Fibrin Monomer Test Research Articles

Reference Value Fibrin Monomer in Healthy Children: A Cross-Sectional Study.

The objective of this study is to determine the fibrin monomer reference intervals in healthy children. This cross-sectional study was conducted in the Hematology Department at Vietnam National Children's Hospital (April 2023 to March 2024). Children without prior history of clotting disorders or anticoagulants use hospitalized in preparation for orthopedic surgery or inguinal hernia surgery were enrolled in the study. The fibrin monomer test method was the quantitative fibrin monomer test on the STA-R system (Diagnostica Stago™, France). Eighty-six children (58 males and 28 females) were enrolled in the study. The median (interquartile range, 2.5th-97.5th) fibrin monomer value of the study subjects was 2.56 (0.11-5.93) µg/mL, with no statistically significant difference in fibrin monomer values among the age groups of 1 month to 3 years, 3 years to 13 years, and 13 years to 18 years. This is the first study conducted in Vietnam to determine reference values of fibrin monomer in children. This information can help in the diagnosis and treatment of early hypercoagulation stage and disseminated intravascular coagulation in children.

Severe bleeding tendency caused by a rare complication of excessive fibrinolysis with disseminated intravascular coagulation in a 51-year-old Japanese man with prostate cancer: a case report

IntroductionDisseminated intravascular coagulation causes thrombotic tendency leading to multiple organ failure and occurs in a wide variety of diseases including malignancy. Disseminated intravascular coagulation is a latent complication in people with prostate cancer.Case presentationA 51-year-old Japanese man with advanced castration-resistant prostate cancer was admitted to our hospital because of extensive purpura and severe anemia. Prolonged plasma coagulation time, hypofibrinogenemia and normal platelet count suggested that a decrease in fibrinogen induced a bleeding tendency causing purpura. However, elevated plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers, with positive fibrin monomer test, manifested disseminated intravascular coagulation and subsequent fibrinolysis. Plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers decreased after administration of low-molecular-weight heparin. However, low fibrinogen and α2-antiplasmin levels were not improved and plasmin-antiplasmin complex did not decrease, which revealed excessive fibrinolysis complicated with disseminated intravascular coagulation. We suspected that prostate cancer cell-derived urokinase-type plasminogen activator caused excessive fibrinolysis. Administration of tranexamic acid for fibrinogenolysis was added together with high-dose anti-androgen therapy (fosfestrol) for prostate cancer. Thereafter, prostate-specific antigen and plasmin-antiplasmin complex decreased, followed by normalized fibrinogen and α2-antiplasmin levels, and the patient eventually recovered from the bleeding tendency. Immunohistochemical staining of the biopsied prostate tissue exhibited that the prostate cancer cells produced tissue factor, the coagulation initiator, and urokinase-type plasminogen activator.ConclusionThis patient with rare complications of disseminated intravascular coagulation and excessive fibrinolysis is a warning case of potential coagulation disorder onset in patients with prostate cancer. We propose that combined administration of tranexamic acid and low-molecular-weight heparin together with high-dose anti-androgen therapy is a useful therapeutic option for patients with this complicated coagulation disorder.

Excessive Perioperative Bleeding

Excessive Perioperative Bleeding

A heparin bonding of the extracorporeal circuit reduces clot formation during prolonged lung assist in goats

Purpose of Study: This study investigated whether heparin bonded artificial lungs with non-microporous polyolefin hollow fibber combined with low dose systemic heparinization could reduce the thrombus formation during prolonged, veno-arterial extracorporeal lung assist (V-A ECLA) in goats. Methods Used: We compared heparin-bonded (HB, 5 goats) and non-heparin bonded circuits (NHB, 5 goats) in ECLA of one week. ACT was kept below 130 s by systemic infusion with a small dose of heparin in the HB group, and 180 to 230 s in the NHB group. Clot formation was assessed by both microscopic and visual examination the circuit after the experiments, and the incidence of systemic complications. Summarize Results: The mean heparin dose give during ECLA was 20.4 ± 3.6U/kg/hr iin HB group, 50.9 ± 14.2 U/kg/hr in NHB group, significantly less in HB group than in NHB group (P < 0.01). The bypass flow rate, platelet aggregation activity, platelet counts, and fibrin monomer test, antithrobin - III activity did not differ between two groups. Macroscopic examinations revealed a lot of clot in all the oxygenators of the NHB group. A goat of NHB group of NHB group developed convulsions and cerebral hemorrhage. The HB artificial membrane lung consisted of those fibers showed a good anticoagulation advantage to decrease clot formations nevertheless a small dose of heparin in ECLA of 7 in goats.

Performances of the Fibrin Monomer Test for the Exclusion of Pulmonary Embolism in Symptomatic Outpatients

Many studies have shown that D-dimer determinations can be used for the exclusion of venous thromboembolism in symptomatic outpatients, depending however on the method of D-dimer measurement. Another related assay, the Fibrin Monomer test which measures soluble fibrin levels in plasma by ELISA, is now available. We have evaluated the performances of this assay for the exclusion of pulmonary embolism (PE) in 426 consecutive outpatients presenting at the emergency ward of our institution. Diagnosis of PE was made by D-dimer measurement, compression ultrasonography, lung scintigraphy, venography and pulmonary angiography. With a cut-off of 3 microg/ml. the sensitivity and the negative predictive value were both 100% (95% CI: 97.1-100 and 96.3-100 respectively) and the specificity 33% (95 % CI: 25.7-38.1). With 4 microg/ml, the corresponding figures were 98.4 (95% CI: 94.4-99.8), 98.3 (95% CI: 94.1-99.8) and 39% (95% CI: 33.6-44.7) respectively. The prevalence of PE was 30%, the exclusion rates were 23 and 27% for either cut-off. When compared with a reference D-dimer assay (Asserachrom D-Di), a good correlation was observed. In conclusion, this is the first study suggesting the interest of this Fibrin Monomer test to rule out PE; these results, however, need to be confirmed by other studies.

The Influence of Blood Taking, Storage Conditions and Interfering Factors on a New Fibrin Monomer Test

Article The Influence of Blood Taking, Storage Conditions and Interfering Factors on a New Fibrin Monomer Test was published on January 1, 1996 in the journal Journal of Laboratory Medicine (volume 20, issue 2).

Comparison of Immunological and Functional Assays for Measurement of Soluble Fibrin

Various assays have been developed for quantitation of soluble fibrin or fibrin monomer in clinical plasma samples, since this parameter directly reflects in vivo thrombin action on fibrinogen. Using plasma samples from healthy blood donors, patients with cerebral ischemic insult, patients with septicemia, and patients with venous thrombosis, we compared two immunologic tests using monoclonal antibodies against fibrin-specific neo-epitopes, and two functional tests based on the cofactor activity of soluble fibrin complexes in tPA-induced plasminogen activation. Test A (Enzymun-Test FM) showed the best discriminating power among normal range and pathological samples. Test B (Fibrinostika soluble fibrin) clearly separated normal range from pathological samples, but failed to discriminate among samples from patients with low grade coagulation activation in septicemia, and massive activation in venous thrombosis. Functional test C (Fibrin monomer test Behring) displayed good discriminating power between normal and pathological range samples, and correlated with test A (r = 0.61), whereas assay D (Coa-Set Fibrin monomer) showed little discriminating power at values below 10 micrograms/ml and little correlation with other assays. Standardization of assays will require further characterization of analytes detected.

Thrombin treated plasma employed as a standard for determination of soluble fibrin

The Coa-set Fibrin Monomer test (CFM-test) is a quantitative method for determination of soluble fibrin in plasma. The fibrin standard of the CFM-test is produced by bathroxobin conversion of purified fibrinogen to fibrin. Plasma treated with minute amounts of thrombin may be considered as a more physiological way of preparing fibrin monomers. Therefore, we have employed such thrombin treated plasma (TTP) as an alternative fibrin standard for the CFM-test. The fibrin concentration of the TTP was determined indirectly by quantitation of released fibrinopeptide A. The TTP was stable during freezing, thawing and storage for 3 months at -70° C. The standard curve obtained using TTP as a standard was linear in the range of 0 – 275 nmol/1 fibrin in plasma, but the slope of the line was less steep than the original standard curve. This difference was probably due to the greater plasminogen activating effect of bathroxobin digested fibrinogen compared to soluble fibrin generated in plasma by thrombin, as observed in a previous study. Because of the less steep slope of the alternative standard curve, fibrin levels in plasma samples from 20 healthy volunteers and 25 patients were found to be higher employing TTP as a standard. Preparation of a fibrin standard by incubation of plasma with minute amounts of thrombin will to some extent mimic the process of fibrin generation in vivo. Since we have found a satisfactory stability of such a standard during freezing, thawing and storage, we think the TTP standard might be useful for quantitation of soluble fibrin in plasma.

Experimental results using nafamostat mesilate as anticoagulant during extracorporeal lung assist for 24 hours in dogs.

We report on the experimental application of nafamostat mesilate (NM, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate, FUT), a new anticoagulant, to extracorporeal lung assist (ECLA) with an artificial membrane lung. Venovenous ECLA, from the jugular vein to the femoral vein, was performed with a hollow-fiber membrane lung at a blood flow rate of approximate 82 ml kg-1 min-1 for 24 h in 7 dogs under anesthesia and hypoventilation. Heparin (10 U ml-1 in a priming lactated Ringer solution of 140 ml, and 200 U kg-1) was administered before blood access cannulation. After start of ECLA, however, no heparin was used, and nafamostat mesilate was continuously infused into the drainage line of the bypass circuit to control activated coagulation time (ACT) at about 150 to 200 s. To maintain the prolonged ACT, 8.0 +/- 1.7 mg kg-1 h-1 of NM was required. Arterial blood pressure and pulse rate decreased significantly. Though fibrin monomer test revealed hypercoagulability after 6 h of ECLA, platelet counts did not significantly decrease. Total blood loss remained less than 40 g. The artificial membrane lung sustained a good gas exchange and low flow resistance throughout ECLA. Macroscopic examination revealed small spotty thrombi in the artificial lung but no major pathologic changes of the visceral organs in the all dogs at autopsy. High-dose NM administration could control blood coagulation and decrease blood loss during ECLA for 24 h without deterioration of the artificial lung and systemic complication other than mild hypotension and bradycardia.

Soluble, cross-linked fibrin(ogen) hybrid oligomers do not stimulate t-PA conversion of plasminogen

Cross-linked hybrid oligomers of fibrinogen and fibrin are found in plasma from fibrinaemic patients and normal individuals as well as in preparations of purified human fibrinogen. The present study was undertaken to see if such hybrid oligomers have the same stimulatory effect on tissue plasminogen activator (t-PA) conversion of plasminogen as do polymeric and monomeric fibrin. Hybrid oligomeric fibrin(ogen) material was provided by subjecting purified human fibrinogen to gel filtration in urea-containing buffer at pH 5.6. Well separated fractions of hybrid oligomeric material and monomeric fibrinogen were thus obtained; Some of this material was converted to soluble polymeric or monomeric fibrin using insolubilized thrombin. Hybrid polymeric fibrin, polymeric fibrin or monomeric fibrin were then added to citrated, normal plasma to 2.5 or 5 per cent of the plasma fibrinogen concentration. The added material was kept in solution by plasma fibrinogen. The “COASET Fibrin Monomer Test” (Kabi,Stocholm,Sweden), based on the ability of fibrin monomers to enhance t-PA mediated plasminogen-plasmin conversion, was used to compare the potential stimulatory effect of the preparations above. The results led to the following conclusions: 1. 1) Cross-linked, soluble fibrin(ogen) hybrid polymers in a concentration of 5 per cent of plasma fibrinogen concentration (w/w) do not stimulate t-PA. 2. 2)Thrombin conversion of the fibrin-fibrinogen hybrid material resulted in an increase in the rate of t-PA mediated plasminogen conversion, corresponding to the one observed with equivalent (w/w) amounts of fibrin monomers. Compared on a mole to mole basis, fibrin oligomers are more powerful than fibrin monomers as stimulators of t-PA activity.

The stimulatory effect of soluble fibrin on plasminogen activation by tissue plasminogen activator as studied by the CDA-set fibrin monomer test

The stimulatory effect of various fibrin preparations on plasminogen activation by tissue plasminogen activator, was studied by the Coa-set Fibrin Monomer test (Kabi). Fibrin obtained by complete conversion of purified fibrinogen demonstrated a greater stimulatory effect on plasminogen activation than did equal amounts of fibrin obtained by partial conversion of fibrinogen. Soluble fibrin generated by treating human plasma with minute amounts of thrombin or bathroxobin, resembled partially converted purified fibrinogen. The plasminogen activating effect of completely converted fibrinogen was similar in thrombin and bathroxobin incubated samples. In preparations of partially converted fibrinogen and in plasma samples, bathroxobin digested fibrinogen expressed a more pronounced stimulatory effect on plasminogen activation than did thrombin digested specimens. The underlying mechanism for these differences are discussed.

インフルエンザウイルスと血小板の相互反応

The interacion between influenza virus and platelets was observed under a transmission electron microscope by mixing virus (PR-8 strain) with PRP of human or rabbits. The adsorption of the virus onto the surface of the platelet was immediately observed. Some of the viruses started to invade into the platelets and were seen in the open canalicular systems. After two minutes, the platelets deformed significantly, marked decreased number of the granules and vacularization were seen. After 5 minutes, the mass of platelet aggergates can be seen. In addition, 2ml of virus suspension was intravenously administered to rabbits to see coagulation and pathological changes. The platelet counts decreased singnficantly, fibrinogen level decreased only after 2 hours, but fibrin monomer test showed negative. The platelet thrombi were observed in pulmonary capillaries and splenic tissues.From the above results, it is suspected that platelet aggregation is partly responsible for the development of thrombocytopenia in the inital stage of viral infection.

心人工弁置換患者における凝血学的指標の検討 フィブリノペプチドＡおよび可溶性フィブリンモノマー複合体を中心として

In 40 patients with prosthetic heart valves and 3 patients who underwent open mitral commissurotomy, fibrinopeptide A (FPA) and soluble fibrin monomer complex (SFMC) were measured by enzyme immunoassay and fibrin monomer test (FM test), respectively. The relationship between these two parameters and either von Willebrand factor antigen (vWF:Ag), antithrombin III (ATIII) or thrombo-test (TTO) were analyzed.FPA was elevated in 41.9% and FM test was positive in 25.6% of the patients. High FPA values were obtained frequently in patients with positive FM test. TTO, vWF:Ag and ATIII were not correlated with plasma concentration of FPA. FM test was not correlated with TTO or vWF:Ag, but positive results in FM test were frequently observed in potients with low plasma level of ATIII.These results indicate that low TTO does not mean suppressed thrombin generation in vivo, and that FPA and FM test would be valuable parameters of hypercoagulability in these patients.

On the Early Detection of Intravascular Coagulation

SummarySince the conception of intravascular coagulation has been introduced in clinical medicine, the interest of clinicians in the early detection of this syndrome is continuously increasing. Therefore small amounts of thrombin and thromboplastin were infused into rabbits and special parameters, such as presence of an activated form of factor V and occurrence of a positive fibrin monomer test, were checked. As it turned out, activation of factor V (proaccelerin, accelerator globulin or AcG) was an earlier sign of intravascular coagulation than the appearance of a positive gelation test, which may occur without changes in fibrinogen or the number of blood platelets. These experiments could be of value for the early detection of intravascular coagulation in man.