Assay Method for the "Fibrin-Stabilizing Factor."

Lóránd, L.; Dickenman, R. C.

doi:10.3181/00379727-89-21711

Cited by 36 publications

(16 citation statements)

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“…In the present case, a general inhibitor to fibrin stabilization was suspected from the urea solubility of clots, which were obtained from recalcified mixtures of normal plasma in different proportions with the patient's plasma (7). However, to demonstrate that the actual target of the inhibitor was the factor XIII system itself, it was necessary to show that the patient's plasma or serum interfered with the ability of the purified human zymogen to mediate amine incorporation into protein upon activation by thrombin and Ca2+.…”

Section: Methodsmentioning

confidence: 92%

Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system.

Lóránd

Velasco

Rinne

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Serum from a patient who died from massive hemorrhage within 4 months after onset of an acquired bleeding disorder at age 85 contained a potent inhibitor of fibrin stabilization. Other parameters of coagulation and fibrinolysis and his bleeding time were within normal limits.The inhibitor was shown to be an IgG with K light chains (IgG Kansas); its specific target was the factor XIII system itself. Although IgG Kansas combined with the virgin lab] form ofthe zymogen, it did not block the thrombin-catalyzed conversion to [a'b]. However, IgG Kansas prevented the subsequent Ca2+-mediated activation of [a'b] to a* + b, where a* denotes the catalytically competent factor XIIa species. IgG Kansas, in contrast to a previously studied autoimmune antibody from a similar bleeding disorder (IgG Warsaw), could also inhibit the transamidating activity of the preactivated a* enzyme.Autoimmune antibodies can cause the premature destruction ofcells or connective tissue constituents. Catastrophic bleeding may occur following the appearance ofantibodies capable of neutralizing one of the coagulation components in the circulation. In this latter category, investigations relating to inhibitors of the fibrin stabilizing factor (factor XIII) system are particularly challenging on account of the molecular complexity of the activation of the zymogen (1-3). Earlier reports (4, 5) described two patients with acquired antibodies specifically targeted against the thrombin and Ca2l-regulated conversion of factor XIII to the XIIIa enzyme, which is normally required to strengthen the fibrin clot by NE-(< glutamyl)lysine side-chain bridges (6). Nevertheless, the two inhibitors could be shown to differ from one another in terms of recognizing the a subunit of the zymogen, which carries the potential catalytic site. The present paper deals with yet another autoimmune inhibitor, which, like the previously studied examples, blocked the activation of factor XIII. However, it could be distinguished from them by virtue ofthe fact that it interfered also with the functioning of the factor XIII. enzyme. This antibody was identified in the plasma and serum of an elderly individual who died of massive hemorrhage. Case ReportAn 85-year-old white male retired farmer was admitted to the hospital for evaluation of a bleeding tendency. He Physical examination revealed dullness to percussion at the right lung base, and edema and tenderness of the right thigh. Hemoglobin was 11.0 g/dl; leukocytes, 6800 per sUI; and platelets, 548,000 per /1. Prothrombin time was 12.2 s (normal, 11.0-13.0 s); activated partial thromboplastin time, 28.7 s (normal, 24.0-38.0 s); fibrinogen, 533 mg/dl; and bleeding time, 5.5 min (normal, 2.5-9.5 min). A clot prepared from the patient's citrated plasma (recalcified by mixing equal parts of plasma and 0.025 M calcium chloride) dissolved in 5 M urea in <24 hr (7). Samples containing various concentrations ofpatient's plasma (ranging from 10% to 95%) were prepared by mixing patient's citrated plasma with citrated pooled norm...

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Section: Methodsmentioning

confidence: 92%

Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system.

Lóránd

Velasco

Rinne

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…The method used for the determination of FSF was based on the principle that clots devoid of FSF are soluble in 1 % monochloracetic acid [29,41]. A twofold dilution series (up to 1:128) of plasma was prepared; 0.1 ml of each dilution was mixed with 0.1 ml of 0.02 M cysteine and incubated at 28° for 10 min to accomplish activation of FSF in the plasma [31].…”

Section: Methodsmentioning

confidence: 99%

“…Ideally, plasma should be preincubated with thrombin to activate the FSF contained therein [29]. Because this was not feasible, the concentration of thrombin was in excess of that needed for clotting, so as to achieve immediate activation of FSF at the time of mixing.…”

Section: Methodsmentioning

confidence: 99%

Changes in Fibrin-stabilizing Factor Levels in Relation to Maternal Hemorrhage and Neonatal Disease

Ambrus

Niswander

et al. 1970

Pediatr Res

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“…7, normal plasma displays no amine-incorporating activity in the absence of thrombin; only the precursor is present. The enzyme is produced transiently (7,28) after the appearance of thrombin. As a transpeptidase, FSF* is similar in its mode of action to other enzymes such as liver transglutaminase and muscle tissue coagulin (31).…”

Section: Discussionmentioning

confidence: 99%

“…An acquired reduction in the steady-state level of the factor in plasma may exist, in conjunction with a variety of diseased states (e.g. myeloma, lead poisoning [see also below], pernicious anemia, liver cirrhosis [28][29][30]). …”

Section: Discussionmentioning

confidence: 99%

Diagnostic and genetic studies on fibrin-stabilizing factor with a new assay based on amine incorporation

Lóránd¹,

Urayama²,

Kiewiet³

et al. 1969

J. Clin. Invest.

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211

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A B S T R A C T Fibrinoligase, the fibrin cross-linking enzyme, transiently appearing during the course of coagulation in normal blood, was shown to catalyze the incorporation of a fluorescent amine, monodansylcadaverine [or N-( 5-aminopentyl) -5-dimethylamino-1-naphthalenesulfonamide] into casein. The reaction provided the basis of a sensitive fluorimetric method for measuring the activity of the enzyme (and also of similar other transpeptidases, such as transglutaminase).In tests involving plasma, certain difficulties had to be overcome which were mainly due to the fact that the enzyme itself does not occur in citrated plasma. Only its precursor (fibrin-stabilizing factor or factor XIII) is present, still requiring limited proteolytic activation by thrombin. Thus, in order to measure amine incorporation with plasma as a source of the factor, thrombin must be added. This necessitated a differential desensitization of the intrinsic fibrinogen so that the latter could not clot and could not thereby interfere with amine incorporation. Also, the thrombin-inactivating capacity of plasma had to be saturated to enable full conversion of the factor to the transpeptidase. Concentrations of casein, monodansylcadaverine, calcium, and hydrogen ions were chosen to permit almost maximal velocity of amine incorporation. A linear relationship with regard to plasma concentration could be obtained only under such conditions. No similar assay is presently available for quantitatively evaluating fibrin-stabilizing factor levels in plasma.

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Assay Method for the "Fibrin-Stabilizing Factor."

Cited by 36 publications

References 0 publications

Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system.

Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system.

Changes in Fibrin-stabilizing Factor Levels in Relation to Maternal Hemorrhage and Neonatal Disease

Diagnostic and genetic studies on fibrin-stabilizing factor with a new assay based on amine incorporation

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