Enhanced retention of in vitro functional activity of platelets from recombinant human thrombopoietin-treated patients following long-term cryopreservation with a platelet-preserving solution (ThromboSol) and 2% DMSO.
Chemotherapy-induced thrombocytopenia represents a significant clinical problem in the management of patients with malignancy. Recombinant human thrombopoietin (rhTPO) is a potent stimulator of platelet production in vivo. The ability to cryopreserve rhTPO-derived platelets would enable the use of autologous platelets during the period of thrombocytopenia. ThromboSol is a platelet-stabilizing formulation consisting of second messenger effectors that inhibit specific activation pathways endogenous to platelets. To investigate the effect of ThromboSol cryopreservation, platelets from rhTPO-treated patients (n = 23) and normal donors were treated with ThromboSol and 2% DMSO and cryopreserved for up to 6 months. The platelets were thawed at different intervals and tested for retention of platelet functional activity in vitro. Following a short-term storage (1 week), the cryopreserved platelets from patients treated with rhTPO exhibited significantly higher retention of functional activities including discoid morphology (70% v 57%), extent of shape change (19% v 13%) stirring shape change (15% v 11%) and hypotonic shock response (56% v 25%), as compared to the cryopreserved platelets from controls. Furthermore, there was no further significant loss of functional activity following cryopreservation for up to 6 months. These findings suggest that cryopreservation of platelets from rhTPO-treated donors may provide a useful novel strategy for autologous or allogeneic donation for subsequent transfusions to manage treatment-related thrombocytopenia.
Department of Bioimmunotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
S
S
Vadhan-Raj
L M
LM
Currie
C
C
Bueso-Ramos
S A
SA
Livesey
J
J
Connor
D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D015925:Cryopreservation / Q000379:methods*; D003451:Cryoprotective Agents / Q000627:therapeutic use*; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D010051:Ovarian Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins; D012509:Sarcoma / Q000628:therapy*; D013921:Thrombocytopenia / Q000209:etiology / Q000628:therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*
D003451:Cryoprotective Agents; D011994:Recombinant Proteins; D013926:Thrombopoietin; D004121:Dimethyl Sulfoxide