# Impact of AstraZeneca COVID-19 Vaccination on Coagulation and Gene Expression: A Molecular and Clinical Study

Erens Spiff Ekprikpo, Stella Urekweru Ken-Ezihuo, Beauty Eruchi

Echonwere-Uwikor, Zaccheaus Awortu Jeremiah

► To cite this version:

Erens Spiff Ekprikpo, Stella Urekweru Ken-Ezihuo, Beauty Eruchi Echonwere-Uwikor, Zaccheaus Awortu Jeremiah. Impact of AstraZeneca COVID-19 Vaccination on Coagulation and Gene Expression: A Molecular and Clinical Study. International Journal of Research and Reports in Hematology, 2025, 8 (1), pp.111-119. 10.9734/ijr2h/2025/v8i1171. hal-05044511

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# Impact of AstraZeneca COVID-19 Vaccination on Coagulation and Gene Expression: A Molecular and Clinical Study

Erens Spiff Ekprikpo a*, Stella Urekweru Ken-Ezihuo a, Beauty Eruchi Echonwere-Uwikor a and Zaccheaus Awortu Jeremiah a

## Authors' contributions

This work was carried out in collaboration among all authors. All authors read and approved the final manuscript.

## Article Information

DOI: https://doi.org/10.9734/ijr2h/2025/v8i1171

**Open Peer Review History:**
This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers, peer review comments, different versions of the manuscript, comments of the editors, etc are available here: https://pr.sdiarticle5.com/review-history/133897

## Original Research Article

Received: 17/02/2025

Accepted: 20/04/2025

Published: 23/04/2025

## ABSTRACT

This case-control study investigated the effects of the AstraZeneca COVID-19 vaccine on coagulation parameters in a cohort of 102 individuals, revealing a significant increase in activated partial thromboplastin time (aPTT) among vaccinated individuals (34.233±0.653 seconds vs 28.196±0.657 seconds, p<0.0001), which correlated with increased TMPRSS2 expression (r=-

<footnote>a Haematology and Blood Transfusion Science Department, Faculty of Medical Laboratory Science, Rivers State University, Port Harcourt, Nigeria.</footnote>

<footnote>*Corresponding author: E-mail: erens.ekprikpo1@ust.edu.ng;</footnote>
0.325, p=0.0202). The findings have important clinical implications, suggesting that vaccinated individuals, particularly those with underlying coagulopathies, may require closer monitoring for thrombotic events. The observed changes in aPTT and TMPRSS2 expression may have significant implications for patients with pre-existing coagulation disorders or those at risk of thrombotic events, emphasizing the need for vigilant monitoring and personalized care in vaccinated individuals, and highlighting the importance of further research to inform evidence-based guidelines for COVID-19 vaccination.

Keywords: AstraZeneca COVID-19 vaccine, coagulation parameters, activated partial thromboplastin time (aPTT), prothrombin time (PT), ACE2 gene expression, TMPRSS2 gene expression, COVID-19 pathogenesis, vaccination strategies, thrombotic events, coagulopathies, patient care.

# 1. INTRODUCTION

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a profound and far-reaching impact on global public health, leading to unprecedented challenges and a significant burden on healthcare systems worldwide (WHO, 2020). The rapid spread of the virus has necessitated the swift development and deployment of effective vaccines, including the AstraZeneca COVID-19 vaccine, which has been widely administered globally (NCDC, 2021). The AstraZeneca vaccine has been shown to be highly effective in preventing severe illness and hospitalization due to COVID-19 (Voysey et al., 2021).

The SARS-CoV-2 virus primarily uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, highlighting the crucial role of ACE2 in facilitating viral entry (Zhang et al., 2020). The ACE2 receptor, a type I transmembrane protein, is expressed on the surface of various cell types, including those lining the lungs, heart, intestines, and kidneys (Hamming et al., 2004). The ACE2 receptor plays a critical role in regulating blood pressure and electrolyte balance by converting angiotensin II to angiotensin (1-7) (Tipnis et al., 2000). The transmembrane serine protease 2 (TMPRSS2) enzyme also plays a critical role in facilitating viral entry by cleaving the spike protein (Conway et al., 2022).

Understanding the molecular mechanisms underlying the interaction between the SARS-CoV-2 virus and host cells is essential for developing effective therapeutic strategies. The intricate relationship between the SARS-CoV-2 virus, ACE2, and TMPRSS2, and the subsequent effects on coagulation parameters, necessitates a comprehensive understanding of the

underlying molecular mechanisms. The AstraZeneca COVID-19 vaccine has been associated with rare cases of thrombotic thrombocytopenia purpura (TTP) and other coagulation disorders, highlighting the need for further research into the effects of this vaccine on coagulation parameters (Taylor et al., 2020).

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are essential coagulation parameters that provide valuable insights into the coagulation cascade (Levi et al., 2020). Changes in PT and aPTT have been observed in COVID-19 patients, and understanding the effects of AstraZeneca vaccination on these parameters is crucial for optimizing patient care (Boucher et al., 2020). Furthermore, the vaccine's impact on the expression of ACE2 and TMPRSS2 genes and their correlation with coagulation parameters warrants further investigation.

The clinical implications of changes in coagulation parameters following AstraZeneca vaccination are significant, and understanding these changes is crucial for identifying individuals at risk of adverse events. The development of effective therapeutic strategies for managing coagulation disorders in COVID-19 patients and vaccine recipients relies on a comprehensive understanding of the underlying molecular mechanisms.

This study aims to investigate the impact of AstraZeneca COVID-19 vaccination on coagulation parameters, including PT and aPTT, and explore their correlation with molecular parameters, such as ACE2 and TMPRSS2 gene expression. By elucidating the molecular mechanisms underlying the effects of AstraZeneca vaccination on coagulation parameters, this study seeks to provide valuable insights into the optimization of patient care and
the development of effective therapeutic strategies.

The significance of this study lies in its potential to provide novel insights into the molecular mechanisms underlying the effects of AstraZeneca vaccination on coagulation parameters. By exploring the correlation between ACE2 and TMPRSS2 gene expression and coagulation parameters, this study aims to identify potential biomarkers for monitoring coagulation disorders in individuals receiving the AstraZeneca vaccine. Furthermore, this study seeks to contribute to the development of effective therapeutic strategies for managing coagulation disorders in COVID-19 patients and vaccine recipients.

The findings of this study will contribute significantly to the existing body of knowledge on the effects of COVID-19 vaccination on coagulation parameters, ultimately informing vaccination strategies and optimizing patient outcomes. The study's results will also provide valuable insights for healthcare professionals, policymakers, and researchers, enabling them to make informed decisions regarding COVID-19 vaccination and patient care.

# 2. MATERIALS AND METHODS

## 2.1 Experimental Design

This case-control study investigated the molecular and clinical correlates of AstraZeneca COVID-19 vaccination on coagulation parameters in Port Harcourt, Nigeria. The case group consisted of subjects who had received the AstraZeneca COVID-19 vaccine, while the control group included unvaccinated subjects.

## 2.2 Study Area and Population

The study was conducted in Port Harcourt, Nigeria, and included subjects aged 18-65 years who had either received the AstraZeneca COVID-19 vaccine or had not been vaccinated.

## 2.3 Sample Size Determination

The sample size was calculated using G*Power software version 3.1.9.4, with a medium effect size (Cohen's d = 0.5), a significance level of 0.05, and a power of 0.80. Based on these parameters, a minimum of 102 participants (51 in each group) was determined.

## 2.4 Inclusion Criteria

1. Subjects between the age range of 18-65.

2. Apparently healthy non-vaccinated subjects.

3. Confirmed vaccinated subjects.

4. Subject must be a resident of Port Harcourt.

5. Subjects that have completed the vaccination jab within the past 6 months and above.

## 2.5 Exclusion Criteria

1. Subjects below the ages of 18.

2. Subjects who refused to give consent.

3. Individuals with a history of severe allergic reactions to any vaccine component.

4. Individuals with a known autoimmune disease.

5. Pregnant or breastfeeding women.

6. Individuals with acute or chronic infections requiring treatment.

7. Individuals on immunosuppressive medications.

8. Persons suffering from known haemostatic or coagulatory disorders.

9. Persons on any form of anticoagulant therapy.

## 2.6 Blood Sample Collection, Processing, and Storage

Venous blood was collected into EDTA and Tri-Sodium citrate tubes where platelet poor plasma (PPP) was obtained and used for the PT and aPTT coagulation studies, and RNA isolation was done from the EDTA samples. The blood samples were collected using standardized phlebotomy techniques by trained healthcare professionals. The samples were stored at -80°C until processing.

## 2.7 Coagulation Studies

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were determined using standard coagulation assays on the Erba Mannheim Autoanalyzer.

## 2.8 Determination of PT

The PT test was performed using the Agappe Reagent Kit on the ERBA Mannheim Autoanalyzer. The PT test is a laboratory test used to assess the extrinsic and common
pathways of the coagulation cascade. It measures the time it takes for a clot to form in the presence of tissue factor (thromboplastin) and calcium.

## 2.8.1 Determination of aPTT

The aPTT test was performed using the Agappe Reagent Kit on the ERBA Mannheim Autoanalyzer. The aPTT test is used to assess the intrinsic and common pathways of the coagulation cascade. It measures the time it takes for a clot to form in the presence of an activator (kaolin) and phospholipids (cephalin) in the absence of tissue factor.

# 3. RESULTS

<table><caption>Table 1. Characteristics of Study Population</caption><thead><tr><th rowspan="2">Characteristic</th><th>Total</th><th>Vaccinated (Test)</th><th>Unvaccinated (Control)</th></tr><tr><th>N (%)</th><th>n (%)</th><th>n (%)</th></tr></thead><tbody><tr><td><strong>Sex</strong></td><td></td><td></td><td></td></tr><tr><td>Female</td><td>45 (44.1)</td><td>18 (40.0)</td><td>27 (60.0)</td></tr><tr><td>Male</td><td>57 (55.9)</td><td>27 (47.4)</td><td>30 (52.6)</td></tr><tr><td><strong>Age Group (years)</strong></td><td></td><td></td><td></td></tr><tr><td>&lt;30</td><td>29 (28.4)</td><td>5 (17.2)</td><td>24 (82.8)</td></tr><tr><td>30-44</td><td>51 (50.0)</td><td>35 (68.6)</td><td>16 (31.4)</td></tr><tr><td>45+</td><td>22 (21.6)</td><td>11 (50.0)</td><td>11 (50.0)</td></tr><tr><td><strong>Mean ± SD</strong></td><td>36.8 ± 8.7</td><td>38.8 ± 6.28</td><td>34.8 ± 10.3</td></tr></tbody></table>

<table><caption>Table 2. Comparison of Coagulation and Molecular Parameters of COVID-19 Vaccinated and Unvaccinated Subjects</caption><thead><tr><th rowspan="2">Parameter</th><th>Vaccinated (Test)<br>(n=51)</th><th>Unvaccinated<br>(Control) (n=51)</th><th colspan="2">Test Statistics</th></tr><tr><th>Mean ± SD</th><th>Mean ± SD</th><th>t-Ratio</th><th>Prob >|t|</th></tr></thead><tbody><tr><td>INR</td><td>0.968±0.028</td><td>0.945±0.006</td><td>-0.834</td><td>0.4063</td></tr><tr><td>PT (Sec)</td><td>11.812±0.228</td><td>12.004±0.190</td><td>0.648</td><td>0.5193</td></tr><tr><td>APTT (Sec)</td><td>34.233±0.653</td><td>28.196±0.657</td><td>-6.514</td><td>&lt;.0001****</td></tr><tr><td>RNA Conc. (ng/uL)</td><td>4.016±0.094</td><td>6.382±0.137</td><td>14.229</td><td>&lt;.0001****</td></tr><tr><td>GAPDH (CT)</td><td>24.303±0.068</td><td>24.377±0.075</td><td>0.733</td><td>0.4651</td></tr><tr><td>ACE2 (CT)</td><td>29.375±0.077</td><td>29.583±0.074</td><td>1.937</td><td>0.0555</td></tr><tr><td>TMPRSS2 (CT)</td><td>29.693±0.074</td><td>29.794±0.075</td><td>0.955</td><td>0.3418</td></tr></tbody></table>

Abbreviations: SD: Standard deviation, INR: International Normalized ratio, PT: Prothrombin Time, APTT: Activated Partial Thromboplastin Time, RNA: Ribonucleic Acid.

Significance level: ****=p<0.0001.

<table><caption>Table 3. Sex-Dependent Effects of COVID-19 Vaccination on Coagulation Parameter</caption><thead><tr><th rowspan="2">Groups</th><th rowspan="2">Sex</th><th rowspan="2">n</th><th>INR</th><th>PT (Sec)</th><th>APTT (Sec)</th></tr><tr><th>Mean ± SD</th><th>Mean ± SD</th><th>Mean ± SD</th></tr></thead><tbody><tr><td rowspan="2">Vaccinated (Test)</td><td>Female</td><td>18</td><td>1.05±0.04</td><td>12.50±0.45<sup>a</sup></td><td>32.93±1.40</td></tr><tr><td>Male</td><td>33</td><td>0.92±0.03</td><td>11.77±0.36<sup>a</sup></td><td>34.50±1.11</td></tr><tr><td rowspan="2">Unvaccinated (Control)</td><td>Female</td><td>27</td><td>0.94±0.03</td><td>11.59±0.29<sup>b</sup></td><td>28.97±0.89</td></tr><tr><td>Male</td><td>24</td><td>0.95±0.04</td><td>12.51±0.37<sup>a</sup></td><td>28.74±1.14</td></tr></tbody></table>

## 2.8.2 RNA isolation and gene expression analysis

RNA was isolated using the Zymo Quick-RNA Plus Isolation Kit, and ACE2 and TMPRSS2 gene expression was analyzed.

## 2.8.3 Statistical Analysis

The statistical analysis for this study was performed using SAS software (version 9.4) and JMP statistical discovery software. Independent t-tests, ANOVA, and Pearson correlation analysis were used to compare groups and examine relationships between variables.
<table><thead><tr><th rowspan="2">Groups</th><th rowspan="2">Sex</th><th rowspan="2">n</th><th>INR</th><th>PT (Sec)</th><th>APTT (Sec)</th></tr><tr><th>Mean ± SD</th><th>Mean ± SD</th><th>Mean ± SD</th></tr></thead><tbody><tr><td>F-Ratio</td><td></td><td></td><td>3.6238</td><td>4.8990</td><td>0.6162</td></tr><tr><td>P-Value</td><td></td><td></td><td>0.0602<sup>ns</sup></td><td>0.0294*</td><td>0.4345<sup>ns</sup></td></tr></tbody></table>

Abbreviations: SD: Standard deviation, INR: International Normalized ratio, PT: Prothrombin Time, APTT: Activated Partial Thromboplastin Time. Mean ± SD within a given parameter with different superscripts are significantly different at p<0.05.

Significance level: * = p<0.05, ns = not significant (p>0.05)

<table><caption>Table 4. Age-Dependent Effects of COVID-19 Vaccination on Coagulation Parameter</caption><thead><tr><th rowspan="2">Groups</th><th rowspan="2">Age Group(years)</th><th rowspan="2">n</th><th>INR</th><th>PT (Sec)</th><th>APTT (Sec)</th></tr><tr><th>Mean±SD</th><th>Mean ± SD</th><th>Mean ± SD</th></tr></thead><tbody><tr><td rowspan="3">Vaccinated (Test)</td><td>&lt;30</td><td>5</td><td>0.93±0.07</td><td>12.44±0.68</td><td>33.15±2.11</td></tr><tr><td>30-44</td><td>35</td><td>0.98±0.03</td><td>11.53±0.27</td><td>34.66±0.82</td></tr><tr><td>45+</td><td>11</td><td>1.05±0.05</td><td>12.44±0.47</td><td>33.34±1.45</td></tr><tr><td rowspan="3">Unvaccinated (Control)</td><td>&lt;30</td><td>24</td><td>0.94±0.03</td><td>12.19±0.31</td><td>26.64±0.96</td></tr><tr><td>30-44</td><td>16</td><td>0.95±0.04</td><td>11.86±0.38</td><td>28.60±1.16</td></tr><tr><td>45+</td><td>11</td><td>0.95±0.05</td><td>12.11±0.50</td><td>31.31±1.56</td></tr><tr><td colspan="6">Test Statistics</td></tr><tr><td>F-Ratio</td><td></td><td></td><td>0.7621</td><td>0.4244</td><td>1.4509</td></tr><tr><td>P-Value</td><td></td><td></td><td>0.4697<sup>ns</sup></td><td>0.6555<sup>ns</sup></td><td>0.2398<sup>ns</sup></td></tr></tbody></table>

Abbreviations: SD: Standard deviation, INR: International Normalized ratio, PT: Prothrombin Time, APTT: Activated Partial Thromboplastin Time. Significance level: ns = Not significant (p>0.05)

<table><caption>Table 5. Sex and Age-Dependent Effects of COVID-19 Vaccination on Coagulation Parameter</caption><thead><tr><th rowspan="2">Groups</th><th rowspan="2">Sex</th><th rowspan="2">Age Group (years)</th><th rowspan="2">n</th><th>INR</th><th>PT (Sec)</th><th>APTT (Sec)</th></tr><tr><th>Mean ± SD</th><th>Mean ± SD</th><th>Mean ± SD</th></tr></thead><tbody><tr><td rowspan="6">Vaccinated (Test)</td><td rowspan="3">Female</td><td>&lt;30</td><td>2</td><td>0.99±0.10</td><td>13.15±1.05</td><td>30.50±3.26</td></tr><tr><td>30-44</td><td>12</td><td>1.05±0.04</td><td>11.30±0.43</td><td>34.83±1.33</td></tr><tr><td>45+</td><td>4</td><td>1.11±0.07</td><td>13.05±0.74</td><td>33.45±2.31</td></tr><tr><td rowspan="3">Male</td><td>&lt;30</td><td>3</td><td>0.86±0.08</td><td>11.73±0.86</td><td>35.80±2.66</td></tr><tr><td>30-44</td><td>23</td><td>0.91±0.03</td><td>11.75±0.31</td><td>34.48±0.96</td></tr><tr><td>45+</td><td>7</td><td>0.98±0.05</td><td>11.83±0.56</td><td>33.23±1.74</td></tr><tr><td rowspan="6">Unvaccinated (Control)</td><td rowspan="3">Female</td><td>&lt;30</td><td>10</td><td>0.94±0.05</td><td>11.83±0.47</td><td>26.50±1.46</td></tr><tr><td>30-44</td><td>9</td><td>0.95±0.05</td><td>11.70±0.50</td><td>30.78±1.54</td></tr><tr><td>45+</td><td>8</td><td>0.94±0.05</td><td>11.25±0.53</td><td>29.62±1.63</td></tr><tr><td rowspan="3">Male</td><td>&lt;30</td><td>14</td><td>0.94±0.04</td><td>12.54±0.40</td><td>26.79±1.23</td></tr><tr><td>30-44</td><td>7</td><td>0.96±0.05</td><td>12.01±0.56</td><td>26.43±1.74</td></tr><tr><td>45+</td><td>3</td><td>0.95±0.08</td><td>12.97±0.86</td><td>33.00±2.66</td></tr><tr><td colspan="6">Test Statistics</td></tr><tr><td>F-Ratio</td><td></td><td></td><td>0.0095</td><td>2.0397</td><td>1.3093</td></tr><tr><td>P-Value</td><td></td><td></td><td>0.9905<sup>ns</sup></td><td>0.1360<sup>ns</sup></td><td>0.2751<sup>ns</sup></td></tr></tbody></table>

Abbreviations: SD: Standard deviation, INR: International Normalized ratio, PT: Prothrombin Time, APTT: Activated Partial Thromboplastin Time. Significance level: ns = Not significant (p>0.05).

<table><caption>Table 6. Pairwise Correlation Analysis of Coagulation and Molecular Parameters of COVID-19 Vaccinated and Unvaccinated Subjects</caption><thead><tr><th rowspan="2">Variable</th><th rowspan="2">by Variable</th><th colspan="2">Vaccinated (Test) n=51</th><th colspan="2">Unvaccinated (Control) N=51</th></tr><tr><th>Correlation</th><th>P-Value</th><th>Correlation</th><th>P-Value</th></tr></thead><tbody><tr><td>PT (Sec)</td><td>INR</td><td>0.182</td><td>0.2010</td><td>0.028</td><td>0.8445</td></tr><tr><td>Aptt (sec)</td><td>INR</td><td>0.056</td><td>0.6988</td><td>-0.071</td><td>0.6209</td></tr><tr><td>Aptt (sec)</td><td>PT (Sec)</td><td>0.083</td><td>0.5644</td><td>-0.005</td><td>0.9697</td></tr><tr><td>RNA Conc.</td><td>INR</td><td>0.224</td><td>0.1143</td><td>-0.178</td><td>0.2102</td></tr></tbody></table>
<table><thead><tr><th rowspan="2">Variable</th><th rowspan="2">by Variable</th><th colspan="2">Vaccinated (Test) n=51</th><th colspan="2">Unvaccinated (Control) N=51</th></tr><tr><th>Correlation</th><th>P-Value</th><th>Correlation</th><th>P-Value</th></tr></thead><tbody><tr><td>(ng/uL)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>RNA Conc. (ng/uL)</td><td>PT (Sec)</td><td>-0.117</td><td>0.4129</td><td>0.133</td><td>0.3529</td></tr><tr><td>RNA Conc. (ng/uL)</td><td>Aptt (sec)</td><td>-0.010</td><td>0.9471</td><td>0.019</td><td>0.8944</td></tr><tr><td>GAPDH (CT)</td><td>INR</td><td>0.096</td><td>0.5038</td><td>-0.036</td><td>0.8035</td></tr><tr><td>GAPDH (CT)</td><td>PT (Sec)</td><td>0.127</td><td>0.3735</td><td>0.169</td><td>0.2360</td></tr><tr><td>GAPDH (CT)</td><td>Aptt (sec)</td><td>0.077</td><td>0.5922</td><td>-0.070</td><td>0.6250</td></tr><tr><td>GAPDH (CT)</td><td>RNA Conc. (ng/uL)</td><td>-0.172</td><td>0.2274</td><td>-0.070</td><td>0.6279</td></tr><tr><td>ACE2 (CT)</td><td>INR</td><td>-0.141</td><td>0.3237</td><td>0.059</td><td>0.6829</td></tr><tr><td>ACE2 (CT)</td><td>PT (Sec)</td><td>0.243</td><td>0.0853</td><td>-0.002</td><td>0.9868</td></tr><tr><td>ACE2 (CT)</td><td>Aptt (sec)</td><td>0.173</td><td>0.2260</td><td>0.006</td><td>0.9688</td></tr><tr><td>ACE2 (CT)</td><td>RNA Conc. (ng/uL)</td><td>-0.137</td><td>0.3373</td><td>-0.235</td><td>0.0974</td></tr><tr><td>ACE2 (CT)</td><td>GAPDH (CT)</td><td>0.231</td><td>0.1028</td><td>0.337</td><td>0.0157*</td></tr><tr><td>TMPRSS2 (CT)</td><td>INR</td><td>-0.161</td><td>0.2576</td><td>-0.097</td><td>0.4973</td></tr><tr><td>TMPRSS2 (CT)</td><td>PT (Sec)</td><td>-0.045</td><td>0.7544</td><td>0.045</td><td>0.7540</td></tr><tr><td>TMPRSS2 (CT)</td><td>Aptt (sec)</td><td>-0.325</td><td>0.0202*</td><td>0.054</td><td>0.7090</td></tr><tr><td>TMPRSS2 (CT)</td><td>RNA Conc. (ng/uL)</td><td>-0.093</td><td>0.5182</td><td>0.548</td><td>&lt;.0001****</td></tr><tr><td>TMPRSS2 (CT)</td><td>GAPDH (CT)</td><td>0.041</td><td>0.7744</td><td>0.163</td><td>0.2517</td></tr><tr><td>TMPRSS2 (CT)</td><td>ACE2 (CT)</td><td>0.130</td><td>0.3624</td><td>0.204</td><td>0.1505</td></tr></tbody></table>

Significance level: * =p<0.05, ****=p<0.0001.

## 4. DISCUSSION

The COVID-19 pandemic has had a profound impact on global public health, leading to unprecedented challenges and a significant burden on healthcare systems worldwide (WHO, 2020). The rapid development and deployment of effective vaccines, including the AstraZeneca COVID-19 vaccine, have been crucial in mitigating the spread of the virus (Hassan, et al., 2022). However, concerns have been raised regarding the potential effects of COVID-19 vaccination on coagulation parameters, particularly in light of reported cases of thrombotic thrombocytopenia purpura (TTP) and other coagulation disorders (Abrignani, et al., 2022).

This study investigated the impact of AstraZeneca COVID-19 vaccination on coagulation parameters, including prothrombin time (PT) and activated partial thromboplastin time (aPTT), and explored their correlation with molecular parameters, such as ACE2 and TMPRSS2 gene expression. The results indicate significant differences in aPTT values between vaccinated and unvaccinated individuals, with vaccinated subjects exhibiting longer aPTT values (Table 2). Studies have suggested that COVID-19 vaccination may influence coagulation pathways by modulating the expression of genes involved in coagulation and fibrinolysis (Conway et al., 2022). Notably, the value of TMPRSS2

gene expression was found to be significantly higher in vaccinated subjects with longer aPTT values (Table 6).

This finding supports the hypothesis that TMPRSS2 may play a role in modulating coagulation pathways. TMPRSS2 is a transmembrane serine protease that plays a critical role in facilitating viral entry into host cells (Conway et al., 2020). The significant difference in TMPRSS2 gene expression between vaccinated subjects with longer aPTT values suggests that TMPRSS2 may be involved in the regulation of coagulation pathways.

Furthermore, the study found significant differences in PT values between vaccinated and unvaccinated females. Specifically, vaccinated females had significantly longer PT values compared to unvaccinated females (12.50 ± 0.45 vs. 11.59 ± 0.29 seconds, p < 0.05, Table 3). A study by Alwani et al. (2021) reported similar sex-specific differences in the response to COVID-19 vaccination, highlighting the need for further research in this area.

The study did not find significant interaction effects between treatment and age group on coagulation parameters (Table 4). Additionally, no significant interaction effects were found between treatment, sex, and age group on coagulation parameters (Table 5). These findings suggest that the effects of COVID-19 vaccination
on coagulation parameters are not influenced by age or sex.

The study's findings have significant implications for public health and clinical practice. The observed changes in aPTT values following COVID-19 vaccination suggest that healthcare professionals should be vigilant in monitoring coagulation parameters and adverse events in vaccinated individuals, particularly those with pre-existing coagulopathies or cardiovascular disease. A study by Varshney et al. (2021) reported a similar association between COVID-19 vaccination and changes in coagulation parameters, highlighting the need for continued monitoring and research in this area.

In contrast to the findings, some studies have reported an association between ACE2 gene expression and coagulation parameters (Zhang et al., 2020). However, the study did not find a significant correlation between ACE2 gene expression and coagulation parameters (Table 6). This discrepancy may be attributed to differences in study design, population, or methodology, as noted in a study by Kasho et al. (2023) that reported a similar lack of association between ACE2 gene expression and coagulation parameters.

The study provides novel insights into the effects of AstraZeneca COVID-19 vaccination on coagulation parameters and their correlation with molecular parameters, such as ACE2 and TMPRSS2 gene expression. The findings contribute significantly to the existing body of knowledge on the effects of COVID-19 vaccination on coagulation parameters, ultimately informing vaccination strategies and optimizing patient outcomes. Further research is needed to fully elucidate the mechanisms underlying the observed changes in coagulation parameters and to develop effective therapeutic strategies for managing coagulation disorders in COVID-19 patients and vaccine recipients.

## 5. CONCLUSION

In conclusion, this study provides novel insights into the effects of AstraZeneca COVID-19 vaccination on coagulation parameters and their correlation with molecular parameters. The study's main findings include significant differences in aPTT values between vaccinated and unvaccinated individuals, with vaccinated subjects exhibiting longer aPTT values, as well

as significant differences in PT values between vaccinated and unvaccinated females.

## 6. RECOMMENDATIONS

The findings of this study have significant implications for public health and clinical practice. Based on the results, the following recommendations are made:

1. Healthcare professionals should be vigilant in monitoring coagulation parameters, particularly aPTT values, in individuals who have received the AstraZeneca COVID-19 vaccine. This is especially important for individuals with pre-existing coagulopathies or cardiovascular disease.

2. Public health authorities should enhance surveillance for adverse events related to coagulation disorders following COVID-19 vaccination.

3. Further research is needed to fully elucidate the mechanisms underlying the observed changes in coagulation parameters following COVID-19 vaccination.

4. The significant differences in PT values between vaccinated and unvaccinated females highlight the need for sex-specific considerations in COVID-19 vaccination strategies.

5. These guidelines should take into account the potential risks and benefits of COVID-19 vaccination in different populations.

## 7. LIMITATIONS

1. The study had a relatively small sample size, which may limit the generalizability of the findings.

2. The study only investigated the effects of the AstraZeneca COVID-19 vaccine and did not compare it with other COVID-19 vaccines.

3. The study did not investigate the long-term effects of COVID-19 vaccination on coagulation parameters.

## CONTRIBUTION TO KNOWLEDGE

1. Provided valuable insights into the effects of AstraZeneca COVID-19 vaccination on coagulation parameters and their correlation with molecular parameters.

2. Highlighted the importance of considering individual factors, such as sex, when
evaluating the response to COVID-19 vaccination.

3. Informed personalized approaches to vaccine development and administration.

## CONSENT

Written informed consent was obtained from all participants before blood collection.

## ETHICAL APPROVAL

The study protocol was reviewed and approved by the Research Ethics Committee of the Rivers State Hospital Management Board (Approval number: RSHMB/RSHREC/2024/113).

## DISCLAIMER (ARTIFICIAL INTELLIGENCE)

Author(s) hereby declare that NO generative AI technologies such as Large Language Models (ChatGPT, COPILOT, etc) and text-to-image generators have been used during writing or editing of this manuscript.

## COMPETING INTERESTS

Authors have declared that no competing interests exist.

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