The <i>in vivo</i> Longevity of Antihaemophilic Factor (Factor VIII)

Abildgaard, Charles F.; Cornet, Jo Ann; Fort, Eleanor; Schulman, Irving

doi:10.1111/j.1365-2141.1964.tb00697.x

Cited by 34 publications

(19 citation statements)

References 13 publications

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“…These results are in agreement with others studying intermediate and high purity concentrates [1,2,14,16,22,26,29,31,39]. Previous results obtained in the same laboratory with lyophilized cryoprecipitate showed a F VIII:C biological half-life of 13 ±2 h [3] and with HPC 1, 11.3 ±3 h [4].…”

Section: Discussionsupporting

confidence: 82%

“…Recovery may vary according to the factor VIII product, the patient and the estimation of factor VIII dose. This study confirms the findings which showed similar recovery with factor VIII concentrates of various purity [26,39], Pre vious studies have shown large variations in recovery from patient to patient [1,2,6,10,34]. The recovery of F VIII:C was not sig nificantly related to the clinical state of the bleeding or nonbleeding patient [1].…”

Section: Discussionsupporting

confidence: 78%

“…In vivo recovery is determined by the ratio between either the F VIIFC plasma level measured at a given interval after infusion, or the highest level obtained in one of several early samples and the ex pected F VIIFC recovery. According to in vestigators, the time of sampling and there fore the assumed peak of F VIIFC plasma levels varies from 5 to 10 min to as late as 1-2 h postinfusion with cryoprecipitate and Cohn fraction I [2,3,31], with interme diate purity [1,16,26,31] and with high purity preparations [9,14,16,26], In this study, the F VIIFC plasma level was as sayed early (15 min) and late (30, 60 min) after infusion and in all cases the peak of F VIII:C was found at 1 h postinfusion. Al though all subjects had a hemorrhage at the time of infusion, it is unlikely that the clini cal status influenced the results.…”

Section: Discussionmentioning

confidence: 99%

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In vitro and in vivo Characterization of Factor VIII Preparations

Allain¹,

Verroust²,

Soulier³

1980

Vox Sanguinis

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An in vitro and in vivo comparison of nine commercial and noncommercial factor VIII preparations was made. These consisted of one lyophilized cryoprecipitate, four intermediate (IPC) and four high purity concentrates (HPC). Protein, fibrinogen, factor VIII complex, IgG, IgM and anti-A and B alloagglutinins levels were measured. These three qualities of product were defined by two ratios: units of F VIII : C per mg of protein and per mg of fibrinogen. They were, respectively, <0.5 and <1 in cryoprecipitate, 0.5-1 and 1-3 in IPC, and >1 and >3 in HPC. The F VIII : C/F VIII : AG ratio ranged from 0.3 to 0.6 and the F VIII : C/F VIII : VWF ratio was always lower than 1. Varying titers of alloagglutinins were found, unrelated to either IgG or IgM levels. Seven of these preparations were injected into several classical hemophilia A patients for treatment of minor hemorrhages. The peak of F VIII : C activity was always found 1 h postinjection. The F VIII : C recovery ranged from 80 to 140% and the half-life from 8 to 15 h. No significant difference was found among these products and the clinical efficacy was similar.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

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In vitro and in vivo Characterization of Factor VIII Preparations

Allain¹,

Verroust²,

Soulier³

1980

Vox Sanguinis

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“…The initial rapid phase showed a mean half-disappearance time of 5.5 hours (range 4.3-6.0 hours), and the slower second component represented a mean biological half-life of 10.8 hours (range 6-14 hours). These results agreed fairly closely with those of other workers, using a variety of preparations containing factor VIII-for example, Shulman et al (1962), Adelson et al (1963, Biggs and Denson (1963), and Abildgaard et al (1964). …”

Section: Total Protein and Fibrinogen Concentrationsupporting

confidence: 92%

Antihaemophilic globulin: preparation by an improved cryoprecipitation method and clinical use.

Brown¹,

Hardisty²,

Kosoy³

et al. 1967

BMJ

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The control of bleeding episodes in haemophilia and the prevention of excessive haemorrhage after surgical procedures depend chiefly on raising the patient's plasma factor VIII concentration to an appropriate haemostatic level, and maintaining this so long as the likelihood of bleeding continues. With whole plasma it is impossible to achieve levels much above 25%, or to maintain values constantly above about 10 % for more than two or three days, without overloading the patient's circulation. In (Pool and Shannon, 1965) Approximately 500 ml. of blood was taken from each donor into a double pack (Fenwal JD-2) by a clean venepuncture. Continuous gentle agitation ensured thorough mixing of the blood and the acid-citrate-dextrose anticoagulant throughout the bleeding. At the end of the blood donation 5 ml. of wellmixed blood was run back out of the pack for factor VIII assay. The blood pack and assay sample were then rapidly cooled to 2-4' C. in a water-bath containing melting crushed ice, and kept at this temperature until they could be transferred to a precooled centrifuge at 40 C. The pack was then centrifuged for 30 minutes at 1,600 g to obtain the maximum yield of platelet-poor plasma, while the assay sample was centrifuged and assayed immediately for factor VIII.Not more than 280 ml. of plasma, free of red cells and buffy coat, was transferred to the 300-ml. satellite pack, which was placed in a cardboard carton and immersed in a mixture of solid CO2 and ethanol at about -70°C. in a large vacuum flask, leaving the attached main blood pack on the bench beside it. The plasma was allowed to remain in the freezing mixture for at least 10 minutes, and then both packs, still joined Rapid MethodBlood was taken into 500-ml. single packs (Fenwal JA-2C), which were handled and centrifuged as in the slow method, described above, to obtain platelet-poor plasma. As much plasma as possible (260-340 ml.) was then transferred to a 600-ml. transfer pack (Fenwal TA-1), which was flattened between two sheets of copper mesh and frozen at about -700 C.In this way, plasma froze as a thin slab more rapidly than in the 300-ml. transfer pack used in the slow method.The plasma was allowed to remain in the freezing mixture for six minutes, and was then transferred to a water-bath at 6-80 C. As soon as the outer layer of plasma began to thaw, the pack was gently kneaded to enable thawing to continue as evenly and rapidly as possible throughout the pack. This process ensured complete thawing of the plasma within 90 minutes. The pack was then centrifuged at 1,600 g for 15 to 20 minutes, and the supernatant plasma removed, leaving 5-15 ml. in the pack with the cryoprecipitate. As double-pack units with attached 600-ml. transfer packs were not available, this was not a closed system and so the plasma was not returned to the red cells.If not used immediately the cryoprecipitate was snap-frozen at -700 C. before storing at -30°C. until use. Administration of ConcentrateAll concentrates were administered intravenously by syringe within ha...

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“…Therefore, the amount of contaminant antihemophilic globulin within the present 'I-fibrinogen should be less than that in the previous 125I-fibrinogen, since exactly the same method of preparation was used (5). Antihemophilic globulin has been reported to have a half-life of several hours (21,22). Therefore, a longer half-life should be expected for the present 131I-fibrinogen compared with that of the previous 125I-fibrinogen (5), if the contaminant antihemophilic globulin played a significant part, and the observed shorter half-life of 13'I-fibrinogen in hemophilia A patients cannot be explained on this basis.…”

Section: Resultsmentioning

confidence: 99%

Studies of the Metabolism and Distribution of Fibrinogen in Patients with Hemophilia A*

Takeda¹,

Chen²

1967

J. Clin. Invest.

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Abstract. Using autologous ""1I-fibrinogen, we made studies of the metabolism and distribution of fibrinogen in 10 patients with hemophilia A. In two patients simultaneous studies of autologous 13I-fibrinogen and homologous 125I-fibrinogen prepared from healthy donors' plasma were carried out. The average value for the plasma volume was 42.1 ± 8.8 ml/kg; for the plasma fibrinogen concentration, 349 + 90 mg/100 ml; for the intravascular fibrinogen, 144 ± 32 mg/kg; for the interstitial fibrinogen, 30 ± 11 mg/kg; for the slower half-life of 11I-fibrinogen, 2.34 + 0.17 days; for the transcapillary transfer rate of fibrinogen, 109 + 37 mg/kg per day; and for the catabolic and synthetic rates of fibrinogen, 51.7 + 13.1 mg/kg per day. Comparison of these results with those of the previous study in healthy male subjects showed that in patients with hemophilia A the catabolic and synthetic rates of fibrinogen are markedly increased, whereas the plasma fibrinogen concentration, intravascular and interstitial fibrinogen, and the transcapillary transfer rate of fibrinogen are not significantly different. The simultaneous studies of autologous 131I-fibrinogen and normal homologous 125I-fibrinogen in two subjects revealed that the two preparations behaved very similarly. Based on these findings, we concluded that our present findings are not due to the qualitative difference between the hemophilia A and normal fibrinogens, but that they are due to the difference in the host condition with respect to the fibrinogen metabolism, which is either an increased rate of direct breakdown of fibrinogen or an increased rate of fibrinogen breakdown after fibrin formation, or both.

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The in vivo Longevity of Antihaemophilic Factor (Factor VIII)

Cited by 34 publications

References 13 publications

In vitro and in vivo Characterization of Factor VIII Preparations

In vitro and in vivo Characterization of Factor VIII Preparations

Antihaemophilic globulin: preparation by an improved cryoprecipitation method and clinical use.

Studies of the Metabolism and Distribution of Fibrinogen in Patients with Hemophilia A*

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