Comparison of Immunological and Functional Assays for Measurement of Soluble Fibrin

1995 ◽  
Vol 74 (02) ◽  
pp. 673-679 ◽  
Author(s):  
C E Dempfle ◽  
S A Pfitzner ◽  
M Dollman ◽  
K Huck ◽  
G Stehle ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Low Grade ◽  
Plasma Samples ◽  
Normal Range ◽  
Soluble Fibrin ◽  
Discriminating Power ◽  
Fibrin Monomer ◽  
Cerebral Ischemic

SummaryVarious 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 μg/ml and little correlation with other assays. Standardization of assays will require further characterization of analytes detected.

Estimation and characterization of soluble fibrin monomer complexes during endotoxin-induced intravascular coagulation

1977 ◽  
Vol 10 (5) ◽  
pp. 711-720 ◽  
Author(s):  
R. Hafter ◽  
G. Müller-Berghaus ◽  
R. von Hugo ◽  
H. Graeff
Keyword(s):  
Soluble Fibrin ◽  
Intravascular Coagulation ◽  
Fibrin Monomer

scholarly journals CHARACTERIZATION OF A CR51-LABELED ENDOTOXIN AND ITS IDENTIFICATION IN PLASMA AND URINE AFTER PARENTERAL ADMINISTRATION

1963 ◽  
Vol 117 (4) ◽  
pp. 561-571 ◽  
Author(s):  
Louis Chedid ◽  
Robert C. Skarnes ◽  
Monique Parant
Keyword(s):  
Intravenous Administration ◽  
Sublethal Dose ◽  
Plasma Samples ◽  
Agar Diffusion ◽  
Degraded Material ◽  
Sublethal Doses ◽  
Heavy Fractions ◽  
Urine Specimens

The incubation of endotoxin with Na2Cr51O4 yielded a product which was well labeled. That the label was fixed on the endotoxin itself was shown by autoradiography on specific lines of precipitation formed in agar. Ultracentrifugation at 40,000 RPM sedimented 80 per cent of the total weight of the starting Boivin preparation. Agar diffusion patterns with subsequent autoradiographs demonstrated that the chromium tag was associated only with the heavy fractions of the pellet. The supernatant contained precipitable, but unlabeled endotoxin. Toxicity measurements showed that more than 99 per cent of the total toxicity resided in the pellet fractions. The chromate-tagged endotoxin was specifically identified in plasma samples taken up to 6 hours after intravenous administration of LD50 or sublethal doses. The endotoxin was not totally detoxified in vivo since plasma collected 6 hours after the injection of even the sublethal dose was toxic when assayed in adrenalectomized mice. The endotoxin was specifically identified in urine specimens but it was no longer toxic or radioactive. Agar diffusion experiments indicated that only degraded material was present.

Participation of Soluble Fibrin Monomer Complexes and Platelet Factor 4 in the Generalized Shwartzman Reaction

1968 ◽  
Vol 20 (01/02) ◽  
pp. 285-295 ◽  
Author(s):  
B Lipiński ◽  
K Worowski ◽  
J Jeljaszewicz ◽  
S Niewiarowski ◽  
L Rejniak
Keyword(s):  
Blood Platelets ◽  
Aminocaproic Acid ◽  
Salmonella Typhi ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Shwartzman Reaction

SummaryThe generalized Shwartzman reaction was produced in rabbits by the typical way of 2 consecutive injections of Salmonella typhi endotoxin. Generalized Shwartzman reaction was also induced by “preparation” of the rabbits with epsilon-aminocaproic acid or mercuric chloride intoxication, followed by a single injection of the endotoxin. Significant impairment of blood fibrinolytic activity resulting from inhibition by endotoxin of a release of the kidney plasminogen activator, was demonstrated in the classical generalized Shwartzman reaction. Inhibition of fibrinolysis led to the accumulation of soluble fibrin monomer complexes in the circulation, detectable in plasma by protamine sulfate precipitation. It is postulated that hypercoagulability, regularly occurring in the generalized Shwartzman phenomen, is due to fibrinolysis inhibition. Endotoxin causes release of platelet factor 4 from rabbit blood platelets both in vitro and in vivo. This factor is thought to be responsible for nonenzymatic intravascular precipitation of fibrin from circulating soluble fibrin monomer complexes. Bilateral cortical necrosis in kidneys is due by fibrin deposition resulting from the disturbance in the equillibrium between blood clotting and fibrinolytic systems and the interaction of accumulated soluble fibrin monomer complexes with platelet factor 4.

scholarly journals A New Enzyme Immunoassay for Soluble Fibrin in Plasma, with a High Discriminating Power for Thrombotic Disorders

1999 ◽  
Vol 81 (01) ◽  
pp. 54-59 ◽  
Author(s):  
G. H. Laterveer-Vreeswijk ◽  
D. Lockwood ◽  
K. Szewczyk ◽  
W. Nieuwenhuizen ◽  
R. Bos
Keyword(s):  
Enzyme Immunoassay ◽  
Solid Phase ◽  
Gamma Chain ◽  
Soluble Fibrin ◽  
Fibrin Formation ◽  
Discriminating Power ◽  
Multistep Process ◽  
Intravascular Coagulopathy ◽  
Buffer Composition

SummaryFibrin formation is a multistep process initiated by thrombin. At first thrombin converts fibrinogen to fibrin molecules which in vivo form soluble complexes with fibrinogen. Soluble fibrin is considered to be an early biochemical marker for intravascular fibrin formation and impending thrombotic events, such as deep venous thrombosis (DVT), pulmonary embolism (PE) and disseminated intravascular coagulopathy (DIC).A new enzyme immunoassay (EIA) was developed on the basis of a monoclonal antibody directed against a fibrin specific neo-epitope located on the gamma-chain of fibrinogen; γ-(312-324). In addition, it was possible to prepare a lyophilized reference material of thrombin-generated soluble fibrin, that allowed for full antigen recovery after reconstitution with buffer. Assay conditions, e.g. solid phase-Ig concentration and buffer composition, sample and conjugate dilution, and incubation times were optimised.The present assay was found to be specific (no interference of homologous antigens) and reproducible (intra-assay CV 4-8%, inter-assay CV 4-9%), and therefore highly suited for measuring soluble fibrin levels in a plasma milieu. The median normal value for soluble fibrin was determined in plasma samples obtained from apparently healthy volunteers (n = 81) and found to be 0.040 μg/ml, with a range (10-90 percentiles) of 0.026-0.059 μg/ml.A retrospective study showed that soluble fibrin levels were highly significantly increased in patients with a confirmed diagnosis of DIC (median 1.042 μg FEU/ml, range 0.160-2.319 μg/ml, n = 21, P <0.0001 vs normal), PE (median 0.527 μg FEU/ml, range 0.084-1.234 μg/ml, n = 29, P <0.0001 vs normal) and DVT (median 0.126 μg FEU/ml, range 0.059-0.878 μg/ml, n = 36, P <0.0001 vs normal), as determined by the Mann-Whitney U-Test.

scholarly journals Soluble Fibrin Monomer Complexes in Patients with Renal Cell Carcinoma

1977 ◽  
Author(s):  
K. Andrassy ◽  
R. Gärtner ◽  
G. Riedasch ◽  
R. Zimmermann ◽  
E. Ritz ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Vascular Tumor ◽  
Low Grade ◽  
Impaired Liver Function ◽  
Soluble Fibrin ◽  
Intravascular Coagulation ◽  
Coagulation Abnormalities ◽  
Fibrin Monomer

Patients with renal cell carcinoma (r. c.) are known to exhibit retention of bromsulphalein, increase in alkaline serum phosphatase (a. p.) and diminution of prothrombin time (Stauffer-syndrome). These abnormalities were thought to reflect impaired liver function. However, the increase in a. p. was shown to be due to appearance of Regan’s isoenzyme. The present study was designed to test the hypothesis that coagulation abnormalities in the patients result from low grade (intratumoral) intravascular coagulation. 26 patients with r. c. with/without metastases were studied preoperatively: Assay of coagulation tests: soluble fibrin monomer complexes (SFMC) by etha-nol gelation and by precipitation with β-alanin and subsequent agarose chromatography according to Hafter and Graeff. – Thrombin coagulase time (t. c.) was abnormal in virtually all patients (23/26); in addition reptilase time (r. t.) (15/26), FDP as meassured by TRCHII (8/26) and staph, clump-test (4/26) and normotest (6/26) were abnormal. T. c. and r. t. were particularly abnormal in 12/26 patients in whom increased cone, of SFMC were found. It is concluded that low grade intravascular ‘coagulation, possibly within the vascular bed of the highly vascular tumor, and to a lesser extent fibrinolysis accounted for the coagulation abnormalities in (non)-metastasing renal cell carcinoma.

scholarly journals 18F-FDG PETCT and 68Ga-DOTA PETCT mismatch with in vivo histopathological characterization of low-grade neuroendocrine pancreatic tumor

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Marcello Moro Queiroz ◽  
Carlos Diego Holanda Lopes ◽  
Alessandra Corte Real Salgues ◽  
Felipe de Galiza Barbosa ◽  
Emerson Shigueaki Abe ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumor ◽  
Standard Uptake Value ◽  
Histopathological Analysis ◽  
Low Grade ◽  
High Grade ◽  
Ki 67

Abstract Background Pancreatic neuroendocrine tumor (PNET) is a subgroup of neuroendocrine tumor (NET) that has unique biology and natural history. The histological classification has a major role in the management of this pathology, but in recent years Gallium 68 dotatate (68Ga-DOTA) scanning is at the center of a discussion about how these imaging technologies can modify clinical management of neuroendocrine tumors and how their results are correlated to Ki67 index. Method We hereby describe a case of a patient that investigated an unspecific stable pancreatic nodule suspected of high-grade NET after evaluation with 68Ga-DOTATOC positron emission tomography—computed tomography (PETCT) and 18F-Fluorodeoxyglucose (18F-FDG) PETCT. Results The images corroborate the hypothesis of high-grade NET based on the standard uptake value (SUV) described in both image exams (16.4 in 18FDG PETCT and 9.2 in 68Ga-DOTATOC PETCT). After surgery, the histopathological analyses revealed a localized grade 2 well-differentiated NET, Ki-67 of 4.7, glucose transport proteins 1 (GLUT1) negative by immunohistochemistry, evidencing a rare case of mismatch between the functional image and the in vivo characterization of the neoplasm. Conclusion Functional imaging of neuroendocrine tumors with different modalities of PETCT is a well-described strategy for evaluating PNET and can dictate conducts in some cases. However, histopathological analysis is crucial to confirm the grade and prognosis related to this disease.

scholarly journals 18F-FDG PETCT and 68Ga-DOTA PETCT Mismatch With in Vivo Histopathological Characterization of Low Grade Neuroendocrine Pancreatic Tumor

2021 ◽  
Author(s):  
Marcello Moro Queiroz ◽  
Carlos Diego Holanda Lopes ◽  
Alessandra Corte Real Salgues ◽  
Felipe de Galiza Barbosa ◽  
Emerson Shigueaki Abe ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumor ◽  
Standard Uptake Value ◽  
Histopathological Analysis ◽  
Low Grade ◽  
High Grade ◽  
Ki 67

Abstract BackgroundPancreatic neuroendocrine tumor (PNET) is a subgroup of neuroendocrine tumor (NET) that has unique biology and natural history. The histological classification has a major role in the management of this pathology, but in recent years Gallium 68 dotatate (68Ga-DOTA) scanning is at the center of a discussion about how these imaging technologies can modify clinical management of neuroendocrine tumors and how their results are correlated to Ki67 index.MethodWe hereby describe a case of a patient that investigated an unspecific stable pancreatic nodule suspected of high-grade NET after evaluation with 68Ga-DOTATOC positron emission tomography - computed tomography (PETCT) and 18F-Fluorodeoxyglucose (18F-FDG) PETCT. ResultsThe images corroborate the hypothesis of high-grade NET based on the standard uptake value (SUV) described in both image exams (16.4 in 18FDG PETCT and 9.2 in 68Ga-DOTATOC PETCT). After surgery, the histopathological analyses revealed a localized grade 2 well differentiated NET, Ki-67 of 4.7, evidencing a rare case of mismatch between the functional image and the in vivo characterization of the neoplasm.ConclusionFunctional imaging of neuroendocrine tumors with different modalities of PETCT is a well-described strategy for evaluating PNET and can dictate conducts in some cases. However, histopathological analysis is crucial to confirm the grade and prognosis related to this disease. Besides the rarity of this case, our patient presented a mismatch between imaging and histopathological analysis, with the former one allowing active surveillance based on a low-grade neuroendocrine tumor.

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