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International Journal of Clinical... Oct 2023We describe a case of acute pancreatitis (AP) and hypofibrinogenemia associated with drug treatment with the aim to increase awareness of uncommon yet possibly...
OBJECTIVE
We describe a case of acute pancreatitis (AP) and hypofibrinogenemia associated with drug treatment with the aim to increase awareness of uncommon yet possibly life-threatening adverse reactions of tigecycline and furosemide.
CASE SUMMARY
A 75-year-old Chinese male was hospitalized for acute non-ST-elevation myocardial infarction and acute heart failure. The patient underwent successful percutaneous coronary intervention and MitraClip. Furosemide was taken since admission. Because was detected in the blood and sputum, the patient was treated with tigecycline from the 14 day of hospitalization. Abnormal pancreatitis parameters were observed, and pancreatic CT was undertaken 12 days after the treatment of tigecycline. AP was diagnosed and symptomatic treatment was carried out, but no significant improvement was observed. On the 33 day of hospitalization, the patient presented with acute upper gastrointestinal bleeding and decreased levels of fibrinogen and platelets. After withdrawal of tigecycline, the coagulation and pancreatitis parameters improved significantly. However, the pancreatitis parameters increased again after stopping somatostatin. Therefore, somatostatin was given again for 1 day, and furosemide was discontinued. After that, the pancreatitis parameters returned to baseline levels after a slight recovery.
CONCLUSION
Clinicians should pay attention to clinical signs, symptoms, and pancreatic enzymes during tigecycline or furosemide treatment, especially when used in combination. In addition, regular monitoring of fibrinogen and platelet count during tigecycline treatment is suggested.
Topics: Male; Humans; Aged; Tigecycline; Anti-Bacterial Agents; Afibrinogenemia; Furosemide; Minocycline; Acute Disease; Pancreatitis; Fibrinogen; Acinetobacter baumannii
PubMed: 37548456
DOI: 10.5414/CP204337 -
Hamostaseologie Dec 2023Our study aimed to analyze the phenotype and genotype of a pedigree with inherited dysfibrinogenemia, and preliminarily elucidate the probable pathogenesis.
OBJECTIVE
Our study aimed to analyze the phenotype and genotype of a pedigree with inherited dysfibrinogenemia, and preliminarily elucidate the probable pathogenesis.
METHODS
The one-stage clotting method was used to test the fibrinogen activity (FIB:C), whereas immunoturbidimetry was performed to quantify the fibrinogen antigen (FIB:Ag). Furthermore, DNA sequence analysis was conducted to confirm the site of mutation. Conservation analysis and protein model analysis were performed using online bioinformatics software.
RESULTS
The FIB:C and FIB:Ag of the proband were 1.28 and 2.20 g/L, respectively. Gene analysis revealed a heterozygous c.293C > A (p.BβAla68Asp) mutation in . Bioinformatics and modeling analysis suggested that the missense mutation could potentially have a deleterious effect on fibrinogen.
CONCLUSION
The BβAla68Asp mutation in exon 2 of may account for the reduced FIB:C levels observed in the pedigree. To our knowledge, this point mutation is the first report in the world.
Topics: Humans; Fibrinogen; Afibrinogenemia; Genotype; Mutation, Missense; Mutation; Hemostatics; Pedigree
PubMed: 37516116
DOI: 10.1055/a-2116-8957 -
Transfusion Aug 2023Cryoprecipitate (CRY) is widely used for treating acquired hypofibrinogenemia. During our study to determine an optimal preparation method, we noticed that the...
BACKGROUND
Cryoprecipitate (CRY) is widely used for treating acquired hypofibrinogenemia. During our study to determine an optimal preparation method, we noticed that the measurement of fibrinogen concentration in CRY had a risk of overestimation. We analyzed this condition and mechanism.
STUDY DESIGN AND METHODS
CRY was prepared from fresh frozen plasma (FFP) under four conditions: A, 30 h thawing time, 2 cycles; B, 24 h thawing time, 2 cycles; C, 30 h thawing time, 1 cycle; and D, 24 h thawing time, 1 cycle. Then, fibrinogen concentrations in CRY and cryosupernatant (CS) were measured by the Clauss method.
RESULTS
Purification (CRY/CRY+CS) and recovery (CRY/FFP) rates in CRY prepared under 2-cycle conditions were higher than those under 1 cycle. However, recovery rates often exceeded 100%, particularly in the case of CRY prepared under A condition, and fibrinogen concentrations calculated by direct measurement were higher than those indirectly calculated from FFP and CS, suggesting an overestimation of fibrinogen values. The level of soluble fibrin monomer complex was considerably higher in CRY prepared under A than under D condition, indicating that CRY adopted a hypercoagulated state. We further found that repeated thawing/freezing increased fibrinogen values as measured by the Clauss method while mechanical vortexing did not.
DISCUSSION
Our findings suggest that direct assessment of fibrinogen contents in CRY prepared by repeated freeze-thawing with a longer thawing period presents a higher risk of overestimation. For the purpose of quality control, we propose an alternative method to indirectly estimate fibrinogen concentrations in CRY from those of CS and FFP.
Topics: Humans; Fibrinogen; Freezing; Hemostatics; Afibrinogenemia; Plasma; Hematologic Agents
PubMed: 37450885
DOI: 10.1111/trf.17483 -
Hamostaseologie Dec 2023Inherited dysfibrinogenemia is a qualitative defect of fibrinogen caused by various mutations among three fibrinogen genes. Dysfibrinogenemia can be associated with...
INTRODUCTION
Inherited dysfibrinogenemia is a qualitative defect of fibrinogen caused by various mutations among three fibrinogen genes. Dysfibrinogenemia can be associated with an increased risk of thrombosis, bleeding, or both. Here, we report a 36-year-old female with dysfibrinogenemia who experienced two successful pregnancies under thromboprophylaxis after cerebral venous sinus thrombosis (CVST).
PATIENTS AND METHODS
In addition to plasmatic coagulation tests, fibrinogen genes , , and were screened using direct genomic DNA sequencing. The structural-functional implications of the detected mutation were analyzed in silico.
RESULTS
Inherited dysfibrinogenemia was diagnosed in an index patient after CVST in a risk situation. Anticoagulation with warfarin was stopped after 12 months when the first pregnancy was planned. Pregnancy and spontaneous delivery (2020) was uncomplicated. A second pregnancy was interrupted because of acute cytomegalovirus infection and the third pregnancy was successful in 2022. Pregnancies were accompanied by thromboprophylaxis with enoxaparin 40 mg once daily until 6 weeks postpartum. Substitution of fibrinogen has not become necessary in the index patient so far. Genetic analysis revealed a novel missense mutation (p. Arg510Cys) in the gene ("fibrinogen Bonn") in the index patient, as well as an asymptomatic sister, and their father who experienced recurrent pulmonary embolism. Surface exposure of wild-type Arg510 suggested the mutated Cys510 to form nonnative disulfide bonds with surface-exposed reactive cysteines from other plasma proteins like albumin leading to formation of aggregates and impaired fibrinolysis.
CONCLUSIONS
Fibrinogen Bonn might be associated with an increased risk of thrombosis, possibly due to impaired polymerization.
Topics: Pregnancy; Female; Humans; Adult; Fibrinogen; Anticoagulants; Venous Thromboembolism; Afibrinogenemia; Venous Thrombosis; Mutation; Thrombosis; Hemostatics
PubMed: 37442158
DOI: 10.1055/a-2094-7191 -
Journal of Thrombosis and Haemostasis :... Oct 2023Conventional clotting tests are not expeditious enough to allow timely targeted interventions in trauma, and current point-of-care analyzers, such as rotational...
BACKGROUND
Conventional clotting tests are not expeditious enough to allow timely targeted interventions in trauma, and current point-of-care analyzers, such as rotational thromboelastometry (ROTEM), have limited sensitivity for hyperfibrinolysis and hypofibrinogenemia.
OBJECTIVES
To evaluate the performance of a recently developed global fibrinolysis capacity (GFC) assay in identifying fibrinolysis and hypofibrinogenemia in trauma patients.
METHODS
Exploratory analysis of a prospective cohort of adult trauma patients admitted to a single UK major trauma center and of commercially available healthy donor samples was performed. Lysis time (LT) was measured in plasma according to the GFC manufacturer's protocol, and a novel fibrinogen-related parameter (percentage reduction in GFC optical density from baseline at 1 minute) was derived from the GFC curve. Hyperfibrinolysis was defined as a tissue factor-activated ROTEM maximum lysis of >15% or LT of ≤30 minutes.
RESULTS
Compared to healthy donors (n = 19), non-tranexamic acid-treated trauma patients (n = 82) showed shortened LT, indicative of hyperfibrinolysis (29 minutes [16-35] vs 43 minutes [40-47]; p < .001). Of the 63 patients without overt ROTEM-hyperfibrinolysis, 31 (49%) had LT of ≤30 minutes, with 26% (8 of 31) of them requiring major transfusions. LT showed increased accuracy compared to maximum lysis in predicting 28-day mortality (area under the receiver operating characteristic curve, 0.96 [0.92-1.00] vs 0.65 [0.49-0.81]; p = .001). Percentage reduction in GFC optical density from baseline at 1 minute showed comparable specificity (76% vs 79%) to ROTEM clot amplitude at 5 minutes from tissue factor-activated ROTEM with cytochalasin D in detecting hypofibrinogenemia but correctly reclassified >50% of the patients with false negative results, leading to higher sensitivity (90% vs 77%).
CONCLUSION
Severe trauma patients are characterized by a hyperfibrinolytic profile upon admission to the emergency department. The GFC assay is more sensitive than ROTEM in capturing hyperfibrinolysis and hypofibrinogenemia but requires further development and automation.
Topics: Adult; Humans; Fibrinolysis; Afibrinogenemia; Thromboplastin; Prospective Studies; Blood Coagulation Disorders; Thrombelastography; Wounds and Injuries
PubMed: 37207863
DOI: 10.1016/j.jtha.2023.05.005 -
Journal of Thrombosis and Haemostasis :... Aug 2023Women with hereditary fibrinogen disorders (HFDs) seem to be at an increased risk of adverse obstetrical outcomes, but epidemiologic data are limited.
BACKGROUND
Women with hereditary fibrinogen disorders (HFDs) seem to be at an increased risk of adverse obstetrical outcomes, but epidemiologic data are limited.
OBJECTIVES
We aimed to determine the prevalence of pregnancy complications; the modalities and management of delivery; and the postpartum events in women with hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia.
METHODS
We conducted a retrospective and prospective multicentric international study.
RESULTS
A total of 425 pregnancies were investigated from 159 women (49, 95, and 15 cases of hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia, respectively). Overall, only 55 (12.9%) pregnancies resulted in an early miscarriage, 3 (0.7%) resulted in a late miscarriage, and 4 (0.9%) resulted in an intrauterine fetal death. The prevalence of live birth was similar among the types of HFDs (P = .31). Obstetrical complications were observed in 54 (17.3%) live birth pregnancies, including vaginal bleeding (14, 4.4%), retroplacental hematoma (13, 4.1%), and thrombosis (4, 1.3%). Most deliveries were spontaneous (218, 74.1%) with a vaginal noninstrumental delivery (195, 63.3%). A neuraxial anesthesia was performed in 116 (40.4%) pregnancies, whereas general or no anesthesia was performed in 71 (16.6%) and 129 (44.9%) pregnancies, respectively. A fibrinogen infusion was administered in 28 (8.9%) deliveries. Postpartum hemorrhages were observed in 62 (19.9%) pregnancies. Postpartum venous thrombotic events occurred in 5 (1.6%) pregnancies. Women with hypofibrinogenemia were at an increased risk of bleeding during the pregnancy (P = .04).
CONCLUSION
Compared with European epidemiologic data, we did not observe a greater frequency of miscarriage, while retroplacental hematoma, postpartum hemorrhage, and thrombosis were more frequent. Delivery was often performed without locoregional anesthesia. Our findings highlight the urgent need for guidance on the management of pregnancy in HFDs.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Afibrinogenemia; Fibrinogen; Gastrointestinal Hemorrhage; Hematoma; Hemostatics; Postpartum Hemorrhage; Prospective Studies; Retrospective Studies; Thrombosis
PubMed: 37172732
DOI: 10.1016/j.jtha.2023.04.035 -
British Journal of Clinical Pharmacology Sep 2023Fibrinogen is the key substrate for coagulation. Fibrinogen pharmacokinetics (PK) after single doses of fibrinogen concentrate (FC), using modelling approaches, has only...
AIMS
Fibrinogen is the key substrate for coagulation. Fibrinogen pharmacokinetics (PK) after single doses of fibrinogen concentrate (FC), using modelling approaches, has only been evaluated in congenital afibrinogenaemic patients. The aims of this study are to characterize the fibrinogen PK in patients with acquired-chronic (cirrhosis) or acute-hypofibrinogenaemia (critical haemorrhage), showing endogenous production. Influencing factors of differences on the fibrinogen PK between subpopulations will be identified.
METHODS
A total of 428 time-concentration values from 132 patients were recorded. Eighty-two out of 428 values were from 41 cirrhotic patients administered with placebo and 90 out of 428 were from 45 cirrhotic patients that were given FC, 161 out of 428 values were from 14 afibrinogenaemic patients and 95 out of 428 values were from 32 severe acute trauma haemorrhagic patients. A turnover model that accounted for endogenous production and exogenous dose was fitted using NONMEM74. The production rate (Ksyn), distribution volume (V), plasma clearance (CL) and concentration yielding to 50% of maximal fibrinogen production (EC50) were estimated.
RESULTS
Fibrinogen disposition was described by a one-compartment model with CL and V values of 0.0456 L·h and 4.34 L·70 kg , respectively. Body weight was statistically significant in V. Three different Ksyn values were identified that increased from 0.00439 g·h (afibrinogenaemia), to 0.0768 g·h (cirrhotics) and 0.1160 g·h (acute severe trauma). EC50 was of 0.460 g·L .
CONCLUSIONS
This model will be key as a support tool for dose calculation to achieve specified target fibrinogen concentrations, in each of the studied populations.
Topics: Humans; Fibrinogen; Afibrinogenemia; Hemorrhage; Blood Coagulation; Liver Cirrhosis
PubMed: 37041125
DOI: 10.1111/bcp.15741 -
The American Surgeon Aug 2023Uncontrolled hemorrhage accounts for up to 40% of trauma-related mortality. Previous reports demonstrate that decreased fibrinogen levels during traumatic hemorrhage are...
INTRODUCTION
Uncontrolled hemorrhage accounts for up to 40% of trauma-related mortality. Previous reports demonstrate that decreased fibrinogen levels during traumatic hemorrhage are associated with worse outcomes. Cryoprecipitate is used to replace fibrinogen for patients in hemorrhagic shock undergoing massive transfusion (MT), though the optimal ratio of cryoprecipitate to fresh frozen plasma (FFP), packed red blood cells (PRBCs), and platelets remains undefined. The purpose of this study is to investigate the effect of admission fibrinogen level and the use of cryoprecipitate on outcomes in trauma patients undergoing MT.
METHODS
A prospective practice management guideline was established to obtain fibrinogen levels on adult trauma patients undergoing MT at a level I trauma center from December 2019 to December 2021. Ten units of cryoprecipitate were administered every other round of MT. Thromboelastography (TEG) was also obtained at the initiation and completion of MT. Patient demographic, injury, transfusion, and outcome data were collected. Hypofibrinogenemic (<200 mg/dL) patients at initiation of MT were compared to patients with a level of 200 mg/dL or greater.
RESULTS
A total of 96 out of 130 patients met criteria and underwent MT with a median admission fibrinogen of 170.5 mg/dL. Hypofibrinogenemia was associated with elevated INR (1.26 vs 1.13, < .001) and abnormal TEG including decreased alpha angle (68.1 vs 73.3, < .001), increased K time (1.7 vs 1.1, < .001), and decreased max amplitude (58 vs 66, < .001). Patients with hypofibrinogenemia received more PRBC (10 vs 7 U, = .002), FFP (9 vs 6 U, = .003), and platelets (2 vs 1 U, = .004) during MT. Hypofibrinogenemic patients demonstrated greater mortality than patients with normal levels (50% vs 23.5%, = .021). Older age, decreased GCS, and elevated injury severity score (ISS) were risk factors for mortality. Increased fibrinogen was associated with lower odds of mortality ( = .001). Age, ISS, and fibrinogen level remained significantly associated with mortality in a multivariable analysis. Overall, fibrinogen in post-MT survivors showed an increase in median level compared to admission (231 vs 177.5 mg/dL, < .001).
CONCLUSION
Trauma patients undergoing MT with decreased admission fibrinogen demonstrate increased mortality. Other mortality risk factors include older age, decreased GCS, and higher ISS. Patients with increased fibrinogen levels had lower odds of mortality in a multivariable model. Post-MT survivors demonstrated significantly higher fibrinogen levels than pre-MT patients. Hypofibrinogenemic patients also had worse TEG parameters and required more PRBCs, FFP, and platelets during MT. Further studies are needed to assess the optimal volume of fibrinogen replacement with cryoprecipitate during MT to improve trauma patient mortality.
Topics: Adult; Humans; Afibrinogenemia; Prospective Studies; Retrospective Studies; Hemorrhage; Fibrinogen; Hemostatics; Trauma Centers; Wounds and Injuries
PubMed: 36908225
DOI: 10.1177/00031348231162711 -
Special Care in Dentistry : Official... 2023Congenital afibrinogenemia is a rare hematologic disorder with an estimated incidence of 1-2 per million people worldwide. It is inherited as an autosomal recessive...
Congenital afibrinogenemia is a rare hematologic disorder with an estimated incidence of 1-2 per million people worldwide. It is inherited as an autosomal recessive trait and is characterized by the inability to synthesize fibrinogen. Clinical features range from minimal bleeding to catastrophic hemorrhage. Because of its rarity, there are not enough clinical guidelines in the management of oral manifestations of patients with this disorder. The following case report presents the dental management of a 4-year-old child with congenital afibrinogenemia under general anesthesia. A multidisciplinary team approach was followed to achieve full mouth rehabilitation, thus improving the overall quality of life of the patient.
PubMed: 36567261
DOI: 10.1111/scd.12814