Vox Sanguinis International Forum on platelet cryopreservation: Summary

The demand for platelets continues to rise, outstripping supply worldwide. In higher-income countries, cancer patients remain platelet transfusion dependent for extended periods, which leads to sporadic and chronic regional shortages that are secondary to uncontrolled fluctuations in supply. In less-developed countries, the supply to demand ratio is critical for obstetric haemorrhage, trauma and medical patients. All countries, however, share the difficulty in providing platelets to rural areas or in support of troops in remote military theatres. Alternatives to conventional 5to 7-day room temperature-stored platelets are needed. Cryopreservation of platelets is likely the best alternative to balance the supply and demand for platelets in cities and less accessible areas. Cryopreserved platelet units (CPP) can be shipped on dry ice and stored for 2 years or more in mechanical freezers or using liquid nitrogen [1]. This controlled supply may be used as a backup to liquid units in well-stocked hospitals, or as the sole source of platelets in remote or underserved settings. Cryopreserved units can be stockpiled for natural disasters, or special HLAor HPA-selected units may be stored for patients who are refractory to platelet transfusions due to antibodies. In addition, cryopreservation reduces the risk of septic transfusion reactions, as bacteria will not proliferate under these conditions. Cryopreservation of platelets has been available since the 1970s, when Valeri published his original method for storing platelets in 6% dimethyl sulphoxide (DMSO) at 80°C [2]. Subsequent work led to an improved ‘no-wash’ method, which removed the DMSO prior to freezing, thus allowing for easier post-thaw utilization [1]. While other methods for cryopreservation have been published [3, 4], most data on CPPs in vitro characteristics, storage duration, autologous survival/recovery, clinical safety and efficacy have been developed using the ‘no-wash’ approach. Extensive in vitro characterization has been performed using CPP resuspended in plasma, saline or platelet additive solutions. These studies have shown that post-thaw platelets, when compared to liquid platelets, are partially activated, contain a distinct microparticle population and exhibit other properties which increase the prothrombotic potential for patients [5, 6]. Autologous studies report that CPP resuspended in saline showed suboptimal 24-h recovery times in healthy volunteers; however, the survival times exceed FDA requirements [5]. These prothrombotic qualities might offer an advantage in some clinical scenarios. Rapid reversal of bleeding is needed for trauma surgery and massive transfusion protocols. However, questions remain concerning the safety of increasing the risk of thrombosis, especially in non-traumatic scenarios. Clinical trials have been launched to better understand the risk/benefit ratio in different populations and characterize the efficacy of CPP versus liquid units. Valeri compared CPP to conventional platelets in the setting of cardiopulmonary bypass surgery. The trial reported no transfusion-related adverse events, reduced blood loss and a lower postprocedural transfusion rate in the CPP cohort. However, there was also a lower posttransfusion increment and a tendency towards decreased platelet survival in the CPP arm. In vitro and clinical laboratory tests upheld the view that the CPP created a more procoagulant effect than liquid-stored platelets [7]. The CLIP trial (cryopreserved versus liquid platelets for surgical bleeding) in Australia and another trial in the Czech Republic are currently enrolling patients. The CLIP trial is a pilot to explore the feasibility and safety of a larger trial [8]. The Czech Republic trial is randomizing heavily bleeding patients to receive either CPP or conventional platelets. Preliminary results indicate no significant differences between the two cohorts for most laboratory parameters; however, the amount of platelets transfused was significantly higher for the conventional platelet cohort (Milos Bohonek, personal communication). Other groups have reported on CPP use in less-controlled clinical settings. The University of Maryland supplied over 700 autologous CPP units for chemotherapy patients and found the cryopreserved units to be safe and efficacious; however, the production of CPP subsided as more HLA-typed platelets became available [9]. The Dutch military has used CPP extensively in the Netherlands led NATO hospital in Afghanistan. Observers reported that