AJR 2001; 177:446-448
© American Roentgen Ray Society
Intraarterial Subclavian Artery Thrombolysis in a Neonate
K. Wolfgang Neff1,
Dietmar Dinter1,
Thomas Schaible2,
Karl-Jürgen Lehmann1 and
Christoph Düber1
1
Department of Clinical Radiology, University of Heidelberg,
Universitätsklinikum Mannheim, Theodor-Kutzer
Ufer 1-3, 68167 Mannheim, Germany.
2
Department of Pediatrics, University of Heidelberg,
Universitätsklinikum Mannheim, 68167 Mannheim,
Germany.
Received November 28, 2000;
accepted after revision February 8, 2001.
Address correspondence to K. W. Neff.
Introduction
Thrombotic vascular occlusion may complicate the clinical course of many
neonatal and pediatric disorders. Traditional treatment of occlusive events in
these patients has included clinical observation, surgical thrombectomy, or
systemic anticoagulation. Thrombolytic therapy is well established and has
been used extensively in adults to treat thrombotic events of different
causes. Several recently published reports on thrombolytic therapy in adults
have summarized the clinical and pharmacologic aspects of different
thrombolytic agents. These drugs are increasingly used to treat thrombotic
disorders in infants and children, although pharmacologic aspects are
different in this age group. We report thrombolysis of subclavian arterial
thrombosis in a full-term neonate.
Case Report
An 8-hr-old, 3.5-kg, full-term male neonate with a swollen and marmorated
left arm occurring 15 min after spontaneous delivery was admitted to our
hospital. The delivery was uncomplicated; shoulder dystocia and delivery by
forceps, for example, were not involved. A review of the case, including
interviews with the parents and obstetricians and a physical examination of
the newborn, revealed no signs of major trauma at birth. The neonate's left
forearm was cold, pale, and pulseless, and palsy of the left hand was
observed. The remainder of the examination was unremarkable.
Laboratory tests showed slightly reduced levels of the following: platelet
count, 111 x 109/L (normal, 150-450 x
109/L); hemoglobin, 13.3 g/dL (normal, 14-20 g/dL); and
erythrocytes, 3.7 x 109/L (normal, 3.9-5.8 x
109/L). The WBC was normal at 15 x 109/L (normal,
6-17 x 109/L). Values for plasma thrombin time, 17 sec
(normal, 16-27 sec); activated partial thromboplastin time, 29 sec (normal,
28-54.5 sec); and fibrinogen, 2.2 g/L (normal, 1.7-4.0 g/L) were within normal
limits, as well as the activities of antithrombin III, 53% (normal, 39-87%);
plasminogen, 38% (normal, 26-70%); protein C, 44% (normal, 17-53%); and
protein S, 31% (normal, 12-60%).
Angiography performed 9 hr after birth with selective catheterization of
the left subclavian artery via the umbilical artery revealed an occlusion of
the proximal left subclavian artery. The angiogram was obtained using a
straight 3.5- French umbilical artery catheter. Two milliliters of diluted
triiodinated isoosmolar contrast agent (iopamidol, Solutrast 300; Byk Gulden,
Konstanz, Germany) was used. Occlusion of the left subclavian artery and poor
collateral formation were shown (Figs.
1A and
1B). Additionally, the left
vertebral artery was occluded. Local thrombolytic treatment was initiated with
recombinant tissue plasminogen activator, tPA (alteplase, Actilyse;
Boehringer, Ingelheim, Germany). High-dose treatment was started for 24 hr
with 0.1 mg/kg of body weight per hour, followed by half-dose treatment for 48
hr via the catheter positioned in the proximal left subclavian artery using
the umbilical artery approach. Twenty-four hours after intraarterial
thrombolysis was begun, the swelling and marmoration of the child's left arm
decreased, and a pulse was detected at the wrist using Doppler sonography.
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Fig. 1A. —9-hour-old, full-term male neonate with left subclavian
artery thrombosis; swollen and marmorated left arm; cold, pale and pulseless
left forearm; and palsy of left hand. Digital subtraction angiogram shows
selective catheterization of left subclavian artery using umbilical artery
approach and revealing proximal occlusion of vessel (arrow) and poor
collateral formation.
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Fig. 1B. —9-hour-old, full-term male neonate with left subclavian
artery thrombosis; swollen and marmorated left arm; cold, pale and pulseless
left forearm; and palsy of left hand. Digital subtraction angiogram later in
that infusion reveals intraluminal filling defect in left subclavian artery
(arrow).
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Selective angiography of the left subclavian artery, performed 3 days after
starting thrombolytic treatment with 1.5 mL of diluted contrast agent, showed
recanalization of the left subclavian and vertebral arteries
(Fig. 1C) but revealed a short
thrombosis of the brachial artery with beginning collateral circulation
(Fig. 1D). Thrombolysis was
continued for 24 hr, supported by continuous IV vasodilatation with 1 mg/kg of
body weight per minute of glyceryl trinitrate (Perlinganit; Schwarz Pharma,
Monheim, Germany) over 48 hr.
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Fig. 1C. —9-hour-old, full-term male neonate with left subclavian
artery thrombosis; swollen and marmorated left arm; cold, pale and pulseless
left forearm; and palsy of left hand. Digital subtraction angiogram after 3
days shows recanalization of left subclavian and vertebral arteries.
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Fig. 1D. —9-hour-old, full-term male neonate with left subclavian
artery thrombosis; swollen and marmorated left arm; cold, pale and pulseless
left forearm; and palsy of left hand. Digital subtraction angiogram of
brachial artery depicts persistent short thrombosis of left brachial artery
(arrow) and beginning collateral circulation.
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A third angiogram, obtained 3 days later with 0.5 mL of diluted contrast
agent, showed a complete recanalization of the left brachial artery in the
elbow region (Figs. 1E and
1F). Therapy with tPA was
stopped and replaced with systemic heparinization (300 U/kg of body weight per
day for 4 weeks). The umbilical artery catheter was removed after the third
angiography. Level-controlled prophylactic antibiotic therapy with ampicillin
and gentamicin (Refobacin; E. Merk, Darmstadt, Germany) was administered over
10 days. At discharge nearly 6 weeks after delivery, levels of protein S,
antithrombin III, plasminogen, and protein C were all within normal limits for
the infant's age.
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Fig. 1E. —9-hour-old, full-term male neonate with left subclavian
artery thrombosis; swollen and marmorated left arm; cold, pale and pulseless
left forearm; and palsy of left hand. Digital subtraction angiogram obtained 6
days after diagnosis shows complete recanalization of left brachial artery and
sufficient forearm runoff.
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Fig. 1F. —9-hour-old, full-term male neonate with left subclavian
artery thrombosis; swollen and marmorated left arm; cold, pale and pulseless
left forearm; and palsy of left hand. Radiograph corresponding to followup
angiogram E shows anatomic orientation with visualization of background
bony structures.
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A follow-up examination conducted 3 months later showed normal findings on
coagulation tests in the infant and his parents. There was no evidence of
recurrent thrombosis. Psychomotor development was normal, and there was a
complete recovery from the hand palsy.
Discussion
Arterial thrombosis in neonates is rare. It is most commonly observed in
children of mothers suffering from gestational diabetes during pregnancy
[1]. It can also result from
congenital disorders that predispose to thromboembolic disease, comprising
activated protein C resistance and deficiencies of protein C, protein S, and
antithrombin III [2].
Hemostatic and fibrinolytic mechanisms in newborns are immature and are not
fully developed until they are 6 months old
[3]. Other predisposing
conditions for thrombolic disease include short-term catheterization (e.g.,
cardiac catheters) and long-term catheterization (e.g., umbilical artery
catheters) [2]. To our
knowledge, only four cases of aortic thrombosis in neonates without indwelling
catheters have been reported. These neonates all had congenital clotting
disorders [4]. In our patient,
a minor birth trauma that caused intimal damage of the left proximal
subclavian artery with consecutive thrombosis and additional incomplete lower
plexus palsy is postulated as the mechanism for thrombosis.
Therapeutic options for arterial thrombosis include observation, surgical
thrombectomy, and intraarterial thrombolysis. Observation of neonates is often
used by clinicians until severe ischemic symptoms such as renal failure or
gangrene occur. Surgical thrombectomy has been attempted with poor results
[5]. In thrombotic vascular
occlusion, direct surgical intervention for repair may be precluded by the
small size of vessels involved.
Intraarterial thrombolytic therapy can be achieved using several different
drugs including streptokinase, urokinase, or tPA, which mediate their
activities by converting endogenous plasminogen to plasmin
[2,
6]. Beyond the widespread use
of thrombolytics, streptokinase requires binding to plasminogen before
becoming a thrombolysis activator, whereas urokinase is a direct plasminogen
activator. Limitations in usage are the nonspecific nature of systemic
thrombolysis and the lack of efficacy in newborns because of diminished levels
of plasminogen in this population.
TPA, a clot-specific thrombolytic agent used frequently in adults, is a
safe and efficacious alternative in newborns. TPA, which occurs naturally in
humans, is a substance with a strong affinity to fibrin. Fibrin-bound
plasminogen (i.e., clot-associated plasminogen) is activated by the tPA-fibrin
complex. The plasminogen is broken down to plasmin at the site of the clot,
initiating clot lysis, whereas non-clot-associated systemic plasminogen is not
activated. TPA has a short half-life allowing for the possibility of
withdrawing treatment in the case of an adverse event. Therefore, tPA has
theoretic advantages in newborns. It is nonantigenic
[3] and is recommended in a
dosage of 0.1-0.5 mg/kg per hour over 2-72 hr
[7], while starting heparin
therapy either during or immediately after completion of thrombolytic therapy.
The neonate should be monitored by measuring fibrinogen, thrombin clotting
time, prothrombin time, and activated partial thromboplastin time.
Significant differences exist in fibrinolytic mechanisms of newborns
compared with adults. Normal neonatal plasma has about 50-70% of the adult
plasminogen level, and plasminogen may be functionally deficient
[3], whereas the levels of
circulating inhibitors (
2-antiplasmin) are the same as those
in adults. In neonates with low levels of plasminogen, freshly frozen plasma
should be given to supply plasminogen that can be activated by the
thrombolytic agent [3].
Although, to our knowledge, no large series are present in the literature
on thrombolytic therapy with tPA, efficacy of treatment is approximately 85%,
and safety of tPA in neonatal thrombosis has been shown
[7,
8]. The use of thrombolytic
therapy in neonates remains a single-case decision and can be extremely
successful, as shown in our patient. Our case shows that it was possible to
save this neonate's arm when there were often few alternative measures
available.
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Introduction
Case Report
