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Case report 205

Inherited thrombophilia-related complications in the
treatment of a biatrial thrombus
Issam Jaloulia, Meriem Mradb, Najiba Fekih-Mrissab, Zied Hajjeja, Anis Lebbia,
Iheb Labbenea, Nasreddine Gritlib and Mustapha Ferjania
The study emphasizes the importance of the high risk of
thromboembolism with inherited thrombophilic factors.
Transesophageal echocardiography revealed large biatrial
masses in an 87-year-old woman with history of nonvalvular
atrial fibrillation, pulmonary embolism, and prescribed oral
anticoagulation for prophylaxis of embolic events. The
surgical removal of the presumed thrombus was declined
by the patient and intravenous anticoagulation with
unfractionated heparin was initiated. Treatment was
complicated by additional embolic events and the patient
succumbed after 14 days due to multiple organ failure.
Testing revealed heterozygosity for both the factor V Leiden
and the methylenetetrahydrofolate reductase C677T
mutations inducing resistance to activated protein C. The
combination of these thrombophilic factors can probably
explain the poor anticoagulant response, embolic events,

Atrial fibrillation is frequently associated with intra-atrial
thrombus formation and subsequent systemic embolization [1]. Large and mobile thrombi in the left atrium are
generally considered to indicate surgical thrombectomy.
However, some patients with soft and low echoic thrombi
have been successfully treated with anticoagulation
therapy, although complete thrombus resolution required
more than 14 days [2]. In the present case, the appearance
of large biatrial thrombus under oral anticoagulant therapy
was a predictive factor for failure of medical treatment.

The patient is an 87-year-old woman with a history of
four miscarriages, deep vein thrombosis of the right lower
limb postmyomectomy, pulmonary embolism treated
medically, and chronic nonvalvular atrial fibrillation diagnosed in 2010. She was taking acenocoumarol (Sintrom;
Novartis Pharma SAS, France) (4 mg/day) as prophylaxis
for embolic events.
She was admitted to the ICU for management of a closed
thoracic trauma. The stay was complicated by the occurrence of facial asymmetry paralysis and right hemiplegia
with suspected ischemic stroke that was subsequently
confirmed by brain MRI. Further, an occurrence of
an acute radial artery ischemia of the right arm with
necrosis of the thumb and index finger, confirmed by
an arterial Doppler ultrasound, required the amputation
of two fingers. The patient had given her informed
consent prior to treatment and all blood analyses.
0957-5235 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

and the failure of resolution of the biatrial masses. Blood
Coagul Fibrinolysis 24:205–207 ß 2013 Wolters Kluwer
Health | Lippincott Williams & Wilkins.

Blood Coagulation and Fibrinolysis 2013, 24:205–207
Keywords: anticoagulation, atrial thrombus, embolic events, thrombophilia

Department of Anesthesia and Intensive Care and bLaboratory of Molecular
Biology, Department of Hematology, Military Hospital of Tunisia, Tunis, Tunisia
Correspondence to Najiba Fekih-Mrissa, Laboratory of Molecular Biology,
Department of Hematology, Military Hospital of Tunisia, 1008 Mont Fleury Tunis,
Tel: +216 22510488; e-mail:
Received 21 July 2012 Revised 30 August 2012
Accepted 14 September 2012

Despite effective intravenous anticoagulation with
30 000 IU/day of unfractionated heparin (1250 IU/h)
with an achieved activated partial thromboplastin time
(APTT) of 70–90 s, the evolution was complicated
by deep vein thrombosis of the right leg, pulmonary
embolism in the right apical segment, and thrombocytopenia due to suspected heparin-induced thrombocytopenia (HIT). This cause, however, was discounted
due to a ‘4T’s’ score that indicated an intermediate probability of HIT, negative indications of antiplatelet factor 4
(PF4) antibodies, and by a prompt return to a normal
platelet count with continuation of heparin therapy.
Given these embolic events, endocarditis, with or
without a patent foramen ovale (PFO), was suspected.
A transesophageal echocardiogram (TEE) did not detect
endocarditis but did reveal a large echogenic multilobulated mass (5 cm  3 cm) originating from the left
atrial appendage (LAA) and attached to the anterior
wall of the nonenlarged left atrium (Fig. 1), a second
mass (3 cm  2 cm) in the right atrium, and normal
left ventricular systolic function with a left ventricular
ejection fraction of 55%. A transthoracic echocardiogram
(TTE), done 2 years ago, had demonstrated a normal
size atria and normal left ventricular systolic function
with an ejection fraction of 60% and without spontaneous
echo contrast.
The differential diagnosis for the identified biatrial
masses included a neoplasm, such as atrial myxomas,
and metastases; however, cardiac MRI confirmed the
thrombotic nature of these masses (Fig. 2). Surgical

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206 Blood Coagulation and Fibrinolysis 2013, Vol 24 No 2

Fig. 1

Fig. 3








Transesophageal echocardiogram. Long axis (08) four chamber view
showing thrombi in the left and right atria (arrow). LA, left atrium; LV, left
ventricle; RA, right atrium; RV, right ventricle.
Computed tomography angiogram. Floating thrombus in the aorta next
T11 and L1 (arrows).

removal was considered as a therapeutic and diagnostic
option, but the patient refused treatment. A thoracoabdominal computed tomography (CT) angiogram revealed
thromboses of the portal vein, inferior vena cava, adrenal
veins, the left external iliac vein, and the presence of two
floating thrombi in the aorta next to T11 and L1 (Fig. 3).
Following 14 days of hospitalization, the patient died
due to multiple organ failure, including respiratory
failure, hemodynamic instability, and renal dysfunction
with severe metabolic acidosis probably related to
thromboses of the renal vessels.
Testing for congenital thrombophilia revealed the
patient to be heterozygous for both the factor V (FV)
Leiden mutation (Arg506Gln) and the methylenetetrahydrofolate reductase (MTHFR) C677T variant. Hemostasis exploration indicated protein C activity at 67%

Fig. 2




Cardiac MRI. Thrombi in the left and right atria (arrows). LA, left atrium;
LV, left ventricle; RA, right atrium; RV, right ventricle.

(normal range 80–130%), protein S activity at 78%
(normal range 60–130%), and antithrombin III activity
at 86% (normal range 80–120%). She tested negative
for antiphospholipid antibodies and had normal homocysteine levels (12.5 mmol/l).

Atrial fibrillation is characterized by the loss of organized
atrial mechanical contraction with decreased flow in
the left atrium resulting in echocardiographic findings
of spontaneous echo contrast and decreased LAA flow
velocities [3].
A higher risk for thromboembolic events is known to
be associated with severe spontaneous echo contrast
and LAA flow velocities less than 0.2 m/s [3,4]. Thrombus
of the left atrium or LAA is demonstrated by TEE in 5–
15% of patients with nonvalvular atrial fibrillation
before initiation of anticoagulation [3]. The resolution
of left atrial thrombi with anticoagulation therapy was
previously confirmed using serial transesophageal examinations in up to 80% of patients with nonvalvular atrial
fibrillation [5,6]. Patients who had larger, denser thrombi
and increased left atrial size, were less likely to respond
to anticoagulant therapy [5]. However, in these studies,
all thrombi were less than 2.5 cm in size and most
were limited to the LAA without extending into the
left atrium.
Thrombolytic therapy has induced the disappearance
of thrombi in some case reports [7–9]. In most patients,
with evidence of right ventricular strain, it may effectively serve to reduce pulmonary vascular resistance,
improve cardiac index, and decrease mortality risk [10].
However, major bleeding (22%) and cerebral hemorrhage
(3%) remain serious considerations [11]. Thrombolysis in
the case of large size thrombus (as in our case) may cause

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Inherited thrombophilia-related complications Jalouli et al. 207

thrombus fragmentation and systemic embolization [11].
Surgical thrombectomy is generally recommended for
free floating ‘ball’ left atrial thrombi, which are more
likely to embolize [12]. It is not clear whether large,
nonmobile thrombi should be managed surgically
or medically with long-term anticoagulation therapy.
The differential diagnosis of a left atrial mass includes
thrombus, primary cardiac tumors (such as atrial
myxomas), and metastases. Atrial myxomas typically arise
in the left atrium from the region of the foramen ovale.
Our patient had a 2-year history of nonvalvular atrial
fibrillation, a large mass attached to the anterior left atrial
wall, and normal TTE 2 years ago. These arguments
are in favor of a thrombus. Coagulation (mediated by
thrombin) and fibrinolysis (mediated by plasmin)
activation should be staged according to the plasma
activity of alpha-2-macroglobulin (a2M) by use of the
normal intravascular coagulation-pathologic intravascular
coagulation and normal intravascular fibrinolysis-pathologic intravascular fibrinolysis system for classification of
coagulation and fibrinolysis, respectively [13]. However,
these tests are not yet available in our laboratories. The
failure of resolution of the left atrial mass after 2 weeks
of therapy with unfractionated heparin and the occurrence of many embolic events can be explained by the
resistance to activated protein C and the presence of
combined heterozygous mutations of the FV Leiden
and MTHFR genes. This case emphasizes the importance of the high risk of thromboembolism in patients
with inherited thrombophilic factors.












The authors would like to thank Dr Christian Winchell
for his valuable help in correcting this article.


Conflicts of interest

The authors declare that they have no conflicts of interest.


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