Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time—Multicenter Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Laboratory Investigations
2.3. Fibrin Clot Properties
2.4. Statistical Analysis
3. Results
3.1. Demographics of Fontan Patients
3.2. Fontan Patient’s vs. Healthy Control Subjects
3.3. Fibrin Clot Properties Markers in Fontan Patients
3.4. Fibrin Clot Properties and Liver-Derived Hemostatic Factors in Fontan Patients
3.5. Fibrin Clot Properties and Liver Function Tests in Fontan Patients
3.6. Fibrin Clot Properties and Endothelium-Derived Hemostatic Factors in Fontan Patients
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | Fontan Patients (n = 66) |
---|---|
Age at Fontan operation (years) | 5.2 ± 3.9 |
Postoperative time (years) | 20.5 [16.3–22.0] |
Preoperative anatomy, n (%) | |
Ventricular septal defect in single ventricle physiology | 40 (60.6) |
Transposition of the great arteries | 29 (43.9) |
Hypoplasia of right ventricle | 19 (28.8) |
Tricuspid atresia | 15 (22.7) |
Double-outlet right ventricle | 9 (13.6) |
Hypoplastic left heart syndrome | 9 (13.6) |
Type of Fontan, n (%) | |
Lateral tunnel | 61 (92.4) |
Extracardiac conduit | 5 (7.6) |
Fenestration, n (%) | 30 (45.5) |
NYHA functional class, n (%) | |
I | 16 (24.2) |
II | 46 (69.7) |
III | 4 (6.1) |
Medication, n (%) | |
NSAID | 40 (60.6) |
Beta blockers | 11 (16.7) |
ACE inhibitors | 8 (12.1) |
NOAC | 10 (15.15) |
Complications, n (%) | |
Hepatic | 28 (42.4) |
Thromboembolic | 8 (12.1) |
Variable | Fontan-Patients (n = 66) | Controls (n = 59) | p-Value |
---|---|---|---|
Age in 2018 (years) | 23.0 [19.3–27.0] | 24.0 [19.0–29.0] | 0.565 |
Male, n (%) | 43 (65.2) | 27 (47.4) | 0.845 |
BMI (kg/m2) | 21.8 [20.4–24.2] | 21.6 [19.2–24.9] | 0.821 |
Resting saturation (%) | 93.0 [92.0–94.0] | 98.0 [97.0–9.0] | <0.001 |
Laboratory investigations | |||
RBC (106/mm3) | 5.3 ± 0.5 | 4.8 ± 0.5 | <0.001 |
WBC (103/mm3) | 5.7 ± 2.0 | 6.2 ± 1.5 | 0.061 |
PLT (103/mm3) | 152.0 [120.0–203.8] | 237.0 [213.0–266.0] | <0.001 |
TC (μmol/L) | 3.7 ± 0.9 | 4.0 ± 0.6 | <0.001 |
LDL cholesterol (μmol/L) | 2.3 ± 0.7 | 2.5 ± 0.6 | 0.017 |
CRP (mg/L) | 1.2 [0.7–2.0] | 0.9 [0.7–1.5] | 0.211 |
Creatinine (µmol/L) | 72.5 [62.3–82.0] | 69 [63.0–85.0) | 0.720 |
ALT (U/L) | 23.5 [18.3–31.0] | 15.5 [13.0–19.3] | <0.001 |
AST (U/L) | 25.0 [21.0–28.8] | 19.0 [17.0–22.0] | <0.001 |
Albumin (g/L) | 42.5 [40.3–44.6] | 40.7 [39.5–43.2] | 0.009 |
Total bilirubin (µmol/L) | 16.1 [10.9–24.2] | 14.0 [12.0–19.0] | 0.271 |
GGTP (U/L) | 59.0 [39.0–115.0] | 12.0 [7.6–16.1] | <0.001 |
aFP (ng/mL) | 2.5 [1.8–4.3] | 2.1 [1.6–3.1] | 0.029 |
APRI | 0.5 ± 0.3 | 0.2 ± 0.1 | <0.001 |
INR | 1.4 ± 0.2 | 1.0 ± 0.1 | <0.001 |
PT (s) | 15.5 ± 2.1 | 11.9 ± 0.6 | <0.001 |
D-dimer (µg/L) | 255.5 [189.8–401.5] | 194.0 [170.0–247.0] | 0.005 |
Endothelin (pg/mL) | 2.5 ± 0.8 | 1.5 ± 0.3 | <0.001 |
Clot characteristics | |||
KS (x 10−9 cm2) | 6.5 ± 1.8 | 7.3 ± 1.1 | 0.005 |
CLT (min) | 114.4 [100.5–141.0] | 104.8 [87.0–116.4] | <0.001 |
Liver-derived hemostatic factors | |||
FV (%) | 59.0 [40.8–75.3] | 79.0 [73.8–82.0] | <0.001 |
FVII (%) | 59.5 [52.5–71.0] | 96.0 [81.5–105.5] | <0.001 |
FVIII (%) | 88.5 [68.0–107.3] | 76.0 [64.5–93.0] | 0.037 |
FIX (%) | 91.5 [78.5–110.5] | 87.0 [80.3–104.0] | 0.721 |
FX (%) | 85.0 [75.8–92.5] | 101.0 [95.0–117.5] | <0.001 |
Fibrinogen (g/dL) | 2.4 ± 0.5 | 2.7 ± 0.5 | 0.003 |
Antithrombin (%) | 94.5 [91.0–101.8] | 101.0 [94.5–106.5] | 0.003 |
Protein S (%) | 90.0 [80.0–100.0] | 94.0 [83.5–109.0] | 0.049 |
Protein C (%) | 97.5 [86.0–112.3] | 109 [98.5–125.5] | <0.001 |
TAFI activity (%) | 94.3 [81.2–101.6] | 101.6 [95.2–109.6] | <0.001 |
TAFI antigen (%) | 85.9 [72.3–103.2] | 99.2 [83.9–112.2] | 0.042 |
Endothelium-derived hemostatic factors | |||
vWF activity (%) | 96.0 [81.8–128.2] | 85.7 [62.4–100.6] | <0.001 |
vWF antigen (%) | 136.9 [118.6–173.7] | 89.9 [71.9–114.4] | <0.001 |
tPA (ng/mL) | 5.4 [3.9–6.9] | 3.6 [2.5–5.5] | <0.001 |
PAI-1 (ng/mL) | 9.9 [6.5–14.7] | 9.4 [5.9–13.0] | 0.423 |
Clinical Variable | Ks ≤ 5.20 × 10−9 cm2 | CLT > 141.0 min | ||||||
---|---|---|---|---|---|---|---|---|
Univariate | Multivariate | Univariate | Multivariate | |||||
Odds Ratio (95% CI) | p-Value | Odds Ratio (95% CI) | p-Value | Odds Ratio (95% CI) | p-Value | Odds Ratio (95% CI) | p-Value | |
Time between surgery and investigation | 1.068 (0.941–1.226) | 0.315 | 1.075 (0.938–1.250) | 0.302 | ||||
RBC | 0.566 (0.178–1.647) | 0.301 | 0.847 (0.260–2.629) | 0.775 | ||||
WBC | 1.059 (0.794–1.647) | 0.680 | 0.777 (0.508–1.092) | 0.159 | ||||
PLT | 1.004 (0.995–1.013) | 0.366 | 1.006 (0.997–1.015) | 0.213 | ||||
LDL cholesterol | 1.721 (0.808–3.893) | 0.156 | 3.653 (1.510–11.400) | 0.003 | 3.802 (1.114-15.794) | 0.033 | ||
CRP | 1.126 (0.978–1.458) | 0.104 | 1.071 (0.933–1.268) | 0.288 | ||||
ALT | 1.011 (0.958–1.063) | 0.667 | 1.004 (0.944–1.058) | 0.883 | ||||
AST | 1.019 (0.945–1.092) | 0.605 | 0.990 (0.899–1.066) | 0.801 | ||||
Albumin | 0.893 (0.752–1.021) | 0.105 | 0.733 (0.547–0.901) | 0.003 | 0.892 (0.767–1.026) | 0.107 | ||
GGTP | 1.004 (0.995–1.015) | 0.437 | 1.008 (0.995–1.020) | 0.223 | ||||
Endothelin | 0.770 (0.313–1.625) | 0.511 | 0.392 (0.109–1.059) | 0.067 | ||||
Ks | 0.738 (0.511–1.019) | 0.066 | ||||||
CLT | 1.026 (1.004–1.052) | 0.021 | ||||||
FV | 1.006 (0.982–1.029) | 0.634 | 1.004 (0.978–1.029) | 0.760 | ||||
FVII | 1.015 (0.980–1.052) | 0.389 | 1.035 (0.997–1.078) | 0.712 | ||||
FVIII | 1.013 (0.991–1.036) | 0.252 | 0.990 (0.965–1.014) | 0.430 | ||||
FIX | 1.041 (1.014–1.074) | 0.003 | 1.015 (0.988–1.042) | 0.280 | ||||
FX | 1.036 (0.997–1.083) | 0.074 | 1.015 (0.974–1.059) | 0.465 | ||||
Fibrinogen | 12.441 (3.238–72.664) | <0.001 | 11.798 (2.658;87.659) | <0.001 | 1.333 (0.403–4.218) | 0.627 | ||
Antithrombin | 1.026 (0.970–1.089) | 0.375 | 1.035 (0.977–1.102) | 0.246 | ||||
Protein S | 1.058 (1.017–1.111) | 0.004 | 1.021 (0.985–1.061) | 0.254 | ||||
Protein C | 1.038 (1.009–1.072) | 0.008 | 1.057 (1.023–1.101) | <0.001 | 1.069 (1.024–1.132) | 0.002 | ||
TAFI activity | 1.088 (1.031–1.162) | 0.001 | 1.080 (1.021–1.156) | 0.005 | ||||
TAFI antigen | 1.045 (1.016–1.080) | 0.002 | 1.040 (1.008;1.078) | 0.012 | 1.031 (1.003–1.063) | 0.028 | ||
vWF activity | 1.014 (0.997–1.032) | 0.110 | 0.996 (0.975–1.014) | 0.682 | ||||
vWF antigen | 1.012 (0.998–1.028) | 0.097 | 0.990 (0.970–1.006) | 0.227 | ||||
tPA | 0.908 (0.691–1.091) | 0.359 | 0.733 (0.502–0.986) | 0.038 | ||||
PAI-1 | 1.032 (0.996–1.081) | 0.085 | 0.986 (0.912–1.029) | 0.577 |
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Skubera, M.; Gołąb, A.; Plicner, D.; Natorska, J.; Ząbczyk, M.; Trojnarska, O.; Mazurek-Kula, A.; Smaś-Suska, M.; Bartczak-Rutkowska, A.; Podolec, P.; et al. Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time—Multicenter Study. J. Clin. Med. 2021, 10, 5976. https://doi.org/10.3390/jcm10245976
Skubera M, Gołąb A, Plicner D, Natorska J, Ząbczyk M, Trojnarska O, Mazurek-Kula A, Smaś-Suska M, Bartczak-Rutkowska A, Podolec P, et al. Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time—Multicenter Study. Journal of Clinical Medicine. 2021; 10(24):5976. https://doi.org/10.3390/jcm10245976
Chicago/Turabian StyleSkubera, Maciej, Aleksandra Gołąb, Dariusz Plicner, Joanna Natorska, Michał Ząbczyk, Olga Trojnarska, Anna Mazurek-Kula, Monika Smaś-Suska, Agnieszka Bartczak-Rutkowska, Piotr Podolec, and et al. 2021. "Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time—Multicenter Study" Journal of Clinical Medicine 10, no. 24: 5976. https://doi.org/10.3390/jcm10245976
APA StyleSkubera, M., Gołąb, A., Plicner, D., Natorska, J., Ząbczyk, M., Trojnarska, O., Mazurek-Kula, A., Smaś-Suska, M., Bartczak-Rutkowska, A., Podolec, P., & Tomkiewicz-Pająk, L. (2021). Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time—Multicenter Study. Journal of Clinical Medicine, 10(24), 5976. https://doi.org/10.3390/jcm10245976