Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination.

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.

Coagulation System Activation for Targeting of COVID-19: Insights into Anticoagulants, Vaccine-Loaded Nanoparticles, and Hypercoagulability in COVID-19 Vaccines.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is currently developing into a rapidly disseminating and an overwhelming worldwide pandemic. In severe COVID-19 cases, hypercoagulability and inflammation are two crucial complications responsible for poor prognosis and mortality. In addition, coagulation system activation and inflammation overlap and produce life-threatening complications, including coagulopathy and cytokine storm, which are associated with overproduction of cytokines and activation of the immune system; they might be a lead cause of organ damage. However, patients with severe COVID-19 who received anticoagulant therapy had lower mortality, especially with elevated D-dimer or fibrin degradation products (FDP). In this regard, the discovery of natural products with anticoagulant potential may help mitigate the numerous side effects of the available synthetic drugs. This review sheds light on blood coagulation and its impact on the complication associated with COVID-19. Furthermore, the sources of natural anticoagulants, the role of nanoparticle formulation in this outbreak, and the prevalence of thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccines are also reviewed. These combined data provide many research ideas related to the possibility of using these anticoagulant agents as a treatment to relieve acute symptoms of COVID-19 infection.

[Update 2021: COVID-19 from the Perspective of Haematology and Haemostaseology]. / Update 2021: COVID-19 aus Sicht der Hämatologie und Hämostaseologie.

Infection with SARS-CoV-2 has a profound influence on the hematopoetic system that mediates clinical symptoms and mortality. Several studies have shown that treatment of the cytokine storm (CRS) with anti-inflammatory drugs like dexamethasone and tocilizumab can significantly improve survival. Systematic reviews confirm the safety of convalescent plasma administration and offer initial indications of its effectiveness in certain groups. COVID-associated coagulopathy (CAC) and vaccine-induced immune thrombotic thrombocytopenia (VITT) represent severe infection- or vaccination associated complications that require a specific diagnostic and therapeutic workup.

[Title: Covid-19-associated coagulopathy]. / COVID-19-assoziierte Koagulopathie.

COVID-19, primarily a respiratory disease, is considered a multi-systemic disease as symptom severity increases. Blood coagulation abnormalities are key features of patients with severe symptoms and indicative of the high risk of both venous and arterial thromboembolism in COVID-19. This prothrombotic condition caused by an interplay of the infectious agent, inflammation, and the blood coagulation system is referred to as COVID-19-associated coagulopathy and characterized by greatly increased D-dimer, high fibrinogen, an extended prothrombin time, and a reduced number of platelets. Due to this high thrombotic potential, prophylactic anticoagulation is recommended in all hospitalized patients. However, the optimal dosage of anticoagulation is still debated. In this article, we provide an overview of the current state of knowledge about COVID-19-associated coagulopathy and discuss clinical therapeutic consequences.

A proposal for the management of COVID-19-induced coagulopathy in adults.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has a high case fatality rate. Most severely ill patients develop a special type of coagulopathy that had not been described before and that is now considered the main cause of death. For this reason, anticoagulant treatment has become one of the cornerstones of the treatment of this infection. However, the rate at which the evidence regarding the use of anticoagulants is generated is quite fast, and sometimes it is difficult to interpret and conflicting. After having performed an extensive review of the published literature, this proposal for the use of anticoagulant treatment is made, taking into account available resources in Mexico.

La infección por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es la causante de la pandemia de enfermedad por coronavirus 2019 (COVID-19), con un índice de letalidad alto. La mayoría de los pacientes graves desarrollan un tipo especial de coagulopatía no descrito hasta ahora y la cual se considera ahora la principal causa de muerte. Por esta razón, el tratamiento anticoagulante se ha convertido en una de las piedras angulares del tratamiento de esta infección. Sin embargo, la velocidad con la que se genera la evidencia respecto al uso de anticoagulantes es muy rápida y, en ocasiones difícil de interpretar y contradictoria. Luego de hacer una revisión extensa de la literatura publicada, se hace esta propuesta para el uso del tratamiento anticoagulante tomando en cuenta los recursos disponibles en México.

[COVID-19: Coagulopathy and thrombosis]. / COVID-19 : coagulopathie et thrombose.

The SARS-CoV-2 virus caused a global pandemic within weeks. Many patients with severe COVID-19 present with coagulation abnormalities, including increase D-dimers. This coagulopathy is associated with an increased risk of death. Furthermore, a substantial proportion of patients with severe COVID-19 develop sometimes unrecognized, venous thromboembolic complications. A better understanding of COVID-19 pathophysiology, in particular hemostatic disorders, will help to choose appropriate treatment strategies. A rigorous thrombotic risk assessment and the implementation of a suitable anticoagulation strategy are required. We review here the characteristics of COVID-19 coagulation laboratory findings in affected patients, the incidence of thromboembolic events and their specificities, and potential therapeutic interventions.

Contribution value of coagulation abnormalities in COVID-19 prognosis: a bright perspective on the laboratory pattern of patients with coronavirus disease 2019.

OBJECTIVE: From the beginning of the novel coronavirus infection (COVID-19) pandemic in the world, much efforts have been accomplished to explain a precise clinical feature for the disease and to find the best therapeutic approach for the patients. Although coagulation abnormalities have found in novel coronavirus infection (COVID-19) patients, still little is known about the association between the disease and changes in coagulation parameters. Our purpose is to evaluate the differences between the coagulation parameters between COVID-19 patients and healthy counterparts. PATIENTS AND METHODS: 63 patients with confirmed COVID-19 infection were admitted to the present study. We evaluated coagulation value in these patients and in 40 healthy individuals. RESULTS: We found that although there was no significant difference between PT and PTT values in patients and healthy counterparts, the fibrinogen values in patients were higher than the control group (p < 0.05). Moreover, the values of fibrin/fibrinogen degradation products (FDP) and D-dimer in all COVID-19 cases were considerably higher than those in control people (p < 0.05). Of note, FDP and D-dimer in patients with regular COVID-19 infection were lower than patients with severe forms. CONCLUSIONS: It seems that the conduction of routine blood coagulation test could be a beneficial supplementary approach for early diagnosis of COVID-19. In addition, our study shed more light on the therapeutic value of anti-coagulant-based treatment for COVID-19 patients, especially for those with severe type of the disease.

COVID-19-associated coagulopathy.

Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized as a systemic disorder inducing a prothrombotic state. The molecular mechanisms underlying the hypercoagulable state seen in patients with COVID-19 is still incompletely understood, although it presumably involves the close link between inflammatory and hemostatic systems. The laboratory coagulation monitoring of severely ill COVID-19 patients is mandatory to identify those patients at increased thrombotic risk and to modulate thromboprophylaxis accordingly. In this review, we summarize the current understanding on the pathogenesis, epidemiology, clinical and laboratory features and management of coagulopathy associated with COVID-19.

Alteraciones de la coagulación en la COVID-19.

Infection with the SARS-CoV-2 virus and the development of all manifestations of COVID-19, predisposes to arterial and venous thromboembolic disease. The coagulation system can be activated by various viruses, including SARS-CoV-2. Vascular endothelial damage, added to the development of disseminated intravascular coagulation, affects the prognosis and mortality from this disease. Treatment is aimed at the prevention, early detection and timely interventions of all coagulation disorders generated by COVID-19. The recommended anticoagulant is low molecular weight heparin, taking into account creatinine clearance, and if major invasive procedures will be performed, unfractionated heparin is a safe option.

La infección por el virus SARS-CoV-2 y el desarrollo de todas las manifestaciones de COVID-19 predisponen a la enfermedad tromboembólica arterial y venosa. El sistema de coagulación puede ser activado por diversos virus, entre ellos el SARS-CoV-2. El daño endotelial vascular, sumado al desarrollo de coagulación intravascular diseminada, afecta el pronóstico y la mortalidad de esta enfermedad. El tratamiento está dirigido a la prevención, la detección temprana y las intervenciones oportunas de todas las alteraciones de la coagulación generadas por la COVID-19. El anticoagulante recomendado es la heparina de bajo peso molecular, tomando en cuenta el aclaramiento de creatinina, y si se realizarán procedimientos invasivos mayores, la heparina no fraccionada es una opción segura.

Coronavirus Disease 2019: Clinical Review.

INTRODUCTION: In December 2019, an outbreak of pneumonia caused by a novel coronavirus occurred in Wuhan, the capital of Central China's Hubei Province and has been declared a public health emergency of international concern by the World Health Organization since January 2020. MATERIAL AND METHODS: A comprehensive search using the PubMed database was carried out to summarize the latest published information about the epidemiology, definition, pathogenesis, clinical characteristics, treatment options, prognosis and prevention of coronavirus disease 2019. DISCUSSION: This new strain of coronavirus, named severe acute respiratory syndrome coronavirus 2, enters human cells that express angiotensin-converting enzyme II receptors, which exist in the respiratory, gastrointestinal and genitourinary tracts and heart, causing coronavirus disease. Transmission occurs essentially through the respiratory tract and the main symptoms are fever, cough and dyspnea. Diagnosis is based on epidemiological, clinical and imaging features and confirmed by nucleic acid testing. CONCLUSION: Despite intensive research, the exact origin of the virus and pathophysiology of coronavirus disease is not yet completely known, and clinically approved vaccines and drugs that target severe acute respiratory syndrome coronavirus 2 are lacking.

Introdução: Em dezembro de 2019, ocorreu um surto de pneumonia causada por uma nova estirpe de coronavírus em Wuhan, a capital da província de Hubei, na China central e foi declarado emergência de saúde pública de âmbito internacional pela Organização Mundial de Saúde, em janeiro de 2020. Material e Métodos: Foi realizada uma pesquisa na base de dados PubMed, de forma a sintetizar a informação mais recentemente publicada sobre a epidemiologia, definição, fisiopatologia, manifestações clínicas, tratamento, prognóstico e prevenção da doença de coronavírus 2019. Discussão: Esta nova estirpe de coronavírus, denominada coronavírus da síndrome respiratória aguda grave 2 infeta células que expressem o recetor da enzima conversora da angiotensina tipo II, existentes nos tratos respiratório, gastrointestinal e geniturinário e no coração, provocando a doença de coronavírus 2019. A transmissão ocorre essencialmente através do trato respiratório e os principais sintomas são febre, tosse e dispneia. O diagnóstico é baseado em critérios epidemiológicos, clínicos e imagiológicos, sendo a confirmação da doença realizada através da análise de ácidos nucleicos. Conclusão: Apesar da extensa investigação, ainda não é totalmente conhecida a origem do vírus, a fisiopatologia da doença e não existem vacinas nem tratamento direcionados a esta nova estirpe de coronavírus.

Coronavirus Disease 2019: Hematological Anomalies and Antithrombotic Therapy.

After the first cases of COVID-19 appeared in Wuhan, China at the end of 2019, the disease quickly become a pandemic that has seriously affected the economic and health systems in more than 200 countries and territories around the world. Although most patients have mild symptoms or are even asymptomatic, there are patients who can develop serious complications such as acute respiratory distress syndrome or venous thromboembolism requiring mechanical ventilation and intensive care. Hence, it is important to identify patients with a higher risk of complications in a timely manner. Thus, the objective of this paper is to review the hematological laboratory parameters that consistently are altered in COVID-19 and to identify their relationship with the severity of the disease. According to 11 selected reports, the frequency of patients aged > 65 years is higher among subjects severely affected or deceased; likewise, males predominantly suffer from comorbidities such as hypertension, diabetes or obesity. Retrospective studies have identified alterations in various hematological and inflammatory parameters as part of the host's response to infection and a secondary increased risk of different thrombotic events. Among these altered parameters, D-dimer, C-reactive protein, and interleukin-6 have been tested as prognostic biomarkers due to their close relationship with the severity of the disease. Actually, they can reliably indicate the use of antithrombotic therapy at prophylactic or therapeutic doses (mainly D-dimer), as has already been established in those patients who, after an individualized assessment, appear to be at high risk for thrombotic events.

Current Overview on Hypercoagulability in COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought many unique pathologies, such as coagulopathy, prompting a desperate need for effective management. COVID-19-associated coagulopathy (CAC) can cause various thromboembolic complications, especially in critically ill patients. The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors. Data on treatment are limited, although prophylactic anticoagulation is advised in all hospitalized patients. Herein, we have comprehensively reviewed the current literature available on CAC and highlight the pathogenesis, clinical features, and management of CAC.

SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection. / Recomendaciones de consenso SEDAR-SEMICYUC sobre el manejo de las alteraciones de la hemostasia en los pacientes graves con infección por COVID-19.

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis.

PPIs and Beyond: A Framework for Managing Anticoagulation-Related Gastrointestinal Bleeding in the Era of COVID-19.

Coronavirus disease of 2019 (COVID-19) can be associated with high morbidity and mortality; patients with severe clinical manifestations may develop significant coagulopathy as well as unexpected thromboembolic complications. In response, centers are increasingly treating selected patients with intermediate-dose prophylactic or even therapeutic dose anticoagulation in order to prevent potentially catastrophic thrombotic complications. With this changing practice, the authors suspect that inpatient gastrointestinal consult teams across the country will be frequently managing COVID-19 patients with gastrointestinal bleeding (GIB). In order to reduce potentially avoidable hospital readmissions for GIB while improving patient outcomes, it is imperative to appropriately risk-stratify patients prior to initiation of anticoagulation. In this review, we discuss how to appropriately identify high-risk patients for GIB and how to mitigate GIB risk with proton-pump inhibitor co-therapy, medication reconciliation, and Helicobacter pylori testing and treating in this complex and morbid population.

Coagulopathy of Coronavirus Disease 2019.

OBJECTIVES: Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose of this review is to provide current knowledge of this serious problem. DESIGN: Narrative review. DATA SOURCES: Online search of published medical literature through PubMed using the term "COVID-19," "SARS," "acute respiratory distress syndrome," "coronavirus," "coagulopathy," "thrombus," and "anticoagulants." STUDY SELECTION AND DATA EXTRACTION: Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles. DATA SYNTHESIS: Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, D-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased D-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. D-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.