PLASMA FRACTIONATION AND BLOOD TRANSFUSION DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY Lijnen, H.R., Collen, D. and Verstraete, M., eds: Synthetic Substrates in Clinical Blood Coagulation Assays. 1980. ISBN 90-247-2409-0 Smit Sibinga, C.Th., Das, P.C. and Forfar, J.O., eds: Paediatrics and Blood Transfusion. 1982. ISBN 90-247-2619-0 Fabris, N., ed: Immunology and Ageing. 1982. ISBN 90-247-2640-9 Homstra, G.: Dietary Fats, Prostanoids and Arterial Thrombosis. 1982. ISBN 90-247-2667-0 Smit Sibinga, C.Th., Das, P.C. and Loghem, van J.J., eds: Blood Transfusion and Prob lems of Bleeding. 1982. ISBN 90-247-3058-9 Dormandy, J., ed: Red Cell Deformability and Filterability. 1983. ISBN 0-89838-578-4 Smit Sibinga, C.Th., Das, P .C. and Taswell, H.F., eds: Quality Assurance in Blood Bank ing and Its Clinical Impact. 1984. ISBN 0-89838-618-7 Besseiaar, A.M.H.P. van den, Gralnick, H.R. and Lewis, S.M., eds: Thromboplastin Calibration and Oral Anticoagulant Control. 1984. ISBN 0-89838-637-3 Fondu, P. and Thijs, 0., eds: Haemostatic Failure in Liver Disease. 1984. ISBN 0-89838-640-3 Smit Sibinga, C.Th., Das, P.C. and Opelz, G., eds: Transplantation and Blood Transfu sion. 1984. ISBN 0-89838-686-1 Schmid-Sch6nbein, H., Wurzinger, L.J. and Zimmerman, R.E., eds: Enzyme Activation in Blood-Perfused Artificial Organs. 1985. ISBN 0-89838-704-3 Dormandy, J., ed: Blood Filtration and Blood Cell Deformability. 1985. ISBN 0-89838-714-0 Smit Sibinga, C.Th., Das, P.C. and Seidl, S., eds: Plasma Fractionation and Blood Transfusion. 1985. ISBN 0-89838-761-2 Plasma Fractionation and Blood Transfusion Proceedings of the Ninth Annual Symposium on Blood Transfusion, Groningen, 1984, organized by the Red Cross Blood Bank Groningen-Drenthe edited by C.Th. SMIT SIBINGA and P.C. DAS Red Cross Blood Bank Groningen-Drenthe The Netherlands S. SEIDL Red Cross Blood Transfusion Service Hessen Frankfurt am Main F.R.G. 1985 MARTINUS NIJHOFF PUBLISHERS • II a member of the KLUWER ACADEMIC PUBLISHERS GROUP BOSTON I DORDRECHT I LANCASTER • Distributors jar the United States and Canada: Kluwer Academic Publishers, 190 Old Derby Street, Hingham, MA 02043, USA jar the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited, Falcon House, Queen Square, Lancaster LAI lRN, UK jar all other countries: Kluwer Academic Publishers Group, Distribution Center, P.O. Box 322, 3300 AH Dordrecht, The Netherlands Library of Congress Cataloging in Publication Data ISBN-13: 978-1-4612-9644-7 e-ISBN-13: 978-1-4613-2631-1 DOl: 10.1007/978-1-4613-2631-1 Copyright © 1985 by Martinus Nijhoff Publishing, Boston. Softcover reprint of the hardcover 1s t edition 1985 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publishers, Martinus Nijhoff Publishing, 190 Old Derby Street, Hingham, MA 02043, USA. m TRAVENOL Acknowledgement This publication has been made possible through the support of Travenol, which is gratefully acknowledged. VII CONTENTS Moderators IX Speakers X Foreword XI Opening adress XIII I. Source material The future blood supply system in the USA: A prognosis (F. Peetoom, S.M. Gaynor) 3 Plasma supply. National and international logistics, whole blood versus plasmapheresis (H.H. Gunson) 9 Processing criteria for recovery of FFP for fractionation (J.K. Smith, D.R. Evans) 15 Donation procedure: Collection lesion, fibrinopeptide A, and factor VIII (C • V. Prowse) 25 Discussion 33 II. Technology of plasma fractionation Small pool versus large pool in plasma fractionation: Reevaluation of a concept (C.Th. Smit Sibinga, P.C. Das) 43 Ethanol fractionation of human plasma: An overview (H.G.J. Brummelhuis) 47 Control of large-scale plasma thawing (P.R. Foster, A.J. Dickson) 57 Contributions to the optimization of factor VIII production: Cryoprecipitation and controlled pore glass adsorption (J. Over, M.P.J. Piet, J.A. Loos, H.P.J. Henrichs, P.J. Hoek, M.A. von Meyenfeldt, J.I.H. Oh) 67 Chromatographic methods of plasma fractionation (J .M. Curling) 79 Polyelectrolyte fractionation technology (S • M. Middleton) 83 Recombinant DNA technology for the production of plasma proteins (W. D. Lake, W. R. Srigley) 89 VIII Column ion exchange chromatographic production of albumin, IV ISG and factor IX from 75,000 to 100,000 litres of plasma per year (A. D. Friesen) 97 Large scale chromatographic experiments for plasma fractionation (F. Hask6, K. Krist6f, M. Salamon, P. Dob6) 105 Discussion 115 III. Safety aspects Preservation of structure and function during isolation of human plasma proteins (Morgenthaler, E. Nydegger) 127 The impact of donor selection of virus transmission (S. Iwarson) 139 Prevention of transmission of virus infections by blood trans- fusions and removal of virus infectivity from clotting factor concentrates (R.J. Gerety) 143 Inactivation of hepatitis viruses (B, non-A/non-B) and retro- viruses in pooled human plasma by means of i3-propiolactone-and UV-treatment (W. Stephan, H. Dichtelmiiller, R. Kotitschke, A.M. Prince, R.R. Friis, H. Bauer) 147 HTLV-I/II and HTLV-III seroprevalence in blood product recipients (T .L. Chorba, J .M. Jason, J .S. McDougal) 155 Sero-epidemiology of the human T-lymphotropic retroviruses HTVL-I and HTLV-III in the Netherlands (J. Goudsmit) 163 Discussion 169 IV. Clinical aspects Needs, quality versus quantity (S. Seidl) 189 Clinical characteristics of the factor VIII protein from various factor VIII concentrates (I.M. Nilsson) 197 Clinical use of polyelectrolyte-fractionated porcine factor VIII (P.B.A. Kernoff) 211 Factor VIII: C assay standardisation (P.C. Das, P.H.M.J. Thijssen, R.L. McShine, C. Th. Smit Sibinga) 217 The current of status of fibronectin in clinical medical practice (E.L. Snyder) 223 Intravenous use of gammaglobulin in 1984 (J.B. Busse!) 231 Discussion 237 IX MODERATORS S. Seidl Red Cross Blood Transfusion Service Hessen (chairman) Frankfurt am Main, FRG H. G.J. Brummelhuis Central Laboratory of the Blood Transfusion Amsterdam, NL R. A. Coutinho Municipal Health Service Amsterdam, Amsterdam, NL H.H. Gunson National Blood Transfusion Service, Manchester, UK J. Over Central Laboratory of the Blood Transfusion Amsterdam, NL F. Peetoom American Red Cross Blood Services Portland, OR, USA J.K. Smith Plasma Fractionation Laboratory, Oxford, UK C. Th. Smit Sibinga Red Cross Blood Bank Groningen-Drenthe Groningen, NL x SPEAKERS J .B. Bussel The New York Hospital-Cornell Medical Center New York, NY, USA J. Curling Pharmacia Fine Chemicals, Uppsala, S P.R. Foster Scottish National Blood Transfusion Service Edinburgh, UK R.J. Gerety Office of Biologics Research and Review Bethesda, MD, USA J. Goudsmit University of Amsterdam, Amsterdam, NL S. Iwarson University of Goteborg, Goteborg, S J .M. Jason Center for Infectious Diseases, Atlanta, GA, USA W.C. Lake Travenol Laboratories Inc. Deerfield, IL, USA S • H. Middleton Speywood Laboratories Ltd, Wexham, UK 1. M. Nilsson Allmanna Sjukhuset, Malmo, S U .E. Nydegger Central Laboratory of the Swiss Blood Transfusion Service, Bern, CH C. V. Prowse Edinburgh and South-East Scotland Regional Blood Transfusion Service Edinburgh, UK E.L. Snyder Yale University, New Haven, CT, USA PREPARED DISCUSSANTS P.C. Das Red Cross Bloodbank Groningen-Drenthe, Groningen, NL A • D. Friesen The Winnipeg Rh Institute Inc., Winnipeg, C F. Hasko National Institute of Haematology and Blood Transfusion, Budapest, H P.B.A. Kernoff Royal Free Hospital, London, UK W. Stephan Biotest Pharma GmbH, Frankfurt, FRG XI FOREWORD Plasma fractionation and blood transfusion are inherently linked. Blood bankers need to have a sincere interest in fractionation and purification techniques in order to understand the need for carefully controlled source material collection and initial processing. Developments point to a shift in technology, implementation and application of plasma fractions to be produced, such that early anticipation from both bloodbankers and fractionators in a joint interest and effort are needed. As usual there is good news and bad news. We are referring in that respect to the exciting presentation about the future of bloodbanking. Although the blood donor still plays a major role in bloodbanking, new technologies could terminate the conventional blood transfusion service in the next 20-40 years. Sooner or later DNA technology will play an important role in bloodbanking and bloodbankers will have to deal with cultivated red cells as a replacement of our donor blood. Several fractionation techniques like column chromatography, controlled pore glass chromatography, heparin double cold precipitation technology and polyelectrolite fractionation are available, which may result in better yields for some of the plasma proteins. These techniques are likely to replace in part the old Cohn fractionation in the near future. For logistic reasons it should be reemphasized that sufficient FVIII yield can be obtained from blood which has been stored for 18 hours. How ever, it should also be kept in mind that significantly better yields are achieved by fast freezing immediately following collection, the use of CPDA anticoagulant or plasmapheresis by machines. -Additionally, the yield may be influenced by the storage technique. It seems also likely to further increase the FVIII yield by applying special absorption techniques and the use of heparin. An important point of discussion at present is whether a centralized fractionation is always advantageous. It is our feeling that there are certainly advantages when some of the plasma proteins, FVIII for in stance, are prepared in regional centres. However, some other plasma proteins still do require a more centralized approach. The solution for the future might be a marriage of both systems. Besides achievements of higher yields and better purities through newly developed fractionation techniques, maintenance of function is a major safety concern in plasma separation. To reduce the transmission of infectious agents, new screening procedures are likely to be introduced in the near future. For instance, reverse transcriptase as a test to detect carriers of non A non B might be around the corner. For hepatitis B effective screening procedures are already available as well