Studies on the Response of Patients with Classic Hemophilia to Transfusion with Concentrates of Antihemophilic Factor

Bennett, Bruce; Ratnoff, Oscar D.

doi:10.1172/jci107076

Cited by 37 publications

(5 citation statements)

References 7 publications

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“…The recoveries, distribution times and elimination times of the injected Factor VII1:C differ too much from patient to patient even when using the same products from the same production line and testing them on the same patient. This has been substantiated by numerous observations reported [I, 2, 3,6,7,9,12,13,14,15,16,17,19,20,21,22,29,30,31,32,33,34,36,38,42,43,451. There has been some speculation on the causes for the different findings.…”

Section: Discussionsupporting

confidence: 70%

“…vious substitutions and the various clinical situations which make an injection essential. Additional differences existing among the various authors concern the factor dosage administered, injection volumes, injection speeds and time intervals, times and techniques used in the taking of blood samples as well as the storage of the plasma obtained until determination of Factor VIII:C (1,2,3,6,7,9,12,13,14,15,16,17,19,20,21,22,29,30,31,32,33,34,36,38,42,43,45). It becomes apparent that these variables make it very difficult to compare the papers dealing with the in vivo behaviour of different Factor Vlll products.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Factor Viii Concentrates in Non‐bleeding Patients

Schimpf

Rothmann

Schumacher

1984

Scandinavian Journal of Haematology

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The comparison of in vivo recovery of Factor VIII:C of 3 Factor VIII concentrates in two consecutive cross‐over studies on non‐bleeding patients suffering from a severe hemophilia A showed in both instances equally strong differences; values more than twice as high were obtained with product C than with product A. The cause for this was found to lie in the different declarations of the products. With calculations based on the results of the in vitro testing of the concentrates, the recoveries of the 3 products largely converged. For this reason one should demand that declarations for all products be made in accordance with uniform rules. In both studies the mean values of the half elimination times (half‐lives) of Factor VIII:C were in each case the same for the 3 products; but in study a) the mean value of half‐lives was distinctly longer (14.1 hrs) than in study b) (10.5 hrs). The recovery, too, was higher in study a) (1.96 YO) per injected unit measured than in study b) (1.4%). This occurred despite identical conditions in both studies. An explanation for this was not found. There was a tendency towards a positive relationship between recovery and body weight. According to the applied cross‐over design, the rank order of the Factor VIII:C recoveries found between the various concentrates were not blurred by the individual differences from patient to patient; nor were they blurred by the strong varying hematocrit values and other unknown factors relating to deviations in recovery, distribution time and elimination time from patient to patient. There can be no doubt as to the advantages of the cross‐over methodoly when performing direct in vivo comparisons.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Comparison of Factor Viii Concentrates in Non‐bleeding Patients

Schimpf

Rothmann

Schumacher

1984

Scandinavian Journal of Haematology

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“…Factor V and factor VIII coagulant activity (VIII: C) were assayed by one-stage techniques based on the correction of the prolonged clotting times of specific factor deficient plasmas [13,14]. Factor VIII-related antigen (VIII R: Ag) was measured by immuno-electrophoresis using antibody to factor VIIIR: Ag produced by Behringwerke (Marburg, FRG) [15]. A normal pool of plasma obtained from 20 healthy male medical students was used as a control.…”

Section: Methodsmentioning

confidence: 99%

Haemostatic changes in diabetic coma

Paton

1981

Diabetologia

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Diabetic coma is frequently associated with thromboembolic complications. A prospective study was undertaken of the haemostatic changes occurring in 15 patients (12 with ketoacidosis, three with the hyperosmolar syndrome) during diabetic coma. When compared with the results after stabilization of the diabetes, ketoacidosis was associated with significantly higher levels of factor VIII coagulant activity, factor VIII-related antigen and fibrin degradation products, a shorter partial thromboplastin time and reduced concentrations of antithrombin III. These results suggest that in uncomplicated ketoacidosis, haematological changes occur which may reflect vascular endothelial damage and intravascular fibrin deposition. Out of three deaths, two patients (both with the hyperosmolar syndrome) had evidence of disseminated intravascular coagulation. To reduce further the mortality and morbidity from diabetic coma, controlled clinical trials of anticoagulant and antiplatelet drugs may be indicated.

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“…The half-life of bovine factor VIII preparations infused into hemophilic dogs are shorter (Table 1) than the 12-14 hrs previ ously reported for the survival of human factor VIII preparations in human subjects (17)(18)(19). This is perhaps not surprising, as the dog has a circulation time of 9.5 sec (20) which is considerably shorter than the 18 sec of man (21).…”

mentioning

confidence: 84%

Kinetic Analysis of Bovine Factor VIII in the Hemophilic Dog

1981

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SummaryBovine factor VIII, which did not contain platelet aggregating factor activity, was infused into hemophilic dogs. Factor VIII procoagulant (VIII: C) levels in the dogs increased dramatically, then decreased in a biphasic manner. The half-life of the longest component was 3-7 hrs. The infusions were hemostatically effective and also caused a prolonged shortening of the activated partial thromboplastin time. These studies demonstrate that the platelet aggregating factor activity of bovine factor VIII is not essential for its maintenance in the circulation and that preparations lacking this activity may be clinically useful. When concentrates of partially purified factor VIII: C (essentially free of both platelet aggregating factor and factor VIII-related antigen) were infused, marked increases in VIII: C levels were also observed, but the half-life was significantly shorter (T1/2 of approximately 1 hr).

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Studies on the Response of Patients with Classic Hemophilia to Transfusion with Concentrates of Antihemophilic Factor

Cited by 37 publications

References 7 publications

Comparison of Factor Viii Concentrates in Non‐bleeding Patients

Comparison of Factor Viii Concentrates in Non‐bleeding Patients

Haemostatic changes in diabetic coma

Kinetic Analysis of Bovine Factor VIII in the Hemophilic Dog

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