The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Analysis of Platelet Receptor mRNA Expression
2.3. Analysis of Platelet Receptor Protein Expression
2.4. Assessment of Serum Levels of GPIbα
3. Discussion
4. Materials and Methods
4.1. Study Groups and Clinical Characteristics
4.2. Sample Collection
4.3. RNA Extraction and cDNA Synthesis
4.4. Real-Time Quantitative PCR Analysis
4.5. Protein Extraction and Quantification
4.6. Elisa
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameter | Bleeders (n = 27) | Non-Bleeders (n = 55) | p-Value |
---|---|---|---|
age at LVAD implantation [y] | 60.9 ± 9.9 | 59.2 ± 9.5 | 0.46 |
male gender | 22 (82%) | 48 (87%) | 0.52 |
body mass index [kg/m2] | 28.3 ± 5.5 | 28.6 ± 5.5 | 0.86 |
blood type * | 0.81 | ||
A | 11 (41%) | 28 (52%) | |
B | 4 (15%) | 5 (9%) | |
AB | 1 (4%) | 2 (4%) | |
0 | 11 (41%) | 19 (35%) | |
etiology of heart disease | 0.35 | ||
NICM | 12 (44%) | 32 (58%) | |
ICM | 15 (56%) | 23 (42%) | |
alcohol abusus | 0.62 | ||
current | 5 (19%) | 6 (11%) | |
former | 14 (52%) | 25 (45%) | |
occasional | 5 (19%) | 13 (24%) | |
unknown | 3 (11%) | 11 (20%) | |
smoking | 0.61 | ||
current | 3 (11%) | 10 (18%) | |
former | 16 (59%) | 29 (53%) | |
never | 3 (11%) | 9 (16%) | |
unknown | 5 (19%) | 7 (13%) | |
pump characteristics | |||
pump speed [rpm] | 5141 ± 571 | 5271 ± 2665 | 0.16 |
pump flow [L/min] | 4.2 ± 0.6 | 4.3 ± 0.7 | 0.27 |
pump power [W] | 3.9 ± 0.5 | 4.0 ± 0.4 | 0.45 |
pulse index | 4.5 ± 2.0 | 4.4 ± 1.6 | 0.82 |
anticoagulation at study begin | |||
Phenprocoumon/warfarin | 27 (100%) | 55 (100%) | 1.00 |
clopidogrel | 7 (26%) | 11 (20%) | 0.58 |
acetylsalicylic acid | 16 (59%) | 45 (82%) | 0.04 |
prasugrel | 1 (4%) | 0 (0%) | 0.33 |
Parameter | Bleeders (n = 27) | Non-Bleeders (n = 55) | p-Value |
---|---|---|---|
thromboembolic event prior LVAD implantation | |||
ischemic stroke | 3 (%) | 9 (%) | 0.74 |
pulmonary embolism | 1 (%) | 1 (%) | 1.00 |
venous thrombosis | 2 (%) | 5 (%) | 1.00 |
ventricle thrombosis | 3 (%) | 14 (%) | 0.16 |
myocardial infarction | 7 (%) | 15 (%) | 1.00 |
hemorrhagic events after LVAD implantation * | |||
gastrointestinal tract bleeding | 12 (44%) | - | |
vascular (epistaxis) | 7 (26%) | - | |
haemothorax | 4 (15%) | - | - |
dermal bleeding (haematoma) | 3 (11%) | - | |
intracranial bleeding | 2 (7%) | - | |
other | 4 (15%) | - | |
thromboembolic event after LVAD implantation | |||
ischemic stroke | 0 (0%) | 3 (6%) | 1.00 |
pAVK | 2 (7%) | 3 (6%) | 1.00 |
pump thrombosis | 0 (0%) | 1 (2%) | 1.00 |
rethoracothomy after LVAD implantation | 13 (48%) | 29 (53%) | 0.82 |
Parameter | Bleeders (n = 27) | Non-Bleeders (n = 55) | p-Value |
---|---|---|---|
erythrocytes [Tpt/L] | 3.8 ± 0.8 | 4.4 ± 0.8 | <0.01 |
hematocrit | 0.3 ± 0.1 | 0.4 ± 0.1 | <0.01 |
hemoglobin [mmol/L] | 7.2 ± 1.3 | 8.3 ± 1.5 | <0.01 |
platelets [×109/L] at study begin | 211 ± 82 | 221 ± 67 | 0.55 |
platelets [×109/L] at bleeding event | 234 ± 115 | - | - |
leucocytes [Gpt/L] | 7.7 ± 2.3 | 7.8 ± 1.9 | 0.83 |
INR | 2.1 ± 0.5 | 2.2 ± 0.4 | 0.10 |
CRP [mg/L] | 12.4 ± 16.4 | 8.2 ± 10.3 | 0.23 |
LDH [µmol/(L/s)] | 3.9 ± 1.0 | 4.2 ± 0.8 | 0.28 |
Parameter | Bleeders (n = 27) | Non-Bleeders (n = 55) | p-Value |
---|---|---|---|
Platelet adhesion assay [%] | |||
ADP | 54 ± 24 | 56 ± 20 | 0.70 |
TRAP-6 | 73 ± 15 | 78 ± 15 | 0.13 |
VASP-phosphorylation | 70 ± 22 | 77 ± 18 | 0.12 |
aPTT [s] | 44.2 ± 7.4 | 42.6 ± 6.4 | 0.32 |
vWF antigen [%] | 198.6 ± 65.5 | 176.1 ± 61.0 | 0.26 |
vWF activity [%] | 136.7 ± 28.7 | 128.5 ± 34.1 | 0.43 |
vWF CB activity [%] | 135.5 ± 41.9 | 116.1 ± 37.3 | 0.22 |
factor VIII, procoagulant [%] | 188.5 ± 62.4 | 171.0 ± 57.5 | 0.36 |
Target | Forward Primer 5′-3′ | Reverse Primer 5′-3′ |
---|---|---|
GPIbα | TGCCAGATCTCACGGTGAAC | AACGAGTGCTCACATCCTGAT |
GPV | CCACTTGCTTTACATCCATGCA | GGAAGAACAAATGAGACTGTGACA |
GPIX | AACAACAGCCTTCAGTCCGT | CAGAGGCGCAGATAGGTGAG |
B2M | AGTATGCCTGCCGTGTGAAC | GCAAGCAAGCAGAATTTGGA |
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Klaeske, K.; Brade, A.; Eifert, S.; Jawad, K.; Saeed, D.; Haunschild, J.; Sieg, F.; Borger, M.A.; Dieterlen, M.-T. The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months. Int. J. Mol. Sci. 2023, 24, 5639. https://doi.org/10.3390/ijms24065639
Klaeske K, Brade A, Eifert S, Jawad K, Saeed D, Haunschild J, Sieg F, Borger MA, Dieterlen M-T. The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months. International Journal of Molecular Sciences. 2023; 24(6):5639. https://doi.org/10.3390/ijms24065639
Chicago/Turabian StyleKlaeske, Kristin, Anneke Brade, Sandra Eifert, Khalil Jawad, Diyar Saeed, Josephina Haunschild, Franz Sieg, Michael A. Borger, and Maja-Theresa Dieterlen. 2023. "The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months" International Journal of Molecular Sciences 24, no. 6: 5639. https://doi.org/10.3390/ijms24065639