Background: Fibrinogen replacement is critical for bleeding patients with dilutional coagulopathy. Cryoprecipitate (cryo) and fibrinogen concentrate (FC) are clinically-utilized fibrinogen supplements, yet which product provides better hemostatic resuscitation remains controversial. Cryo contains additional factors which may enhance hemostatic efficacy.

Aims: To determine if and how additional factors present in cryo contribute to improved rescue of dilutional coagulopathy.

Methods: Healthy human whole blood (WB), cryo, and FC were stained with fluorescent antibodies specific for VWF, CD41, fibrinogen, and FXIII. WB was diluted 3:7 in normal saline to induce dilutional coagulopathy (dWB). dWB was resuscitated 1:5 with cryo (rCr-dWB) or FC (rFC-dWB), and perfused at three different shear rates through a microfluidic model of hemorrhage (a lumen that “bleeds” through an injury site into a collagen/tissue factor-coated extravascular space). Real-time and terminal Z-stack immunofluorescent images of the injury site were acquired. Data was extracted from real-time images using MATLAB. We used AutoQuant to deconvolute Z- stack images and Imaris to generate space filling models of terminal clot structure.  

Results: At all shear rates, rCr-dWB had earlier platelet adhesion/aggregation within the injury site as compared to rFC-dWB (Fig. 1A-C). At high shear, where VWF-mediated capture of platelets is a critical mechanism of hemostasis, rCr-dWB and not rFC-dWB had immediate VWF deposition (Fig. 1A). rCr-dWB achieved close to maximal platelet signal by 4 minutes post-perfusion, whereas rFC-dWB had 25% of maximal platelet signal by 10 minutes post-perfusion (Fig. 1A). Despite early differences, terminal clot composition was similar between rCr-dWb and rFC-dWB at each shear rate (Fig. 1D).

Immunofluorescent signal of platelets and VWF in each resuscitation group (rCr-dWB, solid lines; rFC-dWB, dashed lines) within the injury site over time at (A) high, (B) medium, and (C) low shear. (D) Normalized terminal clot components in each resuscitation group (rCr-dWB and rFC-dWB) at each shear rate as rendered from 3-D space filling models of immunofluorescent Z-stack images.

Conclusions: Resuscitation with cryo results in faster platelet engagement at all shear rates in the microfluidic model of hemorrhage, most likely due to ample VWF immediately available upon resuscitation. Resuscitation with FC failed to recruit platelets into the injury site within 10 minutes.

« Back to ISTH 2021 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/cryoprecipitate-and-not-fibrinogen-concentrate-enhances-early-clot-formation-in-an-in-vitro-microfluidic-model-of-dilutional-coagulopathy/