Vol.2, No.5, 310-314 (2013) Case Reports in Clinical Medicine
Recurrent pulmonary embolism in a boy with
antiphospholipid syndrome
Christian Müller1*, Christian Willaschek1, Mathias Borst2, Reiner Buchhorn1
1Department of Pediatrics, Caritas Krankenhaus, Bad Mergentheim, Germany; *Corresponding Author: muellisin@googlemail.com
2Department of Medicine, Caritas Krankenhaus, Bad Mergentheim, Germany
Received 2 October 2012; revised 16 November 2012; accepted 8 December 2012
Copyright © 2013 Christian Müller et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
We report a 14-year-old patient with recurrent
pulmonary embolism due to catastrophic anti-
phospholipid syndrome (APS) with severe pul-
monary inflammation. We considered elevated
antibodies against cardiolipin and anti-beta2-
glycoprotein-1, but no clinical nor laboratory
manifest atio ns of syst emic lupus erythem atosus
(SLE). Pulmonary embolism had been the first
manifestation of catastrophic APS in this patient.
We prescribed warfarin and systemic corticos-
teroids. A second embolism appeared during
anticoagulation with warfarin. This event led to a
marked decrease of his physical performance
due to his obstructive and restrictive lung dis-
ease. Anticoagulation was changed from enteral
warfarin to subcutaneous enoxaparine. We also
prescribed inhaled corticosteroid which led to
an improvement of his respiratory symptoms
and overall poor physical condition.
Keywords: Pulmonary Embolism; Antiphospholipid
Syndrome; APS; Inhaled Corticosteroid
APS is a rare disease, especially in children [1]. As
opposed to the secondary form of APS occurring in pa-
tients with autoimmune disorders, predominately SLE.
APS is said to be primary if there are no features of SLE
or other autoimmune disorders [1,2].
Clinical manifestations of primary APS are variable
[3]: one feature is pulmonary embolism [4] which in one
case study occurred in 2.1% of patients with APS [5].
Especially in children, pulmonary embolism associ-
ated with APS is rare [6], but may be its first manifesta-
tion [2].
Chronic thromboembolic pulmonary hypertension (CTE-
PH) due to APS is a severe disease with high morbidity
and mortality [2,7]. Histopathologically, there may be
signs of catastrophic APS such as alveolar hemorrhage,
microvascular thrombosis and pulmonary capillaritis, which
is the most severe course of high mortality due to multi-
ple vascular occlusive events [8]. Pulmonary embolism
in APS associated with fever and elevated autoantibodies
are usually caused by SLE. Diagnosis of SLE is based on
clinical and laboratory features according to the classifi-
cation criteria [9-12]. Because there was no evidence of
autoimmune disorders the present case was classified to
primary APS.
We report a 14-year-old male in good overall physical
condition (BMI: 19.6 kg/m2) with no history of severe
diseases. He did not consume any medication, nicotine,
alcohol, or other drugs. The familial history was unre-
markable. He presented with acute chest pain and fever
up to 40˚C having lasted for one week. There was no
trauma recalled by the patient or his family. He presented
with pain, which was located in the right hemithorax and
increased in intensity when in supine position. During
physical examination a reduced respiratory sound over
his right lower pulmonary lobe was found.
Chest x-ray showed a consolidation in the right lower
pulmonary lobe. C-reactive protein (CRP) was elevated
to 9.37 mg/dL. An initial diagnosis of pneumonia was
made and antibiotic therapy (Cefuroxim, Doxycycline,
Gentamicin) was initiated.
Five days later there was no clinical improvement. A
computed tomography (CT) scan of the thorax (Figure 1)
showed signs of past pulmonary embolism in the right
lower lobe. We started effective anticoagulation with
intravenous heparin and enhanced the antibiotic therapy
(Cefuroxim, Doxycycline, Gentamicin and Vancomycin).
An ultrasound examination showed a deep venous throm-
bosis of the left lower extremity. The patient’s clinical
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C. Müller et al. / Case Reports in Clinical Medicine 2 (2013) 310-314 311
Figure 1. Primary thoracic computerized tomography.
conditions deteriorated and because of respiratory failure
with tachypnea he needed supplemental oxygen.
A CT-guided lung biopsy demonstrated changes sug-
gesting a hemorrhagic pulmonary infarct. Moreover, fea-
tures of catastrophic APS such as capillary inflammation,
microvascular thrombosis and alveolar haemorrhage were
found [4,13]. A malignant transformation was excluded
by means of a bone marrow biopsy.
Laboratory analyses demonstrated elevated autoanti-
bodies directed against cardiolipin and anti-beta2-glyco-
protein-1 on several occasions. Antinuclear antibodies,
dsDNA-antibodies, anti-SM-antigen and SSA-antigen were
negative. Based on the laboratory results and the histo-
logical findings the diagnosis of catastrophic APS was
Intravenous glucocorticosteroid therapy (methyl pred-
nisolone 150 mg/d) was begun. Body temperature de-
creased from 39.8˚C to 37.0˚C within twelve hours and
the clinical condition improved. Anticoagulation therapy
was changed from heparin to warfarin [14,15] with a
target INR of 2.0 - 3.0. The patient was equipped with an
INR home monitoring system. Compression stockings
were prescribed.
Two weeks later the patient suddenly felt acute chest
pain in the left hemithorax, consistent with pleuritic pain.
He reported shortness of breath and dyspnea. His body
temperature was normal. The INR was 2.18. A second
CT scan of the thorax showed a new pulmonary embo-
lism in the left lower lobe.
Therapeutic options such as thrombolysis, embolec-
tomy, and plasmapheresis were discussed.
Finally we decided to change the anticoagulation to
subcutaneous enoxaparine (2 × 60 mg/d). Warfarin and
corticosteroid therapy was tapered.
Six weeks later during an outpatient visit the boy com-
plained about generalized malaise. He felt that he was
unable to attend school. Cardiopulmonary exercise (CPX)
testing showed an impressive reduce of peak oxygen
uptake with predominant pulmonary limitation (Table 1).
Pulmonary hypertension was excluded by echocardiogra-
phy. Also congestive heart failure appeared very unlikely
as NT-Pro-BNP levels were normal (Ta bl e 2). However,
heart rate variability was reduced as determined by
Holter ECG.
We decided to treat the suspected pulmonary inflam-
mation with inhaled corticosteroids (fluticasone). A rea-
peted CPX test and Holter ECG showed an impressive
improvement of exercise capacity and heart rate variabil-
ity (Table 1). Nearly 5 months later the patient com-
plained of erythema and urtication after injection of sub-
cutaneous enoxaparine. We changed his anticoagulation
therapy from subcutaneous enoxaparine to moderate-in-
tensity warfarin and low dose acetylsalicylic acid (ASS)
[16]. As before, target INR was 2.0 - 3.0. Laboratory
analyses showed a progressive improvement of CRP and
D-Dimer values (Table 2).
Pulmonary embolism in our patient was the first mani-
festation of primary APS [2]. The diagnostic criteria of
SLE [9] were not met because no organ manifestations
other than deep vein thrombosis with pulmonary embo-
lism were present and specific laboratory features were
negative. However, septic fever unresponsive to antibi-
otics and the impressive clinical improvement after the
first dose of corticosteroids clearly indicate the inflam-
matory origin of our patient’s disease. Systemic corti-
costeroid therapy could be terminated after 5 weeks.
Despite an evidence based anticoagulation with war-
farin [14,15] the patient developed a second pulmonary
embolism two weeks after discharge from hospital. In
this situation he was at risk for the development of
CTEPH that usually has a fatal outcome in APS patients
[4]. Together with the patient and his parents, we decided
against plasmapheresis [17] or local therapies like throm-
bolysis [18-20] or vena cava filter [21,22].
After a therapeutic switch to subcutaneous enoxa-
parine and thereafter to warfarin and low dose ASS [23]
a progressive decrease of D-Dimer values were observed
(Table 2).
We had no evidence for heart failure indicated by
normal pro-BNP values or for pulmonary hypertension
indicated by normal tricuspid regurgitation velocity (Ta-
ble 2). However, for complete clinical recovery and res-
titution of his exercise capacity the patient depended on
inhaled corticosteroid therapy (Table 1), upon our hy-
pothesis of persistent pulmonary inflammation.
In summary, this case shows that pulmonary inflam-
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C. Müller et al. / Case Reports in Clinical Medicine 2 (2013) 310-314
Copyright © 2013 SciRes. OPEN ACCESS
Table 1. Monitoring by spirometry and Holter ECG before and after inhaled corticosteroid.
Before fluticasone After fluticasone Reference values
Vital capacity [L] 2.57 3.09 4.3
FEV1 [L] 1.35 2.76 3.6
FEV1/VC [% pred.] 52.4 107.2 >75
VO2 peak [L/min/m2] 21.1 31.0 >25
VE peak [L/min] 51 86 104
Breathing reserve [%] 0 11 28
RQ 0.97 1.06 >1
Heart rate max [1/min] 173 175 187
Holter ECG
Mean heart rate [1/min] 99 88 85
Triangle index 16 33 22 - 52
pNN50 [%] 1,68 7,58 5 - 47
SDNN [ms] 70 119 102 - 180
RMSSD [ms] 23 36 15 - 39
FEV1: forced exspiratory volume in one second; W: Watts; VE: minute ventilation; RQ: respiratory quotient; VO2: oxygen uptake. Holter ECG: electrocardi-
ography 24 h; pNN50: number of pairs of adjacent NN intervals differing by more than 50 ms divided by the total number of all NN intervals; SDNN: standard
deviation of all NN intervals; RMSSD: the square root of the mean of the square of differences between adjacent NN intervals.
Table 2. Laboratory values and echocardiographic parameters during the whole treatment.
1. embolism acute 1. embolism subacute2. embolism Discharge 2 months later 4 months later Reference
Therapy Antibiotics Corticoid aspirine
warfarin Enoxaparine Enoxaparine
Warfarin ASS
CRP [mg/dl] 6.3 0.4 1.36 1.78 0.18 0.34 0 - 1
INR 1.23 0.99 2.18 1.02 1.1 2.27 0.8 - 1.25
PTT [s] 103.6 76.4 55.3 114.4 104.5 67.3 28 - 40
D-Dimers [μg/l] 7620 2980 900 1730 230 50 0 - 500
NT-proBNP [pg/ml] 64.1 <5 19.6 0 - 85
Cardiolipin IgG 66 14 52 <10
Cardiolipin IgM <5.0 <5.0 <5.0 <7
β-2-Glykoprotein IgG 69 13 40 <10
β-2-Glykoprotein IgM 7 21 3 <12
LVEDD [mm] 42 43 40 44 43 43 35 - 51
FS [%] 42 36 36 45 46 35 >30
TI [m/s] 2.4 2.2 2.2 2.4 2.5 <2.5
(PASP [mmHg]) (28) (25) (25) (28) (30) (20 - 30)
CRP: C-reactive protein; INR: international normalized ratio; PTT: partial thromboplastin time; BNP: N-terminal pro brain natriuretic peptide; LVEDD: left
ventriclular enddiastolic diameter; FS: fractional shortening; TI: tricuspidal regurgitation velocity; PASP systolic pulmonary arterial pressure derived from TI;
Ig: Immunglobuline.
C. Müller et al. / Case Reports in Clinical Medicine 2 (2013) 310-314 313
mation can play an important role in manifestation of
primary APS that requires consequent immunosuppres-
sant treatment. Inflammation and anticoagulation have to
be monitored by D-Dimer values, CRP values and spe-
cific tests that depend upon the regiments.
A critical cardiopulmonary monitoring including echo-
cardiography, ECG, spirometry, CPX and Holter ECG is
necessary to recognize pulmonary hypertension and de-
creased endurance of the patient. Cardiac limitations due
to pulmonary hypertension may be treated by endarter-
ectomy or endothelin receptor antagonist, if patients are
deemed inoperable.
In patients with only pulmonary limitations like in our
case inhaled corticosteroid seems to be a good course of
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C. Müller et al. / Case Reports in Clinical Medicine 2 (2013) 310-314
APS: antiphosphorlipid syndrome
ASS: acetylsalicylic acid
BMI: body mass index
CPX: cardiopulmonary exercise
CT: computed tomography
CTEPH: chronic thromboembol pulmonary hypertension
ECG: electrocardiography
INR: international normalized ratio
SLE: systemic lupus erythematosus
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