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|Title:||Cryopreserved platelets: frozen in a logjam?|
|Authors:||Dumont, Larry J|
Slichter, Sherrill J
|ANZCA/FPM Author:||Reade, MC|
|Citation:||Transfusion 2014-08; 54(8): 1907-10|
|Abstract:||Abstract from Semantic Scholar:I n 1974, Valeri and colleagues published a method for the cryopreservation of platelets (PLTs) in 6% DMSO (CPPs) and provided the initial data on the hemostatic effectiveness of these PLTs. Over the next 30 years, his group published numerous papers describing the in vitro properties of CPPs, in vivo recovery and survival of autologous CPPs, effects of autologous CPP transfusions on bleeding times in aspirin-treated volunteers, animal studies, and one randomized controlled trial comparing allogeneic CPP transfusions to standard liquid-stored PLTs in patients undergoing surgery with cardiopulmonary bypass. Valeri’s CPP method froze and stored the CPPs in a mechanical freezer at −80°C followed by a postthaw wash to remove most of the DMSO before a transfusion. Valeri subsequently published a no-wash method in which most of the DMSO was removed before freezing eliminating the need for a postthaw wash. The accumulated evidence from this portfolio of work describes a CPP phenotype of a partially activated product that has reduced in vivo PLT recoveries and excellent survival compared to PLTs stored in liquid plasma at 20 to 22°C, and was superior to standard PLTs in reducing blood loss and the need for transfusions after heparin reversal in cardiopulmonary bypass patients. Contemporary with Valeri’s work, several other investigators published their findings on DMSO-cryopreserved PLTs. The most extensive experience was from Schiffer’s group at the University of Maryland who used CPP transfusions in the management of chemotherapy patients. This group prepared and transfused more than 700 autologous units to more than 155 patients between 1974 and 1981. The majority of the patients selected to donate autologous PLTs during disease remission were those who had become alloimmune PLT refractory to random-donor PLTs. The autologous PLTs were frozen and stored in liquid nitrogen, washed after thawing, and resuspended in autologous plasma. Schiffer’s summary experience was that the CPPs were safe and hemostatically effective when given during subsequent episodes of chemotherapyinduced thrombocytopenia. However, because of the current availability of large HLA-typed registries of plateletpheresis donors and reduced demand for matched PLTs due to leukoreduction, there is presently little need for autologous frozen PLTs to support alloimmunized patients. The PLT cryopreservation methods reported by others have been diverse: DMSO content of 5% to 10%, freezing at uncontrolled or controlled rates, storage at −80°C in mechanical freezers or in the vapor phase of liquid nitrogen (−120°C), use of various freezing bags, removal or not of the DMSO before transfusion, and resuspension in either plasma or a crystalloid. Recently, the Dutch military have implemented and deployed a deep frozen (−80°C) inventory of CPPs, along with red blood cells (RBCs) and plasma. They implemented the Valeri 6% DMSO, no-wash method for preparing CPPs. CPPs are stored for up to 2 years and then thawed in 5 to 7 minutes at 37°C and resuspended in AB plasma for transfusion. This product has been deployed in various military missions, most notably the NATO International Security Assistance Force in Afghanistan where more than 1000 CPP units were administered to more than 1000 patients. While detailed clinical outcome data are difficult to obtain during combat operations, reports of users indicate that this product is hemostatically effective and safe in this setting. In a prospective audit of 46 patients who received massive transfusions and 234 patients who received less-than-massive transfusions in the Dutch-led NATO hospital in Afghanistan, administration of a high ratio of cryopreserved PLTs to RBCs (1:8 or higher) compared to a lower ratio was associated with increased survival in the massive transfusion group (74% vs. 50%) and no difference in survival in the less-thanmassive transfusion group (86% vs. 90%). One of us (MCR) used this product while deployed to this hospital in 2009 and observed that CPPs produced surprisingly effective hemostasis without the increase in measured PLT count that would be expected of a liquid PLT transfusion. No immediate adverse outcomes were apparent— specifically, no increase in acute lung injury (which might occur due to the higher concentration of microparticles in the CPP) and no increase in thromboembolic complications (which might occur if CPPs are indeed more hemostatically active). Admittedly, observations for complications were not actively made, and no comparison was possible with patients who received liquid PLTs or comparable patients receiving no PLTs at all. The validity of the comparator group depends on circumstances dictated by logistics. While larger combat hospitals in Iraq and Afghanistan have had access to locally collected apheresis PLTs since 2004, the only options in smaller military hospitals are fresh whole blood, CPPs (in the Dutch facility), or no PLTs at all. The major advantages of CPPs are improved availability in remote treatment locations such as military operations and rural medical facilities; bridging inventory shortages due to weekends, holidays, weather, and © 2014 AABB|
Research Support, Non-U.S. Gov't
|Appears in Collections:||Scholarly and Clinical|
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