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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 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Jan 2022To improve the understanding and diagnosis and treatment of congenital dysfibrinogenemia (CD) through analyzing the clinical data of a pediatric patient and his pedigree.
OBJECTIVE
To improve the understanding and diagnosis and treatment of congenital dysfibrinogenemia (CD) through analyzing the clinical data of a pediatric patient and his pedigree.
METHODS
The clinical manifestations, laboratory findings and treatment of a case of CD diagnosed at West China Second University Hospital, Sichuan University and those of its pedigree members were analyzed, and genetic tracing and follow-up were conducted on the patient and its pedigree.
RESULTS
The child has no clinical manifestations at the time of admission. Coagulation function examination showed normal prothrombin time (PT), normal activated partial thrombin time (APTT), significantly prolonged thrombin time (TT), fibrinogen activity (Fg: C<0.5 g/L) measured with the Clauss method, and fibrinogen antigen (Fg: Ag) measured at 2.8 g/L with PT algorithm. Gene sequencing results showed that heterozygous missense mutation c.901C>T (p.Arg301Cys) in exon 8 of gene. Combined with the family history, the child was diagnosed with CD. During the follow-up of 4 months, the patient did not present bleeding, abnormal coagulation or thrombosis, and the coagulation function did not show significant changes compared with the findings obtained on admission.
CONCLUSION
The diagnosis of CD is confirmed mainly based on genetic testing and the treatment is characterized by the principle of precise individualized treatment. No special treatment is needed for patients presenting no clinical manifestations. However, it is important to provide thorough prenatal diagnosis and follow-up services for female patients planning for pregnancy so as to prevent miscarriage and complications caused by postpartum coagulation dysfunction.
Topics: Afibrinogenemia; Child; Female; Fibrinogen; Heterozygote; Humans; Mutation; Pedigree
PubMed: 35048620
DOI: 10.12182/20220160201 -
Blood Mar 2022Genetic variants within the fibrinogen Aα chain encoding the αC-region commonly result in hypodysfibrinogenemia in patients. However, the (patho)physiological...
Genetic variants within the fibrinogen Aα chain encoding the αC-region commonly result in hypodysfibrinogenemia in patients. However, the (patho)physiological consequences and underlying mechanisms of such mutations remain undefined. Here, we generated Fga270 mice carrying a premature termination codon within the Fga gene at residue 271. The Fga270 mutation was compatible with Mendelian inheritance for offspring of heterozygous crosses. Adult Fga270/270 mice were hypofibrinogenemic with ∼10% plasma fibrinogen levels relative to FgaWT/WT mice, linked to 90% reduction in hepatic Fga messenger RNA (mRNA) because of nonsense-mediated decay of the mutant mRNA. Fga270/270 mice had preserved hemostatic potential in vitro and in vivo in models of tail bleeding and laser-induced saphenous vein injury, whereas Fga-/- mice had continuous bleeding. Platelets from FgaWT/WT and Fga270/270 mice displayed comparable initial aggregation following adenosine 5'-diphosphate stimulation, but Fga270/270 platelets quickly disaggregated. Despite ∼10% plasma fibrinogen, the fibrinogen level in Fga270/270 platelets was ∼30% of FgaWT/WT platelets with a compensatory increase in fibronectin. Notably, Fga270/270 mice showed complete protection from thrombosis in the inferior vena cava stasis model. In a model of Staphylococcus aureus peritonitis, Fga270/270 mice supported local, fibrinogen-mediated bacterial clearance and host survival comparable to FgaWT/WT, unlike Fga-/- mice. Decreasing the normal fibrinogen levels to ∼10% with small interfering RNA in mice also provided significant protection from venous thrombosis without compromising hemostatic potential and antimicrobial function. These findings both reveal novel molecular mechanisms underpinning fibrinogen αC-region truncation mutations and highlight the concept that selective fibrinogen reduction may be efficacious for limiting thrombosis while preserving hemostatic and immune protective functions.
Topics: Afibrinogenemia; Animals; Blood Platelets; Fibrinogen; Hemostasis; Mice; Mice, Knockout; Mutation; Platelet Aggregation; Thrombosis
PubMed: 34905618
DOI: 10.1182/blood.2021012537 -
Experimental and Clinical... Mar 2021Liver transplant has occasionally been performed in the presence of congenital afibrinogenemia and has been rarely used to treat it. Historically, to safely manage...
Liver transplant has occasionally been performed in the presence of congenital afibrinogenemia and has been rarely used to treat it. Historically, to safely manage coagulopathy during transplant, these patients have been administered a combination of fresh frozen plasma and cryoprecipitate. In this case report, we discuss the first reported use of recombinant fibrinogen to treat such a patient and the decision-making process considered to balance the thrombotic and hemorrhagic risks.
Topics: Afibrinogenemia; Fibrinogen; Humans; Liver Transplantation; Recombinant Proteins
PubMed: 29766777
DOI: 10.6002/ect.2017.0316 -
The Journal of Pediatric Pharmacology... 2023Fibrinogen deficiencies in neonates can lead to bleeding complications. In this report, we describe a case of congenital afibrinogenemia in a newborn with critical...
Fibrinogen deficiencies in neonates can lead to bleeding complications. In this report, we describe a case of congenital afibrinogenemia in a newborn with critical pulmonary stenosis who presented with bilateral cephalohematomas after an uncomplicated delivery. The initial use of cryoprecipitate was followed by administration of fibrinogen concentrate. We estimated a half-life of 24 to 48 hours with the concentrate product. This patient received fibrinogen replacement and had a subsequent successful cardiac repair. The drug's shorter half-life in this neonate contrasts with prior reports of longer half-life in older patients and is important to note in treating future neonatal patients with this diagnosis.
PubMed: 37303762
DOI: 10.5863/1551-6776-28.3.268 -
Toxins Aug 2022Envenomations that are caused by snakebites are mostly accompanied by venom-induced consumption coagulopathy (VICC) with defibrination. The clinical course of VICC is...
Envenomations that are caused by snakebites are mostly accompanied by venom-induced consumption coagulopathy (VICC) with defibrination. The clinical course of VICC is well described; however, reports about its detailed effects in the hemocoagulation systems of patients are sparse. In this pilot study, we prospectively analyzed the changes in plasma fibrinogen that were caused by the envenomation of six patients by five non-European snakes. Western blot analysis was employed and fibrinogen fragments were visualized with the use of specific anti-human fibrinogen antibodies. All of the studied subjects experienced hypo- or afibrinogenemia. The western blot analysis demonstrated fibrinogenolysis of the fibrinogen chains in all of the cases. Fibrinogenolysis was considered to be a predominant cause of defibrination in , , and envenomation; while, in the cases of VICC that were caused by and envenomation, the splitting of the fibrinogen chains was present less significantly.
Topics: Animals; Antivenins; Disseminated Intravascular Coagulation; Fibrinogen; Humans; Pilot Projects; Snake Bites; Venoms; Viperidae
PubMed: 36006200
DOI: 10.3390/toxins14080538 -
Placenta May 2023SARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and...
INTRODUCTION
SARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. Diffuse placental damage of this kind is rare, but can sometimes lead to obstetric complications, such as intrauterine fetal death (IUFD). The objectives of this study were to identify possible predictors of severe placental lesions.
METHODS
We retrospectively studied 96 placentas from SARS-Cov-2 positive pregnant women who gave birth between March 2020 and March 2022. Cases with and without severe placental lesions were compared in terms of clinical and laboratory findings.
RESULTS
Twelve of the 96 patients had severe placental lesions. There was no significant association with diabetes, obesity or severe clinical maternal disease. In contrast, presence of severe placental lesions was significantly associated with neonatal intensive care, cesarean section, prematurity, IUFD, intrauterine growth restriction (IUGR), gestational age, maternal hypofibrinogenemia and thrombocytopenia. No cases of severe placental lesions were observed in vaccinated patients or in those with the Omicron variant.
DISCUSSION
In these patients, severe placental lesions due to SARS-Cov-2 were significantly associated with the presence of coagulation abnormalities (hypofibrinogenemia and thrombocytopenia), IUGR and gestational age. These results support laboratory and ultrasound monitoring of these parameters in pregnant women with SARS-Cov-2 infection, especially during the second trimester, to predict potential negative fetal outcomes.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Placenta; COVID-19; SARS-CoV-2; Pregnant Women; Cesarean Section; Retrospective Studies; Afibrinogenemia; Stillbirth; Fetal Death; Pregnancy Complications, Infectious; Fetal Growth Retardation
PubMed: 36963271
DOI: 10.1016/j.placenta.2023.03.004 -
Acta Medica Portuguesa Dec 1998The authors present a case of congenital afibrinogenemia. A review of the literature is made, and some aspects of this rare inherited coagulation disorder are suggested... (Review)
Review
The authors present a case of congenital afibrinogenemia. A review of the literature is made, and some aspects of this rare inherited coagulation disorder are suggested and commented on.
Topics: Afibrinogenemia; Cerebral Hemorrhage; Humans; Infant, Newborn; Male
PubMed: 10192988
DOI: No ID Found -
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 -
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