Full text of DOI:10.1007/s005950070110

Surg Today (2000) 30:663–666
Acute Arterial Thrombosis with Antithrombin III Deficiency in
Nephrotic Syndrome: Report of a Case
Motohiro Nishimura, Junichi Shimada, Kazuhiro Ito, Hideyuki Kawachi, and Katsuhiko Nishiyama
Department of Cardiovascular Surgery, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka 564-0013, Japan
Abstract Nephrotic syndrome frequently causes venous
thromboembolic complications. Arterial thrombosis
has rarely been reported and is mainly observed in chil-
dren. Only six cases of lower extremity arterial throm-
bosis in adults have been reported in the literature. The
outcome in these cases was unsatisfactory because of
the high rates of limb loss and recurrence of thrombosis.
We report successful treatment of a 39-year-old man
who suffered from right lower extremity arterial throm-
bosis associated with decreased levels of serum anti-
thrombin III. He was admitted to our hospital with
severe pain in his right foot. No pulse was palpable in
his right dorsalis pedis or posterior tibial arteries. His
right foot was cold and mottled, with a reduced sensa-
tion and motor activity. The laboratory data revealed a
serum total protein concentration of 3.9g/dl and an al-
bumin concentration of 1.5g/dl. The coagulation profile
showed a fibrinogen level of 879mg/dl and antithrombin
III value of 9.5%. Right lower extremity arteriography
showed a complete occlusion of the right deep femoral
artery and popliteal artery, and a filling defect in the
common femoral artery. An emergency thrombectomy
was performed under general anesthesia. The patient
was treated successfully, and surgical treatment was
followed by anticoagulant therapy with 1 000 units of
antithrombin III. A renal biopsy revealed histologic
evidence of minimal change of glomerulonephritis. He
was discharged 3 months later, and no recurrence of
thrombosis has yet been observed.
Introduction
Hypercoagulability is a recognized complication of
nephrotic syndrome, which commonly affects the
venous system. Arterial thrombosis has been only infre-
quently reported and is observed mainly in children.
Reports of lower extremity arterial thrombosis with
nephrotic syndrome have been limited. A review of
the literature revealed only six cases of lower extremity
arterial thrombosis in the adult population. Its manage-
ment is unsatisfactory and contentious because of high
rates of both limb loss and a recurrence of thrombosis.
This report describes a 39-year-old man with nephrotic
syndrome complicated by lower extremity arterial
thrombosis associated with decreased levels of serum
antithrombin III.
Case Report
A previously healthy 39-year-old man was admitted to
our hospital with severe pain in his right foot. His vital
signs were as follows: a blood pressure of 112/84mmHg,
a pulse of 82 beats/min in sinus rhythm, a temperature
of 36.8°C, weight 85kg, and height 170cm. No arterial
pulses were palpable in his right lower leg. The right
foot was cold and mottled with a reduced sensation
and reduced motor activity. Laboratory data revealed a
3
white blood cell count of 13500/mm , a hematocrit of
3
5
1.7%, platelet count of 182000/mm , a sodium con-
Key Words Nephrotic syndrome · Lower extremity ar-
terial thrombosis · Antithrombin III deficiency
centration of 134mEq/l, a potassium concentration of
3.8mEq/l, a chloride concentration of 102mEq/l, a
blood urea nitrogen concentration of 23.1mg/dl, a crea-
tinine concentration of 1.3mg/dl, a serum total protein
concentration of 3.9g/dl, an albumin concentration of
1
.5g/dl, a total cholesterol concentration of 420mg/dl,
and a triglyceride concentration of 508mg/dl. The co-
agulation profile showed a fibrinogen concentration
of 879mg/dl, antithrombin III value of 9.5%, and pro-
Reprint requests to: M. Nishimura
Received: April 5, 1999 / Accepted: January 7, 2000

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M. Nishimura et al.: Arterial Thrombosis in Nephrotic Syndrome
Fig. 1. Arteriogram of the right
lower extremity showing a complete
occlusion of the deep femoral artery
(left) and popliteal artery (right)
thrombin time of 10.5s. Under the diagnosis of acute
right lower extremity arterial occlusion, right lower ex-
tremity arteriography was performed after the adminis-
tration of urokinase and heparin. A complete occlusion
of the right deep femoral artery and popliteal artery was
observed with a filling defect in the common femoral
artery (Fig. 1). Four hours after admission, a thrombec-
tomy was performed through the right common fe-
moral artery under general anesthesia. We advanced a
Fogarty catheter beyond the popliteal artery and trifur-
cation, and also advanced it to the deep femoral artery.
A large amount of the thrombus was extracted. A good
distal arterial flow was reestablished and 1000 units
of antithrombin III were given intravenously. An arte-
rial infusion catheter was inserted into the superficial
femoral artery. The infusion of 10000 units of heparin,
Table 1. Laboratory data on admission and at the time of
discharge
Admission
Discharge
TP (g/dl)
Alb (g/dl)
3.9
1.5
5.3
3.6
T-Cho (mg/dl)
TG (mg/dl)
U-P (g/day)
PT (s)
Fib (mg/dl)
FDP (µg/ml)
AT III (%)
420
508
16
10.5
879
16.5
9.5
251
309
0.1
13.0
368
7.0
111.4
TP, total protein; Alb, albumin; T-Cho, total cholesterol; TG, trigly-
ceride; U-P, urinary protein loss; PT, prothrombin time; Fib, fibrino-
gen; FDP, fibrin degradation product; AT III, antithrombin III
2
40000 units of urokinase, and 10µg of prostaglandin E1
per day was started intraoperatively and continued for
week. As anticoagulant therapy, warfarin (5mg/day)
phritis. He was discharged 3 months later without any
recurrence of thrombosis. Table 1 shows the laboratory
data on admission and at discharge.
1
and aspirin (81mg/day) were administered. An urinary
analysis showed 16g/day protein loss. Prednisolone
therapy was also started with the diagnosis of nephrotic
syndrome. Although enhanced computed tomography
showed an inferior vena cava thrombus, perfusion scin-
tigraphy showed no evidence of pulmonary embolism.
Two weeks later, because no remission in the urinary
protein and serum albumin levels was observed, steroid
pulse therapy (methylprednisolone 1g/day for 3 days)
was prescribed. Thereafter, the patient’s urinary pro-
tein level decreased to less than 0.1g/day and the serum
albumin level was 3.5g/dl. A renal biopsy revealed his-
tologic evidence of minimal change of glomerulone-
Discussion
Thrombotic complications in the venous system in
nephrotic syndrome have been widely reported. Arte-
rial occlusion is rare and has been reported to occur
in the aortic, renal, coronary, mesenteric, axillary, bra-
chial, carotid, middle celebral, ophthalmic, and femoral
arteries. These complications have been recognized as
sequelae of a hypercoagulable state due to the following
factors: (1) altered levels of coagulation factors, (2)
platelet dysfunction, and (3) increased viscosity of the

M. Nishimura et al.: Arterial Thrombosis in Nephrotic Syndrome
665
Table 2. Reported cases of lower extremity arterial thrombosis in adult cases of neph-
rotic syndrome
Case;
First author
Age
Prior
Serum
Renal
Ref.
(years)/sex treatment albumin (g/dl) histology
Outcome
1
2
3
4
5
6
7
. Mukherjee4
24/M
34/M
40/M
25/M
23/M
29/M
39/M
S
D
0.65
—
1.5
0.92
0.7
1.5
1.5
PGN
RAKA
BBKA
RAKA
Recovered
Died
Recovered
Recovered
5
. Patel
FPGN
PGN
PGN
MCGN
MCGN
MCGN
. Nitatori6
S/D
S/D
None
S
6
. Nitatori
7
. Parag
. Khatri8
. Present case
None
PGN, proliferative glomerulonephritis; FPGN, focal proliferative GN; MCGN, minimal change
GN; RAKA, right above-knee amputation; BBKA, bilateral below-knee amputation; S, steroids;
D, diuretics
blood. The mechanism of hypercoagulability, however,
has not yet been clearly elucidated. A reduction in low
molecular weight coagulation factors (XI, XII) results
from an increased loss in the urine, so that levels of high
molecular weight factors (V, VII, VIII, IX, X, XIII)
become elevated as a result of increased protein syn-
thesis. Notably, an elevation in the fibrinogen level is a
significant abnormality in nephrotic syndrome and has
been shown to considerably alter the plasma viscosity.
Antithrombin III, an important anticoagulant factor,
has a molecular weight similar to that of albumin and is
lost in much the same manner. There is also a significant
positive correlation between the serum levels of anti-
thrombin III and albumin. Low levels of antithrombin
III have been shown to occur in as many as 80% of
patients with nephrosis.1 Various other conditions
associated with nephrotic syndrome, including plasma
lipid abnormalities, hypovolemia with hypoalbumin-
emia, hypertension, circulating immune complexes, and
susceptibility to infection, are also considered to be fac-
tors contributing to the hypercoagulable state in neph-
rotic syndrome. Recently, a deficiency in free protein S
has also been implicated as a contributing factor in
Anticoagulation therapy is essential to prevent throm-
bosis, to improve the outcome, and to prevent progres-
sive glomerular mesangial fibrosis. Though Nitatori
6
et al. recommend long-term heparin therapy, heparin
may be ineffective for the treatment of antithrombin III
deficiency in nephrotic syndrome, because the mecha-
nism of heparin is the enhancement of the antithrombin
III activity. However, the extent of antithrombin III
deficiency in nephrosis is usually such that substantial
heparin resistance is not encountered.
Therefore, if extremely low levels of antithrombin III
are documented, operative treatment should be accom-
panied by the administration of antithrombin III so that
adequate anticoagulation can be achieved with heparin.
It is also necessary to closely monitor the occurrence
and recurrence of thrombosis when steroids are admin-
istered because steroids tend to worsen the preexisting
tendency of the blood to coagulate.
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