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1.
Semin Thromb Hemost ; 48(8): 978-987, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2186413

ABSTRACT

Disseminated intravascular coagulation (DIC) has been understood as a consumptive coagulopathy. However, impaired hemostasis is a component of DIC that occurs in a progressive manner. The critical concept of DIC is systemic activation of coagulation with vascular endothelial damage. DIC is the dynamic coagulation/fibrinolysis disorder that can proceed from compensated to decompensated phases, and is not simply impaired hemostasis, a misunderstanding that continues to evoke confusion among clinicians. DIC is a critical step of disease progression that is important to monitor over time. Impaired microcirculation and subsequent organ failure due to pathologic microthrombi formation are the pathophysiologies in sepsis-associated DIC. Impaired hemostasis due to coagulation factor depletion from hemodilution, shock, and hyperfibrinolysis occurs in trauma-associated DIC. Overt-DIC diagnostic criteria have been used clinically for more than 20 years but may not be adequate to detect the compensated phase of DIC, and due to different underlying causes, there is no "one-size-fits-all criteria." Individualized criteria for heterogeneous conditions continue to be proposed to facilitate the diagnosis. We believe that future research will provide therapeutics using new diagnostic criteria. Finally, DIC is also classified as either acute or chronic, and acute DIC results from progressive coagulation activation over a short time and requires urgent management. In this review, we examine the advances in research for DIC.


Subject(s)
Blood Coagulation Disorders , Disseminated Intravascular Coagulation , Humans , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Hemostasis/physiology , Blood Coagulation Disorders/etiology , Fibrinolysis , Dacarbazine
2.
J Nippon Med Sch ; 89(5): 479-486, 2022 Nov 09.
Article in English | MEDLINE | ID: covidwho-2117787

ABSTRACT

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) occasionally develop respiratory failure and coagulopathy. We aimed to determine whether coagulation abnormalities at admission and during the course of hospitalization can predict the liberation from respiratory support in critically ill patients with COVID-19 by combining the results of rotational thromboelastometry (ROTEM) with standard laboratory tests. METHODS: This single-center, retrospective, observational study included 31 consecutive adult patients with COVID-19 who were admitted to the intensive care unit (ICU) and who required respiratory support between April 2021 and August 2021. We divided the patients into two groups according to the liberation from respiratory support and analyzed the differences between the groups. RESULTS: There were 20 patients in the liberation group and 11 in the non-liberation group. There were no significant differences in the overt disseminated intravascular coagulation scores or abnormal counts in the ROTEM parameters at admission between groups, although there was a significant difference in the highest score in the ICU. The Sequential Organ Failure Assessment and sepsis-induced coagulopathy scores were significantly different between both groups at admission and at the time when the highest values were reported during the ICU stay. CONCLUSIONS: High sepsis-induced coagulopathy scores at admission to the ICU were found to be useful predictors of difficulties in the liberation from respiratory support in patients with severe COVID-19. However, increased overt disseminated intravascular coagulation scores and abnormal counts in the ROTEM parameters during the ICU stay were associated with difficulties in the liberation from respiratory support.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Disseminated Intravascular Coagulation , Sepsis , Adult , Humans , COVID-19/complications , Retrospective Studies , Disseminated Intravascular Coagulation/complications , Intensive Care Units , Blood Coagulation Disorders/etiology
3.
Cardiovasc Hematol Agents Med Chem ; 20(3): 178-188, 2022.
Article in English | MEDLINE | ID: covidwho-2039581

ABSTRACT

The post-COVID neurological syndrome has been coined, which describes the functional and structural sequelae of coronavirus infection disease-19 (COVID-19) in the brain. Mild/severe manifestations of the post-COVID neurological syndrome have been identified in approximately 33.00% of COVID-19 survivors. The presence of neurological complications after COVID allowed neuropathologists to investigate in-depth the role of viral infection in neurons. The pathophysiology of the post-COVID neurological syndrome involved the development of a systematic response, including coagulopathy characterized by the formation of microthrombi. Coagulopathy, an old term for a new disease, describes the discrepancy between pro-coagulant and anticoagulant systems due to overexpression of pro-coagulant substances and or their receptors in addition to suppression of the anticoagulant molecules and or their receptors. Vascular endothelial cells and hepatocytes play a central role in the regulation of hemostasis that is disrupted during the acute phase response (APR) of coronavirus-19 (COVID-19). Currently, coagulopathy and inflammation are termed together since both form a complementary system, indicated by the elevation of inflammatory biomarkers (APR) and fibrinolysis biomarkers (D-dimer/fibrin). The later events of the post-COVID neurological syndrome are primarily induced by coagulopathy and direct viral tropism. Therefore, the paper introduces the hypothesis of coagulopathy induced post-COVID neurological syndrome.


Subject(s)
Blood Coagulation Disorders , Brain Injuries , COVID-19 , Anticoagulants , Biomarkers , Blood Coagulation Disorders/etiology , Brain Injuries/complications , COVID-19/complications , Endothelial Cells , Humans , SARS-CoV-2
4.
Int J Hematol ; 116(6): 937-946, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2000116

ABSTRACT

Severe coronavirus disease-19 (COVID-19) has been associated with fibrin-mediated hypercoagulability and thromboembolic complications. To evaluate potential biomarkers of coagulopathy and disease severity in COVID-19, we measured plasma levels of eight biomarkers potentially associated with coagulation, fibrinolysis, and platelet function in 43 controls and 63 COVID-19 patients, including 47 patients admitted to the intensive care unit (ICU) and 16 non-ICU patients. COVID-19 patients showed significantly elevated levels of fibrinogen, tissue plasminogen activator (t-PA), and its inhibitor plasminogen activation inhibitor 1 (PAI-1), as well as ST2 (the receptor for interleukin-33) and von Willebrand factor (vWF) compared to the control group. We found that higher levels of t-PA, ST2, and vWF at the time of admission were associated with lower survival rates, and that thrombotic events were more frequent in patients with initial higher levels of vWF. These results support a predictive role of specific biomarkers such as t-PA and vWF in the pathophysiology of COVID-19. The data provide support for the case that hypercoagulability in COVID-19 is fibrin-mediated, but also highlights the important role that vWF may play in the genesis of thromboses in the pathophysiology of COVID-19. Interventions designed to enhance fibrinolysis might prove to be useful adjuncts in the treatment of coagulopathy in a subset of COVID-19 patients.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombophilia , Thrombosis , Humans , COVID-19/complications , von Willebrand Factor , Tissue Plasminogen Activator , Interleukin-1 Receptor-Like 1 Protein , Thrombosis/etiology , Fibrinolysis , Blood Coagulation Disorders/etiology , Biomarkers , Thrombophilia/complications , Fibrin
5.
Nat Rev Immunol ; 22(10): 639-649, 2022 10.
Article in English | MEDLINE | ID: covidwho-1984398

ABSTRACT

COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex interactions between the innate immune response, the coagulation and fibrinolytic pathways, and the vascular endothelium, resulting in a procoagulant condition. Understanding of the pathogenesis of this condition at the genomic, molecular and cellular levels is needed in order to mitigate thrombosis formation in at-risk patients. In this Perspective, we categorize our current understanding of CAC into three main pathological mechanisms: first, vascular endothelial cell dysfunction; second, a hyper-inflammatory immune response; and last, hypercoagulability. Furthermore, we pose key questions and identify research gaps that need to be addressed to better understand CAC, facilitate improved diagnostics and aid in therapeutic development. Finally, we consider the suitability of different animal models to study CAC.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Animals , Blood Coagulation Disorders/etiology , COVID-19/complications , Endothelium, Vascular , SARS-CoV-2 , Thrombosis/etiology
6.
Int J Lab Hematol ; 44(5): 823-830, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1861349

ABSTRACT

BACKGROUND: COVID-19 associated coagulopathy (CAC) can either be localized or systemic hypercoagulable state with increased risk of thromboembolism. This study looked into the usefulness of Thromboelastography (TEG) and the velocity curve (V-curve) derivative from TEG in diagnosing and differentiating different stages of CAC. MATERIALS AND METHODS: A prospective single cohort study of RT-PCR confirmed COVID-19 patients was carried out for 2 weeks. Severe COVID-19 patients in the adult critical care units with a TEG report were recruited for the study. Citrated kaolin TEG was performed on the day of admission before anticoagulation. TEG parameters included were R and K time, alpha angle, maximum amplitude, clotting index, lysis at 30 min. The first-degree velocity curve of TEG is plotted as V-curve which extrapolates thrombus generation potential. Parameters analyzed were the maximum rate of thrombus generation as well as thrombus generated (TG). RESULTS: The study included 43 patients with an average age of 58.34 (±15.35). TEG as well as V-curve of all the patients were hypercoagulable compared with age-matched reference range. We had 79.06% of patients in hypercoagulable stage. The mortality rate was 32.56% and 30.23% developed thrombotic incidents. Patients who succumbed to death had prolonged PT, aPTT, MA, Ly30, with a reduced TG (p < .05). The presence of fibrinolysis was associated with thromboembolism (OR = 6.76, CI = 1.48-25.82). Repeat TEG was done randomly in 11 patients and revealed a persistent hypercoagulable stage with increasing fibrinolysis activity. CONCLUSION: TEG is a useful tool in diagnosing and categorizing Coagulopathy associated with COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thromboembolism , Thrombophilia , Adult , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , COVID-19/complications , COVID-19/diagnosis , COVID-19 Testing , Cohort Studies , Humans , Middle Aged , Prospective Studies , Thrombelastography , Thrombophilia/complications , Thrombophilia/etiology
7.
Acta Haematol ; 145(3): 282-296, 2022.
Article in English | MEDLINE | ID: covidwho-1832782

ABSTRACT

Coronavirus disease 2019 (COVID-19) has emerged as a pandemic at the end of 2019 and continues to exert an unfavorable worldwide health impact on a large proportion of the population. A remarkable feature of COVID-19 is the precipitation of a hypercoagulable state, mainly in severe cases, leading to micro- and macrothrombosis, respiratory failure, and death. Despite the implementation of various therapeutic regimes, including anticoagulants, a large number of patients suffer from such serious complications. This review aims to describe the current knowledge on the pathophysiology of the coagulation mechanism in COVID-19. We describe the interplay between three important mediators of the disease and how this may lead to a hyperinflammatory and prothrombotic state that affects outcome, namely, the endothelium, the immune system, and the coagulation system. In line with the hypercoagulability state during COVID-19, we further review on the rare but severe vaccine-induced thrombotic thrombocytopenia. We also summarize and comment on available anticoagulant treatment options and include suggestions for some future treatment considerations for COVID-19 anticoagulation therapy.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombophilia , Anticoagulants/therapeutic use , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , COVID-19/complications , Humans , Pandemics , SARS-CoV-2 , Thrombophilia/drug therapy , Thrombophilia/etiology
8.
Int J Mol Sci ; 23(6)2022 Mar 19.
Article in English | MEDLINE | ID: covidwho-1760654

ABSTRACT

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.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19 Vaccines/adverse effects , COVID-19/complications , SARS-CoV-2 , Biomarkers , Blood Coagulation , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/prevention & control , Blood Coagulation Disorders/therapy , Blood Coagulation Tests , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Combined Modality Therapy , Disease Management , Disease Susceptibility , Fibrinolysis , Humans , Prognosis , Treatment Outcome
10.
Am Surg ; 88(5): 1016-1017, 2022 May.
Article in English | MEDLINE | ID: covidwho-1741777

ABSTRACT

Coronavirus disease 2019 (COVID-19) is linked with a hypercoagulable state called COVID-19-associated coagulopathy (CAC). Due to elevated levels of factor VIII and fibrinogen as well as inflammation-linked hyperviscosity of blood, the risk for venous thromboembolism is increased in patients who have CAC. We report the case of a patient with recent COVID-19 infection and no other past medical history who presented after a motorcycle collision with left middle and distal femur fractures, who underwent retrograde intramedullary nailing, and then developed immediate massive bilateral pulmonary emboli. The patient was treated with tissue plasminogen activator administration via bilateral pulmonary artery thrombolysis catheters without improvement, and was then placed on venoarterial extracorporeal membrane oxygenation for subsequent cardiogenic shock. During a 58-day hospital stay, the patient recovered and was discharged with a good long-term prognosis. In this report, we discuss CAC, the role of surgical critical care in the management of the disease, and issues specific to this patient's disease process and treatment.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Extracorporeal Membrane Oxygenation , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , COVID-19/complications , Extracorporeal Membrane Oxygenation/adverse effects , Humans , Shock, Cardiogenic/etiology , Tissue Plasminogen Activator
11.
In Vivo ; 36(2): 954-960, 2022.
Article in English | MEDLINE | ID: covidwho-1732570

ABSTRACT

BACKGROUND/AIM: Multiple reports from all over the world link COVID-19 with endothelial/coagulation disorders as well as a dysregulated immune response. This study tested the hypothesis that immunostimulation will be greater in COVID-19 patients than in patients with H1N1 infection or bacterial sepsis. Also, whether an increase in immune stimulation will be accompanied by a more severely affected endothelium/coagulation system was examined. PATIENTS AND METHODS: Twenty-three septic patients, admitted in the Intensive Care Unit (ICU), were enrolled (9 with SARS-CoV-2, 5 with H1N1 pneumonia, 9 with bacterial sepsis). Myeloperoxidase (MPO) activity along with certain endothelial/coagulation factors were assessed on admission (time point 1) and at either improvement or deterioration (time point 2). RESULTS: MPO levels were significantly higher in COVID-19 patients compared to both other groups. Furthermore, in patients with COVID-19, vWF levels did not differ significantly, fVIII levels were lower while ADAMTS-13 activity was higher compared to patients with H1N1 pneumonia and bacterial sepsis (a trend in the latter). CONCLUSION: Increased immunostimulation was noted in COVID-19 patients compared to other septic patients; however, this was not accompanied by greater disturbance of the clotting system and/or more severe endothelial injury.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Influenza A Virus, H1N1 Subtype , Sepsis , Blood Coagulation Disorders/etiology , COVID-19/complications , Humans , Immunization , SARS-CoV-2 , Sepsis/complications
12.
Ter Arkh ; 93(11): 1255-1263, 2021 Nov 15.
Article in Russian | MEDLINE | ID: covidwho-1698726

ABSTRACT

AIM: To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19. MATERIALS AND METHODS: We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes. RESULTS: Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation. CONCLUSION: The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Disseminated Intravascular Coagulation , Hemostatics , Thrombophilia , Thrombosis , Humans , COVID-19/complications , SARS-CoV-2 , C-Reactive Protein , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/complications , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Thrombophilia/complications , Anticoagulants/therapeutic use , Fibrinogen , Inflammation , Interleukins , Ethanol
13.
Clin Exp Pharmacol Physiol ; 49(4): 483-491, 2022 04.
Article in English | MEDLINE | ID: covidwho-1691664

ABSTRACT

Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.


Subject(s)
Acute Lung Injury/etiology , Blood Coagulation Disorders/etiology , COVID-19/pathology , Cytokine Release Syndrome/etiology , Hemorrhage/etiology , Lipopolysaccharides/adverse effects , Lung Diseases/etiology , Receptor, Angiotensin, Type 1/metabolism , STAT Transcription Factors/metabolism , Signal Transduction , Acute Lung Injury/pathology , Animals , Blood Coagulation Disorders/pathology , COVID-19/etiology , Cytokine Release Syndrome/pathology , Disease Models, Animal , Hemorrhage/pathology , Janus Kinases , Lung Diseases/pathology , Male , Rats , Rats, Wistar
14.
Eur J Med Res ; 27(1): 25, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1690867

ABSTRACT

Coronavirus disease 2019 (COVID-19), with a high prevalence rate, has rapidly infected millions of people around the world. Since viral infections can disrupt the coagulation and homeostasis cascades, various inflammatory and coagulation problems occur due to COVID-19 infection, similar to coronavirus epidemics in 2003 and 2004. According to multiple previous studies, in the present research, we reviewed the most commonly reported problems of COVID-19 patients, such as venous thromboembolism, pulmonary embolism, disseminated intravascular coagulation, etc. and investigated the causes in these patients. Coagulation and inflammatory markers, such as platelets and fibrinogen, C-reactive protein, lactate dehydrogenase, d-dimer, prothrombin time, etc., were also discussed, and the treatment options were briefly reviewed. In addition to coagulation treatments, regular examination of coagulation parameters and thrombotic complications can be helpful in the timely treatment of patients. Therefore, it is helpful to review the coagulation problems in COVID-19 patients. Although all mentioned problems and markers are important in COVID-19, some of them are more valuable in terms of diagnosis and prognosis.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19/complications , SARS-CoV-2 , Blood Coagulation , Blood Coagulation Disorders/therapy , C-Reactive Protein/analysis , COVID-19/blood , Disseminated Intravascular Coagulation/etiology , Fibrin Fibrinogen Degradation Products/analysis , Humans , Partial Thromboplastin Time , Pulmonary Embolism/etiology , Venous Thromboembolism/etiology
16.
Viruses ; 14(2)2022 01 24.
Article in English | MEDLINE | ID: covidwho-1648620

ABSTRACT

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.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/etiology , COVID-19 Vaccines/chemistry , COVID-19/complications , COVID-19/prevention & control , Nanoparticles/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/isolation & purification , Blood Coagulation , Blood Coagulation Disorders/classification , Blood Coagulation Disorders/prevention & control , Blood Coagulation Disorders/virology , COVID-19 Vaccines/administration & dosage , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Humans , Inflammation/etiology , Inflammation/prevention & control , Nanoparticles/chemistry , SARS-CoV-2/pathogenicity , Thrombophilia/etiology
17.
Cell Mol Biol Lett ; 27(1): 6, 2022 Jan 11.
Article in English | MEDLINE | ID: covidwho-1622208

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is associated with a high mortality rate. The majority of deaths in this disease are caused by ARDS (acute respiratory distress syndrome) followed by cytokine storm and coagulation complications. Although alterations in the level of the number of coagulation factors have been detected in samples from COVID-19 patients, the direct molecular mechanism which has been involved in this pathologic process has not been explored yet. The PI3K/AKT signaling pathway is an intracellular pathway which plays a central role in cell survival. Also, in recent years the association between this pathway and coagulopathies has been well clarified. Therefore, based on the evidence on over-activity of the PI3K/AKT signaling pathway in SARS-CoV-2 infection, in the current review, the probable role of this cellular pathway as a therapeutic target for the prevention of coagulation complications in patients with COVID-19 is discussed.


Subject(s)
Blood Coagulation Disorders/etiology , Blood Coagulation , COVID-19/complications , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Animals , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/metabolism , COVID-19/blood , COVID-19/metabolism , Humans , Inflammation/blood , Inflammation/etiology , Inflammation/metabolism , Molecular Targeted Therapy , SARS-CoV-2/physiology
19.
Lancet ; 399(10320): 118-119, 2022 01 08.
Article in English | MEDLINE | ID: covidwho-1612113
20.
Int J Mol Sci ; 22(24)2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1580687

ABSTRACT

COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients.


Subject(s)
Blood Platelets/physiology , COVID-19/blood , Thrombosis/pathology , Blood Coagulation , Blood Coagulation Disorders/etiology , Blood Platelets/metabolism , Blood Platelets/virology , COVID-19/metabolism , Cytokine Release Syndrome , Endothelial Cells/pathology , Fibrin Fibrinogen Degradation Products , Hemostasis , Humans , Inflammation , Phenotype , Platelet Activation/physiology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Thrombocytopenia/metabolism , Thrombosis/metabolism , Thrombosis/virology
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