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.

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.

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.

Identification of D-Dimer-E Complex in Disseminated Intravascular Coagulation (DIC)

1979 ◽  
Author(s):  
A.N. Whitaker ◽  
E.A. Rowe ◽  
P.P. Masci ◽  
P.J. Gaffney
Keyword(s):  
Gel Electrophoresis ◽  
Degradation Products ◽  
Polyacrylamide Gel Electrophoresis ◽  
Stable Complex ◽  
Fibrin Degradation Products ◽  
Pneumococcal Sepsis ◽  
D Antigen ◽  
D Dimer

D-dimer (D2), a product of the plasmin lysis of cross-linked (XL) fibrin, but not of non-XL fibrin or fibrinogen, has been identified in the plasma of patients with DIC due to amniotic fluid embolism. In vitro, D is involved with fragment E as a stable complex (D2-E) but D2 -E has not been identified in vivo before. Fibrin degradation products (FDP) were studied in a patient having fulminant postsplenectomy pneumococcal sepsis and DIC, by immunoprecipitation with anti-fibrinogen (f) and anti-fragment E and characterization by SDS polyacrylamide gel electrophoresis (PAGE). With both antisera soluble HMW fibrin complexes, D2 and E but no X, Y or D were obtained from serum. D2 and E were identified in the supernatant after removing partially XL HMW complexes and fibrinogen from plasma with 2.5 M β-alanine. The presence D antigen in the D2-E complex precipitated by monospecific anti-E was confirmed by crossed Ag-Ab electrophoresis. Crossed Ag-Ab electrophoresis of serum in agarose gave E peaks of slow mobility and no fast-moving free E was found. Thus, D2-E complex exists in vivo and its easy identification, proving the lysis of XL fibrin, would be of value in studying thrombosis. D2-E complex has been identified in other patients with sepsis but at lower concentrations than described above.

scholarly journals Fibrin fragment D-dimer and fibrinogen B beta peptides in plasma as markers of clot lysis during thrombolytic therapy in acute myocardial infarction

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1341-1348 ◽  
Author(s):  
CM Lawler ◽  
EG Bovill ◽  
DC Stump ◽  
DJ Collen ◽  
KG Mann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Degradation Product ◽  
Degradation Products ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Product ◽  
Fibrin Degradation Products ◽  
Group 2 ◽  
D Dimer ◽  
Group 1

Abstract The validity of markers in plasma of in vitro thrombolysis was investigated in 12 patients with extensive fibrinogen breakdown (greater than 80%, group 1) and in 12 patients with minimal breakdown (less than 20%, group 2). The patients were treated with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) in the “Thrombolysis in Myocardial Infarction II” (TIMI II) trial. Cross- linked fibrin degradation product levels were measured with two variant enzyme-linked immunosorbent assays (ELISAs), both using a fibrin fragment D-dimer specific capture antibody. In one instance, a tag antibody was used that cross-reacts with fibrinogen (pan-specific tag ELISA); in the other, the tag antibody was specific for fibrin fragment D (fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin degradation products at baseline were within normal limits with both assays in most patients. At 8 hours after rt-PA infusion, the measured cross-linked fibrin degradation products were increased about twofold to fourfold in group 2 with both assays. However, in group 1, levels were significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2 micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3 micrograms/mL). This observation was most likely a result of detection of fibrinogen degradation products in the pan-specific ELISA. Apparent levels of fibrinopeptide B beta 1–42, a marker of fragment X formation, increased during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and were correlated significantly with the extent of fibrinogen breakdown (r = -0.8). Fibrinopeptide beta 15–42 levels increased from 4.3 +/- 3 pmol/mL to 70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent increase in group 1 could be explained by cross-reactivity of fibrinopeptide B beta 1–42 in the fibrinopeptide beta 15–42 assay. We conclude that cross-linked fibrin degradation product levels as measured with a pan-specific tag ELISA and fibrinopeptide beta 15–42 levels as measured with certain monoclonal antibody-based ELISA are influenced by the extent of fibrinogen degradation. Fibrinopeptide B beta 1–42 is a marker specific for fibrinogen breakdown. Cross-linked fibrin degradation product levels, measured with a fibrin-specific tag ELISA, appear to be markers specific for thrombolysis. Consequently, assays similar to the fibrin- specific tag ELISA may provide more accurate information when correlated with clinical endpoints.

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