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. 2023 Mar 30;12(7):2597.
doi: 10.3390/jcm12072597.

Plasma Soluble Fibrin Is Useful for the Diagnosis of Thrombotic Diseases

Minoru Ezaki  1 , Hideo Wada  2 , Yuhuko Ichikawa  1 , Nozomi Ikeda  1 , Katsuya Shiraki  2 , Akitaka Yamamoto  3 , Isao Moritani  4 , Motomu Shimaoka  5 , Hideto Shimpo  6
Affiliations

Plasma Soluble Fibrin Is Useful for the Diagnosis of Thrombotic Diseases

Minoru Ezaki et al. J Clin Med. .

Abstract

Background: Soluble fibrin (SF) is a form of fibrinogen that is activated by thrombin and is considered to be useful for the diagnosis of the prethrombotic state or thrombosis.

Methods: Plasma levels of fibrin-related markers (FRMs), such as SF, D-dimer, fibrinogen, and fibrin degradation prioduct (FDP) levels in critically ill patients, were examined for the diagnosis of disseminated intravascular coagulation (DIC), venous thromboembolism (VTE), peripheral arterial thromboembolism (PATE), acute myocardial infarction (AMI), and acute cerebral infarction (ACI).

Results: FRMs showed the usefulness in diagnosing DIC and VTE and the cutoff values of D-dimer, FDP, and SF for DIC were 7.2-7.8 μg/mL, 10.0 μg/mL, and 9.5 μg/mL, respectively. The cutoff values of D-dimer and FDP for VTE were similar to the 97.5th percentile values of healthy volunteers, while the cutoff value of SF was 6.9 μg/mL. In AMI and ACI, the cutoff values of D-dimer and FDP were lower than the 97.5 percentile values of healthy volunteers. A receiver operating characteristic analysis for all thrombosis cases showed that an adequate cutoff value in only SF among FRMs was higher than the confidence interval of healthy volunteers. Only SF had high sensitivity for thrombosis, as the FDP/SF ratio was markedly low for ACI, AMI and VTE.

Conclusions: FRMs, especially D-dimer and FDP, were useful for diagnosing thrombosis with hyperfibrinolysis (e.g., DIC). As SF showed high sensitivity for predominantly thrombotic diseases, including arterial thrombosis, such as ACI and AMI, a high SF value suggests the possibility of an association with thrombosis. Finally, SF is the most useful marker for raising suspicion of an association with thrombosis, especially arterial thrombosis.

Keywords: D-dimer; DIC; FDP; soluble fibrin (SF); thrombosis.

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Conflict of interest statement

The measurement of SF and D-dimer levels was partially supported by LSI Medience. In the other points, the authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Plasma levels of soluble fibrin (a), FDP (b) and LPIA-Genesis D-dimer (c) in DIC, VTE, PATE, AMI, ACI, UCS, and HV. DIC, disseminated intravascular coagulation; VTE, venous thromboembolism, PATE, peripheral arterial thromboembolism, AMI, acute myocardial infarction; ACI, acute cerebral infarction; UCS, unidentified clinical syndrome; HV, healthy volunteers; FDP, fibrinogen and fibrin degradation product.
Figure 2
Figure 2
The receiver operating characteristic analysis of soluble fibrin for the diagnosis of thrombosis vs. unidentified clinical syndrome and healthy volunteers. DIC, disseminated intravascular coagulation; VTE, venous thromboembolism, AMI, acute myocardial infarction; ACI, acute cerebral infarction; AUC, area under the curve.
Figure 3
Figure 3
The ratio of FDP/D-dimer or SF in DIC (n = 193), PAVTE (n = 80), AMI (n = 80), ACI (n = 202), UCS (n = 98), and HV (n = 98). DIC, disseminated intravascular coagulation; PAVTE, peripheral arterial and venous thromboembolism, AMI, acute myocardial infarction; ACI, acute cerebral infarction; UCS, unidentified clinical syndrome; HV, healthy volunteers; FDP, fibrinogen and fibrin degradation product; SF, soluble fibrin.
Figure 4
Figure 4
Soluble fibrin. SF, soluble fibrin; FDP, fibrinogen and fibrin degradation product; DIC, disseminated intravascular coagulation; VTE, venous thromboembolism; FPA, fibrinopepetide A.
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