Coagulopathy: A Vicious Indicator of COVID-19

COVID-19 is routinely associated with coagulopathy and complications associated with thrombosis. However, the difference between the coagulopathy, which is associated with COVID-19 and the coagulopathy, which is due to different causes, is that the "COVID-19 associated coagulopathy" shows raised levels of D-Dimer and that of fibrinogen. However, it shows quite some abnormalities in the levels of prothrombin time and also in the platelet count. "Venous thromboembolism" and arterial thrombosis is frequently seen in COVID-19 associated coagulopathy as opposed to "disseminated intravascular coagulopathy". Patients suffering from COVID-19 have many have multiple factors in common for thromboembolism which is associated with "Adult respiratory distress syndrome" from different etiologies like generalized inflammation and being unambulatory. "Cytokine storm" is the hallmark of COVID-19 associated coagulopathy which is distinguished by high levels of IL-6,1, tumour necrosis factor and other cytokines. The clinical features of COVID-19 associated coagulopathy overlap that of some syndromes like antiphos-pholipid syndrome and thrombotic microangiopathy. Studies have shown that patients diagnosed with disseminated intravascular coagulation have a poor prognosis compared to the one's that don't get diagnosed with DIC. The advancement of the condition from coagulopathy in the vasculature of the lungs to DIC in patients who have tested positive for COVID-19 shows that the patient's dysfunction associated with coagulation has evolved from local to generalized state. Investigating the coagulopathies will help in understanding the mechanism of COVID-19 associated coagulopathy.Copyright © International Journal of Research in Pharmaceutical Sciences.

Prevalence and impact of coagulation dysfunction in patients with COVID-19 in Yazd

Covid-19 patients have coagulation complications resulting in poor prognosis. Therefore, this study aimed to investigate the prevalence of coagulation disorders in patients with Covid-19 admitted to Shahid Sadoughi Hospital in Yazd. This study was a cross-sectional study that all patients admitted with a diagnosis of Covid-19 from the beginning of February 2020 to the end of April 2020 were examined for the frequency of coagulation dysfunctions. A total of 441 patients with Covid-19 were included in the study with a mean age of 55.4 years that 47.8 %, 25.6 % and 6.8 % had impaired Prothrombin Time (PT), Partial Thromboplastin Time (PTT) and International Normalized Ratio (INR), respectively.Copyright © 2022, Health Biotechnology and Biopharma. All rights reserved.

D-dimer-driven versus standard prophylactic anticoagulation with fondaparinux in critically ill patients with COVID-19 and coagulopathy: An open-label, randomized controlled trial

Background: Anticoagulation with fondaparinux (FPX) has shown benefit to improve clinical outcomes in hospitalized patients with COVID-19. However, optimal thromboprophylaxis dosing in critically ill patients remains unknown. Purpose(s): To evaluate the effects of D-dimer-driven (DDD) FPX compared with standard prophylactic-dose (SPD) FPX in critically ill patients with COVID-19 and associated coagulopathy. Method(s): This was a single-center, open-label, two-arms, parallel-group, randomized controlled trial conducted between April 1, 2021 and Feb 28, 2022. The eligible COVID-19 patients who were critically ill (defined as a presence of critical care-level organ support at enrollment) and presented with coagulopathy were randomly assigned (1:1 ratio) to receive pragmatically defined regimens of either DDD FPX or SPD FPX throughout hospitalization. The primary efficacy outcome was a composite of all-cause mortality (ACM), acute myocardial infarction (MI), confirmed arterial (ATE) or venous thromboembolisms (VTE), assessed up to 30 days. The secondary efficacy outcomes were 30-day ACM, composite thrombotic events, progression to invasive mechanical ventilation (IMV) or ARDS, and acute kidney injury (AKI). The safety outcomes included major bleeding and clinically relevant non-major bleeding (CRNMB). Outcomes were blindly adjudicated and analysed on a 30-day intention-to-treat basis. Result(s): During allocated period, 270 (58%) of 465 patients were eligible and were equally assigned to DDD and SPD groups. The baseline characteristics were well-matched between groups (all p>0.05). At 30 days, the primary efficacy outcome was met in 49 of 135 patients (36.3%) with DDD FPX versus 47 of 135 patients (34.8%) with SPD FPX (hazard ratio [HR], 1.32;95% CI, 0.89-1.98;p=0.17). DDD group compared with SPD group revealed no significant difference in 30-day ACM (22.9% vs 31.8%;HR, 0.73;p=0.17). At 30 days, DDD group demonstrated no significant reduction in thromboembolism, i.e. acute MI (14.1% vs 11.8%;HR, 1.53;p=0.21);ATE (3.0% vs 3.0%;HR, 1.27;p=0.74);and VTE (2.2% vs 4.4%;HR, 0.69;p=0.59) when compared with SPD group. Among those not on IMV at randomization, DDD group showed no significant reduction in the proportion of patients meeting the need for IMV (18.5% vs 32.6%;HR, 0.72;p=0.18) or progression to ARDS (17.8% vs 27.4%;HR, 0.81;p=0.43). Allocation to DDD FPX had no significant effect on the proportion of patients experiencing AKI within 30 days (17.8% vs 14.8%;HR, 1.36;p=0.39). There was no significant difference between DDD and SPD groups in terms of major bleeding (2.2% vs 0%;HR, 8.35;p=0.35) or CRNMB (3.0% vs 2.2%;HR, 1.70;p=0.48) at 30 days. Conclusion(s): In critically ill patients with COVID-19 and coagulopathy, D-dimer-driven anticoagulation with fondaparinux did not significantly improve clinical outcomes at 30 days as compared to standard prophylacticdose. The risk of bleeding was not significantly increased in this trial. (Table Presented).

Possible consequences of Covid-19 on the nervous system

OBJECTIVES: The aim of the survey was to find out what the possible consequences are of the COVID-19 disease on the nervous system and to propose a method of using artificial intelligence. MATERIAL AND METHODS: Recent research has shown that the risks to patients due to severe acute coronavirus 2 respiratory syndrome (SARS-COV-2) differ most significantly depending on age and the presence of underlying comorbidities such as: cardiovascular disease, hypertension, diabetes and others. The consequences of COVID-19 on the nervous system are especially important. We performed a detailed selection of articles describing the effects of COVID-19 on the nervous system. RESULT(S): We made a clear summary of the main consequences of COVID-19 on the nervous system and suggested a way to use artificial intelligence. CONCLUSION(S): We confirmed research that artificial intelligence methods have the potential to accelerate prediction, especially for the possible consequences of COVID-19 on the nervous system.Copyright © 2020 Neuroendocrinology Letters

Plasma P-selectin is an early marker of thromboembolism in COVID-19

Objectives: The aim of this study was to explore the association of the plasma levels of coagulation proteins with venous thromboembolic events (VTE) in COVID-19 and identify candidate early markers of VTE. Background(s): Coagulopathy and thromboembolism are known complications of SARS-CoV-2 infection. The mechanisms of COVID-19-associated hematologic complications involve endothelial cell and platelet dysfunction and immunothrombosis and have been intensively studied. Yet, a full understanding of the pathogenesis and factors that lead to COVID-19 associated coagulopathy is lacking. Previous studies investigated only small numbers of coagulation proteins together, and they were limited in their ability to adjust for confounders. Method(s): This study was a post-hoc analysis of a previously published dataset (Filbin et al., 2021). We included in our analysis 305 subjects with confirmed SARS-CoV-2 infection who presented to an urban Emergency Department with acute respiratory distress during the first COVID-19 surge in 2020;13 (4.2%) were subsequently diagnosed with venous thromboembolism during hospitalization. Serial samples were obtained on days 0, 3, and 7 and assays were performed on two highly-multiplexed proteomic platforms, that in combination cover 1472 + 4776 proteins. We included 31 coagulation proteins in our analysis. Result(s): Nine coagulation proteins were differentially expressed in patients with thromboembolic events. In multivariable models, day 0 levels of P-selectin, a cell adhesion molecule on the surface of activated endothelial cells, displayed the strongest association with the diagnosis of VTE, independent of disease severity and other confounders (p=0.0025). P-selectin together with D-dimer upon hospital presentation provided better discriminative ability for VTE diagnosis than D-dimer alone (AUROC = 0.834 vs. 0.783). Conclusion(s): Our results suggest that plasma P-selectin is a potential early biomarker for the risk stratification of VTE in COVID-19 disease. Our findings support the importance of endothelial activation in the mechanistic pathway of venous thromboembolism in COVID-19.Copyright © 2023

The post-COVID-19 cardiologic pandemic.

Since the beginning of the COVID-19 pandemic, the implications for cardiology have been clear significantly greater than those caused by other respiratory viral epidemics in the past. Among several cardiovascular consequences of COVID-19 the most significant are: 1) higher risk of COVID-19 in patients with pre-existing cardiovascular disease;2) multiple cardiovascular complications in COVID-19;3) association between COVID-19 and coagulopathy;4) consequences of COVID-19 on cardiovascular pathologies of non-COVID-19 patients;and 5) impact of COVID-19 on clinical trials in cardiology.Copyright © 2022 EDIZIONI MINERVA MEDICA.

COVID-19, Blood Lipid Changes, and Thrombosis.

Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the underlying mechanism(s) remain to be understood. The purpose of this review is to highlight the role of blood lipids in association with thrombosis events observed in COVID-19 patients. Among different types of phospholipases A2 that target cell membrane phospholipids, there is increasing focus on the inflammatory secretory phospholipase A2 IIA (sPLA2-IIA), which is associated with the severity of COVID-19. Analysis indicates increased sPLA2-IIA levels together with eicosanoids in the sera of COVID patients. sPLA2 could metabolise phospholipids in platelets, erythrocytes, and endothelial cells to produce arachidonic acid (ARA) and lysophospholipids. Arachidonic acid in platelets is metabolised to prostaglandin H2 and thromboxane A2, known for their pro-coagulation and vasoconstrictive properties. Lysophospholipids, such as lysophosphatidylcholine, could be metabolised by autotaxin (ATX) and further converted to lysophosphatidic acid (LPA). Increased ATX has been found in the serum of patients with COVID-19, and LPA has recently been found to induce NETosis, a clotting mechanism triggered by the release of extracellular fibres from neutrophils and a key feature of the COVID-19 hypercoagulable state. PLA2 could also catalyse the formation of platelet activating factor (PAF) from membrane ether phospholipids. Many of the above lipid mediators are increased in the blood of patients with COVID-19. Together, findings from analyses of blood lipids in COVID-19 patients suggest an important role for metabolites of sPLA2-IIA in COVID-19-associated coagulopathy (CAC).

Neuroanesthesia practice during COVID-19: A single-center experience

The coronavirus disease 2019 (COVID-19) pandemic is a challenge for all health care providers (HCPs). Anesthesiologists are vulnerable to acquiring the disease during aerosol-generating procedures in operating theater and intensive care units. High index of suspicion, detailed history including travel history, strict hand hygiene, use of face masks, and appropriate personal protective equipment are some ways to minimize the risk of exposure to disease. Neurologic manifestations of COVID-19, modification of anesthesia regimen based on the procedure performed, and HCP safety are some implications relevant to a neuroanesthesiologist. National and international guidelines, recommendations, and position statements help in risk stratification, prioritization, and scheduling of neurosurgery and neurointervention procedures. Institutional protocols can be formulated based on the guidelines wherein each HCP has a definite role in this ever-changing scenario. Mental and physical well-being of HCPs is an integral part of successful management of patients. We present our experience in managing 143 patients during the lockdown period in India.Copyright © 2020 Wolters Kluwer Medknow Publications. All rights reserved.

Multifaceted COVID-19 Associated Coagulopathy: A Case Series

The pathophysiology behind Coronavirus Disease-2019 (COVID-19) has remained blur even after more than two years of onset of the pandemic. Apart from pulmonary parenchymal involvement, widespread vascular thrombosis affecting both pulmonary and extra-pulmonary systems has also been seen to contribute to COVID-19 associated morbidity. This vascular manifestation often remains undiagnosed due to non specific and varied symptoms that range from asymptomatic detection to life threatening presentations. A series of six COVID-19 positive (three male and three female) cases who presented with thrombosis of pulmonary, coronary and cerebral vessels despite being on thromboprophylaxis are reported herein. The age of patients ranged from 32 to 80 years. Out of six patients, three had comorbidities. The most common complication was Pulmonary Thromboembolism (PTE, n=3) followed by Brain infarct (n=2) and Myocardial Infarction (MI, n=1). Out of three patients with PTE, one patient had concurrent Deep Vein Thrombosis (DVT). All patients were managed as per guidelines issued by the Ministry of Health and Family Welfare for severe COVID-19 disease. Out of six patients, three patients died and three were discharged. The series highlights the need for high index of suspicion on the part of the treating physician that could aid in early detection and successful management of this potentially fatal condition.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

Prevalence and Course of Covid-19 in Patients with Congenital Bleeding Disorders in Russia

Introduction: Published data on the course of COVID-19 in patients with congenital bleeding disorders (CBDs) is limited. There are questions about howCOVID-19 affects the course of CBDs and, conversely, how CBDs affect the course of coronavirus infection? Some authors suggest that patients with CBDs to be less severely affected by COVID-19. The aim of the study: analysis of the prevalence and course of COVID-19 in patients with CBDs in Russia. Method(s): A web-based questionnaire was developed to collect data. The survey was conducted in the period from 25.06.2022 to 31.07.2022. A cluster of 187 patients from different regions and cities of Russia were interviewed. Result(s): The average age of patients was 37 years. The survey group consisted of 144 patients with hemophilia A, 16 with hemophilia B, 24 with vonWillebrand's disease and 1 patient with factor VII deficiency. COVID-19 affected 115 (61.5%) of 187 surveyed patients and 22 (19%) patients suffered from coronavirus infection twice. Hospitalisation was required for 14 (12.3%) patients. At the beginning of the disease, 82 (71%) patients were on prophylactic treatment with the factor concentrates;11 (10%) received therapy with emicizumab, 20 (17%) received therapy with the factor concentrates on demand and 2 (1.7%) received bypass agents. During COVID-19 different types of bleeding were observed in 9 (7.8%) patients: hemarthrosis, ecchymosis, hematomas, epistaxis, menorrhagia, haemorrhoid bleeding. Due to COVID-19 the blood coagulation parameters were monitored for 15 (13%) of 115 patients who had been ill. The haemostatic therapy regimen was changed in 19 (16.5%) patients. Anticoagulant therapy was received by 8 (7%) patients. There were no thrombotic cases. A change in the course of the underlying disease after COVID-19 was noted by 21 (18%) patients, of which 11 noted an increase in joint pain and 9 reported the appearance of pain in previously intact joints. Discussion/Conclusion: The absence of thrombotic complications in patients with CBDs and COVID-19 suggests that hypocoagulability state may be protective against COVID-19 hypercoagulability-related adverse effects. However, the aggravating condition is an increase in joint pain and the involvement of new joints possible due to both hemostatic disorders and autoimmune reaction.

Recommendations on the Management of Patients with Immune Thrombocytopenia (ITP) in the Context of SARS-CoV-2 Infection and Vaccination: Consensus Guidelines from a Spanish ITP Expert Group.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with highly variable presentation, characteristics, and clinical course. Thrombocytopenia is a common complication of many viral infections, including SARS-CoV-2. In addition, both de novo ITP and exacerbation of ITP after vaccination against SARS-CoV-2 have been reported. Patients infected with SARS-CoV-2 develop a prothrombotic coagulopathy called COVID-19-associated coagulopathy (CAC). In addition, autoimmune hematological disorders secondary to SARS-CoV-2 infection, mainly ITP and autoimmune hemolytic anemia (AIHA), have been described. Furthermore, SARS-CoV-2 infection has been associated with exacerbation of autoimmune processes, including ITP. In fact, there is evidence of a high relapse rate in patients with preexisting ITP and COVID-19. As for vaccination against SARS-CoV-2, hematological adverse events (HAE) are practically anecdotal. The most common HAE is thrombocytopenia-associated thrombosis syndrome (TTS) linked to vectored virus vaccines. Other HAEs are very rare, but should be considered in patients with previous complement activation disease or autoimmunity. In patients with ITP who are vaccinated against SARS-CoV-2, the main complication is exacerbation of ITP and the bleeding that may result. In fact, this complication occurs in 12% of patients, with splenectomized and refractory patients with more than five lines of previous treatment and platelet counts below 50 × 109/L being the most vulnerable. We conclude that, in general, there is no greater risk of severe SARS-CoV-2 infection in ITP patients than in the general population. Furthermore, no changes are advised in patients with stable ITP, the use of immunosuppressants is discouraged unless there is no other therapeutic option, and patients with ITP are not contraindicated for vaccination against COVID-19.

A case series of coagulopathy in preterm or growth-restricted term neonates born to mothers with antenatal SARS-CoV-2 infection: Neonatal post-COVID-19 coagulopathy?

Paediatric multi-system inflammatory syndrome in the form of multi-system inflammatory syndrome in children (MIS-C) and neonatal multisystem inflammatory syndrome (MIS-N) are being reported all over the world. While MIS-C is seen few weeks after active severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in the same child, MIS-N is proposed to be occurring in neonates after active SARS-CoV-2 infection in the mother in antenatal period and hyperimmune response to the transplacentally transferred maternal IgG antibodies specific to SARS-CoV-2. Most of the cases which develop MIS-N present with cardiac findings in the form of rhythm disturbances. In this article, we report data, clinical presentation and management of 15 preterm and growth-restricted term neonates who presented with bleeding in the first 2 days of life. The coagulopathy could not be explained by the common causes of bleeding in this population and was refractory to the general line of management. Laboratory results had signs of hyperimmune response (raised procalcitonin [PCT], C-reactive protein [CRP]) and remarkably deranged coagulation profile (very high d-dimer levels with normal platelet counts and normal-to-high fibrinogen values). Most of the mothers had history of symptomatic COVID-19 infection in the antenatal period, and although all (including neonates) were negative by real-time polymerase chain reaction for SARS-CoV-2, serological testing showed positivity for IgG fraction of antibodies specific to SARS-CoV-2, but negative for IgM antibodies. This observation was similar to the phenomenon of MIS-N; however in our study, the hyperinflammatory response primarily affected the coagulation system. Although COVID-19 coagulopathy has been described in adults, it has been reported in the presence of severe active SARS-CoV-2 infection, unlike a delay of several weeks seen in our study. Hence, the term 'Neonatal post-COVID-19 coagulopathy' as proposed in this article needs further research and validation.

Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy.

COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19.

Thrombin generation test in COVID-19 related coagulopathy

Introduction: critically ill COVID-19 patients are known to have a coagulopathy characterized by increased levels of D-dimer (DD) associated to a thrombotic risk and a significant increase in mortality. However, it is not known whether the associated COVID-19 coagulopathy is due to a prothrombotic state or is caused by endothelial dysfunction and inflammation. Aim of our study, was to better characterize the hypercoagulability state of COVID-19 patients using Thrombin Generation analyser (ST Genesia, Diagnostica Stago, Asnieres, France). Method(s): a total of 46 non-critically ill hospitalized COVID-19 patients were compared to 19 critically ill COVID-19 patients utilizing calibrated automated thrombography and other biochemical, hematological and coagulation parameters. Result(s): critically ill patients had a significant increase in C reactive protein (CRP), interleukin-6 (IL-6), prothrombin time (PT), DD and a significant decrease in lymphocytes count. No significant differences in Thrombin Generation Test (TGT) parameters were observed between the two groups of patients with the only exception of the "Lag Time" parameter. Discussion(s): the obtained results confirmed increased levels of DD and PT in critically ill COVID-19 patients. Of note, disease severity did not cause an increase in Thrombin Generation when compared to non-critically COVID-19 patients. The significantly prolonged Lag Time in critically ill COVID-19 patients without decreased endogenous thrombin potential suggests an hypocoagulability state in these patients. The relevance of this finding is uncertain and may appear counterintuitive since these patients are expected to have a hypercoagulability status, and requires further research. Copyright © 2022 Biomedia. All rights reserved.

Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Sera from donors of COVID-19 convalescent plasma do not induce procoagulant phenotype in platelets

Background: COVID-19 convalescent plasma (CCP) has been suggested to be beneficial to prevent disease progression in COVID-19. However, concerns have been expressed whether plasma components in CCP can shift the already imbalanced coagulation system to a more hypercoagulable state. Aim(s): To investigate the effect of CCP on platelet phenotype and activation. Method(s): We investigated platelets from CCP donors who had a history of mild COVID-19 infection. Donors who did not have COVID-19 were used as controls (non-CCP donors). We analyzed phosphatidylserine (PS) externalization, CD62p expression, and GPVI shedding in healthy platelets after incubation with sera from CCP and non-CCP donors using flow cytometry. The study protocol was approved by the ethics committee of the University Hospital of Tubingen. (Figure Presented) Results: Forty-seven CCP donors [22 Male, 25 Female;and mean age (+/-SD) 41.4 +/- 13.7 years] with a history of mild COVID-19 infection were included. Median duration after acute COVID-19 infection was 97 days (range, 34-401). Compared to sera from non-CCP donors, sera from CCP donors did not induce higher PS externalization (Fold increase [FI] of PS positive platelets: 1.16% +/- 0.66 vs. 1.51% +/- 0.74, respectively, p = 0.11) or increased the rate of CD62p/PS double positive procoagulant phenotype (FI in CD62p/PS positive platelets: 1.86 +/- 0.87 vs. 1.37 +/- 0.63, respectively, p = 0.10) in platelets from healthy persons. Of note, CD62p expression in healthy platelets after incubation with sera from CCP plasma donors was significantly lower compared to sera from non-CCP donors (FI in CD62p: 2.09 +/- 1.36 vs. 1.16 +/- 0.45, p< 0.01). Sera-mediated GPVI shedding was similar between non-CCP and CCP donors (1.07 +/- 0.16 vs. 1.27 +/- 0.91, p = 0.52). Conclusion(s): Our findings support data from clinical studies, which indicate that transfusion of CCP to treat or prevent severe COVID-19 is not associated with increased risk of exacerbation of the coagulopathy in COVID-19.

Investigation of thrombin generation in COVID-19 patients by a care setting design

Background: The coagulation system showed significant variations in COVID-19 patients. These variations may parallel the disease stage of COVID-19 toward either a hyper-activation or coagulopathy syndrome. Classical clotting tests assist in exploring coagulation disorders, but they are unsuitable to examine prothrombotic conditions. In this regard, thrombin generation assay helps for a global assessment of the coagulation process, being appropriate for investigating hypercoagulable states and bleeding tendency. Aim(s): It was investigated whether thrombin generation assay reveals coagulation variations in COVID-19 patients by a care setting design. Method(s): From October to December 2020, it have been enrolled 27 and 40 patients with a confirmed COVID-19 diagnosis who were hospitalised in an Intensive Care Unit (ICU) and a Medical Ward (MW), respectively. Also, 34 healthy subjects were included in this study. Thrombin generation parameters were evaluated using a Calibrated Automated Thrombogram system. Informed consent and approval by the local medical Ethics Committee were obtained. Result(s): Lag-Time and time-to- peak found in ICU and MW patients were significantly higher than those found in healthy subjects (Kruskal-Wallis test: P < 0.0001). Endogenous-Thrombin- Potential and thrombin-peak observed in ICU and MW patients were significantly lower than those observed in healthy subjects (Kruskal-Wallis test: P < 0.0001). No statistically significant differences in all the parameters measured were observed between ICU and MW patients. Conclusion(s): Thrombin generation assay performed in this study evidenced an acquired coagulopathy in COVID-19 patients that, however, seems to be unrelated to the care setting and, in turn, to the clinical disease severity.

Clinical assessment of coagulation hemostasis in liver cirrhosis associated with COVID-19

Background: Since the beginning of the pandemic, our understanding of the hepatic repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) infection and the resulting coronavirus disease 2019 has significantly progressed. Aim(s): The primary objective of this study was to characterize coagulation hemostasis in patients with COVID-19- associated liver cirrhosis. Method(s): Our study involved 200 patients (confirmed COVID-19 ) with liver cirrhosis, decompensation stage, Child-Pugh class V as the objects of study. I group consisted of 50 patients with liver cirrhosis of HBV etiology, II group 30 patients with HBV + HDV liver cirrhosis, III groups 50 patients with cirrhosis of unknown etiology. The control group consisted of 20 healthy individuals. All patients were tested for coagulogram. Result(s): In group I, activated partial thromboplastin time was 18.4 +/- 2.3 c, prothrombin time was 9.5 +/- 0.6 c, prothrombin index was 126 +/- 6.4, and MNO was 0.79 +/- 0.03. In group II, activated partial thromboplastin time was 15.2 +/- 1.1 c, prothrombin time was 8.2 +/- 0.4 c, prothrombin index was 146 +/- 8.2, and the international normalized ratio was 0.68 +/- 0.02. In group III, was 12.2 +/- 0.8 c, prothrombin time was 7.9 +/- 0.4 c, prothrombin index was 152 +/- 10.4, and the international normalized ratio was 0.66 +/- 0.02. In the control group, activated partial thromboplastin time was 32 +/- 1.8 c, prothrombin time was 12.1 +/- 0.2 c, prothrombin index was 99 +/- 3.7, and the international normalized ratio was 1.01 +/- 0.06. Conclusion(s): To summarize, our findings demonstrate that severe COVID-19 infection is associated with coagulopathy, which is associated with a bad prognosis. COVID-19 coagulopathy, on the other hand, does not appear to be a form of disseminated intravascular coagulation. Additional research is required to elucidate additional probable mechanisms of this coagulopathy, including a thorough examination of the fibrinolytic system.