scholarly journals Factor X Friuli Coagulation Disorder: Almost 50 Years Later

2016 ◽  
Vol 24 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Antonio Girolami ◽  
Elisabetta Cosi ◽  
Claudia Santarossa ◽  
Silvia Ferrari ◽  
Bruno Girolami ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatitis B ◽  
The Other ◽  
Coagulation Disorder ◽  
Bleeding Tendency ◽  
Factor X ◽  
Clotting Time ◽  
Diagnostic Difficulties ◽  
International Event ◽  
Natal Mortality

The story of factor X (FX) Friuli. Factor X Friuli was discovered in 1969 to 1970. However, the story of that disease was an international event since patients with this defect were studied in France and in Italy, and different diagnoses were reached—FVII; FX; combined prothrombin complex; and combined FII, FVII, and FX deficiencies. The diagnostic difficulties were due to the peculiar clotting pattern presented by these patients, namely, prolonged partial thromboplastin time, prolonged prothrombin time but normal Russell viper venom clotting time. Only suitable anti-FX antisera clarified the pattern. Altogether 12 homozygotes and 102 heterozygotes have been followed during 4 decades. Six homozygotes died, 2 of them due to HIV infection and 1 due to hepatitis B liver cirrhosis. The other 3 died of nontransfusion-related morbidity. Bleeding tendency has been moderate in agreement with the extrinsic or intrinsic system assay results—FX level of 4% to 5% is considered normal. Heterozygotes may present occasional bleeding manifestations usually during surgery or delivery. Molecular analysis have shown that the mutation responsible for the defect is a Pro343Ser substitution in exon 8. Chimeric FX Friuli mice have been useful in studying the effect of FX levels on embryonic or natal mortality of these animals. No new homozygote but several heterozygotes have been recently seen. The study of FX Friuli has revolutionized the diagnostic approach to FX deficiencies. The FX should be assayed by all assay systems. The FX Friuli has never been described in any other country, and all patients studied come from the Friuli Meduna River Valley.

scholarly journals Further Studies on the Abnormal Factor X (Factor X Friuli) Coagulation Disorder: A Report of Another Family

Blood ◽  
1971 ◽  
Vol 37 (5) ◽  
pp. 534-541 ◽  
Author(s):  
A. GIROLAMI ◽  
M. LAZZARIN ◽  
R. SCARPA ◽  
A. BRUNETTI
Keyword(s):  
Normal Serum ◽  
Factor Vii ◽  
White Female ◽  
Coagulation Disorder ◽  
Recessive Trait ◽  
Bleeding Tendency ◽  
Factor X ◽  
Clotting Time ◽  
Serum Factors ◽  
Normal Limits

Abstract Another patient with a congenital coagulation disorder due to the presence of an abnormal factor X (factor X Friuli) is presented. The proposita was a 43-yr-old white female who had a bleeding tendency from early childhood (epistaxes, monorrhagias, bleeding after tooth extractions and other surgical procedures, posttraumatic hemarthroses, bleeding from the gums and postpartum hemorrhages). The coagulation work-up demonstrated a prolonged prothrombin time, prolonged partial thromboplastin time, abnormal prothrombin consumption, and abnormal thromboplastin generation corrected by normal serum. Factors II, V, VII, IX, and XII were within normal limits. Platelets, vascular tests and fibrinolysis were normal. Mr. Stuart’s plasma failed to correct the defect of the proposita’s plasma, but a known factor VII deficient plasma was able to correct the abnormality. The factor X assay was low (6-9%) only when tissue thromboplastin, whole or partial, was used. When Factor X was assayed with a Stypven-cephalin mixture, normal or near normal values were observed. Likewise, the Stypven-cephalin clotting time, the Stypven clotting time and the factor II + factor X level using a Stypven-cephalin mixture were normal. The presence of the abnormal factor X was demonstrated immunologically. The defect, like classical factor X deficiency, is transmitted as an autosomal incompletely recessive trait. The mother and the two children of our proposita had factor X levels varying from 38 to 56% of normal and were considered to be heterozygotes.

scholarly journals COL1A1 Gene Expression in Hepatitis B Virus (HBV) Related Hepatocellular Carcinoma (HCC) Egyptian's Patients

2021 ◽  
Vol 11 (1) ◽  
pp. 108-114
Author(s):  
Amal A. Mohamed ◽  
Yousry Esam-Eldin Abo-Amer ◽  
Amyan Aalkhalegy ◽  
Lamiaa Abdelfattah Fathalla ◽  
Mostafa Bedair Elmaghraby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Healthy Volunteers ◽  
Complete Blood Count ◽  
Venous Blood ◽  
The Other ◽  
Col1a1 Gene ◽  
Group 2

Introduction: Collagens are the most abundant proteins in the human body, accounting for one-third of total proteins. Over the last few years, accumulated evidence have indicated that some collagens are differentially expressed in cancer. The aim of the study was to assess COL1A1 gene expression as a novel marker for the progression of hepatitis B cirrhosis into hepatocellular carcinoma. Methods: This cohort study included 348 subjects and was conducted between May 2018 and June 2019. Subjects were divided into 4 groups: group1 included HBV positive hepatocellular carcinoma patients “HCC” (n= 87), group II included HBV positive patients with liver cirrhosis “LC” (n = 87), group III included chronic hepatitis B patients with neither HCC nor cirrhosis “ C-HBV” (n = 87) and group IV consisted of healthy volunteers as controls (n = 87). Fasting venous blood samples (10 ml) were collected from each participant in this study and were used for assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin and alfa-fetoprotein (AFP). Another portion of blood was collected in 2 vacutainer tubes containing EDTA, one for Complete blood count and the other for gene expression of COL1A1. Results: The gene expression of collagen was 6.9 ± 8.8 in group 1 (HBV positive hepatocellular carcinoma patients) and this was a significant increase in comparison with the other groups. In group 2 (HBV positive patients with liver cirrhosis), the gene expression (collagen) was 3.7±1.5 and it was significantly increased when compared with group 4 (healthy volunteers). Conclusion: COL1A1 gene expression can be used as an indicator of the progression of hepatitis B cirrhosis into hepatocellular carcinoma.

Factor X Vorarlberg, A New Variant of Hereditary Factor X Deficiency

1979 ◽  
Author(s):  
K Lechner ◽  
G Mähr ◽  
P Margariteller ◽  
E Deutsch
Keyword(s):  
Sodium Citrate ◽  
Autosomal Recessive Inheritance ◽  
Disc Electrophoresis ◽  
Coagulation Disorder ◽  
Bleeding Tendency ◽  
Factor X ◽  
Activity Factor ◽  
New Variant ◽  
Tissue Thromboplastin ◽  
Heterologous Antibody

The proposita, a 56 years old woman, has a mild bleeding tendency. Prothrombin time was 112 sec (control 17.0 sec), stypven time 13.7 sec (control 11.5 sec) and APTT 54 sec (control 40 sec). Factor I, II (funct.and imm.), V, VII, VIII, IX, XI, XII, AT III were normal. - Factor X activity was < 1% by extrinsic system assay (tissue thromboplastin), 12% by RVV assay and 32% by intrinsic system (APTT) assay. Similar results were obtained when factor X activity was determined using the synthetic substrate S 2222. Immunoassay (antibody neutralisation, heterologous antibody to factor X) demonstrated a decreased level (20%) of immunoreactive factor X. The patient plasma had no inhibitory activity. Factor X activity could be completely absorbed on barium sulfate and eluted with 5% sodium citrate. It was eluted at the same position from a Sephadex G-200 column as normal factor X, but had a slower electrophoretic mobility when subjected to disc electrophoresis. Family studies (22 members studied) suggest an autosomal recessive inheritance. A second unrelated family with the same defect was subsequently detected in the same valley of Vorarlberg (Austria). - It is concluded that this hereditary coagulation disorder is due to a grossly abnormal factor X-molecule.Supported by Ö.F.F.W.F. (grant No. M2-2090)

scholarly journals Development of antitissue factor antibodies in patients after liver surgery

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 96-102 ◽  
Author(s):  
H Tsuda ◽  
S Higashi ◽  
S Iwanaga ◽  
T Kubota ◽  
T Morita ◽  
...  
Keyword(s):  
Liver Surgery ◽  
Factor Viia ◽  
Bleeding Tendency ◽  
Factor X ◽  
Clotting Time ◽  
Immunoblotting Analysis ◽  
Chromogenic Assay ◽  
Coagulation Status ◽  
Factor X Activation ◽  
Clinical Error

After liver surgery, two patients developed unexplainable prolonged prothrombin times (PT) that were not associated with bleeding tendency. The substitution of rabbit thromboplastin for either human or monkey thromboplastin in performing PT tests resulted in a normal clotting time. Tissue factor (TF) procoagulant activity assays and an immunoblotting analysis showed that these patients had developed IgG lambda-type immediate anticoagulants directed against both rabbit and bovine TF that did not crossreact with human or monkey TF. In a chromogenic assay, the patient IgG caused a decrease in both the Km and the Vmax of the factor X activation by rabbit TF-factor VIIa complex. The lack of reactivity of the patient IgG with human TF presumably explained why there was no clinical bleeding. Both patients had been treated earlier with a topical hemostatic agent prepared from bovine corium, microfibrillar collagen hemostat, while undergoing previous surgery. In an immunoblotting analysis, the patient IgG stained a 42-Kd band in the Triton extract of the collagen preparation under either reducing or nonreducing conditions. The Triton extract of the collagen preparation blocked the binding of the patient IgG to bovine TF. Thus, it is suggested that the iatrogenic immunization by intraoperative exposure of bovine TF retained in the collagen preparation may be responsible for the development of anti-TF antibodies in these patients. The anti-TF antibodies resulted in a clinical error in the evaluation of coagulation status after the use of rabbit thromboplastin.

Procoagulant Properties of Ascitic Fluid in Hepatic Cirrhosis

1979 ◽  
Author(s):  
L.L. Phillips ◽  
J.B. Rodgers
Keyword(s):  
Liver Cirrhosis ◽  
Ascitic Fluid ◽  
Hepatic Cirrhosis ◽  
The Other ◽  
Factor V ◽  
Factor X ◽  
Activation Test ◽  
Intermittent Drainage ◽  
Electrolyte Abnormalities

Re-infusion of ascitic fluid into the vasculature of patients with liver cirrhosis corrects many of the protein, fluid, and electrolyte abnormalities. Such infusion can lead to D.I.C. Three such cases are reported here. One had intermittent drainage and re-infusion, the other two had Le Veen shunts installed. All three patients showed laboratory evidence of D.I.C. Ascitic fluid on one patient showed procoagulant material by the thromboplastin activation test. In the presence of ascites from another patient, plasmas deficient in Factors XI, IX, and VIII gave recalcification and non-activated partial thromboplastin times similar to those of normal plasma. RCT’s and PTT’s of normal heparinized plasma and of plasmas deficient in Factors X and VII-X were shortened to a lesser extent. Clotting times of Factor V deficient plasma were prolonged by ascites. These results indicate that an activator of Factor X is present in the ascitic fluid. Additional tests such as RVV and prothrombin times suggest that some activated Factor X and/or tissue activator (endotoxin and leukocytes) may have been formed in vivo.

Factor X Vorarlberg, a New Variant of Hereditary Factor X DeficiencyX

1979 ◽  
Author(s):  
K. Lechner ◽  
G. Mähr ◽  
P. Margariteller ◽  
E. Deutsch
Keyword(s):  
Sodium Citrate ◽  
Autosomal Recessive Inheritance ◽  
Disc Electrophoresis ◽  
Coagulation Disorder ◽  
Bleeding Tendency ◽  
Factor X ◽  
Activity Factor ◽  
New Variant ◽  
Tissue Thromboplastin ◽  
Heterologous Antibody

The proposita, a 56 years old woman, has a mild bleeding tendency. Prothrombin time was 112 sec (control 17.0 sec), stypven time 13.7 sec (control 11.5 sec) and APTT 54 sec (control 40 sec). Factor I, II (funct.and imm.), V, VII, VIII, IX, XI, XII, AT III were normal. - Factor X activity was < 1% by extrinsic system assay (tissue thromboplastin), 12% by RVV assay and 32% by intrinsic system (APTT) assay. Similar results were obtained when factor X activity was determined using the synthetic substrate S 2222, Immunoassay (antibody neutralisation, heterologous antibody to factor X) demonstrated a decreased level (20%) of immunoreactive factor X. The patient plasma had no inhibitory activity. Factor X activity could be completely absorbed on barium sulfate and eluted with 5% sodium citrate. It was eluted at the same position from a Sephadex G-200 column as normal factor X, but nad a slower electrophoretic mobility when subjected to disc electrophoresis. Family studies (22 members studied) suggest an autosomal recessive inheritance, A second unrelated family with the same defect was subsequently detected in the same valley of Vorarlberg (Austria). - It is concluded that this hereditary coagulation disorder is Je to a grossly abnormal factor X-molecule.

Plasma Levels of Protein S, Protein C, and Factor X: Effects of Sex, Hormonal State and Age

1995 ◽  
Vol 74 (05) ◽  
pp. 1271-1275 ◽  
Author(s):  
C M A Henkens ◽  
V J J Bom ◽  
W van der Schaaf ◽  
P M Pelsma ◽  
C Th Smit Sibinga ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Postmenopausal Women ◽  
Protein C ◽  
Blood Donors ◽  
Premenopausal Women ◽  
Protein S ◽  
The Other ◽  
Factor X ◽  
Normal Ranges

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.

Characterization of Recombinant Human Coagulation Factor XFriuli

1996 ◽  
Vol 75 (02) ◽  
pp. 313-317 ◽  
Author(s):  
D J Kim ◽  
A Girolami ◽  
H L James
Keyword(s):  
Catalytic Domain ◽  
Coagulation Factor ◽  
Molecular Size ◽  
Binding Pocket ◽  
Site Directed Mutagenesis ◽  
Bleeding Tendency ◽  
Factor X ◽  
Amino Terminal ◽  
Normal Plasma ◽  
Plasma Factor

SummaryNaturally occurring plasma factor XFriuli (pFXFr) is marginally activated by both the extrinsic and intrinsic coagulation pathways and has impaired catalytic potential. These studies were initiated to obtain confirmation that this molecule is multi-functionally defective due to the substitution of Ser for Pro at position 343 in the catalytic domain. By the Nelson-Long site-directed mutagenesis procedure a construct of cDNA in pRc/CMV was derived for recombinant factor XFriuli (rFXFr) produced in human embryonic (293) kidney cells. The rFXFr was purified and shown to have a molecular size identical to that of normal plasma factor X (pFX) by gel electrophoretic, and amino-terminal sequencing revealed normal processing cleavages. Using recombinant normal plasma factor X (rFXN) as a reference, the post-translational y-carboxy-glutamic acid (Gla) and (β-hydroxy aspartic acid (β-OH-Asp) content of rFXFr was over 85% and close to 100%, respectively, of expected levels. The specific activities of rFXFr in activation and catalytic assays were the same as those of pFXFr. Molecular modeling suggested the involvement of a new H-bond between the side-chains of Ser-343 and Thr-318 as they occur in anti-parallel (3-pleated sheets near the substrate-binding pocket of pFXFr. These results support the conclusion that the observed mutation in pFXFr is responsible for its dysfunctional activation and catalytic potentials, and that it accounts for the moderate bleeding tendency in the homozygous individuals who possess this variant procoagulant.

Procedures for the Quantitative Determination of Autoprothrombin C

1962 ◽  
Vol 08 (03) ◽  
pp. 434-441 ◽  
Author(s):  
Edmond R Cole ◽  
Ewa Marciniak ◽  
Walter H Seegers
Keyword(s):  
Quantitative Determination ◽  
Plasma Sample ◽  
Quantitative Measure ◽  
The Other ◽  
Clotting Time ◽  
Bovine Plasma ◽  
Autoprothrombin C

SummaryTwo quantitative procedures for autoprothrombin C are described. In one of these purified prothrombin is used as a substrate, and the activity of autoprothrombin C can be measured even if thrombin is in the preparation. In this procedure a reaction mixture is used wherein the thrombin titer which develops in 20 minutes is proportional to the autoprothrombin C in the reaction mixture. A unit is defined as the amount which will generate 70 units of thrombin in the standardized reaction mixture. In the other method thrombin interferes with the result, because a standard bovine plasma sample is recalcified and the clotting time is noted. Autoprothrombin C shortens the clotting time, and the extent of this is a quantitative measure of autoprothrombin C activity.

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