Fig 1: Dysregulation of neuroserpin and tissue plasminogen activator (tPA) in plasma and cerebrospinal fluid (CSF) from people with Down syndrome (DS). A, Neuroserpin levels were assessed by Western blotting. No significant change in plasma neuroserpin levels were observed between clinical groups, one‐way analysis of variance (ANOVA), P > .05. B, Neuroserpin levels were found upregulated in CSF from AD‐asymptomatic people with Down syndrome (aDS) and from people with Down syndrome and symptomatic Alzheimer's disease (DSAD) compared to non‐trisomic controls, Kruskal Wallis test P = .001 H = 13.63 and Dunn's post hoc correction; *P < .05; **P < .01. C, tPA levels were reduced in plasma from people with aDS and DSAD, compared to non‐trisomic controls, one‐way ANOVA, F = 12.07, P < .0001 and Bonferroni post hoc correction; *P < .05. D, No change between clinical classifications in CSF levels of tPA, one‐way ANOVA, P > .05. tPA levels were determined by enzyme‐linked immunosorbent assay. Data are displayed in box and whisker plots, in which the median is represented by the horizontal line and the whiskers go from each quartile to the minimum or maximum value. HC, Healthy controls: n = 16, aDS: n = 14, DSAD: n = 22; IOD, integrated optical density
Fig 2: Comparison of Trauma Patient Coagulation Profiles and STIC Component SamplesClot formation profile of trauma patient platelet poor plasma during coagulation after activation with 0.2 U/mL thrombin and 20 mM CaCl2 in (A) mechanical testing and (B) optical turbidity testing. Clot formation profile of pooled platelet poor plasma supplemented with 3.3 mM tPA or 45pM TF after activation with 0.2 U/mL thrombin and 20 mM CaCl2 in (C) mechanical testing and (D) optical turbidity testing. Fibrin polymerization rate comparison in (E) rheometry and (F) optical turbidity testing. (G) Tissue plasminogen activator concentration determined by ELISA, indicating higher tPA concentration associated with increased lysis. Lack of significance indicated by no bar above data, *** p ≤ 0.005, **** p ≤ 0.001 (n ≥ 2 for all samples).
Fig 3: Mechanical and Optical Analysis of STIC and Components on Plasma Clotting.Clot formation profile in PPP control, simulated Trauma Induced Coagulopathy (STIC) and PPP supplemented with individual STIC component, 15 % saline dilution, 3.3 mM tPA, and 45pM TF after activation assessed by (A) rheometer and (B) optical turbidity testing. Sample composition described in Table 2. Comparison of (C) storage modulus and (D) optical density at two time points after clot activation. Fibrin polymerization rate taken from 1 to 40 % during the clotting profile for (E) rheometer and 20 to 70 % during (F) optical turbidity testing. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.005, **** p ≤ 0.001. (n ≥ 3 for all samples).
Fig 4: Mechanical and Optical Analysis of STIC Clotting.Clot formation profile in control and simulated Trauma Induced Coagulopathy (STIC) PPP samples after activation assessed by (A) rheometer and (B) optical turbidity testing. Sample composition described in Table 2, STIC samples contain 45 pM TF, 3.3 mM tPA, and 15 % dilution with saline in addition to the control sample. Comparison of two time points during the plasma clotting formation profile from (C) rheometer and (D) optical turbidity testing. Fibrin polymerization rate taken from 1 to 40 % during the clotting profile for (E) rheometer and 20 to 70 % during (F) optical turbidity testing. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.005, **** p ≤ 0.001. (n ≥ 3 for all samples).
Supplier Page from Abcam for Human Tissue Type Plasminogen Activator ELISA Kit (TPA)