scholarly journals Adverse Outcome in Non-severe COVID-19: Potential Diagnostic Coagulation Tests

Reports ◽  
2021 ◽  
Vol 4 (4) ◽  
pp. 35
Author(s):  
Rossella Cacciola ◽  
Elio Gentilini Gentilini Cacciola ◽  
Veronica Vecchio ◽  
Emma Cacciola
Keyword(s):  
Tissue Factor Pathway Inhibitor ◽  
Early Recognition ◽  
Endothelial Damage ◽  
Clot Lysis ◽  
Clotting Time ◽  
Platelet Factor ◽  
Severe Stage ◽  
Coagulation Tests ◽  
Tissue Factor Pathway ◽  
Clot Formation Time

COVID-19-associated coagulopathy (CAC) identifies the coagulation changes in coronavirus disease 2019 (COVID-19) and is responsible for thrombosis. CAC has been studied in critical and severe stage COVID-19 disease through tests including the D-Dimer (DD), prothrombin time (PT), thromboplastin partial time (PTT), platelet count, fibrinogen (Fib), and platelet factor 4 (PF4) tests. However, these tests have some limitations. The aim of this study was to identify more accurate warning tests for early recognition of CAC and to prevent its deterioration to disseminated intravascular coagulation (DIC). First, we measured Interleukin-1a (IL-1a) and IL-8, and tissue factor pathway inhibitor (TFPI) as inflammation and endothelial damage markers, respectively. Second, we measured thrombin antithrombin complex (TAT), b-Thromboglobulin (b-TG), and thromboelastometric parameters including clotting time (CT), clot formation time (CFT), clot firmness (MCF), and clot lysis at 30 min (LY-30), as markers of coagulation and platelet activation. This study included 100 non-severe patients with COVID-19 that developed pulmonary embolism (PE) compared to 80 healthy patients. IL-1a and IL-8, and TFPI were higher as well as TAT and b-TG and thromboelastometric parameters, indicating hypercoagulability. If confirmed in other studies, these results could help in predicting the deterioration of non-severe COVID-19 disease, thereby reducing hospitalizations and health costs.

The Significance of TFPI in Clotting Assays – Gomparison and Combination with other Anticoagulants

1993 ◽  
Vol 70 (03) ◽  
pp. 448-453 ◽  
Author(s):  
Ole Nordfang ◽  
Hanne I Kristensen ◽  
Sanne Valentin ◽  
Per Østergaard ◽  
Johnny Wadt
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Antithrombin Iii ◽  
Anticoagulant Activity ◽  
Assay System ◽  
Thrombin Inhibitor ◽  
Clotting Time ◽  
Normal Plasma ◽  
Tissue Factor Pathway ◽  
Plasma Heparin

SummaryThe anticoagulant activities of Tissue Factor Pathway Inhibitor (TFPI), heparin and hirudin were compared in intrinsic (APTT) and extrinsic (PT) activated clotting assays. In contrast to the thrombin inhibitor hirudin, heparin was 10 fold more potent in the APTT assay than in the PT assay, indicating that inhibition of intrinsic activation is important for the anticoagulant activity of heparin as measured in an APTT assay. TFPI was most potent in the PT assay and the effect of TFPI was most pronounced in the presence of other anticoagulants (heparin and hirudin). The activities of the two natural anticoagulants antithrombin III (ATIII) and TFPI were compared in a PT assay with very dilute tissue factor. In this assay system TFPI in normal plasma affected the clotting time more than ATIII in the plasma. However, when heparin was added ATIII was the major anticoagulant, but profound Prolongation of the clotting time was only seen when TFPI was also added. In an ATIII deficient plasma heparin did not augment the effect of TFPI, showing that the increased effect of TFPI in the presence of heparin is dependent on the anticoagulant activity of ATIII/heparin. The effect of TFPI at prolonged clotting times was also illustrated by the significant effect of blocking TFPI in the plasma from warfarin-treated patients. Thus TFPI is a major anticoagulant in normal plasma and the effect of TFPI is especially seen at prolonged clotting times.

87 Evaluating Endothelial Dysfunction in Thermally-injured Patients with syndecan-1, Tissue Factor Pathway Inhibitor, and Thrombomodulin as Predictors of Mortality

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S57-S58
Author(s):  
John W Keyloun ◽  
Saira Nisar ◽  
Kathleen Brummel-Ziedins ◽  
Maria Bravo ◽  
Matthew Gissell ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Burn Injury ◽  
Endothelial Damage ◽  
Inhalation Injury ◽  
Burn Patients ◽  
Mixed Effect ◽  
Significant Difference ◽  
Tissue Factor Pathway ◽  
Injured Patients

Abstract Introduction Endotheliopathy in burn patients is largely uncharacterized. Syndecan-1 (SDC-1), thrombomodulin (TM), and tissue factor pathway inhibitor (TFPI) are components of the vascular endothelial glycocalyx. Proteolytic cleavage of these moieties may yield biomarkers for endothelial damage. The aim of this study is to evaluate endotheliopathy after burn injury by monitoring plasma levels of these biomarkers over time to investigate potential relationship to mortality. Methods Burn injured patients presenting to a regional burn center from 2012 to 2017 were prospectively enrolled. Blood samples were collected at 0, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours from admission. Plasma SDC-1, TM, and TFPI levels were quantified by ELISA. Demographic data and injury characteristics were obtained from the medical chart. Patients with concomitant inhalation injury, trauma, or < 10% total body surface area (TBSA) burns were excluded. Statistical analysis was performed using mixed-effect models with Sidak’s correction for multiple comparisons. Significance was set at p =0.05. Data are presented as mean ± standard deviation. Results A cohort of 22 patients was identified with an average age of 45±14 years, TBSA of 30±15%, with 6 patients who died from their injuries. The deceased group was older (59±13 vs. 40±10 years, p = 0.01), and there was no significant difference in burn size. Mean SDC-1 levels were higher in the deceased group at all time points (p=0.0004) and this difference was significant at hour 12 (106±11 vs. 41±31 ng/mL, p = 0.0002), hour 24 (160±39 vs. 35±20 ng/mL, p = 0.04) and hour 72 (100±3 vs. 35±38 ng/mL, p = 0.01). Mean soluble TM levels were higher in the deceased group after hour 12 (p = 0.04) and there was a trend towards higher TFPI levels after hour 12 in the deceased group. Conclusions Biomarkers are elevated in patients following burn injury who die, when inhalation injury and trauma are excluded. Given equivalent TBSA, older patients appear more sensitive to thermally induced glycocalyx degradation. SDC-1 shows the greatest promise as a prognostic indicator as levels tend to be higher among deceased patients on admission and are significantly higher as early as hour 12. Applicability of Research to Practice Reliable assessment of the patient’s endothelial damage may hold predictive value for clinicians and could assist in clinical decision making. Further research must investigate endotheliopathy in burn patients.

Coagulation assessment by rotation thrombelastometry in normal pregnancy

2009 ◽  
Vol 101 (04) ◽  
pp. 755-761 ◽  
Author(s):  
Nicolas Carrabin ◽  
Mehdi Benchaib ◽  
Oriane Fontaine ◽  
Albrice Levrat ◽  
Denis Massignon ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Point Of Care ◽  
Normal Pregnancy ◽  
Clot Lysis ◽  
Clotting Time ◽  
Intrinsic Pathway ◽  
Extrinsic Pathway ◽  
Coagulation Tests ◽  
Maximum Clot Firmness

SummaryWe analysed changes in coagulation during normal pregnancy with a novel point-of-care device based on thrombelastometry (ROTEM®). We compared the results obtained with those of standard coagulation tests in 104 patients: 20 non-pregnant women (controls) and 84 women in the first (T1, n=17), second (T2, n=9) and third (T3, n=58) trimesters of pregnancy. We measured the clotting time (CT), the maximum clot firmness (MCF), the early clot amplitude at 5 and 15 minutes (CA5, CA15) and the clot lysis index (CLI30) with four tests containing specific reagents. (a) The INTEM® test involving ellagic acid activated the intrinsic pathway and (b) the EXTEM® test using tissue factor triggered the extrinsic pathway; (c) The FIBTEM® test based on a platelet inhibitor (cytochalasin D) evaluated the contribution of fibrinogen to clot formation and (d) the APTEM® test was similar to the EXTEM but was based on inhibition in vitro of fibrinolysis by aprotinin. CT and CLI30 were not significantly modified during pregnancy whereas MCF, CA5 and CA15 (INTEM, EXTEM, FIBTEM) increased significantly between the second and third trimesters (e.g. median [interquartile range]: MCF-FIBTEM, 13 [11–16] mm vs. 19 [17–23] mm, respectively, in controls and T3, p< 0.001). EXTEM values were not significantly different from those measured with APTEM. There were significant correlations between the results obtained with ROTEM and those from standard coagulation tests. ROTEM analysis showed a marked increase in coagulability during normal pregnancy. ROTEM values may serve as the basis for future studies in pregnant women.

scholarly journals Enhanced Antifibrinolytic Efficacy of a Plasmin-Specific Kunitz-Inhibitor (60-Residue Y11T/L17R with C-Terminal IEK) of Human Tissue Factor Pathway Inhibitor Type-2 Domain1

2020 ◽  
Vol 9 (11) ◽  
pp. 3684
Author(s):  
Kanagasabai Vadivel ◽  
Anne K. Zaiss ◽  
Yogesh Kumar ◽  
Frank M. Fabian ◽  
Ayman E. A. Ismail ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Human Tissue ◽  
Active Sites ◽  
Tissue Factor Pathway Inhibitor ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Kunitz Inhibitor ◽  
Tissue Factor Pathway ◽  
Inhibitor Type

Current antifibrinolytic agents reduce blood loss by inhibiting plasmin active sites (e.g., aprotinin) or by preventing plasminogen/tissue plasminogen activator (tPA) binding to fibrin clots (e.g., ε-aminocaproic acid and tranexamic acid); however, they have adverse side effects. Here, we expressed 60-residue (NH2NAE…IEKCOOH) Kunitz domain1 (KD1) mutants of human tissue factor pathway inhibitor type-2 that inhibit plasmin as well as plasminogen activation. A single (KD1-L17R-KCOOH) and a double mutant (KD1-Y11T/L17R- KCOOH) were expressed in Escherichia coli as His-tagged constructs, each with enterokinase cleavage sites. KD1-Y11T/L17R-KCOOH was also expressed in Pichia pastoris. KD1-Y11T/L17R-KCOOH inhibited plasmin comparably to aprotinin and bound to the kringle domains of plasminogen/plasmin and tPA with Kd of ~50 nM and ~35 nM, respectively. Importantly, compared to aprotinin, KD1-L17R-KCOOH and KD1-Y11T/L17R-KCOOH did not inhibit kallikrein. Moreover, the antifibrinolytic potential of KD1-Y11T/L17R-KCOOH was better than that of KD1-L17R-KCOOH and similar to that of aprotinin in plasma clot-lysis assays. In thromboelastography experiments, KD1-Y11T/L17R-KCOOH was shown to inhibit fibrinolysis in a dose dependent manner and was comparable to aprotinin at a higher concentration. Further, KD1-Y11T/L17R-KCOOH did not induce cytotoxicity in primary human endothelial cells or fibroblasts. We conclude that KD1-Y11T/L17R-KCOOH is comparable to aprotinin, the most potent known inhibitor of plasmin and can be produced in large amounts using Pichia.

Diurnal Rhythm in Anticoagulant Effect of Heparin during a Low Dose Constant Rate Infusion

1992 ◽  
Vol 68 (01) ◽  
pp. 030-032 ◽  
Author(s):  
J W M Krulder ◽  
A de Boer ◽  
A M H P van den Besselaar ◽  
A F Cohen ◽  
H C Schoemaker ◽  
...  
Keyword(s):  
Control Experiment ◽  
Plasma Concentrations ◽  
Anticoagulant Effect ◽  
Diurnal Rhythms ◽  
Clotting Time ◽  
Platelet Factor ◽  
Constant Rate ◽  
Coagulation Tests ◽  
Rate Infusion

SummaryThe objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning.In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.

Effect of Tissue Factor Pathway Inhibitor (TFPI) in the HEPTEST® Assay and in an Amidolytic Anti Factor Xa Assay for LMW Heparin

1992 ◽  
Vol 68 (03) ◽  
pp. 310-314 ◽  
Author(s):  
Hanne I Kristensen ◽  
Per B Østergaard ◽  
Ole Nordfang ◽  
Ulrich Abildgaard ◽  
Anne Karin Lindahl
Keyword(s):  
Tissue Factor ◽  
Low Molecular Weight Heparin ◽  
Tissue Factor Pathway Inhibitor ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Activity Detection ◽  
Clotting Time ◽  
Heparin Activity ◽  
Tissue Factor Pathway

SummaryBoth the HEPTEST® and amidolytic anti factor Xa assays are currently being used for heparin activity detection in plasma from patients receiving standard heparin or low molecular weight heparin (LMWH). In this study we have investigated the influence of recombinant and endogenous Tissue Factor Pathway Inhibitor (TFPI) on these assays. The HEPTEST® determinations were performed on an ACL 300 R Clottimer using the APTT program which resulted in a longer incubation time with factor Xa than recommended by the manufacturer. rTFPI added to plasma prolonged the HEPTEST® clotting time markedly, but had only a little effect in the amidolytic assay. Antibodies against TFPI (anti-TFPI) abolished these effects. The effect of adding rTFPI and Logiparin® was additive. When anti-TFPI IgG was added to samples of normal plasma, a statistically significant shortening of the HEPTEST® clotting time was seen. When anti-TFPI was added to plasma samples from volunteers who had received Logiparin® by subcutaneous or intravenous injection, then the HEPTEST® clotting time was shortened considerably. For some samples the clotting time was halved. These experiments show that the HEPTEST® clotting time is prolonged not only by heparin-antithrombin III, but also by TFPI released by heparin injection.

Proteolysis of Tissue Factor Pathway Inhibitor (TFPI) by Plasmin: Effect on TFPI Activity

1998 ◽  
Vol 80 (09) ◽  
pp. 423-427 ◽  
Author(s):  
Anguo Li ◽  
Tze-Chein Wun
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Factor Viia ◽  
Anticoagulant Activity ◽  
Limited Proteolysis ◽  
Factor Xa ◽  
Clot Lysis ◽  
Plasma Clot ◽  
Amino Terminal ◽  
Tissue Factor Pathway

SummaryAn important regulator of the initiation of blood coagulation is the plasma glycoprotein, tissue factor pathway inhibitor (TFPI). TFPI inhibits factor Xa and factor VIIa/tissue factor complex, thereby dampens the proteolytic cascade of the tissue factor pathway. Plasma clot lysis is primarily mediated by the fibrinolytic enzyme, plasmin, which is generated through limited proteolysis of plasminogen by endogenous or exogenously administered plaminogen activators. In this study, the interaction of plasmin with recombinant E. coli-derived TFPI (rTFPI) was examined. Plasmin was found to cause a time and concentration dependent proteolysis of rTFPI, resulting in the decrease of anti-factor Xa (measured by chromogenic substrate assay) and anticoagulant (measured by tissue factor-induced clotting assay) activities. Amino-terminal sequencing of the proteolytic fragments revealed that plasmin cleaved rTFPI at K86-T87, R107-G108, R199-A200, K249-G250, and K256-R257. Western blot analysis showed that proteolysis of exogenously added rTFPI also occurred in plasma supplemented with urokinase, and this is accompanied by decrease of anticoagulant activity. These changes were abolished by addition of aprotinin, an inhibitor of plasmin. These data indicate that TFPI is susceptible to proteolysis when plasma fibrinolytic system is activated. The results taken together suggest that plasmin degradation of TFPI may contribute to rethrombosis after thrombolysis, and may contribute to the variability of the efficacy of TFPI in various thrombolysis/reocclusion studies reported previously.

The anticoagulant action of recombinant human activated protein C (rhAPC, Drotrecogin α activated): comparison between cord and adult plasma

2004 ◽  
Vol 91 (05) ◽  
pp. 912-918 ◽  
Author(s):  
Siegfried Gallistl ◽  
Martin Koestenberger ◽  
Katrin Baier ◽  
Peter Fritsch ◽  
Joachim Greilberger ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Protein C ◽  
Tissue Factor Pathway Inhibitor ◽  
Activated Protein C ◽  
Clotting Time ◽  
Promising Candidate ◽  
Anticoagulant Action ◽  
Adult Plasma ◽  
Tissue Factor Pathway

SummaryThe present study was performed to compare the anticoagulant efficiency of recombinant human activated protein C (rhAPC) in cord with that in adult plasma. RhAPC is a promising candidate to improve the outcome of severe sepsis. However, different anticoagulant efficiency of rhAPC in cord compared with adult plasma has to be expected due to physiological low plasma levels of tissue factor pathway inhibitor (TFPI) and antithrombin (AT) present in neonates, two inhibitors known to markedly influence the anticoagulant action of APC. Clot formation was induced in our experiments by addition of high (30 µM) or low (20 pM) amounts of lipidated tissue factor (TF). High amounts of TF are conventionally applied in standard clotting assays, whereas plasma activation with low amounts of TF probably better matches the conditions in vivo. We demonstrate that under low coagulant challenge increasing amounts of rhAPC (0.1 – 0.5 µg/ml final plasma concentration) dose-dependently prolonged clotting time and suppressed thrombin potential and prothrombin fragment 1 + 2 generation in both cord and adult plasma. The same was true for experiments performed under high coagulant challenge when 4 – 16 µg/ml of rhAPC were added. Whereby, cord plasma was significantly more susceptible to addition of rhAPC in the presence of high amounts of TF and adult plasma was significantly more susceptible to addition of rhAPC in the presence of low amounts of TF. We demonstrate that increased anticoagulant efficiency of rhAPC in adult plasma under low coagulant challenge is attributable to the physiological high levels of TFPI and AT present in adults.

Platelet Count, Anti-Heparin/Platelet Factor 4 Antibodies and Tissue Factor Pathway Inhibitor Plasma Antigen Level in Chronic Dialysis

1998 ◽  
Vol 89 (3) ◽  
pp. 115-122 ◽  
Author(s):  
Guido Luzzatto ◽  
Massimo Bertoli ◽  
Giuseppe Cella ◽  
Fabrizio Fabris ◽  
Barbara Zaia ◽  
...  
Keyword(s):  
Platelet Count ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Platelet Factor 4 ◽  
Chronic Dialysis ◽  
Antigen Level ◽  
Platelet Factor ◽  
Tissue Factor Pathway
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