Routine and Advanced Laboratory Tests for Hemostasis Disorders in COVID-19 Patients: A Prospective Cohort Study

Abstract

Background: Thrombosis is frequent during COVID-19 disease, and thus, identifying predictive factors of hemostasis associated with a poor prognosis is of interest. The objective was to explore coagulation disorders as early predictors of worsening critical conditions in the intensive care unit (ICU) using routine and more advanced explorations. Materials: Blood samples within 24 h of ICU admission for viscoelastic point-of-care testing, (VET), advanced laboratory tests: absolute immature platelet count (A-IPC), von Willebrand-GPIb activity (vWF-GpIb), prothrombin fragments 1 + 2 (F1 + 2), and the thrombin generation assay (TGA) were used. An association with worse outcomes was explored using univariable and multivariable analyses. Worsening was defined as death or the need for organ support. Results: An amount of 85 patients with 33 in critical condition were included. A-IPC were lower in worsening patients (9.6 [6.4–12.5] vs. 12.3 [8.3–20.7], p = 0.02) while fibrinogen (6.9 [6.1–7.7] vs. 6.2 [5.4–6.9], p = 0.03), vWF-GpIb (286 [265–389] vs. 268 [216–326], p = 0.03) and F1 + 2 (226 [151–578] vs. 155 [129–248], p = 0.01) were higher. There was no difference observed for D-dimer, TGA or VET. SAPS-II and A-IPC were independently associated with worsening (OR = 1.11 [1.06–1.17] and OR = 0.47 [0.25–0.76] respectively). The association of a SAPS-II ≥ 33 and an A-IPC ≤ 12.6 G/L predicted the worsening of patients (sensitivity 58%, specificity 89%). Conclusions: Immature platelets are early predictors of worsening in severe COVID-19 patients, suggesting a key role of thrombopoiesis in the adaption of an organism to SARS-CoV-2 infection.

Soluble RAGE as a Prognostic Marker of Worsening in Patients Admitted to the ICU for COVID-19 Pneumonia: A Prospective Cohort Study

“…Among them, the alteration of hemostatic processes may be of interest, predominantly because of the higher incidence of thrombotic events during COVID-19 disease. We previously described the alteration in the coagulation process in our cohort, with a particular role identified for immature platelets and thrombin generation assay, whereas d-dimers presented discouraging results [ 3 , 46 ]. On the other hand, clinical parameters such as the ROX index, which quantifies the severity of respiratory failure under HFNC, may predict the respiratory worsening of patients [ 47 ].…”

“…This cohort was described in a previous publication [ 3 ]. Briefly, patients were eligible for inclusion if they presented a “severe” condition related to a documented infection of SARS-CoV-2 (determined by polymerase chain reaction assay), defined as the need for ICU admission because of acute respiratory failure.…”

“…Many efforts have been focused on understanding the mechanisms underlying virus entry into the host system and its pathogenesis, but also to understand the pathophysiological changes. Dysregulated inflammation may participate in the pathological systemic changes observed during COVID-19, triggering endothelium dysfunction, coagulation disorders, and eventually leading to shock [ 1 , 2 , 3 ]. High levels of cytokines, such as interleukin-6 (IL-6), are associated with the severity of the pathology and poor prognosis, and likely explain the beneficial effects of dexamethasone in the most seriously ill patients [ 1 , 4 ].…”

Serial thrombin generation and exploration of alternative anticoagulants in critically ill COVID-19 patients: Observations from Maastricht Intensive Care COVID Cohort

“…Several reports suggest that thrombin generation is enhanced in CAC ( 17 , 29 , 30 ), independent of heparin treatment ( 17 ). However, other studies showed no differences in thrombin generation during various stages of disease severity in SARS-CoV-2 infection, suggesting coagulation exhaustion ( 31 – 33 ). In this paper the results of serial thrombin generation experiments, performed in a cohort of severely COVID-19 patients, admitted to the intensive care unit (ICU) for mechanical ventilation, are presented.…”

Prognostic value of an automated thrombin generation assay in COVID-19 patients entering hospital: A multicentric, prospective observational study

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to the coronavirus disease 2019 (COVID-19) is associated with a multifactorial coagulopathy related to inflammation resulting from the cytokine storm [1] , [2] . Excessive amounts of thrombin are generated with a subsequent hypercoagulability state leading to a high prevalence of thrombotic manifestations, many with fatal outcomes [3] , [4] , [5] . This quickly led teams managing patients hospitalised with severe COVID-19 to raise the question of the informativity of initially performed innovative coagulation tests describing coagulation as a whole on key clinical outcomes.…”