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32 Pulmonary Thromboembolism 321

Alteplase has been successfully used in one dog with tural and pathophysiologic features shared by both
VetBooks.ir ATE, and experimentally induced canine PTE has been venous and arterial thrombi.
Anticoagulants remain the mainstay of antithrombotic
treated with t‐PA therapy.
Currently, the American College of Clinical Pharma­
PTE, the ACCP recommends initial parenteral antico­
cology (ACCP) recommends thrombolytic therapy therapy for people with PTE, however. In people with
for people with hypotension secondary to acute PE. agulation with low molecular weight heparin (LMWH)
Thrombolysis in PTE in the absence of hypotension is or fondaparinux except where renal insufficiency, throm­
not currently recommended, but could be considered in bolytic therapy or poor perfusion mandate the use of IV
patients with echocardiographic evidence of cardiac dys­ unfractionated heparin (UFH). Ongoing anticoagulation
function or in those with high cTnI or NT‐proBNP con­ for people with PTE is recommended for three months,
centrations. A recent trial of normotensive PTE patients although this may be extended in certain cases. Since the
with biomarker and echocardiographic evidence of myo­ advent of the orally active direct Xa inhibitors and direct
cardial damage and dysfunction evaluated thrombolysis thrombin inhibitors, most people are now maintained on
with tenecteplase. Thrombolysis in these patients sig­ these newer medications. The direct oral anticoagulants
nificantly reduced the rate of death due to hemodynamic (DOACs) have equivalent efficacy to warfarin but are
collapse, but at the cost of a significant increase in major associated with significantly lower bleeding risk.
bleeding events. To date, there are no clinical trials of anticoagulants in
Where thrombolytic agents are used, the ACCP rec­ PTE in small animals on which to base recommenda­
ommend they be administered over a short time period tions. Although there is not universal consensus on dos­
via a peripheral catheter rather than a PA catheter. Case age, frequency of administration or monitoring strategy
registry data suggest thrombolytics are used in only 30% for antithrombotics in small animals, ongoing efforts by
of people with massive PTE. In veterinary medicine, no the American College of Veterinary Emergency and
consensus on their administration exists and clinicians Critical Care led to guidelines being published in January
must determine the potential benefits and risks of 2019. As a result of improved understanding and the
administration for individual patients. Recent advances availability of the DOACs, long‐term anticoagulation in
in small animal interventional radiology may provide veterinary medicine is becoming increasingly common.
novel methods or routes for thrombolysis in future. The narrow therapeutic index of warfarin has led to
Based on the ACCP guidelines, thrombolytic therapy increasing use of the DOACs in dogs and cats. Individual
should only be considered in veterinary patients with patient monitoring and dose adjustment of UFH and
hemodynamically unstable acute PTE and where con­ LMWH may enhance efficacy and improve safety and is
tinuous hemodynamic monitoring is available. In appro­ possible using commonly available assays.
priate cases, fibrin‐specific drugs with short half‐lives
(e.g., alteplase) are preferred. Anticoagulants
Unfractionated heparin, a heterogenous mixture of poly­
saccharides, complexes with and amplifies the inhibitory
Antithrombotic Strategies
activity of AT against factor IIa (thrombin) and factor
In PTE anticoagulants and antiplatelet agents are Xa, although factors IXa, XIa, XIIa, and XIII are also
administered to minimize thrombus propagation, inhibited. Thrombin inactivation prevents fibrin forma­
which can be stimulated by embolization, and to reduce tion and reduces thrombin‐induced platelet activation.
risk of recurrence. However, the optimal antithrom­ Variation in the size distribution of heparin molecules in
botic strategy for small animals is not known. Some UFH and unpredictable bioavailability in critical illness
suggest that PTE should be managed with anticoagu­ cause variation in heparin dose–responses, necessitating
lant drugs and that antiplatelet agents are not appropri­ therapeutic monitoring since severe bleeding complica­
ate. Viewing arterial and venous thrombosis as separate tions can result from exceeding the therapeutic range.
pathophysiologic entities is likely an oversimplification, Therapeutic monitoring can be performed using the
however, and there is evidence of overlapping efficacy ACT, aPTT, thrombin generation, viscoelastic testing, or
of antiplatelet and anticoagulant agents in the treat­ anti‐FXa levels. This need for therapeutic monitoring
ment of both venous and arterial thromboembolic con­ reduces the cost benefit of UFH, but individually adjusted
ditions. Platelets are integral to the cell‐based model of dosing may offer benefits over fixed dosing.
hemostasis, and thrombocytosis is associated with an Low molecular weight heparins derive from depolym­
increased risk of PTE in people. In venous thrombosis, erization of UFH and were developed to provide more
tissue factor‐mediated secondary coagulation precedes consistent pharmacokinetic/pharmacodynamic (PK/PD)
platelet activation, but both arms of the hemostatic sys­ profiles than UFH. The reduced size of the LMWH poly­
tem are activated, which correlates with the architec­ saccharides limits their ability to simultaneously bind AT