A New Type of Congenital Dysfibrinogenemia (Fibrinogen Tokyo) with Defective Stabilization of Fibrin Polymers

1975 ◽  
Author(s):  
T. Samori ◽  
M. Yatabe ◽  
M. Ukita ◽  
M. Fujimaki ◽  
K. Fukutake
Keyword(s):  
Factor Xiii ◽  
Fibrinogen Level ◽  
Degradation Products ◽  
Immunological Methods ◽  
Thrombin Time ◽  
Normal Range ◽  
Plasma Factor ◽  
New Type ◽  
Abnormal Pattern ◽  
Assay Methods

A new type of congenital dysfibrinogenemia characterized by abnormal stabilization of fibrin polymers under the normal concentration of plasma factor XIII and normal thrombin time has been discovered in Tokyo.The molecular abnormality of this abnormal fibrinogen are shown by an anodal immunoelectrophoretic mobility and an abnormal pattern of D fragment in fibrinogen degradation products by plasmin digest on Immunoelectrophoresis and crossimmunoelectrophoresis.However, the plasma fibrinogen level of this case measures always in the normal range, when immunological methods or thrombin dependent methods are used, and the decreased level of plasma factor XIII is indicated by the use of assay methods based on clotlysis.

FIBRINOGEN GENOVA III: A NEW CONGENITAL DYSFIBRINOGENEMIA WITH BLEEDING DIATHESIS AND DEFECTIVE LYSIS BY PLASMIN

1987 ◽  
Author(s):  
G Castaman ◽  
F Rodeghiero ◽  
A Galletti ◽  
E Barone ◽  
G Gastaldi
Keyword(s):  
Factor Xiii ◽  
Fibrinogen Level ◽  
Immunological Methods ◽  
Functional Assay ◽  
Thrombin Time ◽  
Bleeding Diathesis ◽  
Normal Pattern ◽  
Sialic Acid Content ◽  
Sds Page ◽  
Normal Controls

A new abnormal fibrinogen was recognized in a woman with lifelong bleeding Symptoms. Patient's plasma exhibited prolonged thrombin and reptilase times. Very low fibrinogen level was obtained by functional assay whereas heat precipitation and immunological methods gave normal fibrinogen values. This pattern was also observed in her daughter. Patient's plasma prolonged thrombin time of normal plasma. Fibrin monomer polymerization of purified fibrinogen was severely impaired, whereas fibrinopeptide A release by thrombin occured at rate and extent indistinguishable from normal. Sialic acid content was normal. SDS-PAGE of purified molecule revealed normal pattern and factor XIII-dependent crosslinking occurred as in normal controls. Lysis by plasmin of fibrinogen examined on SDS-PAGE showed an abnormal degradation profile, only minimal traces of fragments D and E being detectable after prolonged digestion in comparison with normal. Binding of plasminogen and alfa-2-antiplasmin to fibrin was normal. This abnormal fibrinogen has been tentatively called Genova III.

Disseminated Intravascular Coagulation: A Clinical/Laboratory Correlation In 48 Patients

1981 ◽  
Author(s):  
R L Bick
Keyword(s):  
Platelet Count ◽  
Disseminated Intravascular Coagulation ◽  
Clinical Laboratory ◽  
Fibrinogen Level ◽  
Degradation Products ◽  
Severe Bleeding ◽  
Thrombin Time ◽  
Intravascular Coagulation ◽  
At Iii ◽  
Pre Treatment

Disseminated intravascular coagulation (DIC) is a frequent clinical entity spanning from a moderately severe bleeding disorder to a catastrophic, fulminant, and often fatal form usually associated with hemorrhage or, less commonly,as diffuse thromboses. The clinical and laboratory features of DIC remain confusing and controversial. To critically evaluate the usefulness of coagulation tests in aiding in the diagnosis and monitoring of therapy in DIC the clinical and laboratory findings were summarized in 48 patients with DIC. All patients were subjected to a prothrombin time (PT), activated partial thromboplastin time (PTT), reptilase time (RT), thrombin time (TT), fibrin(ogen) degradation products (FDP), platelet count, protamine sulfate test (PSO4), fibrinogen determination, and biological antithrombin-III (AT-III) level at the time of diagnosis. In addition, these same laboratory modalities were used to monitor patients during and after therapy. In this series of 48 patients, 38 patients had acute DIC and 10 patients had chronic DIC. In those patients with acute DIC, 100% of patients presented with hemorrhage and 53% of patients had thrombosis; 26% of patients died of their DIC type syndrome. In those patients with chronic DIC, 100% presented with hemorrhage, 80% presented with thrombosis, and none died of their intravascular clotting process. The probability of a pre-treatment abnormality in acute DIC was: FDP > AT-III = platelet count PS04 > TT > PT > fibrinogen level > PTT > RT. The probability of pre-treatment abnormalties in chronic DIC was: FDP > PSO4 = PT > AT-III = RT platelet count fibrinogen level = TT. These studies suggest the FDP level, the AT-III level, PSO4, and fibrinogen level to be reliable for aiding in the diagnosis of acute DIC. In chronic DIC the fibrinogen level, PS04, PTT, and AT-III level appear to be the most reliable indicies.

Fibrinogen Consumption In Breast Cancer And Its Relation To The Extent And Type Of Metastases

1981 ◽  
Author(s):  
V Pengo ◽  
G Cartei ◽  
D Casara ◽  
C Guerra ◽  
E Bertaglia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Half Life ◽  
Fibrinogen Level ◽  
Degradation Products ◽  
Breast Cancer Patients ◽  
Normal Range ◽  
Fibrin Degradation Products ◽  
Extent Of Disease ◽  
Gelation Test

A subclinical intravascular coagulation-fibrinolysis syndrome (I.C.F.), is commonly present in cancer patients: a shortened fibrinogen halflife, in fact, have been found in most patients with malignancies, not considering, however, the type and extent of disease. 28 breast cancer patients, without bleeding and thromboembolic disorders and not receiving chemo-radiotherapy, have been assessed for the presence of I.C.F. syndrome by mean of radiofibrinogen half-life, fibrinogen level, ethanol gelation test, fibri- nogen/fibrin degradation products (FDP). 16 patients without metastases were studied before surgery, while 12 patients with metastases were studied after more than one month from the operation (7 diffuse metastases, 5 pulmonar metastases). 14 out of 16 patients of the first group, and 6 out of 7 with diffuse metastases showed a markedly shortened fibrinogen half-life (hours) (x=53.9±18.2, x=54.2±16.4 as mean±SD respectively), while all the patients with pulmonar metastases showed a normal fibrinogen half-life (x=84±9.9). Normal range was 73-91 h. FDP were almost always normal. In conclusion the tumor per se determine a fibrinogen consumption without a competent fibrinolysis. Pulmonar metastases don’t promote fibrinogen consumption and/or they don’t need fibrin for their growth and spread,

Analysis of an Inherited Dysfibrinogenemia Pedigree Associated with a Heterozygous Mutation in the FGA Gene

2020 ◽  
Vol 40 (05) ◽  
pp. 642-648
Author(s):  
Shaoxi Li ◽  
Mingshan Wang ◽  
Xiaolong Li ◽  
Qiyu Xu ◽  
Siqi Liu ◽  
...  
Keyword(s):  
Degradation Products ◽  
Structure Stability ◽  
Heterozygous Mutation ◽  
Sequencing Analysis ◽  
Thrombin Time ◽  
The Novel ◽  
Normal Range ◽  
Phenotypic Analysis ◽  
Coagulation Tests ◽  
The One

Abstract Objective This article aims to analyze the phenotype and genotype of an inherited dysfibrinogenemia pedigree associated with a heterozygous mutation in the FGA gene, and to investigate the pathogenesis of this disease. Clinical Presentation The proband of interest is a 29-year-old woman. She was in her 37 weeks of gestation. Routine coagulation tests showed low fibrinogen activity (0.91 g/L; normal range: 2.0–4.0 g/L) and normal fibrinogen antigen (FIB:Ag) level (2.09 g/L; normal range: 2.0–4.0 g/L). Techniques The prothrombin time, activated partial thromboplastin time, thrombin time, and activity of plasma fibrinogen (FIB:C) were detected by the one-stage clotting method. The FIB:Ag, D-dimer, and fibrinogen degradation products were tested by the immunoturbidimetry method. To identify the novel missense mutation, fibrinogen gene sequencing and molecular modeling were performed. We used ClustalX-2.1-win and online bioinformatic software to analyze the conservation and possible effect of the amino acid substitution on fibrinogen. Results Phenotypic analysis revealed that the FIB:C of the proband was significantly reduced while the FIB:Ag was normal. Sequencing analysis detected a heterozygous C.2185G > A point mutation in the FGA gene (AαGlu710Lys). Bioinformatic and modeling analyses indicated that the mutation probably caused harmful effects on fibrinogen. Conclusion The heterozygous mutation of Glu710Lys in the FGA gene was identified that could cause the reduction of the FIB structure stability and result in the dysfibrinogenemia.

Quantitation of the Coagulation Inhibition in Vivo Due to Breakdown Products of Fibrin

1970 ◽  
Vol 23 (03) ◽  
pp. 477-485 ◽  
Author(s):  
P. S Mitchell ◽  
F. K Beller
Keyword(s):  
Blood Clotting ◽  
Fibrinogen Level ◽  
Degradation Products ◽  
Thrombin Time ◽  
Clotting Time ◽  
Human Fibrinogen ◽  
Quantitative Basis ◽  
Coagulation Inhibition

SummaryDegradation products of human fibrinogen were prepared by in vitro lysis of fibrin clots by urokinase activation and injected into rabbits on a quantitative basis. The dose necessary to anticoagulate the animal was equal to 2½ to 3 times the animals’ fibrinogen level. The effect on whole blood clotting time and thrombin time lasted for approximately 2 hrs. The “r” time of the TEG returned to normal after 1 hr while the “Max” value remained abnormal for more than 120 min. Degradation product E was shown to clear more rapidly than D by immunochemical techniques. The overall T ½ clearance was found to be approximately 12 hrs.

scholarly journals Simultaneous Use of Factor XIII and Fibrin Degradation Products in Diagnosing Early Cases of NEC and Neonatal SEPSIS

2021 ◽  
Vol 2 (4) ◽  
pp. 1-10
Author(s):  
Mohammad Abdelmonaem Sharaf ◽  
Heba Ezzat Hashem ◽  
Wafaa O. Ahmed
Keyword(s):  
Neonatal Sepsis ◽  
Factor Xiii ◽  
Degradation Products ◽  
Laboratory Data ◽  
Sepsis Group ◽  
Laboratory Evaluation ◽  
Preterm Neonates ◽  
Fibrin Degradation Products ◽  
Plasma Factor

Purpose: The study examined the use of factor XIII and fibrin degradation products in diagnosing early cases of NEC and neonatal sepsis. Methods: Sixty neonates were divided into two groups. 30 preterm neonates suspected with early NEC Diagnosis of NEC was confirmed by modified Bell’s score and 30 preterm neonates with symptoms of neonatal sepsis; where sepsis was confirmed by blood culture and CRP. Laboratory evaluation of FDPs and plasma factor XIII was done for all the patients. The study was carried out in a tertiary NICU of the pediatric department, Ain Shams University Hospital. All enrolled neonates had a matched mean birth weight and gestational age. They were either moderate preterms >32 weeks, but <34 weeks, and late preterms >34 weeks, but <37 weeks). Results: The results indicate a correlation between FDPs and the laboratory data of group B, and it was found out that FDPs were negatively correlated with TLC, Plate-lets, and CRP, reflecting FDPs increase with bone marrow suppression and progression of sepsis. Factor XIII was significantly lower in the group with NEC as compared to the group of sepsis (p<0.001), while FDPs level was significantly higher in the group with sepsis (p<. 0.001). The correlation between the clinical stages of NEC BELL's score and the level of Initial factor XIII level revealed that the factor level is negatively correlated with stage I of BELL's score. The follow-up revealed that there was no correlation between BELL's score and the level of follow-up factor XIII. On follow-up, the current study demonstrated that TLC, CRP, FDPS, PTT were significantly increased in the sepsis group with p values of 0.021,, 0.001, 0.001 and 0.01. The current study found significantly higher partial thromboplastin time (PTT) in the group with sepsis Conclusion: Factor XIII level can predict early cases of NEC and can differentiate it from neo-natal sepsis.

A Pilot Study To Examine The Effect Of Extracorporeal Membrane Oxygenation (ECMO) On Plasma Factor XIII Levels

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4774-4774 ◽  
Author(s):  
Dimarys Sanchez ◽  
Kimo Stine ◽  
Shelley E. Crary ◽  
Richard Fiser ◽  
Michael Schmitz ◽  
...  
Keyword(s):  
Blood Loss ◽  
Factor Xiii ◽  
Analysis Of Covariance ◽  
Bleeding Complications ◽  
Thrombin Time ◽  
Time Points ◽  
Transfusion Requirements ◽  
Pediatric Study ◽  
Plasma Factor ◽  
The Mean

Background Children with acute, severe cardiopulmonary compromise may require support with ECMO. Adequate anticoagulation without inducing life-threatening hemorrhage plays a critical role in the management of these patients. Recent data from adult studies suggest that patients undergoing cardiac bypass for coronary artery bypass grafting (CABG) often have reduced Factor XIII levels (FXIII). This relative FXIII deficiency may be predictive of hemorrhage or severe blood loss. Such studies have never been conducted in the pediatric population. Our primary objective will be to determine if a relative deficiency in FXIII occurs in children undergoing ECMO and to determine any time dependency of these changes. Our secondary objective will be to determine if blood loss and/or transfusion requirements during ECMO correlates with FXIII levels. Methods Single center ongoing study utilizing a prospective design involving pediatric patients (ages 0-18) undergoing ECMO. Samples for FXIII, D-Dimers, Fibrinogen and Thrombin Time are being drawn at designated time points as follows: prior to or during ECMO cannulation, 2 hours, 24 hours, 3-5 days and 14-21 days after initiation of ECMO and 1-3 days after discontinuation of ECMO. Mixed effects analysis of covariance (ANCOVA) will be used for data analysis. Results To date, fifteen patients have been enrolled and analyses have been conducted for n=7 patients with a total of 36 time points of data. Figure 1a and 1b show the mean and standard deviation (SD) of FXIII and Fibrinogen, respectively. Figure 1c shows the mean ratio of FXIII to Fibrinogen. Error bars represent 1 SD around the mean (central point). Conclusion and Significance This is the first pediatric study evaluating FXIII activity in children undergoing ECMO. Firm conclusions cannot be drawn with the interim analyses conducted to date. If variations in FXIII are found, our results will provide important information towards determining if children undergoing ECMO could potentially benefit from FXIII replacement, in turn minimizing bleeding complications and/or transfusion requirements often encountered with this treatment modality. Disclosures: No relevant conflicts of interest to declare.

The Measurement of Heparin

1973 ◽  
Vol 30 (03) ◽  
pp. 471-479 ◽  
Author(s):  
K. W. E Denson ◽  
John Bonnar
Keyword(s):  
Degradation Products ◽  
Factor Xa ◽  
Assay Method ◽  
Thrombin Time ◽  
Fibrinogen Degradation Products ◽  
Low Levels

SummaryA method for the measurement of heparin utilising the potentiating effect of heparin on the action of anti-factor Xa is described. The effect on the assay of platelet contamination of plasma, the presence of fibrinogen degradation products and low levels of anti-factor Xa have been studied. The assay method has been compared with the calcium thrombin time method and a group of obstetrical patients have been studied using both methods.

Plasma Factor XIII and Platelet Factor XIII in Hyperlipaemia

1976 ◽  
Vol 36 (03) ◽  
pp. 542-550 ◽  
Author(s):  
Mircea P. Cucuianu ◽  
K Miloszewski ◽  
D Porutiu ◽  
M. S Losowsky
Keyword(s):  
Factor Xiii ◽  
Significant Contribution ◽  
Quantitative Assay ◽  
Factor Xii ◽  
Platelet Factor ◽  
Type Iv ◽  
Plasma Factor ◽  
Hepatic Synthesis

SummaryPlasma factor XIII activity measured by a quantitative assay was found to be significantly higher in hypertriglyceridaemic patients (type IV and combined hyperlipoproteinaemia), as compared to normolipaemic controls. No such elevation in plasma factor XIII activity was found in patients with type IIa hyperlipaemia. Plasma pseudocholinesterase was found to parallel the elevated factor XIII activity in hypertriglyceridaemic subjects.In contrast, platelet factor XIII activity was not raised in hyperlipaemic subjects, and plasma factor XIII was found to be normal in a normolipaemic subject with throm-bocythaemia.It was concluded that there is no significant contribution from platelets to plasma factor XIII activity, and that the observed increase in plasma factor XII in hypertriglyceridaemia results from enhanced hepatic synthesis of the enzyme.

Influence of Acute Myocardial Infarction and rt-PA Therapy on Circulating Fibrinogen

1993 ◽  
Vol 69 (04) ◽  
pp. 321-327 ◽  
Author(s):  
E Seifried ◽  
M Oethinger ◽  
P Tanswell ◽  
E Hoegee-de Nobel ◽  
W Nieuwenhuizen
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Thrombolytic Agent ◽  
Degradation Products ◽  
Maximum Plasma ◽  
Normal Range ◽  
Fibrinogen Degradation Products ◽  
Fibrin Degradation Products ◽  
Rebound Phenomenon ◽  
The Mean

SummaryIn 12 patients treated with 100 mg rt-PA/3 h for acute myocardial infarction (AMI), serial fibrinogen levels were measured with the Clauss clotting rate assay (“functional fibrinogen”) and with a new enzyme immunoassay for immunologically intact fibrinogen (“intact fibrinogen”). Levels of functional and “intact fibrinogen” were strikingly different: functional levels were higher at baseline; showed a more pronounced breakdown during rt-PA therapy; and a rebound phenomenon which was not seen for “intact fibrinogen”. The ratio of functional to “intact fibrinogen” was calculated for each individual patient and each time point. The mean ratio (n = 12) was 1.6 at baseline, 1.0 at 90 min, and increased markedly between 8 and 24 h to a maximum of 2.1 (p <0.01), indicating that functionality of circulating fibrinogen changes during AMI and subsequent thrombolytic therapy. The increased ratio of functional to “intact fibrinogen” seems to reflect a more functional fibrinogen at baseline and following rt-PA infusion. This is in keeping with data that the relative amount of fast clotting “intact HMW fibrinogen” of total fibrinogen is increased in initial phase of AMI. The data suggest that about 20% of HMW fibrinogen are converted to partly degraded fibrinogen during rt-PA infusion. The rebound phenomenon exhibited by functional fibrinogen may result from newly synthesized fibrinogen with a high proportion of HMW fibrinogen with its known higher degree of phosphorylation. Fibrinogen- and fibrin degradation products were within normal range at baseline. Upon infusion of the thrombolytic agent, maximum median levels of 5.88 μg/ml and 5.28 μg/ml, respectively, were measured at 90 min. Maximum plasma fibrinogen degradation products represented only 4% of lost “intact fibrinogen”, but they correlatedstrongly and linearly with the extent of “intact fibrinogen” degradation (r = 0.82, p <0.01). In contrast, no correlation was seen between breakdown of “intact fibrinogen” and corresponding levels of fibrin degradation products. We conclude from our data that the ratio of functional to immunologically “intact fibrinogen” may serve as an important index for functionality of fibrinogen and select patients at high risk for early reocclusion. Only a small proportion of degraded functional and “intact fibrinogen”, respectively, is recovered as fibrinogen degradation products. There seems to be a strong correlation between the degree of elevation of fibrinogen degradation products and the intensity of the systemic lytic state, i.e. fibrinogen degradation.

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