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\begin{document}

\title{Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Plasma Levels and
Thr325Ile Genetic Polymorphism in a Cohort of Egyptian Sickle Cell
Disease Patients and Impact on Disease Severity}



\author[1]{Mona Hamdy}%
\author[1]{Iman Shaheen}%
\author[1]{Mohamed Khallaf}%
\author[1]{Yasmeen Selim}%
\affil[1]{Cairo University Kasr Alainy Faculty of Medicine}%


\vspace{-1em}



  
  \date{May 29, 2024}


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\begin{abstract}
\textbf{Background:} Thrombin is a critical protease modulating
thrombosis as well as inflammation which are one of the main
pathophysiological mechanisms in sickle vasculopathy, and its levels
were reported to be high in sickle cell disease (SCD). The
thrombin-thrombomodulin complex activates an inhibitor of fibrinolysis
called TAFI acting by reducing plasmin affinity for its substrate
hindering fibrinolysis. \textbf{Objective:} We aimed to determine the
influence of the Thr325Ile single nucleotide polymorphism on TAFI
antigen levels and potential effects on the severity of SCD in a cohort
of Egyptian patients. \textbf{Methods:} Genotyping of Thr325lle
polymorphism using Taq-Man SNP genotyping assay and TAFI level
measurement using an Enzyme-Linked Immunosorbent Assay (ELISA) were
performed for 80 SCD patients and 80 health control subjects.
\textbf{Results:} Plasma TAFI levels were higher in SCD patients with
Thr325Ile polymorphism, yet the difference was not statistically
significant (p=0.204). SCD patients with polymorphic genotypes had a
greater number of hospital admissions (p=0.03), Ten patients with acute
chest syndrome had the homozygous polymorphic genotype (GG), and all
patients with pulmonary hypertension had the polymorphic genotype (6
were homozygous {[}GG{]} and 5 were heterozygous {[}GA{]}). SCD patients
complicated with pulmonary hypertension showed significantly higher
plasma TAFI levels (p= 0.044). \textbf{Conclusion:} The analysis of
Thr325Ile polymorphism combined with plasma TAFI level possibly suggests
that the analyzed SNP could influence plasma levels and subsequently
disease severity and hospitalization rate, which might be regarded as
predictors for complex disease.%
\end{abstract}%



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\textbf{Hosted file}

\verb`TAFI Paper edited 5Nov2023.docx`  available at \url{https://authorea.com/users/697737/articles/685805-thrombin-activatable-fibrinolysis-inhibitor-tafi-plasma-levels-and-thr325ile-genetic-polymorphism-in-a-cohort-of-egyptian-sickle-cell-disease-patients-and-impact-on-disease-severity}

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