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Blood Coagulation & Fibrinolysis : An... Jan 2024The aim of this study was to evaluate the activated partial thromboplastin time (APTT) and prothrombin time (PT)-based clot waveform analysis (CWA) in patients diagnosed...
The aim of this study was to evaluate the activated partial thromboplastin time (APTT) and prothrombin time (PT)-based clot waveform analysis (CWA) in patients diagnosed with acute promyelocytic leukemia (APL). APTT-based and PT-based CWA parameters of patients diagnosed with APL were analyzed and compared with healthy volunteers. Four APTT-CWA parameters were noted, maximum velocity corresponding to the first peak of the first derivative (max1), maximum acceleration corresponding to the first peak of the second derivative (max2) and the corresponding peak times of max1 and max2 (Tmax1, Tmax2). For the PT-CWA, two PT-CWA parameters were noted, maximum velocity (max1') and the corresponding timing (Tmax1'). The results were expressed in medians. Mann-Whitney U test was used to compare the CWA parameters. Correlations were examined using the Spearman correlation test. Tmax1 and Tmax2 were significantly prolonged in patients with APL in comparison with healthy volunteers. Although max1 and max2 were lower in APL patients compared with healthy volunteers, no significant difference was noted. There was a strong and significant correlation between the DIC score and the parameters max1, max2 and max1' and a very strong and significant correlation between fibrinogen levels and max1, max2 and max1'. When comparing DIC patients with hypofibrinogenemia and DIC without hypofibrinogenemia, a significant difference was noted in max1, max2, Tmax1 and Tmax2. The APTT and PT-based CWA analysis is a good tool to evaluate the bleeding tendency in APL, as it offers a novel approach for evaluating global hemostasis, predicting the bleeding risk and delivering improvements to APL patients management.
Topics: Humans; Leukemia, Promyelocytic, Acute; Afibrinogenemia; Blood Coagulation Tests; Prothrombin Time; Partial Thromboplastin Time; Thrombosis
PubMed: 37994627
DOI: 10.1097/MBC.0000000000001265 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Nov 2023To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD).
OBJECTIVE
To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD).
METHODS
Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation Surveyor software.
RESULTS
The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature.
CONCLUSION
This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".
Topics: Female; Humans; Afibrinogenemia; East Asian People; Fibrinogen; Mothers; Mutation; Pedigree
PubMed: 37906135
DOI: 10.3760/cma.j.cn511374-20220112-00027 -
Scientific Reports Oct 2023Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition in children with sepsis. We herein aimed to identify clinical and laboratory...
Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition in children with sepsis. We herein aimed to identify clinical and laboratory predictors of HLH in children with sepsis. We conducted a retrospective study of 568 children with sepsis admitted to Guangdong Women and Children Hospital from January 2019 to June 2022. HLH, while rare (6.34%), proved to be a highly fatal complication (37.14%) in children with sepsis. Children with HLH had higher levels of aspartate aminotransferase, lactate dehydrogenase, triglycerides, and ferritin than children without HLH; conversely, they displayed decreased levels of neutrophils, hemoglobin, platelets, fibrinogen, and albumin. Additionally, the HLH group showed higher rates of prolonged fever (> 10 days), hepatomegaly, and splenomegaly than the non-HLH group. Our retrospective analysis identified hypofibrinogenemia (OR = 0.440, P = 0.024) as an independent predictor for the development of HLH in patients with sepsis. The optimal cutoff value for fibrinogen was found to be < 2.43 g/L. The area under the curve for diagnosing HLH was 0.80 (95% confidence interval: 0.73-0.87, P < 0.0001), with a sensitivity of 72.41% and specificity of 76.27%. Thus, hypofibrinogenemia emerges as a potentially valuable predictor for HLH in children with sepsis.
Topics: Humans; Child; Female; Lymphohistiocytosis, Hemophagocytic; Retrospective Studies; Afibrinogenemia; Sepsis; Fibrinogen
PubMed: 37863910
DOI: 10.1038/s41598-023-44628-z -
Injury Jan 2024Acute Traumatic Coagulopathy (ATC) is a complex pathological process that is associated with patient mortality and increased blood transfusion requirements. It is... (Observational Study)
Observational Study
BACKGROUND
Acute Traumatic Coagulopathy (ATC) is a complex pathological process that is associated with patient mortality and increased blood transfusion requirements. It is evident on hospital arrival, but there is a paucity of information about the nature of ATC and the characteristics of patients that develop ATC in the pre-hospital setting. The objective of this study was to describe the nature and timing of coagulation dysfunction in a cohort of injured patients and to report on patient and pre-hospital factors associated with the development of ATC in the field.
METHODS
This was a prospective observational study of a convenience sample of trauma patients. Patients had blood taken during the pre-hospital phase of care and evaluated for derangements in Conventional Coagulation Assays (CCA) and Rotational Thromboelastometry (ROTEM). Associations between coagulation derangement and pre-hospital factors and patient outcomes were evaluated.
RESULTS
A total of 216 patients who had either a complete CCA or ROTEM were included in the analysis. One hundred and eighty (83 %) of patients were male, with a median injury severity score of 17 [interquartile range (IQR) 10-27] and median age of 34 years [IQR = 25.0-52.0]. Hypofibrinogenemia was the predominant abnormality seen, (CCA Hypofibrinogenemia: 51/193, 26 %; ROTEM hypofibrinogenemia: 65/204, 32 %). Increased CCA derangement, the presence of ROTEM coagulopathy, worsening INR, worsening FibTEM and decreasing fibrinogen concentration, were all associated with both mortality and early massive transfusion.
CONCLUSION
Clinically significant, multifaceted coagulopathy develops early in the clinical course, with hypofibrinogenemia being the predominant coagulopathy. In keeping with the ED literature, pre-hospital coagulation dysfunction was associated with mortality and early massive transfusion. Further work is required to identify strategies to identify and guide the pre-hospital management of the coagulation dysfunction seen in trauma.
Topics: Humans; Male; Adult; Middle Aged; Female; Afibrinogenemia; Australia; Blood Coagulation; Blood Coagulation Disorders; Thrombelastography; Hospitals; Wounds and Injuries
PubMed: 37858445
DOI: 10.1016/j.injury.2023.111124 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Oct 2023To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.
OBJECTIVE
To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.
METHODS
Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of and and their flanks were amplified by PCR and sequenced to search for gene mutations.
RESULTS
The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were gene g.9308A/G (p.AαThr331Ala) and gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery.
CONCLUSION
Heterozygous mutation of 6233G/A (p.AαArg35His) of gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Topics: Humans; Child; Female; Fibrinogen; Pedigree; Afibrinogenemia; Mutation; Blood Transfusion
PubMed: 37846702
DOI: 10.19746/j.cnki.issn.1009-2137.2023.05.034 -
Blood Coagulation & Fibrinolysis : An... Dec 2023Congenital fibrinogen deficiencies (CFD) are a group of rare bleeding disorders (RBD). Afibrinogenemia as a subclass of these disorders would occurs as a result of...
BACKGROUND
Congenital fibrinogen deficiencies (CFD) are a group of rare bleeding disorders (RBD). Afibrinogenemia as a subclass of these disorders would occurs as a result of mutations in fibrinogen gene. Here in, the sequences of Aα chain of fibrinogen (FGA) in patients with inherited afibrinogenemia disorder in south-eastern of Iran were analysed.
METHODS
The FGA gene exons were amplified using PCR method and the DNA sequences were analysed to study the mutations in Aα chain of Fibrinogen.
RESULTS
Results showed that there was no large deletion in FGA gene. Although a frame shift mutation: c.196_197insT p.Ser66PhefsX10 in a patient and a novel mutation of IVS2-1G>A in two other patients were detected which were different from those detected in European population.
CONCLUSION
Different mutations are responsible of afibrinogenemia deficiency which requires more relevant studies for confirmation. The type and distribution of mutations in fibrinogen gene in Iranian patients is significantly different with reported mutations in European patients.
Topics: Humans; Afibrinogenemia; Iran; Genotype; Fibrinogen; Mutation
PubMed: 37823427
DOI: 10.1097/MBC.0000000000001260 -
Pharmacology 2023The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant...
INTRODUCTION
The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs.
METHODS
We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without.
RESULTS
This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline.
CONCLUSION
A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.
Topics: Humans; Tigecycline; Anti-Bacterial Agents; Retrospective Studies; Fibrinolytic Agents; Cefoperazone; Sulbactam; Afibrinogenemia; Hemorrhage; Fibrinogen; Hemoglobins
PubMed: 37751720
DOI: 10.1159/000532001 -
Journal of Neurosurgery. Pediatrics Nov 2023Hematological consequences of novel antiseizure medications (ASMs) or combined therapies are rarely reported, especially in pediatric patients undergoing surgery for...
OBJECTIVE
Hematological consequences of novel antiseizure medications (ASMs) or combined therapies are rarely reported, especially in pediatric patients undergoing surgery for epilepsy. This study aimed to assess the prevalence and risk factors of coagulation dysfunction in this population and evaluate their relationship with intra- and postoperative bleeding.
METHODS
Three hundred ninety children who underwent surgery for epilepsy and 104 children without epilepsy who underwent nonepilepsy surgery at the authors' center were included in the study. The authors retrospectively collected and analyzed the following clinical data: sex, age, weight, course of epilepsy, antiseizure therapy, first laboratory data after admission, and transfusion-related data.
RESULTS
ASMs were responsible for the higher incidence of coagulation dysfunction in pediatric epilepsy surgery patients. Low body weight (OR 0.95, 95% CI 0.92-0.98) and valproic acid (VPA) therapy (OR 5.13, 95% CI 3.25-8.22) were the most relevant factors leading to coagulation dysfunction. The most common hematological side effects of VPA were thrombocytopenia and hypofibrinogenemia, whereas low body weight was only associated with hypofibrinogenemia. Both VPA and low body weight increased the need for intra- or postoperative transfusion (p < 0.001).
CONCLUSIONS
Pediatric epilepsy surgery patients often take multiple ASMs, resulting in an increased incidence of coagulopathy. VPA levels and low body weight were found to be the main influential factors associated with an increased risk of coagulation dysfunction. Platelet and fibrinogen levels were the main indices that were affected. Both VPA and low body weight were relevant to additional surgery-related transfusion, necessitating the need for increased awareness of preoperative coagulopathy before pediatric epilepsy surgery. Clinical trial registration no.: NCT05675254 (ClinicalTrials.gov).
Topics: Humans; Child; Afibrinogenemia; Prevalence; Retrospective Studies; Epilepsy; Blood Coagulation Disorders; Valproic Acid; Risk Factors; Body Weight; Anticonvulsants
PubMed: 37728406
DOI: 10.3171/2023.6.PEDS23196 -
BMC Pregnancy and Childbirth Sep 2023Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by... (Review)
Review
BACKGROUND
Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by postpartum haemorrhage (PPH).
CASE
Two women diagnosed as preeclampsia and hypofibrinogenemia developed severe PPH after undergoing Cesarean sections. Besides supplement with fibrinogen concentrate and supportive treatment, the second patient got administration of heparin after delivery and bleeding was stopped. The haemorrhage in case 1 didn't disappear until an hysterectomy. The two patients both recovered and were discharged soon.
CONCLUSIONS
Severe preeclampsia patients with hypofibrinogenemia could suffer PPH. It's necessary to detect and master coagulation function. Heparin could be considered to balance hypercoagulation and hypocoagulation to avoid catastrophic haemorrhage and hysterectomy.
Topics: Pregnancy; Humans; Female; Afibrinogenemia; Pre-Eclampsia; Fibrinogen; Postpartum Hemorrhage; Heparin
PubMed: 37658306
DOI: 10.1186/s12884-023-05965-z -
Cureus Jul 2023Afibrinogenemia is an extremely rare bleeding disorder characterized by the absence or severe deficiency of fibrinogen, a major protein involved in the regulation of...
Afibrinogenemia is an extremely rare bleeding disorder characterized by the absence or severe deficiency of fibrinogen, a major protein involved in the regulation of blood clotting. This disorder can have both hemorrhagic and/or thrombotic manifestations. We present the case of a female neonate who was diagnosed with congenital afibrinogenemia within the first two weeks of life. The patient presented with persistent bleeding from the umbilical stump, prompting a thorough investigation and workup. Early diagnosis and management were essential to preventing life-threatening bleeding events.
PubMed: 37637664
DOI: 10.7759/cureus.42542