Experience of using human albumin solution 4.5% in 1195 therapeutic plasma exchange procedures.

The aim of the study was to document the incidence of adverse reactions (ADRs) in subjects undergoing therapeutic plasma exchange with human albumin 4.5% solution (Zenalb 4.5) and to explore whether there were any differences in tolerability with a change from UK to US plasma and a subsequent manufacturing modification. Zenalb 4.5 was initially manufactured from recovered plasma from UK blood donations and later from source plasma from US donors. The modification was a salt diafiltration step. A prospective survey was conducted at three UK aphaeresis units; data from 154 subjects undergoing 1195 plasma exchanges using Zenalb 4.5 were collected. Adverse events with at least a possible relationship to treatment were recorded. There were 20 ADRs per 1195 exchanges (1.7%), experienced by 14 subjects (9.1%). The most common reaction was rigours in 17 exchanges (1.4%) and 12 subjects (7.8%). ADRs occurred in 0.8% (2/250) of plasma exchanges with UK plasma, 0.2% (1/539) using US plasma/original manufacturing method, 4.3% (16/370) using US plasma/modified method and 12.5% (1/8) using US plasma/mixed original and modified methods. Data were incomplete for the remaining 28 exchanges, but no ADRs were reported. Moreover, 17 ADRs occurred over a 14-month period and involved 10 batches manufactured from US plasma (1 original, 9 by modified method). The incidence then returned to the previously lower level. There was no explanation for this cluster of events. Overall, there was no evidence that plasma source or manufacturing method affected tolerability and it was concluded that human albumin 4.5% solution (Zenalb 4.5) is well tolerated during plasma exchange therapy.

Efficacy criteria and cholesterol targets for LDL apheresis.

Low density lipoprotein (LDL) apheresis is now accepted as the treatment of choice for patients with homozygous familial hypercholesterolaemia and for heterozygotes with cardiovascular disease refractory to lipid-lowering drug therapy. However, a paucity of evidence has meant that detailed guidance on the extent of cholesterol reduction required to prevent the onset or progression of cardiovascular disease in these high risk patients is lacking. This review defines criteria for expressing the efficacy of apheresis, proposes target levels of total and LDL cholesterol for homozygotes and heterozygotes based on recent follow-up studies and suggests a scheme for monitoring cardiovascular disease in these patients. Establishing a uniform approach to data collection would facilitate the setting up of national or multi-national registers and might eventually provide the information needed to formulate evidence-based guidelines for LDL apheresis.

An analysis of the optimal timing of peripheral blood stem cell harvesting following priming with cyclophosphamide and G-CSF.

Increasing demand on the apheresis service makes efficient harvesting of peripheral blood stem cells (PBSCs) essential. A total of 168 adult patients with haematological malignancy were primed using low-moderate dose cyclophosphamide (1.5-3 g/m(2)) with G-CSF 5-10 microg/kg per day. Harvesting was booked and peripheral blood (PB) counts first checked between 6 and 10 days post-priming. One hundred and thirty (77%) patients harvested successfully (total harvest yield > or =2 x 10(6) CD34(+)/kg) and the median PBSC collection per procedure was 2.18 x 10(6)/kg (range 0.1-14.5). Only more lines of prior chemotherapy predicted failure to harvest in multivariate analysis (P=0.003). The PB CD34(+) cell count correlated significantly with harvest yield (r=0.8448, P<0.0001). A PB CD34(+) count > or =10/microl predicted a collection of > or =2 x 10(6)/kg (positive-predictive value of 61%, negative-predictive-value 100%). Patients first attending day 9 required significantly fewer visits to achieve a successful harvest than those first attending days 6-8 without increasing the risk of failure. No significant difference in failure rates, number of days attending and total harvest yield was found between days 9 and 10 attendees. Collection from day 9 may however enable higher target yields to be achieved. PB CD34(+) count monitoring should commence and harvesting booked from day 9 to optimize both the harvest and the efficiency of the PBSC harvesting service.

Cell activation and thrombin generation in heparin bonded cardiopulmonary bypass circuits using a novel in vitro model.

OBJECTIVE: It is generally agreed that when the blood contact surfaces of a cardiopulmonary bypass circuit are treated with a layer of heparin molecules the activation of the humoral pathways is attenuated. However, there is still debate as to whether heparin-bonded circuits reduce thrombin generation. This study aims to examine the effects of immobilized heparin on cell activation and thrombin generation in a novel, well controlled model of cardiopulmonary bypass. METHODS: The model used consisted of a heparin-bonded and a non-bonded cardiopulmonary bypass circuit perfused in tandem with the same unit of fresh heparinized (3.3 U/ml) human blood for a period of 6 h. Samples were taken for analysis from the bag just prior to perfusion and at 30, 60, 120 and 360 min of perfusion. Whole blood was used to analyse platelet and white blood cell count, haematocrit and activated coagulation time. Plasma samples were prepared for batch analysis of the cell activation markers p-selectin, elastase and interleukin-8, and the thrombin generation markers thrombin-antithrombin and prothrombin fragment F1 + 2. A sample of tubing was taken from each circuit at the end of the perfusion and prepared for visualization by scanning electron microscopy. RESULTS: Platelet counts were significantly reduced in the non-bonded circuits compared with the heparin-bonded circuits at 30 (22 versus 200 x 10(9)/L P < 0.01), 60 (26 versus 193 x 10(9)/L P < 0.01) and 120 min (28 versus 193 x 10(9)/L P < 0.01) as were white blood cell counts at 30(1.5 versus 2.7 x 10(9)/L P < 0.01), 60 (0.9 versus 2.4 x 10(9)/L P < 0.01), 120 (0.9 versus 1.8 x 10(9)/L P < 0.01) and 360 min (0.4 versus 0.9 x 10(9)/L P < 0.05). The concentration of p-selectin was found to be significantly higher in the non-bonded circuits than in the heparin-bonded circuits at 30 (37 versus 29 ng/ml P < 0.01), 60 (37 versus 28 ng/ml P < 0.01). 120 (42 versus 27 ng/ml P < 0.01) and at 360 min (72 versus 46 ng/ml P < 0.01). Elastase was elevated in the non-bonded circuits at 30 (570 versus 145 micrograms/l P < 0.01), 60 (646 versus 278 micrograms/l P < 0.01) and 120 min (613 versus 403 micrograms/l P < 0.05) and interleukin-8 at 120 (705 versus 520 pg/ml P < 0.05) and 360 min (11326 versus 9910 pg/ml P < 0.05). A similar picture was found for the thrombin generation markers. Thrombin-antithrombin complexes were raised in the non-bonded circuits compared with heparin-bonded circuits at 60 (24 versus 13 micrograms/l P < 0.05) and 120 min (46 versus 17 micrograms/l P < 0.05) as was prothrombin fragment F1 + 2 at 30 (1.1 versus 0.7 nmol/l P < 0.01), 60 (1.3 versus 0.7 nmol/l P < 0.01), 120 (1.8 versus 0.9 nmol/l P < 0.01) and 360 min (15.0 versus 13.6 nmol/l P < 0.05). Scanning electron microscopy revealed a greater amount of adherent material on the non-bonded surface relative to the heparin-bonded surface. CONCLUSIONS: In a cardiopulmonary bypass circuit perfused with human blood the activation of platelets and white blood cells has been seen to be significantly reduced in the presence of a heparin-bonded surface. Thrombin generation due to contact activation of the intrinsic coagulation pathway is also reduced.

Platelet production methods in the United Kingdom.

Platelets had traditionally been produced in the United Kingdom (U.K.) either from random donor blood by centrifugation of the platelet rich plasma or by plateletpheresis using various apheresis machines. The proportions of apheresis versus non-apheresis derived platelets varying from centre to centre depending on local policy. The production of platelets from random donor blood is labour intensive and in the late 1980s and early 1990s, biotechnology manufacturers developed newer automated techniques to derive platelets from buffy coats aiming to produce a more standard product and reduce the labour intensity of platelet production. At the same time, apheresis technology has continued to develop with the aim of maximising platelet yields from single donors by yielding 4-6 single unit equivalent of platelets per donor while eliminating the need for further laboratory processing. The trend in some European countries and in North America has been to move away from platelets recovered from whole blood either by buffy coat method or by centrifugation of platelet-rich plasma to plateletpheresis. Intense pressure is being put on blood centres to introduce newer technologies which are inevitably more expensive methods of platelet production. Since 1992, centres in the U.K. have gradually changed their method of platelet production and a survey was conducted to examine the status of platelet production within the U.K. This has shown that many centres are moving away from the production of random donor unit platelets derived by secondary centrifugation of platelet rich plasma (25%) towards buffy-coat derived platelets (45.3%) while plateletpheresis remains fairly static (29.7).