The Impact of Factor XIII on Coagulation Kinetics and Clot Strength Determined by Thrombelastography

2004 ◽  
Vol 99 (1) ◽  
pp. 120-123 ◽  
Author(s):  
Vance G. Nielsen ◽  
William Q. Gurley ◽  
Thomas M. Burch
Keyword(s):  
Factor Xiii ◽  
Clot Strength ◽  
Coagulation Kinetics ◽  
The Impact

The impact of prepartum factor XIII activity on postpartum blood loss

2019 ◽  
Author(s):  
C Haslinger ◽  
W Korte ◽  
T Hothorn ◽  
R Brun ◽  
C Greenberg ◽  
...  
Keyword(s):  
Blood Loss ◽  
Factor Xiii ◽  
Postpartum Blood Loss ◽  
The Impact

Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years

2008 ◽  
Vol 99 (06) ◽  
pp. 1085-1089 ◽  
Author(s):  
Marianna Politou ◽  
Christoforos Komporozos ◽  
Demosthenes Panagiotakos ◽  
Chrisoula Belessi ◽  
Anthi Travlou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Factor Xiii ◽  
Control Group ◽  
Lower Prevalence ◽  
Premature Coronary Heart Disease ◽  
Acute Mi ◽  
The Impact

SummaryThere are limited and controversial data regarding the impact of factor XIII (FXIII) Val34Leu polymorphism in the pathogenesis of premature myocardial infarction (MI). We examined whether FXIII Val34Leu polymorphism is associated with the development of early MI.We recruited 159 consecutive patients who had survived their first acute MI under the age of 36 years (mean age=32.1 ± 3.6 years, 138 were men). The control group consisted of 121 healthy individuals matched with cases for age and sex, without a family history of premature coronary heart disease (CHD). FXIII Val34Leu polymorphism was tested with polymerase chain reaction and reverse hybridization. There was a lower prevalence of carriers of the Leu34 allele in patients than in controls (30.2 vs. 47.1%, p=0.006). FXIII Val34Leu polymorphism was associated with lower risk for acute MI after adjusting for major cardiovascular risk factors (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.27–0.95, p=0.03). Subgroup analysis according to angiographic findings (“normal” coronary arteries [n=29] or significant CHD [n=130]) showed that only patients with MI and significant CHD had lower prevalence of carriers of the Leu34 allele compared to controls after adjusting for major cardiovascular risk factors (OR = 0.42, 95% CI 0.22–0.83, p=0.01). Our data indicate that FXIII Val34Leu polymorphism has a protective effect against the development of MI under the age of 36 years, particularly in the setting of significant CHD.

Abstract 520: Acoustic Tweezing Thromboelastometry

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Daishen Luo ◽  
Damir Khismatullin ◽  
R. Glynn Holt
Keyword(s):  
Reaction Time ◽  
Whole Blood ◽  
Factor Xiii ◽  
Formation Time ◽  
Plasma Samples ◽  
Clot Strength ◽  
Plasma Coagulation ◽  
Coagulation Status ◽  
Clot Formation Time ◽  
Control Plasma

Background: Critical care patients such as trauma and major surgery patients often develop coagulopathy due to depletion of both pro- and anti-coagulants. They are at high risk of both bleeding and thrombotic complications and require monitoring of their coagulation status. The contact of a blood sample with artificial surfaces and its exposure to clot activators, which happen in all commercially available coagulation analyzers, may lead to improper assessment of blood coagulation and thus errors in predicting bleeding/thrombosis risks. Objective: Real-time assessment of whole blood or blood plasma coagulation by novel non-contact acoustic tweezing technology. Method: 4-5 microliter drops of whole blood collected from healthy volunteers or commercial control plasma were levitated in air by acoustic radiation forces. Their coagulation kinetics including reaction time, fibrin network formation time (FNFT), clot formation time and maximum clot strength was assessed from mechanical (drop shape) and photo-optical (light intensity) data. FNFT was determined as a difference between mechanical and photo-optical reaction times. Results: Whole blood samples were exposed to pro- or anti-coagulants during levitation in the acoustic tweezing device. Changes in the coagulation status between different experimental groups were detected within 10 minutes. Similarly, less than 7 minutes was required to detect significant changes in reaction time, clot formation time and maximum clot strength between low, normal, and high fibrinogen level control plasma samples. FNFT was shown to be significantly reduced in plasma samples with a higher level of Factor XIII. Conclusions: The acoustic tweezing technology integrates photo-optical tests used in plasma coagulation assays with viscoelastic tests used in whole blood analysis. Its key disruptive features are the increased reliability and accuracy due to non-contact measurement, small sample volume requirement, relatively short procedure time (<10 minutes), and the ability to assess the level of Factor XIII function from FNFT measurements. Our technology addresses a current lack of reliable methods to measure blood coagulation in patients with coagulopathy.

Systemic and intestinal levels of factor XIII-A: the impact of inflammation on expression in macrophage subtypes

2015 ◽  
Vol 51 (8) ◽  
pp. 796-807 ◽  
Author(s):  
Christoffer Soendergaard ◽  
Peter Helding Kvist ◽  
Jakob Benedict Seidelin ◽  
Hermann Pelzer ◽  
Ole Haagen Nielsen
Keyword(s):  
Factor Xiii ◽  
The Impact ◽  
Macrophage Subtypes

Coagulation Profile of Children on Extracorporeal Membrane Oxygenation (ECMO) - Is FXIII the Missing Link?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3795-3795
Author(s):  
Thorsten Haas ◽  
Carsten Doell ◽  
Markus Schmugge ◽  
Melissa M. Cushing ◽  
Vincenzo Cannizzaro
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Factor Xiii ◽  
Massive Transfusion ◽  
Complete Blood Count ◽  
Published Data ◽  
Reference Ranges ◽  
Bleeding Management ◽  
Membrane Oxygenation ◽  
Thrombotic Complications ◽  
The Impact

Abstract Background Published data about bleeding management on extracorporeal membrane oxygenation (ECMO) in children is sparse and to date no global transfusion algorithm has been established. Viscoelastic testing can be effective for determining the etiology and management of coagulopathic bleeding during cardiothoracic procedures, but data regarding its usefulness in ECMO patients are scarce. Recently, low factor XIII levels were determined to be a frequent finding in adult ECMO patients(Kalbhenn et al; Perfusion 2015;30:675-82). Methods This is a retrospective analysis of thromboelastometry (ROTEM®) and factor XIII data obtained in children (ages 0 to 18 years) undergoing ECMO since 2013 in a single center children's hospital. Acute bleeding treatment was based on daily ROTEM testing, complete blood count and routine plasmatic coagulation testing. The transfusion algorithm targeted a hemoglobin level >13g dL-1, a Quick's value >50%, a plasma fibrinogen level >1.5g L-1, and a platelet count of >100,000 µL-1. Red blood cells (RBC), solvent detergent (S/D) plasma and platelet apheresis concentrates were exclusively used to maintain hemostasis. Measurement of FXIII levels is not part of routine testing, but was assessed when unexplained bleeding was observed. Results Laboratory and transfusion data from sixteen patients, age 4 (1-15) months [median(IQR)] with a body weight of 6 (3-8) kg were included. Median time on ECMO was 7 (4-9) days. Large volumes of allogeneic blood were transfused to all children, meeting criteria for massive transfusion each individual day on ECMO (Tab.1). Overall, median daily ROTEM measurements were within reference ranges (Tab.2), while median levels of FXIII were decreased despite massive transfusion [FXIII levels 42% (28-51%)]. Conclusion Pediatric ECMO was almost always combined with daily massive transfusion, which led to correction of overall ROTEM values. Notably, despite transfusion of large amounts of plasma, decreased FXIII levels were noted. This finding is supported by results of a study in adult ECMO patients, where FXIII levels <50% were observed in 88% of all patients. Although inherited homozygous FXIII deficiency is usually defined by levels <5%, even mildly to moderately reduced FXIII levels have been reported to contribute to increased bleeding after cardiac surgery(Ternström et al; Thromb Res 2010;126:e128-33). Further studies should be performed to assess the impact of FXIII substitution in pediatric ECMO patients and to investigate whether substitution of FXIII may decrease bleeding without increasing thrombotic complications. Disclosures Haas: CSL Behring: Speakers Bureau; TEM International: Speakers Bureau; Octapharma: Consultancy.

scholarly journals Study of the Effect of Fibrinogen, Factor XIII and Recombinant Activated Factor VII in a Model of Trauma-Induced Coagulopathy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Manuel Quintana ◽  
Kapil Nanwani ◽  
Charbel Maroun ◽  
Elena Elena Muñoz ◽  
Ana María Martínez ◽  
...  
Keyword(s):  
Research Funding ◽  
Factor Xiii ◽  
Clot Formation ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Clot Strength ◽  
Activated Factor Vii ◽  
Trauma Induced Coagulopathy ◽  
Procoagulant Effect

Introduction: Trauma-induced coagulopathy (TIC) is a multifactorial condition secondary to severe trauma. In TIC, early fibrinogen (FI) replacement and low dose of recombinant activated factor VII (rFVIIa) may positively impact outcome. Factor XIII (FXIII), on the other hand, may stimulate in vitro clot formation and clot stability. We hypothesized that combination of FI, rFVIIa and FXIII might normalize clot formation more effectively than the isolated use of each concentrate in a model of TIC. Aim: Evaluation of the procoagulant effect of isolated or combined use of FI, rFVIIa and FXIII in a model of TIC. Methods: TIC in vitro model was obtained by dilution of whole blood from seven healthy controls with isotonic saline (NaCl 0.9%) (2:3 whole blood:saline ratio). FI, rFVIIa and FXIII were spiked in combination or alone until obtaining final levels of 2 g/L, 1 μg/mL and 100 IU/dL respectively. Procoagulant effects of the different concentrates or their mixtures were evaluated by Rotational Thromboelastometry (ROTEM®, Werfen) triggered using starTEM® (calcium chloride 0,2 M) and exTEM® reagent (source of tissue factor) diluted with saline up to 1:100.000 (final dilution) for a better evaluation of both the extrinsic and intrinsic pathways of coagulation. The values of clotting time (CT: time until 2 mm of amplitude, in seconds), amplitude (parameter proportional to the clot strength) at 5 minutes (A5, in mm) and clot formation time (CFT: time from CT to 20 mm of amplitude, in seconds) were evaluated. Statistical analysis of differences was performed by One-Way ANOVA test assuming no paring of data and using the Holm-Sidak's correction for multiple comparisons with a family-wise significance and confidence level of 0.01. Statistical significance was set at p&lt; 0.05. Results/Discussion: Data are summarized in Table I and Figure 1. CT needed the combination of two of more concentrates to reach the normal range suggesting that the administration of FI alone in TIC may not be enough to restore the patients' hemostatic potential. In regard to the clot strength evaluated by A5, the addition of FXIII or rFVIIa alone or in combination did not improve the value of A5 that was only normalized by the addition of FI. This effect of FI was increased in the presence of FXIII or rFVIIa which indicated that normal levels of FI might be required for rFVIIa or FXIII to be effective emphasising the possible benefit of the combinatory therapy. Like observed in A5, the velocity of clot formation evaluated by the CFT was normalised only by the addition of FI. However, the combination of FI plus FXIII + rFVIIa had a stronger effect on CFT compared with the combination of FI + FXIII or FI + rFVIIa, indicating that the improvement of thrombin generation due to rFVIIa plus an increment of fibrin formation and net stabilization through the contribution of higher levels of FI and FXIII respectively, might provide a beneficial synergistic procoagulant effect in TIC. Conclusion: The use of FI in TIC may contribute to increase the patient's hemostatic potential but might not be enough. Combinatory therapies based on the administration of FI, rFVIIa and FXIII might be of better benefit in this setting. Ex-vivo studies using blood of patients with stablished TIC might bring new insights on the possible advantages of this combinatory therapy to design more effective protocols to treat this frequent and life-threatening acquired condition. Disclosures Canales: Sandoz: Honoraria; iQone: Honoraria; Janssen: Speakers Bureau; Janssen: Honoraria; Roche: Speakers Bureau; Karyopharm: Honoraria; Sandoz: Speakers Bureau; Novartis: Honoraria; Takeda: Speakers Bureau; Roche: Honoraria; Sandoz: Honoraria; Janssen: Speakers Bureau; Roche: Speakers Bureau; Sandoz: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Honoraria; Karyopharm: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Roche: Honoraria; Gilead: Honoraria. Butta:NovoNordisk: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; SOBI: Speakers Bureau; Pfizer: Speakers Bureau; ROCHE: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Grifols: Research Funding. Alvarez Román:NovoNordisk,: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; SOBI,: Consultancy, Research Funding, Speakers Bureau; Pfizer,: Research Funding, Speakers Bureau; Roche: Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy; Grifols: Research Funding. Jiménez-Yuste:F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer: Consultancy; Grifols, Novo Nordisk, Takeda, Sobi, Pfizer: Research Funding; F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer, Grifols, Octapharma, CSL Behring, Bayer: Honoraria.

A Novel 3-Base Pair 1834–1836 AAG-Deletion (Lys570Del) Mutation In Factor XIII A Subunit Associated with Factor XIII Deficiency

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1412-1412
Author(s):  
Anamika Singh ◽  
A. Koneti Rao
Keyword(s):  
Factor Xiii ◽  
Bleeding Tendency ◽  
Compound Heterozygosity ◽  
Factor Xiii Deficiency ◽  
Catalytic Core ◽  
A Subunit ◽  
A Chain ◽  
The Impact ◽  
Fxiii Activity ◽  
Fxiii Deficiency

Abstract Abstract 1412 Factor XIII is a transglutaminase that cross-links proteins in plasma, vascular matrix, endothelial cells, platelets and monocytes, and plays a role in atherosclerosis, wound healing, and inflammation. Plasma FXIII molecule is a hetero-tetramer consisting of two catalytic A-subunits and two B-subunits that act as carrier molecules. The gene encoding FXIII A subunit comprises of 15 exons spanning 160 kb and the mature protein contains 731 amino acids. FXIII deficiency is a rare autosomal recessive disorder affecting ∼1 in 1–3 million people. It is characterized by bleeding, impaired wound repair and spontaneous abortions. We report studies from a family where two children son (13 yrs) and daughter (11 yrs) have had a lifelong bleeding tendency and spontaneous intracranial hemorrhages. Both parents were asymptomatic and there was no consanguinity. The results of routine laboratory tests, prothrombin time and activated partial thromboplastin time were normal in all subjects. The plasma FXIII activity by a commercially available chromogenic assay was 5% in the son and <3% in the daughter (normal range 57–192%). The FXIII activity in the father and mother were 198% and 74%, respectively. We have identified a novel deletion mutation, which has not been reported so far in FXIII deficiency. Leukocyte RNA was isolated from the buffy-coat and cDNA was obtained by reverse-transcription PCR using SuperScript First-Strand Synthesis System. The amplified products were cloned in pGEM-T vector (Promega) and sequenced on an automated gene-sequencer. Both children and the father have a novel 3 bp AAG-deletion position 1834–1836 nt in FXIII A chain. This mutation causes a lysine 570 deletion in the ß-barrel 1 of Factor XIII A subunit and has not been reported so far. It may lead to protein misfolding resulting in an unstable protein, and low levels of FXIII. The second major change detected in the two siblings was a A/T substitution at position 737 nt causing Tyr204Phe substitution in the two siblings; this was present in the mother in a heterozygous condition. This mutation has been previously reported in FXIII deficiency and linked to increased risk of haemorrhagic stroke in young women and of miscarriages. The compound heterozygosity for Lys570Del and Tyr204Phe substitution observed in both children is the likely cause of Factor XIII deficiency leading to lifelong bleeding condition. In addition to above, the father had Val34Leu polymorphism, previously reported to be associated with resistance to myocardial infarction. This polymorphism is present in ∼20% of white European, 40% of Pima Native American and 13% of South Asian populations. The mother also had a known A/C polymorphism at 1119 nt position for a synonymous Pro332Pro change. We also found 3 other variations in FXIII A chain in this family. The daughter has Glu216Gly and Asp267Asn change in the protein corresponding to alterations at nucleotide 773 (A/G) and 925 (A/G), respectively. The son and mother had a substitution at 1442 nt (T/C) leading to a Leu439Pro change. These variations, Glu216Gly, Asp267Asn and Leu439Pro found in the two children (Leu439Pro also in mother) are present in the catalytic core domain of the Factor XIII A chain. All of the polymorphisms or mutations reported in this study were heterozygous in the studied subjects. FXIII gene mutations and polymorphisms result in a high level of heterogeneity of disease presentation. Other point mutations in the FXIII A catalytic core as well as mutations in ß-barrel 1 region have been described in association with a hemorrhagic state in FXIII deficiency. Our study documents a new 3-bp 1834–1836 nt AAG-deletion (Lys570Del) in association with FXIII deficiency. We suggest that compound heterozygosity for Lys570Del and Tyr204Phe is the cause of FXIII deficiency in our patients. Further structure-function studies will aid in understanding the impact of these amino acid substitutions or deletions on FXIII function and on the associated bleeding diathesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals In vitro factor XIII supplementation increases clot firmness in Rotation Thromboelastometry (ROTEM®)

2010 ◽  
Vol 104 (08) ◽  
pp. 385-391 ◽  
Author(s):  
Lars Asmis ◽  
Burkhardt Seifert ◽  
Donat Spahn ◽  
Oliver Theusinger ◽  
Werner Baulig
Keyword(s):  
Factor Xiii ◽  
Clot Formation ◽  
Intensive Care Patients ◽  
Essential Parameter ◽  
Α Angle ◽  
The Impact ◽  
Clot Formation Time ◽  
Clot Stability ◽  
Maximum Clot Firmness

SummaryFactor XIII (F XIII) is an essential parameter for final clot stability. The purpose of this study was to determine the impact of the addition of factor (F)XIII on clot stability as assessed by Rotation Thromboelastometry (ROTEM®). In 90 intensive care patients ROTEM® measurements were performed after in vitro addition of F XIII 0.32 IU, 0.63 IU, 1.25 IU and compared to diluent controls (DC; aqua injectabile) resulting in approximate F XIII concentrations of 150, 300 and 600%. Baseline measurements without any additions were also performed. The following ROTEM® parameters were measured in FIBTEM and EXTEM tests: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), maximum lysis (ML), maximum clot elasticity (MCE) and α-angle (αA). Additionally, laboratory values for FXIII, fibrinogen (FBG), platelets and haematocrit were contemporaneously determined. In the perioperative patient population mean FBG concentration was elevated at 5.2 g/l and mean FXIII concentration was low at 62%. The addition of FXIII led to a FBG concentration-dependent increase in MCF both in FIBTEM and EXTEM. Mean increases in MCF (FXIII vs. DC) of approximately 7 mm and 6 mm were observed in FIBTEM and EXTEM, respectively. F XIII addition also led to decreased CFT, increased αA, and reduced ML in FIBTEM and EXTEM. In vitro supplementation of FXIII to supraphysiologic levels increases maximum clot firmness, accelerates clot formation and increases clot stability in EXTEM and FIBTEM as assayed by ROTEM® in perioperative patients with high fibrinogen and low FXIII levels.

Establishment of an International Registry of Patients with Inherited FXIII Deficiency.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2149-2149
Author(s):  
Vytautas Ivaskevicius ◽  
Rainer Seitz ◽  
Hans P. Kohler ◽  
Laszlo Muszbek ◽  
Robert A.S. Ariens ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Working Party ◽  
Splice Site Mutation ◽  
Autosomal Recessive Disorder ◽  
Bleeding Tendency ◽  
Site Mutation ◽  
Impaired Wound Healing ◽  
Thrombosis Research ◽  
The Impact ◽  
Fxiii Deficiency

Abstract Inherited factor XIII (FXIII) deficiency is a rare autosomal recessive disorder affecting approximately one out of one to three million people. FXIII deficiency is characterized by a lifelong bleeding tendency, impaired wound healing and spontaneous abortions in females. In 1993, the European Thrombosis Research Organization (ETRO) Working Party on FXIII initiated a Europe-wide questionnaire on inherited FXIII deficiency. Since 2005, the registry has been endorsed by the Factor XIII Subcommittee of the Scientific and Standardization committee (SSC) of the ISTH. The analysis of 104 European patients demonstrated that the most common bleeding symptoms were subcutaneous bleeding (57%) followed by delayed umbilical cord bleeding (56%), muscle hematoma (49%), hemorrhage after surgery (40%), hemarthrosis (36%), and intracerebral bleeding (34%). Prophylactic treatment was initiated in about 70% of all patients. FXIII-B subunit-deficient patients had a milder phenotype than patients with FXIII-A subunit deficiency.The most frequent mutation affecting the F13A gene was a splice site mutation in intron 5 (IVS5-1G&gt;A).This mutation was found in eight (17%) of 46 analyzed families.The haplotype analysis of patients carrying the IVS5-1A allele was consistent with a founder effect. Recently, we created a new FXIII database website (http://www.f13-database.de) with information about FXIII proteins, genes, mutations and polymorphisms. This website also includes a new questionnaire. Information provided by this questionnaire will allow better understanding of the differences of diagnostic and treatment possibilities in various parts of the world, and it will help to understand the impact of reduced FXIII activity in heterozygous relatives and finally, it will generally increase our knowledge on this rare disease. We hope that our initiative to establish a new international FXIII registry will be actively supported by the community involved in caring for FXIII deficient patients.

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