Evaluation of coagulation status using clot waveform analysis in general ward patients with COVID-19

Abstract

Coronavirus disease (COVID-19)-related systemic cytokine response induces the production of procoagulant factors, which predisposes patients to a prothrombotic state. Viscoelastic testing can identify the degree of hypercoagulability, which is related to outcomes. We aimed to study the changes in clot waveform analysis (CWA) parameters in COVID-19 patients on hospital admission compared to those in a group of healthy individuals. We conducted a retrospective study of COVID-19 patients admitted to general wards and evaluated demographic and clinical parameters as well as laboratory parameters, including coagulation parameters. CWA data from patients (n = 62) with COVID-19 prior to the initiation of anticoagulation therapy were compared with those from healthy controls (n = 67). The measured CWA parameters were min1, min2, max2, and delta change. CWA, fibrinogen, and D-dimer values were higher in COVID-19 patients than in healthy controls (p < 0.001). CWA profiles were consistent with hypercoagulability and characterized by an increase in density, velocity, and acceleration of clot formation. Activated partial thromboplastin time, fibrinogen, D-dimer, and C-reactive protein (CRP) values were higher in patients in whom all CWA parameters were raised than in patients with just a few elevated CWA parameters, while Sequential Organ Failure Assessment scores, prothrombin time, fibrin degradation product levels and platelet counts did not differ between the two groups. CWA variables showed hypercoagulopathy on admission in COVID-19 patients who were hospitalized in the general ward, and this pattern was more pronounced in critically ill patients with elevated fibrinogen, D-dimer, and CRP levels. Our results may help identify patients at high risk of thromboembolism. Keywords COVID-19 • General ward • Clot wave analysis • Hypercoagulability • Fibrinogen Abbreviations CWA Clot wave analysis aPTT Activated partial thromboplastin time CRP C-reactive protein VTE Venous thromboembolic event DIC Disseminated intravascular coagulation, BMI Body mass index SOFA Sequential Organ Failure Assessment PT Prothrombin time Highlights• CWA can provide more precise information regarding alterations in fibrin clot properties, which might represent risk factors for VTE, than fibrinogen assays. • CWA is an economically convenient and simple test that can aid clinical stratification and management by implementing an algorithm into the software of an automated coagulometer.

Effects of Hemodilution on Clot Waveform Analysis Parameters, Clotting Factors, and Thrombin Generation Assays in a Dilutional Model Based on Analysis of 11 Healthy Male Blood Donors

“…The amplitude of CWA curve, characterized by Delta, is determined by the turbidity resulting from the aggregation of fibrin monomers and shows a linear association with fibrinogen concentration. Other studies have also shown that the correlation between fibrinogen and delta was significant, with significantly weaker correlations with other properties [ 11 , 32 ].…”

“…Past studies have suggested that this technique provides useful information for determining the clinical phenotype of patients with hemophilia with significantly low factor levels [ 6 – 8 ] and detecting disseminated intravascular coagulation earlier than conventional methods with high specificity (97.6%) and sensitivity (98%) [ 9 , 10 ]. Moreover, the assay identifies the degree of hypercoagulability and may help identify patients at high risk of thromboembolism [ 11 , 12 ]. CWA could also provide a novel method for monitoring hemostasis in cases of replacement therapy for serious hemorrhage and for monitoring antithrombic therapy to clarify therapeutic efficacy and bleeding risk [ 13 , 14 ].…”

Activated Partial Thromboplastin Time-based Clot Waveform Analysis: A Potential for Application in Acute Myocardial Infarction and Its Complications

“…There is substantial literature on the application of CWA in the diagnosis of and prognostication in haemophilia [15,16], disseminated intravascular coagulation [17,18] and sepsis [19,20]. CWA has also been used to demonstrate and characterise the hypercoagulability in venous thromboembolism [21,22] and COVID-19-associated coagulopathy [23,24]. However, its role in arterial thrombotic events is uncertain.…”

Dynamic Measurement of Clot Formation: The New Wave in Acquired Coagulopathy Assessment?*

“…Consequently, the need for assays providing a more global assessment of coagulation has been recognized (2.3). These tests include thrombin generation assay (TGA), viscoelastic tests (VET) of clot formation (thromboelastography, rotational thromboelastometry [ROTEM]), and (mathematical) analysis of the dynamics of fibrin formation in the PT or aPTT, that is, clot waveform analysis (CWA) (3,4).…”

“…Consequently, the need for assays providing a more global assessment of coagulation has been recognized (2.3). These tests include thrombin generation assay (TGA), viscoelastic tests (VET) of clot formation (thromboelastography, rotational thromboelastometry [ROTEM]), and (mathematical) analysis of the dynamics of fibrin formation in the PT or aPTT, that is, clot waveform analysis (CWA) (3, 4). Although viscoelastic assays to evaluate bleeding and guide clinical management are being used in several clinical scenarios with increasing frequency, the same is not true for either TGA or CWA.…”