61 Allogenic Plasma Unit Reference Ranges for Select Biomarkers and Thrombin and Lysis Dynamics

TL;DR

This study evaluates the coagulation and fibrinolytic properties of fresh frozen plasma units used in burn patient treatment, finding they have normal profiles and do not add significant procoagulant potential.

Contribution

The study provides reference ranges for biomarkers and thrombin dynamics in allogenic plasma units used in burn care, confirming their safety in coagulation profiles.

Findings

FFP units showed peak thrombin levels comparable to reference plasma and a strong response to thrombomodulin.

FFP units had faster lysis onset times with tPA but similar complete lysis times compared to reference plasma.

FVII, FVIII, and PAI-1 levels in FFP units were within normal healthy ranges.

Abstract

Burn patients may be transfused with healthy donor plasma as a part of plasma inclusive resuscitation as part of the treatment of burn shock. Here we performed a comprehensive assessment of fresh frozen plasma (FFP) transfusion units that were subsequently used at a single regional burn center.

Aliquots of FFP units (n=29) that were administered to burn injured patients were collected and frozen. Thrombin generation potential was assessed using the calibrated automated thrombogram protocol. Reactions were conducted in the presence of exogenously added tissue factor (TF) ± thrombomodulin (TM) to assess the contribution of the protein C pathway. Thrombin generation was described by parameters of lag time, peak thrombin, and endogenous thrombin potential. Fibrinolytic potential was assessed using a clot lysis assay where plasma samples were incubated with exogenous TF ± tissue-type plasminogen activator (tPA). Clot formation and lysis dynamics were measured optically, and parameters of clot formation, lysis onset, and lysis completion were extracted. A reference healthy donor plasma pool was run alongside thrombin generation and clot lysis assays. Activity levels of FVII, FVIII, and PAI-1 were measured. Data are presented as mean ± SD.

Peak thrombin levels in transfusion units were 104.4 ± 30.5 nM and 119.5 ± 14.7 nM thrombin in reference plasma. Units had a robust response to the presence of TM with an 80% ± 12% reduction in peak thrombin generated while our reference plasma reduced by 32% ± 13%. Transfusion units appeared to have a faster lysis onset time in response to tPA compared to our reference control plasma (411 ± 179 s vs. 739 ± 165 s, p < 0.005), however the complete lysis time was not significantly different (1116 ± 750 s vs. 1068 ± 104 s, p = 0.7). FVII and FVIII levels were within the accepted normal healthy range (81% ± 25% and 91% ± 33%, respectively, of mean physiological levels). We measured active PAI-1 at 3.8 ± 5.05 U/mL, within reported healthy normal ranges.

FFP units do not present with an abnormal profile of fibrinolytic potential or select biomarkers of coagulation. The robust response of FFP units to TM in TF-initiated thrombin generation assays suggests that administration of these FFP units would not result in a significant source of added procoagulant potential.

FFP administration would not be expected to result in an abnormal contribution to coagulation or fibrinolytic potential.

USAMRAAA - BA190086