Factor XIII deficiency enhances thrombin generation due to impaired fibrin polymerization — An effect corrected by Factor XIII replacement

Pitkänen, Hanna; Jouppila, Annukka; Lemponen, Marja; Ilmakunnas, Minna; Ahonen, Jouni; Lassila, Riitta

doi:10.1016/j.thromres.2016.11.012

Cited by 19 publications

(14 citation statements)

References 27 publications

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“…. [15][16][17][18] In the DSSinduced colitis mouse model, GPRP was given daily by intraperitoneal injection. Compared with the control treatment (distilled water), GPRP significantly inhibited body weight loss and dramatically reduced DSS-induced mortality and shortening of colon length (Figure 2A-C).…”

Section: Q9mentioning

confidence: 99%

Fibrinogen/AKT/Microfilament Axis Promotes Colitis by Enhancing Vascular Permeability

Zhang

Chen

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Section: Q9mentioning

confidence: 99%

Fibrinogen/AKT/Microfilament Axis Promotes Colitis by Enhancing Vascular Permeability

Zhang

Chen

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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“…23 These results are comparable to results of others, who reported shortened lag time with afibrinogenemia and with FXIII deficiency as well. 25,26 The latter group argued that In the case of shortened lag times in patients with absent PAI-1, the higher plasmin levels generated and increased fibrinolysis may result in partial activation of coagulation proteins. For instance, plasmin influences coagulation by (in)activation of factor VII, factor VIII, factor IX, factor X and factor XII.…”

Section: Pai-1 Deficient Population Exhibited Very High Plasmin Genermentioning

confidence: 99%

Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency

et al. 2019

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Introduction Deficiencies of plasminogen and plasminogen activator inhibitor type 1 (PAI‐1) are rare disorders of fibrinolysis. Current laboratory assays for analysis of activity of plasminogen and PAI‐1 do not provide an accurate correlation with clinical phenotype. Methods The Nijmegen Hemostasis Assay (NHA) was used to simultaneously measure thrombin and plasmin generation in 5 patients with plasminogen deficiency (PLGD) and 10 patients with complete PAI‐1 deficiency. Parameters analysed included: lag time ratio, thrombin peak time ratio, thrombin peak height, thrombin potential (AUC), fibrin lysis time, plasmin peak height and plasmin potential. Parameters were expressed as a percentage compared to a reference value of 53 healthy normal controls. Results Patients with PLGD demonstrated a short lag time and thrombin peak time, with normal thrombin peak height but an increased AUC. Plasmin generation was able to be detected in only one (23% plasminogen activity) of the five PLGD patients. All ten PAI‐1 deficient patients demonstrated a short lag and thrombin peak time, low thrombin peak height with normal AUC. Plasmin generation revealed an increased plasmin peak and plasmin potential; interestingly, there was a large variation between individual patients despite all patients having the same homozygous defect. Conclusion Patients with either PLGD or PAI‐1 deficiency show distinct abnormalities in plasmin and thrombin generation in the NHA. The differences observed in the propagation phase of thrombin generation may be explained by plasmin generation. These results suggest that disorders of fibrinolysis also influence coagulation and a global assay measuring both activities may better correlate with clinical outcome.

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“…Our present study indicates that increasing concentrations of FXIII enhance clot strength at xed concentrations of PC (1 IU/ml) and FGN (4 g/l). Consistently, there is further evidence that FXIII de ciency will impair FGN function and brin formation, suggesting an inverse link between low FXIII levels and enhanced thrombin generation, modifying the structure-function relationship of brin to support hemostasis 34 . Data derived from clinical studies propose maintenance of 50-60% of FXIII activity to avoid bleeding tendency in the perioperative setting 35 .…”

Section: Discussionmentioning

confidence: 67%

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

Koller

Kinast

Castellanos

et al. 2021

Preprint

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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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Factor XIII deficiency enhances thrombin generation due to impaired fibrin polymerization — An effect corrected by Factor XIII replacement

Cited by 19 publications

References 27 publications

Fibrinogen/AKT/Microfilament Axis Promotes Colitis by Enhancing Vascular Permeability

Fibrinogen/AKT/Microfilament Axis Promotes Colitis by Enhancing Vascular Permeability

Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency

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

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