The Clinical Significance of Fibrin Monomers

Majed A. Refaai; Paul Riley; Tatsiana Mardovina; Phoenix D. Bell

doi:10.1055/s-0038-1673684

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2018; 118(11): 1856-1866
DOI: 10.1055/s-0038-1673684

Review Article

Georg Thieme Verlag KG Stuttgart · New York

The Clinical Significance of Fibrin Monomers

Majed A. Refaai

¹Department of Pathology and Laboratory Medicine, Thrombosis and Hemostasis Research Laboratory, University of Rochester Medical Center, University of Rochester, Rochester, New York, United States

,

Paul Riley

²Diagnostica Stago, Inc., Parsippany, New Jersey, United States

,

Tatsiana Mardovina

²Diagnostica Stago, Inc., Parsippany, New Jersey, United States

,

Phoenix D. Bell

¹Department of Pathology and Laboratory Medicine, Thrombosis and Hemostasis Research Laboratory, University of Rochester Medical Center, University of Rochester, Rochester, New York, United States

› Author Affiliations

Abstract

Introduction Fibrin monomer (FM) concentrations reflect pro-thrombin activity and have the potential to predict thrombotic events relatively earlier than other haemostatic markers. Most often, FM are compared with D-dimer (DD) as increased DD have been documented in disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT) and pulmonary embolism. Although DD have a high sensitivity and negative predictive value, their specificity is much lower depending on the assay chosen, clinical pre-test probability and patient condition. There are limited reports investigating the utility of FM in hyper-coagulable patients.

Methods We performed a literature search of FM concentrations in hyper-coagulable patients including those with DIC, acute ischaemic stroke, atrial fibrillation, acute myocardial infarction, venous thromboembolism (VTE) and cancer, as well as those who are pregnant or undergoing surgery.

Results FM were increased in patients with DIC and those with malignancy. In contrast, detection of VTE or post-operative DVT development is likely enhanced using both FM and DD concentrations. Similarly, measuring FM concentrations with other biomarker levels may be more beneficial in patients suffering an acute myocardial infarction or acute ischaemic stroke. Lastly, FM concentrations vary substantially throughout pregnancy with no definitive role of FM as of yet.

Conclusion Utilizing FM concentrations to assess hyper-coagulable patients seems promising; however, there are limitations including variations in FM cut-off values, the effect of patient medications and the timing of FM measurement relative to an acute event. Thus, further investigation is required before a true advantage for FM as a haemostatic marker can be established.

Keywords

thrombosis - D-dimers - venous thromboembolic event - fibrin split products - hyper-coagulation

Full Text

References

References
1 Lee MS, Kong J. Heparin: physiology, pharmacology, and clinical application. Rev Cardiovasc Med 2015; 16 (03) 189-199
2 van Wersch JWJ, Ubachs JMH. Blood coagulation and fibrinolysis during normal pregnancy. Eur J Clin Chem Clin Biochem 1991; 29 (01) 45-50
3 Sadanaga T, Mitamura H. Soluble fibrin monomer complex levels during oral anticoagulant therapy do not predict subsequent thromboembolic events in patients with permanent atrial fibrillation. Int J Cardiol 2013; 168 (01) 578-580
4 Wada H, Sakuragawa N. Are fibrin-related markers useful for the diagnosis of thrombosis?. Semin Thromb Hemost 2008; 34 (01) 33-38
5 Ieko M, Naito S, Yoshida M. , et al. Plasma soluble fibrin monomer complex as a marker of coronary thrombotic events in patients with acute myocardial infarction. Tohoku J Exp Med 2009; 219 (01) 25-31
6 Park K-J, Kwon E-H, Kim H-J, Kim S-H. Evaluation of the diagnostic performance of fibrin monomer in disseminated intravascular coagulation. Korean J Lab Med 2011; 31 (03) 143-147
7 Wada H, Wakita Y, Nakase T. , et al. Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation. Am J Hematol 1996; 51 (04) 255-260
8 Singh N, Pati HP, Tyagi S, Upadhyay AD, Saxena R. Evaluation of the diagnostic performance of fibrin monomer in comparison to d-dimer in patients with overt and nonovert disseminated intravascular coagulation. Clin Appl Thromb Hemost 2017; 23 (05) 460-465
9 Selim TE, Ghoneim HR, Khashaba MT, Rakha SA. Plasma soluble fibrin monomer complex is a useful predictor of disseminated intravascular coagulation in neonatal sepsis. Haematologica 2005; 90 (03) 419-421
10 Dempfle C-E, Wurst M, Smolinski M. , et al. Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score. Thromb Haemost 2004; 91 (04) 812-818
11 Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M. ; Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86 (05) 1327-1330
12 Okamoto K, Wada H, Hatada T. , et al; Japanese Society of Thrombosis Hemostasis/DIC subcommittee. Frequency and hemostatic abnormalities in pre-DIC patients. Thromb Res 2010; 126 (01) 74-78
13 Kobayashi N, Maekawa T, Takada M, Tanaka H, Gonmori H. Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. Bibl Haematol 1983; (49) 265-275
14 Subramaniam RM, Snyder B, Heath R, Tawse F, Sleigh J. Diagnosis of lower limb deep venous thrombosis in emergency department patients: performance of Hamilton and modified Wells scores. Ann Emerg Med 2006; 48 (06) 678-685
15 Wells PS, Anderson DR, Bormanis J. , et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997; 350 (9094): 1795-1798
16 Schutgens REG, Haas FJLM, Agterof MJ, Vos M, Biesma DH. The role of fibrin monomers in optimizing the diagnostic work-up of deep vein thrombosis. Thromb Haemost 2007; 97 (05) 807-813
17 Dopsaj V, Bogavac-Stanojevic N, Vasic D. , et al. Excluding deep venous thrombosis in symptomatic outpatients: is fibrin monomer aid to D-dimer analysis?. Blood Coagul Fibrinolysis 2009; 20 (07) 546-551
18 Elias A, Cazanave G, Nguyen F, Elias M, Bongard V, Cambus JP. Comparison of the diagnostic performance of three soluble fibrin monomer tests and a D-dimer assay in patients with clinically suspected deep vein thrombosis of the lower limbs. Haematologica 2004; 89 (04) 499-501
19 Reber G, Bounameaux H, Perrier A, de Moerloose P. Performances of the fibrin monomer test for the exclusion of pulmonary embolism in symptomatic outpatients. Thromb Haemost 1999; 81 (02) 221-223
20 Beer JH, Haeberli A, Vogt A. , et al. Coagulation markers predict survival in cancer patients. Thromb Haemost 2002; 88 (05) 745-749
21 Biggerstaff JP, Seth NB, Meyer TV, Amirkhosravi A, Francis JL. Fibrin monomer increases platelet adherence to tumor cells in a flowing system: a possible role in metastasis?. Thromb Res 1998; 92 (06) (Suppl. 02) S53-S58
22 Seeholzer N, Thürlimann B, Köberle D, Hess D, Korte W. Combining chemotherapy and low-molecular-weight heparin for the treatment of advanced breast cancer: results on clinical response, transforming growth factor-beta 1 and fibrin monomer in a phase II study. Blood Coagul Fibrinolysis 2007; 18 (05) 415-423
23 Tsimafeyeu IV, Demidov LV, Madzhuga AV, Somonova OV, Yelizarova AL. Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma. J Exp Clin Cancer Res 2009; 28 (01) 30-30
24 Fassbender K, Dempfle CE, Mielke O. , et al. Changes in coagulation and fibrinolysis markers in acute ischemic stroke treated with recombinant tissue plasminogen activator. Stroke 1999; 30 (10) 2101-2104
25 Tamura H, Hirono O, Okuyama H. , et al. Elevated serum fibrin-monomer levels are associated with high long-term cerebrovascular event rates in acute ischemic stroke patients. Circ J 2007; 71 (10) 1573-1579
26 Okuyama H, Hirono O, Liu L, Takeishi Y, Kayama T, Kubota I. Higher levels of serum fibrin-monomer reflect hypercoagulable state and thrombus formation in the left atrial appendage in patients with acute ischemic stroke. Circ J 2006; 70 (08) 971-976
27 Hirano K, Takashima S, Dougu N. , et al. Study of hemostatic biomarkers in acute ischemic stroke by clinical subtype. J Stroke Cerebrovasc Dis 2012; 21 (05) 404-410
28 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (02) 263-272
29 Sato M, Suzuki A, Nagata K, Uchiyama S. Increased von Willebrand factor in acute stroke patients with atrial fibrillation. J Stroke Cerebrovasc Dis 2006; 15 (01) 1-7
30 Schlegel D, Kolb SJ, Luciano JM. , et al. Utility of the NIH Stroke Scale as a predictor of hospital disposition. Stroke 2003; 34 (01) 134-137
31 Rivera-Caravaca JM, Roldán V, Romera M. , et al. Soluble fibrin monomer complex and prediction of cardiovascular events in atrial fibrillation: the observational Murcia Atrial Fibrillation Project. J Gen Intern Med 2018; 33 (06) 847-854
32 Tóth NK, Csanádi Z, Hajas O. , et al. Intracardiac hemostasis and fibrinolysis parameters in patients with atrial fibrillation. BioMed Res Int 2017; 2017: 3678017
33 Kontny F, Dempfle CE, Abildgaard U. Fibrin monomer antigen: a novel marker of mortality in acute myocardial infarction. Eur Heart J 1999; 20 (11) 808-812
34 Elged AAE, El-Gamal RA, Bastawy S, Moselhy MS. Soluble fibrin monomer complex assay enhances early and accurate diagnosis of acute myocardial infarction. Int J Clin Exp Pathol 2016; 9 (05) 9
35 Brügger-Andersen T, Hetland Ø, Pönitz V, Grundt H, Nilsen DWT. The effect of primary percutaneous coronary intervention as compared to tenecteplase on myeloperoxidase, pregnancy-associated plasma protein A, soluble fibrin and D-dimer in acute myocardial infarction. Thromb Res 2007; 119 (04) 415-421
36 Onishi H, Kaniyu K, Iwashita M, Tanaka A, Watanabe T. Fibrin monomer complex in normal pregnant women: a potential thrombotic marker in pregnancy. Ann Clin Biochem 2007; 44 (Pt 5): 449-454
37 Joly B, Barbay V, Borg J-Y, Le Cam-Duchez V. Comparison of markers of coagulation activation and thrombin generation test in uncomplicated pregnancies. Thromb Res 2013; 132 (03) 386-391
38 Grossman KB, Arya R, Peixoto AB, Akolekar R, Staboulidou I, Nicolaides KH. Maternal and pregnancy characteristics affect plasma fibrin monomer complexes and D-dimer reference ranges for venous thromboembolism in pregnancy. Am J Obstet Gynecol 2016; 215 (04) 466.e1-466.e8
39 Vogel G, Dempfle C-E, Spannagl M, Leskopf W. The value of quantitative fibrin monomer determination in the early diagnosis of postoperative deep vein thrombosis. Thromb Res 1996; 81 (02) 241-251
40 Hasegawa M, Wada H, Miyazaki S. , et al. The evaluation of fibrin-related markers for diagnosing or predicting acute or subclinical venous thromboembolism in patients undergoing major orthopedic surgery. Clin Appl Thromb Hemost 2018; 24 (01) 107-114
41 Mitani G, Takagaki T, Hamahashi K. , et al. Associations between venous thromboembolism onset, D-dimer, and soluble fibrin monomer complex after total knee arthroplasty. J Orthop Surg 2015; 10: 172
42 Yoshioka K, Kitajima I, Kabata T. , et al. Venous thromboembolism after spine surgery: changes of the fibrin monomer complex and D-dimer level during the perioperative period. J Neurosurg Spine 2010; 13 (05) 594-599
43 Watanabe H, Inoue H, Shiraishi Y. , et al. Difference in the changings of blood coagulation fibrinolysis markers before and after spinal surgery in adolescent and elderly patients. Int J Orthod 2017; 4 (02) 5
44 Kochi M, Shimomura M, Hinoi T. , et al. possible role of soluble fibrin monomer complex after gastroenterological surgery. World J Gastroenterol 2017; 23 (12) 2209-2216
45 Samuelson Bannow BT. Capsule commentary on Rivera-Caravaca et al., soluble fibrin monomer complex and prediction of cardiovascular events in atrial fibrillation: the observational Murcia Atrial Fibrillation Project. J Gen Intern Med 2018; 33 (06) 945