Novel and unexpected clearance mechanisms for cold platelets.

Storage at room temperature is limited to 5 days because of the risk of bacterial growth and loss of platelet functionality. Platelet refrigeration remains impossible, because once chilled, platelets are rapidly removed from circulation. Chilling platelets (<4h) clusters glycoprotein (GP) Ibalpha receptors, and beta(2) integrins on hepatic macrophages recognize clustered beta GlcNAc residues leading to rapid clearance of acutely chilled platelets. Prolonged refrigeration increases the exposure of galactose residues such that, unexpectedly, hepatocytes remove platelets using their asialoglycoprotein receptors. Here we review current knowledge of the mechanisms of platelet removal, the existing knowledge of refrigerated platelet function, and methods to preserve platelet concentrates long-term for transfusion.

[1]  C. Valeri,et al.  Hemostatic effectiveness of platelets stored at 22 degrees C. , 1971, The New England journal of medicine.

[2]  G. Schreiber,et al.  Transfusion‐transmitted bacterial infectionin the United States, 1998 through 2000 , 2001, Transfusion.

[3]  F. Gardner,et al.  Platelet storage at 22 degrees C: role of gas transport across plastic containers in maintenance of viability. , 1975, Blood.

[4]  S. Murphy.  What's so bad about old platelets? , 2002, Transfusion.

[5]  J. Hirsh,et al.  In Vitro and in Vivo Functions of Thrombin-Treated Platelets , 1976, Thrombosis and Haemostasis.

[6]  P. Huijgens,et al.  Correlation between the extent of platelet activation in platelet concentrates and in vitro and in vivo parameters , 2004, Vox sanguinis.

[7]  G. Rock,et al.  Metabolic Changes during Platelet Storage , 1976, Transfusion.

[8]  P. Whitley,et al.  Platelet Storage Lesions in Second‐Generation Containers: Correlation with in vivo Behavior with Storage up to 14 Days , 1990, Vox sanguinis.

[9]  T. Tsuji,et al.  The carbohydrate moiety of human platelet glycocalicin: the structures of the major Asn-linked sugar chains. , 1987, Journal of biochemistry.

[10]  B. Jilma,et al.  Impaired Platelet Function among Platelet Donors , 2001, Thrombosis and Haemostasis.

[11]  F. Gardner,et al.  Room Temperature Storage of Platelets , 2003, Transfusion.

[12]  J. Fridey,et al.  Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial. , 2004, Blood.

[13]  D. Wagner,et al.  P-Selectin and platelet clearance. , 1998, Blood.

[14]  R. Aster,et al.  Studies of Platelet Concentrates Stored at 22 C and 4 C , 1973, Transfusion.

[15]  A. Shanwell,et al.  Storage of buffy‐coat‐derived platelets in additive solutions at 4 °C and 22 °C: flow cytometry analysis of platelet glycoprotein expression , 2007, Vox sanguinis.

[16]  T. Barbui,et al.  The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. , 1997, The New England journal of medicine.

[17]  J. Hartwig,et al.  Dual roles for hepatic lectin receptors in the clearance of chilled platelets , 2009, Nature Medicine.

[18]  H. Rinder,et al.  Platelet storage--time to come in from the cold? , 2003, The New England journal of medicine.

[19]  L. Harker,et al.  Preparation and Storage of Platelet Concentrates: II. STORAGE VARIABLES INFLUENCING PLATELET VIABILITY AND FUNCTION , 1976, British journal of haematology.

[20]  J. Cazenave,et al.  Design of clinical trials to evaluate the efficacy of platelet transfusion: the euroSPRITE trial for components treated with Helinx technology. , 2001, Seminars in hematology.

[21]  P. Perrotta,et al.  Apoptotic activity in stored human platelets , 2003, Transfusion.

[22]  J. Hartwig,et al.  Glycosylation Restores Survival of Chilled Blood Platelets , 2003, Science.

[23]  M. Salama,et al.  Platelet function testing to assess effectiveness of platelet transfusion therapy. , 2004, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[24]  J. White.  Ultrastructural changes in stored platelets. , 1992, Blood cells.

[25]  G. Ehninger,et al.  Safety and cost effectiveness of a 10 x 10(9)/L trigger for prophylactic platelet transfusions compared with the traditional 20 x 10(9)/L trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia. , 1998, Blood.

[26]  E. L. Wallace,et al.  Collection and transfusion of blood and blood components in the United States, 1989 , 1993, Transfusion.

[27]  J. Loscalzo,et al.  In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[28]  W. V. Miller,et al.  Platelet transfusion survey in a regional blood program , 1977, Transfusion.

[29]  M. Brecher,et al.  Transfusion-transmitted bacterial infection. , 1995, Hematology/oncology clinics of North America.

[30]  B. Kim,et al.  The Platelet Response to Hypotonic Shock. Its Value as an Indicator of Platelet Viability After Storage , 1974, Transfusion.

[31]  P. Meer.  Platelet additive solutions: A future perspective , 2007 .

[32]  Hans H Wandall,et al.  Role of sialic acid for platelet life span: exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes. , 2009, Blood.

[33]  E. L. Wallace,et al.  Collection and transfusion of blood and blood components in the United States, 1994 , 1998, Transfusion.

[34]  S. Holme,et al.  The expression of p‐selectin during collection, processing, and storage of platelet concentrates: relationship to loss of in vivo viability , 1997, Transfusion.

[35]  H. Zola,et al.  Purification and preliminary characterization of the glycoprotein Ib complex in the human platelet membrane. , 1985, European journal of biochemistry.

[36]  Y. Ikeda,et al.  Clinical factors influencing posttransfusion platelet increment in patients undergoing hematopoietic progenitor cell transplantation—a prospective analysis , 1998, Transfusion.

[37]  F. Gardner,et al.  The effect of temperature on platelet viability. , 1969, Vox Sanguinis.

[38]  S. Murphy,et al.  The efficacy of synthetic media in the storage of human platelets for transfusion. , 1999, Transfusion medicine reviews.

[39]  F. Gardner,et al.  Platelet storage at 22 degrees C; metabolic, morphologic, and functional studies. , 1971, The Journal of clinical investigation.

[40]  J. Hartwig,et al.  The Macrophage αMβ2 Integrin αM Lectin Domain Mediates the Phagocytosis of Chilled Platelets* , 2005, Journal of Biological Chemistry.

[41]  L. Harker,et al.  Preparation and Storage of Platelet Concentrates: I. FACTORS INFLUENCING THE HARVEST OF VIABLE PLATELETS FROM WHOLE BLOOD , 1976, British journal of haematology.

[42]  N. Rooijen,et al.  In vivo" depletion of macrophages by liposome-mediated "suicide". , 2003 .

[43]  H. Kattlove,et al.  The effect of cold on platelets. II. Platelet function after short-term storage at cold temperatures. , 1972, Blood.

[44]  P. Rebulla,et al.  In vitro assessment of the quality of stored platelet concentrates. The BEST (Biomedical Excellence for Safer Transfusion) Task Force of the International Society of Blood Transfusion. , 1994, Transfusion medicine reviews.

[45]  C. Valeri,et al.  Circulation and distribution of autotransfused fresh, liquid‐preserved and cryopreserved baboon platelets , 2002, Vox sanguinis.

[46]  Rinder Hm,et al.  Activation of platelet concentrate during preparation and storage. , 1992 .

[47]  C. Valeri.  Circulation and Hemostatic Effectiveness of Platelets Stored at 4 C or 22 C: , 2003, Transfusion.

[48]  J. Hartwig,et al.  Mechanism of shape change in chilled human platelets. , 1995, Blood.

[49]  R. Hillman,et al.  Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion , 1991, Transfusion.

[50]  E. Snyder,et al.  Occurrence of the Release Reaction during Preparation and Storage of Platelet Concentrates , 1981, Vox sanguinis.

[51]  H. Gulliksson.  Defining the optimal storage conditions for the long-term storage of platelets. , 2003, Transfusion medicine reviews.

[52]  J. Hartwig,et al.  Mechanisms and implications of platelet discoid shape. , 2003, Blood.

[53]  J. Freedman,et al.  Role of platelet surface glycoprotein Ibα and P‐selectin in the clearance of transfused platelet concentrates , 2004, Transfusion.

[54]  M. Hilgartner,et al.  Platelet function in a patient with thrombasthenia. , 1966, Blood.

[55]  J. AuBuchon,et al.  Preliminary validation of a new standard of efficacy for stored platelets , 2004, Transfusion.

[56]  Paul J. Harrison,et al.  High incidence of defective high‐shear platelet function among platelet donors , 2004, Transfusion.

[57]  M. B. Zucker,et al.  Reversible alterations in platelet morphology produced by anticoagulants and by cold. , 1954, Blood.

[58]  J. Bring,et al.  Evaluation of Platelet Function Using the in vitro Bleeding Time and Corrected Count Increment of Transfused Platelets: Comparison between Platelet Concentrates Derived from Pooled Buffy Coates and Apheresis , 1996, Vox sanguinis.

[59]  C. Prowse,et al.  Storage of platelets in additive solutions: a multicentre study of the in vitro effects of potassium and magnesium , 2003, Vox sanguinis.

[60]  R. Aster,et al.  Relative hemostatic effectiveness of human platelets stored at 4 degrees and 22 degrees C. , 1978, The Journal of laboratory and clinical medicine.

[61]  V. Nizet,et al.  The Ashwell receptor mitigates the lethal coagulopathy of sepsis , 2008, Nature Medicine.

[62]  A. Varki,et al.  Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[63]  C. Valeri.  Hemostatic effectiveness of liquid-preserved and previously frozen human platelets. , 1974, The New England journal of medicine.

[64]  M. Brecher,et al.  Bacterial Contamination of Blood Components , 2005, Clinical Microbiology Reviews.

[65]  W. Ouwehand,et al.  Detection of platelet activation with monoclonal antibodies and flow cytometry. Changes during platelet storage , 1990, Transfusion.

[66]  J. Hartwig,et al.  Galactosylation does not prevent the rapid clearance of long-term, 4°C-stored platelets , 2008 .

[67]  P. Hanfland,et al.  Platelet storage lesions: analysis of platelet membrane glycoproteins and platelet-derived microparticles by fluorescence-activated flow cytometry. , 1993, Transfusion Science.

[68]  F. Gardner,et al.  Effect of storage temperature on maintenance of platelet viability--deleterious effect of refrigerated storage. , 1969, The New England journal of medicine.

[69]  S. Murphy.  Platelet Storage at 22°C , 1982 .

[70]  P. Ljungman,et al.  Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial. , 2003, Blood.

[71]  T. Stossel,et al.  Effect of thrombopoietin alone and a combination of cytochalasin B and ethylene glycol bis(β‐aminoethyl ether) N,N′‐tetraacetic acid‐AM on the survival and function of autologous baboon platelets stored at 4°C for as long as 5 days , 2004, Transfusion.

[72]  S. Slichter.  In vitro Measurements of Platelet Concentrates Stored at 4 and 22°C: Correlation with Posttransfusion Platelet Viability and Function , 1981, Vox sanguinis.

[73]  H. Kattlove.  Platelet Preservation—What Temperature? A Rationale for Strategy , 1974, Transfusion.

[74]  J. Hartwig,et al.  In vitro function and phagocytosis of galactosylated platelet concentrates after long‐term refrigeration , 2007, Transfusion.

[75]  T. Mayadas,et al.  The Clearance Mechanism of Chilled Blood Platelets , 2003, Cell.

[76]  H. Rinder,et al.  Platelet activation and its detection during the preparation of platelets for transfusion. , 1998, Transfusion medicine reviews.

[77]  D. Triulzi,et al.  Detection and significance of alpha granule membrane protein 140 expression on platelets collected by apheresis , 1992, Transfusion.

[78]  J. Akkerman,et al.  Role of glycoprotein Ibα in phagocytosis of platelets by macrophages , 2006, Transfusion.

[79]  J. Harper,et al.  Inhibition of cytokine accumulation and bacterial growth during storage of platelet concentrates at 4° C with retention of in vitro functional activity , 1997, Transfusion.

[80]  L. Harker,et al.  Preparation and Storage of Platelet Concentrates , 2003, Transfusion.