scholarly journals Normalization of Blood Clotting Characteristics Using Prothrombin Complex Concentrate, Fibrinogen and Fxiii In an Albumin Based Fluid: Experimental Studies In Thromboelastometry.

2020 ◽  
Author(s):  
Tobias Koller ◽  
Nadia Kinast ◽  
Andres Guilarte Castellanos ◽  
Sergio Perez Garcia ◽  
Pilar Paniagua Iglesias ◽  
...  
Keyword(s):  
Whole Blood ◽  
Factor Xiii ◽  
Prothrombin Complex Concentrate ◽  
Massive Transfusion ◽  
Experimental Studies ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Fibrinogen Concentrate ◽  
Coagulation Factor Concentrates

Abstract Background: Colloid fluids supplemented with adequate combinations of coagulation factor concentrates with capability to restore coagulation could be a desirable future treatment component in massive transfusion.Methods: Starting from a coagulation factor and blood cell free albumin solution we added Prothrombin Complex Concentrate, Fibrinogen Concentrate and Factor XIII in different combinations and concentrations to analyze their properties to restore thromboelastometry parameters without the use of plasma. Further analysis under presence of platelets was performed for comparability to whole blood conditions.Results: Albumin solutions enriched with Fibrinogen Concentrate, Factor XIII and Prothrombin Complex Concentrate at optimized concentrations show restoring coagulation potential. Prothrombin Complex Concentrate showed sufficient thrombin formation for inducing fibrinogen polymerization. The combination of Prothrombin Complex Concentrate and Fibrinogen Concentrate led to the formation of a stable in vitro fibrin clot. Fibrinogen and Factor XIII showed excellent capacity to improve fibrin clot firmness expressed as Amplitude at 10 minutes and Maximal Clot Firmness. Fibrinogen alone, or in combination with Factor XIII, was able to restore normal Amplitude at 10 minutes and Maximal Clot Firmness values. In the presence of platelets, the thromboelastometry surrogate parameter for thrombin generation (Clotting Time) improves and normalizes when compared to whole blood.Conclusions: Combinations of coagulation factor concentrates suspended in albumin solutions have the capacity to restore thromboelastometry parameters in the absence of plasma. This kind of artificial colloid fluids with coagulation-restoring characteristics might offer new treatment alternatives for massive transfusion.Trial registration: Study registered at the institutional ethic committee “Institut de Recerca, Hospital Santa Creu i Sant Pau, with protocol number IIBSP-CFC-2013-165.

scholarly journals Normalization Of Blood Clotting Characteristics Using Prothrombin Complex Concentrate, Fibrinogen And FXIII In An Albumin Based Fluid: Experimental Studies In Thromboelastometry.

2021 ◽  
Author(s):  
Tobias Koller ◽  
Nadia Kinast ◽  
Andres Guilarte Castellanos ◽  
Sergio Perez Garcia ◽  
Pilar Paniagua Iglesias ◽  
...  
Keyword(s):  
Whole Blood ◽  
Factor Xiii ◽  
Prothrombin Complex Concentrate ◽  
Massive Transfusion ◽  
Experimental Studies ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Fibrinogen Concentrate ◽  
Coagulation Factor Concentrates

Abstract Background: Colloid fluids supplemented with adequate combinations of coagulation factor concentrates with the capability to restore coagulation could be a desirable future treatment component in massive transfusion.Methods: Starting from a coagulation factor and blood cell-free albumin solution we added Prothrombin Complex Concentrate, Fibrinogen Concentrate and Factor XIII in different combinations and concentrations to analyze their properties to restore thromboelastometry parameters without the use of plasma. Further analysis under the presence of platelets was performed for comparability to whole blood conditions.Results: Albumin solutions enriched with Fibrinogen Concentrate, Factor XIII and Prothrombin Complex Concentrate at optimized concentrations show restoring coagulation potential. Prothrombin Complex Concentrate showed sufficient thrombin formation for inducing fibrinogen polymerization. The combination of Prothrombin Complex Concentrate and Fibrinogen Concentrate led to the formation of a stable in vitro fibrin clot. Fibrinogen and Factor XIII showed excellent capacity to improve fibrin clot firmness expressed as Amplitude at 10 minutes and Maximal Clot Firmness. Fibrinogen alone, or in combination with Factor XIII, was able to restore normal Amplitude at 10 minutes and Maximal Clot Firmness values. In the presence of platelets, the thromboelastometry surrogate parameter for thrombin generation (Clotting Time) improves and normalizes when compared to whole blood.Conclusions: Combinations of coagulation factor concentrates suspended in albumin solutions can restore thromboelastometry parameters in the absence of plasma. This kind of artificial colloid fluids with coagulation-restoring characteristics might offer new treatment alternatives for massive transfusion.Trial registration: Study registered at the institutional ethic committee “Institut de Recerca, Hospital Santa Creu i Sant Pau, with protocol number IIBSP-CFC-2013-165.

scholarly journals Normalization of blood clotting characteristics using prothrombin complex concentrate, fibrinogen and FXIII in an albumin based fluid: experimental studies in thromboelastometry

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Tobias Koller ◽  
Nadia Kinast ◽  
Andres Guilarte Castellanos ◽  
Sergio Perez Garcia ◽  
Pilar Paniagua Iglesias ◽  
...  
Keyword(s):  
Whole Blood ◽  
Factor Xiii ◽  
Prothrombin Complex Concentrate ◽  
Massive Transfusion ◽  
Experimental Studies ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Fibrinogen Concentrate ◽  
Coagulation Factor Concentrates

Abstract Background Colloid fluids supplemented with adequate combinations of coagulation factor concentrates with the capability to restore coagulation could be a desirable future treatment component in massive transfusion. Methods Starting from a coagulation factor and blood cell-free albumin solution we added Prothrombin Complex Concentrate, Fibrinogen Concentrate and Factor XIII in different combinations and concentrations to analyze their properties to restore thromboelastometry parameters without the use of plasma. Further analysis under the presence of platelets was performed for comparability to whole blood conditions. Results Albumin solutions enriched with Fibrinogen Concentrate, Factor XIII and Prothrombin Complex Concentrate at optimized concentrations show restoring coagulation potential. Prothrombin Complex Concentrate showed sufficient thrombin formation for inducing fibrinogen polymerization. The combination of Prothrombin Complex Concentrate and Fibrinogen Concentrate led to the formation of a stable in vitro fibrin clot. Fibrinogen and Factor XIII showed excellent capacity to improve fibrin clot firmness expressed as Amplitude at 10 min and Maximal Clot Firmness. Fibrinogen alone, or in combination with Factor XIII, was able to restore normal Amplitude at 10 min and Maximal Clot Firmness values. In the presence of platelets, the thromboelastometry surrogate parameter for thrombin generation (Clotting Time) improves and normalizes when compared to whole blood. Conclusions Combinations of coagulation factor concentrates suspended in albumin solutions can restore thromboelastometry parameters in the absence of plasma. This kind of artificial colloid fluids with coagulation-restoring characteristics might offer new treatment alternatives for massive transfusion. Trial registration Study registered at the institutional ethic committee “Institut de Recerca, Hospital Santa Creu i Sant Pau, with protocol number IIBSP-CFC-2013-165.

scholarly journals Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study

2020 ◽  
Vol 9 (12) ◽  
pp. 3805
Author(s):  
Johannes Gratz ◽  
Christoph J. Schlimp ◽  
Markus Honickel ◽  
Nadine Hochhausen ◽  
Herbert Schöchl ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Prothrombin Complex Concentrate ◽  
Oral Anticoagulants ◽  
Coagulation Factor ◽  
Severe Bleeding ◽  
Crystalloid Solution ◽  
Coagulation Tests ◽  
Coagulation Factor Concentrates ◽  
Dilution Level

Guidelines for the treatment of severe bleeding comprise viscoelastic-test-guided use of coagulation factor concentrates as part of their recommendations. The aim of this study is to investigate the effects of substituting fibrinogen, prothrombin complex concentrate, and a combination of both on conventional coagulation tests, viscoelastic test results, and thrombin generation. Blood was drawn from seven healthy volunteers to obtain platelet-free plasma, which later was diluted by replacing 40%, 60%, 80%, 90%, 95%, and 99% with a crystalloid solution. The diluted samples were spiked with fibrinogen concentrate, prothrombin complex concentrate, a combination of both, or a corresponding amount of crystalloid solution. Up to a dilution level of 95%, viscoelastically determined clotting time was significantly shorter in the group substituted with fibrinogen only in comparison with the additional use of prothrombin complex concentrate. Clot firmness and endogenous thrombin potential remained at relatively stable values up to a dilution level of 95% with the substitution of fibrinogen but not prothrombin complex concentrate. Substitution of prothrombin complex concentrate led to an excessive overshoot of thrombin generation. The results of our study question currently propagated treatment algorithms for bleeding patients that include the use of prothrombin complex concentrate for patients without former intake of oral anticoagulants. Even in severely bleeding patients, thrombin generation might be sufficient to achieve adequate hemostasis.

scholarly journals Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study

2021 ◽  
Vol 10 (10) ◽  
pp. 2068
Author(s):  
Emmanuel Schneck ◽  
Marcus Muelich ◽  
Melanie Markmann ◽  
Fabian Edinger ◽  
Nina Cooper ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Massive Transfusion ◽  
Combined Therapy ◽  
Coagulation Factor ◽  
Fresh Frozen Plasma ◽  
Level Of Evidence ◽  
Major Hemorrhage ◽  
Combined Administration ◽  
Dilutional Coagulopathy

The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3–7.8) mm; 20% dilution fibrinogen: 13.5 (13–17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3–18.8) mm; 40% dilution: 3 (2–3.8) mm; 40% dilution fibrinogen: 8 (7–11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3–11.8) mm; all p < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.

Additive roles of platelets and fibrinogen in whole-blood fibrin clot formation upon dilution as assessed by thromboelastometry

2014 ◽  
Vol 111 (03) ◽  
pp. 447-457 ◽  
Author(s):  
Marisa Ninivaggi ◽  
Gerhardus Kuiper ◽  
Marco Marcus ◽  
Hugo ten Cate ◽  
Marcus Lancé ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Whole Blood ◽  
Blood Cells ◽  
Thrombin Generation ◽  
Prothrombin Complex Concentrate ◽  
Coagulation Factors ◽  
Fibrin Clot ◽  
Clot Formation

SummaryBlood dilution after transfusion fluids leads to diminished coagulant activity monitored by rotational thromboelastometry, assessing elastic fibrin clot formation, or by thrombin generation testing. We aimed to determine the contributions of blood cells (platelets, red blood cells) and plasma factors (fibrinogen, prothrombin complex concentrate) to fibrin clot formation under conditions of haemodilution in vitro or in vivo. Whole blood or plasma diluted in vitro was supplemented with platelets, red cells, fibrinogen or prothrombin complex concentrate (PCC). Thromboelastometry was measured in whole blood as well as plasma; thrombin generation was determined in parallel. Similar tests were performed with blood from 48 patients, obtained before and after massive fluid infusion during cardiothoracic surgery. Addition of platelets or fibrinogen, in additive and independent ways, reversed the impaired fibrin clot formation (thromboelastometry) in diluted whole blood. In contrast, supplementation of red blood cells or prothrombin complex concentrate was ineffective. Platelets and fibrinogen independently restored clot formation in diluted plasma, resulting in thromboelastometry curves approaching those in whole blood. In whole blood from patients undergoing dilution during surgery, elastic clot formation was determined by both the platelet count and the fibrinogen level. Thrombin generation in diluted (patient) plasma was not changed by fibrinogen, but improved markedly by prothrombin complex concentrate. In conclusion, in dilutional coagulopathy, platelets and fibrinogen, but not red blood cells or vitamin K-dependent coagulation factors, independently determine thromboelastometry parameters measured in whole blood and plasma. Clinical decisions for transfusion based on thromboelastometry should take into account the platelet concentration.

scholarly journals Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism

2021 ◽  
Vol 22 (4) ◽  
pp. 1607
Author(s):  
Michał Ząbczyk ◽  
Joanna Natorska ◽  
Anetta Undas
Keyword(s):  
Venous Thromboembolism ◽  
Factor Xiii ◽  
Active Form ◽  
Coagulation Factor ◽  
Proteome Analysis ◽  
Fibrin Clot ◽  
Subsequent Increase ◽  
Vein Thrombosis ◽  
Acute Pe ◽  
Fxiii Activity

Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which crosslinks fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII activation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subsequent increase after several weeks since the index event. Plasma fibrin clot proteome analysis confirms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibrinolysis in acute PE. The current review presents available studies on the role of FXIII in the modulation of fibrin clot properties during acute PE or DVT and following these events. Better understanding of FXIII’s involvement in the pathophysiology of acute VTE might help to improve current therapeutic strategies in patients with acute VTE.

FACTOR XIII CONCENTRATE FOR PROPHYLAXIS OF REBLEEDING IN SUBARACHNOID HEMORRHAGE (SAH) - RESULTS OF A PROSPER TIVE MULTICENTER PILOT STUDY

1987 ◽  
Author(s):  
A Thie ◽  
T h Henze ◽  
D Deggar ◽  
M Obering ◽  
R Clemers ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Pilot Study ◽  
Mortality Rate ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Stage I ◽  
Stage Iii ◽  
Double Blind Study ◽  
Overall Mortality

Rebleeding occurs in subarachnoid hemorrhage (SAH) in 20 - 25 % of patients, with a mortality rate being above 50 %. The cause of rebleeding is considered to be premature fibrinolysis of the fibrin clot surrounding the site of rupture. Since the stability of the fibrin clot is influenced by the activity of coagulation factor XIII, and moreover, a factor XIII deficiency has been reported in SAH patients, the question arises as to whether the incidence of rebleeding can be influenced by the administration of F XIII concentrate.During a period of 6 months, 69 patients with acute SAH were enlisted in an open, prospective, multicenter study. On admission, 5 patients were classified as stage I (7.2%) according to the Hunt and Hess scale, 22 as stage III (31.9%), 11 as stage IV (16%) and 9 as stage V (13%). Aneurysm was confirmed by angiography in 52 patients (75%). All the patients received 10 x 1250 U F XIII concentrate during the first 15 days after the initial hemorrhage. Surgery on the aneurysm was performed between day 3 and 32 (median: day 13) in 35 patients.A total of 7 rebleedings occurred in 6 patients (8.7%), of whom 2 were stage I - II and 4 were stage III - V cases. Cerebral infarction was observed in 10 patients (14.5%), and hydrocephalus requiring shunting occurred in 1 patient. There were no cases of peripheral thromboses or embolisms. After 4 weeks, the overall mortality rate was 26%. (stage I - II: 11.1%, stage III - V: 37.5%).The conventional approach in the prophylaxis of rebleeding in SAH is an early operation or intravenous administration of antifibrinolytics. However, as none of these measures significantly reduce overall mortality, the present pilot study investigated a new, therapeutic approach in which F XIII concentrates were administered in order to stabilize the fibrin clots and prevent premature fibrinolysis. The data so far show that Fibrogammin P is an effective and well tolerated agent for the prophylaxis of post-SAH rebleeding. In order to statistically confirm the results of the pilot study, we have, in the meantime, started a prospective, randomized, placebo-controlled, multicenter double-blind study, which will involve 750 patients over a period of 2 years.

Factor XIII activation peptide is released into plasma upon cleavage by thrombin and shows a different structure compared to its bound form

2007 ◽  
Vol 97 (06) ◽  
pp. 890-898 ◽  
Author(s):  
Verena Schroeder ◽  
Jean-Marc Vuissoz ◽  
Amedeo Caflisch ◽  
Hans Kohler
Keyword(s):  
Human Plasma ◽  
Factor Xiii ◽  
Direct Detection ◽  
Polyclonal Antibodies ◽  
Coagulation Factor ◽  
Highly Sensitive ◽  
Clinical Interest ◽  
Activation Peptide ◽  
Dynamics Simulations

SummaryThe first step of coagulation factor XIII (FXIII) activation involves cleavage of the FXIII activation peptide (FXIII-AP) by thrombin. However, it is not known whether the FXIII-AP is released into plasma upon cleavage or remains attached to activated FXIII. The aim of the present work was to study the structure of free FXIII-AP, develop an assay for FXIII-AP determination in human plasma, and to answer the question whether FXIII-AP is released into plasma. We used ab-initio modeling and molecular dynamics simulations to study the structure of free FXIII-AP. We raised monoclonal and polyclonal antibodies against FXIII-AP and developed a highly sensitive and specific ELISA method for direct detection of FXIII-AP in human plasma. Structural analysis showed a putative different conformation of the free FXIII-AP compared to FXIII-AP bound to the FXIII protein. We concluded that it might be feasible to develop specific antibodies against the free FXIII-AP. Using our new FXIII-AP ELISA, we found high levels of FXIII-AP in in-vitro activated plasma samples and serum. We showed for the first time that FXIIIAP is detached from activated FXIII and is released into plasma, where it can be directly measured. Our findings may be of major clinical interest in regard to a possible new marker in thrombotic disease.

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