scott@vtx-cpd.com

Replying to Daphna S. 10/01/2022 - 09:52

Hello Daphna.

Happy new year! I am so glad that the lesson was helpful!

Let me know if you have any quetions.

Scott 🙂

Replying to Gabriela Gonzalez-Ormerod 07/12/2021 - 18:49

Hello Gaby.

I am really sorry about the delay in getting back to you. It is a really great question. I have summarised some of the antithrombotic treatment information from the consensus statement below:

The terms “thromboprophylaxis” and “antithrombotics” encompass both antiplatelet drugs, designed to inhibit platelet function (primary haemostasis), and anticoagulant drugs, designed to inhibit the activity of clotting factors (secondary haemostasis). Clopidogrel is an antiplatelet and rivaroxaban is an anticoagulant drug.

What we definitely do know is that thromboprophylaxis be provided for all dogs with IMHA, except those with severe thrombocytopenia (platelet count <30 000/μL). A substantial body of evidence indicates that IMHA in dogs is associated with an increased risk of thrombosis, and that thrombotic disease is a leading cause of morbidity and mortality in dogs with IMHA. The pathophysiology of thrombosis in IMHA is complex, involving endothelial activation, intravascular tissue factor expression, procoagulant microparticle generation, platelet activation, and an imbalance of pro- and anticoagulant factors.

The following is a recommendation from the consensus with relatively weak evidence:

''Based on the pathophysiology of venous thromboembolism commonly encountered in dogs with IMHA, we suggest that a regimen incorporating anticoagulants may be preferred for thromboprophylaxis, particularly during the first 2 weeks after diagnosis. The available anticoagulants may be used alone or combined with antiplatelet drugs. If treatment with an anticoagulant, and its associated monitoring, is not available or feasible, we suggest administration of antiplatelet drugs in preference to no antithrombotic drug''.

Many of the anticoagulant drugs can be challenging to monitor/not as widely available, so often antiplatelet drugs are given alone.

Thrombosis in IMHA predominantly affects the venous system, where thrombi form under low-shear conditions. Such thrombi typically are rich in fibrin, and their formation is less dependent upon platelet number or function, providing a rationale for administration of anticoagulant drugs. Although platelet activation can be detected in dogs with IMHA, this phenomenon probably occurs secondary to pathologic tissue factor-mediated thrombin generation, rather than as a primary event. Nevertheless, the cell-based model of haemostasis posits that platelets are integral to haemostasis in vivo. There is thus a rationale for the use of antiplatelet drugs in venous thrombosis. Experimental data support this proposition to some degree, and evidence in humans suggests that antiplatelet drugs do decrease the risk of venous thrombosis. However, this should be viewed in the context of the substantial body of evidence in humans supporting administration of anticoagulants as first line prophylactic drugs for venous thrombosis.

The consensus actually recommends the following:

''We suggest the administration of unfractionated heparin (UFH) with individual dose adjustment (using an anti-Xa assay) in preference to other drugs. This drug should not be used without individual dose adjustment. If this is not available or feasible, we suggest administering injectable low-molecular-weight heparins or direct PO Xa inhibitors. When using injectable low-molecular-weight heparins, we suggest individual dose adjustment (using an anti-Xa assay) may be useful to achieve a therapeutic dose.

Suggested starting dosages for these drugs are:
Unfractionated heparin (IV): 100 U/kg bolus, then 900 U/kg/24 h
Unfractionated heparin (SC): 150-300 U/kg q6h
Dalteparin (SC): 150-175 U/kg q8h
Enoxaparin (SC): 0.8-1.0 mg/kg q6-8h
Rivaroxaban (PO): 1-2 mg/kg q24h

Insufficient evidence is available to make strong recommendations on the choice of anticoagulant in IMHA. The strongest evidence supports the use of individually dose-adjusted UFH. Other anticoagulants including enoxaparin and rivaroxaban appear to be safe and may be efficacious, but RCTs are lacking.

Anti-Xa monitoring is not widely available to veterinarians. If an anti-Xa assay is not available, then it is reasonable to consider the activated clotting time, activated partial thromboplastin time (aPTT), thrombin generation, or viscoelastic tests to monitor anticoagulant treatment. Nomograms for adjustment of UFH treatment using aPTT and thromboelastographic assays have been proposed, but are currently only available in abstract form. The original derivation of UFH aPTT prolongation targets was performed using thrombotic models in dogs.

If antiplatelet drugs are administered, we suggest that clopidogrel be used in preference to aspirin. We suggest that clopidogrel be administered at a dosage of 1.1-4.0 mg/kg PO q24h. A single PO loading dose (eg, double the maintenance dosage or up to 10 mg/kg) may be useful for obtaining therapeutic plasma concentrations rapidly. If aspirin is selected as an antiplatelet drug, it should be administered at a dosage of 1-2 mg/kg q24h and could be combined with clopidogrel.''

In summary using anticoagulant therapy is recommended, but there are inherent challenges with the use of these drugs. Rivaroxaban is probably the most practical. I would probably use in combination with clopidogrel, especially in the first couple of weeks. Something is better than nothing and clopidogrel alone if nothing else!

I will let Liz answer the bit about HCM!

Scott x

Replying to Josie B. 22/12/2021 - 12:40

Hello.

Thank you for your amazing comments. Let me share the pathologists report:

Site Liver

Microscopic Description

Liver: Preservation is moderate and nucleated cellularity is low to moderate. Slide no4 contains
predominantly dense blood. The remaining scans contain variable amounts of fresh blood and small lipid
spaces. There are low to moderate numbers of well-differentiated hepatocytes arranged in sheets and clusters. Low numbers of erythrocytes and focal clusters contain low numbers of small clear punctate
vacuoles. There is rare focal moderate intracanalicullar bile stasis (bile casts). There are rare isolated
slender fusiform mesenchymal cells (presumed to be fibroblasts). Streaked nuclear material is frequently
associated with a parasite clusters and, in these areas, neutrophils and small lymphocytes occasionally
appear overrepresented. Infectious agents and atypical cells are not identified.

Microscopic Interpretation

Moderate focal cholestasis. Mild focal discrete vacuolar change.

Comments

Aspirates have harvested predominantly fresh blood however, within the hepatocytes there is evidence to
support cholestasis and although this is focal, it is moderate. The mild indiscrete vacuolar change is
non-specific and may be associated with elevated metabolic stress associated with inflammation of
varying aetiologies (hepatic and nonhepatic), as well as metabolic disease (e.g. pancreatitis).
Overt inflammation and infectious agents are not identified however this is a relatively small sample. The
fibroblast presence may be compatible with fibrosis however, this requires histopathology for definitive
diagnosis. Given the slightly increased numbers of leukocytes associated with hepatocytes, although overall
leukocyte numbers do not appear elevated mild inflammation cannot be excluded. Biopsy with
histopathology for evaluation of tissue architecture and tissue culture may be of value should changes
persist.

I was interested with your pancreatitis comments, what made you suggest that?

Thanks again for your brilliant comments.

Scott 🙂

Replying to Josie B. 22/12/2021 - 16:36

Hello!

Another brilliant question. Really there can be many extra hepatic causes of increased liver parameters. I think it all has to be taken in the context of the case. There can definitely be increases in liver parameters with more severe dental disease. Mild/moderate increases in ALP in these cases would not stop me from going ahead with the GA in these cases. It is when the increases in ALT become more significant that I start to worry a little more.

With the mild increases in ALT and ALP, it is most likely to be a reactive hepatopathy. I would consider UDCA/sAME as support but would still go ahead with procedure.

Hope that helps.

Scott 🙂

Replying to Gabriela Gonzalez-Ormerod 07/12/2021 - 18:33

Hey Gabriela.

Hope you are well. It is a really interesting drug! I think we will see more and more data over the next few years to support its use!

Scott 🙂

Replying to Alice L 09/12/2021 - 14:11

Hey.

I have spoken to Andy (who works at a dermatology only practice) and they are struggling too.

I will try other places and keep you updated.

Scott 🙂