The Evaluation of Fibrin-Related Markers for Diagnosing or Predicting Acute or Subclinical Venous Thromboembolism in Patients Undergoing Major Orthopedic Surgery

Objective: The cutoff values of fibrin-related markers (FRMs) diagnosing or predicting the occurrence of a venous thromboembolism (VTE) were evaluated. Materials and Methods: Fibrin-related markers such as fibrin monomer complex (FMC), D-dimer, and fibrinogen and fibrin degradation products (FDPs) before surgery were measured in 326 patients undergoing orthopedic surgery to diagnose subclinical VTE or predict postoperative VTE. Results: Although the FMC, D-dimer, and FDP levels were all useful for the diagnosis of acute VTE, the FDP level was not useful for diagnosing subclinical VTE or predicting postoperative VTE. The results of several D-dimer assays closely correlated with other D-dimer assays. There were various cutoff ranges for diagnosing or predicting VTE. Some D-dimer assays were useful for diagnosing low levels of D-dimer and others were useful for diagnosing moderate to high D-dimer levels. Increased D-dimer levels were useful for diagnosing acute (cutoff values: 2.0-5.9 μg/mL) or about 10% of subclinical VTE (cutoff values: 3.4-5.3 μg/mL), for predicting about 10% of postoperative VTE (cutoff values: 3.4-5.3 μg/mL), and for excluding VTE. Conclusion: Although increased D-dimer levels were useful for diagnosing subclinical VTE and predicting the risk of VTE, there were various cutoff values for the diagnosis or prediction of VTE.

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

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211070584 ◽

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.

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613469 ◽

2003 ◽

Vol 89 (05) ◽

pp. 832-836 ◽

Cited By ~ 15

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.

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Antibodies against Fibrinogen in Pregnant Women, in Post Delivery Women and in the Newborns

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615103 ◽

1998 ◽

Vol 79 (05) ◽

pp. 963-968 ◽

Cited By ~ 8

Author(s):

Zdzislawa Kondera-Anasz

Keyword(s):

Pregnant Women ◽

Degradation Products ◽

Parent Molecule ◽

Fibrin Degradation Products ◽

Antigenic Sites ◽

Progressive Loss ◽

Pregnancy And Delivery ◽

Human Sera ◽

Low Levels ◽

D Dimer

SummaryPregnancy and delivery have measurable effects on haemostatic and immunological changes. Degradation of fibrinogen induces significant structural and conformational modulation and leads to the progressive loss of antigenic sites present on the parent molecule but also exposes some new sites. These neoantigens may be recognized by the immune system and may be elicited by the autologous host manifested by the production of autoantibodies. Therefore in the present study, in pregnant and post delivery women and in the newborns, levels of antibodies against fibrinogen, fibrin(ogen) degradation products (FDP) and fibrin degradation products (D-dimer) were examined.Enzyme immunoassay (ELISA) was used to detect and quantitate autoantibodies against fibrinogen (class G immunoglobulin) in human sera. In all sera there were found varying concentrations of autoantibodies and their levels were significantly higher in all pregnant women in comparison with non-pregnant ones. Significantly higher levels were found in Rh immunized and clinically complicated pregnancies.The level of autoantibodies, coagulation and fibrinolytic system components were higher in post delivery women than in normal pregnant women. Also antibodies to fibrinogen were studied in cord serum of newborns in different terms of delivery. The low levels of antibodies in all newborns raise questions of possible foetal-maternal immunologic interactions. Positive correlation between mothers and newborns was demonstrated after delivery at gestational age from 34th to 41st week, and negative in 42nd and more week. There were no significant differences in antibody level among the newborns delivered by the same mothers.It was found that autoantibodies bind selectively to the fibrinogen and fibrinogen fragments X, Y and D. These autoantibodies may represent a new interface between the coagulation and the immune systems which may be significant in controlling the pathologic activities of the cleavage fragments.

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Superiority of Fondaparinux Over Enoxaparin in Preventing Venous Thromboembolism in Major Orthopedic Surgery Using Different Efficacy End Points

Yearbook of Pulmonary Disease ◽

10.1016/s8756-3452(08)70118-x ◽

2006 ◽

Vol 2006 ◽

pp. 148-151

Author(s):

K.L. Lewis

Keyword(s):

Venous Thromboembolism ◽

Orthopedic Surgery ◽

End Points ◽

Major Orthopedic Surgery

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Prophylaxis of Venous Thromboembolism Following Orthopedic Surgery: Mechanical and Pharmacological Approaches and the Need for Extended Prophylaxis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615933 ◽

1999 ◽

Vol 82 (08) ◽

pp. 918-924 ◽

Cited By ~ 5

Author(s):

R.D. Hull ◽

G.F Pineo

Keyword(s):

Clinical Trials ◽

Venous Thromboembolism ◽

Orthopedic Surgery ◽

Total Joint Replacement ◽

Case Series ◽

Pharmacological Agents ◽

Thrombotic Disease ◽

Vein Thrombosis ◽

Major Orthopedic Surgery ◽

Mechanical Devices

IntroductionMajor orthopedic surgery, particularly total joint replacement or hip fracture, represents a high risk of future development of postoperative venous thromboembolism and warrants the routine use of prophylaxis with either mechanical devices or pharmacological agents. The aim of prophylaxis is to prevent fatal pulmonary embolism (PE) and the morbidity of deep vein thrombosis (DVT), particularly the development of post-thrombotic syndrome. Patterns of clinical practice, with respect to the prevention of venous thromboembolism and the appropriate use of anticoagulants for the treatment of thrombotic disease, have been strongly influenced by recent consensus conferences.1,2 Rules of evidence for assessing the literature have been applied to all recommendations regarding the prevention and treatment of thrombotic disease. These results were extrapolated using evidence gleaned from major clinical disorders and are based only on nonrandomized clinical trials or case series.1-3 Data from a large number of Level I clinical trials in patients undergoing orthopedic surgery have provided answers to many of the questions regarding prophylaxis of venous thromboembolism. In this review, we will discuss the prevention of venous thromboembolism following orthopedic surgery and discuss some of the controversial issues where further studies are required.

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

10.1055/s-0038-1643651 ◽

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

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