High D dimers and low global fibrinolysis coexist in COVID19 patients: what is going on in there?

Abstract

Backgroud COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England) 395(10229):1054-62, 2020). While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection. J Am Coll Surg (2020). Available from https :// pubme d.ncbi.nlm.nih.gov/32422 349/ [cited 14 Jun 2020]; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 9(1):19, 2019). We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test. Methods Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371). All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded. The standard laboratory coagulation test and ROTEM were performed simultaneously at 24-48 h after ICU admission. Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection. Results Nineteen patients were included with median SOFA-score of 4 (2-6), DIC-score of 1 (0-3) and SIC-score of 1.8 (0.9). Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8-7.6 g/L), 1000 (600-4200 ng/ml) and 236 (136-364 10 9 /L), respectively. Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased. There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score. Conclusion In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels. We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists. This hypothesis should be confirmed by future studies.

COVID-19 Infection-Related Coagulopathy and Viscoelastic Methods: A Paradigm for Their Clinical Utility in Critical Illness

“…No abnormal fibrinolytic activity was noted. In the same way, nineteen ICU COVID-19 patients were recruited by Ibanez et al and demonstrated clot firmness above the normal range in the EXTEM and FIBTEM tests, while clot lysis was decreased [ 18 ]. Clot firmness and clot lysis were assessed against the normal range and reported levels in the healthy controls, respectively.…”

“…However, a correlation between ROTEM parameters and severity illness scores has not been reported [ 18 ]. It should be also pointed out that, in most cases, ICU COVID-19 patients have longer or normal CT/R values [ 12 , 13 , 17 , 18 , 19 ]. This is the only parameter not supporting the procoagulant profile of critically ill COVID-19 patients.…”

“…In some cases, thromboelastometrical lysis indexes (LIs) proved to be reliable biomarkers for both the early identification [ 25 , 35 ] and prognosis [ 36 ] of patients suffering from sepsis. However, it should be stressed that fibrinolysis impairment in ICU COVID-19 patients has not been a consistent finding, even among studies using the same viscoelastic method [ 13 , 14 , 15 , 18 ]. Contradictory findings have also previously been reported on VMs’ diagnostic capacity to detect abnormal fibrinolysis [ 38 , 39 , 40 ], while concerns have been raised about the sensitivity of VMs for identifying fibrinolysis in all patients [ 41 ].…”

Acute pulmonary embolism in acutely ill COVID-19 patients admitted to internal medicine wards.

“…From the 1 st to 30 th April 2020, 41 acutely ill patients admitted to internal medicine department wards underwent a CTPA because respiratory deterioration after admission, and represent the study population. The median (IRQ) age of the cohort was 71.7 (63-76) years, 30 (73%) were females, the median days (IRQ) since onset of symptoms to hospitalization was 8 (4-12) and the median days (IRQ) since onset of symptoms to CTPA was 11 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). By the end of May 2020 in-hospital mortality of the cohort was 4.88%, with 2 patients still hospitalized and 90% already discharged.…”

“…Although data from different studies indicate that the incidence of venous thromboembolism (VTE) in COVID-19 patients is higher than that seen in similarly ill hospitalized non COVID-19 subjects, the exact prevalence of APE in COVID-19 patients is not known, and the diagnostic value of D-dimer in subjects with acute SARS-CoV-2 infection is not clear [5]. In effect, the increase in mortality associated with elevated D-dimer values in these patients may re ect an increased rate of APE, but it also could be a manifestation of disseminated intravascular coagulation or simply a higher level of systemic in ammation [9]. Therefore, data on the value of D-dimer and other clinical and biochemical markers for the diagnosis of VTE in subjects hospitalized for COVID-19 may improve the diagnostic and therapeutic approach to this disease.…”