J Vet Intern Med 1999;13:382–385
Digital Arterial Thrombosis in a Septicemic Foal
Lisa J. Forrest, A. James Cooley, and Benjamin J. Darien
A 3-day-old Quarter Horse filly presented to the Veteri-
nary Medical Teaching Hospital at the University of
Wisconsin for weakness and recumbency since birth. The
filly was born full term and without complication, although
the mare had a previous history of having had a foal that
died of septicemia. Upon admission, the foal was recum-
bent and appeared emaciated. On physical examination the
oral mucosa was tacky and hyperemic, with abrasions and
a capillary refill time of 3 seconds. Additionally, bilateral
entropion, uveitis, and corneal ulcers were noted. Increased
respiratory effort was detected and all 4 limbs had marked
edema from the carpus or hock distally. Immunoglobulin
G was quantified using a latex agglutination test (Indexx,
Westbrook, ME) and was $ 800 mg/dL. At the time of
admission blood was obtained for bacterial culture, a com-
plete blood count, and determination of serum glucose,
electrolytes, creatinine, total protein, and albumin concen-
tration. The foal was hypoalbuminemic (2 g/dL, reference
range 2.8–3.7 g/dL), hyperbilirubinemic (8.2 mg/dL, ref-
erence range 0.5–3.9g/dL), and had a neutrophilic leuko-
cytosis with a left shift (12,100/mL white cells, reference
range 5,100–10,100/mL; 7,986 segmented neutrophils/mL,
reference range 3,210–8,580/mL; and 2,420 band neutro-
phils/mL, reference range ,50/mL).1,2 An increased inter-
stitial pattern in the caudal dorsal lung and a patchy alveolar
pattern ventrally was noted on thoracic radiographs. Al-
though the interstitial changes in the dorsal lung field were
consistent with hematogenous bacterial pneumonia, the
ventral changes were suggestive of an inhalation or aspi-
ration process. The initial problem list included pulmonary
disease, hyperbilirubinemia, hypoalbuminemia, hematolog-
ic left shift, entropion, uveitis, corneal ulcers, and weak-
ness. Based on the signalment, history, and clinical and
laboratory findings, presumptive diagnoses of septicemia
and pneumonia were made.
Initial therapy included polyionic fluids, flunixin meg-
lumine (0.25 mg/kg IV q8h), systemic antibiotics (amika-
cin, 15 mg/kg IV q24h and ampicillin, 20 mg/kg IV q6h),
sucralfate (1 g PO q6h), cimetidine (300 mg PO q6h), and
a diuretic to reduce limb edema (furosemide, 1 mg/kg IV
q12h). Ocular therapy consisted of topical atropine and an-
tibiotics (tobramycin and cefazolin, hourly, OU). Hypopro-
teinemia was treated with administration of 2 L of equine
plasma (Lake Immunogenetics, Inc, Ontario, NY). The ex-
From the Departments of Surgical Sciences (Forrest), Pathobiol-
ogical Sciences (Cooley), and Medical Sciences (Darien), School of
Veterinary Medicine, University of Wisconsin, Madison, WI.
Reprint requests: Lisa J. Forrest, VMD, Department of Surgical Sci-
ences, School of Veterinary Medicine, University of Wisconsin, 2015
Linden Drive West, Madison, WI 53706; e-mail: FORRESTL@SVM.
VETMED.WISC.EDU.
Received July 22, 1998; Revised November 13, 1998; Accepted Jan-
uary 13, 1999.
Copyright q 1999 by the American College of Veterinary Internal
Medicine
0891-6640/99/1304-0016/$3.00/0
tremities were wrapped with sheet cotton to alleviate ede-
ma. Oral feeding was discontinued and parenteral nutrition
begun 1 day after admission because of persistent abdom-
inal distention and gastric reflux.
After 3 days of therapy the foal was standing and tol-
erating oral feeding. Edema had decreased markedly in the
right forelimb and slightly in the right hindlimb and left
fore, but the left hindlimb remained edematous and had
become cool on palpation. At this same time, the white
blood cell count returned to the normal range, but there
was a persistent left shift (1,771/mL bands) and a mild
thrombocytopenia determined from a citrated sample
(98,000/mL, reference range 120,000–240,000/mL).1,2
Blood cultures were positive for Actinobacillus suis infec-
tion, confirming bacteremia. The antibiotic regimen was not
altered. The coldness in the left hindlimb advanced to the
metatarsal area by day 4. A coagulation profile was sub-
mitted because of the likelihood of systemic hypercoagu-
lation and presence of thromboemboli. In this patient, ac-
tivated partial thromboplastin time (APTT, 42.2 seconds,
reference range 31.2–46.6 seconds), and prothrombin time
(PT, 10.6 seconds, reference range 7–19 seconds) were
within the normal reference range established for foals.
However, fibrinogen (470 mg/dL, reference range 150–300
mg/dL) was increased (consistent with systemic inflam-
mation or infection), and plasma antithrombin III (AT III)
activity (60%, reference range 70–105% AT III activity of
pooled normal foal plasma) was decreased. Because the
foal had previously received 2 L of plasma, the transfusion
of coagulation proteins may have contributed to the nor-
malization of clotting time values and may have accelerated
the consumption of AT III by providing substrate (clotting
proteins) to generate thrombin. The abnormally low AT III
activity was consistent with hypercoagulation and increased
risk of thromboembolization.
Thromboembolism was suspected and digital subtraction
angiography (DSA) was performed on day 5 to evaluate
the digital arterial circulation. Although only the left hind-
limb was clinically abnormal, DSA was performed in both
hindlimbs and the right forelimb because a normal angio-
gram for comparative purposes was important to diagnose
thromboembolism.
After anesthetic induction, 20-gauge, 1.5-inch catheters
were placed in the dorsal metatarsal arteries of the hind-
limbs and the lateral digital artery of the right forelimb. For
each limb approximately 10 mL of positive contrast me-
dium was used and injected as a bolus. The left hindlimb,
which had persistent edema and was cool to the touch, had
no angiographic evidence of perfusion beyond the middle
of the 1st phalanx (Fig 1). The right hindlimb, which was
thought to be normal, had no angiographic evidence of ar-
terial circulation distal to the middle phalanx (Fig 2). In
search for a normal distal extremity angiogram, the right
forelimb was imaged and had normal arterial perfusion (Fig
3).3
Thrombolytic therapy with urokinase (UK, Abbokinase,
 Digital Arterial Thrombosis in a Septicemic Foal
Fig 1. (A) The lateral image of the left hindlimb at the level of the
metatarsal phalangeal joint (large arrowhead) before contrast injection;
this is the mask that is subtracted from subsequent images after con-
trast medium injection. (B) The same anatomical area after angiogra-
phy. Note that contrast medium extends only to the level of the dorsal
artery of the proximal phalanx, a branch of the digital artery (small
arrowhead). The large arrowhead is at the dorsal aspect of the meta-
tarsal phalangeal joint.
Abbott Laboratories, Chicago, IL) was administered as a
continuous infusion in the right hindlimb, as it was the least
affected angiographically, at a rate of 4,000 U/minute for
60 minutes. DSA was repeated before treatment and at 15-
minute intervals during treatment. Reperfusion was not
documented. Because of the poor prognosis of ischemic
necrosis to both hind feet, the owners elected euthanasia.
At necropsy, thrombosis of palmar and plantar digital
arteries and avascular necrosis of the distal limbs were pre-
sent in both hindlimbs and the left forelimb. The right fore-
limb, which had a normal digital angiogram, was normal
at postmortem. Necrotizing pneumonia was diagnosed and
383
Fig 2. (A) The lateral image of the right hindlimb at the level of the
distal interphalangeal joint (large arrowhead) before contrast injection;
this is the mask that is subtracted from subsequent images after con-
trast medium injection. (B) The same anatomical area after angiogra-
phy. Note that contrast medium extends only to the level of the middle
phalanx (small arrowhead). The large arrowhead is at the dorsal aspect
of the distal interphalangeal joint.
Escherichia coli and Enterococcus species were cultured.
Cranioventral foci of pulmonary consolidation and necrosis
contained numerous bacterial colonies.
Neonatal veterinary patients with septicemia have he-
mostatic defects and alterations in coagulation profiles.1,4–7
In the foal reported herein, a diagnosis of septicemia and
hypercoagulation was supported by positive blood cultures,
decreased plasma AT III activity, and thrombocytopenia.
Septicemia more than likely was the cause of the coagu-
lopathy and subsequent thromboembolization. The location
of the thrombi in the peripheral digital arteries, diagnosed
angiographically and confirmed at necropsy, was likely in-
fluenced by the limb edema. In this foal, the distal extrem-
ities may have been compromised as a result of decreased
384 Forrest, Cooley, and Darien
Fig 3. (A) The lateral image of the right front limb at the level of
the distal interphalangeal joint (large arrowhead) before contrast in-
jection; this is the mask that is subtracted from subsequent images
after contrast medium injection. (B) The same anatomical area after
angiography; this represents normal arterial perfusion of the equine
foot. The large arrowhead is at the dorsal aspect of the distal inter-
phalangeal joint. The small arrowheads indicate the ramification of the
branches of the dorsal artery of the distal phalanx in the corium of
the hoof wall. The asterisk (*) is on the middle phalanx and is just
ventral to the dorsal artery of the middle phalanx, a branch of the
digital artery.
perfusion and the compressive effect the edema had on ve-
nous return. Therefore, alteration in blood coagulation fac-
tors, abnormalities in blood flow, and endothelial damage
provided the foundation for this thromboembolic disease.
During sepsis, bacteria and bacterial products are respon-
sible for an increase in circulating endotoxin that induces
the biosynthesis of cytokines and chemokines that amplify
the inflammatory process.1,5 Additionally, endotoxin re-
leased from gram-negative bacteria (eg, A. suis), and cy-
tokines are capable of activating the coagulation cascade
through the generation of macrophage and endothelial cell-
derived tissue factor.4,5 This in turn can result in a hyper-
coagulative state where endothelial cell damage, sticky leu-
kocytes, and enhanced platelet reactivity cause thromboem-
boli formation.5–7 The consequence of tissue ischemia and
necrosis potentiates a circuitous pathway that, if not cor-
rected, can result in disseminated intravascular coagulation
(DIC).
Vasculitis of the peripheral limbs, resulting from system-
ic viral and bacterial infections such as equine influenza,
equine viral arteritis, and Streptococcus species infections,
is believed to be immunologically mediated.8 However, vas-
culitis can also occur secondary to pneumonia, broncho-
pneumonia, and cholangiohepatitis. Because endotoxin can
induce endothelial cell injury and A. suis pneumonia has
been associated with necrotizing pneumonia and thrombo-
sis,9 it is likely that their interaction was responsible, to
some degree, in the pathogenesis of the vasculitis and sub-
sequent limb edema observed in this foal.
In this patient, the plasma AT III activity was markedly
reduced, whereas the APTT and PT values were within the
reference intervals. The normal clotting times could be due
to the lack of sensitivity of global clotting times in pre-
dicting coagulopathies in patients with DIC.1,4 Alternative-
ly, the normal results could be due to the administration of
plasma, which also has clotting proteins and AT III. Ad-
ministration of plasma to hypercoagulable patients can re-
sult in an amplification of the underlying coagulopathy be-
cause plasma is a rich source of substrate (clotting pro-
teins). Amplification of the hypercoagulable condition re-
sults in the continual consumption of AT III, thus
potentiating a prothrombotic state.6,7
Thrombolytic therapy is either delivered systemically (in-
travenously)10 or regionally (intra-arterial), with the latter
technique resulting in better clot resolution in humans and
small animals.11,12 Local (regional) thrombolytic infusions
are most effective in peripheral or coronary arterial diseases
and require substantially less drug than used for systemic
administration. Instead of a loading (systemic) dose, most
protocols for regional therapy utilize a continuous infusion
of 1,000,000 IU for 2–72 hours.13,14 Additionally, because
regional treatment is designed to achieve thrombolysis in
the immediate vicinity of the thrombus, the risk of produc-
ing a lytic state (increased systemic plasmin activity) and
potential hemorrhagic complications is reduced. In the foal
reported herein, regional therapy was used to deliver
240,000 U/hour. Unfortunately, clot resolution was not
achieved. This may be related to chronicity or severity of
the thrombus, or length of time required for thrombolysis,
which can take 24–48 hours.13,15
The success of thrombolytic therapy in arterial occlusive
disease depends on the agent’s ability to interact with and
activate the fibrinolytic system. UK initiates the conversion
of plasminogen to plasmin, leading to thrombolysis. Ther-
apy can fail for a number of reasons including poor patient
selection, inadequate fibrinolytic response, inadequate treat-
ment length, and failure of the thrombolytic agent to reach
the thrombus.12–14 Patients with extensive, occlusive throm-
bosis or long-standing thrombi are more likely to fail ther-
 Digital Arterial Thrombosis in a Septicemic Foal
apy, especially if agents are given systemically rather than
being regionally directed. Although regional therapy was
used in this foal, the catheter was several centimeters prox-
imal to the thrombus site. Successful lysis is linked to the
amount of plasminogen bound to fibrin within the throm-
bus, which decreases with time.13,15,16 Incomplete throm-
bolysis can be due to inadequate plasmin production and to
intravenous therapy delivery where plasminogen activators
are exposed to inhibitors that neutralize their activity. In
human medicine, thrombolytic therapy may continue for as
long as 24 hours. In the foal reported herein, thrombolytic
therapy was terminated after 60 minutes.
Thromboemboli are diagnosed with DSA,7,11,17 angiog-
raphy,11,17,18 and nuclear medicine techniques,17,19 or sus-
pected with clinical signs of septicemia and abnormalities
of the extremities.20 DSA was used in this patient to diag-
nose thromboembolism and to monitor therapeutic attempts
at clot resolution. This imaging technique not only con-
firmed suspected thromboembolism in the left hindlimb, but
also diagnosed thromboembolism in 1 of the 2 other limbs
imaged. Diagnosis of occult thromboembolism is an im-
portant prognostic factor in septic patients. Suspicion of
thromboembolism in 1 extremity should lead to imaging of
other limbs in order to evaluate the potential for occult
thromboembolism, particularly in septicemic patients.
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