012). Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.. Chest , 141 2 Suppl , e351S-e418S . http://doi.org/10.1378/chest.11-2299
4) Berger, J.., Kunichoff, Dennis., Adhikari, S.., Ahuja, T.., Amoroso, N.., Aphinyanaphongs, Y.., Cao, Meng., Goldenberg, R.., Hindenburg, A.., Horowitz, J.., Parnia, S.., Petrilli, C.., Reynolds, H.., Simon, Emma., Slater, J.., Yaghi, S.., Yuriditsky, E.., Hochman, J.., & Horwitz, Leora I.. (2020). Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19. Arteriosclerosis, Thrombosis, and Vascular Biology , 40 , 2539 – 2547.
http://doi.org/10.1161/ATVBAHA.120.314872
5) Demelo-Rodríguez, P.., Cervilla-Muñoz, E.., Ordieres-Ortega, L.., Parra-Virto, A.., Toledano-Macías, M.., Toledo-Samaniego, N.., García-García, Alejandra., García-Fernández-Bravo, Irene., Ji, Z.., de-Miguel-Diez, J.., Alvarez-Sala-Walther, L.., del-Toro-Cervera, J.., Galeano-Valle, Francisco., & Galeano-Valle, Francisco. (2020). Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thrombosis Research , 192 , 23 – 26 . http://doi.org/10.1016/j.thromres.2020.05.018
6) Dessap, A. Mekontso., Deux, J.., Abidi, N.., Lavenu‐Bombled, C.., Melica, G.., Renaud, B.., Godeau, B.., Adnot, S.., Brochard, L.., Brun-Buisson, C.., Galactéros, F.., Rahmouni, A.., Habibi, A.., & Maître, B.. (2011). Pulmonary artery thrombosis during acute chest syndrome in sickle cell disease.. American journal of respiratory and critical care medicine , 184 9 , 1022-9 . http://doi.org/10.1164/rccm.201105-0783OC
7) Douketis, J.., Tosetto, A.., Marcucci, M.., Baglin, T.., Cushman, M.., Eichinger, S.., Palareti, G.., Poli, D.., Tait, R.., & Iorio, A.. (2010). Patient-Level Meta-analysis: Effect of Measurement Timing, Threshold, and Patient Age on Ability of d-Dimer Testing to Assess Recurrence Risk After Unprovoked Venous Thromboembolism. Annals of Internal Medicine , 153 , 523 – 531 . http://doi.org/10.7326/0003-4819-153-8-201010190-00009
8) Douma, R.., Tan, M.., Schutgens, R.., Bates, S.., Perrier, A.., Legnani, C.., Biesma, D.., Ginsberg, Jeffrey S.., Bounameaux, H.., Palareti, G.., Carrier, M.., Mol, G.., Gal, G. Le., Kamphuisen, P.., & Righini, M.. (2012). Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. Haematologica , 97 , 1507 – 1513 . http://doi.org/10.3324/haematol.2011.060657
9) Favresse, J.., Lippi, G.., Roy, P.., Châtelain, B.., Jacqmin, H.., Cate, H. ten., & Mullier, F.. (2018). D-dimer: Preanalytical, analytical, postanalytical variables, and clinical applications. Critical Reviews in Clinical Laboratory Sciences , 55 , 548 – 577 . http://doi.org/10.1080/10408363.2018.1529734
10) Gibson, C.., Spyropoulos, A.., Cohen, A.., Hull, R.., Goldhaber, S.., Yusen, R.., Hernandez, Adrian F.., Korjian, Serge., Daaboul, Y.., Gold, A.., Harrington, R.., & Chi, G.. (2017). The IMPROVEDD VTE Risk Score: Incorporation of D-Dimer into the IMPROVE Score to Improve Venous Thromboembolism Risk Stratification. TH Open: Companion Journal to Thrombosis and Haemostasis , 1 , e56 – e65 . http://doi.org/10.1055/s-0037-1603929
11) Kabrhel, C.., Courtney, D. Mark., Camargo, C.., Plewa, M.., Nordenholz, K.., Moore, C.., Richman, P.., Smithline, H.., Beam, D.., & Kline, J.. (2010). Factors associated with positive D-dimer results in patients evaluated for pulmonary embolism.. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine , 17 6 , 589-97 . http://doi.org/10.1111/j.1553-2712.2010.00765.x
12) Kearon, C.., Wit, K. de., Parpia, S.., Schulman, S.., Afilalo, M.., Hirsch, A.., Spencer, F.., Sharma, Sangita., D’Aragon, F.., Deshaies, J.., Gal, G. Le., Lazo-Langner, A.., Wu, Cynthia., Rudd-Scott, L.., Bates, S.., & Julian, J.. (2019). Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability.. The New England journal of medicine , 381 22 , 2125-2134 . http://doi.org/10.1056/NEJMoa1909159
13) Kesieme, E.., Kesieme, C.., Jebbin, Nze J.., Irekpita, E.., & Dongo, A.. (2011). Deep vein thrombosis: a clinical review. Journal of blood medicine , 2 , 59 – 69 . http://doi.org/10.2147/JBM.S19009
14) Leonard-Lorant, I.., Delabranche, X.., Séverac, F.., Helms, J.., Pauzet, Coralie., Collange, O.., Schneider, F.., Labani, A.., Bilbault, P.., Molière, S.., Leyendecker, P.., Roy, C.., & Ohana, M.. (2020). Acute Pulmonary Embolism in COVID-19 Patients on CT Angiography and Relationship to D-Dimer Levels. Radiology . http://doi.org/10.1148/radiol.2020201561
15) Li, Rui., Shao, H.., Hao, L.., Yu, Baozhan., Qu, P.., Zhou, Yixin., & Chen, Jiying. (2019). Plasma Fibrinogen Exhibits Better Performance Than Plasma D-Dimer in the Diagnosis of Periprosthetic Joint Infection: A Multicenter Retrospective Study. The Journal of Bone and Joint Surgery , 101 , 613–619 . http://doi.org/10.2106/JBJS.18.00624
16) Linkins, L.., & Lapner, S. Takach. (2017). Review of D‐dimer testing: Good, Bad, and Ugly. International Journal of Laboratory Hematology , 39 , 103 – 98 . http://doi.org/10.1111/ijlh.12665
17) Nazerian, P.., Mueller, C.., Soeiro, A.., Leidel, B. A.., Salvadeo, S.., Giachino, F.., Vanni, S.., Grimm, Karin., Oliveira, M.., Pivetta, E.., Lupia, E.., Grifoni, S.., Morello, F.., Capretti, Elisa., Castelli, M.., Gualtieri, S.., Trausi, F.., Battista, S.., Bima, Paolo., Carbone, F.., Tizzani, M.., Veglio, M. G.., Badertscher, P.., Boeddinghaus, J.., Nestelberger, T.., & Twerenbold, R.. (2018). Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study. Circulation, 137, 250–258.
http://doi.org/10.1161/CIRCULATIONAHA.117.029457
18) Olson, J.. (2015). D-dimer: An Overview of Hemostasis and Fibrinolysis, Assays, and Clinical Applications.. Advances in clinical chemistry , 69 , 1-46 . http://doi.org/10.1016/bs.acc.2014.12.001
19) Pol, L. M. van der., Tromeur, C.., Bistervels, I.., Áinle, F. N. Ní., Bemmel, T. van., Bertoletti, L.., Couturaud, F.., Dooren, Yordi van., Elias, A.., Faber, L.., Hofstee, H.., Hulle, T. van der., Kruip, M.., Maignan, M.., Mairuhu, A.., Middeldorp, S.., Nijkeuter, M.., Roy, P.., Sanchez, O.., Schmidt, Jeannot., Wolde, M. ten., Klok, F.., & Huisman, M.. (2019). Pregnancy‐Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. Obstetrical & Gynecological Survey . http://doi.org/10.1097/01.ogx.0000577816.58861.db
20) Poudel, A.., Poudel, Yashasa., Adhikari, A.., Aryal, B.., Dangol, D.., Bajracharya, T.., Maharjan, Anil., & Gautam, R.. (2021). D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS ONE , 16.
http://doi.org/10.1371/journal.pone.0256744
21) Raja, A.., Greenberg, J.., Qaseem, A.., Denberg, Thomas D.., Fitterman, N.., & Schuur, J.. (2015). Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians.. Annals of internal medicine , 163 9 , 701-11 . http://doi.org/10.7326/M14-1772
22) Righini, M.., Es, J. van., Exter, P. D. den., Roy, P.., Verschuren, F.., Ghuysen, A.., Rutschmann, O.., Sanchez, O.., Jaffrelot, M.., Trinh-Duc, A.., Gall, C. le., Moustafa, F.., Principe, A.., Houten, A. V. van., Wolde, M. ten., Douma, R.., Hazelaar, Germa., Erkens, P.., Kralingen, K. V. van., Grootenboers, M.., Durian, M.., Cheung, Y. W.., Meyer, G.., Bounameaux, H.., Huisman, M.., Kamphuisen, P.., & Gal, G. Le. (2014). Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.. JAMA , 311 11 , 1117-24 . http://doi.org/10.1001/jama.2014.2135
23) Riley, R.., Gilbert, Andrea R.., Dalton, Justin B.., Pai, Sheela S.., & Mcpherson, R.. (2016). Widely Used Types and Clinical Applications of D-Dimer Assay.. Laboratory medicine , 47 2 , 90-102 . http://doi.org/10.1093/labmed/lmw001
24) Townsend, L.., Fogarty, Helen., Dyer, A.., Martín-Loeches, I.., Bannan, C.., Nadarajan, P.., Bergin, C.., ‘farrelly, Cliona O., Conlon, N.., Bourke, N.., Ward, Soracha E.., Byrne, M.., Ryan, K.., Connell, Niamh M O’., Sullivan, Jamie M O’., Cheallaigh, C. Ní., & Donnell, James S O’. (2021). Prolonged elevation of D‐dimer levels in convalescent COVID‐19 patients is independent of the acute phase response. Journal of Thrombosis and Haemostasis , 19 , 1064 – 1070 . http://doi.org/10.1111/jth.15267
25) Tripodi, A.. (2011). D-dimer testing in laboratory practice.. Clinical chemistry , 57 9 , 1256-62.
http://doi.org/10.1373/clinchem.2011.166249
26) Venkatesh, Arjun K.., Kline, Jeffrey A.., Courtney, D.., Camargo, Carlos A.., Plewa, Michael C.., Nordenholz, K.., Moore, Christopher L.., Richman, Peter B.., Smithline, Howard A.., Beam, D.., & Kabrhel, C.. (2012). Evaluation of pulmonary embolism in the emergency department and consistency with a national quality measure: quantifying the opportunity for improvement.. Archives of internal medicine , 172 13 , 1028-32 . http://doi.org/10.1001/archinternmed.2012.1804
27) Yu, Bilian., Li, Xin., Chen, Jin., Ouyang, M.., Zhang, Hong., Zhao, Xinge., Tang, L.., Luo, Qin., Xu, Mingjing., Yang, Lizhen., Huang, Guxiang., Liu, Xianling., & Tang, Jianjun. (2020). Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis. Journal of Thrombosis and Thrombolysis , 50 , 548 – 557 . http://doi.org/10.1007/s11239-020-02171-y
28) Zhang, Litao., Yan, Xinsheng., Fan, Q.., Liu, Haiyan., Liu, Xintian., Liu, Zejin., & Zhang, Zhenlu. (2020). D‐dimer levels on admission to predict in‐hospital mortality in patients with Covid‐19. Journal of Thrombosis and Haemostasis , 18 , 1324 – 1329 . http://doi.org/10.1111/jth.14859