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.

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)

Altered Platelet Factor X Activating Activity in Myeloproliferative Disorders

1979 ◽  
Author(s):  
S. Cortellazzo ◽  
M. Colucci ◽  
T. Barbui ◽  
N. Semeraro
Keyword(s):  
Clinical Manifestations ◽  
Myeloproliferative Disorders ◽  
Polycythaemia Vera ◽  
Bleeding Tendency ◽  
Factor X ◽  
Platelet Factor ◽  
Activity Factor ◽  
Coagulant Activity ◽  
History Of ◽  
Abnormal Bleeding

The pathogenesis of the haemostatic disorders in patients with myeloproliferative diseases has not yet been completely elucidated. Several platelet function abnormalities have been reported but they do not always correlate with the clinical manifestations. In this report a recently described platelet coagulant activity (factor X activating activity) was studied in 2 patients with essential thrombocythacmia, 10 with polycythaemia vera, 4 with chronic myeloid leukaemia and 2 with reactive thrombocytosis. It was significantly reduced in the 5 patients with bleeding tendency, and was also reduced in one patient with a history of peripheral ischaemia and in 3 patients with no haemostatic complications. It was either normal or increased in the remaining patients who had no haemostatic complications. In the two subjects with lowest activity (5 and 131) and most serious bleeding, chemotherapy resulted in normalisation of the platelet count and of platelet coagulant activity and in disappearance of the bleeding episodes. Our results suggest an association between bleeding tendency and reduced platelet coagulant activity. These findings may be of relevance to 1) the pathogenesis of abnormal bleeding in patients with myeloproliferative disorders and 2) the understanding of the role of platelet coagulant activities otter than pLatelet factor 3 in disturbed haemostasis.Supported by CNR (Italy).

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 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.

The Activation of Human Factor X in Sodium Citrate: the Role of Factor VII

1976 ◽  
Vol 36 (01) ◽  
pp. 104-114 ◽  
Author(s):  
D. L Aronson ◽  
A. J Mustafa
Keyword(s):  
Sodium Citrate ◽  
Human Factor ◽  
Deae Cellulose ◽  
Factor Ix ◽  
Factor Vii ◽  
Factor X

SummaryHuman factor X was purified by several different procedures yielding products which had varying amounts of factor VII and factor IX. Treatment with CHC13 during the fractionation of the factor X removed 95% of the factor VII and factor IX activity and the resulting factor X activated more slowly when incubated in 25% sodium citrate. Removal of residual factor VII by DEAE cellulose chromatography yielded a factor X which activated still more slowly and less completely. When the factor VII, removed by chromatography, was added to the chromatographed factor X, the ability to be activated in 25% sodium citrate was restored. Confirmatory evidence for the role of factor VII in this reaction was the inhibition of the conversion of the factor X by both DFP and SBTI.

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.

Factor X Deficiency Due to a Compound Heterozygosis Between a New Mutation (Gla72Asp) in Exon 2 and an Already Known one (Gly154Arg) in Exon 5: Factor X Mar Del Plata1)

2019 ◽  
Vol 19 (2) ◽  
pp. 169-173
Author(s):  
Antonio Girolami ◽  
Diana Noemi Garcia de Paoletti ◽  
Marcelo Leonardo Nenkies ◽  
Silvia Ferrari ◽  
Hugo Guglielmone
Keyword(s):  
Bleeding Tendency ◽  
Bleeding Disorders ◽  
Factor X ◽  
Substitution Therapy ◽  
New Mutation ◽  
Exon 2 ◽  
The Third ◽  
The Past ◽  
Factor X Deficiency ◽  
The Family

Background: Investigation of rare bleeding disorders in Latin-America. Objective: The report of a new case of FX deficiency due to a compound heterozygosis. Methods: Accepted clotting procedures were used. Sequencing of DNA was carried out by means of Applied Biosystems Instruments. Results: A compound heterozygote due to the association of a new mutation (Gla72Asp) with an already known mutation (Gly154Arg) of the FX gene is reported. The proposita is a 38 year old female who had a moderate bleeding tendency (menorrhagia, epistaxis, easy bruising). The proposita has never received substitution therapy but in the occasion of a uterine biopsy. The mother was asymptomatic but was a heterozygote for the new mutation. The father was asymptomatic but had deserted the family and could not be investigated. After this abandonment the mother of the proposita re-married with an asymptomatic man and she gave birth to a son who was asymptomatic but was also heterozygous for the new mutation (Gla72Asp). As a consequence it has to be assumed that the first husband of the mother of the proposita was heterozygous for the known mutation (Gly154Arg). Conclusion: This is the third case of a new mutation in the FX gene reported, during the past few years, in Argentina.

Factor X Friuli coagulation disorder

1973 ◽  
Vol 27 (3) ◽  
pp. 151-158 ◽  
Author(s):  
Antonio Girolami ◽  
Arnaldo Carli ◽  
Roberto Falomo ◽  
Luigi Marco
Keyword(s):  
Coagulation Disorder ◽  
Factor X

scholarly journals Active site-blocked factor Xa prevents thrombus formation in the coronary vasculature in parallel with inhibition of extravascular coagulation in a canine thrombosis model

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2059-2066 ◽  
Author(s):  
CR Benedict ◽  
J Ryan ◽  
J Todd ◽  
K Kuwabara ◽  
P Tijburg ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Coronary Thrombosis ◽  
Factor Xa ◽  
Competitive Inhibitor ◽  
Bleeding Tendency ◽  
Factor X ◽  
Total Occlusion ◽  
Coronary Vasculature ◽  
Thrombosis Model ◽  
Activation Mechanisms

Abstract Factor Xa is a central procoagulant enzyme, linking the intrinsic and extrinsic activation mechanisms to the final common pathway of coagulation. To assess its contribution to pathologic thrombosis, studies were performed in a canine coronary thrombosis model. Thrombus formation was initiated by the application of electric current via a needle electrode placed in the lumen of the left circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycinyl-arginyl-factor Xa (Xai), a competitive inhibitor of factor Xa assembly into the prothrombinase complex, Factor X, or heparin. Animals infused with saline or factor X (300 micrograms/kg) developed total occlusion of the vessel due to a fibrin/platelet thrombus in 70 +/- 11 minutes (36 of 36 animals) and 74 +/- 13 minutes (8 of 8 animals), respectively. In contrast, infusion of Xai prevented thrombus formation completely at a dose of 300 micrograms/kg (8 of 8 animals). As the dose of Xai was decreased, its antithrombotic effect was diminished, with a patency rate of only 2 of 6 animals at a dose of 90 micrograms/kg. Xai at 300 micrograms/kg prevented the accumulation of 125I-fibrinogen/fibrin at the site of the coronary thrombus by approximately 63% and decreased deposition of 111In-labeled platelets by approximately 57%. Hemostatic parameters of animals infused with Xai demonstrated prolongation of the PT and dose- dependent increased extravascular bleeding tendency. These data indicate that factor Xa has a comparably important role in thrombus formation and extravascular hemostasis, and contrast with previous results in this same animal model in which IXai selectively prevented clotting in the coronary vasculature.

Coagulation Activation in Extracorporeal Hemodialysis

1997 ◽  
Vol 20 (3) ◽  
pp. 163-165 ◽  
Author(s):  
M. Camici ◽  
L. Evangelisti ◽  
P. Balestri ◽  
L. Cioni ◽  
P. Fundi ◽  
...  
Keyword(s):  
Protein C ◽  
Serum Lipoprotein ◽  
Factor Vii ◽  
Maintenance Hemodialysis ◽  
Factor X ◽  
Lipoprotein A ◽  
Activity Factor ◽  
Before And After ◽  
Protein C Activity

The Authors evaluated the behavior of protein C activity, factor X and factor VII coagulant activity and serum lipoprotein(a) before and after dialytic treatment in patients on maintenance hemodialysis. They observed depressed protein C activity that significantly (p<0.005) increased and became normal immediately after hemodialysis while factor X and factor VII increased (p<0.01; p<0.05) despite heparinization together with amount of serum lipoprotein(a). In vitro incubation (30 'at 37°C) of uremic and healthy blood showed a decrease in serum lipoprotein(a) concentration. After heparin addition (final concentration 0.5 U/ml) lipoprotein(a) increased in the uremic blood only. The clinical and physiopathological implications of these results are discussed.

Sign in / Sign up

Export Citation Format

Share Document