Influence of cryoprecipitate, Factor XIII, and fibrinogen concentrate on hyperfibrinolysis

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.

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

10.21203/rs.3.rs-98928/v2 ◽

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.

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

Scandinavian Journal of Trauma Resuscitation and Emergency Medicine ◽

10.1186/s13049-021-00867-5 ◽

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.

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Effects of fibrinogen concentrate, factor XIII, and thrombin-activatable fibrinolysis inhibitor on clot firmness and fibrinolytic resistance in the model of hyperfibrinolysis

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/igpp.2017.4.8522 ◽

2017 ◽

pp. 44-50

Author(s):

И.А. Будник ◽

О.Л. Морозова ◽

А.А. Цымбал ◽

Б. Шенкман ◽

Ю. Эйнав

Keyword(s):

Factor Xiii ◽

Onset Time ◽

Clot Formation ◽

Clot Lysis ◽

Fibrinogen Concentrate ◽

Thrombin Activatable Fibrinolysis Inhibitor ◽

Antifibrinolytic Agents ◽

Fibrinolysis Inhibitor ◽

Vitro Model

Цель исследования - изучение возможности коррекции формирования кровяного сгустка и его фибринолитической устойчивости с помощью концентратов фибриногена, фактора XIII и активируемого тромбином ингибитора фибринолиза (TAFI) в модели гиперфибринолиза in vitro . Методика. В образцы цитратной крови, полученной от 24 взрослых здоровых добровольцев, добавляли концентрат фибриногена, фактора XIII и/или TAFI. Фибринолиз индуцировали добавлением тканевого активатора плазминогена. Свертывание крови индуцировали рекальцификацией и добавлением препарата тканевого фактора. Формирование и лизис сгустка изучали методом ротационной тромбоэластометрии. Результаты. Индукция фибринолиза не влияла на время свертывания и скорость формирования сгустка, но значительно уменьшала максимальную плотность сгустка и вызывала его лизис. Концентрат фибриногена замедлял скорость лизиса сгустка; концентрат фактора XIII усиливал механическую прочность сгустка и замедлял скорость его лизиса, не влияя при этом на время начала лизиса; TAFI усиливал механическую прочность и значительно отдалял время начала лизиса, оказывая тем самым наибольший корригирующий эффект. Заключение. Полученные данные демонстрируют потенциальную возможность коррекции гемостатического потенциала крови при гиперфибринолизе с помощью концентратов фибриногена, фактора XIII и TAFI, которые могут стать альтернативой традиционным антифибринолитикам. Aim. To investigate effects of fibrinogen concentrate, factor XIII, and thrombin-activatable fibrinolysis inhibitor (TAFI) on clot formation and fibrinolytic resistance using an in vitro model of hyperfibrinolysis. Methods. Citrated whole blood from 24 adult healthy volunteers was supplemented with fibrinogen concentrate, factor XIII, and/or TAFI. Fibrinolysis was induced by tissue plasminogen activator. Clotting was induced by recalcification and addition of tissue factor and monitored using rotation thromboelastometry. Results. Induction of fibrinolysis did not affect clotting time and the rate of clot formation but significantly reduced the maximum clot firmness and caused lysis of a clot. Addition of fibrinogen concentrate to blood reduced the rate of clot lysis without affecting clot firmness or lysis onset time; addition of factor XIII improved clot firmness and reduced clot lysis rate without affecting lysis onset time; TAFI improved clot firmness and considerably delayed the onset of clot lysis thereby providing the greatest antifibrinolytic effect. Conclusion. Fibrinogen concentrate, factor XIII, and TAFI may potentially serve as an alternative to traditional antifibrinolytic agents and be beneficial for the treatment of patients with hyperfibrinolysis.

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Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.1080/00365513.2017.1334128 ◽

2017 ◽

Vol 77 (6) ◽

pp. 397-405 ◽

Cited By ~ 3

Author(s):

David E. Schmidt ◽

Märit Halmin ◽

Agneta Wikman ◽

Anders Östlund ◽

Anna Ågren

Keyword(s):

Factor Xiii ◽

In Vitro Model ◽

Massive Transfusion ◽

Plasma Fibrinogen ◽

Fibrinogen Concentrate ◽

Vitro Model

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P1079 Substitution of coagulation factor XIII partially restores scar healing after myocardial infarction in factor XIII KO mice

European Heart Journal ◽

10.1016/s0195-668x(03)94371-5 ◽

2003 ◽

Vol 24 (5) ◽

pp. 192

Author(s):

M NAHRENDORF

Keyword(s):

Myocardial Infarction ◽

Factor Xiii ◽

Coagulation Factor ◽

Coagulation Factor Xiii ◽

Scar Healing

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Plasminogen-Plasmin System IX. Specific Binding of Tranexamic Acid to Plasmin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647851 ◽

1975 ◽

Vol 33 (03) ◽

pp. 573-585 ◽

Cited By ~ 20

Author(s):

Masahiro Iwamoto

Keyword(s):

Tranexamic Acid ◽

Affinity Chromatography ◽

Dissociation Constant ◽

Factor Xiii ◽

Specific Binding ◽

The Other ◽

Inhibitory Mechanism ◽

Binding Studies ◽

Similar Affinity ◽

Fibrin Structure

SummaryInteractions between tranexamic acid and protein were studied in respect of the antifibrinolytic actions of tranexamic acid. Tranexamic acid did neither show any interaction with fibrinogen or fibrin, nor was incorporated into cross-linked fibrin structure by the action of factor XIII. On the other hand, tranexamic acid bound to human plasmin with a dissociation constant of 3.5 × 10−5 M, which was very close to the inhibition constant (3.6 × 10−5 M) for this compound in inhibiting plasmin-induced fibrinolysis. The binding site of tranexamic acid on plasmin was not the catalytic site of plasmin, because TLCK-blocked plasmin also showed a similar affinity to tranexamic acid (the dissociation constant, 2.9–4.8 × 10−5 M).In the binding studies with the highly purified plasminogen and TLCK-plasmin preparations which were obtained by affinity chromatography on lysine-substituted Sepharose, the molar binding ratio was shown to be 1.5–1.6 moles tranexamic acid per one mole protein.On the basis of these and other findings, a model for the inhibitory mechanism of tranexamic acid is presented.

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New Families with Hereditary Hemorrhagic Trait due to Deficiency of Fibrin Stabilizing Factor (F. XIII)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651295 ◽

1968 ◽

Vol 20 (03/04) ◽

pp. 534-541 ◽

Cited By ~ 3

Author(s):

O Egeberg

Keyword(s):

Factor Xiii ◽

Family Members ◽

Recessive Inheritance ◽

Factor Xiii Deficiency ◽

History Of ◽

Congenital Factor

SummarySevere hemorrhagic disorder due to congenital factor XIII deficiency is described in two unrelated Norwegian girls.Plasma cephalin time was for both patients extraordinarily short during episodes of bleeding and hematomas. No such hyperactivity reaction was demonstrable in unaffected condition some months later.Estimations of blood factor XIII levels revealed a partial defect in the parents of both children, and also in some other family members, consistent with an autosomal incompletely recessive inheritance of the defect. Some of the presumptive heterozygotes had a history of light bleeding phenomenons; whether this was related to their partial lack of factor XIII is so far uncertain.

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