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\title{Pulmonary thromboendarterectomy for pulmonary hypertension linked to
thalassemia}



\author[1]{Mohammad Izzat}%
\author[2]{Hazem Aljasem}%
\author[2]{Ahmad Izzat}%
\affil[1]{Affiliation not available}%
\affil[2]{Damascus University Faculty of Medicine}%


\vspace{-1em}



  
  \date{April 25, 2026}


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\selectlanguage{english}
\begin{abstract}
This report supports the feasibility of surgical pulmonary
thromboendarterectomy in thalassemic patients with chronic
thromboembolic pulmonary hypertension, and highlights the need for a
comprehensive evaluation for both the presence and cause of pulmonary
arterial hypertension prior to determining the likelihood of surgical
cure.%
\end{abstract}%



\sloppy


\textbf{Title}

Pulmonary thromboendarterectomy for pulmonary hypertension linked to
thalassemia

\textbf{Running Head}

Pulmonary hypertension in thalassemia

\textbf{Authors}

Mohammad Bashar \emph{Izzat} , FRCS(CTh), Hazem \emph{Aljasem} , MRCS,
Ahmad Walid \emph{Izzat}

\textbf{Institution}

Department of Surgery, Damascus University Faculty of Medicine,
Damascus, Syria

\textbf{Corresponding author}

Mohammad Bashar Izzat, Department of Surgery, Damascus University
Faculty of Medicine, P.O. Box 33831, Damascus, Syria. Tel.
+(963)113311432, e-mail mbizzat@gmail.com



\textbf{Key Clinical Message}

This report supports the feasibility of pulmonary thromboendarterectomy
in thalassemic patients, and highlights the need for a comprehensive
evaluation of the cause of pulmonary hypertension prior to determining
the likelihood of surgical cure.

\textbf{Key words}

Pulmonary, hypertension, thalassemia, cardiopulmonary bypass, surgery,
heart



\textbf{Introduction}

Pulmonary arterial hypertension (PAH) is a possible complication and a
significant source of morbidity and mortality in patients with
thalassemia syndromes {[}1{]}. Pathogenic mechanisms of PAH in
thalassemia are multifactorial. Chronic hemolysis, reduced nitric oxide
bioavailability, chronic hypercoagulable states and various
disease-directed therapies may play important roles in its development
{[}2{]}. Even though chronic thromboembolic pulmonary hypertension
(CTEPH) is a well-recognized cause of PAH in patients with
\selectlanguage{greek}β-\selectlanguage{english}thalassemia, surgical management of CTEPH has only rarely been
reported in such cases thus far {[}3, 4{]}. We report here the case of a
patient with \selectlanguage{greek}β-\selectlanguage{english}thalassemia complicated with CTEPH who underwent
successful surgical pulmonary thrombo-endarterectomy (PTE). Approval for
writing this report was obtained from the local ethics committee of our
institution, and obtaining individual consent was waived due to the
retrospective nature of the study.

\textbf{Case Report}

This is the case of a 21 years-old male who was diagnosed with
\selectlanguage{greek}β-\selectlanguage{english}thalassemia major at the age of 8 months. He underwent splenectomy at
the age of 10 years, and has been receiving monthly blood transfusions
ever since. Three months prior to admission he presented to a peripheral
emergency department with a sudden episode of dyspnea and central
cyanosis, and was suspected to be infected with covid-19. Chest CT scan
was made and ruled out any interstitial lung involvement, and revealed
the presence of bilateral pulmonary emboli. Anticoagulation therapy with
warfarin was started, but on follow-up the patient developed progressive
exertional dyspnea, deteriorating to NYHA functional class III.

The patient was referred to our institution because of worsening
symptoms. Physical examination showed clinical evidence of right heart
failure and pulmonary hypertension, with a mild drop in arterial oxygen
saturation (93\%). Echocardiography revealed a dilated right atrium (RA)
which contained a large 47\selectlanguage{ngerman}×35×16 mm hyperechogenic mobile mass attached
to the RA free wall near the orifice of the inferior vena cava. The
right ventricle (RV) was severely dilated and dysfunctional, with
tricuspid annular plane systolic excursion (TAPSE) of 13 mm and severe
tricuspid regurgitation. Estimated systolic pulmonary arterial pressure
(PAP) was 85 mmHg. Lung perfusion scintigraphy was not available at our
center. Chest CT angiography showed bilateral defects in the pulmonary
arteries consistent with bilateral chronic pulmonary thromboemboli (fig.
1).

On the basis of this evaluation, the diagnosis of CTEPH was established
and PTE was performed, the technique of which was reported previously
{[}5{]}. Total circulatory arrest time was 45 minutes and total
cardiopulmonary bypass perfusion time was 94 minutes. A large organized
clot was removed from the RA, in addition to removing the thickened
intima and organized thrombi from lobar and segmental pulmonary arteries
of the left middle and lower lobes, as well as from all major branches
on the right.

Early recovery following surgery was uneventful, and the patient was
discharged from ICU on the 4\textsuperscript{th} post-operative day.
Pre-discharge echocardiogram confirmed satisfactory hemodynamic results,
with an improved RV function and an estimated PAP of 45 mmHg. The
patient was discharged home 19 days after surgery on warfarin but no
requirement for supplemental oxygen. Three months after discharge,
significant improvements in clinical status (NYHA class I) and oxygen
saturation (99\%) were noted despite a degree of residual pulmonary
hypertension (PAP of 42 mmHg).

\textbf{Comment}

Valuable advances have been made in understanding the risk factors and
mechanisms responsible for the development of PAH in thalassemic
patients. It is now known that chronic hemolysis with the resulting
nitric oxide depletion can lead to endothelial dysfunction and vascular
remodeling and, in due course, to PAH {[}1{]}. Additionally, vascular
thromboembolic occlusions can also develop due to \emph{in
situ}thrombosis as well as to pulmonary thromboembolism attributable to
the well-recognized hypercoagulable state {[}2{]}. The relative
contribution of hemolysis-related vasculopathy versus pulmonary
thromboembolism in the development of PAH in a specific patient depends
on the severity of the genetic defect and the provided treatment methods
(such as transfusion rates, chelation therapy and splenectomy) {[}1{]}.
This needs to be evaluated in every case individually employing a
detailed and systematic analysis of lung perfusion {[}6{]}.

Conventional management approaches to PAH in thalassemic patients
include hemoglobinopathy-targeted therapy, PAH-specific medications as
well as general supportive treatment. Existing evidence indicates that
currently available drug therapies only temporarily and sporadically
improve symptoms in CTEPH, and remain ineffective in ameliorating the
mechanical obstructions of the pulmonary arteries or in improving
patients' survival {[}7{]}. In this context, given that PTE has been
established as the gold-standard therapy for CTEPH, it is conceivable
that PTE may comprise the only potentially curative therapy for CTEPH in
thalassemic patients.

Experience to date with PTE in thalassemic patients with CTEPH is
limited to small series or isolated case reports, nevertheless these
reports favor PTE as an effective treatment of surgically accessible
CTEPH {[}3, 4{]}. We reported here the successful performance of PTE
surgery in a thalassemic patient with CTEPH irresponsive medical
treatment. Pre-operative assessment indicated that this patient was an
appropriate candidate for PTE despite a slightly increased potential
surgical risk owing to the underlying thalassemia. The post-operative
course was relatively uneventful, and was coupled with an early
substantial improvement in hemodynamics and functional status.

It is notable that the post-operative reduction in PAP in our patient
was less than that commonly expected following PTE {[}3{]} which is
likely to be due to the multifactorial nature of PAH in thalassemia. In
fact, concern remains that the chronic hemolysis-related vasculopathy in
the distal vessels may place thalassemic patients at increased risk of
residual or recurrent PAH after PTE {[}4{]}. Therefore, long-term
results of PTE in thalassemic patients remains to be elucidated through
long-term follow-up. It is noteworthy here that balloon pulmonary
angioplasty has recently been proposed as a potential new therapeutic
option for this process {[}8{]}.

In conclusion, this case report supports the feasibility of PTE in
thalassemic patients with surgically accessible CTEPH. Given the
complexity of the pathophysiology of PAH in thalassemia, a comprehensive
evaluation for both the presence and cause of PAH is imperative prior to
determining the likelihood of surgical cure in each individual patient.

\textbf{Author contributions}

\selectlanguage{english}* Mohammad Bashar Izzat: Concept and study design, data interpretation,
and writing the manuscript.

\selectlanguage{english}* Hazem Aljasem: Data interpretation and approval of manuscript.

\selectlanguage{english}* Ahmad Walid Izzat: Data interpretation and approval of manuscript.



\textbf{Compliance with Ethical Standards}

\begin{itemize}
\tightlist
\item
  No funding was received for this study
\item
  The author has declared that no conflict of interest exists
\item
  All procedures performed in this study were in accordance with the
  ethical standards of the Damascus University Research Ethics Committee
  and with the 1964 Helsinki declaration and its later amendments
\item
  Informed consent was obtained from the participant included in the
  study
\end{itemize}



\textbf{Acknowledgments}

Financial and material support: none to declare



\textbf{References}

\begin{enumerate}
\tightlist
\item
  Fraidenburg DR, Machado RF. Pulmonary hypertension associated with
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\item
  Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia.
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\item
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\item
  Roggero S, Vullo S, Volpe G, Piga A, Albera C. Management of pulmonary
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\item
  Jamieson SW, Auger WR, Fedullo PF, \emph{et al} . Experience and
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\item
  Simonneau G, Robbins IM, Beghetti M, \emph{et al} . Updated clinical
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\item
  Scholzel BE, Post MC, Plokker HT, Snijder RJ. Clinical worsening
  during long-term follow-up in inoperable chronic thromboembolic
  pulmonary hypertension. Lung 2011; 190:161--167
\item
  Karyofyllis P, Tsiapras D, Papadopoulou V, \emph{et al} . Balloon
  pulmonary angioplasty is a promising option in thalassemic patients
  with inoperable chronic thromboembolic pulmonary hypertension. J
  Thromb Thrombolysis 2018, 46:516-520
\end{enumerate}

\textbf{Figure legends}

Fig. 1 - Chest CT angiography showing defects in the right (long arrows)
and left (arrow heads) pulmonary arteries in keeping with bilateral
chronic pulmonary thromboemboli.\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/figure1/figure1}

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