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1.
Platelets ; 33(1): 48-53, 2022 Jan 02.
Article in English | MEDLINE | ID: covidwho-1541393

ABSTRACT

Coagulopathy is an evident complication of COVID-19 with predominance of a prothrombotic state. Platelet activation plays a key role. The terms "hyper-reactivity" and "hyperactivity" used in recent literature may not be clear or sufficient to explain the pathological events involved in COVID-related thrombosis (CRT). Inflammation may play a bigger role compared to thrombosis in COVID-related mortality because a smaller percentage of patients with COVID-19 die due to direct effects of thrombosis. Not all COVID-19 patients have thrombocytopenia and a few show thrombocytosis. We believe the platelet pathology is more complex than just activation or hyper-activation, particularly due to the platelets' role in inflammation. Understanding the pathology and consequences of platelets' role may help optimize management strategies and diminish CRT-associated morbidity and mortality. In this viewpoint report, we examine the published evidence of platelet hyper-reactivity in COVID-19 with a focused analysis of the key pathologies, diverse alterations, disease outcomes, and therapeutic targets. We believe that COVID-19 is a disease of inflammation and pathologic platelets, and based on the complexity and diverse pathologies, we propose the term "thrombocytopathy" as a more reflective term of the platelets' involvement in COVID-19. In our opinion, thrombocytopathy is the unpredictable pathologic alterations of platelets in function, morphology and number, caused by different factors with a variety of presentations.


Subject(s)
Blood Platelets/pathology , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Pulmonary Embolism/complications , SARS-CoV-2/pathogenicity , Abciximab/therapeutic use , Acute Disease , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Blood Platelets/drug effects , Blood Platelets/virology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Clopidogrel/therapeutic use , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Fibrinolytic Agents/therapeutic use , Humans , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Platelet Activation/drug effects , Pulmonary Embolism/diagnosis , Pulmonary Embolism/drug therapy , Pulmonary Embolism/virology , Treatment Outcome
2.
Diabetes Metab Syndr ; 16(1): 102356, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1536514

ABSTRACT

BACKGROUND AND AIMS: The novel coronavirus disease (COVID-19) caused by SARS-CoV-2 has turned the world topsy-turvy since its onset in 2019. The thromboinflammatory complications of this disease are common in critically ill patients and associated with poor prognosis. Symmetrical peripheral gangrene (SPG) is characterized by symmetrical distal gangrene in absence of any large vessel occlusion or vasculitis and it is usually associated with critical illness. Our aim was to report the clinical profile and outcome of patients diagnosed with SPG associated with COVID-19. To the best of our knowledge, no such similar cases have been reported till date. METHODS: In this case series, we have discussed the clinical presentation, laboratory parameters and outcome in a series of two patients of SPG associated with COVID-19 and also compared those findings. Due to paucity of data, we also reviewed the literature on this under-diagnosed and rarely reported condition and association. RESULTS: Two consecutive patients (both males, age range: 37-42 years, mean: 39.5 years) were admitted with the diagnosis of COVID-19 associated SPG. Both patients had clinical and laboratory evidence of disseminated intravascular coagulation (DIC). Leucopenia was noted in both patients. Despite vigorous therapy, both patients succumbed to their illness within a fortnight of admission. CONCLUSION: SPG in the background of COVID-19 portends a fatal outcome. Physicians should be aware of its grim prognosis.


Subject(s)
COVID-19/complications , Gangrene/etiology , Adult , COVID-19/diagnosis , Critical Illness , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/virology , Fatal Outcome , Gangrene/diagnosis , Humans , India , Leukopenia/diagnosis , Leukopenia/virology , Male , Prognosis , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/virology
4.
Arch Med Res ; 52(8): 788-797, 2021 11.
Article in English | MEDLINE | ID: covidwho-1329672

ABSTRACT

The diagnostic criteria of overt disseminated intravascular coagulation (DIC) were established by the International Society on Thrombosis and Haemostasis (ISTH) in 2001. Since then, DIC has long been associated with adverse outcomes. However, recent advances in sepsis shed light on the role of coagulation disorders in the progression of sepsis. Currently, inflammation and coagulation are recognized as the two drivers that promote organ dysfunction in sepsis and septic shock. The ISTH has published new diagnostic criteria for improved management, namely sepsis-induced coagulopathy (SIC), in 2017. SIC is a pragmatic scoring system composed of platelet count, prothrombin time, and organ dysfunction score to detect the early-stage of sepsis-associated DIC. Since overt DIC represents an uncompensated coagulation disorder, a two-step approach using SIC and overt DIC criteria is a novel strategy to evaluate the severity and manage this challenging complication. Although there is no globally agreed on anticoagulant therapy for DIC, the Japanese Surviving Sepsis Campaign Guidelines 2020 recommend using antithrombin and recombinant thrombomodulin for sepsis associated DIC. Since research in this area has been previously reported, an international collaborative study is necessary to develop future diagnostic tools and treatment strategies.


Subject(s)
Blood Coagulation Disorders , Disseminated Intravascular Coagulation , Sepsis , Shock, Septic , Thrombosis , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/therapy , Humans , Sepsis/complications , Sepsis/diagnosis
5.
Anaesthesiol Intensive Ther ; 53(2): 108-114, 2021.
Article in English | MEDLINE | ID: covidwho-1308509

ABSTRACT

INTRODUCTION: Infection with SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome requiring mechanical ventilation under the conditions of the Intensive Care Unit (ICU). The state of hypercoagulation described in COVID-19 may deepen respiratory failure, leading to increased mortality. The aim of the presented study is to characterise the haemostatic profile based on the results of clotting system parameters and risk assessment of thromboembolic complications of patients hospitalised in the ICU. MATERIAL AND METHODS: This retrospective study covered the first 10 adult patients hospitalised in the ICU of the Hospital for Infectious Diseases in Warsaw in the second quarter of 2020. Demographic, clinical and laboratory parameters of the coagulation system and the risk of thromboembolic complications were assessed. Well known criteria of haemostatic disorders were used to classify the observed derangements. RESULTS: The most frequently observed deviations in the coagulation system were high concentrations of D-dimer and fibrinogen. In select cases the clotting time was prolonged. No severe thrombocytopenia was observed. All patients presented a high risk of thromboembolic complications as assesed by the Padua score. The observed clotting abnormalities did not meet the criteria for DIC (disseminated intravascular coagulation) and SIC (sepsis-induced coagulopathy) diagnosis. CONCLUSIONS: The main elements of coagulopathy that were observed in our cases differ from those usually seen in patients with recognised sepsis. The unique haemostatic profile of COVID-19 patients treated in the ICU has been described as CAC (COVID-19-associated coagulopathy).


Subject(s)
COVID-19/complications , COVID-19/therapy , Disseminated Intravascular Coagulation/diagnosis , Sepsis/diagnosis , Adult , Blood Coagulation Tests/methods , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inflammation Mediators/blood , Intensive Care Units , Male , Middle Aged , Poland , Retrospective Studies , Sepsis/blood , Sepsis/etiology
6.
Molecules ; 25(19)2020 Sep 24.
Article in English | MEDLINE | ID: covidwho-1302391

ABSTRACT

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Peptides/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory System Agents/therapeutic use , Acute Disease , Anti-Inflammatory Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Betacoronavirus/drug effects , Betacoronavirus/growth & development , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Host-Pathogen Interactions/drug effects , Humans , Immunologic Factors/chemical synthesis , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Pandemics , Peptides/chemical synthesis , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/prevention & control , Respiratory Insufficiency/virology , Respiratory System Agents/chemical synthesis , SARS-CoV-2 , Structure-Activity Relationship
7.
J Stroke Cerebrovasc Dis ; 30(9): 105938, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1281473

ABSTRACT

Coronavirus is a novel human pathogen causing fulminant respiratory syndrome (COVID-19). Although COVID-19 is primarily a disease of the lungs with florid respiratory manifestations, there are increasing reports of cardiovascular, musculoskeletal, gastrointestinal, and thromboembolic complications. Developing an effective and reliable vaccine was emergently pursued to control the catastrophic spread of the global pandemic. We report a fatal case of vaccine-induced immune thrombotic thrombocytopenia (VITT) after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. We attribute this fatal thrombotic condition to the vaccine due to the remarkable temporal relationship. The proposed mechanism of VITT is production of rogue antibodies against platelet factor-4 resulting in massive platelet aggregation. Healthcare providers should be aware of the possibility of such fatal complication, and the vaccine recipients should be warned about the symptoms of VITT.


Subject(s)
COVID-19 Vaccines/adverse effects , Disseminated Intravascular Coagulation/chemically induced , Purpura, Thrombotic Thrombocytopenic/chemically induced , Sagittal Sinus Thrombosis/etiology , Vaccination/adverse effects , Adult , COVID-19 Vaccines/administration & dosage , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/physiopathology , Fatal Outcome , Female , Humans , Purpura, Thrombotic Thrombocytopenic/blood , Purpura, Thrombotic Thrombocytopenic/diagnosis , Purpura, Thrombotic Thrombocytopenic/physiopathology , Sagittal Sinus Thrombosis/diagnostic imaging , Sagittal Sinus Thrombosis/physiopathology , Treatment Outcome
8.
Viruses ; 13(6)2021 06 01.
Article in English | MEDLINE | ID: covidwho-1259619

ABSTRACT

In recent weeks, adverse reactions have been reported after administration of Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , COVID-19/immunology , Clinical Laboratory Techniques , Dexamethasone/therapeutic use , Disseminated Intravascular Coagulation/drug therapy , Enoxaparin/therapeutic use , Female , Humans , Middle Aged , SARS-CoV-2/immunology , Vaccination
9.
J Thromb Thrombolysis ; 52(1): 338-344, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1204923

ABSTRACT

Coronavirus disease (COVID-19) initiates several life-threatening complications including coagulopathies with a unique characteristic that made this problem challenging. Here we presented 4 cases of RT-PCR positive patients that have experienced deadly intraperitoneal hemorrhage with fourth WHO Bleeding Grade after overcoming their respiratory phase. COVID-19 could induce several coagulopathies with different features that besides iatrogenic interventions increases its mortality and morbidity due to lack of clinical evidence based on well-designed randomized clinical trials on anticoagulation therapies (AT) and administration of varieties of newly approved and non-approved medicines. This report showed the urgent need for investigation on the pathophysiology of COVID-19-associated coagulopathy esp. in hemorrhagic events which are needed to make the best therapeutic decision.


Subject(s)
Blood Coagulation , COVID-19/complications , Disseminated Intravascular Coagulation/etiology , Hemorrhage/etiology , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/therapy , Fatal Outcome , Hemorrhage/blood , Hemorrhage/diagnosis , Hospital Mortality , Humans , Male , Middle Aged , Peritoneum
10.
Sci Rep ; 11(1): 7792, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1174699

ABSTRACT

SARS-CoV-2 infection increases the risk of thrombosis by different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with thromboembolic risk and unfavorable prognosis. We aim to systematically and comprehensively evaluate the association between thrombin generation parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 patients. A total of 127 hospitalized patients with confirmed COVID-19, 24 hospitalized patients with SARS-CoV-2-negative pneumonia and 12 healthy subjects were included. Clinical characteristics, thrombin generation triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed. Despite the frequent use of heparin, COVID-19 patients had similar thrombin generation to healthy controls. In COVID-19 patients, the thrombin generation lag-time positively correlated with markers of cell lysis (LDH), inflammation (CRP, IL-6) and coagulation (D-dimer), while the endogenous thrombin potential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with fibrinogen levels. Patients with more prolonged lag-time and decreased ETP had higher peak ISTH-DIC scores, and had more severe disease (vascular events and death). The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p = 0.006), and with the occurrence of major adverse events (composite end-point of vascular events and death) (HR 2.38; p = 0.004). The thrombin generation ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19.


Subject(s)
COVID-19/diagnosis , Thrombin/analysis , Adult , Aged , Blood Coagulation Tests , COVID-19/blood , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/diagnosis , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Male , Middle Aged , Prognosis , SARS-CoV-2/isolation & purification , Thrombosis/blood , Thrombosis/diagnosis
11.
J Stroke Cerebrovasc Dis ; 30(7): 105805, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1171128

ABSTRACT

INTRODUCTION: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke. METHODS: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted. RESULTS: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes.


Subject(s)
Arrhythmias, Cardiac/epidemiology , COVID-19/epidemiology , Disseminated Intravascular Coagulation/epidemiology , Ischemic Stroke/epidemiology , Venous Thromboembolism/epidemiology , Adult , Aged , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/mortality , Arrhythmias, Cardiac/therapy , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/therapy , Female , Hospital Mortality , Hospitalization , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Ischemic Stroke/therapy , Male , Middle Aged , Observational Studies as Topic , Prevalence , Prognosis , Risk Assessment , Risk Factors , Time Factors , Venous Thromboembolism/diagnosis , Venous Thromboembolism/mortality , Venous Thromboembolism/therapy
12.
Minerva Med ; 112(6): 701-712, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1134671

ABSTRACT

INTRODUCTION: Disseminated intravascular coagulation (DIC) has long been understood as a condition where both thrombotic and hemostatic abnormalities coexist. DIC is a difficult complication for clinicians to manage as it is due to multiple underlying complications of pathophysiologic abnormalities in diverse disease states. Ongoing research continues to define the meaning of DIC, evaluate therapeutic options, and how it presents with the complex paradigm of systemic activation of coagulation. In this review we introduce the current topics regarding this difficult situation. EVIDENCE ACQUISITION: Online search of published medical literature through MEDLINE and Web of Science using the term "disseminated intravascular coagulation," "coagulopathy," "coagulation disorder," "hemostasis," "fibrinolysis," "thrombus" and "anticoagulants." EVIDENCE SYNTHESIS: Articles were chosen for inclusion based on their relevance to disseminated intravascular coagulation, coagulopathy, hemostasis and thrombosis in sepsis, COVID-19, trauma, and obstetrics. Reference lists were reviewed to identify additional relevant articles. CONCLUSIONS: DIC is recognized as a pathologically triggered and dysregulated systemic activation of coagulation in response to various noxious stimuli. DIC's phenotype and clinical manifestations can vary from prothrombotic to hemorrhagic, depending on the underlying diseases. However, the fundamental mechanisms of systemic and vascular endothelial dysfunction can be explained as different phases of the acute response, with an initial prothrombotic phase that can commonly change to hemostatic insufficiency. Thrombin is the key initiator of the pathophysiologic process along with endothelial injury and initially fibrinolysis activation followed by fibrinolysis suppression. There is no established approach for managing DIC beyond initially treating the underlying disease and replacement therapy for the management of coagulopathy. Targeting anticoagulation therapy with antithrombin concentrates and recombinant thrombomodulin for the prevention of microthrombus formation, and antifibrinolytic therapy using tranexamic acid for the coagulopathy after massive bleeding, continue to be studied as therapeutic options.


Subject(s)
Blood Coagulation Disorders/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/physiopathology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/physiopathology , Humans
13.
Vopr Virusol ; 66(1): 40-46, 2021 03 07.
Article in Russian | MEDLINE | ID: covidwho-1120830

ABSTRACT

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.


Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , COVID-19/drug therapy , Coronary Disease/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Hypertension/drug therapy , Intracranial Arteriosclerosis/drug therapy , Acetylcysteine/therapeutic use , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Atrial Fibrillation/diagnosis , Atrial Fibrillation/mortality , Atrial Fibrillation/virology , Azithromycin/therapeutic use , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Cohort Studies , Comorbidity , Coronary Disease/diagnosis , Coronary Disease/mortality , Coronary Disease/virology , Dabigatran/therapeutic use , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Female , Humans , Hypertension/diagnosis , Hypertension/mortality , Hypertension/virology , Indoles/therapeutic use , Interferon alpha-2/therapeutic use , Intracranial Arteriosclerosis/diagnosis , Intracranial Arteriosclerosis/mortality , Intracranial Arteriosclerosis/virology , Male , Middle Aged , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Rivaroxaban/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Severity of Illness Index , Survival Analysis
14.
Int J Hematol ; 113(3): 320-329, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1064612

ABSTRACT

BACKGROUND: Disseminated intravascular coagulation (DIC) is noted in severe cases of coronavirus disease 2019 (COVID-19). Recently, a number of studies evaluating the diagnosis and treatment of DIC in COVID-19 patients have been reported. OBJECTIVE: The aim of this study is to identify existing gaps where further research is needed on the diagnosis and treatment of DIC complicated by COVID-19. METHODS: We used the PRISMA Extension for Scoping Reviews. MEDLINE, CENTRAL, WHO-ICTRP, ClinicalTrial.gov and PROSPERO were searched from their inception to 6 October 2020. RESULTS: Seven studies were selected; five were already published and two are ongoing. DIC was diagnosed using the International Society on Thrombosis and Hemostasis (ISTH) DIC score (n = 4) and the sepsis-induced coagulopathy (SIC) DIC score (n = 5). Seven studies examined the effectiveness of low molecular weight heparin (LMWH); of these, four studies used a prophylactic dose and five used a therapeutic dose of LMWH. A prophylactic dose of unfractionated heparin (UFH) was investigated in two studies. CONCLUSION: Studies on DIC diagnostic criteria and anticoagulants were limited to the ISTH or SIC scores and heparinoids, particularly LMWH. Further studies are needed to compare these with other available DIC scoring systems and anticoagulants.


Subject(s)
COVID-19/complications , COVID-19/virology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/therapy , SARS-CoV-2 , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Blood Coagulation , Blood Coagulation Tests , Disease Management , Disease Susceptibility , Disseminated Intravascular Coagulation/blood , Humans , Prognosis , Treatment Outcome
15.
Med Intensiva (Engl Ed) ; 45(1): 42-55, 2021.
Article in English, Spanish | MEDLINE | ID: covidwho-1065468

ABSTRACT

During the new pandemic caused by SARS-CoV-2, there is short knowledge regarding the management of different disease areas, such as coagulopathy and interpretation of D-dimer levels, its association with disseminated intravascular coagulation (DIC) and controversy about the benefit of anticoagulation. Thus, a systematic review has been performed to define the role of D-dimer in the disease, the prevalence of DIC and the usefulness of anticoagulant treatment in these patients. A literature search was performed to analyze the studies of COVID-19 patients. Four recommendations were drawn based on expert opinion and scientific knowledge, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the disease and there is no evidence on the benefit of starting anticoagulant treatment based only on isolated laboratory data.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/blood , COVID-19/blood , Disseminated Intravascular Coagulation/blood , Fibrin Fibrinogen Degradation Products/analysis , SARS-CoV-2 , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/mortality , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/mortality , Critical Illness , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/epidemiology , Humans , Medical Overuse , Observational Studies as Topic , Pandemics , Prevalence , Prognosis
16.
Haemophilia ; 27(1): 41-48, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1066683

ABSTRACT

INTRODUCTION: The SARS-CoV-2 coronavirus-induced infection (COVID-19) can be associated with a coagulopathy mainly responsible for pulmonary microvasculature thrombosis and systemic thromboembolic manifestations. The pathophysiology and management of the COVID-19 coagulopathy are likely more complex in patients with inherited bleeding diseases such as haemophilia. These individuals might indeed present with both bleeding and thrombotic complications and require simultaneous antithrombotic and haemostatic treatments. OBJECTIVE: We propose practical guidance for the diagnosis and management of COVID-19 coagulopathy in persons with haemophilia. RESULTS: Continuation of regular haemostatic treatment is recommended for ambulatory patients. For patients requiring hospital admission and on replacement therapy with factors VIII or IX concentrates, prophylaxis with concentrates should be intensified according to the risk of bleeding complications and associated with prophylactic doses of LMWH. For patients on nonreplacement therapy, emicizumab should be continued and possibly combined with factor VIII and prophylactic doses of LMWH depending on the risk of bleeding and thrombosis. Dose escalation of LMWH tailored to the risk of thrombosis can be employed but not supported by evidence. CONCLUSIONS: These practical recommendations are based on the current literature on COVID-19 with its impact on haemostasis, indications and modalities for thromboprophylaxis mainly in nonhaemophilic patients and how that is likely to affect persons with haemophilia in different circumstances. They will need to be tailored to each patient's clinical status and validated in future studies.


Subject(s)
COVID-19/complications , Disseminated Intravascular Coagulation/complications , Hemophilia A/complications , Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/therapy , Disease Management , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/therapy , Factor IX/therapeutic use , Factor VIII/therapeutic use , Hemophilia A/diagnosis , Hemophilia A/therapy , Heparin, Low-Molecular-Weight/therapeutic use , Humans
17.
J Neurovirol ; 27(1): 35-51, 2021 02.
Article in English | MEDLINE | ID: covidwho-1061059

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.


Subject(s)
Atherosclerosis/complications , COVID-19/complications , Disseminated Intravascular Coagulation/complications , Hemorrhage/complications , Hyperglycemia/complications , Stroke/complications , Thrombosis/complications , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Atherosclerosis/diagnosis , Atherosclerosis/drug therapy , Atherosclerosis/virology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Cardiovascular Agents/therapeutic use , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Extracellular Traps/drug effects , Extracellular Traps/immunology , Hemorrhage/diagnosis , Hemorrhage/drug therapy , Hemorrhage/virology , Humans , Hyperglycemia/diagnosis , Hyperglycemia/drug therapy , Hyperglycemia/virology , Inflammation , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Stroke/diagnosis , Stroke/drug therapy , Stroke/virology , Thrombosis/diagnosis , Thrombosis/drug therapy , Thrombosis/virology
18.
Clin Lab ; 67(1)2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-1045291

ABSTRACT

BACKGROUND: In 2020, the SARS-CoV-2 virus spread worldwide and infected more that 10 million people, causing more than 500,000 deaths worldwide. The infection has systemic effects on the respiratory and cardiovascular systems; thus, patients can present a variety of symptoms from asymptomatic to rapid deaths. In this paper, we present the first case of post-mortem SARS-CoV-2 molecular testing in Western part of Romania in a deceased with disseminated intravascular coagulation (DIC) and elevated D-dimer levels. METHODS: During the autopsy which took place at the Institute of Forensic Medicine from Timisoara, Romania, blood sample was collected in a vacutainer with EDTA and sent to the Laboratory of Forensic Genetics from Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. Viral RNA extraction was performed automated on the Maxwell 48 RSC Extraction System (Promega, USA) using the Maxwell RSC Viral Total Nucleic Acid Purification kit (Promega, USA). After RNA extraction, the samples were amplified on a 7500 real-time PCR (Applied Biosystems, USA) using the genesig® Real-Time PCR Assay (Primer Design, UK). RESULTS: The molecular testing showed a cycle threshold value of 23.4 (1.2 x 106 copies/mL), indicating increased viral loads, which correlated with the laboratory analysis results, especially with D-dimer levels. CONCLUSIONS: In cases of coagulopathy of SARS-CoV-2, patients in hospitals should be monitored closely for thrombosis development. Thus D-dimer can be used as prognostic marker in monitoring the evolution of SARS-CoV-2 infected patients.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Disseminated Intravascular Coagulation/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Autopsy , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/virology , Cause of Death , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/virology , Fatal Outcome , Humans , Multiple Organ Failure/virology , Predictive Value of Tests , Romania , Up-Regulation
19.
Thromb Res ; 199: 132-142, 2021 03.
Article in English | MEDLINE | ID: covidwho-1014833

ABSTRACT

BACKGROUND: Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear. OBJECTIVES: We aimed to analyze the characteristics of patients with a confirmed thrombotic complication including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. METHODS: Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3 2020, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. RESULTS: Among 1127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). Forty-three patients (62%) suffered venous thromboembolism, 18 (26%) arterial episodes and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic complication where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR = 18, 95% CI: 2.4-142, p < .05). CONCLUSIONS: Despite quasi-universal thromboprophylaxis, COVID-19 lead to a myriad of arterial and venous thrombotic events. Considering the subgroup of patients with thrombotic episodes, arterial events appeared earlier in the course of disease and conferred very poor prognosis, and an ISTH DIC score ≥ 3 at presentation was identified as a potential predictor of mortality. Severity-adjusted thromboprophylaxis seemed to decrease the number of events and could have influenced mortality. Randomized controlled trials are eagerly awaited.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Heparin, Low-Molecular-Weight/therapeutic use , Thrombosis/drug therapy , Thrombosis/etiology , Aged , Aged, 80 and over , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Thrombophilia/diagnosis , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombosis/diagnosis , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
20.
Ter Arkh ; 92(11): 51-56, 2020 Dec 26.
Article in Russian | MEDLINE | ID: covidwho-1013631

ABSTRACT

AIM: Clinical characteristics of disseminated intravascular coagulation (DIC) in COVID-19 infection and assessment of the effectiveness of complex therapy for this syndrome at the stages of prevention and treatment of various complications. MATERIALS AND METHODS: The study of publications was carried out through search engines on the Internet using keywords. To diagnose the infection, the COVID-19 program was used on the MeDiCase platform, which is publicly available on www.medicase.pro, which suggests a diagnosis with a sensitivity of 89.47%. The study included 85 patients with acute COVID-19 with mild to moderate disease, aged 11 to 81 years. The presence of the pathogen was confirmed immunologically in 12% of patients; in other cases, the diagnosis was based on the results of an automated survey in the MeDiCase system. All patients, according to the MGNOT recommendations, were prescribed one of the oral direct anticoagulants - Eliquis at a dose of 5 mg 2 times a day, Ksarelto at a dose of 10 mg 2 times a day or Pradax at a dose of 110 mg 2 times a day for at least 2 weeks. All other drugs with antiviral, immunomodulatory effects, antibiotics were canceled. RESULTS: The presence of DIC is substantiated by the morphological picture of changes in organs and tissues, clinical (hematoma-petechial type of bleeding in combination with thromboembolic syndrome and the presence of thrombovasculitis) and laboratory changes: an increase in the level of soluble fibrin-monomer complexes, D-dimer, hyperfibrinogenaemia, less often - thrombocytopenia, violation of fibrinolytic activity. The phenomenon of consumption of clotting factors and profuse bleeding are rare. Direct anticoagulants, fresh frozen plasma transfusions and plasmapheresis are used in the treatment of disseminated intravascular coagulation. The paper presents its own positive results of early prescription at the outpatient stage of direct oral anticoagulants in prophylactic doses (no case of disease progression), individual cases of the use of fresh frozen plasma and plasapheresis. CONCLUSION: DIC syndrome with the development of thrombovasculitis is the most important pathogenetic mechanism for the development of microthrombotic and hemorrhagic disorders in organs during infection with COVID-19, leading to dysfunction of the lungs, brain and other nerve tissues, kidneys, thromboembolic complications, etc. Many symptoms of the disease may be associated with a violation of the nervous regulation of the functions of organs and systems. Prevention of thrombovasculitis is effective already at the stage of the first manifestation of the disease with the outpatient use of direct anticoagulants (oral, low molecular weight heparins). In case of more severe manifestations (complications) of the disease, additional use of freshly frozen plasma and plasmapheresis is effective.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Disseminated Intravascular Coagulation , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants , Child , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/prevention & control , Humans , Middle Aged , SARS-CoV-2 , Young Adult
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