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1.
Biology Bulletin Reviews ; 12(4):406-413, 2022.
Article in English | ProQuest Central | ID: covidwho-1950031

ABSTRACT

This is a review of data on the impact of COVID-19 on blood clotting. An important feature of the pathogenesis of severe acute respiratory syndrome caused by the SARS-Co-2 coronavirus is the risk of thrombotic complications including microvascular thrombosis, venous thromboembolism, and stroke. These thrombotic complications, like thrombocytopenia, are markers of the severe form of COVID-19 and are associated with multiple organ failure and increased mortality. One of the central mechanisms of this pathology is dysregulation of the adhesive protein P-selectin. The study of the mechanisms of changes in hemostasis and vascular pathology, and the role in these processes of biomarkers of thrombogenesis, and primarily of P-selectin of various origins (platelets, endothelial cells, and plasma), can bring some clarity to the understanding of the pathogenesis and therapy of COVID-19.

2.
Journal of Hypertension ; 40:e148, 2022.
Article in English | EMBASE | ID: covidwho-1937701

ABSTRACT

Objective: The purpose is to identify the peculiarities of the parameters of red blood cells (RBC) and hemostasis in patients with strokes associated with coronavirus infection. Design and method: A total of 124 patients (48.5 + 1.9 years) with impairments of cerebral circulation due to COVID-19 (confirmed by positive PCR test) had been examined. Among them, 74 patients had ischemic stroke, 25- transient ischaemic attack, 17- intracerebral hemorrhage, 8- subarachnoid hemorrhage. The parameters of hemostasis were measured by standard methods, electrical, viscoelastic parameters of RBC - by dielectrophoresis. Results: 71 patients (the 1st group) showed signs of intravascular coagulation and thrombosis: accelerated platelet-leukocyte aggregation, increased levels of coagulation products, reduced fibrinolysis activity (p = 0.001-0.04). The levels of D-dimer, fibrinogen, ESR, platelet count were higher in this group compared to the second one (p < 0.01). A moderate increase of RBC summarized rigidity, viscosity was noted. The level of RBC hemolysis was associated with platelet count (r = 0.735,p = 0.03), D-dimer (r = 0.482, p < 0.05), fibrinogen level (r = 0.374, p = 0.04). In 2nd group (53 persons), the markers of thrombosis had moderate deviations. Sharply reduced RBC deformability with increased summarized rigidity, viscosity was dominant coupled with the background of high electrical conductivity of cell membranes compared to the indicators in the 1st group (p < 0.01). There was a decrease of membrane capacity, surface charge, cell dipole moment, polarizability than those in the 1st group (p = 0.0001-0.05). A sharp decrease of RBC deformability creates obstacles to overcoming small-diameter capillaries, leading to violations of microcirculatory blood flow. RBC deformability was associated with levels of ferritin (r = 0.451, p = 0.02), HbA1c (r = 0.480, p = 0.03), uric acid (r = -0.371, p < 0.05), LDL cholesterol (r = 0.461, p = 0.02). Incubation of blood samples in vitro for 10 min with riboflavin, nicotinamide, inosine, which ensures RBC energy metabolism, restored the reduced RBC deformability (p < 0.01), altered cell morphology (p = 0.04), decreased RBC aggregation (p < 0.001). Conclusions: The revealed features of parameters of RBC hemostasis in stroke patients with coronavirus infection are associated with two independent pathogenetic mechanisms: thrombotic and hemorheologic. The thrombotic variant is due to procoagulant state and an activity of inflammation. The hemorheologic variant is caused by decrease of RBC energy metabolism, activity of enzymes.

3.
J Thromb Haemost ; 2022 Jul 03.
Article in English | MEDLINE | ID: covidwho-1916259

ABSTRACT

BACKGROUND: Severe COVID-19 disease is associated with thrombotic complications and extensive fibrin deposition. This study investigates whether the hemostatic complications in COVID-19 disease arise due to dysregulation of the fibrinolytic system. METHODS: This prospective study analyzed fibrinolytic profiles of 113 patients hospitalized with COVID-19 disease with 24 patients with non-COVID-19 respiratory infection and healthy controls. Antigens were quantified by Ella system or ELISA, clot lysis by turbidimetric assay, and plasminogen activator inhibitor-1 (PAI-1)/plasmin activity using chromogenic substrates. Clot structure was visualized by confocal microscopy. RESULTS: PAI-1 and its cofactor, vitronectin, are significantly elevated in patients with COVID-19 disease compared with those with non-COVID-19 respiratory infection and healthy control groups. Thrombin activatable fibrinolysis inhibitor and tissue plasminogen activator were elevated in patients with COVID-19 disease relative to healthy controls. PAI-1 and tissue plasminogen activator (tPA) were associated with more severe COVID-19 disease severity. Clots formed from COVID-19 plasma demonstrate an altered fibrin network, with attenuated fiber length and increased branching. Functional studies reveal that plasmin generation and clot lysis were markedly attenuated in COVID-19 disease, while PAI-1 activity was elevated. Clot lysis time significantly correlated with PAI-1 levels. Stratification of COVID-19 samples according to PAI-1 levels reveals significantly faster lysis when using the PAI-1 resistant (tPA) variant, tenecteplase, over alteplase lysis. CONCLUSION: This study shows that the suboptimal fibrinolytic response in COVID-19 disease is directly attributable to elevated levels of PAI-1, which attenuate plasmin generation. These data highlight the important prognostic potential of PAI-1 and the possibility of using pre-existing drugs, such as tenecteplase, to treat COVID-19 disease and potentially other respiratory diseases.

4.
Vox Sanguinis ; 117(SUPPL 1):269, 2022.
Article in English | EMBASE | ID: covidwho-1916362

ABSTRACT

Background: In approximately 30% of COVID-19 cases, the hospitalized patients are developing venous thrombo-embolic complications, due to imune-mediated hypercoagulable responce and inadequate thromboprophylaxis. D-dimer elevattion can be seen in severe critically ill COVID-19 patients. and those with other medical conditions associated with increased thrombotic risk. Aims: The aim of the study was to analyse the fibrinolytic activity, and to monitor the anticoagulation therapy in the hospitalized COVID-19 patients at the Clinic for Infectious Diseases and Febrile States in Skopje. Methods: In a retrospective study, 1728 patients with COVID -19 infection hospitalized at the Clinic for Infectious Diseases and Febrile States with COVID-19 from March-September 2020 were analized. The D-dimers level was measured with the coagulometer Dade Behring BCS XP-Siemens with commercial reagents from Siemens. The anti-factor Xa level was measured with chromogenic anti-Xa assay. Results: Analized data from 1728 hospitalized patients showed increased level of D-dimers. The average level was 1974 ng/ml (0- 500 ng/ml). Peak D-dimer levels were seen in some patients during the hospitalization period (>35,000 ng/ml). Patients received anticoagulation therapy with low-molecular heparin. The anti-factor Xa assay was analized in nine patients, three of them were in the prophylactic range (0.2-0.5 IE), and 6 were in the therapeutic range (0.5-1.2 IE). Summary/Conclusions: Increased D-dimers in hospitalized patients with severe COVID-19 are common laboratory findings, and the are prognostic marker for in-hospital mortality. Prolonged immobility and other risk factors for VTE in those patients may lead to thrombotic complications. The dosage regimen of low molecular weight heparin must be evaluated in every patient, especially in patients with severe renal impairment, low platelet count and weight disproportions, in order for appropritate anticoagulation and avoiding the associated bleeding risk.

5.
ASAIO Journal ; 68(SUPPL 1):6, 2022.
Article in English | EMBASE | ID: covidwho-1912996

ABSTRACT

Introduction: Management of coagulation remains the foremost challenge during extracorporeal life support (ECLS). Thromboelastography (TEG) and other viscoelastic clotting tests have shown utility for assessing coagulation status in trauma and ECLS patients and have also been utilized in COVID 19 patients. However, with few exceptions, these methods are performed in a laboratory setting, not at the bedside, and rely on cumbersome, non-portable equipment. The Viscoelastic Coagulation Monitor (VCM;Entegrion;Durham, NC) is a portable device/test developed for use at the bedside and outside hospitals to assess clot formation and lysis using a small sample of whole blood. Blood coagulation is activated by contact with the glass surface on the cartridge, and measurements are derived pertaining to clot formation, stability, and lysis - similar to metrics obtained by the TEG 5000 (Haemonetics;Boston, MA). In a recent study, the relationship of VCM results and heparin dose administered in 36 COVID-19 patients was investigated;however, use of VCM for ECLS with application of heparinase has not been reported. We investigated efficacy of the VCM for coagulation monitoring during 72 hours of continuous ECLS in swine and hypothesized that the VCM with heparinase correlates with TEG heparinase. Methods: Female Yorkshire swine (n=3, 53.4±1.6kg) were anesthetized, mechanically ventilated, and systemically heparinized. Blood samples were collected at baseline, post ECLS, 6, 24, 48, and 72-hours post ECLS initiation. For the VCM, 350μL of whole blood was added to a 0.05 IU heparinase vial, mixed, and then added to a VCM cartridge. For TEG, 340μL of citrated whole blood was added to 20μL 0.2 M CaCl2, and samples were activated with a kaolin reagent. Heparinase cups (Haemonetics;Boston, MA) were used for testing. Spearman correlation was performed to compare standard VCM metrics (clotting time [CT], clot formation time [CFT], alpha, maximum clot firmness [MCF], clot retraction/fibrinolysis [LI30]) to the respective TEG metrics (reaction time [R], clot formation time [K], alpha, maximum amplitude [MA], clot retraction/fibrinolysis [LY30]), and also to other conventional coagulation measurements such as prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FIB), and platelet count (PLT) for each timepoint. A p-value of 0.05 was used for significance. Results: All VCM metrics significantly correlated with the respective TEG measurements (see Table 1). Both VCM and TEG show the same positive and negative correlation relationships for clot formation time, clot kinetics, and clot retraction with conventional coagulation tests (see Table 2). Additionally, clotting time and maximum clot firmness did not show moderate or significant correlation with conventional tests. Prothrombin time did not correlate with any values. Conclusion: The VCM is comparable to TEG in assessing coagulation status in heparinized swine and can be used during austere care with ECLS application. In the next round of experiments, we will validate the VCM in clinically-relevant trauma with and without ECLS.

6.
Italian Journal of Medicine ; 16(SUPPL 1):5, 2022.
Article in English | EMBASE | ID: covidwho-1912951

ABSTRACT

Case Report: A 78-year-old female presented to our observation for asthenia, low-grade fever and arthralgia from some months. Past medical history: at September 2020 SARS-Cov 2 infection with asymptomatic course;at July 2021 second SARS-CoV2 infection complicated by interstitial pneumonia with one intercurrent dose of ChAdOx1 nCoV-19 vaccine. Diagnostic tests revealed acute renal failure, severe anemia subjected to blood transfusions, COVID-19 RT-PCR negativity and p-ANCA positivity. CT thorax showed 5% lung involvement suggestive of outcomes of COVID- 19. Renal needle biopsy diagnosed with rapidly progressive paucimmune glomerulonephritis, therefore she started steroids and first infusion of Rituximab. Discussion: The relationship between SARS-CoV-2 and ANCA-vasculitis could involve high virus affinity for ACE2 receptors, with endothelial cell invasion, activation of the inflammatory cascade, cytokine storm, abnormalities in the coagulation/fibrinolytic system, thrombotic microangiopathy, and endothelial cell damage. ANCA is produced by cytokines, activated neutrophils, and macrophages, with induction of vasculitis by neutrophil extracellular traps, including onset of necrotizing crescentic glomerulonephritis. Furthermore the virus could directly damage renal tissues. In literature ANCA-vasculitis in the setting of COVID-19 has been already reported in 5 patients. Conclusions: COVID-19 may be a trigger of this life-threatening autoimmune disease. More clinical and experimental investigations are necessary to further establish and confirm a causal link between these diseases.

7.
Front Cardiovasc Med ; 9: 896362, 2022.
Article in English | MEDLINE | ID: covidwho-1911024

ABSTRACT

Introduction: In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods: Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results: Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion: This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.

8.
Front Endocrinol (Lausanne) ; 13: 877010, 2022.
Article in English | MEDLINE | ID: covidwho-1902948

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 5 million people worldwide. It is imperative to identify the disease severity and intervene with effective therapy as early as possible. Previous studies have shown that low free triiodothyronine (FT3) may possess the predictive value on COVID-19 prognosis. Methods: In this retrospective cohort study, 15-day clinical and laboratory data of 186 hospitalized patients of COVID-19 after admission were analyzed. Groups were based on the disease severity of COVID-19, survival or non-survival, and presence or absence of euthyroid sick syndrome (ESS). Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between FT3 with clinic parameters of multiple time points. Results: The non-survival patients had significant lower levels of FT3 (3.24 ± 0.42 vs. 4.19 ± 0.08 pmol/L, p < 0.05) and thyroid-stimulating hormone (TSH) (0.69 ± 0.19 vs. 2.32 ± 0.2 uIU/ml, p < 0.05), and the FT3 of severe patients was significantly lower than that of non-severe patients (3.67 ± 0.14 vs. 4.33 ± 0.09 pmol/L, p < 0.05). Fifty-nine cases of COVID-19 patients were diagnosed with ESS. Compared with non-ESS patients, those with ESS were older and had higher proportions of fever, shortness of breath, hypertension, diabetes, severe disease, and mortality. In addition, the correlation analysis between FT3 and clinical parameters showed that FT3 were positively related to the lymphocyte count and albumin and negatively correlated with C-reactive protein, erythrocyte sedimentation rate, and D-dimer at all time points in the first 15 days after admission. Conclusion: Low FT3 had a significant predictive value on the prognosis of COVID-19 patients, and FT3 was significantly related with clinic parameters of inflammation/coagulopathy/fibrinolysis.


Subject(s)
COVID-19 , Euthyroid Sick Syndromes , COVID-19/complications , Fibrinolysis , Humans , Inflammation/complications , Retrospective Studies
9.
Topics in Antiviral Medicine ; 30(1 SUPPL):9, 2022.
Article in English | EMBASE | ID: covidwho-1880599

ABSTRACT

Background: Life threatening thrombotic events involving both the arterial and venous systems are prominently present in SARS-CoV-2 infected individuals presenting with severe COVID-19. Abnormal clotting also occurs in asymptomatically or mildly infected individuals and in people experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). Clinical management of this clotting disorder has proven difficult in part because these fibrin clots are highly resistant to plasmin-mediated fibrinolysis. Methods: An array of different binding, biochemical, microscopic, and in vivo assays were performed in these studies. All experiments were performed at least three times in triplicate and reported differences were shown to be statistically significant. Results: We find that SARS-CoV-2 Spike directly binds to the terminal clotting factors, fibrinogen and fibrin (Kd of 5.3 μ M and 0.4 μ M respectively). Mixing Spike and plasma accelerates fibrin polymerization. Scanning electron microscopy reveals an abnormal clot structure with finer, denser, and roughened fibrin fibers. Scanning peptide competition assays indicate Spike binds fibrin at three sites: 1) the plasmin cleavage site needed for fibrinolysis;2) a site involved in innate immune signaling via fibrin binding to Complement Receptor 3 (CR3);and 3) a site with no known function. Examination of mice injected 24h earlier with Spike pseudotyped HIV-ΔEnv virions reveals extensive intra-and extravascular fibrin deposition in the lung accompanied by endothelial activation, loss of tight junctions, increased influx of macrophages, and the generation of high levels of reactive oxygen species. This thromboinflammatory response is not observed when Bald virions are injected or when Spike pseudotyped virions are injected into mice lacking fibrinogen. Intriguingly, these Spike-induced proinflammatory effects are blocked by an anti-fibrin monoclonal antibody, 5B8, which interferes with fibrin binding to CR3. Conclusion: Our findings reveal that the SARS-CoV-2 Spike protein binding to fibrinogen/fibrin results in the formation of structurally abnormal, fibrinolysis-resistant blood clots whose inflammatory effects are effectively neutralized by a specific fibrin-targeting monoclonal antibody. While COVID-19 clotting was thought to occur as a result of systemic inflammation, our findings suggest clotting during SARS-CoV-2 infection in fact is a driver of inflammation. Targeting fibrin could lead to novel therapeutic approaches for patients with acute COVID-19 and PASC.

10.
Rinsho Ketsueki ; 63(5): 471-480, 2022.
Article in Japanese | MEDLINE | ID: covidwho-1879649

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and is known to have thrombotic complications. Various-sized thrombosis occurs in the arteries and veins, especially in lung tissue. The prevention and treatment of thrombosis is an important issue that is directly linked to its prognosis. Additionally, the drastic fibrinolytic enhancement and lethal bleeding in some severe COVID-19 are important issues. The efficacy of antiplatelet for COVID-19 is controversial. Thus, warfarin or tranexamic acid alone should be avoided. Heparin is effective for mild to moderate COVID-19 but is ineffective in severe cases since the anticoagulant activity of heparin is insufficient or heparin increases major bleeding. In severe COVID-19 cases with drastic fibrinolytic enhancement, heparin and nafamostat combination therapy may avoid lethal bleeding. In COVID-19 clinical practice, not only the coagulation activation was evaluated but also the fibrinolytic activation to consider treatment strategies.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants/therapeutic use , COVID-19/complications , Fibrinolytic Agents/therapeutic use , Hemorrhage/drug therapy , Heparin , Humans , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control
11.
Int J Hematol ; 115(6): 826-837, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1872733

ABSTRACT

Coagulation and fibrinolytic mechanisms are enhanced in patients with coronavirus (COVID-19), but disturbances in the balance of both functions in COVID-19 patients remain unclear. We assessed global coagulation and fibrinolysis in plasma from 167 COVID-19 patients (mild/moderate/severe: 62/88/17, respectively) on admission using clot-fibrinolysis waveform analysis (CFWA). Maximum coagulation velocity (|min1|) and maximum fibrinolysis velocity (|FL-min1|) were expressed as ratios relative to normal plasma. Ten patients (6.0%) developed thrombosis, 5 (3.0%) had bleeding tendency, and 13 (7.8%) died during admission. FDP levels increased with severity of COVID-19 symptoms (mild/moderate/severe; median 2.7/4.9/9.9 µg/mL, respectively). The |min1| ratios were elevated in all categories (1.27/1.61/1.58) in keeping with enhanced coagulation potential, with significant differences between mild cases and moderate to severe cases. The |FL-min1| ratios were also elevated in all groups (1.19/1.39/1.40), reflecting enhanced fibrinolytic potential. These data identified coagulation dominance in moderate to severe cases, but balanced coagulation and fibrinolysis in mild cases. There were significant differences in FDP and TAT, but no significant differences in |min1| or |FL-min1| ratios, between patients with and without thrombosis. CFWA monitoring of coagulation and fibrinolysis dynamics could provide valuable data for understanding hemostatic changes and disease status in COVID-19 patients.


Subject(s)
COVID-19 , Thrombosis , Blood Coagulation , Fibrinolysis , Hemostasis , Humans , Thrombosis/etiology
12.
Front Surg ; 9: 889999, 2022.
Article in English | MEDLINE | ID: covidwho-1862702

ABSTRACT

Early in the coronavirus disease 2019 (COVID-19) pandemic, global governing bodies prioritized transmissibility-based precautions and hospital capacity as the foundation for delay of elective procedures. As elective surgical volumes increased, convalescent COVID-19 patients faced increased postoperative morbidity and mortality and clinicians had limited evidence for stratifying individual risk in this population. Clear evidence now demonstrates that those recovering from COVID-19 have increased postoperative morbidity and mortality. These data-in conjunction with the recent American Society of Anesthesiologists guidelines-offer the evidence necessary to expand the early pandemic guidelines and guide the surgeon's preoperative risk assessment. Here, we argue elective surgeries should still be delayed on a personalized basis to maximize postoperative outcomes. We outline a framework for stratifying the individual COVID-19 patient's fitness for surgery based on the symptoms and severity of acute or convalescent COVID-19 illness, coagulopathy assessment, and acuity of the surgical procedure. Although the most common manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19 pneumonitis, every system in the body is potentially afflicted by an endotheliitis. This endothelial derangement most often manifests as a hypercoagulable state on admission with associated occult and symptomatic venous and arterial thromboembolisms. The delicate balance between hyper and hypocoagulable states is defined by the local immune-thrombotic crosstalk that results commonly in a hemostatic derangement known as fibrinolytic shutdown. In tandem, the hemostatic derangements that occur during acute COVID-19 infection affect not only the timing of surgical procedures, but also the incidence of postoperative hemostatic complications related to COVID-19-associated coagulopathy (CAC). Traditional methods of thromboprophylaxis and treatment of thromboses after surgery require a tailored approach guided by an understanding of the pathophysiologic underpinnings of the COVID-19 patient. Likewise, a prolonged period of risk for developing hemostatic complications following hospitalization due to COVID-19 has resulted in guidelines from differing societies that recommend varying periods of delay following SARS-CoV-2 infection. In conclusion, we propose the perioperative, personalized assessment of COVID-19 patients' CAC using viscoelastic hemostatic assays and fluorescent microclot analysis.

13.
National Journal of Physiology, Pharmacy and Pharmacology ; 12(5):639-642, 2022.
Article in English | EMBASE | ID: covidwho-1863182

ABSTRACT

Background: Although most of the COVID-19 patients presented with mild symptoms and recovered, a considerable number of cases became serious with poor prognosis in an unpredictable manner. They mostly presented with respiratory symptoms and coagulation abnormalities with thrombosis and multi-organ failure. Hence, timely prediction of these cases with the early intervention might decrease mortality. Aims and Objectives: The objectives of this were to determine whether values of fibrinogen, fibrin degradation products (FDP), and D-dimer level correlates with disease severity in COVID-19 patients. Materials and Methods: This observational cross-sectional study was done on total 400 hospitalized COVID-19 adult patients where patients were categorized into moderate and severe cases as per guideline of Government of India. Patients with pre-existing coagulation disorder or receiving anticoagulant drugs were excluded from the study. FDP, fibrinogen, and D-dimer values of these two groups were evaluated and compared statistically to determine their significance. Results: Overall mean and standard deviation of fibrinogen, FDP, and D-dimer were 607.48 ± 177.73, 34.93 ± 29.2, and 6.23 ± 6.48 for severe category, while for moderate category disease, they were 389.77 ± 110.16, 10.79 ± 10.47, and 1.96 ± 3.3, respectively. Unpaired t-test showed that the study parameters are significantly higher in severe COVID-19 patients compared to moderate ones. Conclusion: It was concluded that elevated level of D-dimer, fibrinogen, and FDP is indicator of disease progression in COVID-19. Thus, regular estimation of these simple coagulation parameters may predict disease severity and help in adequate management.

14.
Int J Lab Hematol ; 2022 May 24.
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.

15.
Int J Mol Sci ; 23(9)2022 May 09.
Article in English | MEDLINE | ID: covidwho-1847346

ABSTRACT

The fibrinolytic system is composed of the protease plasmin, its precursor plasminogen and their respective activators, tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), counteracted by their inhibitors, plasminogen activator inhibitor type 1 (PAI-1), plasminogen activator inhibitor type 2 (PAI-2), protein C inhibitor (PCI), thrombin activable fibrinolysis inhibitor (TAFI), protease nexin 1 (PN-1) and neuroserpin. The action of plasmin is counteracted by α2-antiplasmin, α2-macroglobulin, TAFI, and other serine protease inhibitors (antithrombin and α2-antitrypsin) and PN-1 (protease nexin 1). These components are essential regulators of many physiologic processes. They are also involved in the pathogenesis of many disorders. Recent advancements in our understanding of these processes enable the opportunity of drug development in treating many of these disorders.


Subject(s)
Fibrinolysin , Fibrinolysis , Fibrinolysin/metabolism , Fibrinolysis/physiology , Plasminogen/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Protease Nexins , Tissue Plasminogen Activator/metabolism , Urokinase-Type Plasminogen Activator/metabolism , alpha-2-Antiplasmin
16.
Cardiology Letters ; 30(5):238-245, 2022.
Article in Slovak | EMBASE | ID: covidwho-1818476

ABSTRACT

In 2020, the last periodic snapshot of the SLOVAKS registry, dedicated to the management of patients with ACS, took place in Slovakia. Results: 1450 patients were analyzed, with the proportion of STEMI representing 41.5%. Primary reperfusion therapy was performed in 89.1% of patients (pPCI 88.7%, fibrinolysis 0.4%). The median of total ischemic interval was 260 min, which was an insignificant prolongation compared to year 2015 (230.5 min) (p = 0.277). At the time of the COVID19 pandemic, the expected significant increase in the total ischemic interval was probably offset by the widespread use of the telemedicine communication platform STEMI, which led to a significant increase in the ability of EMS crews to provide STEMI ECG diagnostics in the field (38.8 vs. 61.4%), and increase primary transports to pPCI centers (48.45 vs. 62.2%). Of all pPCI cases, up to 37.4% were performed outside the recommended time limit (within 120 minutes of the ECG) and 63.5% outside the optimal time limit (within 90 minutes of the ECG). Patient hesitation (median of symptoms-ECG interval 150 min) and patient transport had a decisive share in unnecessary time losses, as up to 37.8% of STEMIs were transported to the primary PCI by secondary transport. STEMI hospitalization lethality was 4.5%. Conclusion: At the time of the COVID19 pandemic, the Slovak health care system maintained a high quality of management for patients with acute STEMI and there was no significant deterioration in the monitored quality parameters. Despite several positive trends (high concentration of emergency medical crews, unlimited availability of modern drugs, availability of invasive management 24/7, increased ability of emergency medical crews to provide ECG diagnostics of STEMI in the field) several deficiencies can be identified in the health care system. Above all, these are inappropriate time losses caused by patients, but also by the health care system due to unnecessary so-called secondary transports. A significant part of the patients met the indication for prehospital administration of fibrinolytics and so-called pharmacoinvasive procedure. The disappearance of this procedure from medical practice is medically unjustifiable. Fig. 8, Tab. 7, Ref. 12, on-line full text (Free, PDF) www.cardiologyletters.sk.

17.
Int J Lab Hematol ; 2022 Apr 22.
Article in English | MEDLINE | ID: covidwho-1807101

ABSTRACT

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by marked hypoxaemia and lung oedema, often accompanied by disordered blood coagulation and fibrinolytic systems, endothelial damage and intravascular fibrin deposition. PATIENTS/METHODS: We present a retrospective observational study of 104 patients admitted to hospital with COVID-19. Plasma samples were collected within 72 h of admission. In addition to routine coagulation and haematology testing, soluble thrombomodulin (sTM), thrombin-antithrombin (TAT), tissue plasminogen activator-plasminogen activator inhibitor 1 complex (tPAI-C) and plasmin-α2 antiplasmin complex (PIC) were performed by automated chemiluminescent enzyme immunoassays. RESULTS: Significantly higher levels of D-dimer, TAT, sTM and tPAI-C were observed in non-survivors compared to survivors. To confirm which parameters were independent risk factors for mortality, multiple logistic regression was performed on D-dimer, TAT. sTM, tPAI-C and PIC data. Only increasing sTM was significantly associated with mortality, with an odds ratio of 1.065 for each 1.0 TU/mL increment (95% CI 1.025-1.115). CONCLUSIONS: Of the haemostatic variables measured, sTM, which can be rapidly assayed, is the best independent predictor of mortality in patients hospitalized with COVID-19, and this suggests that endothelial dysfunction plays an important role in disease progression.

19.
European Heart Journal Cardiovascular Imaging ; 23(SUPPL 1):i622, 2022.
Article in English | EMBASE | ID: covidwho-1795301

ABSTRACT

Purpose: We want to evaluate clinical, laboratory profiles and intra-hospital outcome in patients with acute PE treated in intensive care unit in the period of COVID-19 pandemic. Methods: This is a single center, retrospective cohort study of patients with confirmed acute PE admitted in Intensive Cardiac Care Unit of a tertiary level university hospital between January and December 2020. Detailed history, risk factors, laboratory parameters and treatment strategy based on patient risk were assessed. All patients underwent 2-dimensional echocardiography, lower limb venous Doppler and CT pulmonary angiography (CTPA). sPESI score and intra-hospital outcomes were evaluated in all patients. Nasopharyngeal smear and realtime reverse transcriptase-polymerase chain reaction (RT-PCR) assay was performed in order to confirm COVID-19 infection. Results: We studied 47 patients with acute PE treated in our ICU, with mean age 58.6 ± 19.4 years. Eight patients (17%) had massive PE (central thrombus) and 39 (83%) had sub massive PE (subsegmental thrombus) confirmed by CTPA. Six patients (12,7%) had history of deep vein thrombosis (DVT), 3 patients (6,3%) had history of prior PE, 4 patients (8,5%) were operated within 3 months, 7 patients (14,8%) had history of malignancy, 24 patient's had increased body weight and obesity (51%). Twelve patients (25,5%) were tested for COVID 19 with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and 3 come positive (12.5%). Eight patients were high risk with shock (17%), intermediate high risk were 29 patients (61.7%) and intermediate low risk were 10 patients (21.3%). sPESI score was >1 in all 47 patients. Abnormal RV function with PAH was found in 32 patients (68%). Five high risk, unstable patients died within 72 hours of admission, resulting in an overall ICU mortality rate of 10,6% and 62.5% mortality rate in patients with cardiogenic shock. Patients with PE and COVID-19 had significantly higher D-dimer and hs-Troponin I levels comparing to the patients with patients negative for COVID-19. Multivariate logistic regression analysis showed thrombolytic therapy OR 2.145 (95% CI: 1.105-4,512), D-Dimers >4.500 ng/ml OR 1.893 (95% CI: 0.932-3.241), high risk PE OR 3.98 (95% CI: 1.396-5.641) and acute renal failure OR 2.421 (95% CI: 1.105-4.762) as independent mortality predictors. Eight patients have been treated with fibrinolysis (t-PA), and 39 patients with Heparin therapy. 40 survived patients were discharged with NOAC treatment (95,2%). Conclusions: Pulmonary embolism cardiology clinic ICU admission in the period of COVID-19 pandemic decreased, with increase of PE severity, patients risk and mortality rate. Thrombolytic therapy, D-Dimers >4.500 ng/ml, high risk PE and acute renal failure were independent mortality predictors. Thrombolysis was successful treatment for high risk patients with low bleeding risk.

20.
Critical Care ; 26(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1793842

ABSTRACT

Introduction: A significant degree of mortality and morbidity in COVID-19 is due to thromboembolic disease. Changes in coagulation markers have been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. We sought to investigate how coagulation markers change over the course of COVID-19 infection and whether they might predict disease severity. Methods: Patients were recruited from a single University Teaching Hospital ED at the time of presentation. Those with a positive PCR test were followed up throughout their stay. Rotational thromboelastometry (ROTEM) was performed on arrival, after 24 h, 3-5 days and 7 days, alongside routine haematological and biochemical testing. ROTEM values at each of these time points were analysed, and compared. Length of stay and patient outcome were also recorded for subgroup analysis. The ROTEM parameters selected for analysis were both EXTEM and INTEM Clotting Time (CT), Clot Formation Time (CFT), Maximal Clot Firmness (MCF), Alpha Angle (Alpha) and Maximum Lysis Percentage (ML). This reflects clot formation kinetics, mechanical strength and clot breakdown via both extrinsic and intrinsic pathways. Results: EXTEM (7.64 ± 5.53 vs 11.83 ± 6.30) and INTEM ML (4.69 ± 3.55 vs 9.95 ± 5.22) were significantly reduced in those who died vs patients with a prolonged hospital stay. Over time there were no patterns of change to ROTEM values in any outcome group. Conclusions: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of COVID-19 compared with those who survive a prolonged hospital stay to discharge was the extent to which fibrinolysis could occur. Failure to break clots down could be a significant mechanism in the mortality and morbidity of COVID-19.

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