The role of rotational thromboelastometry during the COVID-19 pandemic: a narrative review

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is currently recognized as a global health crisis. This viral infection is frequently associated with hypercoagulability, with a high incidence of thromboembolic complications that can be fatal. In many situations, the standard coagulation tests (SCT) fail to detect this state of hypercoagulability in patients with COVID-19 since clotting times are either not or only mildly affected. The role of viscoelastic tests such as rotational thromboelastometry (ROTEM®) during this pandemic is explored in this review. COVID-19-associated coagulopathy, as measured using the rotational thromboelastometry parameters, can vary from hypercoagulability due to increased fibrin polymerization and decreased fibrinolysis to bleeding from hypocoagulability. The use of a multimodal diagnostic and monitoring approach, including both rotational thromboelastometry and SCT, such as plasma fibrinogen and D-dimer concentrations, is recommended. Rotational thromboelastometry provides comprehensive information about the full coagulation status of each patient and detects individual variations. Since COVID-19-associated coagulopathy is a very dynamic process, the phenotype can change during the course of infection and in response to anticoagulation therapy. Data from published literature provide evidence that the combination of rotational thromboelastometry and SCT analysis is helpful in detecting hemostasis issues, guiding anticoagulant therapy, and improving outcomes in COVID-19 patients. However, more research is needed to develop evidence-based guidelines and protocols.

Keywords: Anticoagulants; Blood coagulation disorders; COVID-19; Fibrinolysis; SARSCoV-2; Thrombelastography; Thrombophilia.

Fig. 1.

ROTEM^® parameters and indices. A5: clot firmness amplitude 5 min after coagulation time (CT) in mm, A10: clot firmness amplitude 10 min after CT in mm, CFT: clot formation time in seconds (time from 2 to 20 mm clot firmness), CT: coagulation time in seconds (time from test start to 2 mm clot firmness), FDPs: fibrin(ogen) degrading products, F XIII: coagulation factor XIII, LI30: lysis index 30 min after CT in % (residual clot firmness in percentage of MCF), LI45: lysis index 45 min after CT in %, LI60: lysis index 60 min after CT in %, LOT: lysis onset time in seconds (time from CT to 15% fibrinolysis = 85% residual clot firmness compared to MCF), and LT: lysis time in seconds (time from CT to 90% fibrinolysis = 10% residual clot firmness compared to MCF). Courtesy of Klaus Görlinger, Munich, Germany.

Fig. 2.

COVID-19-associated coagulopathy. Diagnostic value of D-dimer, fibrinogen, anti-Xa activity, and rotational thromboelastometry parameters. CT: coagulation time in seconds, EXTEM: ROTEM^® test assessing the extrinsic coagulation pathway, FIBTEM: ROTEM^® test assessing fibrin contribution to clot firmness, HEPTEM: ROTEM^® test assessing the intrinsic coagulation pathway with elimination of heparin-like effects by heparinase, INTEM: ROTEM^® test assessing the intrinsic coagulation pathway which is sensitive to heparin-like effects, LI60: lysis index 60 min after CT in % of MCF, LMWH: low molecular weight heparin, MCF: maximum clot firmness in mm, ML: maximum lysis in % of MCF, NAHEPTEM: native ROTEM^® test with elimination of heparin-like effects by heparinase, NATEM: native ROTEM^® test which is sensitive to LMWH, and UFH: unfractionated heparin. Courtesy of Klaus Görlinger, Munich, Germany.

Fig. 3.

TPATEM/TPA-test findings in COVID-19 patients. Representative TPATEM curves from a healthy donor (green curve), a COVID-19 patient without thrombosis (black curve), and a COVID-19 patient with thrombosis (red curve). In COVID-19 patients, LOT and LT are prolonged, and MCF and LI30 are increased compared with those in healthy controls after r-tPA challenge (TPATEM = EXTEM + 0.625 µg/ml r-tPA). CF: clot firmness in mm, CT: coagulation time in seconds, EXTEM: ROTEM^® test assessing the extrinsic coagulation pathway, LI30: lysis index 30 min after CT in % of MCF, LOT: lysis onset time in seconds, MCF: maximum clot firmness in mm, ML: maximum lysis in % of MCF, and r-tPA: recombinant tissue plasminogen activator. Courtesy of Klaus Görlinger, Munich, Germany.