Article of the month | May 2021
Improving COVID-19 outcomes with the viscoelasticity of coagulating blood
by Dr. Dimitria Bonizol Camasao
Senior Application Specialist, Rheolution Inc.
Coronavirus Disease 2019 (COVID-19) is marked by its speed and scale of transmission. The disease has been challenging health professionals and the scientific community in every aspect of its development. The progression of the disease and the presence of blood coagulation disorders have often been associated with poor clinical outcomes. One major challenge faced by doctors is the selection of a suitable treatment, given the extremely diverse clinical profiles of the patients. For this reason, a one-treatment-for-all regime can be unsuccessful and even dangerous. A personalized patient-oriented approach is therefore sought out.
In this publication, we will report the results of a study conducted by a team of clinicians and researchers from the Western Michigan University, University of Texas and healthcare-related offices across the United States . In the study “176: Optimizing Outcomes for COVID-19 Coagulopathy Through Thromboelastography and Platelet Mapping” published in the Critical Care Medicine Journal early this year, the authors showed that the viscoelastic changes of the coagulating blood can give complementary and personalized information on the patient’s coagulation state. Before going into more details of the study, let’s review how COVID-19 and blood coagulation disorders are related.
How the body reacts to viruses
The human body naturally reacts to the invasion of pathogens (microbes that cause diseases). The first rapid reaction is known as innate immune response which is not specific to a particular pathogen and involves a group of proteins and phagocytic (white blood) cells. Phagocytes can quickly begin fighting an infection by killing the invading pathogens. These cells also release pro-inflammatory molecules, which cause blood vessels to become “leaky”, allowing the recruitment of inflammatory cells and molecules from the blood to the infected site to help binding and killing the pathogen.
The inflammation that occurs is part of the immune response to protect us from many pathogens. However, when pathogens stimulate a very strong response, the inflammation may damage tissues and impair organ function. This is what is happening in a number of COVID-19 positive patients that suffer from the progression of the disease. The strong inflammatory response can affect their coagulation system, which is responsible for mediating blood clotting after an injury. Specifically, the role of the coagulation system in the body is to coordinate a group of cells and proteins to the site of the injury to form a clot that stops blood loss.
Blood coagulation disorders in COVID-19 patients
Most of the mild to severe COVID-19 cases show a disturbance in blood coagulation. In patients with hypercoagulability, cells and proteins involved in the clot formation are present in higher quantities in the blood which can lead to the formation and growth of undesired clots. These clots can cause thrombotic complications by narrowing or even preventing the passage of blood flow to the downstream vessels and tissues. In patients with hypocoagulability, the natural process of the body to prevent uncontrolled bleeding is impaired, consisting in a risk for hemorrhage.
Treatments for COVID-19-related coagulation disorders
There are some molecules involved in the process of coagulation that are normally measured using a blood sample from the patient to detect abnormalities. These results are used to determine prophylactic (preventive) or therapeutic treatments. For example, heparins are often prescribed to decrease the risk of thromboembolic complications in hospitalized COVID patients. However, these conventional tests only give some information about a few specific pathways involved in the coagulation cascade and therefore they do not provide the current coagulation state of the patient. For this reason, determining an optimal treatment and its dosage for COVID patients with their many clinical profiles is challenging.
Viscoelastic methods (VM) such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are another type of tests used for coagulation management. In these tests, a blood sample is inserted in the instrument where it is expected to coagulate (form a blood clot) in presence of specific reagents. VM measures the effects of the viscoelastic changes during blood clot formation. The results provide an overall view of the whole coagulation process including the initiation time, formation profile, clot strength and lysis. Complementary to the conventional tests mentioned above, viscoelastic results can help in determining a personalized treatment for the patient.
Viscoelastic methods and COVID-19
The authors of the study investigated the potential of using TEG and platelet (blood cells that help clot formation) mapping (PM) to accurately characterize the coagulation state of COVID-19 patients and to guide medical therapy aiming to reduce complications and improve outcomes.
TEG and PM was performed in whole blood samples of 65 COVID-19 positive patients on admission and again after 48 and 72 hours whenever possible. Patients were divided into 2 groups according to the results: 1) non-coagulopathic state (NC-TEG) and 2) persistent coagulopathic condition, either hyper- or hypo-coagulable (C-TEG).
A first interesting observation was that the levels of some conventional coagulation tests such as D-dimer, CRP and ferritin, while significantly elevated in the sickest patients, could not differentiate coagulopathic from non-coagulopathic patients.
Clinical outcomes showed that C-TEG patients nearly had a 40-fold increased risk for mechanical ventilation, 2.7 for acute kidney injury, 33.7 dialysis and 13.3-fold increased risk of death with 75% C-TEG patients dying compared to 2% NC-TEG patients. TEG-PM guided anti-platelet treatment decreased mortality by 73%. In contrast, indiscriminate anticoagulation (heparin/enoxaparin) resulted in 3.6-fold increased risk of death.
The research community is now starting to understand the potential of using VE methods as a point of care device to improve outcomes. Further studies need to be conducted with adequate sample size to (1) establish reference ranges or common cut-off values for healthy, hypo- and hypercoagulability conditions  and (2) to investigate different strategies to combine results from VE methods and conventional coagulation assays to compose a personalized and effective anticoagulant, antiplatelet or fibrinolytic therapy.
 Hranjec, T., Pepe, P., Estreicher, M., Rogers, B., Solomon, R., Hennessy, S., … & Sawyer, R. (2021). 176: Optimizing Outcomes for COVID-19 Coagulopathy Through Thromboelastography and Platelet Mapping. Critical Care Medicine, 49(1), 73.
 Tsantes, A. E., Tsantes, A. G., Kokoris, S. I., Bonovas, S., Frantzeskaki, F., Tsangaris, I., & Kopterides, P. (2020). COVID-19 infection-related coagulopathy and viscoelastic methods: a paradigm for their clinical utility in critical illness. Diagnostics, 10(10), 817.
The human body has a natural mechanism to stop bleeding after an injury. Platelets migrate to the site of injury and start to form a soft blood clot. This activates other clotting factors in the bloodstream triggering a chain reaction to form a harder blood clot that will stay firmly in place.
The ElastoSens™ Bio was used to analyze the effects of hemostatic agents (HAs) on blood coagulation. The technology identified HAs that can alter clotting independently of the body's natural processes. These findings can optimize current HAs and aid in developing new ones.
Scientists from Dalhousie University, led by Dr. Mark Joseph Filiaggi, investigated the sodium polyphosphate (NaPP) polymer as a potential hemostatic agent. They tested six formulations of the biomaterial, with varying degrees of polymerization and types of divalent cations. The hemostatic potential of these formulations was evaluated using various blood clotting assays. The biomaterial was mixed with coagulation reagents and recalcified blood or plasma in a tube, which was then shaken to visually assess blood or plasma flow. The clotting time was noted as the time required to achieve no flow. Surgifoam®, a commercial hemostatic agent, was used as a control.
The viscoelastic properties of coagulating blood can be correlated with several diseases and genetic conditions that affect the natural blood coagulation process including bleeding disorders, hemophilia, rare factor deficiencies, von Willebrand disease and platelet function disorders. Therefore, the evaluation of blood clot properties can be valuable for the study, diagnosis and eventually treatment of these diseases.