Factors influencing platelet clumping during peripheral blood hematopoietic stem cell collection

Abstract

BACKGROUND Platelet clumping is a common occurrence during peripheral blood hematopoietic stem cell (HSC) collection using the Spectra Optia mononuclear cell (MNC) protocol. If clumping persists, it may prevent continuation of the collection and interfere with proper MNC separation. This study is the first to report the incidence of clumping, identify precollection factors associated with platelet clumping, and describe the degree to which platelet clumping interferes with HSC product yield. STUDY DESIGN AND METHODS In total, 258 HSC collections performed on 116 patients using the Optia MNC protocol were reviewed. Collections utilized heparin in anticoagulant citrate dextrose to facilitate large-volume leukapheresis. Linear and logistic regression models were utilized to determine which precollection factors were predictive of platelet clumping and whether clumping was associated with product yield or collection efficiency. RESULTS Platelet clumping was observed in 63% of collections. Multivariable analysis revealed that a lower white blood cell count was an independent predictor of clumping occurrence. Chemotherapy mobilization and a lower peripheral blood CD34+ cell count were predictors of the degree of clumping. Procedures with clumping had higher collection efficiency but lower blood volume processed on average, resulting in no difference in collection yields. Citrate toxicity did not correlate with clumping. CONCLUSION Although platelet clumping is a common technical problem seen during HSC collection, the total CD34+ cell-collection yields were not affected by clumping. WBC count, mobilization approach, and peripheral blood CD34+ cell count can help predict clumping and potentially drive interventions to proactively manage clumping.

Platelet‐rich aggregates in MNC collection circuit

“…Platelet clumping has been reported with hematopoietic stem cell (HSC) collections, with the potential association of factors such as underlying disease, mobilization approach, peripheral CD34+ counts, low WBC counts, and insufficient anticoagulation 1,2 . While it is unclear what predisposed our patient to the formation of these aggregates, a closer look showed them to be rich in platelets and similar in composition to what has been observed in HSC collections.…”

“…It has been proposed in HSC collections that a greater proportion of younger and larger platelets during periods of hematopoietic recovery may be more functionally active and lead to excess clotting. 2 Given the close proximity of our patient's collection to the completion of his second round of salvage chemotherapy, we speculate that he may have still been experiencing ongoing hematopoietic recovery during collection, which contributed to the excess clumping observed.…”

PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells

“…Although the physiological roles of PAR1 and PAR4 in thrombin-induced calcium signaling, granule secretion, GPIIb/IIIa activation, and platelet aggregation have been extensively studied, their distinct roles in thrombin-induced shape change have not been clearly elucidated [ 9 , 11 , 12 , 14 , 22 ]. However, platelets that are easily aggregate with agonists are stable for only 5 days, and the functions are variable depending on the donor, so an efficient in vitro cellular model to replace platelets is needed [ 23 , 24 , 25 ]. Therefore, in this study, we established an in vitro cellular model for thrombin-induced morphological changes in platelets using MEG-01 cells, a human megakaryoblastic leukemia cell line.…”

Process and procedural adjustments to improve CD34+ collection efficiency of hematopoietic progenitor cell collections in sickle cell disease

“…13 For example, platelet clumping may contribute to unstable interfaces and thus lower CD34+ CE. 14 Platelets and WBCs are abnormally activated in SCD 15,16 contribute to coagulation activation, 17 and may be further activated with plerixafor mobilization and leukapheresis. 12,18,19 SCD is associated with increases in platelet-neutrophil and platelet-monocyte aggregates 15,18 and CD34+ cell-RBC aggregates, 16 which might contribute to unstable interfaces.…”