Are Fibrin-Related Markers Useful for the Diagnosis of Thrombosis?

ABSTRACT

Fibrin-related markers (FRMs), such as fibrin and fibrinogen degradation products (FDPs), D-dimer, and soluble fibrin (SF), are considered to be useful for the diagnosis of thrombosis. However, the evidence for the making of a diagnosis of thrombosis based on FRMs is, as yet, not fully established. Levels of FRMs are significantly elevated in patients with thrombosis, such as deep vein thrombosis, disseminated intravascular coagulation, and so on. In Japan, the D-dimer assay test result might be 2-fold higher than results for those assays commonly used in Europe and North America. The levels of SF are significantly elevated in patients before the onset of thrombosis, thus suggesting that the SF assay is useful not only for the diagnosis of thrombosis but also for diagnosing a prethrombotic state. Overall, elevated levels of FRMs indicate a high risk for thrombosis, and they are thus considered to be useful for the diagnosis of thrombosis.

KEYWORDS

D-dimer - soluble fibrin (SF) - fibrinogen degradation products (FDPs) - thrombosis

REFERENCES

• 1 Linkins L A, Bates S M, Ginsberg J S, Kearon C. Use of different D-dimer levels to exclude venous thromboembolism depending on clinical pretest probability.  J Thromb Haemost. 2004;  2 1256-1260
• 2 Wada H. Disseminated intravascular coagulation.  Clin Chim Acta. 2004;  344 13-21
• 3 Heit J A, Silverstein M D, Mohr D N et al.. The epidemiology of venous thromboembolism in the community.  Thromb Haemost. 2001;  86 452-463
• 4 Wells P S, Anderson D R, Rodger M et al.. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis.  N Engl J Med. 2003;  349 1227-1235
• 5 Fedullo P F, Tapson V F. The evaluation of suspected pulmonary embolism.  N Engl J Med. 2003;  349 1247-1255
• 6 Wada H, Wakita Y, Nakase T et al.. Outcome of disseminated intravascular coagulation in relation to the score when treatment was begun.  Thromb Haemost. 1995;  74 848-852
• 7 Soe G, Kohno I, Inuzuka K, Itoh Y, Matsuda M. A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives: its application to the measurement of soluble fibrin in plasma.  Blood. 1996;  88 2109-2117
• 8 Kaneko T, Wada H, Onishi K et al.. Cutoff values of D-dimer and FDP in plasma for the diagnosis of thrombosis.  Vasc Dis Prevent. 2008;  , (in press)
• 9 Colman R W, Robby S J, Minna J D. Disseminated intravascular coagulation (DIC): an approach.  Am J Med. 1972;  52 679-689
• 10 Taylor Jr F B, Toh C H, Hoots W K, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation - on behalf of the Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH).  Thromb Haemost. 2001;  86 1327-1330
• 11 Nieuwenhuizen W. A reference material for harmonization of D-dimer assays.  Thromb Haemost. 1997;  77 1031-1033
• 12 Dempfle C E, Zips S, Ergül H, Heene D L. The FACT study group: the fibrin assay comparison trial (FACT).  Thromb Haemost. 2001;  85 671-678
• 13 Ota S, Wada H, Nobori T et al.. Diagnosis of deep vein thrombosis by plasma-soluble fibrin or D-dimer.  Am J Hematol. 2005;  79 274-280
• 14 Wada H, Kobayashi T, Abe Y et al.. Elevated levels of soluble fibrin or D-dimer indicate high risk of thrombosis.  J Thromb Haemost. 2006;  4 1253-1258
• 15 Minamikawa K, Wada H, Wakita Y et al.. Increased activated protein C-protein C inhibitor complex levels in patients with pulmonary embolism.  Thromb Haemost. 1994;  71 192-194
• 16 Yamada N, Wada H, Nakase T et al.. Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis.  Blood Coagul Fibrinolysis. 1995;  6 627-633
• 17 Wada H, Mori Y, Shimura M et al.. Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries.  Am J Hematol. 1998;  58 189-194
• 18 Wada H, Mori Y, Kaneko T et al.. Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia.  Am J Hematol. 1993;  44 112-116
• 19 Kline J A, Wells P S. Methodology for a rapid protocol to rule out pulmonary embolism in the emergency department.  Am J Emerg Med. 2003;  42 266-275
• 20 Dempfle C E. The use of soluble fibrin in evaluating the acute and chronic hypercoagulable state.  Thromb Haemost. 1999;  82 673-683
• 21 Asakura H, Suga Y, Yoshida T et al.. Pathophysiology of disseminated intravascular coagulation (DIC) progresses at a different rate in tissue factor-induced and lipopolysaccharide-induced DIC models in rats.  Blood Coagul Fibrinolysis. 2003;  14 221-228
• 22 Brass E P, Forman W B, Edwards R V, Lindan O. Fibrin formation; the role of fibrinogen-fibrin monomer complex.  Thromb Haemost. 1976;  36 37-48
• 23 Hamano A, Tanaka S, Takeda Y, Umeda M, Sakata Y. A novel monoclonal antibody to fibrin monomer and soluble fibrin for the detection of soluble fibrin in plasma.  Clin Chim Acta. 2002;  318 25-32
• 24 Suzuki A, Ebinuma H, Matsuo M, Miyazaki O, Yago H. The monoclonal antibody that recognize an epitope in the C-terminal region of the fibrinogen α-chain reacts with soluble fibrin and fibrin monomer generated by thrombin but not with those formed as plasmin degradation products.  Thromb Res. 2007;  121 377-385
• 25 Wada H, Sase T, Matsumoto T et al.. Increased soluble fibrin in plasma from disseminated intravascular coagulation.  Clin Appl Thromb Hemost. 2003;  9 233-240
• 26 Nieuwenhuizen W. Soluble fibrin as a molecular marker for a pre-thrombotic state: a mini-review.  Blood Coagul Fibrinolysis. 1993;  4 93-96
• 27 Sumida Y, Wada H, Fuzii M et al.. Increased soluble fibrin monomer and soluble thrombomodulin levels in non-insulin- dependent-daibetes mellitus.  Blood Coagul Fibrinol. 1977;  8 303-307
• 28 Nielsen N E, Siegbahn A, Swahn E. Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics.  J Intern Med. 2000;  248 151-158
• 29 Ieko M, Nakabayashi T, Tarumi T et al.. Soluble fibrin monomer degradation products as a potentially useful marker for hypercoagulable states with accelerated fibrinolysis.  Clin Chim Acta. 2007;  386 38-45
• 30 Wada H, Sakuragawa N, Shiku H. Hemostatic molecular markers before onset of disseminated intravascular coagulation in leukemic patients.  Semin Thromb Hemost. 1998;  24 293-297
• 31 Watanabe R, Wada H, Yamamuro M et al.. Good or poor responses of hemostatic molecular markers in patients with hematopoietic disorders after treatment of disseminated intravascular coagulation.  Clin Appl Thromb Hemost. 2003;  9 71-78
• 32 Matsumoto T, Wada H, Nobori T et al.. Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with disseminated intravascular coagulation.  Clin Appl Thromb Hemost. 2005;  11 391-400