Solving an unusual clotting event during thawing of peripheral blood hematopoietic progenitor cell product

Abstract

Although rare, hematopoietic progenitor cell (HPC) products clotting upon thawing presents enormous challenge. Peripheral blood HPC product was collected from a 10-year-old sibling donor, using acid-citrate-dextrose Formula A (ACD-A) ratio of 1:15 and additional heparin. Most of the product was freshly infused with no apparent clotting, and two additional aliquots were cryopreserved in dimethyl sulfoxide and human serum albumin for future infusion. Two months later one aliquot was thawed and issued in a syringe. At the time of issue no clotting was observed, but the infusion was stopped due to massive product clotting (see figure, A). Cell clumping is caused by multiple factors such as plasma cryofibrinogens and can be overcome by adding anticoagulants and altering cryopreservation practices. 1,2 We experienced only one similar event of 500 products collected over the past 5 years. Since our investigation found no unusual practices in the collection and processing of the recent product, we took extra measures to prevent clotting when thawing the last aliquot. These included adding ACD-A in 1:8 ratio, further dilution with Plasmalyte A, and filtration. The product was issued and administered successfully. To test our practice, a small postthaw sample was transferred into a tube before addition of the anticoagulant. This original unmanipulated sample clotted within 1 hour while the manipulated one did not (see figure, B), proving that ACD-A prevented clotting. Most collection facilities try to avoid using higher volumes of ACD-A due to its possible toxicity. 3 Adding anticoagulant to the final apheresis product might be an optional way to reduce the probability of similar events.