This retrospective study examined 38 critically ill dogs receiving dalteparin anticoagulation therapy monitored with anti-Xa assays. The most common underlying diseases were hematological (45%) and protein losing (18%) diseases. Pretreatment TEG found 34/35 dogs were hypercoagulable. While dalteparin was generally well tolerated, reliably achieving the target anti-Xa activity range was inconsistent, with dogs having higher pretreatment G values on TEG less likely to achieve the target range. Serial anti-Xa monitoring allowed for dose adjustments but target ranges were still inconsistently reached. Guidelines for dose adjustment based on anti-Xa levels may be needed.

1. Retrospective Study Journal of Veterinary Emergency and Critical Care 24(4) 2014, pp 421–428
doi: 10.1111/vec.12206
Clinical experience of anti-Xa monitoring
in critically ill dogs receiving dalteparin
Alex M. Lynch, BVSc(Hons); Armelle M. deLaforcade, DVM, DACVECC and Claire R. Sharp, BSc
BVMS(Hons), MS, DACVECC
Abstract
Objectives – To describe a population of critically ill dogs receiving dalteparin monitored with an anti-Xa assay,
to assess the potential utility of serial monitoring, and to investigate the association between pre-treatment
thromboelastography (TEG) and the ability to achieve targeted anti-Xa activity.
Design – Descriptive retrospective study.
Setting – Veterinary teaching hospital.
Animals – Thirty-eight client-owned dogs receiving dalteparin and monitored with an anti-Xa assay.
Interventions – None.
Measurements and Main Results – Medical records were retrospectively reviewed for signalment, underlying
disease, clinicopathological data, occurrence of thromboembolic events, complications, and outcome. Thirty-
eight dogs receiving dalteparin were monitored with an anti-Xa assay. Diseases included hematological disease,
protein-losing disease, neoplastic disease, and septic processes. Pretreatment hypercoagulability was present in
34/35 dogs by assessment of TEG. Five cases of thromboembolism were confirmed prior to starting treatment
and 4 cases occurred during hospitalization. Bleeding complications were rare (3/38) and 29/38 dogs survived
to discharge. Interpretation of the anti-Xa assay allowed for dose adjustment although reliable achievement of
target anti-Xa activity was not demonstrated. Dogs with higher G values on pretreatment TEG were significantly
less likely to achieve the target anti-Xa activity (ie, be above or below the target range).
Conclusions – Dalteparin was well tolerated in a heterogeneous population of dogs. However, dose adjustment
in response to anti-Xa activity interpretation inconsistently resulted in subsequent attainment of the target
anti-Xa range. Development of guidelines may be warranted to more consistently achieve the target range.
Dogs that appear more hypercoagulable on pre-treatment TEG may require closer monitoring and greater dose
adjustment to achieve the target anti-Xa range.
(J Vet Emerg Crit Care 2014; 24(4): 421–428) doi: 10.1111/vec.12206
Keywords: anticoagulation, canine, low molecular weight heparin, thromboelastography, canine
Introduction
Thromboembolic disease represents a significant but
under-recognized cause of morbidity and mortality in
critically ill people and animals.1–5
Numerous disease
processes have previously been associated with hyper-
coagulability and hence the potential for developing
From the Section of Emergency and Critical Care, Department of Clinical
Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton,
MA 01536.
The authors declare no conflict of interests.
Off prints will not be available from the authors.
Presented in part at the American College of Veterinary Internal Medicine
(ACVIM) Forum, New Orleans, LA, USA, May 2012.
Address correspondence and offprint requests to
Dr. Armelle M. deLaforcade, The Section of Emergency and Criti-
cal Care, Department of Clinical Sciences, Tufts Cummings School of
Veterinary Medicine, North Grafton, MA 01536, USA. Email: Armelle.
delaforcade@tufts.edu
Submitted January 16, 2013; Accepted May 26, 2014.
Abbreviations
IMHA immune mediated hemolytic anemia
TEG thromboelastography
CT computed tomography
LMWH low molecular weight heparin
PLN protein losing nephropathy
UFH unfractionated heparin
thromboembolic complications in animals.3,4,6–9
Conse-
quently, there is increasing interest in the use of anticoag-
ulants for the treatment and prevention of thromboem-
bolism in veterinary medicine.
Low molecular weight heparin (LMWH) (eg,
dalteparin) is a commonly employed method of throm-
boprophylaxis in human medicine. In comparison to
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Veterinary Emergency and Critical Care Society 2014 421

2. A. M. Lynch et al.
unfractionated heparin (UFH), it has a number of per-
ceived advantages in people. These include more pre-
dictable pharmacokinetics making routine monitoring
obsolete in most individuals, a longer duration of action
and in some circumstances fewer adverse effects.10–13
Low molecular weight heparin is used with increasing
frequency in veterinary medicine although clear advan-
tages over UFH have not been demonstrated in dogs.14
The anticoagulant effect associated with LMWH ad-
ministration occurs primarily via augmentation of the
inhibitory effect of antithrombin on factor Xa. How-
ever, alternative mechanisms for anticoagulation over
and above that of factor Xa inhibition have also been
suggested.15
LMWH therapy can be monitored in dogs
by use of a chromogenic anti-Xa assay (specific for the
particular LMWH used), which is commercially avail-
able although its availability is not widespread. While
the target therapeutic anti-Xa activity for dalteparin (0.5–
1.0 U/mL) is extrapolated from human data,16
both ar-
terial and venous models of thrombosis in dogs have
demonstrated antithrombotic effects of dalteparin at
analogous anti-Xa activity.17,18
The target range corre-
sponds to peak plasma anti-Xa activity and is derived
from studies involving normal dogs. In these dogs peak
activity was reported as being achieved 2–4 hours after
subcutaneous dalteparin administration.19
However, the
pharmacokinetics of dalteparin in dogs predisposed to
thromboembolic disease is not known and may differ
from normal dogs. Likewise, it is unclear if attainment
of anti-Xa activity corresponds to reduced risk of throm-
boembolism in dogs. No data currently exist regarding
guidelines for dose adjustment of LMWH based on in-
terpretation of the anti-Xa result. Likewise, in dogs it is
unclear if specific patients receiving LMWH would ben-
efit from serial anti-Xa monitoring.
Traditional tests of hemostasis (eg, platelet count,
prothrombin time, activated partial thromboplas-
tin time) are established methods of detecting
hypocoagulability.20
However, these methods do not
enable detection of hypercoagulability and hence its
potential contribution toward the increased risk of
thromboembolism. Viscoelastic hemostatic tests such
as thromboelastography (TEG) give an overall repre-
sentation of clot formation and allow for detection of
hypercoagulability.21
As such, TEG has become a use-
ful addition to the hemostatic tests available for both
clinical and research use in dogs particularly for disease
associated with thromboembolic risk.3,6–8,20–24
The aim of this study was to retrospectively describe
a population of critically ill dogs receiving dalteparin
monitored with an anti-Xa assay and specifically assess
how many dogs achieved the target anti-Xa range for
dalteparin. Additional aims were to assess the potential
utility of serial anti-Xa monitoring in this patient popu-
lation at risk of thromboembolic disease, and to inves-
tigate the association between pretreatment TEG results
and the ability to achieve targeted anti-Xa levels.
Materials and Methods
The medical records of dogs receiving dalteparina
that
were monitored with at least one anti-Xa assay between
September 2010 and March 2012 were retrospectively re-
viewed. This timeframe coincided with the introduction
of an electronic laboratory database enabling identifi-
cation of patients monitored by anti-Xa activity. Dogs
receiving dalteparin monitored with at least one anti-Xa
assay were eligible for inclusion. Dogs receiving LMWH
other than dalteparin or UFH were excluded from
analysis.
Information collected from the medical record in-
cluded signalment, underlying disease process, clin-
icopathological data, documentation of confirmed
thromboembolic events before starting anticoagula-
tion, adverse effects during hospitalization, develop-
ment of thromboembolic complications while receiving
dalteparin, concurrent medications, whether single or se-
rial anti-Xa monitoring was performed, and survival to
discharge. In dogs in which TEG was performed, hyper-
coagulability was determined by interpretation of the
G value. The number of hours following administra-
tion of dalteparin at which point blood was collected for
the anti-Xa assay was recorded. For dogs serially moni-
tored with anti-Xa activity levels, dose adjustment was
recorded along with the reason for adjustment.
Laboratory testing
The anti-Xa assay and kaolin-activated TEG were per-
formed at the Clinical Sciences Coagulation Laboratory
at the authors’ institution. All other laboratory tests were
performed at the Clinical Pathology Laboratory at the
same center. A commercially available chromogenic anti-
Xa assayb
was used. Whole blood was collected by care-
ful direct venipuncture of either a central or peripheral
vein, using minimum stasis, and a 21-G needle attached
to a 5 mL syringe. For coagulation assays, 1.8 mL of
whole blood was immediately transferred to a 2 mL 3.8%
sodium citrate plastic tube to provide a 1:9 ratio of cit-
rate to whole blood. TEG was performed first as previ-
ously described.3
The remaining sample was then cen-
trifuged at 4°C, consistent with previous publications,19
for 10 minutes at 1,620 × g before harvesting the platelet
poor plasma. The anti-Xa assay was calibrated using a
3 point dilution standard curve with dalteparina
using
stored normal canine plasma. The stored plasma used
represented pooled plasma from healthy canine blood
donors, owned by staff at the authors’ institution, that
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3. Anti-Xa monitoring in dogs receiving dalteparin
were deemed healthy based on annual physical exami-
nation, routine laboratory testing and screening for infec-
tious disease endemic to the area. A minimum volume
of 500 ␮L of the plasma was then placed on the ACL
Elitec
according to established assay protocols in order
to obtain anti-Xa activity. For determination of PCV and
platelet count, 1 mL of whole blood was immediately
transferred to a plastic tube containing 7.5% potassium
EDTA.
Statistical Methods
Normality was assessed via the Kolmogorov-Smirnov
test. Normally distributed data are presented as mean ±
standard deviation and non-normally distributed data
are presented as median (range). Descriptive statistics
were used to summarize patient and clinicopathological
characteristics. An ROC curve analysis was applied to
compare pretreatment TEG variables with the likelihood
of being in the anti-Xa range. Statistical significance was
set at P 0.05.
Results
Thirty-eight dogs, of the following breeds, were eligi-
ble for inclusion: 6 mix breeds, 5 Golden Retrievers, 4
Labrador Retrievers, 2 Standard Poodles, 2 Beagles, 2
Shetland Sheepdogs, and 1 each of Pug, Yorkshire Ter-
rier, Rottweiler, Cocker Spaniel, Miniature Schnauzer,
Jack Russell Terrier, West Highland White Terrier,
Chihuahua, English Springer Spaniel, German Short
Haired Pointer, Samoyed, Bichon Frise, Doberman, Ger-
man Shepherd Dog, Greyhound, Dachshund, and Bor-
zoi. Of these dogs, 21 were female (17 spayed) and 17
were male (12 neutered). The median age of the dogs
was 7.3 years (1–14 years) and the median bodyweight
was 23.2 kg (4–40 kg). A variety of underlying dis-
ease processes were represented in this study population
(Table 1). The most common reason for anticoagulation
was hematological disease (17/38), specifically immune
mediated hemolytic anemia (IMHA) in 16 dogs.
The PCV was available in 35 dogs at the time of ad-
mission. The median PCV was 27% (5–61%) (reference
interval 39–55%). Thirty-one dogs were anemic; 15 dogs
were severely anemic (PCV 19%), 10 dogs were mod-
erately anemic (PCV between 20 and 29%), and 6 dogs
had a mild anemia (PCV between 30 and 39%). Platelet
count was available in 32 dogs at the time of admis-
sion. The median platelet count was 221 × 109
/L [221 ×
103
/␮L] (14–744 × 109
/L [14–744 × 103
/␮L]) (reference
interval 180–525 × 109
/L [180–525 × 103
/␮L]). Fourteen
dogs were thrombocytopenic; 3 dogs had severe throm-
bocytopenia ( 50 × 109
/L [50 × 103
/␮L), 5 dogs had
moderate thrombocytopenia (50–100 × 109
/L [50–100 ×
Table 1: Underlying disease states in a population of dogs re-
ceiving dalteparin
General disease Specific
category disease Number (%)
Hematological disease 17 (45)
IMHA 16 (42)
PRCA 1 (3)
Protein losing disease 7 (18)
PLN 4 (10)
PLE 3 (8)
Neoplastic disease 5 (13)
Splenic mass 2 (5)
Lymphoma 1 (3)
Myeloid leukemia 1 (3)
Right atrial mass 1 (3)
Miscellaneous 5 (13)
Chylothorax 1 (3)
Gall bladder mucocoele 1 (3)
Polytrauma 1 (3)
Pancreatitis/diabetes mellitus 1 (3)
Immune-mediated myositis 1 (3)
Septic process 4 (10)
Infective endocarditis 2 (5)
Abdominal sepsis 1 (3)
Pyothorax 1 (3)
IMHA, immune-mediated hemolytic anemia; PRCA, pure red cell aplasia;
PLN, protein losing nephropathy; PLE, protein losing enteropathy
103
/␮L), and 6 dogs were mildly thrombocytopenic
(100–180 × 109
/L [100–180 × 103
/␮L]).
Thromboelastography was performed in 35 dogs. The
3 dogs for which anticoagulation was instituted with-
out TEG being performed included one dog with pro-
tein losing enteropathy (PLE) with a low antithrombin
activity level. The remaining dogs were hospitalized for
septic peritonitis and vestibular signs, both of which had
thromboembolism confirmed by advanced imaging. The
results of baseline TEG variables are presented in Table 2
along with the association between these variables and
the likelihood of not attaining the target anti-Xa range.
Based upon interpretation of the G value, 34/35 dogs
were classified as hypercoagulable (G value 6.9 Kd/s)
on their initial TEG. There was a significant association
between increasing values of G and the likelihood of
not being in the therapeutic anti-Xa range (P = 0.038,
AUC = 0.70).
Prior to initiating anticoagulation, 5 dogs had con-
firmed thromboembolism. One dog with PLN presented
with paraplegia due to bilateral iliac arterial thrombo-
sis. The remaining 4 dogs had venous thromboembolism
confirmed by diagnostic imaging. In 3 dogs, pulmonary
thromboembolism was confirmed with CT angiography
and the other dog had neoplasia with disseminated ab-
dominal venous thromboemboli detected by ultrasonog-
raphy. Corticosteroids were initiated after performing
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4. A. M. Lynch et al.
Table 2: Baseline thromboelastrography variables and the association between these variables and the ability to achieve target anti-Xa
range
Significance of association between
variable and likelihood of being
TEG variable Mean ± SD Reference range out anti-Xa range
R (min) 4.34 ± 1.38 3–4 P 0.05
K (min) 1.35 ± 0.81 1–2 P 0.05
␣ (degrees) 70.76 ± 15.1 61–66 P 0.05
MA (mm) 71.62 ± 11.09 54–58 P 0.05
G (Kd/s) 14.86 ± 6.35 5.7–6.9 P = 0.038
TEG in 20 dogs during their hospitalization as part of
the treatment plan for their underlying disease. Thirty
dogs also received concurrent platelet inhibition with
oral clopidogrel.
The dose and dosing frequency of dalteparin was at
the discretion of the primary clinician. Mean initial start-
ing dose of dalteparin was 150 U/kg SQ. Most patients
received dalteparin twice daily (15/38), although three
times daily (14/38) and four times daily (1/38) were also
recorded. The exact timing of blood sampling for the
anti-Xa activity could only be estimated from retrospec-
tive review of medical records. It is standard practice in
the authors’ hospital to aim for blood sampling at 2 hours
postadministration of dalteparin to reflect peak activity.
However, from the review of medical records, blood sam-
pling was performed between 2 and 4 hours postdosage.
From initial anti-Xa assay results, 15/38 dogs achieved
the target range, 14/38 dogs were above range (7 receiv-
ing twice daily dalteparin and 7 receiving three times
daily dosing), and 9/38 dogs were below range (6 on
twice daily dosing and 3 on three times daily dosing).
Serial anti-Xa monitoring was performed in 25 dogs.
From review of the medical records, it was evident that
dalteparin dose adjustments were made in 19 of these
25 dogs, 16 of which were based on interpretation of
the preceding anti-Xa activity. In the remaining 3 dogs,
dose adjustment occurred at the discretion of the attend-
ing clinician, due to concerns of adverse bleeding effects
potentially attributable to dalteparin administration. In
those dogs in which anti-Xa interpretation guided dose
adjustment, 8/16 dogs had a lower dose of dalteparin
given at the same frequency. In 6/16 dogs, the same dose
was given less frequently and in the remaining 2 dogs
a higher dose was given at the same frequency. Follow-
ing dose adjustment based on interpretation of anti-Xa,
ultimately 21/25 dogs achieved or exceeded the target
range. Comparison of first and last anti-Xa activity are
represented in Table 3. Following dose adjustment, no
dogs that were originally below range remained below
range. However, 4 dogs originally above range remained
above range.The median cost of dalteparin was $352.99
USD ($59.16–$1466.91 USD) for the dogs in the study.
New thromboembolic events were documented in 4
dogs during their hospitalization period while receiving
dalteparin. Three dogs developed an acute onset of res-
piratory difficulty clinically concerning for pulmonary
thromboembolism. Two were confirmed with CT an-
giography and there was a high index of suspicion in the
other dog from interpretation of arterial blood gases. An-
other dog had multiple pulmonary thromboemboli and
a cranial vena caval thrombus confirmed with advanced
imaging following development of facial edema and
pleural effusion in the postoperative period after surgery
for septic peritonitis. All 4 dogs that developed throm-
boembolic complications had attained the target anti-
Xa range between 1–3 days before the thromboembolic
event. The anti-Xa activity at the time of development
of clinical signs of thromboembolism was however un-
available. All dogs that developed new thromboembolic
complications were receiving clopidogrel concurrently.
Bleeding complications occurred in 3 dogs receiv-
ing dalteparin. In 2 dogs, minor subcutaneous hemor-
rhage associated with the injection site was reported and
dalteparin was discontinued in these dogs. One of these
dogs had PLN and moderate thrombocytopenia (78 ×
109
/L [78 × 103
/␮L) at the time of bleeding and was
not receiving a platelet inhibitor. It is possible, although
unlikely, that the bleeding noted in this dog was associ-
ated with thrombocytopenia. Another dog had protein
losing enteropathy with evidence of thrombocytosis (666
× 109
/L [666 × 103
/␮L]) and was receiving clopidogrel
in addition to dalteparin.
One dog had more significant hemorrhage, develop-
ing hemoperitoneum and cutaneous bleeding, due to
a dosing error resulting in an approximately 10 times
overdose of dalteparin. This dog received supportive
measures including fresh frozen plasma transfusion and
survived to discharge. This dog was mildly thrombo-
cytopenic (146 × 109
/L [146 × 103
/␮L]) at the time of
hemorrhage, which may have been due to consump-
tion, since no baseline platelet count was available for
this dog. This dog also received clopidogrel concur-
rently. Anti-Xa activity was unavailable at the time of
documenting the bleeding events; however, all dogs had
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5. Anti-Xa monitoring in dogs receiving dalteparin
Table 3: Comparison of first and last anti-Xa activity in a population of dogs receiving dalteparin
LAST ANTI-Xa VALUE (units/mL)
Below range (0.5) In range (0.5–1.0) Above range (1.0)
FIRST ANTI-Xa VALUE (units/mL)
Below range (0.5) 0 1 2
In range (0.5–1.0) 1 2 1
Above range (1.0) 2 3 4
Figure 1: Correlation between the thromboelastography-derived G value and likelihood of achieving desired anti-Xa range in popu-
lation of dogs receiving dalteparin.
attained the target anti-Xa range prior to these events.
Seven dogs were euthanized during their hospitalization
period due to clinical deterioration, while 2 dogs died
naturally. Ultimately, 29 dogs survived to discharge and
12 dogs continued to receive dalteparin at home, admin-
istered by their owners. Dalteparin was continued for an
additional 7 days in these dogs, with a tapering schedule
consisting of the same dose administered at a decreasing
frequency from twice daily (for 3 days) to once daily (for
the next 4 days).
Discussion
This study outlines the clinical experience gained at one
institution, where dogs receiving dalteparin were mon-
itored by means of an anti-Xa activity assay. Many of
the underlying diseases affecting this group of dogs re-
flect those conditions associated with hypercoagulabil-
ity previously described in the veterinary literature, par-
ticularly hematological disease, protein losing disease,
neoplasia, and septic processes.3,6–9
Some diseases af-
fecting these dogs are less commonly associated with
the use of anticoagulation. However, the authors re-
viewed the medical record of these dogs and agreed that
the administration of dalteparin in these cases based on
clinical presentation, diagnostic imaging findings, and
laboratory information was justifiable. This study
demonstrates that dalteparin was well tolerated in this
heterogeneous population of hospitalized dogs.
Previous reports regarding dalteparin use, at a dose
of 100 U/kg SQ twice daily in dogs, demonstrated dif-
ficulty in achieving target anti-Xa activity, indicating ei-
ther higher doses or more frequent administration are
required.14
In our study, the mean starting dose for dal-
teparin was 150 U/kg and dosing frequency was at the
discretion of the primary clinician. From the initial anti-
Xa assay results in our study, 15/38 dogs achieved the
target anti-Xa range and 14/38 dogs were above the
target range. Suboptimal dosing of anticoagulants may
be associated with reduced clinical efficacy;25
however,
there is a lack of information to guide dose adjustment
in those patients that do not achieve the target anti-Xa
range.
When the first and last anti-Xa activity was compared,
none of the dogs initially below range remained be-
low range following dose adjustment. However, 4 dogs
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6. A. M. Lynch et al.
initially above range remained above range. The method
by which dose adjustment occurred was chosen em-
pirically by the attending clinician, since no specific
guidelines for dose adjustment currently exist. This con-
sisted of either altering the dose of dalteparin (10/16) or
the frequency of administration (6/16). Although inter-
pretation of anti-Xa activity did allow for dose adjust-
ment, the consistency with which target anti-Xa activity
was achieved was poor. The retrospective nature of this
study precludes assessment of the optimal method by
which dose adjustment can be achieved, (ie, via chang-
ing dose administered or dosing frequency). Adjusting
doses of LMWH to ensure attainment of target anti-Xa
activity may be associated with improved clinical out-
come, since dogs with IMHA that received individually
adjusted doses of UFH based on anti-Xa interpretation
had a demonstrated survival benefit.26
In that study, a
nomogram was used to guide dose adjustment. The de-
velopment of similar guidelines for dalteparin warrants
further investigation, given the potential positive impact
this may have on clinical outcome.
Thromboelastography has become a commonly used
research and clinical tool in veterinary medicine
offering an unparalleled assessment of overall
hemostasis.3,4,6–9,22–24
From retrospective review of medi-
cal records, standardization of blood sampling technique
could not be accurately assessed. However, it is common
practice to perform minimally traumatic venipuncture
at the authors’ institution to help reduce the risk of pre-
analytical variation between samples.27
As in previous
studies, we used the G value or elastic shear modulus, a
mathematical manipulation of the MA, d
to assess over-
all hypercoagulability.4,23
Higher G values before initi-
ating treatment with dalteparin were significantly as-
sociated with an increased chance of not attaining the
target anti-Xa activity. The explanation for this associa-
tion is not immediately clear since this implies that dogs
that are more hypercoagulable (based on G value) are
less likely to achieve the target anti-Xa range. This rep-
resents both those patients that are relatively easier to
anticoagulate (ie, those above target range) and those
more difficult (ie, those remaining below range). Un-
fortunately, given the small number of dogs in this ret-
rospective study, insufficient numbers are available to
better statistically characterize the correlation between
risk of hypercoagulability and ability to attain the tar-
get range. The apparent association from these pilot
data however does warrant further investigation given
that pre-treatment TEG could help identify a subpopu-
lation of dogs that would benefit from closer therapeutic
monitoring.
Interpretation of MA and hence G in the face of ane-
mia has been discussed as a potential point of contention
in the clinical application of TEG.28
This is especially rel-
evant to this study since a large number of dogs (31/38)
receiving dalteparin were anemic, 16 of which had a PCV
below 19%. Lower red cell mass, which is a common find-
ing in critically ill dogs, may be associated with artefac-
tual hypercoagulability. In contrast, Greyhounds, with
a natural tendency for higher PCV, have hypocoagula-
ble TEG tracings.29,30
This finding appears in agreement
with the clinical observation of increased bleeding ten-
dency in this breed.29,30
Irrespective of the PCV, throm-
boembolism remains a real concern for both morbidity
and mortality in critically ill dogs, especially in dogs
with IMHA. However, assessment of thromboembolic
risk via interpretation of TEG values alone in anemic
dogs should be done so with caution.
The occurrence of hemorrhagic complications in this
patient population was low. In people, there is no con-
vincing evidence to suggest LMWH offers an advantage
over UFH in terms of bleeding risk.31
Minor subcuta-
neous hemorrhage was seen in 2 dogs but was clinically
insignificant. Both of these dogs were within the thera-
peutic anti-Xa range. Major bleeding was documented
in one dog that received an inadvertently excessive dose
of dalteparin. Four new cases of thromboembolism were
documented during the hospitalization period. Three of
these patients with IMHA developed respiratory diffi-
culty and were diagnosed with pulmonary thromboem-
bolism. These dogs all had anti-Xa activity in range at an
earlier point in their hospital stay but an anti-Xa activity
was unavailable for the dogs at the time of develop-
ing clinical signs of thromboembolism. Since dalteparin
has no inherent fibrinolytic properties, it is possible that
these dogs had occult thromboemboli prior to initiat-
ing dalteparin and therefore do not represent failure of
dalteparin efficacy. However, the possibility that dal-
teparin was ineffective in preventing new thromoem-
boli cannot be excluded given the retrospective nature
of this study. Further prospective studies are warranted
to assess whether attaining the target anti-Xa acitivity
is associated with a reduction in the development of
thromboembolism in dogs with naturally occurring dis-
ease and improved outcome. Overall survival to dis-
charge was 76.3% but follow up beyond discharge was
unavailable.
There are a number of limitations to this study, many
of which are related to the nature of the study being
small and retrospective. Given that the information was
derived from medical records, the completeness of these
records and the lack of standardization of treatment prac-
tices hinder clear interpretation of dalteparin usage in
this population. The heterogeneity of dose adjustment is
one limitation since the decision to alter dose or dosing
interval was made by the attending clinician in response
to the prior anti-Xa activity. Neither strategy was as-
sociated with accurate achievement of the target range
from this study. In response to this, a more standardized
approach of altering the subsequent dalteparin dose (eg,
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7. Anti-Xa monitoring in dogs receiving dalteparin
by altering the dose by 50 units/kg), rather than chang-
ing dosing interval in response to the preceding anti-Xa
result is currently being trialled at the authors’ hospital.
Prospective evaluation of the optimal method by which
dalteparin dose should be altered in response to anti-Xa
activity would be warranted. Another limitation of the
study is that the exact timing of blood sampling for the
anti-Xa activity was estimated. While the significance of
this inhomogeneity with respect to interpretation of the
anti-Xa activity is unclear, since peak activity is cited as
occurring between 2 and 4 hours in dogs,19
this incon-
sistency is considered a limitation of this retrospective
study.
Only pretreatment TEG was performed in these dogs.
In people, TEG has been investigated as a potential
method of monitoring LMWH therapy and may offer
some advantages over anti-Xa assessment.32
Two stud-
ies in normal dogs have investigated the potential
application of TEG in monitoring the resultant progres-
sive hypocoagulability that develops when LMWH is
administered.33,34
However, the utility of TEG for moni-
toring purposes in critically ill dogs may warrant further
investigation, given the potential increased availability
of TEG compared to anti-Xa monitoring. Given that
these dogs represent clinical cases seen in the authors’
hospital, definitive antemortem and post-mortem
diagnosis of thromboembolism was available in only
select cases. As such, it is not possible to fully ascertain
the efficacy of dalteparin on the clinical outcome in
these dogs from this retrospective study. Additionally,
concurrent use of corticosteroids, platelet inhibitors and
the presence of anemia all impact upon interpretation
of pretreatment TEG and thus clinical outcome in this
group of dogs.
This retrospective study provides preliminary infor-
mation regarding anti-Xa monitoring in dogs receiving
dalteparin. Based on this study, dalteparin appears to
be a well tolerated anticoagulant in a group of critically
ill dogs with a variety of diseases. Reliable attainment
of therapeutic anti-Xa activity by clinician led dose ad-
justment was not demonstrated based upon these data.
Protocol driven anticoagulation strategies may be war-
ranted since this may improve the reliability of attaining
target anti-Xactivity, which may positively impact clini-
cal outcome. In addition, further prospective studies in-
vestigating the association between TEG and the ability
to attain therapeutic target anti-Xa activity activity in a
larger population of dogs are indicated.
Footnotes
a
Fragmin, Pfizer, New York, NY.
b
Hemosil Heparin assay, Instrumentation Laboratory, Bedford, MA.
c
ACL Elite, Beckmann Coulter, Miami, FL.
d
G value = 5000 × MA/(100-MA).
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