scholarly journals D-Dimer and Fibrin Degradation Products Impair Platelet Signaling: Plasma D-Dimer Is a Predictor and Mediator of Platelet Dysfunction During Trauma

2020 ◽  
Vol 5 (6) ◽  
pp. 1253-1264
Author(s):  
Christopher C Verni ◽  
Antonio Davila ◽  
Carrie A Sims ◽  
Scott L Diamond
Keyword(s):  
Degradation Products ◽  
Calcium Mobilization ◽  
Factor Xiiia ◽  
Platelet Glycoprotein ◽  
Trauma Patients ◽  
Platelet Dysfunction ◽  
Soluble Fibrin ◽  
Glycoprotein Vi ◽  
Fibrin Degradation Products ◽  
D Dimer

Abstract Background Platelet dysfunction often accompanies trauma-induced coagulopathy. Because soluble fibrin impairs platelet glycoprotein VI (GPVI) signaling and platelets of trauma patients can display impaired calcium mobilization, we explored the role of fibrinolysis on platelet dysfunction during trauma. Methods Convulxin-induced GPVI calcium mobilization was investigated in healthy platelet-rich plasma (PRP) pretreated with thrombin and tissue plasminogen activator (tPA). Blood samples from healthy participants (n = 7) and trauma patients (n = 22) were tested for platelet calcium mobilization, plasma D-dimer, platelet D-dimer binding (via flow cytometry), and platelet lumi-aggregometry. Results For healthy platelets, maximal platelet dysfunction was observed when cross-linked soluble fibrin (no tPA) or cross-linked fibrin degradation products (FDPs) were generated in suspension before convulxin stimulation. Lack of fibrin polymerization (inhibited by Gly-Pro-Arg-Pro [GPRP]) or lack of factor XIIIa cross-linking (T101-inhibited) restored GPVI signaling, whereas non–cross-linked FDPs only partially blocked signaling induced by convulxin. In addition, D-dimer added to healthy PRP impaired platelet aggregation and dense granule release induced by various agonists. Plasma D-dimer level was strongly correlated (R = 0.8236) with platelet dysfunction as measured by platelet calcium mobilization induced with various agonists. By 48 to 120 h after trauma, plasma D-dimer levels declined, and platelet function increased significantly but not to healthy levels. Trauma platelets displayed elevated D-dimer binding that was only partially reduced by αIIbβ3-inhibitor GR144053. After 60-minute incubation, washed healthy platelets resuspended in plasma from trauma patients captured approximately 10 000 D-dimer equivalents per platelet. Conclusions During trauma, D-dimer and FDPs inhibit platelets, potentially via GPVI and integrin αIIbβ3 engagement, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype.

Measurement of soluble fibrin monomer-fibrinogen complex in plasmas derived from patients with various underlying clinical situations

2003 ◽  
Vol 89 (05) ◽  
pp. 832-836 ◽  
Author(s):  
Yumiko Kazahaya ◽  
Yuichi Shintani ◽  
Kensuke Yamazumi ◽  
Yutaka Eguchi ◽  
Shin Koga ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Disseminated Intravascular Coagulation ◽  
Degradation Products ◽  
Research Society ◽  
Distinct Entity ◽  
Soluble Fibrin ◽  
Intravascular Coagulation ◽  
Fibrin Degradation Products ◽  
Fibrin Monomer ◽  
D Dimer

SummaryWe previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D1 domain-containing plasmic fragments such as fragments X, Y, and D1, but not intact fibrinogen or cross-linked fibrin degradation products (XDP). Here, we tentatively named such complexes, soluble fibrin monomer (FM) -fibrinogen complex.By utilizing IF-43, we have developed a kit to measure soluble FM-fibrinogen complex and compared the profiles with those of two established molecular markers for thrombo-embolic disorders: i.e. the thrombin-antithrombin complex (TAT) and the D-dimer in plasma of patients who underwent surgery without any thrombo-embolic complications. The result indicated that soluble FM-fibrinogen complex is a distinct entity from the two established molecular markers. We have also attempted to observe their profiles in patients with the disseminated intravascular coagulation syndrome (DIC). Although the profiles of soluble FM-fibrinogen complex in individual patients appeared to vary from one patient to the other, the plasma level of soluble FM-fibrinogen complex was found to be increased at the initial phase of disseminated intravascular coagulation syndrome. Thus, the soluble FM-fibrinogen complex may serve as an independent molecular marker for the detection of thrombin generation and the diagnosis of thrombosis. The soluble FM-fibrinogen complex may also serve as a risk factor for thrombosis, because it may precipitate as insoluble complexes beyond its threshold in plasma, or when it is modified by thrombin.Part of this paper was originally presented at the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

scholarly journals Coagulation profile tests as a predictor for adult trauma patients’ mortality

2019 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Ahmed Fawzy ◽  
Magdy Lolah ◽  
Samah Saad Ibrahim ◽  
Alaa Efat Hassan
Keyword(s):  
Partial Thromboplastin Time ◽  
Degradation Products ◽  
Characteristic Curve ◽  
P Value ◽  
Trauma Patients ◽  
Coagulation Profile ◽  
Fibrin Degradation Products ◽  
Trauma Induced Coagulopathy ◽  
Significant Difference ◽  
D Dimer

Background: Coagulopathy is commonly observed in poly-traumatized patients and is a known contributor to trauma mortality. Although, the incidence of coagulopathy is strongly associated with the severity of the injury, coagulopathy itself exerts an independent factor on mortality.Methods: This is a prospective, observational study on 100 trauma patients. All patients were evaluated using the modified shock index (MSI). Coagulation profile tests including platelet count, prothrombin time (PT), partial thromboplastin time (PTT), D-dimer and fibrinogen/fibrin degradation products (FDPs) were performed for all patients on admission and at 12 hours intervals. Statistically, a logistic regression analysis was performed of coagulation profile tests to determine the incidence of trauma induced coagulopathy (TIC) and its impact on 24 hours mortality. Correlation between clinical and laboratory status was done.Results: There was a statistically significant difference between the dead and the survived patients in the coagulation profile tests and MSI. The best cut-off point of each parameter of coagulation profile tests (PLT count, PT, PTT, d-dimer, FDPs) and MSI was calculated using receiver operating characteristic curve and were <173 × 109/l, >18.7 s, >31 s, >5 mg/l, > 321.5 mg/l and 1.6 respectively. Trauma induced coagulopathy in our study was defined by more than 2 of the following: PLT <173 × 109/l, PT >18.7 s, activated partial thromboplastin time (APTT) >31 s, D-dimer >5 mg/l and FDPs>321.5 mg/l with a p value 0.001 and associated with increased mortality.Conclusions: The incidence of trauma induced coagulopathy early after trauma is high and its severity is related to the injury itself. It is independent predictor of mortality. TIC was developed with presence of more than 2 of the coagulopathy parameters.

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

2004 ◽  
Vol 91 (04) ◽  
pp. 812-818 ◽  
Author(s):  
Michael Wurst ◽  
Mathias Smolinski ◽  
Stephan Lorenz ◽  
Alexandra Osika ◽  
Daniela Olenik ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Degradation Products ◽  
Surgical Intensive Care ◽  
Soluble Fibrin ◽  
Fibrin Formation ◽  
Fibrin Degradation Products ◽  
Distribution Of Values ◽  
Prognostic Power ◽  
D Dimer ◽  
Selection Of

SummaryThe overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.

D-dimer antigen: current concepts and future prospects

Blood ◽  
2009 ◽  
Vol 113 (13) ◽  
pp. 2878-2887 ◽  
Author(s):  
Soheir S. Adam ◽  
Nigel S. Key ◽  
Charles S. Greenberg
Keyword(s):  
Degradation Products ◽  
Fibrin Clot ◽  
Factor Xiiia ◽  
Clinical Settings ◽  
Fibrin Gel ◽  
Covalent Bonds ◽  
Clinical Utilization ◽  
Fibrin Degradation Products ◽  
Plasma Factor ◽  
D Dimer

AbstractThe D-dimer antigen is a unique marker of fibrin degradation that is formed by the sequential action of 3 enzymes: thrombin, factor XIIIa, and plasmin. First, thrombin cleaves fibrinogen producing fibrin monomers, which polymerize and serve as a template for factor XIIIa and plasmin formation. Second, thrombin activates plasma factor XIII bound to fibrin polymers to produce the active transglutaminase, factor XIIIa. Factor XIIIa catalyzes the formation of covalent bonds between D-domains in the polymerized fibrin. Finally, plasmin degrades the crosslinked fibrin to release fibrin degradation products and expose the D-dimer antigen. D-dimer antigen can exist on fibrin degradation products derived from soluble fibrin before its incorporation into a fibrin gel, or after the fibrin clot has been degraded by plasmin. The clinical utility of D-dimer measurement has been established in some scenarios, most notably for the exclusion of VTE. This article consists of 2 sections: in the first, the dynamics of D-dimer antigen formation is discussed and an overview of commercially available D-dimer assays is provided. The second section reviews available evidence for the clinical utilization of D-dimer antigen measurement in VTE, as well as emerging areas of D-dimer utilization as a marker of coagulation activation in other clinical settings.

MONOCLONAL ANTIBODIES OF THE IgM AND IgG CLASS SPECIFIC FOR CROSSLINKED FIBRIN DEGRADATION PRODUCTS

1987 ◽  
Author(s):  
P J Gaffney ◽  
L J Creighton ◽  
A Curry ◽  
B MacMahon ◽  
R Thorpe
Keyword(s):  
Monoclonal Antibodies ◽  
Thrombolytic Therapy ◽  
Epitope Mapping ◽  
Degradation Products ◽  
Subcutaneous Route ◽  
Fibrin Degradation Products ◽  
Conformational Epitopes ◽  
Immunoglobulin Class Switching ◽  
Unique Specificity ◽  
D Dimer

Monoclonal antibodies (mabs) to crosslinked fibrin degradation products (XL-FDP) having the general formula D/Y[X]nY/D (known as X-oligomer) and D-D (known as D dimer) have been raised in balb/C mice by both a novel mtrasplenic and a conventional subcutaneous route of immunisation and by combinations of both these procedures. Mabs to X-oligomers (NIBn 52 and NIBn 123) obtained by an intrasplenic procedure have been demonstrated to crossreact only with X-oligomer in a 2-site ELISA procedure and not with D dimer or whole fibrinogen and have been shown to be of value m the examination of clinical material obtained from patients with various types of thrombosis and have also been useful in monitoring the efficacy of thrombolytic therapy. The X-oligomer mabs are immunoglobulins of the M class. It was demonstrated that their unique specificity for conformational epitopes on the large X-oligomer fragments does not reside in the IgM structure since alterative immunisation procedures have been used to generate mabs of the IgG class which have the same specificity. Using immunoglobulin class switching in culture rather than during immunisation was suggested by certain cell lines which produced both IgM and IgG specific for X-oligomer. This latter point needs rigorous validation.Immunoglobulin G type mabs to highly purified D dimer were raised by conventional subcutaneous immunisation of balb/C mice. One of these, NIBn-11, was found to crossreact with PVC-immobilised X-oligomer and D dimer but not with fibrinogen. However NIBn-11 did not bind to D dimer in a 2-site ELISA procedure while crossreactmg quite avidly with X-oligomer. This suggests that the D dimer epitope to which NIBn-11 is directed is expressed in some conformations and not m others and that these conformations are always expressed in the complex X-oligomer group of fragments. These mabs, whilst of value in measuring certain unique fibrin fragments m plasma, are useful in the epitope mapping of fibrinogen/fibrin and their plasmm-mediated

scholarly journals D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases

2022 ◽  
Vol 28 ◽  
pp. 107602962110705
Author(s):  
Nozomi Ikeda ◽  
Hideo Wada ◽  
Yuhuko Ichikawa ◽  
Minoru Ezaki ◽  
Motoko Tanaka ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Critically Ill ◽  
Disseminated Intravascular Coagulation ◽  
Critically Ill Patients ◽  
Degradation Products ◽  
Intravascular Coagulation ◽  
Fibrin Degradation Products ◽  
Peripheral Arterial ◽  
Thrombotic Diseases ◽  
D Dimer

Introduction Although D-dimer is a useful biomarker of thrombosis, there are many D-dimer kits, with high and low fibrinogen and fibrin degradation products (FDP)/ D-dimer ratios. Methods Plasma D-dimer levels were measured using three different kits in critically ill patients to examine the usefulness of such measurements for detecting the thrombotic diseases and determining the correlation with the FDP and FDP/D-dimer ratio. Results Although three D-dimer kits showed marked utility for diagnosing disseminated intravascular coagulation (DIC) and peripheral arterial and venous thromboembolism (PAVTE), the D-dimer levels determined using the three kits varied among diseases. Indeed, one D-dimer kit showed a high FDP/D-dimer ratio, and another kit showed a low FDP/D-dimer ratio. D-dimer kit with low FDP/D-dimer ratio tended to have high cut-off values and low specificity for diagnosing DIC and PAVTE. In D-dimer kit with high FDP/D-dimer ratio, FDP/D-dimer ratios in patients with thrombosis was significantly higher than that in patients without thrombosis. Conclusion All three D-dimer kits show utility for detecting thrombotic diseases. However, the D-dimer levels determined using the kits varied due to differences in the FDP/D-dimer ratio. In combination with the FDP level, a D-dimer kit with a high FDP/D-dimer ratio may be useful.

PLASMA LEVELS OF FRAGMENT D-DIMER OF CROSSLINKED FIBRIN DURING THROMBOLYTIC THERAPY WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR

1987 ◽  
Author(s):  
P Declerck ◽  
P Mombaerts ◽  
P Holvoet ◽  
D Collen
Keyword(s):  
Thrombolytic Therapy ◽  
Plasma Levels ◽  
Degradation Products ◽  
Fibrin Clot ◽  
Tissue Type ◽  
Fibrin Degradation Products ◽  
Type Plasminogen Activator ◽  
Rate Of Increase ◽  
Significant Difference ◽  
D Dimer

Plasma levels of crosslinked fibrin degradation products (XLDP) were measured before and at the end of the administration of rt-PA (40 to 100 mg over 1.5 to 8 hours) in healthy volunteers (n=5) and patients with deep venous thrombosis (DVT) (n=8), pulmonary embolism (PE) (n=16)and myocardial infarction(MI)(n=10). Determinations were performed using our newly developed ELISA, specific for crosslinked fibrin derivatives, based on two monoclonal antibodies (15C5 and 8D3H2) raised against purified human fragment D-dimer. All plasma samples were collected on citrate and trasylol. Results are expressed as mean and range of D-dimer equivalents (μg/ml).Baseline levels in patients with MI are only slightly elevated. The increased levels inDVT and PE are in agreement with previous studies. After infusion of rt-PA a small increase of XLDP is seen even innormal subjects. A very marked increasof XLDP is detected in patients with PE and DVT but not in patients with MI. This may reflect differences in the amounts of fibrin clot dissolved in these patient groups.No significant correlation was found between the increase of XLDP and success of therapy, although a significant difference in D-dimer levels was formed between the two groups with PE: successful (n=ll): 116 (range 61-192) vs. unsuccessful (n=5): 68 (36-155).Thus, XLDP are already elevated under baseline conditions in patients with DVT and PE and increase very markedly during thrombolytic therapy. The absolute levels after thrombolytic therapy do not strictly correlate with success of therapy. It could be useful to measure D-dimer levels during early stages of therapy, because the rate of increase of XLDP levels might correlate with the efficacy of thrombolytic treatment.

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