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Blood Transfusion = Trasfusione Del... Sep 2008Rare inherited coagulation disorders (RICD) represent a group of inherited deficiencies of clotting factors characterized by a low prevalence in the general population... (Review)
Review
Rare inherited coagulation disorders (RICD) represent a group of inherited deficiencies of clotting factors characterized by a low prevalence in the general population (usually around 1:1,000,000 inhabitants) and, in severe cases (homozygous or compound heterozygotes), by the invariable occurrence of bleeding after invasive procedures if not adequately treated. Furthermore, spontaneous or post-traumatic severe bleeding may occur, as usually observed in patients with haemophilia, although less frequently. The clinical picture of patients with RICD may, however, be complicated by particular situations not encountered in haemophiliacs, such as gynaecological bleeding. The availability of virally-inactivated plasma-derived concentrates of the missing factors, apart from factor V, has rendered surgery and prophylaxis more feasible in these disorders, thus reducing the risk of life-threatening episodes and significantly improving the quality of life of affected patients. The goal for the future is to render this treatment accessible to all patients with these disorders, also to those living in developing countries.
Topics: Abortion, Habitual; Adult; Afibrinogenemia; Blood Coagulation Disorders, Inherited; Blood Coagulation Factors; Blood Loss, Surgical; Child; Female; Genotype; Hemorrhage; Humans; Infant, Newborn; Male; Postoperative Hemorrhage; Prevalence; Secondary Prevention; Virus Activation
PubMed: 19105509
DOI: 10.2450/2008.0036-08 -
International Journal of Molecular... Dec 2017p.R375W (Fibrinogen Aguadilla) is one out of seven identified mutations (Brescia, Aguadilla, Angers, Al du Pont, Pisa, Beograd, and Ankara) causing hepatic storage of...
p.R375W (Fibrinogen Aguadilla) is one out of seven identified mutations (Brescia, Aguadilla, Angers, Al du Pont, Pisa, Beograd, and Ankara) causing hepatic storage of the mutant fibrinogen γ. The Aguadilla mutation has been reported in children from the Caribbean, Europe, Japan, Saudi Arabia, Turkey, and China. All reported children presented with a variable degree of histologically proven chronic liver disease and low plasma fibrinogen levels. In addition, one Japanese and one Turkish child had concomitant hypo-APOB-lipoproteinemia of unknown origin. We report here on an additional child from Turkey with hypofibrinogenemia due to the Aguadilla mutation, massive hepatic storage of the mutant protein, and severe hypo-APOB-lipoproteinemia. The liver biopsy of the patient was studied by light microscopy, electron microscopy (EM), and immunohistochemistry. The investigation included the DNA sequencing of the three and genes and the analysis of the encoded protein structures. Six additional Fibrinogen Storage Disease (FSD) patients with either the Aguadilla, Ankara, or Brescia mutations were investigated with the same methodology. A molecular analysis revealed the fibrinogen gamma p.R375W mutation (Aguadilla) but no changes in the and genes. and genes showed no abnormalities in the other study cases. Light microscopy and EM studies of liver tissue samples from the child led to the demonstration of the simultaneous accumulation of both fibrinogen and APOB in the same inclusions. Interestingly enough, APOB-containing lipid droplets were entrapped within the fibrinogen inclusions in the hepatocytic Endoplasmic Reticulum (ER). Similar histological, immunohistochemical, EM, and molecular genetics findings were found in the other six FSD cases associated with the Aguadilla, as well as with the Ankara and Brescia mutations. The simultaneous retention of fibrinogen and APOB-lipoproteins in FSD can be detected in routinely stained histological sections. The analysis of protein structures unraveled the pathomorphogenesis of this unexpected phenomenon. Fibrinogen gamma chain mutations provoke conformational changes in the region of the globular domain involved in the "end-to-end" interaction, thus impairing the D-dimer formation. Each monomeric fibrinogen gamma chain is left with an abnormal exposure of hydrophobic patches that become available for interactions with APOB and lipids, causing their intracellular retention and impairment of export as a secondary unavoidable phenomenon.
Topics: Afibrinogenemia; Apolipoprotein B-100; Child, Preschool; Endoplasmic Reticulum; Female; Fibrinogen; Hepatocytes; Humans; Hypolipoproteinemias; Liver; Liver Diseases; Male; Middle Aged; Mutation; Protein Conformation; Structure-Activity Relationship
PubMed: 29244742
DOI: 10.3390/ijms18122717 -
The Turkish Journal of Pediatrics 2020In this retrospective report the aim was to present the experience about bleeding characteristics and management of minor surgeries in rare bleeding disorders (RBDs).
BACKGROUND AND OBJECTIVES
In this retrospective report the aim was to present the experience about bleeding characteristics and management of minor surgeries in rare bleeding disorders (RBDs).
METHODS
Twenty-six patients were included; with Factor (F) V, FV+VIII, VII, FXI deficiency and afibrinogenemia. Six of the patients were asymptomatic.
RESULTS
Fifty-three percent of the patients suffered from mucosal bleeding. Life-threatening bleedings were observed only in the patients with afibrinogenemia and good hemostatic control could only be provided with plasma-derived (pd)-fibrinogen concentrate. Twelve of the patients had undergone 17 minor surgeries. In the patients with FVII and FXI deficiencies with plasma F:C activity between 20-47%, there was a history of uneventful tooth extractions, circumcisions and a pilonidal sinus operation performed without any replacement treatment, whereas one patient with plasma F:C activity of FVII 47% had a history of poor hemostatic control during an adeno-tonsillectomy operation. Although some of these patients were asymptomatic to be on the safe side, minor operations were performed with preoperative administration of one dose of (pd)-fibrinogen concentrate to one afibrinogenemia patient, recombinant active FVII (rFVIIa) to 2 FVII deficient patients and fresh frozen plasma (FFP) to 3 FXI deficient and 1 FVII deficient patients plus postoperatively tranexamic acid (TXA) for 5-7 days. Only with one dose of the replacement therapy just before surgeries good hemostatic control was achieved and none of them had bleeding neither during nor after the surgeries.
CONCLUSION
We suggest that minor operations must be performed with preoperative replacement therapies plus 5-7 days of antifibrinolytics under close observation of the hematologist and the surgeon.
Topics: Afibrinogenemia; Child; Hematology; Hemorrhage; Humans; Male; Minor Surgical Procedures; Retrospective Studies
PubMed: 32779411
DOI: 10.24953/turkjped.2020.04.008 -
World Journal of Clinical Cases Nov 2021Venom-induced consumption coagulopathy (VICC) is characterized by coagulation dysfunction accompanied by decreased coagulation factor activity and fibrinogen (FBG)...
BACKGROUND
Venom-induced consumption coagulopathy (VICC) is characterized by coagulation dysfunction accompanied by decreased coagulation factor activity and fibrinogen (FBG) concentrations. We report a patient with VICC caused by snake bite who manifested persistent FBG deficiency without abnormal coagulation factor activity. This information may be helpful in diagnosing and treating VICC.
CASE SUMMARY
A 49-year-old man who had been bitten by a snake 13 h previously was admitted to the Emergency Department of our hospital with visible swelling of a finger and a bleeding puncture site. The provisional diagnosis was VICC, this being made based on persistent bleeding from the puncture site and subcutaneous hemorrhage. Laboratory evidence of coagulation abnormalities, including fibrinolysis, and findings on thromboelastography confirmed VICC. He had persistent afibrinogenemia requiring intravenous infusions of cryoprecipitate and fresh frozen plasma, together with continuous large doses of human FBG. After this treatment, the patient's right upper limb swelling improved significantly and his subcutaneous hemorrhage resolved. All of his abnormal laboratory findings returned to normal by day 25. During 6 months' of follow-up, the patient had no further hemorrhagic events.
CONCLUSION
Hemorrhagic snake venom can result in coagulation dysfunction characterized by persistent FBG deficiency without abnormal coagulation factor activity.
PubMed: 34904110
DOI: 10.12998/wjcc.v9.i33.10355 -
Seminars in Liver Disease Nov 2015
Topics: Afibrinogenemia; Carcinoma, Hepatocellular; Hepatolenticular Degeneration; Humans; Liver Neoplasms
PubMed: 26676817
DOI: 10.1055/s-0035-1568133 -
PloS One 2018Viscoelastic near-patient assays of global hemostasis have been found useful and cost-effective in perioperative settings. Shortcomings of current systems include... (Comparative Study)
Comparative Study
BACKGROUND
Viscoelastic near-patient assays of global hemostasis have been found useful and cost-effective in perioperative settings. Shortcomings of current systems include substantial laboratory intensity, user-dependent reproducibility, relatively large sample volumes, sensitivity to ambient vibration and limited comparability between techniques and devices. The aim of this study was to assess feasibility of a new, resonance-based viscoelastic whole blood methodology (TEG6s) in cardiac surgery with cardiopulmonary bypass (CPB) and to compare the parameters this system produces with the ROTEM delta system and standard coagulation tests.
METHODS
In a prospective evaluation study, twenty-three consecutive cardiac surgery patients underwent hemostasis management according to current guidelines, using the ROTEM delta system and standard coagulation tests. Blood samples were collected prior to CPB before anesthetic induction (pre-CPB), during CPB on rewarming (CPB), and 10 minutes after heparin reversal with protamine (post-CPB). ROTEM and standard coagulation test results were compared with TEG6s parameters, which were concurrently determined using its multi-channel microfluidic cartridge system.
RESULTS
TEG6s provided quantifiable results pre-CPB and post-CPB, but only R (clotting time) of CKH (kaolin with heparinase) was measurable during CPB (full heparinization). Spearman's correlation coefficient (rs) was 0.78 for fibrinogen levels and MA CFF (functional fibrinogen). Correlation of several TEG6s parameters was good (0.77 to 0.91) with MCF FIBTEM, and poor (<0.56) with prothrombin time and activated partial thromboplastin time (<0.44). Rs with platelet count was moderate (0.70, MA CK; 0.73, MA CRT). Accuracy of MA CFF for detection of fibrinogen deficiency < 1.5 g/L was high (ROC-AUC 0.93).
CONCLUSIONS
The TEG6s system, which is based on resonance viscoelastic methodology, appears to be feasible for POC hemostasis assessment in cardiac surgery. Its correlations with standard coagulation parameters are quite similar to those of ROTEM and there is good diagnostic accuracy for fibrinogen levels lower than 1.5 g/L. During full heparinization, TEG6s testing is limited to R measurement. Larger studies are needed to assess superiority over other POC systems.
Topics: Adult; Afibrinogenemia; Aged; Blood Coagulation; Blood Coagulation Tests; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Feasibility Studies; Female; Humans; Intraoperative Complications; Male; Middle Aged; Monitoring, Intraoperative; Practice Guidelines as Topic; Prospective Studies; Reproducibility of Results
PubMed: 30571781
DOI: 10.1371/journal.pone.0209360 -
British Medical Journal Jul 1964
Topics: Abortion, Induced; Afibrinogenemia; Congenital Abnormalities; Emergencies; England; Female; Humans; Labor Presentation; Obstetric Labor Complications; Obstetrics; Postpartum Hemorrhage; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Puerperal Disorders; Resuscitation; Twins; Uterine Hemorrhage; Uterus
PubMed: 14147758
DOI: No ID Found -
Hereditas Feb 2024Congenital fibrinogen disorders are a group of coagulation deficiencies caused by fibrinogen defects and are divided into four types, including afibrinogenemia,...
Congenital fibrinogen disorders are a group of coagulation deficiencies caused by fibrinogen defects and are divided into four types, including afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. In this study, we collected a family with hypofibrinogenemia, and genetics analysis identify a novel pathogenic variants (c.668G > C, p.Arg223Thr) in the FGG gene. And electron microscope observation revealed significant changes in the ultrastructure of fibrin of the proband. Our research expands the phenotypic and genetic spectrum associated with the FGG gene, which would facilitate in genetic counselling and prenatal genetic diagnosis.
Topics: Humans; Afibrinogenemia; Asian People; China; Fibrinogen; Mutation
PubMed: 38374144
DOI: 10.1186/s41065-024-00313-3 -
The Journal of Extra-corporeal... Jun 2022Disseminated intravascular coagulation (DIC) is a life-threatening hematologic derangement characterized by dysregulated thrombin generation and excessive fibrinolysis....
Disseminated intravascular coagulation (DIC) is a life-threatening hematologic derangement characterized by dysregulated thrombin generation and excessive fibrinolysis. However, DIC is poorly characterized in the extracorporeal membrane oxygenation (ECMO) population, and the underlying mechanisms are not well understood. Several mechanisms contribute to DIC in ECMO, including consumption of coagulation factors, acquired von Willebrand's syndrome leading to thrombocytopenia, and hyperfibrinolysis. There are few case reports of DIC in adult ECMO patients. Most are in the context of venoarterial ECMO, which is typically used in the setting of cardiogenic shock and cardiac arrest. These disease states themselves are known to be associated with DIC, liver failure, impaired anticoagulant mechanisms, and increased fibrinolysis. We present an unusual case of a 74-year-old man who developed overt DIC during veno-venous (VV) ECMO. DIC resulted in clinical bleeding and severe hypofibrinogenemia requiring massive cryoprecipitate transfusion of 87 pooled units. When the patient was decannulated from ECMO, his platelet count and fibrinogen concentration improved within 24 hours, suggesting that ECMO was a proximate cause of his DIC.
Topics: Adult; Afibrinogenemia; Aged; Disseminated Intravascular Coagulation; Extracorporeal Membrane Oxygenation; Heart Arrest; Humans; Male
PubMed: 35928342
DOI: 10.1182/ject-148-152 -
Medicina (Kaunas, Lithuania) Jul 2019Both in the pathogenesis of type 2 diabetes (DM 2) and Peripheral Arterial Disease (PAD), a vital role is played by endothelial dysfunction. Metabolic disorders found...
Both in the pathogenesis of type 2 diabetes (DM 2) and Peripheral Arterial Disease (PAD), a vital role is played by endothelial dysfunction. Metabolic disorders found in DM 2 (hyperglycemia, insulin resistance), endothelial dysfunction, and increased inflammation lead to intensified atherothrombosis. The fibrinolysis system comprises a natural compensatory mechanism in case of hypercoagulability. The aim of this study was to assess concentrations of selected fibrinolysis parameters in the blood of patients with symptomatic PAD, including in particular concurrent DM 2 and other cardiovascular factors. In the group of 80 patients with PAD (27 F/53 M) and 30 healthy volunteers (10 F/20 M), the following parameters were measured: Concentrations of fibrinogen, tissue-Plasminogen Activator (t-PA Ag), Plasminogen Activator Inhibitor-1 (PAI-1 Ag), D-dimer, and platelet (PLT) count. In the blood of patients with PAD and concomitant DM 2 significantly higher concentrations of fibrinogen were found in comparison with patients with PAD and without diabetes ( = 0.044). No significant impact was observed in individuals with atherosclerotic complications (manifested by coronary artery disease, atherosclerosis of cerebral arteries) and selected cardiovascular risk factors (smoking, LDL and triglyceride concentrations, BP values) on the levels of t-PA, PAI-1, D-dimer, and PLT count. It was found that t-PA Ag and PAI-1 Ag values tended to rise along with a BMI increase in the subgroups of subjects (with normal body mass, overweight, and obesity), but no statistically significant differences were observed. However, two significant positive correlations were reported between t-PA Ag and BMI, as well as between PAI-1 Ag and BMI. Type 2 diabetes in peripheral arterial disease affects the concentration of fibrinogen causing its increase, which is connected with the inflammation and prothrombotic process in the course of both conditions. The concurrence of atherosclerosis of coronary or cerebral arteries, smoking, LDL and TG concentrations, and BP value do not have a significant impact on the levels of analyzed fibrinolysis parameters. A positive correlation between BMI and t-PA Ag and PAI-1 Ag concentrations needs to be supported in further studies on a larger number of overweight and obese patients.
Topics: Acute Coronary Syndrome; Afibrinogenemia; Aged; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Fibrinogen; Fibrinolysis; Healthy Volunteers; Humans; Male; Middle Aged; Peripheral Arterial Disease; Plasminogen Activator Inhibitor 1; Risk Factors; Tissue Plasminogen Activator
PubMed: 31336615
DOI: 10.3390/medicina55070395