Thrombotic Events in Homozygotes with a Proven or Highly Probable Arg304Gln Factor VII Mutation (FVII Padua)1): Only Limited Replacement Therapy is Needed in Case of Surgery

2019 ◽  
Vol 19 (3) ◽  
pp. 233-238
Author(s):  
Antonio Girolami ◽  
Elisabetta Cosi ◽  
Silvia Ferrari ◽  
Bruno Girolami ◽  
Maria L. Randi
Keyword(s):  
Replacement Therapy ◽  
Thrombotic Event ◽  
Factor Vii ◽  
Compound Heterozygous ◽  
Activity Levels ◽  
High Prevalence ◽  
Molecular Studies ◽  
Tissue Thromboplastin ◽  
The Difference ◽  
Compound Heterozygotes

Objective: To investigate the prevalence of thrombotic events among patients with proven or highly probable homozygosis for the Arg304Gln (Factor VII Padua) defect or compound heterozygosis containing the Arg304Gln mutation. Methods: Homozygotes and compound heterozygotes proven by molecular studies to have the Arg304Gln mutation were gathered from personal files and from two PubMed searches. In addition, patients with probable homozygosis on the basis of clotting tests (discrepancies among Factor VII activity levels according to the tissue thromboplastin used) were also gathered. Results: 30 proven homozygotes and 17 probable ones were gathered together with 8 compound heterozygotes. In the latter use, the associated mutation was Cys135Arg (twice), Gly180Arg, Arg304Trp, Arg315Trp, His348Gln, Gly365Cys. The prevalence of venous thrombotic events was 16.6, 11.8 and 11.1 percent, respectively for the three groups of patients. Heterozygotes showed no thrombotic event. The difference for proven homozygotes was statistically significant, while for the other groups only a trend was present. Conclusion: proven homozygous or compound heterozygous patients with the Arg304Gln mutation showed a higher than expected incidence of thrombotic events. The same is true for probable cases gathered only on the basis of clotting tests. These patients, because of their frequent lack of bleeding and for their relatively high prevalence of thrombosis should probably receive only limited replacement therapy in case of surgical procedures.

The Role of Factor IX in Tissue Thromboplastin Induced Coagulation

1982 ◽  
Vol 48 (01) ◽  
pp. 054-058 ◽  
Author(s):  
A M H P van den Besselaar ◽  
I E Ram ◽  
G H J Alderkamp ◽  
R M Bertina
Keyword(s):  
Human Factor ◽  
Factor Ix ◽  
Factor Vii ◽  
Factor Xii ◽  
Factor Xi ◽  
Proteolytic Activation ◽  
Human Factor Ix ◽  
Tissue Thromboplastin ◽  
The Difference

SummaryTissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various deficient plasmas were determined as a function of apoprotein concentration, keeping the phospholipid concentration constant. The clotting times of a factor XII-deficient plasma were the same as those of a factor XII/factor IX-deficient plasma, except at very low apoprotein concentrations. However, under those conditions the difference in clotting times was independent of the presence of anti-factor VII serum. Similar observations were made for factor XI-deficient plasma in comparison with factor XI/factor IX-deficient plasma. These results indicate that activation of factor IX by factor VII/tissue thromboplastin does not significantly contribute to plasma coagulation.

Longterm Prophylactic Treatment with Recombinant Factor VIIa (NovoSeven) in Severe Congenital Factor VII Deficient Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4503-4503
Author(s):  
Andrea Gerhardt ◽  
Rudiger E. Scharf ◽  
Rainer B. Zotz
Keyword(s):  
Replacement Therapy ◽  
Missense Mutation ◽  
Half Life ◽  
Prophylactic Treatment ◽  
Factor Vii ◽  
Bleeding Complications ◽  
Compound Heterozygous ◽  
Short Half Life ◽  
Bleeding Episodes ◽  
Fvii Deficiency

Abstract Background: Treatment of congenital FVII deficiency consists of replacement therapy with plasmic FVII concentrates or recombinant FVIIa (rFVIIa). Relatively small amounts of rFVIIa are required for replacement therapy in FVII deficient patients. Because of its short half-life of approximately 3 hours rFVIIa has not been regarded as a routine prophylactic treatment option for FVII deficiency. Case Reports: We report on our experience of prophylactic treatment with rFVIIa in two FVII deficient patients. Patient one is 43-year-old male with severe FVII deficiency (<1% activity) associated with compound heterozygous Gly78Asp and heterozygous Cys194Tyr mutations. After birth, he experienced severe tissue bleeding complications and later on various joint bleedings with consecutive hemophilic arthropathy. He is now on treatment with rFVII (1.2 mg 3 times per week) since 28 months. Patient two is a 36-year-old male with FVII deficiency of <1% FVII activity. He experienced recurrent mucosal bleeding episodes and large skin hematomas. His genetic defect consists in a homozygous missense mutation (1061 C>T, Ala354Val), a heterozygous missense mutation (218 T>A, Leu73Gln), and a heterozygous frameshift mutation (1391delC, Pro464HisfsX32). The patient is on prophylactic treatment with rFVII (1.2 mg 3 times per week) since 22 months. Since substitution with rFVII, no spontaneous bleeding episodes occurred and no side effects were observed in both patients. In conclusion, prophylactic treatment with rFVIIa in FVII deficient patients appears to be an effective and safe therapeutic option. The mechanisms by which rFVIIa prevents bleeding episodes despite a short half-life of 3 hours remains to be elucidated.

Compound-Heterozygous Mutations in the Plasminogen Gene Predispose to the Development of Ligneous Conjunctivitis

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3457-3466 ◽  
Author(s):  
Volker Schuster ◽  
Silvia Seidenspinner ◽  
Petra Zeitler ◽  
Cornelia Escher ◽  
Uwe Pleyer ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Residual Activity ◽  
Compound Heterozygous ◽  
Type I ◽  
Activity Levels ◽  
Missense Mutations ◽  
Site Mutation ◽  
Ligneous Conjunctivitis ◽  
Compound Heterozygous Mutations ◽  
Compound Heterozygotes

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 → Glu/Arg513 → His, Lys19 → Glu/Arg216 → His, and Lys19 → Glu/Leu128 → Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.

The Activation of Human Factor IX

1975 ◽  
Vol 33 (03) ◽  
pp. 553-563 ◽  
Author(s):  
B Østerud ◽  
K Laake ◽  
H Prydz
Keyword(s):  
Molecular Weight ◽  
Sodium Dodecyl ◽  
Apparent Molecular Weight ◽  
Factor Ix ◽  
Factor Vii ◽  
Activate Factor ◽  
Human Factor Ix ◽  
Factor Xia ◽  
Tissue Thromboplastin ◽  
Native Factor

SummaryThe activation of factor IX purified from human plasma has been studied. Factor XIa and kallikrein separately activated factor IX to factor IXa. In both cases factor IX a had an apparent molecular weight of about 42–45000 in sodium dodecyl sul-phate-polyacrylamide disc gel electrophoresis compared with a molecular weight of about 70000 for the native factor IX. The activation by XIa required Ca2+-ions whereas Ca2+-ions did not influence the activation by kallikrein. A mixture of tissue thromboplastin and factor VII or RusselPs-viper venom alone did not activate factor IX. Trypsin activated and plasmin inactivated factor IX.

PENGENDALIAN KADAR GLUKOSA DARAH OLEH TEH HIJAU DAN ATAU TEH DAUN MURBEI PADA TIKUS DIABETES

2010 ◽  
Vol 5 (2) ◽  
pp. 87
Author(s):  
Rusman Efendi ◽  
Evy Damayanthi ◽  
Lilik Kustiyah ◽  
Nastiti Kusumorini
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Green Tea ◽  
Glucose Level ◽  
Diabetic Rats ◽  
Feed Consumption ◽  
Font Size ◽  
High Prevalence ◽  
The Difference ◽  
Control Diabetes

<p class="MsoNormal" style="margin: 0cm 7.1pt 6pt 14.2pt; text-align: justify; text-indent: 1cm;"><span style="font-size: 10pt;">Diabetes mellitus is degeneratif disease with high prevalence that happens in many countries. Several studies had been done to control diabetes by using green tea, mullberry leaf  tea, and their mixture. The aim of this research was to analyze the influence of the administration green tea, mullbery leaf tea, and their mixtures to blood glucose level of diabetic rats both during 120 minutes after administration. This research had four phases, first to determine the best mullberry leaf tea, second to fourth phases respectively, determine turnover of blood glucose level on normal rats; attempt during 120 minutes on diabetic rats.  The result of research during 120 minutes have showed that blood glucose level on diabetic rats which were administered by green tea, mullberry leaf tea and their mixture is significantly difference with diabetic rats which were administered by water. Blood glucose level at baseline increased at 30<sup>th </sup>minutes and showed the difference significantly and then until 60<sup>th</sup> and 120<sup>th</sup> minutes and relatively stable. During 120 minutes after feed consumption, inhibition of blood glucose level occured increasingly on diabetic rats which were administered by green tea, mullberry leaf tea, and their mixture compared to diabetic rats which were administered by water.</span></p>

scholarly journals Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thomas J. Wilkinson ◽  
Daniel G. D. Nixon ◽  
Jared Palmer ◽  
Courtney J. Lightfoot ◽  
Alice C. Smith
Keyword(s):  
Kidney Disease ◽  
Early Stage ◽  
Symptom Burden ◽  
Final Analysis ◽  
Physical Symptoms ◽  
Disease Trajectory ◽  
High Prevalence ◽  
Comparative Group ◽  
The Difference ◽  
Disease Stages

Abstract Background Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population. Methods Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom. Results In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was ‘feeling tired’; and 4) being female independently increased the likelihood of reporting more symptoms. Conclusions Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue. Trial registration The study was registered prospectively as ISRCTN11596292.

Abstract P211: Single High Na + Ingestion Leads To An Increase In Oxidative Stress And Triggers Inflammation.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ginette Bordcoch ◽  
Ivan Tavera Busso ◽  
Juan Masjoan Juncos ◽  
Luis I Juncos
Keyword(s):  
Oxidative Stress ◽  
The United States ◽  
Male Rats ◽  
Control Group ◽  
Aortic Tissue ◽  
Tissue Samples ◽  
Extracellular Signal ◽  
High Prevalence ◽  
Markers Of Oxidative Stress ◽  
The Difference

Hypertension has been linked to a progressive increased in oxidative stress and inflammation. The high prevalence of hypertension poses a great risk to public health as 108 million adults in the United States have the condition. For that reason, a better understanding of the link between a high Na+ intake and the development of hypertension is of crucial importance. We hypothesize that a single ingestion of a high Na+ solution leads to increased oxidative stress and triggers an inflammatory response. Wistar 200-250 g male rats had gastric infusions through the esophagus. Groups were infused with 8 mL liquid Vaseline (Control), 8 mL of NaCl 0.684 M (4% m/v), and 8 mL of NaCl 1.368 M (8% m/v). After infusion, blood was collected at different time points during the first hour. Tissue samples were obtained from the aorta, heart, and kidney. Electron Microscopy (EM) was performed on all tissues, which were also analyzed for molecular markers of oxidative stress: Superoxide Dismutase (SOD) and Malondialdehyde (MDA), and an inflammation marker: Extracellular Signal-Regulated Kinase (ERK). At 2 and a half minutes, serum Na+ concentration was unchanged in the control group compared to an increase observed in animals receiving 4% and 8% Na+ with concentrations of 135±1.4 mEq/L, 141±2.0 mEq/L, and 140±1.2 mEq/L respectively. At the 1-hour time point after infusion, the difference was further increased in the 8% group with serum concentrations of 135±1.8 mEq/L, 140±1.5 mEq/L, and 152±1mEq/L respectively (p<0.05). There was an increase in oxidative stress in the aorta from values of 36.22±4.64 mU/mg SOD and 0.131±0.013 pg/mL MDA in the control group, to 47.11±4.89 mU/mg SOD and 0.291±0.022 pg/mL MDA in the 8% group (p<0.05 in both cases). The same was observed in the heart, where values were: 174.6125.26 mU/mg SOD, 0.026±0.007 pg/mL MDA in controls, and 259.22±21.98 mU/mg SOD, 0.215±0.073 pg/mL MDA in 8% group (p<0.05 both cases). Increased ERK in aortic tissue, values of 0.29±0.03 pg/mL in controls, 2.68±0.18 pg/mL in 4% group and 3.97±0.68pg/mL in 8% group (p<0.05) suggest increased inflammation. We conclude that the elevation in serum Na+ concentration that follows Na+ ingestion leads to increased oxidative stress and inflammation.

INHERITED FACTOR-VII DEFECT IN A NEGRO FAMILY

PEDIATRICS ◽  
1961 ◽  
Vol 27 (2) ◽  
pp. 204-213
Author(s):  
Helen I. Glueck ◽  
James M. Sutherland
Keyword(s):  
Prothrombin Time ◽  
Factor Vii ◽  
Homozygous State ◽  
Control Value ◽  
One Stage ◽  
First Case ◽  
Severe Deficiency ◽  
Low Levels ◽  
The Difference ◽  
The One

A case of factor-VII deficiency of a congenital nature in a Negro male child has been reported. As far as can be determined, this is the first case reported in this race. The defect was detected at 6 hours of age. Prothrombin, as contrasted to factor VII, after initially low levels normally found in infants, rose to adult levels. The patient's one-stage prothrombin time has ranged between 25 to 35 second (normal 11 to 12 seconds). In spite of this, he has never shown any manifestations of hemorrhage. The patient's family was studied and the findings indicate that the patient's defect represented a homozygous state and that both parents with a less severe deficiency were heterozygous for the trait. The defect is an autosomal disorder directly inherited. It is clinically apparent and easily detected only in the homozygous state. The heterozygous state is characterized by a very slight prolongation of the one-stage prothrombin time, the difference from the control value being so minimal as to be overlooked. In one subject studied, an aunt of the propositus, the quantitative defect (42% of normal) could not be regularly detected by the usual methods. Only by using the plasma of the propositus as the test plasma, was the defect in her plasma detected, thus explaining the transmission of the trait to her offspring. These findings explain the difficulties previously encountered in understanding the inheritance of the disorder.

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