Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics
Abstract
:1. Introduction
2. Results
2.1. Study Population
2.2. Thrombin Inhibition Capacity Is Reduced in Most Patients with Antithrombin Mutations
2.3. Influence of Antithrombin Level on Thrombin Inhibition Kinetics
3. Discussion
4. Materials and Methods
4.1. Reagents and Materials
4.2. Patients and Samples
4.3. Laboratory Analysis of Blood Samples
4.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Properties | Human Thrombin Inhibition Assessed | Bovine Thrombin Inhibition Assessed | |
---|---|---|---|
Demographics | Mean age (range), years | 35 (4–82) | 34 (4–71) |
Males/females | 12/24 | 5/14 | |
Thrombosis history of study subjects 1 | Asymptomatic subjects | 11 | 4 |
Deep vein thrombosis | 19 | 13 | |
Pulmonary embolism | 11 | 5 | |
Other venous thrombosis | 5 | 4 | |
Arterial thrombosis | 2 | 1 | |
SERPINC1 mutations 2 | c.89T>A | 3 | - |
c.391C>T (thereof homozygous) | 11 (5) | 6 (3) | |
c.462_464del | 3 | 3 | |
c.1058C>T | 2 | 2 | |
c.1153G>A | 3 | 2 | |
c.74G>A, c.236G>A, c.470A>G, c.481C>T, c.1347del G, c.1355T>C | 1 each | 1 each | |
c.248T>A, c.331T>A, c.379T>C, c.569A>C, c.721G>T, c.805G>A, c.1246G>T, exon 1–7 large deletion | 1 each | - |
Nucleotide Exchange 1 | Amino Acid Exchange 1 | Antithrombin Activity, Thrombin-Based 2 | Half-Life of Human Thrombin 2 | Half-Life of Bovine Thrombin 2 |
---|---|---|---|---|
c.236G>A | p.Arg79His | 100% | 50.2 s | 101.2 s |
c.1246G>T | p.Ala416Ser | 77% | 62.3 s | - |
c.74G>A | p.Gly25Asp | 66% | 69.8 s | 181.1 s |
c.805G>A | p.Glu269Lys | 62% | 75.7 s | - |
c.1347del G | p.Leu449fsX9 | 81% | 87.5 s | 195.0 s |
c.462_464del | p.Phe155fs | 52 (52–53)% | 92.3 (83.8–107.0) s | 168.5 (148.1–184.5) s |
c.1355T>C | p.Ile452Thr | 84% | 98.8 s | 117.9 s |
c.391C>T | p.Leu131Phe | 77 (71–84)% | 104.9 (60.6–137.4) s | 207.3 (134.3–255.5) s |
c.248T>A | p.Leu83Gln | 61% | 106.1 s | - |
c.1153G>A | p.Gly385Ser | 58 (57–59)% | 106.7 (85.5–123.6) s | 174.1 (151.6–196.6) s |
c.721G>T | p.Glu241Ter | 52% | 109.1 s | - |
c.89T>A | p.Val30Glu | 77 (76–79)% | 119.7 (92.7–153.3) s | - |
c.1058C>T | p.Pro353Leu | 58 (56–60)% | 135.6 (106.7–164.5) s | 272.2 (197.4–347.0) s |
c.481C>T | p.Arg161Ter | 51% | 139.2 s | 203.8 s |
c.470A>G | p.Lys157Arg | 59% | 140.0 s | 169.7 s |
Exon 1–7 large deletion | - | 54% | 154.5 s | - |
c.391C>T (homozygous) | p.Leu131Phe | 55 (47–60)% | 154.7 (125.9–177.6) s | 263.4 (229.0–331.7) s |
c.569A>C | p.Tyr190Ser | 63% | 164.3 s | - |
c.379T>A | p.Cys127Arg | 51% | 206.6 s | - |
c.331T>A | p.Ser111Thr | 65% | 221.7 s | - |
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Reda, S.; Müller, J.; Pavlova, A.; Pezeshkpoor, B.; Oldenburg, J.; Pötzsch, B.; Rühl, H. Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics. Int. J. Mol. Sci. 2021, 22, 2119. https://doi.org/10.3390/ijms22042119
Reda S, Müller J, Pavlova A, Pezeshkpoor B, Oldenburg J, Pötzsch B, Rühl H. Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics. International Journal of Molecular Sciences. 2021; 22(4):2119. https://doi.org/10.3390/ijms22042119
Chicago/Turabian StyleReda, Sara, Jens Müller, Anna Pavlova, Behnaz Pezeshkpoor, Johannes Oldenburg, Bernd Pötzsch, and Heiko Rühl. 2021. "Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics" International Journal of Molecular Sciences 22, no. 4: 2119. https://doi.org/10.3390/ijms22042119