key: cord-0888646-gfao3cnm
authors: Madathil, Ronson; Tabatabai, Ali; Rabin, Joseph; Menne, Ashley R.; Henderson, Reney; Mazzeffi, Michael; Scalea, Thomas; Tanaka, Kenichi
title: Thromboelastometry and D-dimer elevation in COVID-19
date: 2020-05-21
journal: J Cardiothorac Vasc Anesth
DOI: 10.1053/j.jvca.2020.05.020
sha: 4105b71f333d3c6f3a96608fd4eb7e175aff872c
doc_id: 888646
cord_uid: gfao3cnm

nan

Severe elevation of D-dimer is a hallmark of septic shock, and is a predictor of mortality in COVID-19 disease 1 . D-dimer reflects the extent of plasmin-mediated degradation of crosslinked fibrin, thereby intravascular coagulation. Use of thromboelastometry has gained popularity to assess systemic fibrinolysis in liver transplantation and major trauma 2 , but its utility has not been fully elaborated in the critical care setting 3 . We therefore analyzed the laboratory and thromboelastometry data from 11 critically ill patients receiving mechanical lung ventilation and intensive care support for COVID-19 at the R Adams Cowley Shock Trauma Center over a two-day period. The Institutional Review Board approved the study. Patients were characterized as follows (median [25-75% quartiles] or percentage; median age of 53 (45.5-65.5), body mass index 28.1 (27.1-34.6), 64% male, 54.5% hypertensive 54.5%, and 45.5% diabetic. Patients were dichotomized into two groups based on D-dimer levels of 5-times the upper limit of normal (649 ng/ml fibrinogen equivalent unit [FEU] ). Three of 6 patients in the high Ddimer group were on extracorporeal membrane oxygenation support. Despite highly significant C-reactive protein (CRP) and D-dimer elevations in the latter group, systemic fibrinolysis was not detected either on EXTEM or FIBTEM (maximal lysis, 0%). D-dimer has a half-life of about 8 hours, and reflects in vivo thrombus formation 4 . On the other hand, thromboelastometry only measures the reserve hemostasis capacity in the collected blood using a high-dose coagulation trigger (e.g., tissue factor). Tissue plasminogen activator (tPA) is an important trigger of fibrinolysis in vivo, but its half-life is normally less than 3 min 5 . Circulating interleukin-6 and plasminogen activator inhibitor-1 levels are increased in the presence of virus-infected adipocytes and monocytes 6 . Systemic fibrinolysis is thus unlikely to occur in COVID-19 patients with cytokine storm. Raza, et al. previously showed that only 5% of trauma patients had fibrinolysis on ROTEM, while 57% of patients had moderate fibrinolysis with a median D-dimer level of 38,687 ng/ml 7 . In our patients, a median D-dimer FEU of 15,465 ng/ml and fibrinogen 680 mg/dl represent that only 0.08% of fibrinogen was converted to D-dimer. In contrast, Raza, et al.'s data show that 1.84% of fibrinogen (median, 210 mg/dl) was converted to D-dimer. Taken together, critically ill COVID-19 patients demonstrate significant elevations in D-dimer consistent with microvascular thromboses, but only small fractions of fibrin seem to be locally broken down, and no systemic fibrinolysis is observed.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management

Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review

Point of care D-dimer testing in the emergency department: a bioequivalence study

Clearance of tissue plasminogen activator (TPA) and TPA/plasminogen activator inhibitor type 1 (PAI-1) complex: relationship to elevated TPA antigen in patients with high PAI-1 activity levels

Intracellular infections enhance interleukin-6 and plasminogen activator inhibitor 1 production by cocultivated human adipocytes and THP-1 monocytes

The incidence and magnitude of fibrinolytic activation in trauma patients

EXTEM and FIBTEM reagents contain polybrene that neutralize heparin. Five patients in the high Ddimer group were on intravenous heparin

ng/ml FEU; Fibrinogen 216-438 mg/dl; Hematocrit 37-50%sec; EXTEM-CT 43-82 sec; EXTEM-A10 46-67 mm; FIBTEM-A10 7-24 mm

Abbreviations: CT, clotting time

A10, clot amplitude at 10 minutes; CRP, C-reactive protein