In-vivo Recovery Research Articles

Prestorage white cell reduction in saline-adenine-glucose-mannitol red cells by use of an integral filter: evaluation of storage values and invivo recovery.

Prestorage white cell (WBC) reduction in blood components may decrease the incidence of adverse reactions and improve component quality. A bottom-and-top system with an integral third-generation WBC-reduction filter has been studied. Whole blood was collected from 30 healthy donors: from 20 by using a blood container system with an integral filter and from 10 controls by using a standard blood container system. Ten test units were buffy coat-depleted, stored for 72 hours at 4 degrees C, and then filtered, while an additional 10 test units were buffy coat-depleted and filtered at room temperature within 8 hours of collection. All units were stored at 4 degrees C for 42 days and sampled weekly. The mean WBC content of the 72-hour, 4 degrees C units was 0.33 x 10(6), that of the room-temperature units was 2.6 x 10(6), and that of the buffy coat-depleted controls was 460 x 10(6) (p < 0.0005). No significant differences were found among lactate, glucose, sodium, potassium, and plasma hemoglobin levels in the three groups. ATP and 2,3 DPG levels were significantly better preserved in control units than in 72-hour, 4 degrees C units (p = 0.016 and p = 0.032, respectively), but not better than in the room-temperature units. Significant differences were observed between pH values in filtered units and both groups of test units (p = 0.016). In biologic terms however, these differences were small. Red cells from an additional eight healthy volunteer donors were processed by an 8-hour room-temperature method and stored for 35 days. Studies in vivo 24-hour recovery of autologous red cells were performed by transfusing a radiolabeled (51Cr plus 131I-albumin) aliquot after 35 days' storage. Good recovery (mean > 80%) was found by both the single- and double-isotope-label methods. Recovery was significantly greater when calculated by the single-isotope method (p = 0.02). The combination of buffy coat removal and filtration in the blood container system with an integral filter achieved effective WBC reduction (> or = 3 log10 reduction from whole blood) without biologically significant detriment to in vitro or in vivo storage values.

Pharmacokinetics of two pasteurized Factor VIII concentrates by different and multicenter assays of Factor VIII activity

We assessed the pharmacokinetic characteristics of a new high-purity pasteurized FVIII concentrate in comparison with an intermediate purity pasteurized concentrate, produced by the same manufacturer. The study was designed as a cross-over single-dose pharmacokinetic investigation in 8 non-bleeding patients with severe hemophilia A. All patients were given 25 IU/kg of each of the two concentrates, with an interval of at least one week between the two administrations. Decay curves were assessed by collecting 10 serial blood samples over 36 hours following the end of infusion. The concentration of Factor VIII in blood samples was determined in triplicate in three different laboratories using each of the following assay methods: a one-stage clotting assay, a two-stage clotting assay, and a two-stage chromogenic-peptide substrate assay. All pharmacokinetic parameters were calculated by model-independent methods. The two products were found to differ significantly both in the clearance, which was on average 13.8% lower for Haemate P, and in the in-vivo recovery, which was 11.7% lower for Factor VIII:C P on the average. In comparison with previous pharmacokinetic data obtained from other heated Factor VIII concentrates, the clearance of Haemate P was found to be significantly slower, while the half-life of both products was longer. No differences were observed in the Vd-area. These findings indicate that the purification procedures to which both products are subjected do not increase the in-vivo rate of plasma disappearance of Factor VIII.

Pharmacokinetics of a new heat-treated concentrate of factor VIII estimated by model-independent methods

We evaluated the pharmacokinetic properties of Kryobulin TIM3, a new heat-treated Factor VIII concentrate which has recently become available in Europe. Twelve patients with classic hemophilia were studied. In each patient, Factor VIII was given as a single dose (ranging from 11.6 to 30.3 units/kg) after which eight serial blood samples were drawn to characterize the disappearance of Factor VIII from the plasma. Model-independent (noncompartmental) methods were used for pharmacokinetic analysis. The following pharmacokinetic parameters of Factor VIII (mean±SD) were estimated: clearance = 3.83 ± 0.99 ml/h/kg; mean residence time = 15.9±4.5 h; volume of distribution at steady state = 55.6±9.3 ml/kg; in-vivo recovery = 129±29 %. The pharmacokinetic parameters of Kryobulin TIM3 obtained in our study are very similar to those previously reported for the untreated concentrate. Thus, our findings suggest that the dosing guidelines previously available for the untreated concentrate need not be revised when using the treated product.

Use of heat-treated clotting-factor concentrates in patients with haemophilia and a high exposure to HTLV-III.

In a group of 126 Australian patients with haemophilia, who were receiving lyophilized clotting-factor concentrates prepared from locally collected plasma, a high prevalence of antibody to human T-cell lymphotropic virus III (HTLV-III) was demonstrated in those with severe disease. Patients with moderate or mild disease had a much lower prevalence of HTLV-III antibody. After heat treatment of lyophilized factor VIII and factor IX concentrates (60 degrees C for 72 hours) to inactivate the virus, the losses of activity of an intermediate-purity and of a fibrinogen-poor factor VIII concentrate, and of the coagulant activity of a factor IX concentrate, were within acceptable limits. The solubility of the intermediate-purity factor VIII concentrate was markedly decreased; the fibrinogen-poor factor VIII concentrate and the factor IX concentrate were readily soluble. In-vivo recovery and survival of heated concentrates were equivalent to those of the unheated products, and they were effective in the treatment of spontaneous and traumatic haemorrhages.

MODIFIED METHOD FOR THE IN-VIVO RECOVERY OF FERTILIZED OVA IN SWINE

A convenient source of fertilized ova at the appropriate stage of development is a prerequisite for successful ovum transfer. Since it has not yet been possible to fertilize freshly ovulated, or even follicular oocytes, which have been obtained from slaughter-house material, in vitro, or after transfer to inseminated sows in vivo, the only remaining sources of fertilized eggs are from naturally or artificially inseminated sows during the first days following ovulation. In particular, if the technique of simultaneous, reciprocal egg transfer between individuals is to be employed, it is important to recover the ova from the living animal. Judicious planning of transfer experiments necessitates the recovery of a maximal proportion of the ovulated eggs in a cleaved stage. Hitherto, only a few experiments on the in-vivo recovery of swine ova have been described. Schmidt &