Screening Coagulation Assays, Factor XIII and D-Dimer

Author(s):  
Dorothy M. Adcock ◽  
Brian F. Poirier
2021 ◽  
pp. 11-23
Author(s):  
Dorothy M. Adcock ◽  
Brian F. Poirier

Author(s):  
Ning Tang ◽  
Ziyong Sun ◽  
Dengju Li ◽  
Jun Yang ◽  
Shiyu Yin ◽  
...  

AbstractBackground:D-dimer has been used to rule out pulmonary embolism (PE). Based on previous reports of decreased concentrations of coagulation factor XIII (FXIII) in venous thromboembolism, and no change in FXIII concentration in patients with acute cardiovascular disease, we evaluated the benefit of simultaneously measuring D-dimer and FXIII concentrations for diagnosing PE.Methods:In this prospective single-center study, we enrolled 209 patients initially suspected of having PE, and measured their D-dimer and FXIII concentrations. Forty-one patients were diagnosed with PE and 168 with other final diagnoses, including acute coronary syndrome (ACS); aortic dissection (AD); spontaneous pneumothorax (SP); other respiratory, heart, digestive and nervous diseases; and uncertain diagnoses.Results:Patients with PE had significantly higher D-dimer and lower FXIII concentrations than did patients without PE. Combined D-dimer and FXIII measurements provided a higher positive predictive value (76.6%) for PE than single tests, especially in patients with Wells score >4.0 (89.3%). Specifically, patients with AD or ACS showed higher FXIII concentrations and mean platelet volumes than did patients with PE or SP, and patients with PE and AD had higher D-dimer concentrations than did other patients. At the thresholds of 69.0% for FXIII and 1.10 μg/mL for D-dimer, 123/151 patients (81.5%) with serious diseases (PE, AD, ACS and SP) were correctly distinguished.Conclusions:Combined measurement of D-dimer and FXIII helps distinguish PE from serious diseases with similar symptoms and appears to relate to increased FXIII release from active platelets in cardiovascular disease.


2021 ◽  
Vol 27 ◽  
pp. 107602962110503
Author(s):  
Mark Jaradeh ◽  
Nausheen Baig ◽  
Emily Bontekoe ◽  
Mirjana Mitrovic ◽  
Darko Antic ◽  
...  

Introduction Thrombo-inflammatory biomarkers play an important role in the pathogenesis of lymphoma. We aimed to characterize the interrelationship of thrombo-inflammatory biomarkers and blood cellular indices in lymphoma patients. Materials and Methods Ninety-eight lymphoma patient samples were collected from Lymphoma Center of Clinic of Hematology, University of Belgrade, Serbia. Normal controls (n = 50) represented plasma from healthy individuals. Plasminogen activator inhibitor (PAI-1), D-Dimer, factor XIII, C-reactive protein (CRP), microparticles (Mp), Von Willebrand factor (vWF), total protein S, urokinase-type plasminogen activator (uPA), tumor necrosis factor (TNF α), β2-glycoprotein I ( β2GPI), and fibronectin levels were measured utilizing commercially-available ELISA methods. Thrombin generation profile (TGA) was measured using a fluorometric kinetic assay. Platelets, leukocytes, lymphocytes, and neutrophils were measured in conjunction with the complete blood profile. Results Statistically significant differences were noted in levels of PAI-1, D-Dimer, factor XIII, CRP, microparticles, vWF, uPA, TNF α, β2GPI, fibronectin, and TGA when compared to normal (all P values < .001). Platelet to leukocyte ratio (PLA) correlated to TNF α and fibronectin ( R = −0.31 and −0.53, respectively) and the platelet to neutrophil ratio (PNR) correlated to factor XIII and β2GPI ( R = 0.40 and 0.40, respectively). Conclusion Plasma samples from lymphoma patients demonstrated a significantly altered thrombo-inflammatory biomarker profile that has notable correlations to blood cellular indices.


2019 ◽  
Vol 28 ◽  
pp. 175-182 ◽  
Author(s):  
Shu Sun ◽  
Morten Asser Karsdal ◽  
Joachim Høg Mortensen ◽  
Yunyun Luo ◽  
Jens Kjeldsen ◽  
...  

Background & Aims: Crohn’s disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot. Methods: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin. Results: Crohn’s disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn’s disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95% CI 0.83-0.97), 0.78 (95% CI 0.67-0.87) and 0.85 (95% CI 0.75-0.93), respectively. Conclusion: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261429
Author(s):  
Ekaterina M. Koltsova ◽  
Maria A. Sorokina ◽  
Alexandra S. Pisaryuk ◽  
Nikita M. Povalyaev ◽  
Anastasia A. Ignatova ◽  
...  

Background Coagulation system is heavily involved into the process of infective endocarditis (IE) vegetation formation and can facilitate further embolization. In this study we aimed to assess the coagulation and platelet state in IE implementing a wide range of standard and global laboratory assays. We also aim to determine whether prothrombotic genetic polymorphisms play any role in embolization and mortality in IE patients. Methods 37 patients with IE were enrolled into the study. Coagulation was assessed using standard coagulation assays (activated partial thromboplastin time (APTT), prothrombin, fibrinogen, D-dimer concentrations) and integral assays (thromboelastography (TEG) and thrombodynamics (TD)). Platelet functional activity was estimated by flow cytometry. Single nuclear polymorphisms of coagulation system genes were studied. Results Fibrinogen concentration and fibrinogen-dependent parameters of TEG and TD were increased in patients indicating systemic inflammation. In majority of patients clot growth rate in thrombodynamics was significantly shifted towards hypercoagulation in consistency with D-dimers elevation. However, in some patients prothrombin, thromboelastography and thrombodynamics were shifted towards hypocoagulation. Resting platelets were characterized by glycoprotein IIb-IIIa activation and degranulation. In patients with fatal IE, we observed a significant decrease in fibrinogen and thrombodynamics. In patients with embolism, we observed a significant decrease in the TEG R parameter. No association of embolism or mortality with genetic polymorphisms was found in our cohort. Conclusions Our findings suggest that coagulation in patients with infective endocarditis is characterized by general hypercoagulability and platelet pre-activation. Some patients, however, have hypocoagulant coagulation profile, which presumably can indicate progressing of hypercoagulation into consumption coagulopathy.


2014 ◽  
Vol 111 (06) ◽  
pp. 1031-1040 ◽  
Author(s):  
Anat Rabinovich ◽  
Jacqueline M. Cohen ◽  
Susan R. Kahn

SummaryThe post thrombotic syndrome (PTS) develops in 20–40% of deep venous thrombosis (DVT) patients. Risk factors for PTS have not been well elucidated. Identification of risk factors would facilitate individualised risk assessment for PTS. We conducted a systematic review to determine whether biomarkers of fibrinolysis or endothelial dysfunction can predict the risk for PTS among DVT patients. Studies were identified by searching the electronic databases PubMed, EMBASE, Scopus and Web of science. We included studies published between 1990 and 2013, measured biomarker levels in adult DVT patients, and reported rates of PTS development. Fourteen studies were included: 11 investigated the association between D-dimer and PTS; three examined fibrinogen; two measured von Willebrand factor; one measured plasminogen activator inhibitor-1; one assessed ADAMTS-13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats) and one measured factor XIII activity. Studies varied with regards to inclusion criteria, definition of PTS, time point and method of biomarker measurement. We were unable to meta-analyse results due to marked clinical heterogeneity. Descriptively, a significant association with PTS was found for D-dimer in four studies and factor XIII in one study. Further prospective research is needed to elucidate whether these markers might be useful to predict PTS development.


1975 ◽  
Vol 49 (2) ◽  
pp. 149-156 ◽  
Author(s):  
P. J. Gaffney ◽  
D. A. Lane ◽  
M. Brasher

1. The factor XIII-mediated cross-linked α chains in fibrin have no effect on the nature of the fragments released during the solubilization of fibrin by plasmin. 2. Besides the known D dimer and E fragments solubilized during the lysis of cross-linked fibrin, other fragments have been observed on sodium dodecyl sulphate-polyacrylamide gel electrophoresis which have a molecular weight of about 135 000. After prolonged plasmin digestion, these fragments (U fragments) were no longer evident on the gels and the high-molecular-weight E antigen was absent. It is assumed that the E antigen was associated with the U fragments. These fragments also cross-reacted with an anti-D serum. 3. The U fragments have been tentatively presumed to be a factor XIII-mediated cross-linked D–E complex since they degrade only after prolonged degradation with plasmin. Whereas it is known that the fibrin D dimer fragment contains the cross-linked γ chain residues of the originating fibrin, the presumed covalent cross-linking of the D–E fragments has not been proved. 4. The presence of these high-molecular-weight fragments, containing the E antigen, in cross-linked human fibrin digests should be taken into account in the development of D dimer assays to monitor fibrin lysis in vivo.


2018 ◽  
Vol 40 (6) ◽  
pp. 637-644 ◽  
Author(s):  
Steve Kitchen ◽  
Ulrich Geisen ◽  
Janos Kappelmayer ◽  
Peter Quehenberger ◽  
Anna Lowe ◽  
...  

2018 ◽  
Vol 46 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Ekaterina M. Koltsova ◽  
Anna N. Balandina ◽  
Konstantin I. Grischuk ◽  
Margarita A. Shpilyuk ◽  
Elena A. Seregina ◽  
...  

Abstract Introduction: The incidence of venous thromboembolism (VTE) after cesarean section is up to 0.6%, and the widespread use of cesarean section draws attention to this group. The dosage and duration of low-molecular-weight heparin (LMWH) prophylaxis after delivery is estimated by anamnestic risk-scales; however, the predictive potency for an individual patient’s risk can be low. Laboratory hemostasis assays are expected to solve this problem. The aim of this study was to estimate the potency of tests to reflect the coagulation state of patients receiving LMWH in the early postpartum period. Materials and methods: We conducted an observational study on 97 women undergoing cesarean section. Standard coagulation tests (Fg, APTT, prothrombin, D-dimer), an anti-Xa assay, rotation thromboelastometry and thrombodynamics/thrombodynamics-4D were performed. Coagulation assay parameters were compared in groups formed in the presence or absence of LMWH to estimate the laboratory assays’ sensitivity to anticoagulation. Results: Coagulation assays revealed hypercoagulation after delivery and a tendency toward normalization of coagulation during early postpartum. The thromboprophylaxis results revealed a higher percentage of coagulation parameters within the normal range in the LMWH group. Conclusion: This research is potentially beneficial for the application of thrombodynamics and thrombodynamics-4D in monitoring coagulation among patients with high VTE risk who receive thromboprophylaxis with heparin.


1979 ◽  
Author(s):  
W. Edgar ◽  
M.J. Warrell ◽  
P.A. Warrell ◽  
C.R.M. Prentice

Studies on fibrinogen, fibrinogen-fibrin soluble complexes and FDP were made on eleven patients in Nigeria who had defibrination following Echis carinatus bite. On admission, before treatment with antivenom, all patients had non-clotting blood, reduced or zero fibrinogen levels, low factor Xtll levels and increased concentrations of soluble complexes and FDP, The fibrin component of the soluble complexes, separated by fibrinogen-sepharose chromatography, consisted of both intact fibrin and fibrin degraded at the ∞ chain. After isolation by Biogel chromatography the soluble complexes were also found to contain γ dimer chains. The FDP consisted of several X species, Y, D and D-dimer, and fragment E. The major fragment in all patients was D, but a few samples contained significant quantities of D-dimer, indicating in vivo activation of factor XIII. Fibrinopeptide A studies showed degraded fibrinogen, as well as fibrin, in the soluble complexes and degradation products, suggesting that fibrinogenolysis, in addition to fibrinolysis, had occurred, probably as a result of secondary activation of the fibrinolytic system in response to defibrination.


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