Human plasminogen is a β-globulin (2 % carbohydrate, molecular weight 90 KD), which in its native form has NH2-terminal glutamic acid (Glu-plasminogen) whose primary structure is known (31, 37, 38). From human plasma plasminogen can easily be isolated by affinity chromatography techniques (10, 25, and Table 1). Plasminogen is synthesized in many organs. The production site of the zymogen may be the liver (21), the eosinophiles (3) or the kindney (15). The plasma-plasminogen level is low in newborns (22) and even lower in the premature infant (2). In healthy adults it is found in plasma or serum in a concentration of 200 mg/l (= 2 μM, 22, 39). The half-life of the native (Glu-) plasminogen is 2.24 ± 0.29 days (6). Two types of Glu-plasminogen occur in human plasma, which differ in their carbohydrate composition as well as in their content of sialic acid. Genetic variants (see Mayr, 3.1.); of plasminogen have been reported (16) after isoelectric focusing of human plasma in polyacrylamide gels. Three patterns were found, two completely different and the third most likely a mixture of the other two. Characteristical functional properties of plasminogen are related to its molecular structure, e.g. its in vivo specificity for fibrin in contrast to the fairly unspecific in vitro activity of plasmin. Glu-plasminogen is easily converted by limited plasmic digestion to modified forms with NH2-terminal lysine, valine or methionine (35, 36), which are commonly designated Lys-plasminogen” (26) displaying a plasma half-life time of 0,8 days (6). Lys-plasminogen forms are easily converted to plasmin which results in the formation of two-chain molecule (Lys-plasmin) from the single-chain monomer (zymogen).
SummaryThis study was performed to evaluate the influence of different routes of administration on the efficacy of DDAVP treatment. Ten healthy volunteers received DDAVP intranasally (i.n.), subcutaneously (s.c.) and intravenously (i.v.) in a randomized cross-over trial. Factor XII and high molecular weight (HMW)-kininogen levels increased only slightly after DDAVP administration. The mean increase of factor VIII: C was 3.1 (i. v.), 2.3 (s. c.), and 1.3 (i.n.) - fold over baseline. Ristocetin cofactor (von Willebrand factor antigen) increased 3.1 (2.5), 2.0 (2.3) and 1.2 (1.2) - fold over baseline mean values after i.v., s.c. and i.n. DDAVP, respectively. The half-disappearance time of factor VIII and von Willebrand factor (vWF) after DDAVP ranged from five (factor VIII: C) to eight hours (vWF). The mean increase of fibrinolytic activity was more pronounced after i.v. DDAVP. The antidiuretic effect was moderate with no apparent differences between the routes of application. This study provides further evidence that both i.v. and s.c. DDAVP administration result in an appropriate and reliable stimulation of haemostasis. An additional advantage of s. c. administration is its suitability for home treatment.
SummaryFactor VIII :C recovery and half-life was measured in 16 hemophilia A patients under comprehensively standardized conditions. Each patient received the same lot of a steam-treated high purity FVIII concentrate at a dose of 19-33 U/kg body weight. A comparison was made between the one-stage assay, the two-stage assay and a chromogenic substrate test for FVIII :C determination using a FXa-sensitive chromogenic substrate. Factor VIII :C potency of the administered FVIII concentrate was measured using calibration curves derived from a concentrate standard and FVIII: C plasma levels were read from calibration curves derived from a plasma standard. The chromogenic assay showed a good reproducibility at FVIII: C levels between 0.015 and 0.50 U/ml. The FVIII :C recoveries calculated from the results of the one-stage assay, the two-stage assay and the chromogenic substrate test were 109 ± 20, 92 ± 14 and 81 ± 11% (x ± SD), respectively. The elimination half-lives of FVIII :C were calculated by non-linear least square analysis using a modified computerized Gauss-Newton algorithm. The half-lives calculated from the FVIII: C plasma levels measured by the one-stage assay, the two-stage assay and the chromogenic test were 23.8 ± 6.4, 22.2 ± 5.7 and 17.1 ± 4.8 h (x ± SD), respectively. No previous study has reported such long half-life values. Our findings indicate that measurements of recoveries and half-lives by the chromogenic FVIII :C assay and by computerized nonlinear least square analysis allow the possibility of individualized FVIII replacement therapy.
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