Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection
Abstract
:1. Introduction
2. Results
2.1. Altered Standard Coagulation Tests in CHC-Infected Patients
2.2. Normal Functional Whole Blood Hemostasis in CHC-Infected Patients
2.3. Impaired Whole Blood Platelet Aggregation in Patients with CHC Infection
2.4. Minor Changes in Functional Hemostasis after Treatment
3. Discussion
4. Methods
4.1. Patients
4.2. Blood Sampling
4.3. Conventional Plasma Based and Functional Haemostatic Whole-Blood Tests
4.4. Tromboelastography (TEG)
4.5. Impedance Aggregometry (Multiplate)
4.6. Statistics and Data
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
CVD | Cardiovascular disease |
CHC | Chronic Hepatitis C |
HCV | Hepatitis C virus |
SVR | Sustained Virological Response |
TEG | Tromboelastography |
HCC | Hepatocellular carcinoma |
vWF | Von Willebrand factor |
APTT | Activated partial thromboplastin time |
INR | International normalized ratio |
HIV | Human immunodeficiency virus |
DAA | Direct-acting antivirals |
DVT | Deep vein thrombosis |
EASL | European Association for the Study of the Liver |
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Baseline Characteristics | HCV Infected with No or Mild Fibrosis (n = 43) * | HCV Infected with Advanced Fibrosis (n = 39) | Healthy Controls (n = 39) | p-Value | HCV Infected + Treatment (n = 33) |
---|---|---|---|---|---|
Gender, n (Male) (m%) | 27 (62.8) | 23 (59) | 20 (51.3) | 0.495 | 21 (61.8) |
Age, year, median (IQR) | 49 (37–56) | 57 (50–61) L | 51 (42–56) | 0.001 | 55 (45–60) |
Current smoker n (%) | 18 (42) L | 15 (38) | 10 (25) | 0.358 | 18 (53) |
HCV-RNA at inclusion, IU/mL, median, (IQR) | 1.2 × 106 (0.28 × 106–3.00 × 106) | 1.6 × 106 (0.68 × 106–4.05 × 106) | N/A | 0.166 | 1.55 × 106 (0.8 × 106–3.8 × 106) |
Years since diagnosis of HCV infection, median (IQR) | 14 (6–23) | 10 (3–27) | N/A | 0.266 | 11 (5–25) |
Genotype 1/2/3/4 n | 22/8/9/3 | 18/2/16/3 | N/A | N/A | 20/1/12/1 |
Fibroscan kPa, median (IQR) | 5.7 (4.7–6.2) | 14.1 (11.1–21.3) | N/A | <0.001 | 13.5 (6.6–20.2) |
Bilirubin level, µmol/L, median (IQR) | 7 (6–10) | 11 (6–16) | N/A | 0.009 | 11 (6–16) |
Albumin level, g/L, median (IQR) | 39 (37–40) | 37 (34–38) | N/A | 0.002 | 36 (34–38) |
Creatinine level, µmol/L, medicn (IQR) | 75 (68–86) | 68 (61–80) | N/A | 0.068 | 70 (62–82) |
INR, median (IQR) | 1.1 (1.1–1.2) | 1.1 (1.1–1.2) L | 1.0 (1.0–1.1) | 0.002 | 1.1 (1.0–1.2) |
Patients with presence of portal hypertension/esophagal varices at enrollment (n) | 5/2 | 4/2 | |||
Treatment used, n A(r+)/B(r+)/C(r+)/D(r+)/E(r+) | 5(2)/17(10)/5(0)/3(0)/3(1) | ||||
Treatment duration, n 8/12/16/24 weeks | 8/19/3/3 |
Coagulation Tests | Normal Range | HCV Infected with Advanced Fibrosis | HCV Infected with no or Mild Fibrosis | p-Value | Healthy Controls |
---|---|---|---|---|---|
Standard coagulation tests | |||||
Platelet count, median (IQR) | 145–390 × 109 cells/L | 139 (113–187) L | 232 (184–267) L | <0.001 | 254 (230–293) |
Coagulation factors II-VII-X, median (IQR) | >0.60 arb.units/L | 0.76 (0.6–0.86) L | 0.88 (0.76–1.03) | 0.002 | 0.93 (0.81–1.06) |
D-dimer, median (IQR) | >0.5 mg FEU/L | 0.3 (0.3–0.4) L | 0.3 (0.3–0.3) | 0.002 | 0.3 (0.3–0.3) |
Above threshold, n (%) | 8 (21) L | 1 (2) | 0.009 | 0 (0) | |
Antithrombin, median (IQR) | 0.83–1.15 × 103 IU/L | 0.86 (0.7–0.92) L | 1.01 (0.95–1.11) L | 0.001 | 1.10 (1.05–1.16) |
APTT, median (IQR) | 25–37 s | 28 (26–30) | 28 (27–30) | 0.738 | 29 (28–31) |
Fibrinogen, median (IQR) | 5.3–10.3 µmol/L | 8.5 (7.6–10) | 8.1 (7.1–9.5) L | 0.333 | 8.7 (8.1–10.2) |
Whole blood functional hemostasis tests | |||||
R, median (IQR) | 4–9 min | 6,7 (5.7–7.9) | 6.4 (5.5–7.5) | 0.239 | 6.8 (5.8–7.6) |
Angle, median (IQR) | 55–78 degrees | 65 (61–68) | 67 (64–69) | 0.122 | 67 (62–69) |
MA, median (IQR) | 51–69 mm | 58 (54–61) | 61 (57–63) | 0.044 | 52 (56–66) |
Ly30, %, median (IQR) | 0–4% | 0.9 (0.0–2.6) | 1.4 (0.2–3.2) | 0.393 | 1.6 (0.3–4.0) |
Coagulation in CHC-Infected Patients before and after Treatment against HCV | Pre Treatment | Post Treatment | p-Value | Healthy Controls |
---|---|---|---|---|
Standard coagulation tests | ||||
Platelet count, median (IQR) | 166 (113–209) L | 170 (118–230) L | 0.033 | 254 (230–293) |
Coagulation factors II-VII-X, median (IQR) | 0.79 (0.63–0.86) L | 0.73 (0.62–0.90) L | 0.837 | 0.93 (0.81–1.06) |
D-dimer, median (IQR) | 0.3 (0.3–0.4) L | 0.3 (0.3–0.4) L | 0.495 | 0.3 (0.3–0.3) |
Above threshold (%) | 5 (14) L | 4 (12) L | 0 (0) | |
Antithrombin, median (IQR) | 0.88 (0.73–1.05) L | 0.93 (0.80–0.98) L | 0.865 | 1.10 (1.05–1.16) |
APTT, median (IQR) | 29 (27–30) | 28 (26–31) | 0.116 | 29 (28–31) |
Fibrinogen, median (IQR) | 8.2 (7.2–10.1) | 9.6 (8.4–10.7) | 0.001 | 8.7 (8.1–10.2) |
Whole blood functional hemostasis tests | ||||
R, median (IQR) | 6.6 (5.8–7.6) | 6.4 (5.5–7.2) | 0.543 | 6.8 (5.8–7.6) |
Angle, median (IQR) | 65 (60–67) | 66 (60–69) | 0.294 | 67 (62–69) |
MA, median (IQR) | 58 (54–61) | 59 (54–64) | 0.058 | 52 (56–66) |
Ly30, %, median (IQR) | 0.8 (0.7–2.4) | 1.2 (1.2–3.4) | 0.808 | 1.6 (0.3–4.0) |
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Nielsen, N.S.; Jespersen, S.; Gaardbo, J.C.; Arnbjerg, C.J.; Clausen, M.R.; Kjær, M.; Gerstoft, J.; Ballegaard, V.; Ostrowski, S.R.; Nielsen, S.D. Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection. Int. J. Mol. Sci. 2017, 18, 1016. https://doi.org/10.3390/ijms18051016
Nielsen NS, Jespersen S, Gaardbo JC, Arnbjerg CJ, Clausen MR, Kjær M, Gerstoft J, Ballegaard V, Ostrowski SR, Nielsen SD. Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection. International Journal of Molecular Sciences. 2017; 18(5):1016. https://doi.org/10.3390/ijms18051016
Chicago/Turabian StyleNielsen, Nick S., Sofie Jespersen, Julie C. Gaardbo, Caroline J. Arnbjerg, Mette R. Clausen, Mette Kjær, Jan Gerstoft, Vibe Ballegaard, Sisse R. Ostrowski, and Susanne D. Nielsen. 2017. "Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection" International Journal of Molecular Sciences 18, no. 5: 1016. https://doi.org/10.3390/ijms18051016