Factor VII Padua 2: another factor VII abnormality with defective ox brain thromboplastin activation and a complex hereditary pattern

Abstract A new factor VII abnormality is presented. The propositus was a 9-yr- old child who presented a mild bleeding tendency characterized by epistaxis and easy bruising. The parents were not consanguineous, but they came from the same area. The laboratory features were mild prolongation of prothrombin time and P.P. test and normal partial thromboplastin and Stypven cephalin clotting times. The Thrombotest was moderately prolonged. Factor VII was 40%-50% of normal using rabbit or human brain thromboplastin, but only 13%-24% using ox brain thromboplastin. Factor VII cross-reacting material (CRM) was about 50% of normal. The father, a paternal aunt, and a paternal cousin showed similar clinical and laboratory findings. The brother of the propositus, the mother, and other members of her family showed about 50% factor VII activity and CRM and were considered to be heterozygotes for true factor VII deficiency. Similar findings were also present in the father and in the brother of the affected cousin. The defect in the propositus seems to consist of a double heterozygosity between abnormal factor VII and heterozygous factor VII true deficiency. The factor VII abnormality appears to consist of abnormal reactivity toward ox brain tissue thromboplastins and appears to be different from previously described factor VII abnormalities. The name factor VII Paudua2 is proposed for this condition.

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Factor VII Padua 2: another factor VII abnormality with defective ox brain thromboplastin activation and a complex hereditary pattern

Blood ◽

10.1182/blood.v54.1.46.bloodjournal54146 ◽

1979 ◽

Vol 54 (1) ◽

pp. 46-53 ◽

Cited By ~ 1

Author(s):

A Girolami ◽

G Cattarozzi ◽

R Dal Bo Zanon ◽

F Toffanin

Keyword(s):

Human Brain ◽

Prothrombin Time ◽

Factor Vii ◽

Bleeding Tendency ◽

Laboratory Findings ◽

Her Family ◽

Laboratory Features ◽

Paternal Aunt ◽

Double Heterozygosity ◽

Thromboplastin Factor

A new factor VII abnormality is presented. The propositus was a 9-yr- old child who presented a mild bleeding tendency characterized by epistaxis and easy bruising. The parents were not consanguineous, but they came from the same area. The laboratory features were mild prolongation of prothrombin time and P.P. test and normal partial thromboplastin and Stypven cephalin clotting times. The Thrombotest was moderately prolonged. Factor VII was 40%-50% of normal using rabbit or human brain thromboplastin, but only 13%-24% using ox brain thromboplastin. Factor VII cross-reacting material (CRM) was about 50% of normal. The father, a paternal aunt, and a paternal cousin showed similar clinical and laboratory findings. The brother of the propositus, the mother, and other members of her family showed about 50% factor VII activity and CRM and were considered to be heterozygotes for true factor VII deficiency. Similar findings were also present in the father and in the brother of the affected cousin. The defect in the propositus seems to consist of a double heterozygosity between abnormal factor VII and heterozygous factor VII true deficiency. The factor VII abnormality appears to consist of abnormal reactivity toward ox brain tissue thromboplastins and appears to be different from previously described factor VII abnormalities. The name factor VII Paudua2 is proposed for this condition.

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RASopathies and Hemostatic Abnormalities: Key Role of Platelet Dysfunction

10.21203/rs.3.rs-417615/v1 ◽

2021 ◽

Author(s):

Di Candia Francesca ◽

Marchetti Valeria ◽

Cirillo Ferdinando ◽

Di Minno Alessandro ◽

Rosano Carmen ◽

...

Keyword(s):

Coagulation Factor ◽

Screening Tests ◽

Factor Vii ◽

Bleeding Complications ◽

Bleeding Tendency ◽

Factor X ◽

Platelet Response ◽

Platelet Dysfunction ◽

Clotting Factors ◽

Laboratory Findings

Abstract Background: Bleeding anomalies occur in patients affected by Noonan syndrome. No study has been performed in patients with molecularly confirmed RASopathy. We aimed to characterize the frequency and types of bleeding disorders in patients with RASopathies and evaluate any significant association with laboratory findings. Patients and methods: Forty-nine individuals (PTPN11, n=27; SOS1, n=7; RIT1, n=3; SPRED1, n=1; LZTR1, N=3; RAF1, n=2; BRAF, n=4; MEK1, n=1; MEK2, n=1), and 49 age- and sex-matched controls were enrolled in the study. The “Paediatric Bleeding Questionnaire Scoring Key” was administered to patients and families. Laboratory screening tests including clotting factors dosing, platelet count, prothrombin time, and partial thromboplastin time, were employed both in patients and controls to characterize the bleeding diathesis. A subgroup of 29/49 patients and 29/49 controls was also tested for platelet function. Results: Regardless the gene involved, pathological bleeding scores were recorded in 14 (28.5%) patients. Among these, 7 were mutated in PTPN11 (26% of total cases with PTPN11 mutations), 3 in SOS1 (43%), 2 in RIT1 (67%), 1 in BRAF (25%), and 1 in MEK1. Compared to patients with normal bleeding scores, those with pathologic bleeding score showed higher prevalence of splenomegaly (p=0.006), prolonged aPTT (p = 0.04), lower levels of coagulation factor V (FV) (p = 0.001), factor VII (FVII) (p = 0.003), factor X (FX) (p = 0.0008) and factor XIII (FXIII) (p = 0.002), higher vWAg (p = 0.04), and lower platelet sensitivity to Ristocetin (p = 0.001), arachidonic acid (AA) (p = 0.009) and collagen (p = 0.01). The presence of hematomas inversely correlated with FV (p = 0.002), FVII (p = 0.003), FX (p = 0.002) and FXIII (p = 0.004) levels, and directly correlated with platelet response to collagen (p = 0.02) and AA (p = 0.01). The presence of splenomegaly directly correlated with occurrence of hematoma (p=0.006), platelet response to Ristocetin (p = 0.04) and AA (p = 0.04), and inversely correlated with FV levels (p = 0.03).Conclusions: Patients with RASopaties and a bleeding tendency exhibit multiple coagulation-related laboratory abnormalities, including platelet-related disorders. Splenomegaly is frequently detected and might be a suggestive sign for qualitative platelet dysfunction. A comprehensive clinical assessment should be carried out at diagnosis, during the follow-up and before any surgical procedures. Since there is currently no consensus on management of bleeding complications, it is important that physicians closely monitor these patients.

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Von-Willebrand-Syndrom Typ 1 und Schwangerschaft

Hämostaseologie ◽

10.1055/s-0037-1619742 ◽

2011 ◽

Vol 31 (S 01) ◽

pp. S11-S13 ◽

Cited By ~ 1

Author(s):

J. Oppermann ◽

A. Siegemund ◽

R. Schobess ◽

U. Scholz

Keyword(s):

Clinical Presentation ◽

Bleeding Disorder ◽

Bleeding Tendency ◽

Laboratory Findings ◽

Mucous Membranes ◽

Von Willebrand

SummaryThe von Willebrand-Jürgens syndrome (VWJS) type 1 is a common hereditary bleeding disorder with a bleeding tendency located especially in the mucous membranes. Women suffering from VWJS type 1 show menorrhagia and prolonged postoperative bleedings. During pregnancy the clinical presentation varies by the increase of the von Willebrand factors.In this article the laboratory findings and the clinical presentation of patients with VWJS during pregnancy was examined. The necessity of interventions during pregnancy and at the time of delivery was under consideration.

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Two-Stage Procedure for the Quantitative Determination of Autoprothrombin III Concentration and Some Applications

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655029 ◽

1967 ◽

Vol 18 (01/02) ◽

pp. 198-210 ◽

Cited By ~ 5

Author(s):

Ronald S Reno ◽

Walter H Seegers

Keyword(s):

Prothrombin Time ◽

Factor Vii ◽

Two Stage ◽

Pronounced Increase ◽

One Stage ◽

Assay Procedure ◽

Bovine Plasma ◽

The One ◽

Autoprothrombin C

SummaryA two-stage assay procedure was developed for the determination of the autoprothrombin C titre which can be developed from prothrombin or autoprothrombin III containing solutions. The proenzyme is activated by Russell’s viper venom and the autoprothrombin C activity that appears is measured by its ability to shorten the partial thromboplastin time of bovine plasma.Using the assay, the autoprothrombin C titre was determined in the plasma of several species, as well as the percentage of it remaining in the serum from blood clotted in glass test tubes. Much autoprothrombin III remains in human serum. With sufficient thromboplastin it was completely utilized. Plasma from selected patients with coagulation disorders was assayed and only Stuart plasma was abnormal. In so-called factor VII, IX, and P.T.A. deficiency the autoprothrombin C titre and thrombin titre that could be developed was normal. In one case (prethrombin irregularity) practically no thrombin titre developed but the amount of autoprothrombin C which generated was in the normal range.Dogs were treated with Dicumarol and the autoprothrombin C titre that could be developed from their plasmas decreased until only traces could be detected. This coincided with a lowering of the thrombin titre that could be developed and a prolongation of the one-stage prothrombin time. While the Dicumarol was acting, the dogs were given an infusion of purified bovine prothrombin and the levels of autoprothrombin C, thrombin and one-stage prothrombin time were followed for several hours. The tests became normal immediately after the infusion and then went back to preinfusion levels over a period of 24 hrs.In other dogs the effect of Dicumarol was reversed by giving vitamin K1 intravenously. The effect of the vitamin was noticed as early as 20 min after administration.In response to vitamin K the most pronounced increase was with that portion of the prothrombin molecule which yields thrombin. The proportion of that protein with respect to the precursor of autoprothrombin C increased during the first hour and then started to go down and after 3 hrs was equal to the proportion normally found in plasma.

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Use of Different Tissue Thromboplastins in the Control of Anticoagulant-Therapy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656198 ◽

1958 ◽

Vol 02 (05/06) ◽

pp. 462-480 ◽

Cited By ~ 1

Author(s):

Marc Verstraete ◽

Patricia A. Clark ◽

Irving S. Wright

Keyword(s):

Prothrombin Time ◽

Anticoagulant Therapy ◽

Factor Vii ◽

Rabbit Brain ◽

Minor Role ◽

Rabbit Lung ◽

Coagulation Mechanism ◽

Time Test ◽

The One ◽

A Minor

SummaryAn analysis of the results of prothrombin time tests with different types of thromboplastins sheds some light on the problem why the administration of coumarin is difficult to standardize in different centers. Our present ideas on the subject, based on experimental data may be summarized as follows.Several factors of the clotting mechanism are influenced by coumarin derivatives. The action of some of these factors is by-passed in the 1-stage prothrombin time test. The decrease of the prothrombin and factor VII levels may be evaluated in the 1-stage prothrombin time determination (Quick-test). The prolongation of the prothrombin times are, however, predominantly due to the decrease of factor VII activity, the prothrombin content remaining around 50 per cent of normal during an adequate anticoagulant therapy. It is unlikely that this degree of depression of prothrombin is of major significance in interfering with the coagulation mechanism in the protection against thromboembolism. It may, however, play a minor role, which has yet to be evaluated quantitatively. An exact evaluation of factor VII is, therefore, important for the guidance of anticoagulant therapy and the method of choice is the one which is most sensitive to changes in factor VII concentration. The 1-stage prothrombin time test with a rabbit lung thromboplastin seems the most suitable method because rabbit brain preparations exhibit a factor VII-like activity that is not present in rabbit lung preparations.

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SURGERY IN A HEMOPHILIAC CHILD WITH INTRACRANIAL HEMORRHAGE

PEDIATRICS ◽

10.1542/peds.28.5.800 ◽

1961 ◽

Vol 28 (5) ◽

pp. 800-804

Author(s):

John H. Fuerth ◽

Paul Teng ◽

Erwin Goldenberg

Keyword(s):

Los Angeles ◽

Type A ◽

Bleeding Tendency ◽

Laboratory Findings ◽

Excessive Bleeding ◽

Surgical Interventions ◽

Fatal Hemorrhage ◽

History Of ◽

System 2 ◽

The Central Nervous System

THE UNUSUAL bleeding tendency in hemophiliacs has been known since biblical times, and its hazards have been recognized in even such simple surgical procedures as circumcision.1 Perhaps the most dangerous complication of hemophilia is bleeding into the central nervous system.2 It therefore seems worthwhile to report the case of a 2-year-old hemophiliac who survived several intracranial hemorrhages, with two surgical interventions, but who 4 months later had a fourth and fatal hemorrhage. CASE REPORT History D. H. was a 2-year-old hemophiliac with numerous admissions to the Kaiser Foundation Hospital, Los Angeles, for bleeding episodes. He was born at another hospital, was circumcised shortly after birth and had excessive bleeding following this. His first admission was at the age of 1 year for bleeding following a tongue bite. At that time he had an abnormal result of a prothrombin consumption test, with 55% residual prothrombin in the serum. The prothrombin consumption was corrected by fresh normal plasma and barium sulfate adsorbed plasma, but not by serum or plasma from a known hemophiliac type A. The diagnosis of hemophilia type A was thus established. He had two brothers who were investigated and found to be normal. There was no abnormal bleeding tendency on his father's side, but two uncles of his mother and two first cousins were said to be "bleeders." No further details were known. Physical and Laboratory Findings The boy was admitted to the hospital on the evening of October 13, 1957, with a history of vomiting and progressive lethargy of 2 days' duration.

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INHERITED FACTOR-VII DEFECT IN A NEGRO FAMILY

PEDIATRICS ◽

10.1542/peds.27.2.204 ◽

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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Use of recombinant activated factor VII

Medicina ◽

10.3390/medicina45030032 ◽

2009 ◽

Vol 45 (3) ◽

pp. 248

Author(s):

Dagmara Reingardienė ◽

Robertas Lažauskas

Keyword(s):

Prothrombin Time ◽

Liver Diseases ◽

Hemophilia A ◽

Tissue Injury ◽

Factor Vii ◽

Recombinant Activated Factor Vii ◽

Congenital Deficiency ◽

Activated Factor Vii ◽

Life Threatening ◽

Hemostatic Disorders

Recombinant activated factor VII (rFVIIa) has been used in the treatment of various congenital and acquired hemostatic disorders for more than 10 years. Hemostasis is initiated by the FVIIa bound to tissue factor (TF), which constitutes only approximately 1% of total amount of the FVII protein existing in the blood. rFVII becomes activated only after the binding to the TF, released at the site of tissue injury. The efficiency of rFVIIa in the treatment of such life-threatening hemorrhagic states like hemophilia reaches up to 76–84%. rFVIIa is successfully used in the treatment of congenital deficiency of factor VII. It normalizes prothrombin time in the patients with the liver diseases and in cases of overdose of indirect anticoagulants. It is also useful for patients suffering from thrombocytopenia, thrombocyte function disorders, hemophilia A and B with development of inhibitors. rFVIIa allows overcoming uncontrollable hemorrhages, etc. It is supposed that rFVIIa is becoming a universal hemostatic drug.

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Predictors of mortality in adult patients with dengue: a study from South India

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20181495 ◽

2018 ◽

Vol 6 (5) ◽

pp. 1605 ◽

Cited By ~ 1

Author(s):

Vasudeva Acharya ◽

Mohammed Fahad Khan ◽

Srinivas Kosuru ◽

Sneha Mallya

Keyword(s):

Renal Failure ◽

Prothrombin Time ◽

Tertiary Care ◽

P Value ◽

Bleeding Tendency ◽

Care Hospital ◽

Laboratory Parameters ◽

Prolonged Prothrombin Time ◽

Risk Of Death ◽

Increased Risk

Background: Dengue is one of the important causes of acute febrile illnesses in India. Dengue can be a fatal disease, however there are no reliable markers which can predict mortality among these patients.Methods: A prospective cross sectional study was done in patients who were admitted to a tertiary care hospital with features of dengue fever. A total of 364 patients with IgM dengue serology positive were included in the study. Relevant clinical and laboratory parameters were collected from all patients. Association between clinico-laboratory parameters with mortality was studied using appropriate statistical methods.Results: Among the 364 patients recruited in this study, 14 (3.85%) patients died. Mortality among patients with age group 18-40 years was 2.04%, in patients aged above 40 years was 7.56%. Mortality among patients with hypotension was 42.42% (14 out of 33), bleeding manifestations was 15.38% (8/52), platelets <20,000/mm3 was 10.41% (10/96), ALT >200 was 13.04% (6/46), AST>200 was 12.34% (10/81), prolonged prothrombin time was 60%(12/20), renal failure was 28%(14/50), encephalopathy was 31.57% (6/19), multi organ dysfunction syndrome(MODS) was 43.33% (13/30), acute respiratory distress syndrome (ARDS) was 45.45% (5/11), pleural effusion was 7.5% (6/80).Conclusions: The overall mortality in the present study was 3.85%. Following variables were associated with increased risk of death among the dengue patients: Age >40 years, presence of hypotension, platelets <20000 cells/mm3, ALT>200U/L, AST>200U/L, prolonged prothrombin time, presence of renal failure, encephalopathy, MODS, ARDS and bleeding tendency (p value <0.05). Early identification of factors associated with mortality can help to make appropriate decision on care required.

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