Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AFIBRINOGENEMIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2005

[Congenital afibrinogenemia associated with a novel nonsense mutation in the FGA gene].

OBJECTIVE: To identify the genetic defect underlying congenital afibrinogenemia in a Chinese family. METHODS: Plasma fibrinogen (Fg) was assessed by both Clauss method and immunonephelometry. Genomic DNA was isolated from peripheral blood of the proband and 13 members of her family. All the exons and exon-intron boundaries of the three fibrinogen genes (FGA, FGB, FGG) were amplified by PCR followed by direct sequencing. Restriction endonuclease analysis was performed for the PCR products of the family members and 50 healthy donors to exclude gene polymorphism. RESULTS: No Fg was detected in the plasma of the proband and her father by Clauss method, while low levels (< 0.02 g/L) were detected by immunonephelometry. A homozygous C to T mutation was found in the two cases at nucleotide 3108 in exon 4 of FGA gene, resulting in a null mutation which encoded severely truncated alpha-chains owing to its premature termination at the Gln 150 codon. The C-->T mutation eliminated a unique recognition site for restriction enzyme RsaI. The PCR amplified fragments of the proband and her father could not be digested by RsaI, showing that they are homozygous. Her mother and some family members are heterozygous at this site since the fragment could partly be digested, while the same fragment of controls could be completely digested as expected. CONCLUSION: The Gln (CAG)-->150stop (TAG) nonsense mutation in FGA gene is a novel genetic defect of congenital afibrinogenemia which, to our knowledge, has not been described before.

Adolescent↗
PubMed2005

[Fibrinogen beta chain gene mutation contributes to one congenital afibrinogenemia].

OBJECTIVE: To identify the fibrinogen (Fg) gene mutations in a Chinese pedigree of congenital afibrinogenemia. METHODS: The plasma Fg activity and protein of the proband and his family members were detected. Genomic DNA was isolated from the peripheral blood mononuclear cells. All the exons and exon-intron boundaries of fibrinogen gene were amplified by PCR and sequenced thereafter. RESULTS: Two mutations, 7972 del G in FGB and T2543A in FGG, were found in the proband. CONCLUSIONS: FGG2543 is a polymorphism site, which lead to the polymorphism of gamma144 I/K. The G deletion at base 7972 of FGB contributes to the frameshift mutation after amino acid 419, resulting in the truncated beta chain without the terminal 27 amino acids. The latter may contributes to the pathogenetic mechanisms in Chinese congenital afibrinogenemia patients. The G deletion at base 7972 of FGB is identified for the first time.

Adult↗
PubMedDate not supplied

[Afibrinogenemia: description of a case with recurrent intracranial bleeding].

INTRODUCTION: Congenital afibrinogenemia is a very rare autosomal recessive disorder of the coagulation. The lack of fibrinogen makes the blood inclotting and patients suffer from bleeding at a minimal trauma. It is usually noticed within the first few days of life because of the umbilical cord bleeding. Intracerebral hematoma is infrequent. CASE DESCRIPTION: 46-year-old woman who suffers from congenital afibrinogenemia and has five episodes of intracerebral bleeding, all of them in the posterior circulation. As a complication, she also presents an epilepticus status and the therapy with concentrated fibrinogen caused pulmonary thromboembolism. CONCLUSIONS: After analysing the cases described in literature, there are evidences that the majority of the intracerebral hematoma are located in the posterior circulation. A few patients developed major thomboemolisms following infusion with concentrated fibrinogen and there are only isolated descriptions of beneficial prophylactic effects. So, it is would necessary studies more extensive research to achieve effectiveness in the prevention of the bleeding.

Adult↗
PubMed1991

[Congenital afibrinogenemia with bleeding, bone cysts and antibodies to fibrinogen].

Congenital afibrinogenemia is a rare hereditary disorder which has been described in only 150 families. The main clinical manifestations include spontaneous bleeding into the skin and into the gastrointestinal and genitourinary tracts. Skeletal manifestations are seldom reported. Laboratory findings include coagulation disorders corrected by administration of plasma, cryoprecipitate or fibrinogen. Development of antibodies to treatment with fibrinogen is rare. We report congenital afibrinogenemia in a 25-year-old man with rare complications which included skeletal manifestations such as bone cysts, and the development of antibodies to fibrinogen. Fibrinogen levels could only be maintained in the normal range by continuous infusion of cryoprecipitate, but not by bolus injections.

Adult↗
PubMed1991

[Genetic study of congenital afibrinogenemia. Review of 12 cases].

Twelve cases of congenital afibrinogenemia in 11 families are reported. A family study was performed in six cases. The parents were genetically related in 8 of the 11 families. In half the cases another sibling had the disease. In every case the direct ascendants were unaffected. On the basis of results of plasma fibrinogen assays, "unprotected" heterozygotes with no more than 2.5 g/l fibrinogen and "protected" heterozygotes with normal fibrinogen levels were differentiated. Identification of "unprotected" heterozygotes is essential for genetic counselling. The reason for this variable phenotypic expression of congenital afibrinogenemia is unclear.

Afibrinogenemia↗
PubMed1995

Effect of fibrinogen substitution in afibrinogenemia on hemorheology and platelet function.

Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen. Fibrinogen and thrombin time were not measurable before, but became detectable within 30 min after substitution, parallelled by an increase in ADP-induced platelet aggregation from < 10% to 32%. Platelet adhesion, measured by Stagnation Point Flow Adhesio- Aggregometry, was not detectable prior to substitution but attained normal values thereafter. Scanning electron microscopy of adhering platelets revealed pseudopodia protrusion and spreading. Morphometry revealed two populations of spread platelets one of which demonstrated inhibited spreading as compared to healthy controls. Immunoelectron microscopy revealed normal GPIIb/IIIa receptor expression, both before and after substitution. Dynamic and kinematic viscosity of plasma and whole blood remained below the 99.9% confidence border of a healthy control group. In afibrinogenemia fibrinogen levels as low as 10% of normal concentration sufficed to normalize coagulation, platelet adhesion, and, partially, spreading.

Adult↗
PubMed1979

Platelet fibrinogen: subcellular localization by means of immunofluorescent studies in normals and in congenital afibrinogenemia.

We have studied the site of fibrinogen localization in normal platelets and in the platelets of a patient with congenital afibrinogenemia (CA). The methods employed were: direct immunofluorescence technique (DIT) and indirect immunofluorescence technique (IIT). By means of the DIT normal platelets were shown to have a clear peripheral staining. Such staining disappeared after treatment with proteolytic enzymes and after specific blocking experiments. Such peripheral staining of platelets was absent in congenital afibrinogenemia even after fibrinogen infusion. By means of the IIT platelets were shown to have a considerable amount of fibrinogen. Such protein was demonstrated to represent an important part of platelet surface, since intact platelets were able to absorb completely a specific antifibrinogen antiserum.

Afibrinogenemia↗
PubMed1998

[Clinico-radiological dissociation in cerebral hemorrhage caused by afibrinogenemia].

INTRODUCTION: Congenital afibrinogenemia is a very rare hereditary anomaly of coagulation. Only 150 cases have been published. Clinical manifestation in the form of some type of bleeding is similar to that of other congenital coagulopathies, although the pattern of presentation is different. Spontaneous bleeding is rare, but slight injury, which may be unnoticed, may trigger it off. In spite of being a congenital condition, it may be of late onset, as in our patient, with bleeding episodes occurring in the second decade of life. CLINICAL CASE: We describe a woman who had several episodes of bleeding, two of which were intracerebral. The principal feature of this was dissociation between the clinical findings and their detection by neuro-imaging. Substitutive therapy led to the disappearance of symptoms. CONCLUSION: Cerebral haemorrhage in the presence of afibrinogenemia may fail to be detected early on CT. On clinical suspicion of bleeding, early substitutive treatment should be started.

Adult↗
PubMed1998

Treatment of congenital afibrinogenemia with cryoprecipitate collected through a plasmapheresis program using dedicated donors.

A child with afibrinogenemia was evaluated for prophylactic cryoprecipitate transfusion due to recurrent episodes of traumatic bleeding. The parents would only consider ongoing transfusion therapy if a limited donor program could be established. Automated plasmapheresis was performed on a regular basis on the patient's parents and a limited number of selected donors. Studies on the initial units collected demonstrated that a single 500 mL plasmapheresis yielded a mean of 606 mg fibrinogen in the cryoprecipitate, which was stored in two bags. A total of 166 U of cryoprecipitate from 84 individual plasmapheresis donations were transfused prophylactically every 2-3 weeks over a 16-month period. Compared to transfusions from random donors, the use of a limited number of apheresis donors resulted in a donor exposure reduction of 87%. Clinically, the patient has had minimal bleeding during this period.

Afibrinogenemia↗
PubMed2004

Pregnancy-related thrombosis in a woman with congenital afibrinogenemia: a report of two successful pregnancies.

We managed two pregnancies in a woman with congenital afibrinogenemia with increasing amounts of cryoprecipitate to achieve a pre-infusion fibrinogen level of 60 mg/dL. The first pregnancy resulted in placental abruption at 36 weeks, in spite of recent cryoprecipitate infusion. Both placentas showed infarction. Post-partum ovarian and renal vein thromboses complicated the second pregnancy. Mean FVIII (344%) and vWF Antigen (323%) were elevated prior to cryoprecipitate infusion, with mean post-infusion levels of 367% and 363%. The clearance of fibrinogen after cryoprecipitate infusion increased during the course of pregnancy. A paradoxical prothrombotic state with embolization may play a role in the observed complications of pregnancy.

Afibrinogenemia↗
PubMed1994

Congenital afibrinogenemia.

Congenital afibrinogenemia is a rare disorder with unusual clinical manifestations. The disease is inherited as an autosomal recessive trait and consanguinity is common among affected families. Clinical manifestations range from minimal bleeding to catastrophic hemorrhage. Congenitally afibrinogenemic patients seem to be peculiarly susceptible to spontaneous rupture of the spleen. Coagulation tests which depend on clot formation as an end point may be infinitely prolonged and abnormalities of platelet function are usually present. The diagnosis is established by demonstrating trace or no immunoreactive fibrinogen. The disease is caused by markedly reduced or absent synthesis of fibrinogen by liver cells, but the genetic defect remains unknown. Bleeding episodes can be effectively treated with cryoprecipitate. Purified virally inactivated fibrinogen concentrates have been used in Europe and may soon be widely available.

Afibrinogenemia↗
PubMed1985

First report of case of congenital afibrinogenemia with successful delivery.

We report a case in which pregnancy was sustained in a woman with congenital afibrinogenemia with delivery by cesarean section. From this case it appears that a plasma fibrinogen level greater than 60 mg/dl would maintain implantation of the placenta and fetus even in the event of complications occurring during pregnancy.

Adult↗
PubMed1985

Congenital afibrinogenemia and recurrent early abortion: a case report.

The role of the fibrinogen molecule in the maintenance of normal pregnancy is not yet well understood; however, several cases have been previously reported in which failure to complete normal pregnancy was associated with either hypofibrinogenemia, dysfibrinogenemia, or deficiency in factor XIII (fibrin-stabilizing factor) which is important for the crosslinking of the fibrin. A case of congenital afibrinogenemia is described. The patient, a 22-yr-old woman, who suffered from a moderate hemorrhagic tendency associated with very low (less than 10 mg/dl) plasma fibrinogen levels, had three consecutive spontaneous abortions. In view of the previous cases reported, the question is raised whether patients with low or abnormal fibrinogen should be treated with plasma transfusions in order to maintain a normal pregnancy.

Abortion, Habitual↗
PubMedDate not supplied

Successful treatment of two brothers with congenital afibrinogenemia for splenic rupture using heat- and solvent detergent-treated fibrinogen concentrates.

PURPOSE: This report describes life-threatening spontaneous splenic rupture in two brothers with congenital afibrinogenemia. PATIENTS: Two brothers, aged 11 and 14 years, had intra-abdominal bleeding due to splenic rupture confirmed by ECHO ultrasonography and computed tomography scans. RESULTS: Splenectomy was performed after administration of heat- and solvent-detergent treated fibrinogen concentrates. CONCLUSIONS: Hemostatic treatment for splenic rupture using heat- and solvent detergent-treated fibrinogen concentrates was effective. Careful attention must be paid to the risk of splenic rupture during the growth spurt in physically active children with this rare coagulation disorder.

Adolescent↗
PubMed1980

Congenital afibrinogenemia in 10 offspring of uncle-niece marriages.

Two unrelated large sibships, including 10 cases of congenital afibrinogenemia among 27 sibs, are reported. Both sibships were the product of uncle-niece marriages. They were not selected for any particular clinical manifestation and should provide some information on genetic fitness. Six of the patients died in childhood, two affected boys are adolescent and two affected patients are young women. Two of the four survivors had spontaneous ruptures of the spleen. Fitness in this very rare disease seems to be close to zero and the inheritance is autosomal recessive.

Adolescent↗
PubMed2005

Afibrinogenemia and a circulating antibody against fibrinogen in a Bichon Frise dog.

A 1.5-year-old female Bichon Frise dog was evaluated for a life-threatening hemorrhagic condition that occurred after ovariohysterectomy, requiring 4 whole-blood transfusions. A hemostatic profile, including activated clotting time (ACT), one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), buccal mucosal bleeding time, and specific assays (heat-precipitation microhematocrit method and electroimmunoassay) for fibrinogen, were performed to investigate the coagulopathy. Clotting times for all tests having a fibrin clot endpoint (ACT, OSPT, APTT) and buccal mucosal bleeding time were prolonged. Plasma fibrinogen was not detected by heat-precipitation microhematocrit method or electroimmunoassay. Using the Ellis-Stransky method, a mixture of patient plasma and normal canine plasma with known fibrinogen content yielded substantially less than the calculated fibrinogen concentration, indicating the presence of an interfering substance. The interferent properties of the patient's plasma were retained following heat precipitation at 56 degrees C indicating the absence of a pyroglobulin or an abnormal fibrinogen molecule. Radial immunodiffusion assay using the patient's plasma and activated thrombin confirmed the existence of an inhibitor to the formation of fibrin. Western blot analysis using the patient's plasma identified an IgG antibody that reacted with the Beta- and gamma- but not the Alpha-subunits of canine fibrinogen. Antibody was detected in samples taken 8, 16, and 68 days after the surgery; peak titers were evident at day 16. These results supported a diagnosis of afibrinogenemia with a circulating antibody inhibitor to fibrin clot formation that developed secondary to blood transfusion.

Afibrinogenemia↗
PubMed1996

Congenital afibrinogenemia with successful delivery.

We experienced a case of congenital afibrinogenemia and successfully performed cesarean section with administration of fibrinogen. The patient was administered fibrinogen every week to sustain a fibrinogen level above 60 mg/ dl according to our previously reported first case. Pregnancy course was uneventful, and fetal growth was normal, but unfortunately placental abruption occurred after the spontaneous onset of labor at 37 weeks gestation. The fibrinogen level before labor was 96 mg/dl, but decreased to 33 mg/dl when placental abruption was diagnosed. During and after the operation, it was increased to 147 and 199 mg/dl, respectively, through infusion of 10 g of fibrinogen, and massive bleeding was stopped. Two grams of fibrinogen were infused daily after cesarean section, and postpartum hemorrhage was normal. It is obvious that fibrinogen is an extremely important factor in maintaining pregnancy, and we conclude that fibrinogen level must be at least 60 mg/dl during pregnancy, 120 mg/dl during surgery and 150 mg/dl during labor, if possible as high as 200 mg/dl under the continuous infusion of fibrinogen to prevent placental abruption.

Adult↗
PubMed1979

Delayed-type hypersensitivity skin reactions in congenital afibrinogenemia lack fibrin deposition and induration.

Induration is a characteristic feature of delayed-type hypersensitivity skin reactions and is the usual measure of their intensity. The precise basis of induration has not been established, although activation of the clotting system with consequent fibrin deposition has been clearly implicated. In this study, two subjects with congenital afibrinogenemia, a genetic defect in fibrinogen synthesis, were skin tested with standard microbial antigens: streptokinase-streptodornase, monilia, mumps, and tuberculin purified protein derivative. One positive delayed reaction from each subject was biopsied at 40-48 h and compared with 23 biopsies of similar skin tests in normal volunteers. The eight skin tests in the afibrinogenic subjects lacked induration, although the erythema was similar in size (10-34 mm in diameter), intensity, and time-course to those in normals. Biopsies from the two strongest reactions from the afibrinogenemic subjects showed a typical perivascular mononuclear infiltrate. No more than traces of fibrin/fibrinogen were detected by immunofluorescence, in striking contrast to the abundant fibrin/fibrinogen deposition in 23 positive, indurated reactions in normal subjects. These findings indicate that fibrinogen itself is essential for the development of induration in delayed-type skin reactions in man. As judged by 1-mum sections and fluorescence, this is probably a result of the formation of an extravascular fibrin gel.

Adult↗