Page 261 - Small Animal Internal Medicine, 6th Edition

CHAPTER 12 Thromboembolic Disease 233

because the anticoagulant proteins have a shorter half-life and are made based on the total weekly dose, which may
than most procoagulant factors. Therefore unfractionated require some variation in day-to-day doses. Drug admin-
VetBooks.ir heparin or LMWH is given concurrently for 2 to 4 days istration and blood sampling times should be consistent.
If the INR increases excessively, warfarin is discontinued
after warfarin is initiated. There is wide variability in dose
response to warfarin and potential for serious bleeding.
orally or subcutaneously) until the PT is normal and the
Warfarin is highly protein bound; concurrent use of other and vitamin K 1 administered (1-2 mg/kg/day administered
protein-bound drugs or change in serum protein concentra- packed cell volume (PCV) is stable. Transfusion with fresh-
tion can markedly alter the anticoagulant effect. Intensive frozen plasma, packed red blood cells, or whole fresh blood
monitoring is required and frequent dose adjustments might sometimes is necessary.
be necessary initially. Uneven distribution of drug within the Direct factor Xa inhibitors are emerging as attractive
tablets is reported, so compounding rather than administer- alternatives to warfarin for long-term management of throm-
ing tablet fragments is recommended. botic disease in dogs. In people, these oral medications have
The initial recommended dose of warfarin is 0.05 to equal or superior efficacy to warfarin with reduced risk of
0.2 mg/kg PO q24h. After initiation of treatment, the dose bleeding. The favorable adverse effect profile also means less
is adjusted based on PT and international normalization monitoring and increased convenience. Fondaparinux
ratio (INR). INR is a more precise method of serial coagula- (Arixtra) is a synthetic pentasaccharide that binds to both
tion monitoring recommended to prevent problems related AT and factor Xa with high affinity, thus selectively inhibit-
to variation in commercial PT assays. The INR is calculated ing factor Xa. Rivaroxaban (Xarelto) and apixaban (Eliquis)
by dividing the animal’s PT by the control PT and raising directly bind to and inhibit factor Xa without involvement
the quotient to the power of the international sensitivity of AT. Although there are published doses in cats for all three
index (ISI) of the thromboplastin used in the assay, or INR factor Xa inhibitors, rivaroxaban is the only drug with clini-
= (animal PT/control PT) . The ISI is provided with each cal dosing information described in dogs. A dose of rivar-
ISI
batch of thromboplastin made. Extrapolation from human oxaban 0.5 to 1.0 mg/kg PO q24h appears to be well tolerated
data suggests that an INR of 2 to 3 provides therapeutic anti- and was associated with decreased thrombus size in a small
coagulation with less chance for bleeding. Heparin overlap number of dogs. Although further research will be required
until the INR is greater than 2 is recommended. A coagula- to establish efficacy and ideal dosing protocols, these drugs
tion panel, INR, and platelet count are evaluated at baseline provide an exciting alternative to warfarin in dogs with
before warfarin administration. INR is then rechecked 1 aortic thrombosis.
to 3 days after initiation of warfarin and then at progres-
sively increasing time intervals, with INR values guiding
dose adjustments and time interval until the next recheck VENOUS THROMBOSIS
(see Table 12.1). Dose adjustments are small (5%-20%)
Thrombosis in large veins is more likely to be clinically
evident than thrombosis in small vessels. Cranial vena caval
thrombosis in dogs has been associated with many disease
TABLE 12.1 processes causing hypercoagulability, including IMHA and/

Guidelines for Adjusting Total Weekly Warfarin Dose* or immune-mediated thrombocytopenia, sepsis, neoplasia,
protein-losing nephropathies, fungal disease, cardiac disease,
TOTAL WEEKLY WARFARIN RECHECK and glucocorticoid therapy. Most cases have more than one
INR DOSE ADJUSTMENT INR IN predisposing factor. An indwelling jugular catheter or per-
manent pacemaker lead increases the risk for cranial caval
1.0-1.4 Increase TWD by 10%-20% 1 week thrombosis, probably by causing vascular endothelial damage
1.5-1.9 Increase TWD by 5%-10% 2 weeks or laminar flow disruption or by acting as a nidus for clot
2.0-3.0 No change in TWD 4-6 weeks formation.
3.1-4.0 Decrease TWD by 5%-10% 2 weeks Portal vein thrombosis, along with DIC, has occurred
4.1-5.0 Stop warfarin for 1 day 1 week in dogs with pancreatitis and pancreatic necrosis. Peritoni-
Decrease TWD 10%-20% tis, neoplasia, hepatitis, protein-losing nephropathy, IMHA,
>5.0 Stop warfarin until INR < 3.0 1 week and vasculitis have also been diagnosed occasionally in dogs
Decrease TWD 20%-40% with portal thrombosis. A high proportion of dogs with
incidental portal or splenic vein thrombosis were receiving
INR = (animal PT/control PT) ISI corticosteroids.
Control PT, Laboratory reference mean prothrombin time; INR, Venous thrombosis produces signs related to increased
international normalized ratio; ISI, international sensitivity index (of venous pressure upstream from the obstruction. Portal vein
the thromboplastin reagent); TWD, total weekly warfarin dose. thrombosis can result in ascites. Thrombosis of the cranial
*See text for additional information.
Modified from Winter RL et al.: Aortic thrombosis in dogs: vena cava can lead to the cranial caval syndrome, character-
presentation, therapy, and outcome in 26 cases, J Vet Cardiol ized by bilaterally symmetric subcutaneous edema of the
14:333, 2012. head, neck, and forelimbs. Another cause of this syndrome