Novel treatment (new drug/intervention; established drug/procedure in new situation)

A unique presentation of four thrombotic events at a time
Ali Raza Rajani,1 Kosar Hussain,2 Fahad Omar Baslaib,1 Ghazi Ahmad Radaideh1
1

Department of Cardiology, Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates
Department of Internal Medicine, Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates

2

Correspondence to Dr Ali Raza Rajani, arrajani@dha.gov.ae

Summary
A 72-year-old man was referred to our hospital as a case of postcardiac arrest following a long distance air flight. Work-up in the
emergency department revealed the presence of deep vein thrombosis (DVT), bilateral pulmonary embolism, inferior STEMI (ST elevation
myocardial infarction) and ischaemic stroke. He received thrombolysis by recombinant tissue plasminogen activator (tPA) following which
his haemodynamic status improved, but he developed haemorrhagic transformation of the stroke as a complication. The haemorrhagic
lesion gradually resolved with conservative management, leaving behind a residual neurological deficit. His haemodynamic status was
stable after the management. Although a diagnosis of right-to-left shunt lesion was highly suggestive in this condition, it could not be
confirmed on the transthoracic echocardiogram. Our patient had a unique presentation of multiple thrombi in different organs that caused
significant morbidity and haemodynamic instability. There are no well-established guidelines that discuss the acute management of such
cases. This situation requires a careful assessment and management of the patient by a multidisciplinary team.

BACKGROUND
Such cases will be encountered more frequently with
increasing ease of travel between different continents.
This situation requires a careful assessment and management of the patient by a multidisciplinary team. There is
very limited research done on this condition and no guidelines are available to guide physicians on this topic.

CASE PRESENTATION
A 72-year-old man landed transit in our city after he travelled a long-distance flight of 15 h duration. His medical
history included ischaemic heart disease for which he had
percutaneous coronary intervention conducted 5 years
ago. While at the airport, he developed sudden onset of
dyspnoea lasting for 20 min, after which he felt dizzy and
collapsed. Cardiopulmonary resuscitation was done for
3 min but no shock was delivered and he was immediately
shifted to our hospital. While transporting him, the paramedic staff noted that he was not moving the left side of
his body. On arrival at the emergency department, the
patient was unresponsive with a Glasgow Coma Scale
(GCS) of 4/15. Examination revealed an obese man with
blood pressure of 182/90 mm Hg, pulse of 95 beats/min,
pulse oximetry of 94% on high flow oxygen.
Cardiovascular and respiratory systems were unremarkable. The patient was intubated while he was being resuscitated in emergency department.

was 197 pg/ml, D-dimer was 6.09, random blood sugar was
188 mg/dl, procalcitonin 0.02 ng/ml, prothrombin time 15 s
with international normalised ratio of 1.26, aPTT 29.9 s.
Electrolytes and renal function tests were normal at the time
of admission. Antidouble-stranded DNA antibodies and antinuclear factors were negative. Anticardiolipin antibodies
(IgG and IgM), β-2-glycoprotein levels, phosphatidyl serine
antibodies (IgG and IgM) were all negative. Thrombophilia
screening which included assays for antithrombin III, protein
C, protein S, activated protein C resistance (APCR) were all
within the normal range for this patient.
Bedside echocardiography showed dilated right heart
chambers with grade 2/4 tricuspid regurgitation and right
ventricular systolic pressure (RVSP) of 40 mm Hg. The
mid-basal septum and inferior segment was akinetic with
an ejection fraction of 40%.
In view of the history of long travel and the clinical
presentation the patient underwent CT pulmonary angiography which showed multiple filling defects in the peripheral branches of the left and the right main pulmonary
arteries suggestive of bilateral pulmonary embolism
(figure 2). Doppler ultrasound of the lower limbs confirmed the presence of deep vein thrombosis (DVT) in the
left superficial femoral vein.
Brain CT scan that was done initially did not show any
significant abnormality except age-related cortical involutional changes. Stroke was diagnosed clinically as he was
noted not to be moving the left side of his body.

INVESTIGATIONS
His ECG showed sinus rhythm with STelevation in inferior
leads and ST depression from V2 to V6, I and aVL (figure 1).
The blood investigations showed haemoglobin 15 g/dl,
white blood cells 18×103/μl, platelets 182×103/μl. Cardiac
enzymes: creatine kinase was 77 U/l that rose to 737 U/l and
Creatine Kinase myoglobin (CK-MB) was 17 U/l and then it
became 109 U/l and troponin was 0.05 ng/ml then it rose to
greater than 2 ng/ml. brain natriuretic peptide (Pro-BNP)
BMJ Case Reports 2012; doi:10.1136/bcr-2012-007221

DIFFERENTIAL DIAGNOSIS
▸ Patent foramen ovale
▸ Ventricular septal defect
▸ Atrial septal defect
▸ Patent ductus arteriosus
▸ Arterio-venous malformation
▸ Thrombophilia
▸ Antiphospholipid syndrome
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Figure 1 ECG at admission showing sinus rhythm with ST elevation in inferior leads.

TREATMENT
It was decided to administer thrombolytic therapy in
view of his pulmonary embolism and inferior ST elevation
myocardial infarction (STEMI). Taking into account the
presence of left-sided hemiplegia and normal brain CT,
possibility of early ischaemic stroke was considered. Since
the patient had presented within 3 h of onset of
symptom, this was within the window period for administration of thrombolysis for stroke cases. Recombinant
tissue plasminogen activator (tPA) was given as per the
protocol. Blood pressure at the time of thrombolytic was
122/83 mm Hg and pulse was 72 beats/min.
After giving tPA, the patient was shifted to Coronary
Care Unit. He then developed a self-limiting episode of
upper gastrointestinal bleeding, which caused an acute

Figure 2 CT pulmonary angiogram showing bilateral pulmonary
embolism.
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drop in haemoglobin level. He was transfused 2 units
packed red blood cells. However his haemodynamic
parameters remained stable and he responded to conservative management with proton pump inhibitors.
Low-molecular-weight heparin (LMWH) was started after
48 h. His GCS improved to 11/15. But he continued to
require ventilatory support and was still unable to move
the left side of his body. A follow-up brain CT after 5 days
showed a large right hemispheric haemorrhagic infarction
at the territory of the right middle cerebral, posterior cerebral and cerebellar arteries without any significant midline
shift (figure 3). The neuromedical team was consulted and
they advised to withhold all antiplatelet and anticoagulant

Figure 3 Brain CT showing large right hemispheric hypodense
area with patchy area of bleeding seen at the temporal lobe with
associated mass effect but no significant midline shift.
BMJ Case Reports 2012; doi:10.1136/bcr-2012-007221

medications, which could be restarted after 2 weeks if
patient’s condition remained stable. In the meantime his
neurological status remained stable and he did not require
any urgent neurosurgical intervention. Follow-up brain CT
showed gradual resolution of the haemorrhagic infarction
(figure 4). He was then gradually started on regular
physiotherapy.
Angiography was not planned due to the patient’s
current condition. Transthoracic bubble contrast echocardiography was done but it did not show any shunt across
interatrial septum, but the patient was unable to perform
Valsalva manoeuvre due to poor respiratory effort. It was
planned to do a transoesophageal echocardiography (TEE)
as it is a more sensitive tool for identification of patent
foramen ovale (PFO). However, the patient’s relatives
arranged for air ambulance in order to transfer him to his
own home country for further medical care.

OUTCOME AND FOLLOW-UP
The patient was admitted in our hospital for over a
month and was then transported to his own home
country for further medical care. At discharge the patient
was haemodynamically stable and able to maintain
oxygen saturation in room air. Power in the left side was
2/5. His discharge medications included antihypertensives,
pantoprazole, LMWH, clopidogrel and statin. He was
advised to continue anticoagulation for 6 months and to
undergo TEE and work-up for occult malignancy in his
home country.

DISCUSSION
The patient had four thrombotic events—DVT, acute pulmonary embolism, inferior STEMI and stroke. In a scientific statement by American Heart Association in 2011,
the indications for fibrinolysis in pulmonary embolism are

Figure 4 Follow-up brain CT showing resolving haemorrhagic
infarction.
BMJ Case Reports 2012; doi:10.1136/bcr-2012-007221

clearly outlined. They introduced a subcategory of acute
pulmonary embolism without systemic hypotension, but
with either right ventricular (RV) dysfunction or myocardial necrosis. They termed this as submassive pulmonary
embolism and such patients with evidence of worsening
respiratory insufficiency, severe RV dysfunction or major
myocardial necrosis may be considered for fibrinolysis.1
Since our patient had signs of respiratory failure, echocardiographic features of RV dysfunction (RV hypokinesis
and right ventricular systolic pressure (RVSP) of
40 mm Hg) and elevated troponin which are evidence of
increased severity of pulmonary embolism, he was considered for thrombolysis. Moreover, the beneficial effects of
thrombolysis may also extend to the concurrently existing
STEMI and ischaemic stroke, as he presented within the
window period for both events.
Since the patient had both venous and arterial thrombosis at the same time, the possibility of paradoxical
embolisation was considered. He had developed DVT due
to prolonged period of immobilisation during the flight.
The thrombus then dislodged from the leg veins and
migrated to the pulmonary arteries where it caused a
bilateral acute pulmonary embolism. This raised the right
heart pressures which subsequently caused a right-to-left
shunting of circulation through a probable intracardiac
defect, causing a paradoxical embolism to the coronaries
and right hemispheric circulation. The ischaemic stroke
lesion then underwent haemorrhagic transformation as a
complication of the thrombolytic therapy. Although angiography could not be done due to patient’s condition, the
classic ECG changes, pattern of elevation of cardiac
enzymes and the echocardiography features are highly
suggestive of STEMI.
Such a right−left shunt could be either caused by a
cardiac or an extracardiac lesion. Such defects include
PFO, atrial septal defect, ventricular septal defect, patent
ductus arteriosus and pulmonary arterio-venous malformation. PFO is considered by far the most commonly
observed cardiac shunt that is seen in over 25% of the
population.2 Paradoxical embolisation is considered an
uncommon yet serious consequence of DVT. Paradoxical
embolisation has also been known to occur as a complication of thrombolytic therapy in patients with massive
pulmonary embolism who have a pre-existing right-to-left
communication.3 4 There is now increasing interest in
recognising cases of non-cerebral paradoxical embolism in
patients with a shunt lesion. Such cases accounted for
only 2.9% of the referrals to a specialised centre for the
evaluation of PFO.5 Such diverse and relatively rarer presentations include acute limb ischaemia,4 6 7 renal infarction,8 9 ischaemia of the digestive tract10 and also
myocardial infarction.11 12 Knobloch et al13 reported a
similar case in a young man with myocardial infarction,
popliteal artery occlusion and carotid thrombus. The
patient was then retrospectively found to have pulmonary
embolism and PFO, which led to the diagnosis of paradoxical embolism. Another case report by Ménager et al14
described a 64-year-old patient with myocardial infarction,
pulmonary embolism and evidence of multiple cerebral
infarcts. He was then found to have a thrombus in the
right atrium with PFO. A recent interesting study by
Wöhrle et al 15 has shown the presence of subclinical myocardial infarctions that was demonstrated by cardiac MRI
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in 10.8% of patients with PFO after a first cryptogenic
cerebral ischaemic event.
Echocardiography with contrast, especially TEE is an
important tool that is used in the work-up of patients
with suspected intra-cardiac shunts.16 17 Such right-to-left
shunting can appear transiently in normal individuals due
to common daily activities like coughing or Valsalva manoeuvre.17 It may also occur due to cases of pathological
elevation in the right heart pressures.
The management of such cases is controversial. A study
by Furlan et al18 concluded that closure of a PFO with a
device did not offer a greater benefit than medical therapy
alone for the prevention of recurrent stroke or transient
ischemic attack (TIA). However, a meta-analysis by
Agarwal et al19 has estimated that the incidence of recurrent neurological events in patients with PFO who were
managed by transcatheter closure was 0.8 events, as compared to 5 events/100 person-years in patients who underwent medical management.
Studies have shown that certain cardiovascular risk
factors are also associated with venous thromboembolism.20 21 They include older age22 and obesity.23 24 Other
possible diagnosis that was considered in this patient was
antiphospholipid syndrome and thrombophilia; however,
the results of blood tests did not favour the diagnosis.
Our patient had a unique presentation of thrombus in
multiple sites that caused significant haemodynamic
instability. There are no well-established guidelines which
discuss the acute management of such cases.

2.

3.
4.

5.
6.

7.

8.
9.

10.
11.

12.

13.
14.

15.

Learning points
16.

▸ Patients who present with concomitant multiple site
thrombosis require careful assessment and
management by a multidisciplinary team.
▸ Patients with acute pulmonary embolism or deep vein
thrombosis who also present with symptoms or signs
of arterial embolisation should be evaluated for a shunt
lesion.
▸ A high index of suspicion is needed for paradoxical
embolism in cases of unexplained arterial occlusion.
▸ Other possible diagnosis to consider in such cases
include thrombophilia and antiphospholipid syndrome.

17.

18.

19.

20.
21.

Competing interests None.

22.

Patient consent Obtained.

23.

REFERENCES

24.

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submassive pulmonary embolism, iliofemoral deep vein thrombosis, and

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BMJ Case Reports 2012; doi:10.1136/bcr-2012-007221

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