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Case report 1
Hemodynamic and symptomatic improvement after delayed
thrombolysis with Reteplase in a patient with massive
bilateral pulmonary emboli
Babak Sharif-Kashania, Arda Kianib, Mehrdad Bakhshayesh-Karamc,
Faezeh Sheybani-Afshara, Neda Behzadniad and Farah Naghash-Zadeha
Most patients surviving the acute phase of pulmonary
embolism will recover with no residue. But, 2–4% of
patients will progress to chronic thromboembolic
pulmonary hypertension. In this group, usually a
‘Honey moon’ period is seen but a few may show
progression with ongoing symptoms despite medical
treatment. In this case report, we review a patient in
whom delayed thrombolytic therapy was administered
due to progressive symptoms after 21 days. Her
condition was stabilized. The early posttreatment
computed tomographic pulmonary angiography
(CTPA) showed incomplete resolution, but after
6 months she was functional class I with a normal
CTPA and echocardiography. Blood Coagul Fibrinolysis
Introduction
Pulmonary embolism is the most common cause of death
from cardiovascular disease and ranks third after heart
attack and stroke [1]. The morbidity and mortality associated with venous thromboembolism (VTE) may be
reduced with earlier diagnosis and treatment [2]. Yet,
2–4% of patients will progress to chronic thromboembolic pulmonary hypertension (CTEPH) [1]. However,
data regarding the effect of delayed treatment of VTE on
the acute syndrome as well as its progression to CTEPH
are sparse [3].
Different mechanisms are involved in the setting of
pulmonary hypertension due to pulmonary embolism
including physical obstruction, in situ thrombosis and
small arterial involvement.
Case report
A 27-year-old woman was referred to our center because
of progressive shortness of breath starting 3 weeks ago.
During this period, she had been evaluated at other
centers and, in spite of there being no conclusive
evidence, had been treated for allergic and obstructive
airway disease with no apparent improvement.
Prior to this illness, she enjoyed the benefits of full health
and was an active athlete. She was married, had no
children and was on no long-term medication. She was
a nonsmoker and had no history of chemical or environmental exposure. Her family history revealed no significant finding also. Three weeks before she became
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Blood Coagulation and Fibrinolysis 2014, 25:000–000
Keywords: delayed diagnosis, pulmonary embolism, thrombolytic therapy
a
Lung Transplantation Research Center, bTracheal Diseases Research Center,
Pediatric Respiratory Diseases Research Center and dChronic Respiratory
Diseases Research Center, National Research Institute of Tuberculosis and Lung
Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
c
Correspondence to Babak Sharif-Kashani, MD, NRITLD, Shaheed Bahonar
Avenue, Darabad 1956944413, Tehran, Iran
Tel: +982127122626; fax: +982126109490;
e-mail: [email protected]
Received 7 October 2013 Accepted 26 December 2013
symptomatic, she had started taking Cyproterone acetate
for mild menstrual problems.
She was a thin young woman who was symptomatic at
rest. Her physical examination revealed tachypnea,
tachycardia and central cyanosis while breathing room
air. Her blood pressure and body temperature were
normal. The jugular veins were engorged, and central
venous pressure was elevated. The rest of the physical
examination was normal except for a loud P2 and a II/VI
systolic murmur best heard over the left sternal border.
She had no peripheral edema or ascites. The patient was
admitted with the possibility of pulmonary emboli.
A radiograph X-ray was reported to be normal. The
electrocardiogram showed right ventricle strain and sinus
tachycardia, and the O2 saturation on room air was 85%.
D-dimer was elevated, and the pro-brain natriuretic
peptide level was 2075 pg/ml. Screening tests for thrombophilia as well as for rheumatologic tests were negative.
A transthoracic echocardiographic study showed moderate pulmonary hypertension and failure of the right
ventricle (RV) with mild RV/right atrium (RA) enlargement (right ventricular systolic pressure ¼ 45 mmHg,
tricuspid annular plane systolic excursion ¼ 1.7 cm, RV
diameter ¼ 31 mm, RA diameter ¼ 33 mm). No clot was
detected in the heart chambers, and Doppler sonographic
examination of the lower extremities was negative for
deep vein thrombosis. An initial computed tomographic
pulmonary angiography (CTPA) was consistent with
bilateral pulmonary emboli (Fig. 1). Although anticoagulation as well as supportive measures were started,
DOI:10.1097/MBC.0000000000000087
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Fig. 1
Fig. 2
Admission CTPA. CTPA, computed tomographic pulmonary
angiography.
Early postthrombolytic therapy CTPA. CTPA, computed tomographic
pulmonary angiography.
treatment with Reteplase was initiated because of progressive symptoms. An early post-treatment CTPA
showed minimal decrease in the emboli burden
(Fig. 2). But the 6-month follow-up CTPA was completely normal (Fig. 3), and she was completely asymptomatic with a normal echocardiography.
Discussion
If pulmonary embolism is missed or untreated, then it has
a high mortality (26–30%) [4,5]. Patients can be stratified
into high risk and nonhigh-risk pulmonary embolism
using immediate bedside clinical assessment for the
presence or absence of clinical markers as well as laboratory tests [6]. Thrombolytic therapy has very few absolute
contraindications and should be considered the first line
of treatment in patients with high-risk pulmonary embolism presenting with cardiogenic shock and/or persistent
arterial hypotension [6]. After thorough consideration,
thrombolytic therapy may also be used in selected
patients with intermediate-risk pulmonary embolism
[6,7]. In case of an absolute contraindication to thrombolytic therapy or failure of thrombolysis, pulmonary embolectomy should be considered [6].
The nonspecific nature of pulmonary embolism clinical
presentation can cause a delay in diagnosis. A recent
study showed that 18% of the patients have a diagnostic
delay (>7 days) [8].
Several studies have shown the efficacy of early thrombolytic treatment on resolving the thromboembolic
burden and improving the hemodynamic. Best results
are seen if the treatment is initiated within 48 h, but in
symptomatic patients, effective thrombolysis can be
initiated up to 14 days after the acute episode
[3,6,9,10]. There is no strong evidence for thrombolytic
therapy after this period.
In our case, symptoms had started 21 days ago, and
despite routine treatment, the patient showed progressive worsening. It has been shown that factors other than
the mechanical obstruction are involved in the process of
pulmonary embolism including in situ thrombosis, release
of vasoactive substances from platelets as well as an
insufficient thrombolysis response. It seems that thrombolytic therapy if effective can reverse these mechanisms
as well as reducing the emboli burden [11–15].
In this case, despite the initial anticoagulation, the
clinical laboratory tests and echocardiographic findings
were indicative of progression. In this case, the involvement of the pulmonary arterial system could be due to the
factors meditated above.
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Delayed thrombolysis Sharif-Kashani et al. 3
Fig. 3
Six-month follow-up CTPA. CTPA, computed tomographic pulmonary angiography.
The noncomplete resolution of thromboembolism in the
early posttreatment CTPA is also in favor of these mechanisms. In particular, the clinical improvement despite
reversal of in situ thrombosis, improving oxygenation and
decreasing the shear factors in small arteries.
3
A computed tomography scan after 6 months showed no
emboli material in the pulmonary arterial system.
6
4
5
Conclusion
Many patients with a diagnostic delay respond to anticoagulation, but some may have progressive symptoms.
Despite standard medical treatment, the symptoms of
our patient were progressing, and she was severely symptomatic. Although thrombolytic therapy seems to be
more effective during the early days following pulmonary
embolism, in cases of ongoing and progressive disease, a
delayed thrombolytic therapy may reverse the course of
the disease by acting on the emboli mass as well as
reversing in situ mechanisms.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
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