Fibrinogen Complex Research Articles

Animal Models of Aging Research

Ageing is associated with increased hypercoagulability, due to a slow rise of several coagulation factors, factor VIII, fibrinogen and thrombin-antithrombin complexes, markers of fibrinolysis and progressively defective Protein C activation, yet compatible with life at very high age. Mice, naturally aged up to 24 months, likewise show a progressive elevation of coagulation factors, triggering enhanced thrombogenicity during acute injury-induced thrombus formation. To overcome the still gradual natural ageing in mice, several mouse models of premature ageing were characterized, in an effort to allow for more rapid ageing-induced manifestations of natural thrombogenicity. Thus, the Klotho gene, encoding a type-I membrane protein, related to beta-glucosidases underlies degenerative processes, including arteriosclerosis and osteoporosis, observed in chronic renal failure. Mutations within this protein are associated with ageing and bone loss. Defective Klotho gene expression in the mouse accelerates degeneration of multiple age-sensitive traits, whereas its overexpression extends murine life span. The multidomain protein kinases Bub1 and BubR1 are central components of the mitotic checkpoint for spindle assembly (SAC) and self-monitor the eukaryotic cell cycle. Despite their amino acid sequence conservation and similar domain organization, BUB1 and BUBR1 perform different functions in the SAC. Various p53 mutant mice with a BubR1 insufficiency display early onset of ageing-associated phenotypes, whereas the BubR1H/H mouse is characterized by simultaneous vascular defects. Progerin mouse models show phenotypes ranging from being largely restricted to the vascular system to models with a broader progeria-like phenotype (severe growth retardation, fragile bones, alopecia, skin defects and reduced viability). The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus, but the most widespread mouse model of premature ageing consists of a circadian clock gene mutant mouse, the brain and muscle arnt like protein-1 (Bmal1). Mice deficient in this circadian transcription factor have impaired circadian behavior and demonstrate loss of rhythmicity in the expression of target genes. Bmal1-/- mice have reduced lifespan (maximum around 50 weeks) and display symptoms of premature ageing, including sarcopenia, cataracts, less subcutaneous fat, organ shrinkage, and others. Their early ageing phenotype correlates with increased levels of reactive oxygen species in some but not all tissues. These findings and data on CLOCK/BMAL1-dependent control of stress responses were evoked to explain the early onset of age-related pathologies in the absence of Bmal1. Their reduced lifespan is still long enough to enable intervention studies on heart function, renal integrity, tissue degeneration and thrombogenicity, including diet feeding and fat composition studies, analysis of the progressive prothrombotic state and anti-oxidant intervention studies for longevity assessment. Combined though, all these studies raise cautiousness, because no single mouse model can phenocopy human ageing perfectly: even when murine alopecia signals premature ageing, p16INK-4A measurements via qPCR do not always rise, as such is the case during natural mouse ageing and some organs deteriorate more slowly than others (e.g. vascular media and smooth muscle cells), coupled to different exposure/sensitivity to oxidative stress or environmental factors. Also, the major advantage of most accelerated ageing models, i.e. their rapid onset of ageing may insufficiently favor several risk factors, i.e. age-related thrombogenicity factors developing chronically, gradullay deteriorating with ageing. The fragile Bmal1-/- mouse model represents a well-studied compromise, its defects in different organs being well-documented, with a life-span, long enough to allow intervention studies. Disclosures No relevant conflicts of interest to declare.

COMPARATIVE EFFICACY OF ENZYME MEDICATION WITH THROMBOLYTIC EFFECT IN ATRIUM THROMBOSIS AND SPONTANEOUS ECHO-CONTRAST PHENOMENON IN PATIENTS WITH ATRIAL FIBRILLATION

Aim. To assess efficacy of Thrombovazim® in combination antithrombotic therapy in atrial fibrillation (AF) with intra-atrial clots of spontaneous echo-contrasting found by echocardiography. Material and methods. Totally 28 patients included with persisting atrial fibrillation: 20 with thrombosis of the left atrium appendage and 8 with the phenomenon of spontaneous echo-contrasting of II-III grate in atrium by transesophageal ultrasound contrast study (TEECS). Among patients with left appendage thrombosis there were 15 men and 5 women, mean age 60,3±1,6. Among those with spontaneous echocontrasting — 4 men and 4 women, mean age 58,2±1,2. After detecting the thrombus or spontaneous echo-contrasting phenomenon all patients were prescribed Thrombovazim® in dosage 800U t.i.d. for 7 days with standard warfarin therapy. Results. On the control TEECS at the 8th day of therapy among 20 patients with previously diagnosed left appendage thrombosis in 19 were found the absence of clots. Level of total fibrinogen and soluble fibrin-monomers complexes in Thrombovazim® intake did not change. In all patients with spontaneous echocontrasting phenomenon after Thrombovazim® course this phenomenon still existed, so Thrombovazim® was not effective in this phenomenon elimination. There were no side effects of Thrombovazim®. Conclusion. In atrial fibrillation patients and thrombus in left atrium appendage the use of Thrombovazim® 800U t. i.d. per os at the background of standard therapy by warfarin during 7 days in 95% leads to the lysis of clots without side effects. In spontaneous echo-contrasting phenomenon in atrial fibrillation Thrombovazim® 800U t. i.d. per os with standard therapy for 7 days does not lead to this phenomenon elimination. The lack of effect of Thrombovazim® in the phenomenon of spontaneous echo-contrasting indirectly suggests that there are not fibrin strands in this phenomenon.

The State of Coagulation Hemostasis and Fibrinolysis in Children With Essential Arterial Hypertension

Children with essential hypertension and increased risk of thrombotic complications are characterized by history of familial thrombosis, increased levels of fibrinogen and soluble fibrin-monomer complexes, activity and content of von Willebrand factor, activity of plasminogen.

Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes

The significance of borderline changes in kidney allograft biopsies is widely debated. To help resolve this, we studied differences in intrarenal gene expression patterns between early clinical and 3-month protocol biopsies, all of which had borderline histologic changes. The gene expression profiles in training set of patients by microarray analysis and data were validated in a larger cohort using RT-qPCR. There was greater expression of immunity- and inflammation-related genes in the early clinical biopsies compared to the 3-month protocol biopsies with borderline changes. In early clinically manifested borderline changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes. Regression modeling identified higher donor age and expression of macrophage receptor CLEC5A as risk factors for progression. In the 3-month protocol biopsies with borderline changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. The discrimination power of fibrinogen was confirmed by cross-validation on two independent cohorts. Thus, our study highlights variations in gene expression between clinical and subclinical borderline changes despite similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those with borderline changes who received grafts from older donors.

Regulation of integrins in platelets.

Blood platelets prevent bleeding after trauma by forming occlusive aggregates at sites of vascular injury. Platelet aggregation is mediated by the integrin heterodimer αIIbβ3 and occurs when platelet agonists generated at the injury site convert αIIbβ3 from its resting to its active conformation. Active αIIbβ3 is then able to bind macromolecular ligands such as fibrinogen that crosslink adjacent platelets into hemostatic aggregates. Platelets circulate in a plasma milieu containing high concentrations of the principal αIIbβ3 ligand fibrinogen. Thus, αIIbβ3 activity is tightly regulated to prevent the spontaneous formation of platelet aggregates. αIIbβ3 activity is regulated at least three levels. First, intramolecular interactions involving motifs located in the membrane-proximal stalk regions, transmembrane domains, and the membrane-proximal cytosolic tails of αIIb and β3 maintain αIIbβ3 in its inactive conformation. Transmembrane domain interactions appear particularly important because disrupting these interactions causes constitutive αIIbβ3 activation. Second, the agonist-stimulated binding of the cytosolic proteins talin and kindlin-3 to the β3 cytosolic tail rapidly causes αIIbβ3 activation by disrupting the intramolecular interactions constraining αIIbβ3 activity. Third, the strength of ligand binding to active αIIbβ3 seems to be allosterically regulated. Thus, αIIbβ3 exists in a minimum of three interconvertible states: an inactive (resting) state that does not interact with ligands and two active ligand binding states that differ in their affinity for fibrinogen and in the mechanical stability of fibrinogen complexes they form.

2014 Consensus conference on viscoelastic test–based transfusion guidelines for early trauma resuscitation

There has been an increased interest in the use of viscoelastic testing to guide blood product replacement during the acute resuscitation of the injured patient. Currently, no uniformly accepted guidelines exist for how this technology should be integrated into clinical care. In September 2014, an international multidisciplinary group of leaders in the field of trauma coagulopathy and resuscitation was assembled for a 2-day consensus conference in Philadelphia, Pennsylvania. This panel included trauma surgeons, hematologists, blood bank specialists, anesthesiologists, and the lay public.Nine questions regarding the impact of viscoelastic testing in the early resuscitation of trauma patients were developed before the conference by panel consensus. Early use was defined as baseline viscoelastic test result thresholds obtained within the first minutes of hospital arrival-when conventional laboratory results are not available. The available data for each question were then reviewed in person using standardized presentations by the expert panel. A consensus summary document was then developed and reviewed by the panel in an open forum. Finally, a two-round Delphi poll was administered to the panel of experts regarding viscoelastic thresholds for triggering the initiation of specific treatments including fibrinogen, platelets, plasma, and prothrombin complex concentrates. This report summarizes the findings and recommendations of this consensus conference.

Evaluation of fibrinogen concentrates and prothrombin complex concentrates on coagulation changes in a hypothermic in vitro model using thromboelastometry and thromboelastography

Background. Hypothermic coagulopathy is very challenging in bleeding trauma patients. Therefore, we decided to evaluate the efficacy of fibrinogen and prothrombin complex in 30°C hypothermia in vitro to investigate if higher levels of fibrinogen and prothrombin complex concentrate can compensate for the hypothermic effect on coagulation as measured by thromboelastometry/thromboelastography. Methods. Blood samples were obtained from 12 healthy volunteers (six men and six women) in our study. Measurements were performed at 37°C and 30°C simultaneously, then at 30°C with adding fibrinogen and prothrombin complex and in the last step samples with added coagulation factors were warmed back to 37°C. Results. We found that 30°C hypothermic coagulopathy can be detected both by thromboelastometry and thromboelastography. Hypothermic coagulopathy can be restored by fibrinogen to the point where the results do not significantly differ from 37°C values (p > 0.05). After warming the sample with fibrinogen to 37°C, the thrombodynamic potential index was not significantly different from baseline (p > 0.05), although there was a trend to prothrombotic status. The addition of prothrombin complex concentrate to 30°C hypothermic sample was not able to correct hypothermic coagulopathy in vitro. Conclusions. Coagulopathy caused by the 30°C hypothermia in vitro model can be corrected by fibrinogen concentrate compared to prothrombin complex concentrate. In spite of a tendency to prothrombotic status, this was not significant with the use of the recommended dose of fibrinogen even after warming the blood to 37°C. However, measurement performed at 37°C seems to be safer than at 30°C.

Fibrinogen and prothrombin complex concentrate in trauma coagulopathy

BackgroundCoagulopathy after injury contributes to hemorrhage and death. Treatment with specific coagulation factors could decrease hemorrhage and mortality. Our aim was to compare fibrinogen and prothrombin complex concentrate (PCC) in a rabbit model of hemorrhagic shock. Materials and methodsNew Zealand white rabbits were anesthetized. Blood was withdrawn to a mean arterial pressure (MAP) of 30–40 mm Hg for 30 min. Animals were resuscitated with lactated Ringer to a MAP of 50–60 mm Hg and randomized to receive 100 mg/kg of fibrinogen, PCC 25 IU/kg, or lactated Ringer. A liver injury was created. A MAP of 50–60 mm Hg was maintained for 60 min. The primary outcome was blood loss, and secondary outcomes were fluid administered and coagulopathy as measured by plasma-based tests. ResultsThere were eight animals in each group. Median blood loss was significantly higher in the fibrinogen group, at 122 mL (95% confidence interval [CI], 75–194), when compared with that in the control group, 35 mL (95% CI, 23–46; P value = 0.001), and the PCC group, 26 mL (95% CI, 4–54; P value = 0.002). Resuscitation fluid requirement was highest in the fibrinogen group, at 374 mL (95% CI, 274–519), and lowest in the PCC group, at 238 mL (95% CI, 212–309) (P = 0.01). Plasma-based coagulation tests were not different among groups. ConclusionsIn a rabbit model, PCC did not have a significant effect on blood loss. Fibrinogen increased blood loss and fluid requirements.

Relationship of pericardial fat with biomarkers of inflammation and hemostasis, and cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis

ObjectivePericardial fat may increase the risk of cardiovascular disease (CVD) by increasing circulating levels of inflammation and hemostasis biomarkers. We investigated the associations of pericardial fat with inflammation and hemostasis biomarkers, as well as incident CVD events, and whether there are any ethnic differences in these associations. MethodsWe analyzed results from 6415 participants from the Multi-Ethnic Study of Atherosclerosis who had measurements of pericardial fat volume and circulating levels of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, factor VIII, D-dimer and plasmin-antiplasmin complex (PAP), and had a mean follow-up period of 9.5 years. Incident CVD event was defined as any adjudicated CVD event. ResultsAfter adjusting for confounding factors, pericardial fat volume was positively associated with natural log (ln) of IL-6 levels, but inversely associated with ln D-dimer and ln PAP levels (β = 0.067, −0.032, and −0.105 respectively, all P < 0.05). Although a larger pericardial fat volume was associated with a higher risk of incident CVD, the association was attenuated to borderline significance after adjusting for traditional cardiovascular risk factors (P = 0.050). There was a borderline significant ethnicity interaction (P = 0.080), whereby the association between pericardial fat volume and incident CVD was significant in Hispanic Americans, even after further adjusting for biomarkers of inflammation and hemostasis (hazard ratio = 1.31 per SD increase, 95% confidence interval 1.09–1.57, P = 0.004). ConclusionPericardial fat was associated with several inflammation and hemostasis biomarkers. The association of pericardial fat with incident CVD events was independent of these biomarkers only among Hispanic Americans.

Practical management of major blood loss.

The pathophysiology of bleeding, regardless of cause, is complex and ill understood. For traumatic or sudden unexpected haemorrhage, the use of transfusion packs with red cells, fresh frozen plasma, cryoprecipitate and platelets being given in ratios of between 1:1 and 1:3 seems reasonable. This removes the requirement for 'wait and see tests' and should be part of an overall resuscitation and stabilisation plan that may improve outcome following sudden haemorrhage. The replacement of fresh frozen plasma and cryoprecipitate with low-volume, targeted concentrates is attractive. There is increasing evidence for the efficacy and safety of fibrinogen concentrates as a single agent. The combination of fibrinogen and prothrombin complex concentrates could be powerful and has the possibility to the management of bleeding and improve outcome in patients but, as yet, remains unproven.

Adjunct agents for bleeding.

This review provides a summary of the most recent clinical trials evaluating the hemostatic agents for the treatment of coagulopathy associated with critical bleeding. In particular, antifibrinolytic agents (i.e., aprotinin, tranexamic and ε-aminocaproic acids), desmopressin, recombinant activated factor VII, fibrinogen and prothrombin complex concentrates are evaluated. Among the various therapeutic options available, tranexamic acid is emerging as the most promising. Indeed, a recent randomized trial has shown a benefit survival of the early administration of tranexamic acid in patients with trauma-induced coagulopathy. Although preliminary data document a potential therapeutic role for prohemostatic pharmacologic approaches, further evidence arising from randomized controlled trials is needed to assess the safety and efficacy of such agents in the setting of critical bleeding.

Resuscitative goals and new strategies in severe trauma patient resuscitation

Traumatic injuries represent a major health problem all over the world. In recent years we have witnessed profound changes in the paradigm of severe trauma patient resuscitation; new concepts regarding acute coagulopathy in trauma have been proposed; and there has been an expansion of specific commercial products related to hemostasis, among other aspects. New strategies in severe trauma management include the early identification of those injuries that are life threatening and require surgical hemostasis, tolerance of moderate hypotension, rational intravascular volume replacement, prevention of hypothermia, correction of acidosis, optimization of oxygen carriers, and identification of those factors required by the patient (fresh frozen plasma, platelets, tranexamic acid, fibrinogen, cryoprecipitates and prothrombin complex). However, despite such advances, further evidence is required to improve survival rates in severe trauma patients.

Objetivos y nuevas estrategias de resucitación en el paciente traumatizado grave

Traumatic injuries represent a major health problem all over the world. In recent years we have witnessed profound changes in the paradigm of severe trauma patient resuscitation, new concepts regarding acute coagulopathy in trauma have been proposed, and there has been an expansion of specific commercial products related to hemostasis, among other aspects. New strategies in severe trauma management include the early identification of those injuries that are life threatening and require surgical hemostasis, tolerance of moderate hypotension, rational intravascular volume replacement, prevention of hypothermia, correction of acidosis, optimization of oxygen carriers, and identification of those factors required by the patient (fresh frozen plasma, platelets, tranexamic acid, fibrinogen, cryoprecipitates and prothrombin complex). However, despite such advances, further evidence is required to improve survival rates in severe trauma patients.

ESA guidelines on the management of severe perioperative bleeding

ESA guidelines on the management of severe perioperative bleeding

Novel approaches in management of perioperative coagulopathy

The recent advances in hemostatic monitoring, and discussion of the clinical implications of hemostatic therapies based on different blood components and factor concentrates. Implementing suitable laboratory tests and transfusion protocols is highly recommended because the laboratory test guided, protocol-driven transfusion approach reduces blood component utilization, and possibly leads to improved outcomes. Timely assessment of coagulation has been difficult using conventional coagulation tests, but thrombocytopenia, fibrin polymerization defects, and fibrinolysis can be quickly assessed on thromboelastometry. The latter testing can be applied to guide the dosing of fibrinogen and prothrombin complex concentrate, which are selectively used to correct fibrinogen deficiency, and improve thrombin generation in acquired coagulopathy. These therapeutic approaches are novel, and potentially effective in reducing the exposure to allogeneic components (e.g., plasma and platelets) and side-effects of transfusion. Although the accessibility of different therapies among different countries, tranexamic acid is widely available, and is an effective blood conservation measure with a good safety profile in various surgical settings. Our understanding of perioperative coagulopathy, diagnostic tools, and therapeutic approaches has evolved in recent years. Additional multidisciplinary efforts are required to understand the optimal combinations, cost-effectiveness, and safety profiles of allogeneic components, and available factor concentrates.

Human Fibrinogen Adsorption on Latex Particles at pH 7.4 Studied by Electrophoretic Mobility and AFM Measurements

Human fibrinogen adsorption on negatively charged latex particles was investigated using the electrophoretic and the concentration depletion methods. Measurements were conducted at pH 7.4 and in the range of ionic strength of 10(-3) - 0.15 M NaCl. Firstly, the bulk physicochemical properties of fibrinogen were characterized. The zeta potential and the uncompensated (electrokinetic) charges of the protein were determined from the electrophoretic measurements. Next, systematic experiments were performed to determine the dependencies of the electrophoretic mobility of latex on the amount of adsorbed protein. Electrophoretic mobility increased significantly upon fibrinogen adsorption that was proven irreversible. The maximum coverage of fibrinogen on latex particles determined via the concentration depletion method varied between 1.9 mg m(-2) and 3.2 mg m(-2) for 10(-3) and 0.15 M NaCl, respectively. The changes in the maximum coverage were interpreted as due to electrostatic repulsion among adsorbed protein molecules. Additionally, the stability of latex covered by fibrinogen was determined. It was proven that cyclic changes of ionic strength from 10(-3) to 0.15 M NaCl did not change the electrophoretic mobility. Based on these observations, it was concluded that there were no conformational changes within adsorbed fibrinogen molecules. The experimental data, allowed one to elaborate a robust procedure of preparing latex particles covered by fibrinogen of designed coverage and molecule distribution.

Synthesis and characterization of CREKA-conjugated iron oxide nanoparticles for hyperthermia applications

One of the current challenges in the systemic delivery of nanoparticles in cancer therapy applications is the lack of effective tumor localization. Iron oxide nanoparticles (IONPs) coated with crosslinked dextran were functionalized with the tumor-homing peptide CREKA, which binds to fibrinogen complexes in the extracellular matrix of tumors. This allows for the homing of these nanoparticles to tumor tissue. The IONP core allows for particle heating upon exposure to an alternating magnetic field (AMF), while the dextran coating stabilizes the particles in suspension and decreases the cytotoxicity of the system. Magnetically mediated hyperthermia (MMH) allows for the heating of tumor tissue to increase the efficacy of traditional cancer treatments using IONPs. While MMH provides the opportunity for localized heating, this method is currently limited by the lack of particle penetration into tumor tissue, even after effective targeted delivery to the tumor site. The CREKA-conjugated nanoparticles presented were characterized for their size, stability, heating capabilities and biocompatibility. The particles had a hydrated diameter of 52nm, were stable in phosphate buffered saline solution and media with 10% v/v fetal bovine serum over at least 12h, and generated enough heat to raise solution temperatures well into the hyperthermia range (41–45°C) when exposed to an AMF, owing to an average specific absorption rate of 83.5Wg−1. Cytotoxicity studies demonstrated that the particles have low cytotoxicity over long exposure times at low concentrations. A fibrinogen clotting assay was used to determine the binding affinity of CREKA-conjugated particles, which was significantly greater than the binding affinity of dextran, only coated IONPs demonstrating the potential for this particle system to effectively home to a variety of tumor locations. Finally, it was shown that in vitro MMH increased the effects of cisplatin compared with cisplatin or MMH treatments alone.

Additive roles of platelets and fibrinogen in whole-blood fibrin clot formation upon dilution as assessed by thromboelastometry

Blood dilution after transfusion fluids leads to diminished coagulant activity monitored by rotational thromboelastometry, assessing elastic fibrin clot formation, or by thrombin generation testing. We aimed to determine the contributions of blood cells (platelets, red blood cells) and plasma factors (fibrinogen, prothrombin complex concentrate) to fibrin clot formation under conditions of haemodilution in vitro or in vivo.Whole blood or plasma diluted in vitro was supplemented with platelets, red cells, fibrinogen or prothrombin complex concentrate (PCC). Thromboelastometry was measured in whole blood as well as plasma; thrombin generation was determined in parallel. Similar tests were performed with blood from 48 patients, obtained before and after massive fluid infusion during cardiothoracic surgery.Addition of platelets or fibrinogen, in additive and independent ways, reversed the impaired fibrin clot formation (thromboelastometry) in diluted whole blood. In contrast, supplementation of red blood cells or prothrombin complex concentrate was ineffective. Platelets and fibrinogen independently restored clot formation in diluted plasma, resulting in thromboelastometry curves approaching those in whole blood. In whole blood from patients undergoing dilution during surgery, elastic clot formation was determined by both the platelet count and the fibrinogen level. Thrombin generation in diluted (patient) plasma was not changed by fibrinogen, but improved markedly by prothrombin complex concentrate. In conclusion, in dilutional coagulopathy, platelets and fibrinogen, but not red blood cells or vitamin K-dependent coagulation factors, independently determine thromboelastometry parameters measured in whole blood and plasma. Clinical decisions for transfusion based on thromboelastometry should take into account the platelet concentration.

Postpartal subclinical endometritis alters transcriptome profiles in liver and adipose tissue of dairy cows.

Transcriptome alterations in liver and adipose tissue of cows with subclinical endometritis (SCE) at 29 d postpartum were evaluated. Bioinformatics analysis was performed using the Dynamic Impact Approach by means of KEGG and DAVID databases. Milk production, blood metabolites (non-esterified fatty acids, magnesium), and disease biomarkers (albumin, aspartate aminotransferase) did not differ greatly between healthy and SCE cows. In liver tissue of cows with SCE, alterations in gene expression revealed an activation of complement and coagulation cascade, steroid hormone biosynthesis, apoptosis, inflammation, oxidative stress, MAPK signaling, and the formation of fibrinogen complex. Bioinformatics analysis also revealed an inhibition of vitamin B3 and B6 metabolism with SCE. In adipose, the most activated pathways by SCE were nicotinate and nicotinamide metabolism, long-chain fatty acid transport, oxidative phosphorylation, inflammation, T cell and B cell receptor signaling, and mTOR signaling. Results indicate that SCE in dairy cattle during early lactation induces molecular alterations in liver and adipose tissue indicative of immune activation and cellular stress.

Clinical usefulness of measurement of plasma soluble fibrin levels in critically ill patients

The soluble fibrin monomer fibrinogen complex (SF) is a complex coupling fibrin monomer and fibrinogen molecules. As the level of SF reflects the thrombin generation activity in plasma, we may estimate the early-activated state of blood coagulation by the measurement of SF. The aim of this study is to evaluate the clinical usefulness of SF for the hypercoagulated state.