- Open Access
D-dimer specificity and clinical context: an old unlearned story
Critical Care volume 25, Article number: 101 (2021)
D-dimer, a degradation product of activated fibrin, is considered a sensitive biomarker for thromboembolic events. Unfortunately, the D-dimer does not show as much specificity. Other conditions than venous thrombosis can also raise D-dimer level, such as pregnancy, renal failure, sepsis. An elevated D-dimer value is not sufficient to establish the diagnosis of pulmonary thromboembolism. Plasma D-dimers levels could be determined by the lysis of extra-vascular rather than intra-vascular fibrin. In the ADJUST-PE study, approximately 10% of patients with an age-adjusted D-dimer above the significant cut-off showed no angiographic evidence of pulmonary embolism . In a cohort of 98 patients, Kutinsky et al. found 12 with D-dimer > 500 ng/mL who had no angiographic evidence of pulmonary embolism and 8 with D-dimer < 250 ng/mL who did have pulmonary embolism .
D-dimer has a negative prognostic role in the COVID-19 patient's population. Numerous studies confirm this value, although the mechanisms are not fully understood. A component responsible for high D-dimer levels could be a peculiar form of disseminated intravascular coagulation. Up to 40% of patients with COVID-19 have some form of thromboembolism (i.e., DVT or PE). However, as many as 76% of patients have an elevated D-dimer .
We read the review by Susen et al., which identifies D-dimer as a reliable guide for the dosage of anticoagulant therapy in COVID-19 patients . Due to the previously mentioned limitations, this strategy has never been validated, even for non-COVID-19 patients. Some authors proposed a low molecular weight heparin prophylactic regimen adjusted-doses based on D-dimer levels in some specific non-COVID-19 populations. However, these populations are not comparable to the COVID-19 patients.
Furthermore, the D-dimer dose adjustment of anticoagulant prophylaxis has not been proven effective even in COVID-19 patients, although some scientific societies suggest the possibility of stratifying patients based on serum D-dimer levels. This strategy's rationale is at least controversial: even in overt disseminated intravascular coagulation (DIC), the D-dimer is unreliable since its specificity varies considerably with the cut-off value. Approximately 20% of patients with a D-dimer value greater than 2.2 μg/mL do not have DIC .
Finally, it should be considered that the ISTH SSC on Fibrinolysis group has identified several technical pitfalls detected in current studies on D-dimer in COVID-19 cases.
In conclusion, D-Dimer guided-anticoagulation management does not seem supported enough by evidence-based recommendations. Studies that specifically address this issue are needed before evidence-based recommendations can be made.
Availability of data materials
Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A, Rutschmann OT, Sanchez O, Jaffrelot M, Trinh-Duc A, Le Gall C, Moustafa F, Principe A, Van Houten AA, Ten Wolde M, Douma RA, Hazelaar G, Erkens PM, Van Kralingen KW, Grootenboers MJ, Durian MF, Cheung YW, Meyer G, Bounameaux H, Huisman MV, Kamphuisen PW, Le Gal G. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA. 2014;311:1117–24.
Kutinsky I, Blakley S, Roche V. Normal D-dimer levels in patients with pulmonary embolism. Arch Intern Med. 1999;159:1569–72.
Berger JS, Kunichoff D, Adhikari S, Ahuja T, Amoroso N, Aphinyanaphongs Y, Cao M, Goldenberg R, Hindenburg A, Horowitz J, Parnia S, Petrilli C, Reynolds H, Simon E, Slater J, Yaghi S, Yuriditsky E, Hochman J, Horwitz LI. Prevalence and outcomes of D-Dimer elevation in hospitalized patients with COVID-19. Arterioscler Thromb Vasc Biol. 2020;40:2539–47.
Susen S, Tacquard CA, Godon A, Mansour A, Garrigue D, Nguyen P, Godier A, Testa S, Levy JH, Albaladejo P, Gruel Y. GIHP and GFHT. Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring. Crit Care. 2020;24:364.
Li WJ, Sha M, Ma W, Zhang ZP, Wu YJ, Shi DM. Efficacy evaluation of D-dimer and modified criteria in overt and nonovert disseminated intravascular coagulation diagnosis. Int J Lab Hematol. 2016;38:151–9.
No fund was used to conduct this study.
Ethical approval and consent to participate
Conflict for publication
All authors declare they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Marin, M., Orso, D., Federici, N. et al. D-dimer specificity and clinical context: an old unlearned story. Crit Care 25, 101 (2021). https://doi.org/10.1186/s13054-021-03532-6