Casi clinici
Massive pulmonary embolism in a woman
with leiomyomatous uterus causing pelvic
deep venous thrombosis
Marco Falcone, Pietro Serra
Deep venous thrombosis (DVT) is a serious illness sometimes causing death due to acute pulmonary
thromboembolism (PTE). Blood stasis of the pelvic vein is a major etiologic factor for DVT.
Occasionally a large myomatous uterus can cause compression of the pelvic venous system leading to DVT. We describe a very rare case of massive pulmonary embolism in a 39-year-old
woman with multiple uterine myomas and no other recognized risk factors for PTE and DVT.
The patient was successfully treated with thrombolytic and anticoagulation therapy associated
with total hysterectomy.
(Ann Ital Med Int 2005; 20: 104-107)
Key words: Heparin resistance; Pulmonary embolism; Uterine leiomyoma.
Introduction
been reporting recurrent right leg swelling and menorrhagia
that was not investigated by a gynecologist. On admission
the patient was dyspnoic, her pulse rate was 104 b/min, respiratory rate 36 breaths/min, blood pressure 140/80 mmHg.
Breath sounds were normal, and cardiac examination was
not remarkable. A unilateral edema of the right ankle and
calf was noted as well as a positive Homan’s sign of the
right leg. Her body mass index was 35.7 kg/m2. Due to her
large abdomen circumference no masses were palpable on
the lower abdomen. Arterial blood gas analysis (room
air) showed: PaO2 69 mmHg, PaCO2 33 mmHg, pH 7.45,
HCO3- 26.5 mEq/L. An ECG revealed normal sinus
rhythm. Chest X-ray showed a clear lung field without cardiomegaly. Laboratory findings revealed a hemoglobin
level 8.9 g/dL with indices demonstrating an iron deficiency anemia, platelet count 293 000/mm3 and a normal
coagulation profile. However, since D-dimer levels were
elevated (988 µg/L), a pulmonary embolism was suspected. A spiral computed tomography (CT) of the chest
with contrast medium showed tapering of the right pulmonary artery and a normal left pulmonary artery.
Abdominal CT scan showed an enlarged right shifted
uterus (Fig. 1) with three voluminous lesions (probably
referred to myomas) determining compression on the
right pelvic veins. At Doppler flow ultrasonography, a
thrombus was found in the right leg at the level of the
popliteal vein. On the basis of these findings anticoagulation therapy was started with intravenous heparin (1100
U/hour) and oral warfarin (2 mg/day).
However, during the days following admission, the
patient required > 40 000 U/24 hours (up to 1800 U/hour)
heparin to prolong the activated partial thromboplastin time
added to the therapeutic range. On day 4, despite intensive
Intravascular deep venous thrombosis (DVT) is a serious illness that sometimes causes death due to acute pulmonary thromboembolism (PTE). DVT has been reported to be caused by pregnancy, surgical procedures, longterm bed rest, bone fractures, cancer, antiphospholipid syndrome, use of oral contraceptives, and long-haul air travel1-4. Obesity is not a clear risk factor1. Very rarely a
large myomatous uterus can determine a compression of
the pelvic venous system causing DVT5-7. However to the
best of our knowledge there are only a very few English
language previous reports of PTE associated with uterine
myomas8,9. We report an additional case of massive pulmonary embolism in a 39-year-old woman with multiple
uterine myomas and no other recognized risk factors for
PTE and DVT. The patient was successfully treated with
thrombolytic and anticoagulation therapy associated with
total hysterectomy. No relapse has been observed after a
16-month follow-up.
Case report
A 39-year-old woman was admitted to our Department
for acute dyspnea and palpitation onset associated with pain
and swelling of the right leg. The patient was nulliparous,
non-smoker, and denied alcohol or illicit drug use. No history of oral contraceptive use, prior surgery, as well as a
personal or family history of coagulopathies were documented. During the 5 months prior to admission, she has
III Clinica Medica, Cattedra di Medicina Interna III (Direttore:
Prof. Pietro Serra), Università degli Studi “La Sapienza”, Policlinico
Umberto I di Roma
© 2005 CEPI Srl
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Marco Falcone - Pietro Serra
FIGURE 1. Abdominal computed tomography showing an
FIGURE 2. Chest computed tomography showing a massive
bilateral pulmonary embolism with “saddle emboli” in the left
and right pulmonary arteries.
enlarged uterus with voluminous lesions proximal to the right
pelvic deep veins.
and prolonged anticoagulation, an acute dyspnea relapse,
associated with tachypnea, hypotension, pleuritic chest
pain, and jugular vein distension was observed. Arterial
blood gas analysis (room air) showed: PaO2 44 mmHg,
PaCO2 29.9 mmHg, pH 7.48, HCO3- 22.3. The ECG
revealed inverted T waves in leads V1-V4, while a transthoracic echocardiogram revealed a dilated and hypokinetic
right ventricle with a 68 mmHg pulmonary artery systolic
pressure calculated using the Bernoulli formula. An urgent
chest CT scan showed the presence of “saddle” emboli at
the biforcation of the main right and left pulmonary arteries (Fig. 2). The abdominal CT scan also showed a proximal deep vein thrombosis extended to the right femoral
and external iliac veins. A catheter-directed thrombolytic therapy with intrapulmonary artery infusion of recombinant tissue plasminogen activator plus urokinase was performed. This procedure was associated with mechanical
thrombus fragmentation and insertion of an inferior vena
cava filter. After this treatment the patient’s respiratory status dramatically improved, and approximately 24 hours
later pulmonary angiography showed a bilateral clot resolution.
Plasma levels of antithrombin III, protein C, protein S,
lupus-anticoagulant, and homocysteine were normal.
Factor V Leiden and prothrombin G20210A mutations
were absent. The myomatous uterus was considered to be
the sole cause of DVT and PTE, and after 12 days an
uneventful total hysterectomy was performed. Gross
pathologic inspection revealed an enlarged uterus (18 16 13 cm) with three voluminous intramural myomas.
Histologic examination showed uniform, benign cells
consistent with leiomyomata.
The patient’s clinical conditions definitively improved
and she was discharged without symptoms of respiratory impairment on hospital day 38. No relapse has been
observed after a 16-month follow-up.
Discussion
Although DVT and PTE are known to be complications
of gynecologic surgery, particularly during hysterectomy10,
hysterectomy performed to treat thromboembolic disease
is a very rare phenomenon. Large uterine tumors, such as
leiomyoma, can cause a compression of the surrounding
structures and cause various clinical syndromes, such as
hydroureter and hydronephrosis, mesenteric vein thrombosis, acute intestinal gangrene, and cases of acute
abdomen11,12. However, a large leiomyomatous uterus
occasionally can determine DVT due to the pelvic venous
system stasis secondary to compression5-7. The occurrence of PTE secondary to DVT and uterine myoma has
been reported only twice in the English literature8,9.
Myomas are rare before menarche, often enlarge during pregnancy, and diminish in size following menopause
or castration, which is accompanied by a significant reduction in circulating estrogen. This is why the probability of
intraperitoneal organ compression by uterine myomas is
particularly high in the reproductive period. In fact, as confirmed by literature data, an association of DVT or PTE
with myomatous uterus occurs in pre-menopause patients
(range 39-51 years5-9).
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Ann Ital Med Int Vol 20, N 2 Aprile-Giugno 2005
In the classic triad of Virchow, the factors of stasis, disruption of the vascular endothelium and changes in the
coagulation pathways have all been recognized as risks for
DVT developing. Some previous reports of women with
uterine myomas and DVT were complicated by risk factors, such as high-dose norethisterone acetate, history of
venous insufficiency, prior DVT or lower extremity vein
stripping5,6. On the contrary in our patient the unique
predisposing factor for DVT was the large myomatous
uterus that induced chronic venous stasis in the pelvis and
lower limbs.
Intravenous heparin is the recommended drug to start anticoagulation in patients with PTE. However, a special feature of this case was the low effectiveness of intravenous
heparin during the first days of treatment, a fact that probably favored the recurrence of PTE 4 days after presentation. There is a considerable in vivo variation in response
to a fixed dose of heparin among individuals; this is partly due to the pharmacokinetic limitations of heparin, in addition to the difficulties encountered in measuring its desired
anticoagulant effect. In the context of venous thromboembolism, heparin resistance is defined as the need for
> 35 000 U/24 hours to prolong the activated partial thromboplastin time added to the therapeutic range 13 .
Pharmacokinetic limitations are caused by the binding of
heparin to plasma proteins including platelet factor 4, fibrinogen, factor VIII and histidine-rich glycoprotein13-15. As
many heparin-binding proteins are acute-phase reactants,
heparin resistance is often encountered in acutely ill
patients, in patients with malignancies, and during perior post-partum periods14. Heparin resistance has also
been associated with drug-induced causes including aprotinin and nitroglycerin (although the latter is controversial),
and low antithrombin levels14,15. None of these recognized
risk factors for heparin resistance was present in our
patient.
Pelvic vein compression by an enlarged myomatous
uterus is a strict indication for hysterectomy. However, the
existence of PTE may often require thrombolytic therapy
and inferior vena cava filters (Table I)16, and the management of such cases could be more difficult than those
without pre-operative DVT. In our case the catheterdirected thrombolysis associated with embolus fragmentation rapidly reestablished pulmonary blood flow. Catheter
fragmentation followed by intrapulmonary thrombolytic
infusion is an aggressive technique used to achieve a
rapid thrombus resolution, improving hemodynamic conditions in most patients. Recent experimental in vitro and
in vivo evidence17 suggests that, in case of a massive pulmonary occlusion due to an embolus, a vortex proximal
to the occluding embolus can form, and any fluids infused
TABLE I. Accepted indications for inferior vena cava filter insertion.
Patients with evidence of pulmonary embolus or inferior vena
cava, iliac, or femoral-popliteal DVT and one or more of the
following
Contraindications to anticoagulation
Anticoagulation complications
Anticoagulation failure
Recurrent PTE despite adequate therapy
Inability to achieve adequate anticoagulation
Massive pulmonary embolism with residual deep venous
thrombus in a patient at risk for further PTE
Free-floating iliofemoral or inferior vena cava thrombus
Severe cardiopulmonary disease and DVT (cor pulmonale with
pulmonary hypertension)
Poor compliance with anticoagulation therapy
DVT = deep venous thrombosis; PTE = pulmonary thromboembolism.
From Grassi et al.16, modified.
proximally to the pulmonary artery occlusion will make
only evanescent contact with the thrombus edge, and the
fluid is washed into the non-occluded ipsilateral and contralateral pulmonary arteries. After embolus fragmentation
the infused fluid is completely carried into the formerly
occluded artery. It should be outlined that this technique
is not routinely used, and should be considered only when
facilities and expertise are readily available18. However,
our case and some evidence support this practice, especially
in cases of massive bilateral life-threatening PTE.
In conclusion we have described a rare case of massive
pulmonary embolism due to a large leiomyomatous uterus.
The patient was successfully treated with anticoagulation and direct thrombolytic therapy followed by hysterectomy and no relapse occurred during a 16-month
follow-up.
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Manuscript received on 23.11.2004; accepted on 8.2.2005.
Address for correspondence:
Dr. Marco Falcone, III Clinica Medica, Dipartimento di Medicina Clinica, Università degli Studi “La Sapienza”, Policlinico Umberto I, Viale
del Policlinico 37, 00185 Roma. E-mail: [email protected]
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