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Biomedical subjects

C K Kasper

Publications and source records attributed to C K Kasper.

120 records · Page 7Linked to original sources

Surgical operation in hemophilia B. Use of factor IX concentrate.

A concentrate containing plasma clotting factors II, VII, IX and X was used to secure hemostasis for a herniorrhaphy, an osteotomy of a femur, a cup arthroplasty of a hip, and a tonsillectomy in patients with factor IX deficiency. After single infusions of concentrate, the net increase in plasma factor IX activity was 0.7 to 1.0 percent for each in-vitro unit of factor IX infused per kilogram of body weight. After large infusions of concentrate in two patients, the disappearance pattern of factor IX had two phases: a first component with half-disappearance times of 4.4 and 6 hours, and a second component with half-disappearance times of 26 and 32.6 hours.

Adolescent↗

Hemophilia A: polymorphism detectable by a factor 8 antibody.

Plasma from 54 patients with hemophilia A was tested for neutralizing activity with a human antibody to factor VIII. The plasma from 52 patients had no demonstrable neutralizing activity. Two plasma samples had neutralizing activity equivalent to that of normal plasma despite the lack of factor VIII clotting activity. Apparently, most patients with hemophilia A do not synthesize factor VIII, whereas a few synthesize an inactive molecule with a presumed genetic structural mutation of the active site but with antigenic determinants in common with normal factor VIII. Thus, hemophilia A is a disease caused by more than a single genetic mechanism.

Antigen-Antibody Reactions↗

A protocol for cryoprecipitate production.

A three-year contract research program to study the production of cryoprecipitate has been completed. The investigators have collaborated to propose changes in the methods of production of cryoprecipitate. The investigators believe that the problem of low and variable yield of cryoprecipitate can be overcome and cryoprecipitate can be produced which contains, on an average, at least 100 Factor VIII units in nearly every bag. It is emphasized that breaches of technique and time delays in cryoprecipitate processing must be scrupulously avoided to achieve optimum, standardized yields.

Blood Donors↗

Determinants of factor VIII recovery in cryoprecipitate.

Many aspects of the production of cryoprecipitate were studied to determine which methods resulted in the greatest recovery of Factor VIII. The following recommendations resulted: 1) blood should be mixed with anticoagulant throughout phlebotomy; 2) blood should be centrifuged within a few hours of collection; 3) larger satellite bags should be used to contain the usual volume of plasma, for example, 200 ml of plasma should be frozen in a 600-ml capacity bag; 4) plasma should be centrifuged as soon as thawing is complete; 5) cryoprecipitate should be refrozen on dry ice; 6) cryoprecipitate should be stored at or below -30 C.; and 7) prolonged storage of frozen plasma or cryoprecipitate should be avoided. Variations in Factor VIII content from one bag of cryoprecipitate to another, under uniform production conditions, depends largely on two donor-specific attributes which tend to remain constant from time to time, namely, the donor's plasma Factor VIII level and the cryoprecipitability of his Factor VIII.

Blood Donors↗

Factor VIII preservation following collection into commercial plasmapheresis systems.

The two-stage method of Pool and Robinson was used in determining plasma Factor VIII activity following contact with four commercially available plastic blood and pooling bag films. Employing a two-arm double plasmapheresis technique, it was shown that Factor VIII activity in whole blood initially drawn into BB-69 and PL-130 blood bags decreased only slightly from in vivo levels for activity in PL-130 blood bags (t equal 3.2317, p. less than 0.01). Factor VIII activity fell to 98 and 90 per cent preservation levels from an initial 104 per cent in vivo activity, for BB-69 and PL-130 respectively. Factor VIII activity in plasma collected in Ellay and PL-146 pooling bags, both decreased significantly to 85 and 86 per cent, respectively, after three hours storage at room temperature (24 to 25.5 C). Following five weeks storage (-30 C) in Ellay and PL-146 pooling bags, Factor VIII activity significantly (p less than 0.005) fell to 79 and 77 per cent, respectively. No significant differences were observed when Factor VIII activity levels were compared in BB-69 versus PL-130 or Ellay versus PL-146 plastic film systems.

Blood Banks↗

Evaluation of two viral inactivation methods for the preparation of safer factor VIII and factor IX concentrates.

We report here the results of our evaluation of two procedures to eliminate viruses in factor VIII and factor IX coagulation factor concentrates. Both procedures were equally effective in the in vitro destruction of marker viruses. However, in a controlled infectivity test in chimpanzees, treatment at 60 degrees C for 20 hours inactivated greater than 500 and less than 10,000 chimpanzee infectious doses (CID) of hepatitis B virus, while treatment at 98 degrees C for 30 minutes inactivated less than 500 CID. Both methods were successful in preventing infection with an undetermined amount of an indeterminate non-A, non-B hepatitis agent. The 60 degrees C, 20-hour treatment method rendered 5.25 logs of the putative acquired immune deficiency syndrome virus, human T-cell lymphotrophic virus III/lymphadenopathy virus, added to factor VIII or factor IX concentrates, undetectable. Heat-treated factor VIII and factor IX complex concentrates prepared by these methods were tested against corresponding untreated control lots. There was no significant difference in the plasma recovery or plasma half-life of the factor (p greater than 0.05). The treated concentrates were equivalent to the control concentrates with respect to vital signs, clinical laboratory studies, and adverse reactions. The heat-treated concentrates appeared bioequivalent to the untreated concentrates with the additional benefit of inactivation of potentially present infectious viruses.

Animals↗

The pharmacology of a new pasteurized antihemophilic factor concentrate derived from human blood plasma.

The pharmacology of a new pasteurized factor VIII (FVIII) concentrate derived from human blood plasma was studied in 23 adults with hemophilia A. In Part 1 of the study involving six nonbleeding subjects, the mean increase in FVIII activity was 1.43 +/- 0.34 U per ml 10 minutes after an intravenous dose of 50 U per kg. The intravascular survival kinetics in these six patients showed a biphasic decay curve with an initial mean half-life of 5.1 +/- 1.2 hours probably representing early redistribution, and a late half-life of 13.3 +/- 4.9 hours. In Part 2 of the study, the activity at 10 minutes was measured in another 17 patients, as well as in one patient already studied in Part 1. The mean increase in activity with the 24 observations was 1.13 +/- 0.37 U per ml with a mean FVIII dosage of 51.0 +/- 2.6 U per kg of body weight. Only one patient had an allergic reaction, which did not recur when the patient was given a second lot.

Adult↗