D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Is viscoelastometric testing a good tool to assess hemostasis of COVID-19 patients?

Background : Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Aims : Our main aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. Our secondary aims were: (i) to analyze the impact of anticoagulation and the methods used to neutralize heparin, (ii) to see whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) to point out results from studies with enhanced fibrinolysis modified tests. Methods : We performed a systematic search in PubMed and Scopus databases, until December 31st, 2020 (Figure 1). VETs methods and parameters, as well as patients ' features and outcomes were extracted. Results : VET was performed for 1063 patients (893 ICU and 170 non-ICU, n = 44 studies). There was a huge heterogeneity concerning study design, the VET device (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization by heparinase and/or polybrene), timing of assay, and definition of hypercoagulable state. The common findings were an increased clot mechanical strength mainly due to an excessive fibrinogen component with impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. This profile was associated with an uncontrolled thrombin generation despite a standard thromboprophylaxis. However, only 4 studies out of 16 that addressed this point found an association of VETs with thrombotic events. Functional fibrinogen assessed by VET showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern tended to normalization after an enhancement in thromboprophylaxis. Notably, only 4 studies out of 25 using ROTEM reported data where heparin is neutralized by heparinase (HEPTEM). Conclusions : The heterogeneity among VET studies and small sample sizes do not permit to point out an association between the illdefined hypercoagulable state and thrombotic events.

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory.

Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.