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\begin{document}

\title{A case of Concomitant Pulmonary embolism and Pulmonary Tuberculosis in
the era of COVID 19, a matter of cautious approach.}



\author[1]{Sinda Dakhlia}%
\author[1]{Phool Iqbal}%
\author[1]{Muhammad Abubakar}%
\author[1]{Sabeen Zara}%
\author[1]{Muhammad Murtaza}%
\author[1]{Adel Al Bozom}%
\author[1]{Nedia Neffati}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\selectlanguage{english}
\begin{abstract}
Pulmonary Tuberculosis (PTB) and Novel Coronavirus disease 2019 (COVID
19) primarily affect the lungs. Both diseases present with fever, cough,
and shortness of breath and possess thrombotic potential as well.
Therefore in COVID 19 pandemic, PTB must be taken into consideration for
suspected cases in order to avoid fatal consequences.%
\end{abstract}%



\sloppy


\textbf{TITLE:}

\textbf{A case of Concomitant Pulmonary embolism and Pulmonary
Tuberculosis in the era of COVID 19, a matter of cautious approach.}

\textbf{Introduction:}

Globally, PTB is a significant concern for ill health. According to
World Health Organization (WHO), Tuberculosis (TB) remains a major
threat to public health, with an estimated 10 million diagnosed cases in
2018 with stable cases in the next recent years and an estimated 1.5
million TB-related deaths in 2018 {[}1{]}. PTB is a chronic disease of
the lungs that can disseminate in various organs along with rare
complications that can be life-threatening, such as pulmonary embolism
{[}2{]}. The association of pulmonary embolism with Tuberculosis was
first reported in an observational study by Morgan in 1950 in which the
incidence of PE associated with active TB was 23.4\% compared to 23.1\%
of PE cases in entire series of 634 autopsies {[}2{]}. A disease like
PTB, which is prevailing for many centuries, can easily be overlooked
due to the ongoing COVID 19 pandemic and its apprehension in the
community.

\textbf{Keywords} : Pulmonary Tuberculosis, Pulmonary embolism,
Thromboembolism, COVID 19, SARS- CoV-2, Anti-coagulation.

\textbf{Clinical key message:}

TB is known to the world for many years. It is associated with various
complications and rarely with pulmonary embolism. However, due to its
commonalities of presenting features with COVID 19, it can easily be
missed and may be life-threatening.

\textbf{Case presentation:}

A 34 years old Mauritanian gentleman with no past medical history
presented with a history of fever and productive cough from 2 weeks.
Fever was intermittent, a high grade in nature with no diurnal
variation. It was associated with productive cough with mild streaks of
hemoptysis from one week. There was no history of night sweats, joint
pains, or significant unintentional weight loss. Family history was
unremarkable for any disease. There was no drug abuse, recent travel, or
sick contact.

On clinical examination, the patient was in mild distress due to cough
and high-grade fever of 39.3 C. His blood pressure at presentation was
normal; however, he had mild tachypnea from 20-24/min, tachycardia of
102/min with normal oxygen saturation at room air. On auscultation of
the chest, there was bronchial breathing in the right lung's middle zone
and crackles in the lower zone, respectively. The left side of the lung
revealed decreased air entry in the middle zone. The rest of the
systemic examination was unremarkable. A Chest XR showed extensive
non-homogenous infiltrates in the right lung and left middle zone of the
lung, respectively, as shown in the figure: 1. Due to the ongoing COVID
19 pandemic, he was kept under airborne isolation and screened for SARS-
CoV-2 virus by real time reverse transcriptase-polymerase chain reaction
(rRT-PCR) from the nasopharyngeal sample using gene Xpert technology. It
was inconclusive initially. Sepsis workup including blood cultures,
urine cultures, respiratory viral panel PCR was negative. There was a
clinical suspicion of PTB; therefore, sputum for Acid Fast Bacillus
(AFB) PCR, smear, and culture was sent. His sputum for AFB came positive
for active PTB. And was immediately started on anti TB medications.

His fever started to settle down but the patient had persistent sinus
tachycardia and tachypnea. ECG and cardiac markers were normal. An
urgent CT pulmonary angiogram (CTPA) was ordered to rule out PE. CTPA
revealed lung air space disease with new consolidation areas suggestive
of an underlying infective process like pulmonary tuberculosis or COVID
19. An acute filling defect was identified in the left lower lobe
anterior and lateral segments of the pulmonary arteries impressive of
pulmonary embolism, as shown in the figure: 2. Repeat COVID 19 screening
test was negative. Family history did not reveal any thromboembolic
disease in the first-degree relative. Thrombophilia workup, including
protein C and S, anti-thrombin activity, Factor V Leiden, and
prothrombin gene mutations, was unremarkable. Based on clinical
presentation and further investigations, he was labeled and treated as a
case of active PTB complicated with PE. He was started immediately on
therapeutic anticoagulation with low molecular weight heparin (LMWH) as
an inpatient and was discharged on Rivaroxaban, a new oral anticoagulant
(NOAC), with follow-up of 6 weeks. During the follow-up period, he
remained stable.

\textbf{Discussion:}

Tuberculosis is a disease known to the world for ages and primarily
affects the respiratory system. It can spread to any organ like the
brain, heart, abdomen, bones, etc., leading to grave complications like
meningitis, pericarditis, perforation of the intestines, and
osteomyelitis, and severe life-threatening sepsis as well {[}3{]}.
Rarely, it can also complicate to cause PE.

TB has the potential to cause venous thrombois and has been described in
a few studies. A retrospective review conducted on 3293 tuberculosis
patients showed that 46 had coexisting diagnosed venous thromboembolism
(VTE) with a mean age: 53.4 \selectlanguage{ngerman}±19.6 years {[}4{]}. None of the 46 reported
cases received thromboprophylaxis before the VTE events as they were
fully ambulatory until they developed VTE. In 2019 a retrospective
analysis of 7,905 patients diagnosed with Tuberculosis, 0.6\% exhibited
pulmonary thromboembolism (PTE), deep venous thrombosis (DVT), or both
at or after the time of diagnosing TB {[}5{]}. Another reported case
described an unusual left-arm DVT site in an asymptomatic young PTB
patient {[}6{]}.

Tuberculosis, pulmonary, and extra-pulmonary, has been suggested as an
independent risk factor for venous thromboembolism (VTE). An underlying
mechanism is yet unclear, but it is described as multifactorial in the
literature. All three components of Virchow's triad, i.e.,
hypercoagulability, venous stasis, and endothelial dysfunction, maybe a
possibility to cause VTE in TB {[}7{]}. Other factors that also
contribute to TB's thrombogenic state include reactive thrombocytosis,
anemia, and release of pro-inflammatory cytokines damaging the vascular
endothelium during the disease process {[}7{]}. Turken et al. described
a hypercoagulable state in active TB due to the imbalance between the
pro-coagulant and anticoagulant factors such as increased fibrinogen,
factor VIII plasminogen activator inhibitor 1 plasma levels, and
depressed anti-thrombin III and protein C levels in the first month of
treatment {[}8{]}.

Early initiation of anti TB medications has been described to decrease
the hypercoagulable state in TB patients {[}5{]}. In terms of treatment,
LMWH is safer and requires minimal monitoring {[}5{]}. The overall
morbidity and mortality are also decreased. Moreover, oral
anticoagulation, especially with warfarin, needs carefully monitored
because of hepatic enzyme induction by anti-tuberculosis drugs that
increase the hepatic clearance of oral anticoagulant, resulting in
higher doses of the drug; therefore, NOACs can also be considered
{[}2,5{]}.

Our patient was young, ambulatory, and did not have any risk factors for
thromboembolism like decreased mobility, malignancy, immunocompromised
state, or hereditary thrombophilia diseases. He was kept on a
prophylactic dose to prevent thromboembolism during his hospital stay,
and still, he developed pulmonary embolism. Thus, it signifies the risk
of developing PE in TB patients.

\textbf{Conclusion:}

Due to the ongoing COVID 19 pandemic, PTB can easily be overlooked and
associated VTE or PE can be devastating to one's life. We aim to
highlight the association of PTB with PE in the current era of COVID 19
pandemic, which is a fatal condition and needs prompt action. Although,
VTE and TB possess a strong association, but TB complicating as PE has
been scarcely reported in the literature. Timely diagnosis and
management can prevent life threatening complication and death.

\textbf{Authors details with order of contribution:}

\textbf{Dr. Sinda Dakhlia, MBBS\textsuperscript{1}}

Email: 14006677@rcsi.com

Contribution: Case identification, manuscript writing and literature
review

\textbf{Dr. Phool Iqbal} , \textbf{MBBS\textsuperscript{1}}

Email: dr.phooliqbal89@gmail.com

Contribution: Case identification, Manuscript writing and literature
review.

\textbf{Dr. Muhammad Abubakar, MBBS\textsuperscript{1}}

Email: Mabubakar@hamad.qa

Contribution: Manuscript writing

\textbf{Dr. Sabeen Zara} , \textbf{MBBS\textsuperscript{1}}

Email: SZara1@hamad.qa

Contribution: Manuscript writing

\textbf{Dr. Muhammad Murtaza, MBBS\textsuperscript{1}}

Email: MMurtaza1@hamad.qa

Contribution: Literature review

\textbf{Dr. Adel Al Bozom, MBBS\textsuperscript{1}}

Email: adel.bozom@hotmail.com

Contribution: Literature review

\textbf{Dr. Nedia Neffati, MD\textsuperscript{1}.}

Email: NNEFFATI@hamad.qa

Contribution: Manuscript review, literature review, supervision

\textbf{Affiliation: Hamad Medical Corporation, Doha,
Qatar\textsuperscript{1}}

\textbf{Department: Internal Medicine Department.}

\textbf{Acknowledgements:}

I would like to thank Dr. Abdel-Naser~Elzouki, senior consultant of
Internal Medicine at Hamad Medical Corporation for always supporting
young researchers at our institute. I would like to thank the patient
for giving us the consent and following as well for this manuscript.
Open Access funding provided by the Qatar National Library.

\textbf{Conflict of interest:}

All authors of this manuscript have no conflict of interest to declare.

\textbf{References:}

\begin{enumerate}
\tightlist
\item
  Ding C, Wang S, Shangguan Y, Feng X, Guo W, Shi P, et al. Epidemic
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\item
  Ekukwe NC, Bain LE, Jingi AM, Sylvia K, Mintom P, Menanga A. Bilateral
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\item
  Adigun R, Singh R. Tuberculosis. StatPearls. Treasure Island (FL)2020.
\item
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\item
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\item
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\item
  Amitesh Gupta PM, Abhishek Faye, Debdutta Bandyopadhyay, and Rupak
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  thromboembolism: A case series and review of literature. Lung India
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\item
  Bansal S UK, Joshi JM. . Systemic thrombosis due to pulmonary
  tuberculosis. Natl Med J India 2017;30:201-2. 2017(Available from:
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\end{enumerate}

\textbf{Figure captions/Legends:}

\textbf{Figure 1:} Chest XR: extensive non-homogenous infiltrates in the
right lung and left middle zone marked with black arrows.

\textbf{Figure: 2:} CT pulmonary angiogram (CTPA) remarkable for
consolidation marked with a white arrow on the right side and area of
filling defect in the left pulmonary artery marked with red arrow.

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