ABSTRACT
Introduction: The lack of a history of the course of a new coronavirus infection and the lack of data from randomised trials makes it difficult to choose the right treatment tactics and prescribe adequate prophylaxis in patients who have suffered from COVID-19. Comorbid patients with cardiovascular diseases and endothelial dysfunction have a high risk of a severe course of COVID-19 and subsequent thrombotic complications, which manifest clinically as cardiomyopathy;venous thrombo-embolism (deep vein thrombosis and pulmonary embolism);pulmonary thrombosis in situ;stroke;arterial thrombangiitis;rarely, arterial peripheral thrombosis and microvascular thrombosis, in the lungs, liver, kidneys, brain, etc.;and mild disseminated intravascular coagulation syndrome. The role of endothelial dysfunction in the development of severe complications is underestimated. In the pathogenesis of COVID-19, the defeat of the microcirculatory bed plays a crucial role. The SARS-CoV-2 virus causes associated endotheliitis damage to the endothelium due to virus entry and cytokine storm. Endotheliitis leads to the release of tissue factor, which leads to the formation of an excess of thrombin and fibrin;the body tries to cover the virus with these and prevent its spread, which entails negative side effect such as thrombosis Methods: Sixty-six patients who had COVID-19 were examined (42 women and 24 men;mean age 48 years [range 20 – 80 years]). Patients complained of a feeling of paraesthesia, mainly in the lower extremities, a feeling of heaviness, stiffness in the popliteal region, an increased vascular pattern on the entire surface of the skin, a burning sensation in all vessels, and a feeling of weakness. Ultrasound colour duplex scanning showed no signs of thrombosis in the large vessels. Using a high frequency ultrasound Doppler and a 25 MHz sensor, the nailbed of the first finger of the upper limb was examined. The microcirculatory images were analysed by the shape and spectrum of the curves. Twenty patients received prophylaxis with rivaroxaban 10 mg daily (group 1) and 46 patients did not (group 2). The control examination was carried out four weeks after the start of therapy: sulodexide one capsule twice daily. The coagulogram parameters were also studied. Results: A depletion in spectral characteristics was seen in patients after COVID-19 disease, in comparison to microcirculatory images recorded in healthy individuals. Predominantly, the red part of the spectrum was recorded in patients after COVID-19, the lighter part of the spectrum was not recorded. Group 1 patients had higher amplitude parameters than group 2, but they also registered a depletion in spectral characteristics. Soluble fibrin monomer complexes were increased 4 – 5 times, D-dimer 2 – 2.5 times, and antithrombin III 1.5 times. The international normalised ratio, activated partial thromboplastin time, fibrinogen, prothrombin according to Quick, prothrombin time, clotting time, and bleeding time were within the reference intervals both before and after treatment. Upon repeat examination four weeks after the course of sulodexide therapy, the spectral characteristics were normalised, and the coagulogram parameters were also normalised. Conclusion: The red part of the spectrum, according to the Doppler criteria, corresponds to the fastest particles moving in the middle of the stream. The lighter part of the spectrum corresponds to particles moving more slowly. The reduction in spectral characteristics in patients after COVID-19 disease corresponds to parietal stasis and readiness for thrombosis, which was confirmed by the coagulogram data. Examination of the nailbed using high frequency ultrasound Doppler in patients who have COVID-19 allows the identification of stasis of the parietal blood flow, which corresponds to a prethrombotic state. The prescription of sulodexide allows for an improvement in the condition of patients and normalisation of microcirculation indicators
ABSTRACT
Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in corona virus disease 2019 (COVID-19) associated coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill COVID-19 patients with an associated elevation of d-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes-thrombin, Factor XIIIa and plasmin-must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein, we describe a novel method illuminating aspects of this unexplored area. In addition, we created an in vitro blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing the determination of soluble fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows the determination of the SF level at which fibrin microclots begin to form.
ABSTRACT
Background: In some patients, SARS-CoV-2 infection induces cytokine storm, hypercoagulability and endothelial cell activation leading to worsening of COVID-19, intubation and death. Prompt identification of patients at risk of intubation or death is un unmet need. Objective: To derive a prognostic score for the risk of intubation or death in patients with critical COVID-19 by assessing biomarkers of hypercoagulability, endothelial cell activation and inflammation and a large panel of clinical analytes. Methods: We conducted a prospective, observational monocentric study enrolling 118 patients with COVID-19 admitted in the intensive care unit. At the 1st day of ICU admission all patients were assessed for the following biomarkers : protein C, protein S, antithrombin, D-Dimer, fibrin monomers, factors VIIa, V, XII, XII, VIII, von Willebrand antigen, fibrinogen, procoagulant phospholipid dependent clotting time, TFPI, thrombomodulin, P-selectin, heparinase, microparticles exposing tissue factor, IL-6, complement C3a, C5a, thrombin generation, prothrombin time, activated partial thromboplastin time, hemogram, platelet count) and clinical predictors. The clinical outcomes were intubation and mortality during hospitalization in ICU. Results: The intubation and mortality rate were 70 % and 18% respectively. Multivariate analysis led to the derivation of the COMPASS- COVID19-ICU score composed of P-Selectin, D-Dimer, free TFPI, TF activity, IL-6 and FXII, age and duration of hospitalization. The score predicted the risk of intubation or death with high sensitivity and specificity (0.90 and 0.92, respectively). Conclusions and Relevance: Critical COVID-19 is related with severe endothelial cell activation and hypercoagulability orchestrated in the context of inflammation. The COMPASS-COVID19-ICU score is an accurate predictive model for the evaluation of the risk of mechanical ventilation and death in patients with critical COVID-19. The assessment with the COMPASS- COVID-19-ICU score is feasible in tertiary hospitals. In this context it could be placed in the diagnostic procedure of personalized medical management and prompt therapeutic intervention. Disclosures: Terpos: Novartis: Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Genesis: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;BMS: Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;GSK: Honoraria, Research Funding. Dimopoulos: Amgen: Honoraria;BMS: Honoraria;Takeda: Honoraria;Beigene: Honoraria;Janssen: Honoraria.