Spray‐dried plasma deficient in high‐molecular‐weight multimers of von Willebrand factor retains hemostatic properties

Abstract

BACKGROUND: Dried plasmas can overcome logistical barriers that prevent fresh frozen plasma (FFP) usage in acute resuscitation, but processing of these products can detrimentally alter the composition. Spraydried plasma (SpDP) from single units is deficient in high-molecular-weight multimers of von Willebrand factor (vWF), a critical facilitator of platelet adhesion and thrombus formation. We hypothesized that converting high-molecular-weight multimers to smaller-molecularweight multimers would retain vWF's capacity to mediate platelet adhesion.STUDY DESIGN AND METHODS: SpDP obtained from untreated FFP was reconstituted with glycinehydrochloric acid (HCl) and glycine (20 mM:50 mM) or pretreated with glycine-HCl (20 mM) or glycine-glycine-HCl (20 mM:50 mM) and reconstituted with water. In vitro hemostatic potential of SpDPs versus FFP or FFP spiked with 70 mM of glycine was evaluated, leading to a more detailed in vitro study of glycine-HCl-glycine (20 mM:50 mM) pretreated SpDP. Plasmas were combined with RBCs and platelets to observe global coagulation response. RESULTS:While vWF-ristocetin cofactor activity is significantly decreased (−41.13%; p < .0001) in SpDP, a model of vWF-mediated platelet adhesion to collagen under flow showed enhanced function (+13%; p < .01). Fewer microparticles, particularly of platelet origin, were observed in SpDP versus FFP (p < .0001). Small but significant differences in thromboelastography results were observed, although SpDP and FFP were within normal ranges. CONCLUSION: Comparable coagulability wasobserved in FFP and SpDP. The apparent paradox between vWF-ristocetin cofactor assay and vWF-mediated platelet adhesion may be explained by the increase in smaller multimers of vWF in SpDP, producing different outcomes in these assays.

A microfluidic analysis of thrombus formation in reconstituted whole blood samples comparing spray‐dried plasma versus fresh frozen plasma

“…In combination with other pre-clinical studies [12,19] that have shown SpDP to be equivalent to FFP with respect to thrombin generation and endothelial interactions, this study supports the development of inhuman studies to evaluate the efficacy and safety of SpDP in preventing and reversing trauma-related coagulopathy.…”

“…Using a protocol approved by the local institutional review board, whole blood from consented healthy adult volunteers was collected into 3·2% sodium citrate (Becton, Dickinson and Company, Franklin Lakes, NJ, USA). Donor FFP was collected and shipped to the Velico (Beverly, MA, USA) for SpDP manufacturing [8,11,19]. Following collection, the whole blood (WB) was centrifuged at 200 g for 12 min after which the platelet rich plasma (PRP) was removed from the red blood cell concentrate (RBCs).…”

Dried Plasma for Trauma Resuscitation

“…Factor levels were greater than 80% of FFP for all factors, except FXIII (74%) and vWF (60%). In vitro study of this spray-dried plasma found that, despite a reduction in high molecular weight vWF multimers, platelet adhesion was not impaired and overall clot characteristics remained within the normal range for FFP [106]. In a study of another spray-dried plasma, Spinella et al reported that, despite reductions in individual factor levels during spray-drying, thrombin generation was greater with spray-dried plasma than with FFP and liquid plasma [48], raising the possibility of increased thrombotic issues.…”

Spray‐dried plasma: A post‐traumatic blood “bridge” for life‐saving resuscitation

“…Clotting Factor levels were greater than 80% of FFP for all factors, except FXIII (74%) and von Willebrand ristocetin cofactor activity was 60% of FFP. Using a microfluidic channel in vitro assay (BioFlux) to simulate bleeding in‐vivo, ODP plasma did not impair platelet adhesion and overall clot characteristics were normal 54, 55 . These results occurred despite a diminution in high‐molecular‐weight multimers of vWF which is a known effect of the spray drying process.…”

“…Using a microfluidic channel in vitro assay (BioFlux) to simulate bleeding in-vivo, ODP plasma did not impair platelet adhesion and overall clot characteristics were normal. 54,55 These results occurred despite a diminution in high-molecular-weight multimers of vWF which is a known effect of the spray drying process. Bercovitz et al, compared microfluidic assay clot generation (using platelets from patients with severe von Willebrand disease and resuspended in ODP and found no difference between the ODP sample and its control.…”