Clinical influence of preoperative factor XIII activity in patients undergoing pancreatoduodenectomy

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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Plasma Factor XIII and Platelet Factor XIII in Hyperlipaemia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648075 ◽

1976 ◽

Vol 36 (03) ◽

pp. 542-550 ◽

Cited By ~ 6

Author(s):

Mircea P. Cucuianu ◽

K Miloszewski ◽

D Porutiu ◽

M. S Losowsky

Keyword(s):

Factor Xiii ◽

Significant Contribution ◽

Quantitative Assay ◽

Factor Xii ◽

Platelet Factor ◽

Type Iv ◽

Plasma Factor ◽

Hepatic Synthesis

SummaryPlasma factor XIII activity measured by a quantitative assay was found to be significantly higher in hypertriglyceridaemic patients (type IV and combined hyperlipoproteinaemia), as compared to normolipaemic controls. No such elevation in plasma factor XIII activity was found in patients with type IIa hyperlipaemia. Plasma pseudocholinesterase was found to parallel the elevated factor XIII activity in hypertriglyceridaemic subjects.In contrast, platelet factor XIII activity was not raised in hyperlipaemic subjects, and plasma factor XIII was found to be normal in a normolipaemic subject with throm-bocythaemia.It was concluded that there is no significant contribution from platelets to plasma factor XIII activity, and that the observed increase in plasma factor XII in hypertriglyceridaemia results from enhanced hepatic synthesis of the enzyme.

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Cross-Linked αsγt-Chain Hybrids in Plasma Clots Studied by 1D- and 2D Electrophoresis and Western Blotting

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649601 ◽

1993 ◽

Vol 70 (03) ◽

pp. 438-442 ◽

Cited By ~ 6

Author(s):

B Grøn ◽

C Filion-Myklebust ◽

S Bjørnsen ◽

P Haidaris ◽

F Brosstad

Keyword(s):

Molecular Weight ◽

Monoclonal Antibodies ◽

Human Plasma ◽

Western Blotting ◽

Isoelectric Point ◽

Factor Xiii ◽

Cross Linking ◽

2D Electrophoresis ◽

Complex Phenomenon ◽

Fibrinopeptide A

SummaryFibrinogen and fibrin related chains in reduced human plasma as well as the bonds interlinking partially cross-linked fibrin from plasma clots have been studied by means of 1D- and 2D electrophoresis and Western blotting. Immunovisualization of reduced plasma or partially cross-linked fibrin with monoclonal antibodies specific for the α-chains or the γ-chains have shown that several bands represent material belonging to both chains. In order to decide whether these bands constitute αγ-chain hybrids or superimposed α- and γ-chain dimers, the cross-linked material was separated according to both isoelectric point (pI) and molecular weight (MW) using Pharmacia’s Multiphor II system. Western blotting of the second dimension gels revealed that partially cross-linked fibrin contains αsγt-chain hybrids and γ- polymers, in addition to the well-known γ-dimers and α-polymers. The main αsγt-chain hybrid has a pI between that of the α- and the γ-chains, a MW of about 200 kDa and contains Aα-chains with intact fibrinopeptide A (FPA). It was also observed that soluble fibrinogen/fibrin complexes as well as partially cross-linked fibrin contain degraded α-dimers with MWs close to the γ-dimers. These findings demonstrate that factor XIII-catalyzed cross-linking of fibrin is a more complex phenomenon than earlier recognized.

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Pharmacokinetics and Tolerability of Factor XIII Concentrates Prepared from Human Placenta or Plasma: a Crossover Randomised Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649787 ◽

1995 ◽

Vol 74 (02) ◽

pp. 622-625 ◽

Cited By ~ 29

Author(s):

H H Brackmann ◽

R Egbring ◽

A Ferster ◽

P Fondu ◽

J M Girardel ◽

...

Keyword(s):

Factor Xiii ◽

Bleeding Events ◽

Serious Adverse Events ◽

Double Blind ◽

Randomised Study ◽

The Mean ◽

Blind Crossover Study ◽

Double Blind Crossover Study ◽

Fxiii Activity ◽

Observation Period

SummaryThe pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma.Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.

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Protection from Hg-Inactivation of Factor XIII by Mercaptalbumin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654244 ◽

1970 ◽

Vol 24 (03/04) ◽

pp. 352-355 ◽

Cited By ~ 2

Author(s):

P Fantl

Keyword(s):

Blood Plasma ◽

Factor Xiii ◽

Active Component ◽

Plasma Albumin ◽

Plasma Factor ◽

Mercuric Ions

SummaryThe blood plasma factor XIII (fibrin stabilizing factor) is inactivated by mercuric ions and can be reactivated by serum - or plasma albumin of which the active component is mercaptalbumin. A relation between mercaptalbumin concentration and factor XIII activity is pointed out.

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Platelet Accumulation on Fibrin-coated Polyethylene: Role of Platelet Activation and Factor XIII

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653880 ◽

1995 ◽

Vol 73 (05) ◽

pp. 850-856 ◽

Cited By ~ 14

Author(s):

F D Rubens ◽

D W Perry ◽

M W C Hatton ◽

P D Bishop ◽

M A Packham ◽

...

Keyword(s):

Factor Xiii ◽

Cross Linking ◽

Internal Diameter ◽

Static System ◽

Graft Occlusion ◽

Platelet Binding ◽

Coated Surface ◽

Platelet Accumulation ◽

Polyethylene Tubing

SummaryPlatelet accumulation on small- and medium-calibre vascular grafts plays a significant role in graft occlusion. We examined platelet accumulation on the surface of fibrin-coated polyethylene tubing (internal diameter 0.17 cm) during 10 min of flow (l0ml/min) at high wall shear rate (764 s-1). Washed platelets labelled with 51Cr were resuspended in Tyrode solution containing albumin, apyrase and red blood cells (hematocrit 40%). When the thrombin that was used to form the fibrin-coated surface was inactivated with FPRCH2C1 before perfusion of the tubes with the platelet:red blood cell suspension, the accumulation of platelets was 59,840 ± 27,960 platelets per mm2, whereas accumulation on fibrin with residual active thrombin was 316,750 ± 32,560 platelets per mm2 (n = 4). When the fibrin on the surface was cross-linked by including recombinant factor XIII (rFXIII) in the fibrinogen solution used to prepare the fibrin-coated surface, platelet accumulation, after thrombin neutralization, was reduced by the cross-linking from 46,974 ± 9702 to 36,818 ± 7964 platelets per mm2 (n = 12, p <0.01). Platelet accumulation on tubes coated with D-dimer was ten times less than on tubes coated with D-domain; this finding also supports the observation that cross-linking of fibrin with the formation of γ-γ dimers reduces platelet accumulation on the fibrin-coated surface. Thrombin-activated platelets themselves were shown to cross-link fibrin when they had adhered to it during perfusion, or in a static system in which thrombin was used to form clots from FXIII-free fibrinogen in the presence of platelets. Thus, cross-linking of fibrin by FXIII in plasma or from platelets probably decreases the reactivity of the fibrin-containing thrombi to platelets by altering the lysine residue at or near the platelet-binding site of each of the γ-chains of the fibrinogen which was converted into the fibrin of these thrombi.

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Determination of Factor XIII Activity and of Factor XIII Inhibitors Using an Ammonium-Sensitive Electrode

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665256 ◽

1983 ◽

Vol 50 (02) ◽

pp. 563-566 ◽

Cited By ~ 3

Author(s):

P Hellstern ◽

K Schilz ◽

G von Blohn ◽

E Wenzel

Keyword(s):

Factor Xiii ◽

Normal Subjects ◽

The Other ◽

Activity Measurement ◽

Factor Xiii Deficiency ◽

Assay Procedure ◽

Stabilization Factor ◽

Release Method ◽

Sensitive Electrode

SummaryAn assay for rapid factor XIII activity measurement has been developed based on the determination of the ammonium released during fibrin stabilization. Factor XIII was activated by thrombin and calcium. Ammonium was measured by an ammonium-sensitive electrode. It was demonstrated that the assay procedure yields accurate and precise results and that factor XIII-catalyzed fibrin stabilization can be measured kinetically. The amount of ammonium released during the first 90 min of fibrin stabilization was found to be 7.8 ± 0.5 moles per mole fibrinogen, which is in agreement with the findings of other authors. In 15 normal subjects and in 15 patients suffering from diseases with suspected factor XIII deficiency there was a satisfactory correlation between the results obtained by the “ammonium-release-method”, Bohn’s method, and the immunological assay (r1 = 0.65; r2= 0.70; p<0.01). In 3 of 5 patients with paraproteinemias the values of factor XIII activity determined by the ammonium-release method were markedly lower than those estimated by the other methods. It could be shown that inhibitor mechanisms were responsible for these discrepancies.

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Defective Fibrin Crosslinking in Acute Leukemia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661210 ◽

1984 ◽

Vol 52 (03) ◽

pp. 343-346 ◽

Cited By ~ 1

Author(s):

F Rodeghiero ◽

T Barbui ◽

A Dal Belin-Peruffo ◽

E Dini

Keyword(s):

Acute Leukemia ◽

Factor Xiii ◽

Factor Xiii Deficiency ◽

Coagulation Abnormalities ◽

Normal Plasma ◽

Transamidating Activity

SummaryFibrin crosslinking was assayed in 22 patients with acute leukemia showing secondary coagulation abnormalities of variable severity. In 9 patients fibrin crosslinking was found to be normal, whereas 10 patients presented impaired polymerization of α-chains and 3 of both α- and γ-chains.Only a rough correlation was found between transamidating activity of factor XIII and the fibrin crosslinking pattern in these patients. Moreover, incomplete fibrin crosslinkage occurred at levels of factor XIII far in excess of that required for full polymerization of fibrin in “normal” plasma. This latter finding suggests that, in addition to factor XIII deficiency, other causes are responsible for thehigh rate of fibrin crosslinking impairment in acute leukemia.

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