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\begin{document}

\title{Spontaneous hemothorax in a 10-year-old boy with COVID-19.}



\author[1]{Abir Boussetta}%
\author[1]{Nesrine Abida}%
\author[1]{Manel Jellouli}%
\author[2]{tahar gargah}%
\affil[1]{University of Tunis El Manar Faculty of Medicine of Tunis}%
\affil[2]{Charles Nicolle Hospital}%


\vspace{-1em}



  
  \date{June 02, 2024}


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\selectlanguage{english}
\begin{abstract}
Spontaneous hemothorax occurs in the absence of trauma or iatrogenic
causes. Etiologies of spontaneous hemothorax in children include
connective tissue disease, neoplasia and coagulopathy which is
associated with thromboembolic events. We present the case of a
10-year-old chronic hemodialysis patient with spontaneous hemothorax
with a concurrent COVID 19 infection.%
\end{abstract}%



\sloppy


\textbf{Spontaneous hemothorax in a 10-year-old boy with~COVID-19.}

Abir Boussetta\textsuperscript{1-2-3}, Nesrine
Abida\textsuperscript{1-2}, Manel Jellouli\textsuperscript{1-2-3}, Tahar
Garagah\textsuperscript{1-2-3}(1) Pediatric department, Charles Nicolle
Hospital, Tunis, Tunisia

(2) University of Tunis El Manar-Faculty of Medicine of Tunis

(3) Research Laboratory of Immunopathology and Immunology of Renal
Transplantation (LR03SP01), Charles Nicolle hospital of Tunis, Tunis
Tunisia

\textbf{Correspondence:} Abir Boussetta- Pediatric department, Charles
Nicolle Hospital, Tunis, Tunisia- University of Tunis El Manar-Faculty
of Medicine of Tunis- Research Laboratory of Immunopathology and
Immunology of Renal Transplantation (LR03SP01), Charles Nicolle hospital
of Tunis, Tunis Tunisia.

Tel: (+216)22685409

Email: abir.bousetta@gmail.com

\textbf{Acknowledgments:} All authors contributed to the elaboration of
this article

\textbf{Contribution:}

\begin{itemize}
\tightlist
\item
  Abir boussetta wrote the article, managed the patient
\item
  Nesrine Abida contributed in the writing of this article
\item
  Manel jellouli and Tahar gargah revised the article and contributed in
  the management of the patient
\end{itemize}

\textbf{Conflict of interest:} The authors declare that no conflict of
interest exists

\textbf{Availability of data and materials:} All data underlying the
findings are fully available

\textbf{Ethics approval and consent to participate:} No ethical
committee approval was required for this case report by the Department,
because this article does not contain any studies with human
participants or animals. Informed consent was obtained from the patient
included in this study.

\textbf{Consent for publication:} Parents gave their written consent to
use personal data of their child

for the publication of this case report and any accompanying images.

\textbf{Spontaneous hemothorax in a 10-year-old boy with~COVID-19.}

\textbf{ABSTRACT:}

Spontaneous hemothorax occurs in the absence of trauma or iatrogenic
causes. Etiologies of spontaneous hemothorax in children include
connective tissue disease, neoplasia and coagulopathy which is
associated with thromboembolic events. We present the case of a
10-year-old chronic hemodialysis patient with spontaneous hemothorax
with a concurrent COVID 19 infection.

\textbf{KEY WORDS:}

SARS-COV-2 - chronic kidney disease - pediatric - Spontaneous hemothorax

\textbf{BACKGROUND:}

The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has
emerged as a novel human pathogen in December 2019 and was declared a
pandemic by the World Health Organization (WHO) on March 11, 2020 (1).
Since its discovery, this once thought to be a respiratory illness is
now considered as a multisystemic disease with multiple organ
involvement including clotting disorders (2). Coagulopathy in Covid 19
infection is associated rather with thromboembolic events than bleeding
tendency (1). Hemorrhagic events related to the Covid 19 disease are at
the moment strictly limited to case reports.

We here by present the case of a 10-year-old chronic hemodialysis
patient with spontaneous hemothorax with a concurrent COVID 19
infection.

\textbf{OBSERVATION:}

A 10-year-old boy with poor vascular access, had been on renal
replacement therapy for the past 6 years. The native kidney disease was
reflux nephropathy progressing to end-stage renal failure. Peritoneal
dialysis was initially started but had to be switched to hemodialysis
due to recurrent peritonitis with peritoneal catheter dysfunction.

The Patient was admitted to our emergency department for a sudden-onset
of a respiratory distress with chest pain. There was no history of
trauma. The patient had no contact with suspected or diagnosed COVID-19
patients.

On admission, his weight and height were 23 kg and 107 cm, respectively.
The patient's heart rate was 137 bpm. His respiratory rate was 54
breaths per minute. He was grunting and had intercostal recession. blood
pressure was 110/50 mmHg and oxygen saturation in room air was 95\%.
Dullness to percussion with decreased breath sounds on the left lung
field were also noted without crackles nor wheeze.

Blood analysis revealed a hemoglobin level of 64 g/L, a platelet counts
of 113.10\textsuperscript{3} per mm\textsuperscript{3} with a
lymphopenia of 590/mm\textsuperscript{3}

Prothrombin time (PT) was found to be normal. Partial thromboplastin
time (PTT) was high with a value of 46.5 seconds and a ratio of 1.55.
Liver function blood tests were normal and C reactive protein was found
to be normal.

Chest X-ray noted left sided pleural effusion with shift of the
mediastinum to the right (Figure 1). Thoracentesis was performed with
ultrasound guidance allowing the drainage of only few milliliters (ml)
of blood suggesting a clotted Hemothorax. Bacterial cultures of the
pleural fluid were negative for both non-specific organisms and
tuberculosis. Polymerase Chain Reaction (PCR) of the COVID 19 virus was
performed on both nasopharyngeal swab and on the removed fluid were
found to be positive.

The patient was transfused with packed red blood cells to achieve a
hemoglobin concentration of 92 g/L.

A thoracic CT scan was performed showing a massive and compressive
right-sided pleural effusion without extravasation of contrast agent
(Figure 2).

Thoracoscopy allowed the unclotting of the hemothorax and the evacuation
of 700 ml of blood. The pleural cavity per-procedure's investigation
showed no active bleeding. A chest tube was inserted at the end of
procedure and was removed 5 days later.

The patient was discharged after 10 days and was clinically
asymptomatic.

\textbf{DISCUSSION:}

Hemothorax is defined as a pleural fluid with a hematocrit level greater
than 50\% of the patient's blood. It is a clinical entity caused in most
cases by trauma or iatrogenic causes through procedures such as pleural
biopsies or central line insertion (3).

Spontaneous hemothorax (SH) involves the accumulation of blood within
the pleural space in the absence of trauma or iatrogenic causes(3). It
is extremely rare in the pediatric population with data limited to few
case reports (4).

Spontaneous hemothorax etiologies in children include connective tissue
disease, neoplasia, arteriovenous malformations, multiple exostosis and
coagulopathy (3).

Approximately 20\%-50\% of hospitalized patients with COVID-19 have
hematologic changes in coagulation tests (1).

Coagulopathy in Covid 19 infection is associated rather with
thromboembolic events than bleeding tendency.

The pathogenesis of SARS-CoV-2-induced coagulopathy is not yet fully
understood. It has been proven that the SARS-CoV-2 enters the host via
the angiotensin converting enzyme receptor 2, which is expressed in
cells including endothelial cells (5).

Recent evidence showed that the virus can induce endothelial activation
directly or by an immune-mediated mechanism in the presence of a locally
dysregulated inflammation. Activated endothelial cells release high
numbers of ultra large von Willebrand factor (vWF) multimers. Under
normal circumstances, vWF flows in intact vessels together with
platelets and erythrocytes without binding to any blood element.
Elevated microcirculatory shear stress due to endothelial cell
dysfunction leads the unfolding of vWF from a globular structure to an
extended chain structure exposing its binding sites. Long strands of vWF
multimers becoming functionally active. It has been proven that a
functional imbalance in vWF multimer sizes can lead to either
microcirculation bleeding or thrombosis (5).

While a meta-analysis comprising 28,173 patients with COVID-19 estimated
an in-hospital prevalence of venous thromboembolism of 14.1\% (6),
Researchers reported a case of spontaneous retroperitoneal hematoma in a
47-year-old woman with a COVID-19 concurrent infection. She had no
medical priors and was not taking any medication(7).

Others reported 6 cases of abdominal bleeding associated with COVID-19
infection. Five of them used low/medium dosage heparin while the sixth
took a high dose for pulmonary embolism. Laboratory investigations
showed a normal PTT and PT, excluding a possible adverse effect from
anticoagulant therapy (8).

In addition, 2 cases of massive intracranial hemorrhage have been
reported in patients being treated with VV-ECMO for COVID-19, with
normal PTT and in the absence of other risk factors that could predict
such complication(9). Patients with chronic kidney disease (CKD) have a
paradoxical hemostatic potential with increased rates of bleeding
associated with a higher risk of thromboembolic events. Bleeding events
have been reported in 24--50\% of patients on HD (10). Increased
bleeding is essentially due to platelet dysfunction and alterations in
the coagulation cascade with deranged vWF and platelet interactions
(10).

CKD was the major risk factor of bleeding in our patient. In the absence
other relevant findings, we concluded that the spontaneous hemothorax
was due to the covid 19 vasculopathy probably by rupture of small chest
wall vessels in a predisposed pediatric patient.

\textbf{CONCLUSION:}

The relationship between the SARS COV2 virus infection and bleeding
events are still at this point hypothetical. We report this case to
emphasize on the need of further research focusing on the pathogenesis
of such complication. While screening covid 19 patients for
thromboembolic events is common practice, clinicians should keep in mind
the bleeding risk especially in predisposed individuals.

\textbf{ACKNOWLEDGMENT}

All co-authors contributed to patient management.

\textbf{CONFLICT OF INTEREST}

Authors do not declare any conflict of interests.

\subsection*{AUTHORS CONTRIBUTION}

{\label{authors-contribution}}

AB: conceived the study and helping in writing the paper. NA: wrote the
paper. MJ: contributed to the management of the patient. TG: supervised
and aprobated the project.

\subsection*{ETHICAL APPROVAL}

{\label{ethical-approval}}

Mother's consent has been obtained before submission.

\subsection*{CONSENT}

{\label{consent}}

Written informed consent was obtained from the patient's mother to
publish this report in accordance with the journal's patient consent
policy.

\textbf{REFERENCES}

1. G\selectlanguage{ngerman}ómez-Mesa JE, Galindo-Coral S, Montes MC, Muñoz Martin AJ.
Thrombosis and Coagulopathy in COVID-19. Curr Probl Cardiol.
2021;46(3):100742.

2. Roberts CM, Levi M, McKee M, Schilling R, Lim WS, Grocott MPW.
COVID-19: a complex multisystem disorder. Br J Anaesth.
2020;125(3):238\selectlanguage{english}-42.

3. Broderick SR. Hemothorax: Etiology, diagnosis, and management. Thorac
Surg Clin. 2013;23(1):89\selectlanguage{english}-96, vi\selectlanguage{english}-vii.

4. Martinez FJ, Villanueva AG, Pickering R, Becker FS, Smith DR.
Spontaneous hemothorax. Report of 6 cases and review of the literature.
Medicine (Baltimore). 1992;71(6):354\selectlanguage{english}-68.

5. Pla\selectlanguage{polish}š\selectlanguage{english}ek J, Gumulec J, M\selectlanguage{ngerman}áca J, \selectlanguage{polish}Š\selectlanguage{english}karda J, Proch\selectlanguage{ngerman}ázka V, Grézl T, et al.
COVID-19 associated coagulopathy: Mechanisms and host-directed
treatment. The American Journal of the Medical Sciences.
2022;363(6):465\selectlanguage{english}-75.

6. Jenner WJ, Gorog DA. Incidence of thrombotic complications in
COVID-19. J Thromb Thrombolysis. 2021;52(4):999\selectlanguage{english}-1006.

7. Tanal M, Celayir MF, Kale ZS. Unexpected tendency to bleeding in
COVID-19 patients: A case of spontaneous retroperitoneal hematoma. SAGE
Open Med Case Rep. 2021;9:2050313X211067907.

8. Sposato B, Croci L, Di Tomassi M, Puttini C, Olivieri C, Alessandri
M, et al. Spontaneous abdominal bleeding associated with SARS-CoV-2
infection: causality or coincidence? Acta Biomed. 2021;92(2):e2021199.

9. Heman-Ackah SM, Su YS, Spadola M, Petrov D, Chen HI, Schuster J, et
al. Neurologically Devastating Intraparenchymal Hemorrhage in COVID-19
Patients on Extracorporeal Membrane Oxygenation: A Case Series.
Neurosurgery. 2020;87(2):E147\selectlanguage{english}-51.

10. Nunns GR, Moore EE, Chapman MP, Moore HB, Stettler GR, Peltz E, et
al. The hypercoagulability paradox of chronic kidney disease: The role
of fibrinogen. Am J Surg. 2017;214(6):1215\selectlanguage{english}-8.

\textbf{Hosted file}

\verb`Figures case report hemothorax.docx`  available at \url{https://authorea.com/users/494385/articles/576472-spontaneous-hemothorax-in-a-10-year-old-boy-with-covid-19}

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