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1.
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
3.
Sci Rep ; 12(1): 637, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621276

ABSTRACT

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.


Subject(s)
Blood Coagulation , COVID-19/blood , COVID-19/therapy , Adult , Blood Coagulation Tests , Blood Preservation , Blood Transfusion , Female , Humans , Immunization, Passive , Male , Middle Aged
4.
Front Immunol ; 12: 762782, 2021.
Article in English | MEDLINE | ID: covidwho-1593084

ABSTRACT

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ 2 = 34.812), and FDP (p < 0.002, χ 2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.


Subject(s)
Blood Coagulation Disorders/blood , Blood Coagulation Tests/methods , Blood Coagulation , COVID-19/complications , Adult , Aged , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/diagnosis , Blood Coagulation Factors/metabolism , COVID-19/virology , Female , Fibrin/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Homeostasis , Humans , Male , Middle Aged , Partial Thromboplastin Time , Prognosis , Protein C/metabolism , Prothrombin Time , SARS-CoV-2/genetics , SARS-CoV-2/physiology
5.
Int J Lab Hematol ; 44(2): 407-413, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1528379

ABSTRACT

INTRODUCTION: The high incidence of thrombotic events in patients with COVID-19 affects health care worldwide and results in an increased workload in haemostasis laboratories due to more frequent testing of D-dimer, haemostatic parameters and anti-Xa tests. However, the impact of this increase in assay requests on the quality of performance in haemostasis laboratories remains unclear. In this study, the impact of the COVID-19 pandemic on the quality of performance and management of haemostasis laboratories was evaluated. METHODS: The impact on the quality of performance was studied using external quality assessment data from 2019 to 2020 derived from ECAT surveys. A questionnaire was sent to Dutch haemostasis laboratories to identify challenges and management strategies. Furthermore, the number of assays performed in 2019 and 2020 was supplied by four Dutch hospitals, located in regions with different disease incidence. RESULTS: No differences in response rate nor the quality of the measurements were observed between the EQA surveys in 2019 and 2020. The questionnaire results showed a large increase of >25% in the number of test requests for anti-Xa, D-dimer and fibrinogen assays in 2020 compared to 2019. Extreme peaks in test requests were also observed in the four evaluated hospitals. Additionally, 84% of the respondents indicated that they had experienced increased work pressure, and increased sick leave was observed in 71% of the participating laboratories. CONCLUSIONS: The enormous increase in test requests, especially for D-dimer assays and anti-Xa activity, did not affect the quality of performance within haemostatic laboratories during the COVID-19 pandemic.


Subject(s)
COVID-19 , Blood Coagulation Tests , COVID-19/epidemiology , Hemostasis , Humans , Laboratories , Pandemics , Quality Assurance, Health Care
6.
Open Heart ; 8(2)2021 11.
Article in English | MEDLINE | ID: covidwho-1523054

ABSTRACT

BACKGROUND: Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring. OBJECTIVE: To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic. METHODS: With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England. RESULTS: 20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420). CONCLUSIONS: Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.


Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation/drug effects , COVID-19 , Drug Substitution/standards , Factor Xa Inhibitors/administration & dosage , Practice Guidelines as Topic/standards , Practice Patterns, Physicians'/standards , State Medicine/standards , Warfarin/administration & dosage , Aged , Anticoagulants/adverse effects , Blood Coagulation Tests , Drug Monitoring , Drug Prescriptions , Drug Substitution/adverse effects , Drug Utilization/standards , England , Factor Xa Inhibitors/adverse effects , Female , Humans , Male , Middle Aged , Patient Safety , Primary Health Care/standards , Retrospective Studies , Risk Assessment , Risk Factors , Warfarin/adverse effects
7.
Scand J Clin Lab Invest ; 81(8): 653-660, 2021 12.
Article in English | MEDLINE | ID: covidwho-1521954

ABSTRACT

Coagulation disturbances are common in severe COVID-19 infection. We examined laboratory markers in COVID-19 patients during the first wave of the pandemic in Finland. We analysed a wide panel of coagulation tests (IL ACL TOP 750/500®) from anonymously collected samples of 78 hospitalized COVID-19 patients in intensive care units (ICUs; n = 34) or medical wards (n = 44) at Helsinki University Hospital in April-May 2020. These coagulation data were supplemented with the laboratory information system results, including complete blood count and C reactive protein (CRP). Coagulation and inflammatory markers were elevated in most: FVIII in 52%, fibrinogen 77%, D-dimer 74%, CRP 94%, platelet count 37%. Anaemia was common, especially in men (73% vs. 44% in women), and overall weakly correlated with FVIII (women R2 = 0.48, men R2 = 0.24). ICU patients had higher fibrinogen and D-dimer levels (p < .01). Men admitted to the ICU also had higher platelet count, leukocytes and FVIII and lower haemoglobin than the non-ICU patients. None of the patients met the disseminated intravascular coagulation (DIC) criteria, but 31% had a D-dimer level of at least 1.5 mg/L. Presence of both anaemia and high D-dimer together with FVIII is independently associated with ICU admission. Antithrombin was reduced in 47% of the patients but did not distinguish severity. Overall, CRP was associated with coagulation activation. Elevated FVIII, fibrinogen and D-dimer reflected a strong inflammatory response and were characteristic of hospitalized COVID-19 patients. The patients were often anaemic, as is typical in severe inflammation, while anaemia was also associated with coagulation activity.


Subject(s)
Anemia/virology , Blood Coagulation Disorders/virology , Blood Coagulation , COVID-19/complications , Adolescent , Adult , Aged , Aged, 80 and over , Antithrombins , Big Data , Blood Coagulation Tests , C-Reactive Protein , Female , Fibrin Fibrinogen Degradation Products , Fibrinogen , Finland/epidemiology , Humans , Intensive Care Units , Male , Middle Aged , Platelet Count , Retrospective Studies , Young Adult
8.
J Thromb Haemost ; 19(12): 2918-2929, 2021 12.
Article in English | MEDLINE | ID: covidwho-1526389

ABSTRACT

Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations. Routine coagulation assays and even more specialized tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay allowing the dynamic continuous and simultaneous recording of the combined effects of both thrombin generation and thrombin inactivation. TGA thus reflects the result of procoagulant and anticoagulant activities in blood and plasma. Because of this unique feature, TGA has been widely used in a wide array of settings from both research, clinical and pharmaceutical perspectives. This includes diagnosis, prognosis, prophylaxis, and treatment of inherited and acquired bleeding and thrombotic disorders. In addition, TGA has been shown to provide relevant information for the diagnosis of coagulopathies induced by infectious diseases, comprising also disturbance of the coagulation system in COVID-19, or for the assessment of early recurrence in breast cancer. This review article aims to document most clinical applications of TGA.


Subject(s)
Blood Coagulation Tests , Thrombin , Blood Coagulation Disorders/diagnosis , COVID-19 , Humans , Neoplasm Recurrence, Local , SARS-CoV-2
9.
J Clin Anesth ; 75: 110484, 2021 12.
Article in English | MEDLINE | ID: covidwho-1514199

ABSTRACT

OBJECTIVE: To determine the normal values for non-activated thromboelastometry parameters among pregnant women. DESIGN: Prospective, observational study. SETTING: Tertiary care hospital. PATIENTS: Non-laboring women at term gestation without history of bleeding or clotting disorder or anticoagulation use. INTERVENTIONS: Venous blood samples were collected and ROTEM® was performed using NATEM and NaHEPTEM assays. MEASUREMENTS: Reference ranges were derived by calculating 2.5 and 97.5 percentiles for the following parameters: clotting time (CT), clot formation time (CFT), amplitude at 10 (A10) and 20 min (A20), alpha angle, maximum clot firmness (MCF), and lysis index at 30 (LI30) and 60 min (LI60). The NATEM/NaHEPTEM CT ratio was calculated to determine the baseline ratio in term pregnant women. MAIN RESULTS: 146 women were screened and 120 were enrolled. The median age was 34 years [31-36], median gestational age was 39.1 weeks [38.3-39.3], and median parity was 1 [0-2]. Median pre-delivery platelet and hematocrit levels were within the normal ranges. The reference ranges for NATEM parameters were: CT (232-759 (s)), CFT (69-243 (s)), alpha angle (50-77 (°)), A10 (44-69 (mm)), A20 (54-75 (mm)), MCF (57-77 (mm)), LI30 (100-100 (%)), LI60 (90-100 (%)). The reference ranges for NaHEPTEM parameters were: CT (224-717 (s)), CFT (66-210 (s)), alpha angle (53-77 (°)), A10 (44-67 (mm)), A20 (55-73 (mm)), MCF (58-74 (mm)), LI30 (99-100 (%)), LI60 (90-100 (%)). The NATEM to NaHEPTEM CT ratio reference range was 0.73-1.3. CONCLUSIONS: This study is the first to our knowledge to report reference ranges for non-activated ROTEM® tests with and without heparinase in non-laboring term pregnant women. These reference ranges may serve as a baseline comparison and may be useful for future research on anticoagulation management in pregnancy.


Subject(s)
Pregnant Women , Thrombelastography , Adult , Blood Coagulation Tests , Female , Heparin Lyase , Humans , Infant , Pregnancy , Prospective Studies
10.
Semin Thromb Hemost ; 48(1): 31-54, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1493298

ABSTRACT

Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3-4, and 7-8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin-antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis (n = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.


Subject(s)
COVID-19 , Thrombosis , Blood Coagulation Tests , Cohort Studies , Critical Care , Fibrinolysis , Hemostasis , Humans , Prospective Studies , SARS-CoV-2 , Thrombelastography , Thrombin
12.
Platelets ; 33(4): 520-530, 2022 May 19.
Article in English | MEDLINE | ID: covidwho-1347990

ABSTRACT

We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Blood Coagulation , Blood Coagulation Tests , Hemostasis , Humans , Thrombelastography
13.
Int J Lab Hematol ; 43 Suppl 1: 36-42, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1319316

ABSTRACT

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.


Subject(s)
Blood Coagulation Tests , COVID-19/blood , SARS-CoV-2 , Thrombophilia/etiology , Antibodies, Antiphospholipid/blood , Biomarkers/blood , Blood Coagulation Factors/analysis , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Factor Xa/analysis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Fibrinolysis , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Partial Thromboplastin Time , Platelet Count , Prothrombin Time , Thrombelastography , Thrombin/biosynthesis , Thrombophilia/blood , Thrombophilia/drug therapy
14.
J Thromb Haemost ; 18(7): 1747-1751, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317985

ABSTRACT

BACKGROUND: Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. OBJECTIVES: Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. METHODS: Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. RESULTS: At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 µg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2  = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). CONCLUSION: The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.


Subject(s)
Betacoronavirus/pathogenicity , Blood Coagulation Disorders/blood , Blood Coagulation , Coronavirus Infections/blood , Pneumonia, Viral/blood , Aged , Anticoagulants/administration & dosage , Biomarkers/blood , Blood Coagulation/drug effects , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/virology , Blood Coagulation Tests , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Fibrinolytic Agents/administration & dosage , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Treatment Outcome
15.
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
16.
Int J Lab Hematol ; 43(6): 1302-1308, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1288297

ABSTRACT

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.


Subject(s)
COVID-19/blood , Lymphocyte Count , SARS-CoV-2 , Adult , Aged , Biomarkers/blood , Blood Cell Count , Blood Coagulation Tests , Blood Proteins/analysis , COVID-19/mortality , China/epidemiology , Creatinine/blood , Female , Hospital Mortality , Hospitals, General/statistics & numerical data , Humans , Lymphopenia/blood , Lymphopenia/etiology , Male , Mass Screening , Middle Aged , Patient Admission , Prognosis , Retrospective Studies , Severity of Illness Index , Treatment Outcome
17.
Clin Appl Thromb Hemost ; 27: 10760296211027653, 2021.
Article in English | MEDLINE | ID: covidwho-1286792

ABSTRACT

Identifying a hypercoagulable state in patients with COVID-19 may help identify those at risk for virus-induced thromboembolic events and improve clinical outcomes using personalized therapeutic approaches. Herein, we aimed to perform a global assessment of the patients' hemostatic system with COVID-19 using rotational thromboelastometry (ROTEM) and to describe whether patients with different disease severities present different coagulation profiles. Together with 37 healthy volunteers, a total of 65 patients were included and then classified as having mild, moderate, and severe disease depending on clinical severity. Peripheral blood samples were collected and analyzed using a ROTEM Coagulation Analyzer. Also, complete blood count and coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels were measured at admission. EXTEM and INTEM MCF (P < 0.001) values were significantly higher and the EXTEM CFT (P = 0.002) value was significantly lower in patients with COVID-19 when compared with controls. In particular, patients with the severe disease showed a significant decrease in CFT (P < 0.001) and an increase in MCF (P < 0.001) in both INTEM and EXTEM assays compared with patients with the non-severe disease. Correlation analysis revealed significant correlations between ROTEM parameters and other coagulation parameters. There were significant positive correlations between fibrinogen, D-dimer, platelet count, and MCF in both EXTEM and INTEM assays. Our data demonstrate thromboelastographic signs of hypercoagulability in patients with COVID-19, which is more pronounced in patients with increased disease severity. Therefore, ROTEM analysis can classify subsets of patients with COVID-19 at significant thrombotic risk and assist in clinical decisions.


Subject(s)
COVID-19/blood , SARS-CoV-2 , Thrombelastography , Thrombophilia/etiology , Adult , Blood Cell Count , Blood Coagulation Tests , Blood Proteins/analysis , Case-Control Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/diagnosis
18.
Heart Surg Forum ; 24(3): E564-E574, 2021 06 23.
Article in English | MEDLINE | ID: covidwho-1282335

ABSTRACT

BACKGROUND: Our aim of this study was to evaluate the cardiac symptoms, coronary angiographic results, and clinical outcomes of patients with confirmed COVID-19 and ST-segment elevation with myocardial infarction (STEMI) or myocardial ischemia. MATERIAL AND METHODS: Thirty-seven patients, who already were confirmed with COVID-19 using reverse transcriptase-polymerase chain reaction (RT-PCR), were admitted to our hospital due to chest pain with STEMI. The median patient age was 66 years (range: 27-84 years). Female/male ratio was 22/15. We performed a second RT-PCR test in all patients. We investigated myocardial enzymes (creatine kinase myocardial band (CK-MB), cardiac troponin-I (c-TnI), and C-reactive protein (CRP), and liver enzymes (alanine amino transferase (ALT) and aspartate amino transferase (AST) also were measured. Blood d-dimer, thromboplastin time (PT), partial thromboplastin time (PTT), and fibrinogen were investigated. Transcutaneous oxygen saturation was monitored for each patient in the emergency department (ED). To evaluate myocardial wall abnormalities, transthoracic echocardiography was performed. RESULTS: Coronary artery disorders requiring revascularization were detected in 25 patients (67.5%). There was no evidence of coronary artery disease in the remaining 12 patients. Out of 25, nine coronary artery disease patients had a history of coronary intervention (24.3%). All patients had high levels of myocardial enzyme release. Percutaneous coronary interventions (PCI) were performed in patients with culprit lesion(s). Success rate of PCI was 87.5% (N = 21). The median number of stent use was 2.9±0.7 (range: 1-4). Because PCI failed in four patients, we suggested elective coronary artery bypass grafting (CABG) surgery after medical treatment. Six patients required re-intervention owing to early stent thrombosis (30%). Seven patients died after PCI (33.3%). For patients with negative or positive RT-PCR test results, we performed thoracic computed tomography (CT), which is a sensitive diagnostic method for COVID-19. Interlobular septal and pleural thickening with patchy bronchiectasis in the bilateral or unilaterally lower and/or middle lobe(s) were the main pathologies in 24 patients. D-dimer, fibrinogen, and CRP levels were high in 11 PCI patients with bilaterally pulmonary involvement by COVID-19 (52.3%), while fibrin degradation products did not significantly change. For three patients with normal coronary arteries with a transient hypokinesia or hypokinesia as result of myocarditis, we decided to perform atypical Takotsubo cardiomyopathy. We medically treated using inodilator (levosimendan), diuretic, angiotensin-converting enzyme inhibitors and beta-blockers. To prevent the risk of thromboembolism, we also administered a heparin drip. The myocardial contractility of the apex did improve, and patients were discharged from the hospital, with the exception of one young female patient. She is following in the ICU with stabil hemodynamics. CONCLUSION: Chest pain with STEMI can develop in patients with confirmed COVID-19. Nearly one-third of patients had COVID-19 with chest pain and concomitant STEMI and normal coronary angiography (32.4%). Urgent PCI may be performed in hemodynamically unstable patients with high mortality. Complications, including sudden cardiac arrest, severe ventricular arrhythmia, and Takotsubo cardiomyopathy, related to COVID-19 patients with normal coronary arteries.


Subject(s)
COVID-19/complications , Coronary Artery Bypass , Percutaneous Coronary Intervention/methods , ST Elevation Myocardial Infarction/surgery , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Coagulation Tests , Coronary Angiography , Echocardiography , Female , Humans , Male , Middle Aged , Pneumonia, Viral/complications , SARS-CoV-2 , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/etiology , Tomography, X-Ray Computed
19.
Sensors (Basel) ; 21(8)2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1178411

ABSTRACT

Prothrombin time (PT) is a significant coagulation (hemostasis) biomarker used to diagnose several thromboembolic and hemorrhagic complications based on its direct correlation with the physiological blood clotting time. Among the entire set of PT dependents, candidates with cardiovascular ailments are the major set of the population requiring lifelong anticoagulation therapy and supervised PT administration. Additionally, the increasing incidence of COVID affected by complications in coagulation dynamics has been strikingly evident. Prolonged PT along with sepsis-induced coagulopathy (SIC score > 3) has been found to be very common in critical COVID or CAC-affected cases. Considering the growing significance of an efficient point-of-care PT assaying platform to counter the increasing fatalities associated with cardio-compromised and coagulation aberrations propping up from CAC cases, the following review discusses the evolution of lab-based PT to point of care (PoC) PT assays. Recent advances in the field of PoC PT devices utilizing optics, acoustics, and mechanical and electrochemical methods in microsensors to detect blood coagulation are further elaborated. Thus, the following review holistically aims to motivate the future PT assay designers/researchers by detailing the relevance of PT and associated protocols for cardio compromised and COVID affected along with the intricacies of previously engineered PoC PT diagnostics.


Subject(s)
COVID-19 , Blood Coagulation Tests , Humans , International Normalized Ratio , Prothrombin Time , SARS-CoV-2
20.
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
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